Encyclopedia of Forensic e Bookand Legal Medicine

ROAD TRAFFIC ACCIDENTS, AIRBAG-RELATED INJURIES AND DEATHS 1
ROAD TRAFFIC ACCIDENTS, AIRBAG-RELATED INJURIES AND DEATHS

W S Smock, University of Louisville Hospital, Louisville, KY, USA
2005, Elsevier Ltd. All Rights Reserved.
Introduction
Annually, road traffic accidents in the USA and Canada result in the loss of tens of thousands of lives, inflict hundreds of thousands of serious injuries, cost the health and insurance industries billions of dollars, and consume countless hours of investigative effort on the part of local and state law enforcement. Of all the myriad forensic and legal questions that an accident investigator and the courts need to address, two of the most significant civil and criminal issues are: how fatal or life-threatening injuries were sustained and determining who was driving. The airbag has played a role in both of these forensic issues. Designed and promoted as a life-saving device, the airbag has made good on its promise. The National Highway Transportation Safety Administration (NHTSA) estimates that some 14 000 lives have been spared as a result of airbag deployment. Unfortunately, the same life-saving device has also been responsible for at least 239 deaths of men, women, and children. Thousands of other motorists have sustained severe nonfatal injuries as a result of airbag deployment including cervical spine fractures, retinal detachments, closed head injuries, and comminuted fractures and amputations of the hand and upper extremity. Ironically, many of the injuries and deaths are not occurring at high speeds but in low- and moderate-speed collisions.
produced catastrophic injuries including cardiac rupture, hepatic rupture, splenic rupture, aortic and vena cava transection, atlantooccipital dislocation, cervical spine fractures, and severe closed head injury. A General Motors study indicated many of the exposures were at loading severities beyond the level representing an estimate of nearly 100% risk of severe injury. Well before airbags were placed in standard production, the testing and data were clear: airbag deployment could inflict serious and fatal injuries. Unfortunately, soon after airbag-equipped vehicles were marketed in the USA and Canada in 1989 and 1990, the serious and life-threatening injuries that were originally observed in the industrys laboratories using animal models began to be observed on the nations highways in the human population. The first six driver airbag-related deaths were women of short stature. It was also noted that their fatal injuries could be sustained even if they were lap and chest belt restrained. The injuries initially seen in these six women included massive head injuries with diffuse axonal injury, subdural and epidural hematomas, and skull fractures. Subsequently, additional airbag-induced fatal injuries in restrained and unrestrained occupants have included atlantooccipital dislocations, cervical spine fractures, brainstem lacerations, cardiac perforations and valvular injuries, aortic transection, pulmonary contusions, and multiple rib fractures.
Mechanisms of Injury
Sodium azide is the explosive propellant used to initiate the deployment cycle in most airbag designs in use today (Figure 1). When sodium azide is ignited, the deploying airbag explodes, filling with nitrogen gas and carbon dioxide, and moves rapidly rearward toward the occupant at speeds of up to 210 mph (336 kph). Reconstruction of the injuries incurred during deployment can be traced to the system component inflicting them: the canvas-covered airbag, the airbag module cover, or both (Figure 2). Obviously, the types of injuries that result from impact with the canvas airbag are different from those that result from impact with its module cover. There are three phases to describe airbag deployment: punch out, catapult, and bag slap. Injuries can be inflicted at any point during the deployment process.
The History of Airbag Research and Development

The airbag was first patented in 1952 and Ford and General Motors began experimenting with these early prototypes in the late 1950s. Research and testing by the automotive industry revealed in the early 1960s that the forces of airbag deployment had the potential to induce serious and fatal injuries, particularly to children. Testing demonstrated that there was sufficient force associated with airbag deployment to amputate the steel-hinged arm from a test dummy and traumatically eject a child from a vehicle. Live-animal testing by the automotive industry
2 ROAD TRAFFIC ACCIDENTS, AIRBAG-RELATED INJURIES AND DEATHS
and facial injuries occur as the result of cervical spine hyperextension and direct trauma.
Bag Slap
This is the final stage of deployment, which occurs at the bags peak excursion. Appropriately named, this happens when the canvas bags fabric may slap the occupants face or arms, resulting in injuries to the eye and epithelium.
Airbag Tethers and Covers

Figure 1 Sodium azide is an explosive propellant that is the source of nitrogen gas for airbag inflation. Toxic byproducts of sodium azide combustion may cause damage to pulmonary tissue.
Figure 2 The canvas airbag and the module cover are both capable of inflicting serious and fatal injuries. Reproduced with permission Smock WS. Accident Investigation: Airbag-related Injuries and Deaths. In: Encyclopedia of Forensic Sciences. Edited by Jan A Siegel, Pekka J Saukko, Geoffery C Knupfer. Academic Press: London. 2000 with permission from Elsevier.
Phases of Airbag Deployment

Punch Out
Early airbag designs in some vehicles did not include the use of an internal tethering system to limit the rearward excursion of the bag. Untethered airbags can extend beyond 21 in (53 cm) (Figure 3) compared to 1214 in (3035 cm) of excursion in tethered models. This excessive rearward movement has been responsible for severe injuries to the face and in particular to the eyes. Even the properly restrained, nonnear positioned occupant can sustain severe injuries from untethered airbags. The airbag module covers are located in the steering wheel on the drivers side and in the dashboard panel on the passenger side. As the bag deploys, the module cover is also propelled outward at speeds of up to 210 mph (336 kph). Most steering wheel designs house the horn within the airbag module compartment, which is an invitation for devastating upper extremity injuries (Figure 4). Hand and arm injuries observed in individuals whose extremities were in contact with the module at the moment of its rupture include: degloving, fracture, dislocation, fracture dislocation, and amputations (partial and complete of digits and forearms) (Figure 5). If the module cover makes contact with an occupants face, head, or neck, skull fractures and severe or fatal head injuries, and decapitations have also been observed. The drivers side cover is generally made
This is the initial stage of deployment. If the bag makes contact at this stage, the following injuries can result: atlantooccipital dislocation, cervical spine fracture with brainstem transection, cardiac, liver, and splenic lacerations, diffuse axonal injuries, subdural and epidural hematomas, and decapitation. Impact with the upper extremity during this phase will result in massive fractures, degloving, and amputations.
Catapult
This is the mid-stage of deployment when the rapidly inflating bag catapults or drives the head and neck rearward. This occurs with sufficient energy to rupture blood vessels, tear ligaments, rupture globes, and fracture cervical vertebrae. The neck
Figure 3 Untethered airbags can extend well into the restrained occupants space. This airbag from a Nissan Maxima extended 21 in (53 cm) rearward and was responsible for this patients total loss of vision from a ruptured globe.
Figure 4 Air bag module covers with built-in horn activation buttons are an invitation for serious injuries to the upper extremity (Figures 5, 2128).
Figure 6 Air bag module covers constructed with a metal frame are exceedingly dangerous and can easily amputate the hand or forearm. Reproduced with permission Smock WS. Accident Investigation: Airbag-related Injuries and Deaths. In: Encyclopedia of Forensic Sciences. Edited by Jan A Siegel, Pekka J Saukko and Geoffrey Ckuupter Academic Press London 2000 with permission from Elsevier.
Figure 5 An open fracture with degloving of the forearm from impact with an airbag module cover.
with a rubberized plastic type of material, while the passenger side may have a metal housing (Figure 6). Contact with either type can prove fatal.
Mechanism of Injury
Ocular Injuries
Figure 7 Massive ocular trauma from a passenger-side airbag. The patient sustained globe rupture and orbital fractures from impact with a cane that was propelled into his face (Figure 11).
The eyes are extremely vulnerable to direct and indirect airbag-induced trauma in both the restrained and unrestrained occupant. These injuries range from corneal abrasions secondary to direct contact with the airbag to alkali chemical burns from contact with unburned sodium azide and sodium hydroxide to retinal detachment and globe rupture from the blunt force trauma of the expanding bag (Figures 7, 8, and 9). Direct trauma Impact to the globe and facial structure from the bag during the punch out or catapult stage may be catastrophic. Globe rupture, lens dislocation, blowout fractures, and retinal detachment are among the most serious ocular injuries reported. External signs of ocular trauma include periorbital
Figure 8 Chemosis and hyphema from a passenger-side airbag.
Figure 9 Periorbital contusions and abrasions from a passenger-side airbag.
Figure 11 Any objects, like this walking cane, caught in the path of the deploying airbag, can be propelled into the face and eyes of the passenger (Figure 7).
Figure 10 Air bag impacts to glass lenses have resulted in incised wounds to the globe.
(Figure 12). The intermediate objects may also display damage and evidence of trace material (Figure 11). Examination of eyeglass frames and lens will also be of benefit to the forensic investigator (Figure 13).
Cranial and Intracranial Injuries
lacerations and contusions, hyphemas, and corneal abrasions. The wearing of eyeglasses with plastic lenses has proven to be of benefit in the prevention of corneal abrasions, as it offers a degree of barrier protection between the eyes and the deploying bag, whereas eyeglasses with glass lenses have been responsible for lacerations of the globe when glass fragments are driven into the eye (Figure 10). In severe corneal abrasions, the airbags weave pattern can be visualized imprinted on the cornea. Indirect trauma The eyes are also vulnerable to trauma from intermediate objects. The most common indirect object is the hand, accidentally caught in the path of the module cover or bag, which is propelled rapidly upward into the globe. Other examples include pipes, canes, cell phones, and pets (Figure 11). The transfer of blood, facial tissue, eyebrow hair, and eye or facial makeup to the bag will assist the investigator in determining that the airbag component was responsible for the injuries observed
When acceleration forces are applied to the cranial vault, a variety of traumatic injuries to the brain and surrounding structures will result. These injuries are caused by direct blunt trauma (module cover) and rapid accelerations (airbag) of the brain tissue and vessels. These include subdural and epidural hematomas, cortical contusions, diffuse axonal injury, atlantooccipital dislocations, skull fractures, and brainstem transections (Figure 14). The most common cranial injury associated with airbag deployment is that of facial abrasion (Figure 15). The abrasions result from a sliding contact between the bag and the face and tend to be deep. A forensic examination of both the bag and the module cover is warranted to look for evidence of transferred material or physical damage from contact. Hair, blood, epithelial tissue, and makeup are the materials most commonly transferred to the bag. The module cover is also an important source of transferred material. Module cover design dictates
Figure 14 Subdural and subarachnoid hemorrhage from cranial impact in a restrained, short-statured, female driver of a 1990 Ford Taurus.
Figure 12 Blood, tissue, and makeup are easily transferred to the airbag. This trace evidence will facilitate the determination of the etiology of an occupants injuries and in the determination of an occupants role, driver or passenger.
Figure 15 Facial abrasions are the most common airbaginduced facial injury.
of the module cover or transfer of facial tissue or hair is evidence of traumatic impact during deployment (Figure 17).
Cervical Spine Injuries
Figure 13 Examination of eyeglass frames will assist the investigator in the reconstruction of ocular injuries.
how far the arc of the module flap will extend on deployment. Asymmetrical covers, those that do not split in the middle, will have a longer arc and will therefore have a higher risk of impacting an occupants face or upper extremity (Figure 16). Cranial impact from the module cover occurs more frequently with unrestrained occupants but also occurs with short-statured restrained drivers. Tearing
When a driver or passenger sustains a blow from an airbag or module cover the cervical spine is at risk. The rapid and violent hyperextension of the cervical spine can disrupt the anatomical structures and easily exceed human tolerances. Injuries commonly seen as a result of this rapid hyperextension include atlantooccipital dislocation, comminuted fractures of one or more upper cervical vertebrae, rupture of the anterior and posterior longitudinal spinal ligaments, vertebral artery injury, and cervical spine disarticulation with transection of the cervical cord (Figure 18). The majority of these injuries are associated with
Figure 16 Module covers that split in an asymmetrical manner are more likely to impact facial structures because of a longer arc on opening. This Ford module cover extends 5 1/2 in (14 cm) from the steering wheel hub.
Figure 18 The rapid and forceful hyperextension of the neck and cervical spine from the airbag resulted in a C2 fracture with a vertebral artery injury.
(Figure 19). These injuries should correspond to the transference of epithelial tissue to the airbag or module cover.
Thoracic Injuries
Figure 17 The tearing of this thick module cover occurred when the cover impacted the left side of the face of the women in Figure 14. Reproduced with permission Smock WS. Accident Investigation: Airbag-related Injuries and Deaths. In: Encyclopedia of Forensic Sciences. Edited by Jan A Siegel, Pekka J Saukko, Geoffery C Knupfer. Academic Press: London. 2000 with permission from Elsevier.
the upper cervical vertebrae, although lower cervical vertebrae injuries have been observed. Deep abrasions overlying the victims chin and neck area are evidence of airbag-induced hyperextension
Substantial blunt thoracic trauma, from the airbag or module cover, can occur to the restrained or unrestrained occupant. Severe and fatal thoracic injuries, historically only associated with high-velocity motor vehicle collisions, are occurring from impacts with airbags. Aortic transactions, cardiac and valvular lacerations, pulmonary contusions and lacerations, and sternal and rib fractures are common, even in very low-speed collisions. The forward positioned occupant, restrained or unrestrained, is most at risk. Many victims who sustain thoracic injuries have translated forward, toward the module cover, due to preimpact braking.
Figure 19 Deep abrasions under the chin from a hyperextension injury to the neck (Figure 18).
Figure 21 Radiograph of the forearm of a driver who was attempting to blow the horn at the time of airbag deployment. The driver was restrained.
Figure 20 An airbag cutoff switch should be considered for occupants who cannot sit at least 12 in (30 cm) from the airbag module (www.airbagonoff.com).
Figure 22 Partial thumb amputation from a passenger airbag.
Examination of the module cover for fabric imprints or tears will provide evidence of impact.
Abdominal Injuries
The abdominal organs are also at significant risk for direct blunt trauma. Severe and fatal abdominal injuries associated with airbags include liver laceration, splenic laceration, pancreatic laceration, diaphragmatic rupture, and vena cava transection. Placental abruption and fetal demise can also occur from blunt airbag trauma. Pregnant occupants, both driver and passenger, should move their seats back as far as possible from the airbag module. If the abdomen of a pregnant woman is not at least 12 in (30 cm) from the steering wheel the driver should consider installing an airbag cutoff switch (Figure 20).
Upper Extremity Injuries
The upper extremities are especially vulnerable to traumatic injury from the deploying bag and its module cover. Upper extremity injuries in motor vehicle
collisions have increased more than 400% since the introduction of airbags. When an individuals hand or forearm is on or near the module cover at the moment of deployment, the occupant can expect to sustain multiple fractures, and/or tissue degloving or amputation of fingers, hand, or forearm (Figures 21, 22, 23, and 24). Vehicles with the horn activation button located within the module cover pose a significantly increased risk of injury to the occupants upper extremities at the moment of deployment. Many of these upper extremity injuries are associated with an occupants attempt to blow the horn just prior to a collision. Despite the propensity for a drivers to sound a warning prior to a collision, neither the NHTSA nor the automobile manufacturers has taken the necessary steps to warn drivers of this hazard. Forces from airbag deployment may be transmitted to the hand, wrist or forearm and may even involve the humerus (Figure 25). It is not unusual to see significantly comminuted fractures involving the wrist,
Figure 25 Radiograph of proximal humeral fracture and comminuted elbow fracture from a passenger side airbag.
Figure 23 Placement of the forearm over the module cover at the moment of deployment will result in severe fractures.
Figure 26 Radiograph of a comminuted elbow fracture caused by a blow from the module cover.
Figure 24 Comminuted fractures of a wrist from the placement of the passengers hand on the deploying module cover.
forearm, elbow, and distal humerus (Figures 26 and 27). The vehicles whose module covers are of a higher mass have the capacity to inflict more severe injuries. Some of the worst offenders are module covers located on the passenger side, which may have a soft coating of plastic on the exterior but have an underlying piece of rigid metal (Figure 6). The placement of hands on the passenger-side dashboard, in a bracing maneuver, has resulted in the traumatic amputation of hands and forearms (Figure 28). Examination of the module cover is extremely beneficial to the reconstruction of upper extremity injuries. Deformation of the module cover is evidence of arm placement on or near the cover
Figure 27 Radiograph of a comminuted elbow fracture with dislocation from module cover impact.
during deployment (Figure 29). Fabric imprints may also be transferred to the cover (Figure 30). Nonpatterned scuffmarks may be present (Figure 31). Blood from open fractures may be deposited on both the bag and module cover (Figure 32).
Figure 28 Partial hand amputation from placement on the passenger module cover in a bracing maneuver (Figure 29).
Figure 30 Fabric imprint on module cover is evidence of module cover impact with the patients forearm.
Figure 29 Deformation of the passenger module cover from arm placement (Figure 30).
Lower Extremity Injuries
The resting of an occupants foot or feet on the passenger module cover during deployment will result in comminuted fractures and soft tissue injury to the feet, ankles, and lower legs. The term airbag ankle was coined in 2000 when a 13-year-old girl sustained a comminuted fracture above the ankle from impact with the module cover (Figure 33). Inspection of the module cover may reveal pattern or material transfer. Imprints of the sole of a shoe have been found on passenger module covers (Figures 33 and 34). Nonpatterned scuffing may also be present on the cover as evidence of contact.
Respiratory Injuries
Figure 31 Nonpatterned scuffmark on module cover from hand placement. Injuries of each occupant can be matched to module cover damage.
Airbag deployment is initiated by the ignition of sodium azide. The byproducts of combustion as well as other inert materials within the airbag produce a large volume of gas and a white cloud of residue within the
Figure 32 Blood on the airbag can be matched to an occupant, driver, or passenger.
unburned sodium azide present within this powder as well. Inhalation of these materials can result in a chemical pneumonitis or induce of asthma-type symptoms, and they have been reported to be toxic to the pulmonary tissue.
Determination of Occupant Role

The second principal forensic issue related to airbag deployment is the ability of evidence from the state of the airbag to assist in the determination of an occupants role, driver or passenger. Locards principle regarding the transfer of physical evidence between two impacting objects is dramatically observed in the case of airbags and injuries induced by airbag module covers. The transfer of evidence to the airbag itself may take various forms: blood, epithelial tissue, and hair. The transfer of makeup is also commonly observed, including the deposition of lipstick, rouge and mascara to the airbag (Figure 12). The analysis of the blood spatter pattern on the bag could assist the investigator in determining the position of the occupant and the configuration of the steering wheel at the moment of air bag deployment. Examination of the airbag module cover may reveal the presence of trace evidence. Depending upon the design of the module cover, there may actually be tearing or bending of the module cover, indicative of contact with an occupants more rigid (bony) surface: face or forearm. Scuff-type marks on the module cover indicate contact with an object, frequently the forearm (Figure 31). Fabric imprints may also be seen on close inspection (Figure 30). Forensic investigators, in cases where the role of the occupants is unclear or denied by involved parties, should perform forensic evaluations on all of the vehicles occupants to document the presence or absence of airbag-induced injuries. Processing of the vehicles in a timely fashion by forensic evidence technicians will help insure that valuable evidence on the bag, module cover, or other interior components does not degrade with time and will be photographically documented. Vehicles should be covered with a tarp at the scene to prevent hair or fibers from being blown away during towing to an indoor garage.
Figure 33 Comminuted distal tibia and fibula fractures from placement of the foot on the module cover at the time of deployment, a.k.a. airbag ankle.
Figure 34 Pattern of the imprint on the module cover matched the sole of the passengers shoe.
Side Airbags
Beginning in 1995, automobile manufacturers began installing several different types of side airbags including seat-mounted, door-mounted, window-curtain, and inflatable-tubular types. The first reported injury from a side airbag occurred in December 1996 and involved a 3-year-old child. The side airbag was a door-mounted type. It was not until October 1999,
vehicle. Many occupants have thought that this indicated a vehicle fire. The principal components of this gas and white cloud are nitrogen and carbon dioxide with cornstarch, talc, sodium bicarbonate, and metallic oxides. There may be a small percentage of
that NHTSA issued a consumer advisory regarding the potential dangers of side airbags. The advisory stated children who are seated in close proximity to a side airbag may be at risk of serious or fatal injury, especially if the childs head, neck or chest is in close proximity to the airbag at the time of deployment. To date, NHTSA has not reported any fatalities and fewer than 15 injuries from side airbags. As in frontal airbags, the injuries are similarly attributed to the force of deployment from the airbag itself and/or the module cover. The risks for injuries to the head, neck, and thorax of both adult and child occupants that lean against the side-mounted module are real. The forensic investigator should employ the same techniques for investigating side airbag incidents as are utilized in the investigation of frontal airbag injuries.
Conclusion
The airbag, despite claims of being a life-saving device, has clearly demonstrated that it can induce serious and fatal injuries to restrained and unrestrained adults and children. Fortunately with the reduction of airbag deployment aggressivity beginning in 1997, the numbers of severe and fatal injures have declined. Forensic investigators must understand the mechanisms of airbag-induced injuries in order to reconstruct how, why, and in whom these injuries occur. The transfer of material between airbag, module cover, and occupant, and the presence of airbag-specific injuries, will be a tremendous asset to the forensic investigator and the courts in determining, beyond a reasonable doubt, the role, driver or passenger, of a vehicles occupants.
Further Reading
Duma SM, Kress TA, Porta DJ, et al. (1996) Airbag-induced eye injuries: a report of 25 cases. Journal of TraumaInjury Infection and Critical Care 41: 114119. Hollands CM, Winston FK, Stafford PW, Lau HT (1996) Lethal airbag injury in an infant. Pediatric Emergency Care 12: 201202. Huelke DF, Moore JL, Compton TW, Samuels J, Levine RS (1995) Upper extremity injuries related to airbag deployments. Journal of Trauma-Injury Infection and Critical Care 38: 482488. Jumbelic MI (1995) Fatal injuries in a minor traffic collision. Journal of Forensic Sciences 40: 492494. Lau IV, Horsch JD, Viano DC, Andrzejak DV (1993) Mechanism of injury from air bag deployment load. Accident Analysis and Prevention 25: 2945.
Lee WB, OHalloran HS, Pearson A, Sen HA, Reddy SHK (2001) Airbags and bilateral eye injury: five case reports and a review of the literature. Journal of Emergency Medicine 20: 129134. Mohamed AA, Banerjee A (1998) Patterns of injury associated with automobile airbag use. Postgraduate Medical Journal 74: 455458. National Highway Traffic Safety Administration (1999) Consumer Advisory: Side Impact Airbags. Available online at: www.nhtsa.dot.gov/nhtsa/announce/press/1999/ ca101499.html. NCSA (National Center for Statistics and Analysis of the National Highway Traffic Safety Administration) (2004) Airbag Fatality Summary Report, 4th Quarter, 2003. Available online at: http://www-nrd.nhtsa.dot. gov/departments/nrd-30/ncsa/SCI.html. NCSA (National Center for Statistics and Analysis of the National Highway Traffic Safety Administration) (2004) Fatality and Serious Injury Summary Report. Available online at: http://www-nrd.nhtsa.dot.gov/pdf/ nrd-30/NCSA/SCI/4Q_2003/ABFSISR.pdf. NCSA (National Center for Statistics and Analysis of the National Highway Traffic Safety Administration) (2004) SCI Side Airbag Cases Summary. Available online at: http://www-nrd.nhtsa.dot.gov/pdf/nrd-30/NCSA/ SCI/4Q_2003/SABCST.pdf. Pearlman JA, Au Eong KG, Kuhn F, Pieramici DJ (2001) Airbags and eye injuries: epidemiology, spectrum of injury, and analysis of risk factors. Survey of Ophthalmology 46: 234242. Prasad AK, Samaha RR, Louden AE (2001) Evaluation of Injury Risk from Side Impact Airbags. Available online at: http://www-nrd.nhtsa.dot.gov/pdf/nrd-01/NRDmtgs/ 2001/1001aloke.pdf. Prasad AK, Samaha RR, Louden AE (2002) Side Air Bag Research: Static Testing of Side Impact Air Bags Using Three and Six Year Old Hybrid III Dummies and the 12 Month CRABI Dummy, pp. 1270. Available online at: http://www-nrd.nhtsa.dot.gov/pdf/nrd-01/ NRDmtgs/2002/011802SAB.pdf. Shah GK, Penne R, Grand MG (2001) Purtschers retinopathy secondary to airbag injury. Retina, the Journal of Retinal and Vitreous Diseases 21: 6869. Smock WS (2000) Airbag related injuries and deaths. In: Siegel JA, Sauuko PJ, Knupfer GC (eds.) Encyclopedia of Forensic Sciences, pp. 18. San Diego, CA: Academic Press. Smock WS, Nichols GR (1995) Airbag module cover injuries. Journal of Trauma-Injury Infection and Critical Care 38: 489493. Willis BK, Smith JL, Falkner LD, Vernon DD, Walker M (1996) Fatal air bag mediated craniocervical trauma in a child. Pediatric Neurosurgery 24: 323327. Yasuo T, Wakiyama H, Amemiya T (1999) Ocular injury caused by an air bag for a driver wearing eyeglasses. Japanese Journal of Ophthalmology 43: 23.
12 ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/Sobriety Tests and Drug Recognition
ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE

Contents Sobriety Tests and Drug Recognition General Driving Offense
Sobriety Tests and Drug Recognition

R Tunbridge, Transport Research Laboratory, Wokingham, UK S G Collier, National Drug Recognition Training Unit, Northampton, UK
Introduction and Background

This article covers the topics of drug recognition training (DRT) and standardized field sobriety tests (SFST), which have recently been introduced as means of aiding the identification of drivers under the influence of drugs. The description given here is based on the practice applied in the UK; however, this was developed from well-established techniques used since the 1980s in the USA. The current legal context of sobriety testing in the UK is also described. Furthermore, similar adaptations of the US techniques have been widely applied across Europe and also in Australia. The article starts with a brief but necessarily detailed background on the issue of drugs and driving, and associated legal issues, as these have provided the raison de tre for the development of DRT and SFST. These intimately related, but essentially separate issues are then covered in depth.
Driving under the Influence of Drugs Background
The topic of drugs and driving has recently become regarded as a significant road safety issue. Until the mid-1980s there were very few studies showing evidence that impaired driving due to drugs was a significant problem. A Transport Research Laboratory (TRL) study to measure the incidence of drugs in fatal road accident casualties showed that the incidence of medicinal drugs (5.5%) and illicit drugs (3%) was relatively low in comparison to alcohol, which was found in 35% of cases.
However, much recent evidence has suggested that illicit drug taking in the UK has increased considerably since the mid-1980s. A further study of incidence of drugs in road fatalities was therefore commissioned by the Department for Transport. This began in October 1996 and was completed in June 2000. Interim results from this study in 1997 showed a sixfold increase in the incidence of illicit drugs found in drivers. This increase was confirmed by separate studies of drug driving undertaken in Scotland in 1997. This alarming increase in the level of drug-related driving prompted the UK government to seek initiatives to combat it. One particular issue was a recognition of the general lack of police training in recognizing drug-impaired drivers; this hindered the detection of such drivers and thereby any effective countermeasures. In response to this deficiency, the UK Home Office sent two police officers to the USA to study the Drug Evaluation and Classification (DEC) program which involved a system of training drug recognition experts (DREs). This system was subsequently adapted for use by UK police forces to train traffic officers in recognizing drug-impaired drivers. The training system developed for the UK has two principal components: DRT (Drug Recognition Training) and field impairment testing (FIT). DRT is a system to identify the signs and symptoms associated with the effects of drugs. The system classifies drugs into six main groups. These are similar to those used for chemical analysis. The second (FIT) is a systematic standardized method of examination to determine impairment. This system is intended for use at the roadside by police or at the police station by forensic physicians (FPs). Together with DRT and other observations made on the driver, FIT provides a strong indication of whether a driver is impaired. The DEC system from which it is derived has been in use in the USA since the 1980s and is a widely accepted method for assessing drug-impaired drivers. However, before introduction of DRT and FIT in the UK, evaluation trials of the UK version were
ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/Sobriety Tests and Drug Recognition 13
conducted in six police force areas in the summer of 1999. These trials showed that, of those drivers who failed a FIT test and were required to give an evidential blood sample, 92% proved positive for drugs that may impair driving performance. This is similar to routine results obtained by DREs in the USA. In addition, in two-thirds of cases the correct drug group was identified. It was concluded that DRT and FIT represent easily applied techniques that police can use to detect persons impaired through drugs. Apart from recommending wider police training in the use of these techniques, the evaluation also recommended that FPs receive training in FIT. Subsequent to an Association of Chief Police Officers (ACPO) conference in August 2000, an increasing number of traffic officers have received training in these techniques.
Driving under the Influence of Drugs Legal Issues
Since the wider introduction of the technique of impairment testing subsequent to August 2000, the subject of driving under the influence of drugs has gained considerable momentum. At the heart of a prosecution for driving whilst unfit through drink or drugs, there is a requirement to provide evidence that a person was unfit to drive. Recent changes in UK legislation will help to make that determination simpler for the police officer. The Railways and Transport Safety Act 2003 made sweeping changes to Section 6 of the Road Traffic Act 1988, in respect of police powers to request roadside tests. This has given police officers mandatory powers to undertake roadside DRT and FIT as well as to test drivers for the presence of appropriate drugs in a sample of saliva or sweat when an appropriate device has been approved. In the past the legislation has only provided guidance in defining terms used within the Acts, and for the purpose of Section 4, Road Traffic Act 1988 defines unfit to drive as the persons ability to drive properly is for the time being impaired. Throughout any unfitness case, there is a need for the prosecution to prove that impairment was due to some causal connection with drink or drugs and that proper control of the vehicle was impaired. This has been a fundamental concept in UK legislation since the early 1920s and has barely changed. The introduction of the Railways and Transport Safety Act in July 2003 changed the way in which police officers deal with suspected drugged drivers. Whereas the previous Section 6 of the Road Traffic Act only dealt with the provision of a breath specimen, it now covers both the impairment tests and, when one becomes available, a roadside drug-screening device.
Not only does the offense reinforce Section 4, by the introduction of the term is unfit to drive because of a drug, but it still does not make it an offense to drive with a drug in the body: the person must be seen to be under the influence of the drug. There is no reference in the Act as to what this influence is and it has been left for this reference to be made within the Codes of Practice which are required to be adhered to by officers performing the tests. Table 1 includes the basic wording of the Railways and Transport Safety Act as it applies to drug-impaired driving. In the following section, the FITs proposed for application under the new Act are described in some detail. It is important to consider, however, that although these tests have been widely used in the USA for some time and are being increasingly used in countries across Europe, including the UK, they do not provide an unequivocal determination of driver impairment. Legal challenges have been made to the use of such tests in the USA and several commentators in the UK have also expressed reservations as to their use. Currently, the word impairment is not defined within the Road Traffic Act 1988. However, when a police officer is considering an arrest for the offense within section 4 of the Act (driving whilst unfit through drink or drugs), an assessment of whether a driver is
Table 1 Section 6 Road Traffic Act 1988, as amended by Section 107 & Schedule 7 Railways & Transport Safety Act 2003
Section 6(1)
A constable in uniform, may require a person to co-operate with any one or more preliminary tests, administered to the person by the constable or another constable.
Section 6(27)
If a constable in uniform reasonably suspects, that a person is, or has been, driving, attempting to drive, or is in charge of a motor vehicle on a road or other public place, and (a) Has alcohol or a drug in his body or is under the influence of a drug. (b) While having alcohol or a drug in his body or is unfit to drive because of a drug. (c) And is committing or has committed a moving traffic offence. (d) Or has been involved in an accident and the constable has reasonable cause to believe that the person driving was attempting to drive or in charge of that motor vehicle. And without reasonable excuse fails to co-operate with a preliminary test, shall be guilty of an offence. NB Note that the offence extends only to a motor vehicle and not a mechanically propelled vehicle.
Section 6B(1)
A constable administering a preliminary impairment test, shall observe the person in the performance of tasks specified by the constable, and makes such observations about the persons physical state as the constable thinks expedient. Data from Levine B (1999) Principles of Forensic Toxicology. American Association for Clinical Chemistry, USA.
impaired is based upon all the available evidence. This includes: . proof of driving and the circumstances that led to the driver being stopped by the police, e.g., a traffic offense, an accident, or erratic driving . the interview with the driver, e.g., the manner of speech, demeanor, etc. . evidence that may come from any independent witnesses . application of drug recognition techniques . administration of a field impairment test . the professional judgment of the police officer as to whether or not the driver is impaired. Further safeguards against a wrongful conviction, following arrest on suspicion for an offense under section 4, are built into the police station procedures. Before an officer can require a blood or urine sample from a suspect, an FP must determine and advise the officer that the driver has a condition that might be due to some drug (Section 7 (3) (c) Road Traffic Act 1988). The examination by the FP is used to determine whether the apparent impairment of a driver might be due to some other condition (e.g., disease, injury, or infirmity). Without the advice of the FP, an officer cannot require a driver to provide a specimen of blood or urine for analysis. Therefore, although the application of FIT at the roadside may indicate a degree of impairment, it would not be used in isolation of the other available evidence. In summary, the determination of impairment is the decision of the court, based on the evidence placed before it, which may be provided by bystanders, police officers, an FP, and finally the results of any toxicological analysis undertaken. The provisions of the Railways and Transport Safety Act have not changed this legal requirement.
Field Impairment Testing
assessment of horizontal and vertical gaze nystagmus, is replaced by examination of the pupils. This was thought to be more appropriate for European conditions. Many of the most reliable and useful psychophysical tests utilize the concept of divided attention to ascertain if a persons ability to drive is impaired. Driving is a complex divided-attention task composed of many subconscious and conscious actions. The typical mental and physical activity that a driver must be able to do is to carry out tasks that divide the persons attention. Impairment tests that simulate divided-attention characteristics have a good chance of identifying the impaired driver. The best of these tests exercises the same mental and physical functions that a person needs to drive safely, i.e.: . . . . . . . information-processing short-term memory judgment and decision-making balance clear vision small-muscle control coordination of limbs.
The Railways and Transport Safety Act 2003 requires a Code of Practice for the administration of impairment tests for drivers. Although the FITs described below have been applied in a formalized way since their introduction in 2000, there were minor differences in the application of these tests in Scotland, and England and Wales. In the Railways and Transport Safety Act 2003 the tests are described as preliminary impairment tests and the Code of Practice will describe them as such. In all other respects they will be identical to the FIT described above. The FIT assessment used in the UK and Europe is essentially identical to the US SFST assessment except that the first test in the SFST, which is an
Drug consumption can substantially degrade a persons ability to divide attention. Under the influence of drugs or alcohol, drivers often ignore the less critical components of the driving task in order to concentrate their attention on the more vital driving tasks. However, different drugs affect different aspects of the skills required for safe driving in different ways. Alcohol has a more detrimental effect on the control processes of driving, e.g., hazard perception, whereas cannabis first affects detrimentally the automatic process of driving, e.g., steering ability. Any test that requires a person to demonstrate two or more of these capabilities simultaneously is potentially a good psychophysical test. The tests must also be relatively simple to perform when sober, but sufficiently complex to divide the persons attention when not sober. The preliminary impairment test process is a systematic and standardized method of examining a subject to determine whether or not that person is impaired. A trained officer will never reach a conclusion based upon one element of the examination, but instead on the totality of facts that emerge. The tests carried out by a police officer or FP involve examination of the persons eyes, the pupillary examination, followed by four psychophysical tests: 1. 2. 3. 4. the modified Romberg balance test the walk-and-turn test the one-leg-stand test the finger-to-nose test. A brief description of the tests is given below.
The pupillary examination In the UK police officers are not currently permitted to carry out any tests on the eye other than pupil comparison. In the USA the SFSTs make use of horizontal and vertical gaze nystagmus tests, which have been shown to be sensitive to impairment by alcohol and certain other drugs. The size of a persons pupils is compared against a standard pupil size chart. Under normal circumstances the size of pupils is between 3 and 6.5 mm. The tests can be conducted in most lighting conditions, although they should not be conducted in direct sunlight. In order to instruct the person as to the nature of the pupillary examination and how the individual is expected to perform, this and the following divided-attention tasks are carried out according to formalized wording. This is given in the National Manual of Guidance form, Drink Drive, F (MG/ DD/F) (see Table 2). It is accepted that both pupil dilation and constriction are not only drug-induced, and that there may be some medical conditions, or the use of prescribed medicines, that may cause the size of a persons pupils to change. Drug recognition officers are acquainted with these medical causes as part of their training. The psychophysical tests The four psychophysical or divided-attention tests adopted by the UK police follow systematic administration, documentation, and interpretation. The tests require a reasonably smooth and flat surface. To be able to perform the tests, the subject should be free of any physical disability. Such disabilities may include inner-ear disorders, obesity, and disabilities due to aging. However, it will not preclude any of the tests being carried out as long as they are taken into consideration when the evaluation is made. The observational indicators of impairment for the walk-and-turn test and the one-leg-stand test have been validated through various trials and studies in the USA carried out since 1977. These studies validated the observations made by DREs and SFST officers in both laboratory and field conditions. The modified Romberg balance test The Romberg (or Rhomberg) test is an indicator of the state of the suspects internal clock and ability to balance. The administration of certain drugs will either speed up or slow down the suspects internal clock and may cause the suspect to sway from side to side, back to front, or round in a circle. The test comprises two stages: the instructions stage and the performance stage. During the instructions stage the suspect is asked to stand up straight with feet together, both heels and toes, with hands down
by the sides. The performance stage involves the subject standing in the start position, but with the head tilted backwards slightly and eyes closed. During the test the subject must estimate the passage of 30 s. The officer should time the test for 30 s and record the results. Any estimation of between 25 and 35 s is considered to be acceptable for most people; however experience has shown that this is not always the case and the officer should review the results in the light of evidence seen in the other tests. Some authorities consider estimations between 20 and 40 s to be acceptable. The test should be terminated if it cannot be completed in safety or the actual time exceeds 90 s. The major observations which need to be recorded for this test are: 1. the subjects inability to follow instructions 2. an inability to stand still or steady with feet together 3. body/eyelid tremors 4. body sway 5. the amount of time that has passed between start and end of the test 6. any statement or unusual sounds made by the subject while performing the test. The walk-and-turn test This test requires the subject to stand with the heel of one foot touching the toe of the other foot. The individual is asked to walk along a real or imaginary line and must turn in the prescribed manner. It is a test that divides attention between balancing and information-processing. The test comprises two stages: the instructions stage and the walking stage. During the instructions stage, the subject is told to stand with the right foot in front of the left, touching heel to toe. The subject must remain in that position while the rest of the instructions for the test are given. Experience has shown that the subject, if significantly impaired, will find it progressively difficult to remain in that position and will step out of the position. The walking stage involves the subject walking nine heel-to-toe steps along the line, turning about in the manner demonstrated and then taking another nine heel-to-toe steps back along the line. During the walking the subject should count each step out loud and not stop while walking. Both stages are important parts of the test and evidence often comes to light during both stages. Of all of the preliminary impairment tests, this test is generally considered amongst drug recognition experts to provide the most comprehensive observational indicators of impairment.

Table 2 THE PRELIMINARY IMPAIRMENT TESTS INSTRUCTIONS TO SUBJECT (Reproduced by permission of the Home Office)
(Important Note the words reproduced below relate to the current MG/DD/F, following the enabling legislation for Section 107 and Schedule 7 Railways & Transport Safety Act 2003, which amends Section 6 Road Traffic Act, this form of words will change to reflect the new legislation.)
Table 2 Continued ONE LEG STAND

Stand with your feet together and your arms by your sides. Maintain that position while I give you the remaining instructions. Do not begin until I tell you to start. Do you understand? YES/NO When I tell you to start you must raise your right foot six to eight inches off the ground, keeping your leg straight and your toes pointing forward, with your foot parallel to the ground (demonstrate). You must keep your arms by your sides and keep looking at your elevated foot while counting out loud in the following manner, one thousand and one, one thousand and two and so on until I tell you to stop. Do you understand? YES/NO
Additional Warning
I would like you to perform a series of tests to enable me to ascertain whether there are grounds to suspect your ability to drive is impaired by drink or drugs. (I must tell you that you are not under arrest and you need not remain with me.) You are not obliged to participate in the tests but if you do participate, the results may be given in evidence. The tests are simple and part of my evaluation will be based on your ability to follow instructions. If you do not understand any of the instructions, please tell me so that I can clarify them. Not to be read if the person has
Repeat procedure with each foot FINGER AND NOSE TEST

Stand with your feet together and your arms in this position. (demonstrate extending both hands out in front, palms side up and closed with the index finger of both hands extended). Maintain that position while I give you the remaining instructions. Do not begin until I tell you to start. When I tell you to start you must tilt your head back slightly (demonstrate) and close your eyes. When I tell you which hand to move, you must touch the tip of your nose with the tip of that finger and lower your hand once you have done so (demonstrate). Do you understand? YES/NO
already been arrested

Do you understand? YES/NO Do you agree to participate in these tests? YES/NO As I explain the tests to you, if you have any medical condition or disability which may affect your ability to undertake the test or its result, please tell me before the test is started. Do you understand? YES/NO Do you have any medical condition or disability that you wish to tell me about before I start the tests? YES/NO
Call out the hands in the following order, left, right, left, right, right, left. Data from Levine B (1999) Principles of Forensic Toxicology. American Association for Clinical Chemistry, USA.
PUPILLARY EXAMINATION
I am going to examine the size of your pupils, comparing them to this gauge, which I will hold up to the side of your face. All I require you to do is look straight ahead and keep your eyes open. Do you understand? YES/NO
Indicate L and R on the pupil gauge for pupil size as appropriate Note condition of eyes: Watery YES/NO Reddening YES/NO ROMBERG TEST
Stand up straight with your feet together and your arms down by your sides. Maintain that position while I give you the remaining instructions. Do not begin until I tell you to do so. When I tell you to start, you must tilt your head back slightly and close your eyes (demonstrate but do not close your eyes). Keep your head tilted backwards with your eyes closed until you think that 30 seconds has passed, then bring your head forward and say Stop . Do you understand? YES/NO
There are eight validated observations for this test. The first two observations are checked strictly during the instructions stage and can only be accumulated once. The next six observations are checked during the performance stage: 1. lack of balance during instructions 2. starts walking too soon 3. misses heel to toe (to document this observation a gap of at least 112 cm (0.5 in.) is necessary) 4. steps off the line 5. stops walking (includes pauses to regain balance) 6. raises arms to balance (a movement of more than 15 cm (6 in.) is required) 7. takes the wrong number of steps (mistakes in the verbal count do not justify an observation) 8. turns improperly (this observation should be documented if the subject staggers, stumbles, or falls during the turning movement, or if the subject turns in any other way than instructed). The one-leg-stand test This test requires the subject to stand on one leg whilst the other leg is extended out in front and 1520 cm (68 in.) off the ground. The test requires the subject to divide attention between balance and counting and again comprises two stages. The instructions stage requires the subject to stand in the modified position of attention as seen in
WALK AND TURN TEST Identify a real or imaginary line. Do not use a kerb or anywhere the subject may fall. Place your left foot on the line.
Place your right foot on the line in front of your left touching heel to toe (demonstrate). Put your arms by your sides and keep them there throughout the entire test. Maintain that position whilst I give you the remaining instructions. Do you understand? YES/NO When I say start, you must take nine heel to toe steps along the line. On each step the heel of the foot must be placed against the toe of the other foot (demonstrate). When the ninth step has been taken, you must leave the front foot on the line and turn around using a series of small steps with the other foot. After turning you must take another nine heel to toe steps along the line. You must watch your feet at all times and count each step out loud. Once you start walking do not stop until you have completed the test. (demonstrate complete test) Do you understand? YES/NO
previous tests and to remain in this position until the instructions are completed. During the balance and counting stage, the subject, when told to start, raises the right foot 15 20 cm (68 in.) off the ground, keeping the leg straight and the toes pointing forward. During this time the individual should count out loud in the following manner one thousand and one, one thousand and two and so on until told to stop. There are four validated observational indicators to this test: 1. places foot on ground 2. raises arms (more than 15 cm (6 in.)) to balance 3. sways, whether from front to back or side to side. This requires a very noticeable sway or rotational movement of the subjects elevated foot or body 4. hopping. The test may be terminated if the subject cannot complete it safely. The observer should take note of any body tremors or any statement made by the subject during the test. The finger-to-nose test The finger-to-nose test is a test of coordination and depth perception. Certain drugs may cause the subject to have an altered depth perception, whilst others will cause slow and lethargic movement, whereby the subject will misjudge the location of the nose completely. This test requires the subject to bring the tip of the index finger up to touch the tip of the nose, with the head tilted backwards and eyes closed. The finger-to-nose test differs from other tests in that the examiner will continue to instruct the subject throughout the test. During the instructions stage the subject is told to stand upright with feet together. He/she must extend both hands with the index finger extended and the rest of the fist closed. During the command stage the subject is told to touch the tip of the nose with the tip of the finger as indicated by the examiner, in the following sequence, left, right, left, right, right, left. The finger-to-nose test is not considered to the same extent of validated observational indicators as the other tests. However, experience has shown that individuals who are impaired sometimes miss the tip of their nose and sometimes fail to use the hand indicated. The examiner may see the following: 1. Where did the tip of the finger touch? This shows the subjects depth perception when attempting to touch the nose. Was the speed of bringing the finger to the nose slow or fast, for example was the subject fishing for the end of the nose, or did
the subject poke the face as a result of misjudging the nose in space? 2. Was the correct hand used? 3. Was there body sway? 4. Was the subject able to follow instructions? The formal administration of these tests as required by the UK Home Office is shown in Table 2.
Drug Recognition Training

For the purposes of drug influence recognition training, the World Health Organization provides the most concise definition of a drug: Any substance that, if taken into a living organism, may modify one or more of its functions. Drugs can be categorized according to many factors, one of which is the visible signs and symptoms that result from a person taking a substance. For the purpose of drug influence recognition there are six main drug groups: 1. 2. 3. 4. 5. 6. cannabis opiates central nervous system (CNS) stimulants CNS depressants hallucinogens inhalants.
Cannabis
Cannabis derives primarily from the various species of the plant Cannabis sativa. The principal psychoactive ingredients in cannabis are: 1. delta-9-tetrahydrocannabinol (D9 THC), commonly referred to as THC 2. delta-8-tetrahydrocannabinol (D8 THC) is also a psychoactive, but minor, constituent of cannabis 3. 9-carboxy-THC (THC-COOH) is the most common and rapidly produced metabolite but it is not psychoactive. Possible effects of cannabis From the viewpoint of driving, studies with cannabis show that it first seems to affect all tasks requiring psychomotor skills and continuous attention. Thus, tracking tasks, which are very sensitive to short-term changes in attention, are sensitive to cannabis impairment. Alternatively, integration processes and higher cognitive functions are not as time-critical. A short attention lapse can be compensated for by increased activity later. In the case of the overall driving task, it seems that the negative effects of these short-term distortions can be reduced by lowering the difficulty, and hence
the time-critical aspects, of the task. This would explain the frequently reported observation that drivers under the influence of cannabis drive at notably reduced speeds. A recent study suggests that drivers under the influence of cannabis were aware of their impairment and attempted to drive more cautiously, but reacted more slowly to other driving tasks, e.g., braking. It confirmed that cannabis has a measurable effect on psychomotor performance and tracking ability. Onset and duration of effects Subjects will begin to feel and exhibit the effects of cannabis intoxication within seconds of inhaling the smoke; peak plasma levels are reached between 7 and 10 min. The impairment effects usually peak 25 min after smoking. Substantial effects have usually worn off after 1 h, but some measurable impairment may continue up to 4 h. Blood tests may well disclose the presence of THC long after the effects have worn off. The common immunoassay tests for THC look for the metabolites of the drug, principally THC-COOH. Blood tests may disclose the presence of this metabolite at least 3 days after smoking and some urine tests may indicate the presence of THC metabolites for 2845 days. Cannabis expected roadside observations . . . . . . . . . smell characteristic poor coordination and balance impaired perception of time and distance whites of eyes (sclera) markedly reddish increased appetite disorientation poor attention span relaxed inhibitions pupils possibly dilated.
People develop tolerance for opiates fairly rapidly. An opiate user who has developed tolerance and who has taken his/her normal dose for the drug may exhibit little evidence of intellectual or physical impairment. For example, a heroin addict who may have taken the usual dose may be able to drive without apparent detrimental effect and perform adequately on the impairment tests. Cancer patients who are treated with opiates also may not exhibit impairment, owing to marked tolerance development. Onset and duration of effects Dependent upon the particular substance, opiates can be injected, smoked, or taken orally. The onset will be within seconds if injected or smoked, although longer if taken orally. The psychological effects include a feeling of pleasure or euphoria; and relief from pain. The duration of the effects will vary greatly depending on the substance, the manner of consumption, and tolerance of the user. Generally, opiate effects will last 46 h, except methadone, which lasts up to 12 h. Opiates are detectable in the blood for the period of time of influence. Certain opiate derivatives, e.g., heroin, are converted back to morphine after ingestion. As the physical effects begin to disappear, withdrawal signs start to emerge. These withdrawal signs can become severe if the user does not take another dose. Opiates expected roadside observations . . . . . . . . . constricted pupils (characteristic of opiates) hippus may be present during withdrawal sleepy appearance (ptosis) slow reflexes low, slow speech possible facial itching dry mouth possible euphoria cold skin.
Opiates (Opioids)
The term opiate is derived from drugs obtained from the opium poppy (Papaver somniferum). Morphine is found in opium and is a natural alkaloid. Heroin (diamorphine) is the most widely abused opium derivative. A second subcategory of synthetic opiates is produced from a variety of nonopiate substances. The best known of these is methadone. Possible effects of opiates The effects that an opiate user will experience and exhibit depend on the tolerance that the user has developed for the drug.
Central Nervous System Stimulants
CNS stimulants can be defined as those drugs that speed up the activity of the CNS (Table 3). Cocaine Cocaine is a substance that occurs in the leaves of several species of plant, including a plant bush (Erythroxylon coca) found in South America. In common use, it is usually found in powder form, although in recent years, crack (named after the crackling sound it makes as it is being produced) is also prevalent. Cocaine powder is usually snorted or injected although, as with crack, it can be smoked.

Table 3 Central nervous system stimulants: onset and duration of effects
Stimulant Means of administration Onset Duration
Amphetamine Methamphetamine Ecstasy Cocaine Cocaine Cocaine
Injected By mouth Smoked Injected Snorted
Seconds 2030 min Seconds Seconds 30 s (not as fast as smoked or injected cocaine)
48 h 46 h 510 min 4590 min 3090 min
Amphetamines Medically used amphetamines are generally produced in tablet and capsule form and are used to treat various conditions, from hyperactivity to appetite control. The illicit form common to the UK is amphetamine sulfate, which is usually found in powder form and can be injected, smoked, or inhaled. Methamphetamine and dexamphetamine are also widely abused. Ecstasy and ecstasy analogs The two most common ecstasy analogs are 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) and methylenedioxyamphetamine (MDA). Possible effects of CNS stimulants Cocaine and amphetamines produce euphoria. A feeling of super strength and absolute self-confidence may also be present. With cocaine, but not with amphetamine, there will also be an anesthetic effect, i.e., a dulling of pain. Stimulant users tend to become hyperactive, extremely nervous, and unable to stand still. Onset and duration of effects Stimulants can be snorted, injected, or smoked, with the normal method of ingestion for amphetamine sulfate being injection, while ecstasy is taken in tablet form. In general, cocaine is a fairly fast-acting, but shortduration drug. Because of this a user can present some difficulty to the trained officer. The suspect may be markedly impaired when arrested, but by the time he/ she is seen by the FP, the effects of the cocaine may have worn off. It is therefore imperative that a full record is made at the time of the arrest so the examiner can see that there is a change in the suspects demeanor. Central nervous system stimulants expected roadside observations . . . . . . dilated pupils eyelid tremors restlessness/anxiety inability to keep quiet euphoria easily irritated
. grinding teeth (bruxism) . impaired perception of time.

Central Nervous System Depressants
CNS depressants can be defined as those drugs that slow down the activity of the CNS. They first affect those areas of the brain that control a persons conscious, voluntary actions (control processes). Alcohol Alcohol is the most common, and most widely abused, CNS depressant. With some notable exceptions, most CNS depressants have effects similar to alcohol. Benzodiazepines Benzodiazepines are generally designed to be taken orally; however many illicit users may break tablets down for injection purposes. Gamma-hydroxybutyrate (GHB) GHB is most often available as an odorless and colorless liquid with a salty taste. Possible effects of CNS depressants CNS depressants have general effects similar to alcohol, namely reduced social inhibition, slowed reflexes, impaired judgment and concentration and coordination. Speech may be slurred, mumbled, and incoherent. Paradoxical behavior may occur, such as euphoria, depression, laughing, or crying for no apparent reason. Onset and duration of CNS depressants CNS depressants subject to misuse are short-, medium-, or long-acting. Onset and duration are as follows: Short-acting Effects are apparent in 1015 min, and dissipate in around 4 h. Intermediate-acting and last 68 h. Effects are apparent in 30 min,
Long-acting Effects are seen after an hour and last for between 8 and 14 h.
Central nervous system depressants expected roadside observations . . . . . . normal pupil size (but may be dilated) watery eyes droopy eyelids (ptosis) drowsiness thick, slurred, slow speech uncoordinated slow, sluggish reactions.
a controlled environment as bad stimuli and good stimuli are magnified. Flashbacks may occur; this is the reemergence of some aspect of the hallucinogen experience in the absence of the drug. One common type of hallucination produced by these drugs is synthesthesia, which is a transposing of sensory modes. For example, seeing a particular sight may cause the user to perceive sound. Onset and duration of effects LSD will take effect within 2030 min of use while it will take longer with magic mushrooms, between 6090 min, before there is any noticeable effect. The effects from magic mushrooms will generally wear off after 3 h. LSD is relatively long-lasting and the effects could remain visible for anything up to 10 or 12 h. Hallucinogens expected roadside observations . . . . . . . . pupils possibly dilated dazed appearance uncoordinated poor balance distorted time and distance perception sweating, goosebumps (piloerection) paranoia nausea hallucinations/synthesthesia.
Hallucinogens
Hallucinogens can be defined as drugs that cause hallucinations. A hallucination can be defined as: a sensory experience of something that does not exist outside of the mind. It may involve hearing, seeing, smelling, tasting, or feeling something that isnt really there, or it may involve distorted sensory perceptions. Ketamine Ketamine is a dissociative anesthetic and also a CNS depressant, but may produce hallucinations. It is used as a veterinary anesthetic, and is frequently abused. It is found as capsules, powder, crystals, or tablets. Phenyl cyclohexl piperidine (PCP) Commonly contracted to phencyclidine (PCP or angel dust) is found as a white crystalline powder. Depending on dose, it can act as an anesthetic, depressant, stimulant, or hallucinogen. It was formerly used as a veterinary anesthetic. Lysergic acid diethylamide Lysergic acid diethylamide (LSD) is a synthetically prepared hallucinogen and has no medical use. In its pure form it is a white, odorless crystalline powder. In the UK, however, it is most commonly found converted into its liquid form and applied to blotting-paper squares or tabs. It is the most common form of hallucinogen and probably the best known. Magic mushrooms (psilocybin) Psilocybin is a naturally occurring hallucinogenic drug that can be found in various species of wild-growing mushrooms, in the UK notably the liberty cap. These mushrooms can be eaten fresh or allowed to dry and eaten later. These mushrooms contain two related compounds: 1. psilocin (4-hydroxy-N,N-dimethyltryptamine) 2. psilocybin (4-phosphoryloxy-N,N dimethyltryptamine). Possible effects of hallucinogens Hallucinogens allow the human senses to experience stimuli at a much greater intensity than normal. As a result, many people take great care to take hallucinogens in
Inhalants
Inhalants are breathable chemicals that produce mindaltering effects. The most common types of inhalants encountered in the UK are volatile solvents and aerosols. Volatile solvents comprise a large number of readily available substances such as glue, paints, nail varnish remover, thinners, and lacquers. They are described as volatile because the solvent evaporates in the air. The commonest active ingredient in solvents is toluene. Aerosols are chemicals that are discharged from a pressurized container. Intoxicating effects are more often caused by the propellant as opposed to the chemical for which the product was sold. Commonly abused aerosols include hairsprays, deodorants, and insecticides. Abused aerosols contain various hydrocarbon gases, principally butane and propane, that produce drug-like effects. Some inhalant users prefer to put the volatile solvent in a plastic bag or crisp packet; others soak rags or socks and then sniff the fumes. Possible effects of inhalants Inhalants generally produce acute intoxication similar to alcohol. Nausea, vomiting, sneezing, and coughing may occur. There may also be giddiness, tachycardia, sedation, poor coordination, and slurred speech.
ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/General 21
Onset of effects and duration of effects Inhalants are all ingested orally by inhaling the vapors and the effects are felt almost immediately. The duration of the effects ranges from a few seconds up to 2 h, depending on the substance used. Glue, paint, petrol, and other commonly abused inhalants could last up to 8 h. Inhalants expected roadside observations . . . . . . . . . . pupils possibly dilated dizzy/light-headed/nausea smell residue around face bloodshot, watery eyes disorientation and confusion distorted time and distance perception flushed, sweaty appearance intense headache noncommunicative/slurred speech.
See Also
Road Traffic, Determination of Fitness To Drive: General; Driving Offense; Road Traffic, Global Overview of Drug and Alcohol Statistics
Everest JT, Tunbridge RJ, Widdop B (1989) The Incidence of Drugs in Road Accident Fatalities. TRRL report RR202. Crowthorne, UK: Transport and Road Research Laboratory. Fleming P, Stewart D (1998) Drugs and Driving: Training Implications for Police Officers and Police Surgeons. Police Research Group. London: Home Office. Sexton BF, Tunbridge RJ, Brook-Carter N, et al. (2000) The Incidence of Cannabis on Driving. TRL report 477. Crowthorne, UK: Transport Research Laboratory. Tharp L, Burns M, Moskowitz H (1981) Development and Field Test of Psychophysical Tests for DWI Arrests. US Department of Transportation report no. DOT-HS805-864. Los Angeles, CA: Southern California Research Institute. Townley L, Ede R, Collier SG (2003) Forensic Practice in Criminal Cases, Chapter 14, Drugs, Toxicology & Related Areas of Expertise. London: The Law Society. Tunbridge RJ, Keigan M, James FJ (2000) Recognising Drug Use and Drug Related Impairment in Drivers at the Roadside. TRL report 464. Crowthorne, UK: Transport Research Laboratory. Tunbridge RJ, Keigan M, James FJ (2001) The Incidence of Drugs and Alcohol in Road Accident Fatalities. TRL report 495. Crowthorne, UK: Transport Research Laboratory. Walsh JM, Cangianell LA (undated) New Training in Illicit Drug Detection in Drivers. Bethesda, MD: The Walsh Groups.
Further Reading
Anonymous (2002) Drug Evaluation and Classification Training, Instructors Manual. Washington, DC: National Highways, Transport Safety Administration (NHTSA)/ International Association of Chiefs of Police (IACP). Anderson S, Schweitz L, Snyder E (1983) Field Evaluation of Behavioural Test Battery for DWI. US Department of Transportation report no. DOT-HS-806-475. Washington, DC: US Department of Transportation. Boorman M (2000) Detection of Drug Impaired Drivers SFST. Melbourne, Australia: Traffic Alcohol Section, Technical Unit, Victoria Police. Burns M, Dioquino (1997) A Florida Validation study of SFSTs. US Department of Transportation Report No AL-97-05-14-01. Burns M, Pitkin (1995) Colerado validation study of the SFST Battery. Colorado Department of Transportation Report. Burns M, Moskowitz H (1977) Psychophysical Tests for DWI. US Department of Transportation report no. DOTHS-802-424. Los Angeles, CA: Southern California Research Institute. Collier SG (2004) National Drug Recognition & Field Impairment Testing Aide Memoir. Newnham, UK: New Police Bookshop. Collier SG (2004) Drug Influence Recognition & Field Impairment Testing A Review of the Scientific Evidence of Effectiveness. Unpublished but available from author.
General
C H Wecht and S A Koehler, Allegheny County Coroner, Pittsburgh, PA, USA
Introduction
This article will review medical conditions and medications that may impair the drivers performance. The role of the physician in assessing drivers fitness, and methods of assessing and screening in the USA and other countries are also reviewed. This article will also provide an overview of the US population aged 65 and over, the causes of mortality among the elderly, and an analysis of elderly drivers.
Determination of Driver Fitness

Drivers Family and Caregivers Insight into Their Deficits
Drivers, especially those with cognitive disorders such as dementia and Parkinson disease (PD), tend to overestimate their driving performance abilities and are
22 ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/General
less likely to report driving problems to their physicians. These drivers seldom stop driving on their own. More commonly, they have stopped after intervention by family (24%), family and patient jointly (13%), the family doctor (18%), or memory clinic (11%). Almost half the patients found to be demented while undergoing first-time evaluations in a geriatric clinic were still driving; younger and male demented drivers were less likely to stop driving despite significant cognitive impairment. A high percentage of individuals with Alzheimer disease (AD) who failed a road test for driving competency considered themselves to be safe drivers. Family and other caregivers also provided an unreliable assessment of the perceptions of the driving ability of impaired drivers. Studies have found long periods between the caregivers perception that the patient should stop driving and actual cessation up to 4 years in some cases. Therefore, it is the role of the physician to determine the medical fitness of the driver.
Role of the Medical Community in Assessing Driving Fitness
Guide to Assessing and Counseling Older Drivers at www.ama-assn.org/go/olderdrivers. Below are some medical conditions that physicians should be aware of that may impair a drivers ability to operate a motor vehicle safely and the degree of restriction these conditions entail.
Cardiovascular Medical Conditions That May Impair the Driver

Atrial Flutter/Fibrillation (Bradycardia or Rapid Ventricular Response)
Once the heart rate and symptoms have been treated, there should be no restrictions on driving privileges.
Cardiac Conditions That Cause Sudden, Unpredictable Loss of Consciousness
Physicians play a key role in determining if their patients should continue their driving privileges. Therefore, they require knowledge of driving reporting laws, skill in identifying risky drivers, and in counseling patient and family on strategies for driving cessation. In addition, they should know how to refer marginal drivers for driving training. When physicians are assessing the fitness of one of their patients, the physical examination should be directed toward the identification of any existing conditions and the degree of functional compromise. Medical or surgical control of the condition, duration of satisfactory control, and patient reliability are important considerations. However, it has been shown that the knowledge of doctors in reporting laws is weak. It has also been shown that 28% of all geriatricians do not know how to report patients with dementia who are potentially dangerous drivers. In 1999, the American Medical Association adopted a new ethical guideline stating that it is desirable and ethical for physicians to notify a state licencing authority about patients who, because of a medical condition, may be unsafe to drive. Physicians need knowledge of driving reporting laws and skills in identifying risky drivers and counseling patient and family on strategies for driving cessation. They should know how to refer marginal drivers for driving training. State-by-state criteria for the medical conditions that physicians are required to report, where to obtain the forms, and where to mail are available on the American Medical Association website entitled Physicians
The main consideration in determining medical fitness to drive for individuals with cardiac conditions is the risk of presyncope or syncope due to brady- or tachyarrhythmia. Where individuals have a known arrhythmia, the physician should identify and treat the underlying cause, if possible, and recommend temporary driving cessation until control of symptoms has been achieved.
Cardiac Disease from Structural or Functional Abnormality
Two major considerations in determining medical fitness to drive are the risk of presyncope or syncope due to low cardiac output and the presence of cognitive deficits due to chronic cerebral ischemia. Drivers who experience presyncope, syncope, extreme fatigue, or dyspnea at rest or at the wheel should cease driving. Physicians should refer patients with clinically significant cognitive changes for a cognitive testing and to a driving rehabilitation specialist (DRS) for evaluation. Cardiac surgery involving median sternotomy Drivers may resume driving 4 weeks after coronary artery bypass grafting (CABG) and/or valve replacement surgery, and within 8 weeks of heart transplant, depending on resolution of cardiac symptoms and the patients course of recovery. In the absence of surgical and postsurgical complications, the main limitation to driving is the risk of sternal disruption following median sternotomy. If clinically significant cognitive changes persist following the patients physical recovery, cognitive testing and fitness evaluated by a DRS are recommended before the patient is permitted to resume driving.
ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/General 23 Congestive Heart Failure
Physicians should reassess a drivers fitness with congestive heart failure (CHF) every 6 months or as needed depending on the clinical course and control of symptoms. Individuals with functional class III CHF (marked limitation of activity but no symptoms at rest, working capacity 24 METs (metabolic equivalents)) should be reassessed at least every 6 months.
High-Grade Atrioventricular (AV) Block
(EP) testing, and the VT is noninducible at repeated EP testing. Drivers may resume driving after 6 months without arrhythmic events if they are on empiric antiarrhythmic therapy (with or without an ICD), or have an ICD alone without additional antiarrhythmic therapy. No restrictions apply if the individual is asymptomatic during documented episodes.
Sick Sinus Syndrome, Sinus Bradycardial Sinus Exit Block, Sinus Arrest
Individuals with symptomatic AV block corrected without a pacemaker may only resume driving after they have been asymptomatic for 4 weeks and electrocardiogram (ECG) documentation shows resolution of the block.
Hypertrophic Obstructive Cardiomyopathy
Drivers who experience syncope or presyncope should stop driving until they have been treated.
Pacemaker
Individuals with symptomatic disease can be managed with pacemaker implantation. Physicians should be alert to clinically significant cognitive deficits due to chronic cerebral ischemia. Those with significant cognitive changes should be referred to a driver rehabilitation specialist for a driver evaluation. No restrictions apply if the individual is asymptomatic during documented episodes. Regular medical follow-up is recommended to monitor cardiac rhythm and cognitive abilities.
Sustained Ventricular Tachycardia
An individual may resume driving 1 week after pacemaker insertion if no longer experiencing presyncope or syncope; ECG shows normal sensing and capture; and pacemaker performs within the manufacturers specifications.
Paroxysmal Supraventricular Tachycardia or WolffParkinsonWhite Syndrome
Individuals with a history of symptomatic tachycardia may resume driving after being asymptomatic for 6 months and on antiarrhythmic therapy. Drivers who undergo radiofrequency ablation may resume driving after 6 months if there is no recurrence of symptoms, or sooner if no preexcitation or arrhythmias are detected on repeated electrophysiology testing. No restrictions apply if the individual is asymptomatic during documented episodes.
Percutaneous Transluminal Coronary Angioplasty (PTCA)
Individuals with VT may resume driving after 3 months if they are on antiarrhythmic therapy (with or without an ICD), guided by invasive EP testing, and VT is noninducible at repeated EP testing. Drivers may resume driving after 6 months without arrhythmic events if they are on empiric antiarrhythmic therapy (with and without an ICD), or have an ICD alone without additional antiarrythmic therapy.
Time-Limited Restrictions
The length of time of the driving restriction following cardiac procedures is based on the patients recovery from the procedure itself and from the underlying disease for which the procedure was performed.
Unstable Coronary Syndrome (Unstable Angina or Myocardial Infarction)
A driver may resume driving 48 h to a week after successful PTCA and/or stenting procedures, depending on the patients baseline conditions and course of recovery from the procedure and underlying coronary artery disease.
Prolonged, Nonsustained Ventricular Tachycardia (VT)
Individuals with unstable coronary syndrome should not drive if they experience symptoms at rest or at the wheel. Drivers may resume driving when they have been stable and asymptomatic for 14 weeks, as determined by a cardiologist following treatment of the underlying coronary disease. Drivers may resume within 1 week of successful revascularization by PTCA and 4 weeks after CABG.
Valvular Disease
Individuals with symptomatic VT may resume driving after 3 months if they are on antiarrhythmic therapy with or without an internal cardioverter defibrillator (ICD) guided by invasive electrophysiologic
Drivers who experience syncope or presyncope should stop driving until the underlying disease has been corrected.
Neurological Conditions That May Impair the Driver

Neurological conditions that can affect ones driving performance range from conditions that progress with time such as those caused by dementia, multiple sclerosis, and PD, and those that occur rapidly, caused by stroke and cerebrovascular accident. Insults to the cerebral vascular system may cause a wide variety of symptoms, including sensory deficits, motor deficits, and cognitive impairment. These symptoms range from mild to severe and may resolve almost immediately or persist for years. During evaluations the physician must take into account the individuals unique constellation of symptoms, severity of symptoms, course of recovery, and baseline functions when making recommendations concerning driving privileges. Among drivers, individuals with dementia are more likely to continue to drive even when it is highly unsafe for them to operate a vehicle.
Brain Tumors
driving privileges must be withheld. Physicians with patients that have a history of dementia are recommended to perform a focused medical assessment that includes history of driving difficulty from family members or caregiver and an evaluation of cognitive abilities, including memory, attention, judgment, and visuospatial abilities. Physicians should be aware that patients with progressive dementia require serial assessment, including a formal assessment of driving skills consisting of an on-road driving assessment performed by a DRS.
Recommendations to continue driving should be based on the type of tumor, location, rate of growth, type of treatment, presence of seizure, and presence of cognitive or perceptual impairment. Due to the progressive nature of certain types of tumors, the evaluation of fitness to drive needs to be done serially.
Dementia
Individuals with dementia are often undetected and undiagnosed until late in the course of the disease. Initially, family and physicians may assume that the individuals decline in cognitive function is part of the normal aging process. Physicians are encouraged to be alert to the signs and symptoms of dementia and to pursue an early diagnosis. Early diagnosis is the first step in promoting driving safety for a dementia patent. The second step is intervention, which includes medication to slow the course of the disease, and counseling to prepare the individual for eventual driving cessation. When the assessment shows that the driver poses a significant safety risk, driving must cease. With early planning among the patient, family, and driver, the transition between driving and nondriving can be less traumatic. The Alzheimers Association position statement on driving states:
A diagnosis of dementia is not, on its own, a sufficient reason to withdraw driving privileges. A significant number of drivers with dementia are found to be competent to drive in the early stages of the illness. Therefore, the determining factor in withdrawing driving privileges should be based on the individuals driving ability. When the individual poses a serious risk to self or others,
Dementia of the Alzheimer type (DAT) Individuals with DAT have revealed an increased driving accident rate even with questionable or mild severity. Accident statistics show an increased risk for those with very mild and mild DAT. A number of studies have shown that individuals with even very mild or mild DAT are 23 times more likely to be in a crash compared to healthy age-matched controls, and that a high percentage of these individuals stopped driving only after having an accident. Among persons with AD, the increase in crash risk develops toward the end of the third year and more than doubles in the fourth year. Patients who have had AD for more than 2 years should have their driving ability closely monitored if they are to continue driving as the overall risk to society increases over time. Optimum timing and type of screening for the cognitively impaired driver are still uncertain. Most recommend retesting every 6 months, although a clear-cut policy intended chiefly for primary care physicians is still lacking. In 1996, the California Department of Motor Vehicles revised its policy to revoke the drivers license automatically only of persons with moderate or advanced dementia, and to enable those with very mild dementia to demonstrate the capacity to drive through a reexamination process.
Migraine and Recurrent Headache Syndrome
Individuals with recurrent headaches should be cautioned against driving when experiencing neurologic manifestations (visual disturbances or dizziness), when distracted by pain, and while on any barbiturate, narcotic, or narcotic-like analgesic.
Multiple Sclerosis
Driving recommendations should be based on the types of symptoms and level of symptom involvement. Physicians should be alert to deficits that are subtle but have a strong potential to impair driving performance, such as muscle weakness, sensory loss, fatigue, cognitive or perceptual deficits, and symptoms of optic neuritis. Drivers evaluation should include an on-road driving assessment performed by
a DRS and serial evaluation as the patients symptoms evolve and progress.
Parkinson Disease
Individuals with advanced PD may be at increased risk of motor vehicle crashes due to both motor and cognitive dysfunction. Drivers typically complained particularly of difficulty managing pedals and assessing distances properly. Persons with mild PD experience problems with diminished visual contrast sensitivity, slower verbal learning, and slower setshifting and executive tasks, all of which theoretically might affect driving. In moderately advanced disease, once patients begin to suffer motor freezing, they also perform poorly on dual tasks; when quizzed while walking, both their stride length and verbal fluency decline, reflecting frontal lobe compromise. Driving recommendations should be based on the level of motor and cognitive syndrome involvement, patients response to treatment, and presence and extent of any medication side-effects. Serial physical and cognitive evaluations are recommended every 612 months due to the progressive nature of the disease. The driver assessment should consist of an on-road driving assessment performed by a DRS. The United Parkinson Disease Rating Scale (UPDRS) and the Trial Making B test results both correlated well with driving performance.
Peripheral Neuropathy
been seizure-free for 3 months. The 3 month interval may be lengthened or shortened based on the presence of favorable or unfavorable modifiers. The following modifiers would increase the interval: noncompliance with medications, alcohol and/or drug abuse in the past 3 months, an increased number of seizures in the past 12 months, previous bad driving record, structure brain lesions, noncorrectable brain function or metabolic condition, frequent seizures after seizure-free interval, and previous crashes due to seizures in the past 5 years. The optimal minimal seizure-free interval to minimize seizure-related crashes is still unknown. In the USA, the seizure-free interval mandated by regulatory authorities varies from 2 years to as little as 3 months. Currently, six states in the USA and five provinces in Canada mandate that the physician report to the state anyone with epilepsy. Patient with seizure and the law Health providers must counsel their patients about the imperativeness and advantages of reporting the seizure disorder to the appropriate licencing authority. Patients should understand that this process not only improves public safety but also shields the driver from litigation should he/she have a seizure while driving, provided that individuals have not been otherwise negligent. If patients do not report their disorder and recurrent seizures, and do not obtain the physicians statement, they may face civil liability and criminal prosecution in the event of an accident related to a seizure. In addition, if the physician believes that the patient has not self-reported and is endangering the public by driving, the physician should have the right to report the patient (with immunity). Moreover, the epileptic drivers insurance company may deny coverage for the accident, particularly when the facts show that the individual failed to take the prescribed antiepileptic medication appropriately. For those patients who have controlled their seizures successfully, the physician may offer a statement to the licencing authority, usually on specified forms, confirming that the individuals seizures are controlled. With this statement, the physician asserts the opinion that, if licenced to drive, the person will not present an unreasonable risk to public safety. Generally, state medical review boards then review the driving application and physician statement and render a decision on whether to grant the license. State laws protect the physician from liability for violating patient confidentiality for statements about driving risk presented to the state, provided the statement is made in good faith and with reasonable belief of its accuracy. However, filling out the forms for the state authority is not enough. Providers may ask
Lower-extremity deficits in sensation and proprioception may be exceedingly dangerous for driving, as the driver may be unable to control the foot pedals or may confuse the accelerator with the brake pedal. If deficits in sensation and proprioception are identified, referral to a DRS is recommended.
Seizure Disorder
Epidemiological studies have determined that the riskiest drivers with epilepsy were those who were the most noncompliant with their prescribed medications and were the most likely to drive illegally without a license. Studies found that over 50% of persons with epilepsy drove illegally without completing a sufficiently long seizure-free interval or did not report breakthrough seizures to their physicians in states with mandatory doctor-reporting requirements. Those persons with epilepsy who abuse alcohol are clearly at much higher risk. According to the Consensus Statements on Driving Licencing in Epilepsy, from the American Academy of Neurology, American Epilepsy Society, and the Epilepsy Foundation of America, individuals with seizure disorder should not drive until they have
patients to sign in the medical record that they have received and understood counseling about driving risks and their obligations to report their disorder. Providers have an obligation to use reasonable care to protect potential victims and prevent harm to the public. Physicians who fail to counsel patients about driving risks from uncontrolled seizures, or who fail to document such counseling, may face future direct liability exposure, even to other individuals and third parties injured in seizure-related accidents.
Stroke
until they have undergone medical assessment and appropriate treatment.
Traumatic Brain Injury That May Impair the Driver

Individuals with traumatic brain injury should not drive until symptoms have stabilized or resolved. Traditionally, most driving rehabilitation programs have focused on the operational level, with emphasis on handling the vehicle and use of controls and mirrors, rather than tactical and strategic skills, where the deficits may lie for drivers with traumatic brain injury.
Vascular Malformation
Individuals with a history of stroke are at an increased driving-related risk due to decreased cognitive and psychomotor abilities. Individuals with acute motor, sensory, or cognitive deficits should not drive. Depending on the severity of residual symptoms and the degree of recovery, the driving restrictions may be permanent or temporary. All drivers with moderate to severe residual hemiparesis should be prohibited from driving before undergoing driving assessment. Even if symptoms improve to the extent that they are mild or completely resolved, the individual should undergo a driver assessment test such as the Washington University Road Test, as reaction time may continue to be affected. Perceptual tests such as the Motor-free Visual Perception Test (MVPT) and Trail Making B Test have also been shown to be predictive of on-road performance.
Subarachnoid Hemorrhage
Following the detection of a brain aneurysm or arteriovenous malformation, the individual should cease driving until assessed by a neurosurgeon. The individual may resume driving if the risk of a bleed is small, an embolization procedure has been successfully completed, and/or the patient is free of medical contraindications to driving, such as uncontrolled seizures or significant perceptual or cognitive impairment.
Metabolic Conditions That May Impair the Driver

Individuals in the acute phase of metabolic disorders (diabetes, Cushing disease, Addison disease, hyperfunction of the adrenal medulla, and thyroid disorder) may experience signs and symptoms that are incompatible with safe driving.
Insulin-Dependent Diabetes Mellitus
Individuals with subarachnoid hemorrhage should not drive until symptoms have stabilized or resolved, and following a medical assessment performed by a DRS.
Syncope
Syncope may result from various cardiovascular and noncardiovascular causes; it is recurrent in up to 33% of cases. The most common cause of syncope is cardiac arrhythmias. Driving restrictions for neurally mediated syncope should be based on the severity of the presenting event. No driving restrictions are necessary for infrequent syncope that occurs with warning and with clear precipitating causes. Individuals with severe syncope may resume driving after adequate control of the arrhythmia has been documented and/or pacemaker implantation. Driving cessation is recommended for individuals who continue to experience unpredictable symptoms after treatment with medications and pacemaker insertion.
Transient Ischemic Attacks
In individuals demonstrating satisfactory control of the diabetes, able to recognize the warning symptoms of hypoglycemia, and meeting visual standards, there are no restrictions for operating a motor vehicle. Drivers should not drive during acute hypoglycemic and hyperglycemic episodes. Individuals who experience recurrent hypoglycemic or hyperglycemic attacks should not drive until they have been free of significant hypoglycemic or hyperglycemic attacks for 3 months.
Noninsulin-Dependent Diabetes Mellitus
If the drivers condition is managed by lifestyle changes and/or oral medication, there are no restrictions to driving privileges.
Hypothyroidism
Individuals who experience a single or recurrent transient ischemic attacks should refrain from driving
If the hypothyroidism condition is not treated satisfactorily, the following symptoms may compromise
safe driving: cognitive impairment, drowsiness, and fatigue. If residual cognitive deficits continue despite treatment, the individual may consider on-road assessment performed by a DRS.
Respiratory Conditions That May Impair the Driver

Chronic Obstructive Pulmonary Disease (COPD)
Individuals with COPD should not drive if they suffer dyspnea at rest or at the wheel (even with supplemental oxygen), excessive fatigue, or have significant cognitive impairment. If individuals require supplemental oxygen to maintain a hemoglobin saturation of 90% or greater, they should use oxygen at all times while driving. Due to the often tenuous oxygenation status of these individuals, they should be counseled to avoid driving when they have other respiratory symptoms that may indicate concomitant illness or exacerbation of COPD (new cough, increased sputum production, change in sputum color or fever). Because COPD is a progressive disease, periodic reevaluations for symptoms and oxygenation status are required. Driver assessment should consist of an on-road driving assessment performed by a DRS with the drivers oxygen saturation measured during the on-road assessment.
Texas, and Utah have guidelines for narcolepsy. Physicians may consider using scoring tools such as the Epworth Sleepiness Scale to assess the patients level of daytime drowsiness. In 1991, the US Federal Highway Administration recommended that drivers with suspected or untreated sleep apnea not be medically qualified for commercial motor vehicle operation until the diagnosis has been eliminated or adequately treated. Two states, California and Texas, currently have guidelines addressing sleep apnea. Currently, the impact of these regulations on crash rates or on the practice of sleep medicine has not been assessed.
Sensory Conditions That May Impair the Driver

Visual Acuity
Renal Condition That May Impair the Driver

Chronic Renal Disease
Drivers with chronic renal disease have no restrictions unless they experience symptoms such as cognitive impairment, impaired psychomotor function, seizures, or extreme fatigue from anemia. Individuals who require hemodialysis can drive without restriction if they comply with nutrition and fluid restriction. Certain medications used to treat the side-effects of hemodialysis may cause impairment to ones driving ability. In addition, the dialysis itself may result in hypotension, confusion, or agitation in many patients. These effects may require avoiding driving during the immediate postdialysis period. If the physician is concerned, the patient should take an on-road driving assessment performed by a DRS.
The NHTSA (National Highway Traffic Safety Administration) has established guidelines for unrestricted drivers license and states that a driver must have 20/25 static near visual acuity in each eye (with correction less than 10 D), monocular visual fields of 120 in each eye, and binocular visual fields of 70 to the right and to the left in the horizontal meridian. Many common eye conditions require special consideration but lack set standards, including impairments of color vision and dark adaptation; heterophoria; stereopsis; monocular vision; refractive states; and telescopic lenses. Both dynamic visual acuity and static acuity decline with age, however, with dynamic acuity, the ability to resolve details of moving objects deteriorates more rapidly.
Visual Attention
Sleeping Disorders That May Impair the Driver

Individuals with sleeping disorders such as narcolepsy and sleep apnea should cease driving upon diagnosis but resume driving upon treatment. Only six US states California, Maryland, North Carolina, Oregon,
Older drivers with 40% or greater impairment in their useful field of view (UFOV) which stems from decline in visual sensory function, visual processing speed, and/or visual attention skills appear to be at an increased crash risk. Older adults who failed the UFOV task have been shown to have 34 times more accidents overall and 15 times more intersection accidents than older adults who passed the UFOV task. The NHSTA recommends that the UFOV protocol be incorporated as a diagnostic test of cognitive deficits, to predict driving impairments for license renewal applicants. The formal testing of UFOV can be performed at the physicians office.
Cataracts
Individuals with moderately advanced cataracts (20/40 to 20/60) suffer more at-fault car crashes than individuals without cataracts. Fortunately, visual impairment from cataracts is correctable with
surgery to 20/40 acuity or better in most cases. An eye specialist should counsel patients regarding the dangers associated with driving with cataracts and suggest driving restrictions (e.g., at night/dusk, in reduced-visibility conditions such as rain, fog) until surgery has been performed.
Hearing Loss
Relatively few studies have examined the relationship between hearing impairment and the risk of motor vehicle crashes. Of these studies, none has demonstrated a significant relationship between hearing impairment and the risk of crash; therefore, there are currently no restrictions.
Vertigo
Drivers with acute vertigo should cease driving until symptoms have fully resolved. Individuals with chronic vertiginous disorder are strongly recommended to undergo driver assessment consisting of an on-road driving assessment performed by a DRS before resuming driving. The medications commonly used to treat these conditions have a significant potential to impair driving skills.
effort to prescribe nonimpairing medications. However, if prescriptions that can impair driving need to be prescribed, physicians should counsel the patient regarding the side-effects. Therefore, physicians should counsel their patients of the specific symptoms and side-effects associated with the prescribed medication and inform them to alert the physician if these symptoms occur. When prescribing new medications, the physician should consider the present regimen of prescriptions, nonprescription medications, and seasonally prescribed medications. The combinations of drugs may affect drug metabolism and excretion, producing additive or synergistic interactions. A physician may consider formal psychomotor testing consisting of an on-road driving assessment performed by a DRS while off and on the medication to determine the extent of impairment. Below is a partial list of medications, their effects on the driver, and recommendations regarding driving a motor vehicle.
Anticholinergics
Deficits of the Extremities That May Impair the Driver

Deformities of the feet (toenail irregularities, calluses, bunions, hammer toes), impairment of gait and balance, and drivers who indicate that their feet or legs feel cold have all been shown to increase car collisions. Older drivers with poor flexibility of arms, legs, and neck are at increased crash risk. Epidemiological studies have reported that older women who could not extend their arms above shoulder height were more than twice as likely to crash their vehicles. In another study, limited neck range of motion was independently associated with adverse driving events.
The anticholinergic effects that can impair driving performance include blurred vision, sedation, confusion, ataxia, tremulousness, and myoclonic jerking. Individuals should be advised that psychomotor and cognitive impairment may be present even in the absence of subjective symptoms. Subtle deficits in attention, memory, and reasoning may occur with therapeutic dosage of anticholinergic drugs without signs of frank toxicity. These deficits have often been mistaken for symptoms of early dementia in elderly patients.
Anticonvulsants
Medications and Their Effects on Drivers Fitness

Many commonly used prescriptions and over-thecounter medications can impair driving performance. In general, any drug with prominent central nervous system effects has the potential to impair an individuals ability to operate a motor vehicle. The level of impairment varies between medications within the same therapeutic class, and in combination with other medications or alcohol. Side-effects that may affect driving performance range from drowsiness, blurred vision, and slow reaction time, to extrapyramidal side-effects. Physicians should make every
Individuals should temporarily cease driving during the time of medication initiation, withdrawal, or dosage change due to the risk of recurrent seizure and potential medication side-effects that may impair driving performance. If there is a significant risk of recurrent seizure during medication withdrawal or change, the individual should immediately cease driving for at least 3 months. If an individual experiences a seizure after medication withdrawal or change, he/she should not drive for 1 month after resuming a previously effective medication regimen.
Antidepressants
Driving impairment varies among the different classes of antidepressants, and even within certain classes of antidepressants. In general, antidepressants that possess antagonistic activity at cholinergic, alpha1-adrenergic, and histaminergic receptors are the most impairing. Individuals should be advised not to
drive during the initial phase of antidepressant dosage adjustment(s) if they experience drowsiness, lightheadedness, or other side-effects that may impair driving performance. Bupropion The side-effects of bupropion (Wellbutrin or Zyban) include anxiety, restlessness, and insomnia. Patients should be counseled about these side-effects and their potential to impair driving performance. Bupropion may cause seizure at high doses. It should not be prescribed to individuals with a history of epilepsy, brain injury, or eating disorder. Monoamine oxidase inhibitors The side-effects of monoamine oxidase inhibitors that may impair driving performance include blurred vision, overstimulation, insomnia, orthostatic hypotension (with transient cognitive deficits), and hypertensive crisis. Tricyclic antidepressants Tricyclic antidepressants have been shown to impair psychomotor function, motor coordination, and open-road driving. Common side-effects of tricyclic antidepressants that may impair driving performance include sedation, blurred vision, orthostatic hypotension, tremor, excitement, and heart palpitation. Studies have indicated an increase in the risk of drivers involved in motor vehicle crashes who take tricyclic antidepressants. Tricyclic antidepressants should be avoided in individuals who wish to continue driving. If nonimpairing alternatives are not available, the physician should advise patients of the potential side-effects and recommend temporary driving cessation during the initial phase of medication initiation/dosage adjustment.
Antiemetics
impairment. Therefore, individuals taking sedating antihistamines should be advised not to drive while on medication. In contrast, nonsedating antihistamines do not produce this type of impairment if taken at the recommended dosage. However, higher-than-recommended doses may impair driving performance. Antihypertensives The common side-effects of antihypertensives, such as lightheadedness, dizziness, and fatigue, coupled with the properties of hypotensives, may impair driving performance. In addition, antihypertensives with a prominent central nervous system effect, including beta-blockers and sympatholytic drugs such as clonidine, guanfacine, and methyldopa, may cause sedation, confusion, insomnia, and nervousness. Individuals taking antihypertensives should be advised that they may cause electrolyte imbalance and affect driving. Antiparkinsonians There are several classes of medication to treat PD, including levodopa, antimuscarinics, amantadine, and dopamine agonists. Common side-effects of these drugs that may impair driving include excessive daytime sleeping, lightheadedness, dizziness, blurred vision, and confusion. Sudden irresistible attacks of sleep have been shown as a side-effect with the dopamine agonist drugs pramipexole and ropinirole. Based on the extent of the disease, the physician may order the patient to undergo formal psychomotor testing or driving evaluation performed by a DRS. Although levodopa improves memory and verbal fluency, it worsens simultaneous visual and auditory reaction times. Trihexyphenidyl, another popular medication for PD, impairs attention, learning, and free recall. Antipsychotics Most, if not all, antipsychotic medications have a strong potential to impair driving performance through various central nervous system effects. The classic antipsychotics are heavily sedating, and all produce extrapyramidal side-effects. Modern drugs have a lower tendency to cause extrapyramidal side-effects; they too are sedating. Patients should be counseled about these side-effects and advised not to drive if they experience side-effects that are severe enough to impair driving performance. The individual may consider formal psychomotor testing consisting of an on-road driving assessment performed by a DRS.
Benzodiazepines (Sedatives/Anxiolytics)
Numerous classes of drugs, including antihistamines, antipsychotics, cannabinoids, benzodiazepines, 5hydroxytryptamine antagonists, and glucocorticoids are used for their antiemetic effects. Side-effects of antiemetics that may impair driving performance include sedation, blurred vision, headache, confusion, and dystonias. Significant driving impairment may be present even in the absence of subjective symptoms. Antihistamines The older antihistamines such as diphenhydramine and chlorpheniramine have pronounced central nervous system effects. Sedating antihistamines have been shown to impair psychomotor performance, simulated driving, and open-road driving. Individuals may experience impairment even in the absence of subjective symptoms of
Benzodiazepine use has demonstrated impairment to vision, attention, motor coordination, and driving
performance. Evening dosage of long-acting benzodiazepines has been shown markedly to impair psychomotor function the following day. Benzodiazepine-like hypnotics such as zolpidem and zaleplon have a rapid rate of elimination; therefore psychomotor functions and skills to safely operate a motor vehicle have been shown 5 hours after taking zalepon and 9 hours after taking zolpidem. Individuals taking long-acting drugs or those during the daytime should be advised of the potential for impairment, even in the absence of subjective symptoms. Individuals should also be advised to avoid driving, particularly during the initial phase of dosage adjustment.
Muscle Relaxants
Most skeletal muscle relaxants (carisoprodol and cyclobenzaprine) have significant central nervous system effects. Drivers should be advised regarding the side-effects and recommended not to drive during the initial phase of dosage adjustment.
Stimulants
The common side-effects of stimulants (amphetamines and methylphenidates) that may affect driving performance include euphoria, overconfidence, nervousness, irritability, anxiety, insomnia, headache, and rebound effects as the stimulants wear off. Drivers should be advised regarding the side-effects and recommended not to drive during the initial phase of dosage adjustment.
Standardized Tests for Driving Performance

There are a number of methods to test driving performance. These range from cognitive testing to real-life on-road driving assessments. Cognitive measures such as the Clinical Dementia Rating (CDR) scale, Sternberg memory search test, visual tracking and the UFOV examination, the Boston test, and the MMSE (Mini Mental State Examination) test can all be used to assess cognitive function and level of driving impairment. The American Academy of Neurology recommended using the CDR to assess individuals with DAT. The MMSE was found to be a significant predictor of final on-road driving performance results, but not of crashes and traffic violations. The Boston naming test has also been shown to be a predictor of driving ability. Physicians who have concerns that their patients may be unsafe to drive should refer these individuals to a DRS. A standardized road test may be the only appropriate means of determining driving competence in people diagnosed with neurological and
physical impairment. The DRS conducts closedcourse, off-road, and on-road performance testing. Closed-course testing allows assessment of a persons ability to track, steer, and brake a car, but yields limited information on actual driving behavior. Testing in stationary training cars is not adequate for persons with central neurological disorders. It is useful in drivers recovering from a stroke or traumatic brain injury, as a prelude to formal on-road examinations. A popular standardized on-road measure is the Washington University Road Test (WURT) of driving performance, that is commonly used in driving research in the elderly and a wide range of cognitively impaired population. The WURT is a 45-min in-traffic road test along a predetermined route. The opencourse test is conducted in traffic and assesses several typical driving skills such as maintaining speed, obeying traffic signs, signaling, turning, changing lanes, and negotiating intersections. The road test provides an accurate and reliable functional assessment of driving ability and the testretest reliability is high. The methods developed and employed in the USA for testing drivers performance and the presence of illicit drugs have been adapted by countries in Europe and Australia. In the UK two drug recognition systems are used, Drug Recognition Training (DRT) and Field Impairment Testing (FIT). The DRT combined with the FIT system is used to identify the signs and symptoms associated with the effects of drugs and the assessment of the drivers drug impairment. A version of the American field sobriety test of drivers, FIT was introduced with minor differences in Scotland, England, and Wales in 2000. The main difference between the US and UK and European field sobriety tests is that horizontal and vertical gaze nystagmus is replaced by an examination of the pupils.
Government Regulation
The US federal government and individual states play the central role in licencing drivers. The drivers licencing regulation is specific for each state. The ultimate decision to remove driving privileges rests in the hands of the local drivers licencing authority. In 1991, 46 states had restrictions regarding individuals with seizures; 26 states limited drivers who have episodic loss of consciousness from other medical causes; and eight states had laws regarding individuals with known cardiac arrhythmias. Therefore, the physicians role is simply advisory.
The Role of the Postmortem Examination

The legislation and medical guidelines are based primarily on empirical and statistical data. The information generated from postmortem examinations and a
review of the drivers past medical history are critical for the refinement and future generations of sound medical guidelines. The postmortem examination of a driver involved in a fatal motor vehicle crash is the final assessment of the performance of the driver and his/her physician. Throughout the USA all fatal motor vehicle crashes require a postmortem examination. The forensic pathologist is able to review the drivers medical records and the results of the postmortem examination of the internal organs and the results of toxicological analysis.
Motor Vehicle Crashes
Americans: Age 65 and Over

Population
In 1980, the US population of individuals aged 65 and over represented 26.5 million (11.3%) of the total US population. Ten years later this population increased to 30.9 million, 12.5% of the total population. Based on projections, by the year 2025 more than 18% of the US population will be 65 and older, and by 2040 the elderly will represent 20% (68 million) of the US population. The percentage of individuals aged 85 and older is increasing at a faster rate than ever before.
Mortality
Accidents were the fourth leading cause of death in the USA in 1999; motor vehicle accidents accounted for over half of these deaths. Automobile crashes in the USA in 1999 claimed the lives of 40 000 individuals and disabled 2.2 million. The pattern of motor vehicle crashes and fatal motor vehicle accidents in the USA is U-shaped. The number of fatal motor vehicle accidents is high among drivers aged 1624 years old; it then steadily decreases until the age of 4555. After the age of 55, it starts to increase, with the greatest increase occurring after the age of 60. The accident rates for drivers aged 1619 is 28 per million miles driven, whereas in adults older than 85 years the rate jumps to 85 accidents per million miles driven.
Profile of Elderly Drivers
The two leading causes of natural death among individuals aged 65 and over are cancer and heart disease. Among unintentional injuries resulting in death, the two leading causes in the 6574-year-old group are motor vehicle accidents and falls. The Insurance Institute for Highway Safety estimates that, by the year 2030, 25% of all fatal traffic crashes will involve drivers 65 and older.
Number of Licenced Drivers
Currently, older drivers represent only a fraction of the total driving public. However, they represent the fastest-growing segment of the driving population. In 1980, there were 13.3 million licenced older drivers, representing 9.3% of all drivers in the USA. By 1991, there were 21.8 million, representing 13%, with 6.6 million (4%) drivers over 85 years old. The Federal Highway Administration reported that in 1996 there were 15 648 000 licenced drivers aged 6574 years, and 9 522 000, aged 75 and over. It has been estimated that, by the year 2020, more than 15% of drivers will be older than 65 years. The National Institute on Aging estimates that, by 2030, there will be an estimated 40 million licenced drivers, with 25% of all drivers aged 65 and over, and about 9 million of these aged 85 and over.
Driving is an economic, social, and recreational necessity for most Americans and plays a central role in the lives of adults, especially older adults, who rely on the private automobile for 88% of their transportation needs. Individuals with preexisting medical conditions and/or those who develop conditions that can affect their driving performance will result in a conflict between reasonable transportation opportunities, the role of physicians, and societys need to protect public safety. Most seniors are as capable of driving safely as their younger counterparts, and when they become aware that they have a problem, they typically act responsibly by limiting or modifying their driving habits. Older drivers in general drive less, drive less at night, avoid heavy traffic times and complicated roadways, and limit their geographic area. Evergrowing traffic volumes, congestion, and novel highway features and vehicle technologies demand greater attention by drivers. They incur accidents in situations that require astute perception, problem-solving ability, immediate reactions, and agile decisionmaking. However, older drivers are overrepresented when fatalities or crashes are adjusted for vehicle miles traveled. They commit more driving errors, such as failure to yield right-of-way, incorrect lane changes, and improper turning, particularly lefthand turns, and turning from the wrong lane. When they crash, elderly drivers are more likely to incur injury and death. As a group, people older than 65 years nonetheless have fewer accidents than any other age group, largely because they drive fewer kilometers. Those older than 75 years are twice as likely as the average driver, per mile driven, to crash their cars, while those older than 85 are 2.5 times more likely, even without adjustment for miles driven. Men
32 ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/Driving Offense
are 24 times more likely to crash than women, even when adjusted for the increased time men spend driving, though this difference begins to disappear later in life.
See Also
Road Traffic, Determination of Fitness To Drive: Sobriety Tests and Drug Recognition; Driving Offense; Road Traffic, Global Overview of Drug and Alcohol Statistics
Future Reading
Brayne C, Dufouil C, Ahmed A (2000) Very old drivers: findings from a population cohort of people aged 84 and over. International Journal of Epidemiology 29: 704707. Campbell GH, Lutsep HL (2003) Driving and neurological disease. Available at www.emedicine.com/neuro/ topic594.htm. Cooper PJ, Tallman K, Tuokko H (1993) Vehicle crash involvement and cognitive deficit in older drivers. Journal of Safety Research 24: 917. Cox DJ, Penberthy JK, Zrebiec J, et al. (2003) Diabetes and driving mishaps: frequency and correlations from a multinational survey. Diabetes Care 26: 23292334. Dobb AR, Heller RB, Schopflocher D (1998) A comparative approach to identify unsafe older drivers. Accident, Analysis and Prevention 30: 363370. Dubinsky RM, Stein AC, Lyons K (2000) Practice parameter: risk of driving and Alzheimers disease (evidence-based review): report of the quality standards of the Subcommittee of the American Academy of Neurology. Neurology 54: 22052211. Frier BM (2000) Hypoglycemia and driving performance. Diabetes Care 23: 148150. Gastaut H, Zifkin BG (1987) The risk of automobile accidents with seizures occurring while driving in relation to seizure type. Neurology 37: 16131616. Hansotia P, Broste SK (1999) The effect of epilepsy or diabetes mellitus on the risk of automobile accidents. New England Journal of Medicine 324: 2226. Kahn P (2000) Vision and automobile driving. Fitness in Parkinsons disease. National Parkinson Foundation XXI: issue 3: 16. Kakaiya R, Tisovec R, Fulkerson P (2000) Evaluation of fitness to drive. Postgraduate Medicine 107: 229236. Lyman JM, McGwin G, Sims RV (2001) Factors related to driving difficulty and habits in older drivers. Accident, Analysis and Prevention 33: 413421. Older drivers (age 66). Available at www.aahp.org/links/ NHYSA_Site/older_driver.html. Raedt RD, Krisoffersen IP (2000) The relationship between cognitive/neuropsychological factors and car driving performance in older adults. Journal of the American Geriatric Society 48: 16641668. Raedt RD, Krisoffersen IP (2001) Predicting at-fault car accidents of older drivers. Accident, Analysis and Prevention 33: 809819.
Simpson CS, Klein GJ, Brennan FJ (2000) Impact of a mandatory physician reporting system for cardiac patients potentially unfit to drive. Canadian Journal of Cardiology 16: 12571263. Songer TJ, LaPorte RE, Dorman JS (1988) Motor vehicle accidents and insulin-dependent diabetes. Diabetes Care 11: 701707. Songer TJ, Lave LB, LaPorte RE (1993) The risks of licensing persons with diabetes to drive trucks. Risk Analysis 13: 319326. Wang CC, Kosinski CJ, Schwartzberg JG, Shanklin AV (2003) Physicians guide to assessing and counseling older drivers. Available at http://www.ama-assn.org/go/ olderdrivers.
Driving Offense
C H Wecht and S A Koehler, Allegheny County Coroner, Pittsburgh, PA, USA
Introduction
This article will provide an overview of driving offenses created by the intake of drugs, including alcohol, and unsafe driving behavior. In addition, antemortem and postmortem forensic evaluation of driver behavior and level of impairment will be reviewed.
Postmortem Forensic Toxicology

Individuals involved in a fatal motor vehicle accident undergo from a postmortem examination, complete with toxicological analysis, to simply an analysis of blood drawn from the heart, to no blood for analysis in some areas. Postmortem forensic toxicology analysis is conducted to ascertain what role alcohol or other drugs may have played in the drivers ability to operate a vehicle safely. Specimens are obtained during the postmortem examination for this purpose. Blood is the most important specimen obtained during postmortem examination for forensic toxicology analysis. The sample of blood should be obtained from the heart and from a peripheral site such as the femoral or jugular veins. In addition to blood, vitreous humor from the eye, urine from the bladder, and bile from the gallbladder are also collected during the postmortem examination. After these fluids have been collected they undergo toxicological analysis. Techniques used for this identification include spectrophotometry, chromatography, and immunoassay.
ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/Driving Offense 33
Human Performance Toxicology

The branch of forensic toxicology that focuses on the relationship between the presence of a drug and the associated behavioral changes or human performance is termed behavioral toxicology. The field of behavioral toxicology combines the disciplines of psychology, toxicology, and pharmacology. Behavioral toxicology focuses on both licit and illicit drugs and evaluates the effects of therapeutic drugs when administered in the prescribed manner for their normal medical application, as well as when they are incorrectly administered or abused.
The Effects of Alcohol
drivers with alcoholism. Not surprisingly, very few physicians in practice ever do. Certain other behaviors inflate accident rates as well. A history of a previous serious accident, especially when the driver was at fault, presents an increased risk (and insurance premiums). The relative risk of a crash while driving a sports car is 1.3 and while talking on a cellular phone it is estimated to be 4.3. As automakers bring more satellite-based telecommunications to drivers e-mail, traffic reports, navigational systems the temptation to multitask increases, further distracting motorists. Driving under the influence of alcohol (DUIA) and driving under the influence of drugs (DUID) Driving under the influence (DUI) The first legislation making DUI an offense in the USA was passed in 1939. A joint meeting of the Committee to Study Problems of Motor Vehicle Accidents (a special committee of the American Medical Association) and the Committee on Alcohol and Other Drugs established the offense levels of DUI based on BAC levels. Later, the committee name was changed to the Committee on Alcohol and Drugs. The committee also formulated the basis of the Chemical Test Section of the Uniform Vehicle Code. In 1960, the Committee on Alcohol and Drugs released the recommendations that DUI laws use the level of 0.10 g dl1 BAC as presumptive evidence of guilt. The Uniform Vehicle Code was amended to reflect this recommendation in 1962. The relative probability of having an accident by BAC is shown in Table 1. In 1971, the Committee stated that alcohol, regardless of previous experience with this compound, impaired driving performance at a BAC of 0.08 g dl1 or greater. The standardized field sobriety tests were developed in the late 1970s. The sobriety tests When a police officer encounters a possibly impaired driver, he/she initiates a threephase evaluation process called the DUI arrest decision process. Phase 1 involves the initial observation
Alcohol produces a wide range of behavioral effects such as decreased visual acuity and peripheral vision, and these effects increase significantly as the blood alcohol concentration (BAC) rises above 0.07 g dl1. At a BAC of 0.08 g dl1, sensitivity to pain decreases. Reaction time is impaired at 0.05 g dl1. Those who consume alcohol irresponsibly face a much higher risk of driving accidents. Three drinks in 60 min for an average man or in 90 min for an average woman will raise the blood alcohol level to 0.05% (0.01 mmol l1), a level at which the risk for crash doubles. In the USA, the vast majority of states specify 0.10% as the legal definition of impairment, and a few have lowered the legal limit to 0.08%. Generally, two 45-ml (1.5-oz) drinks of spirits result in a blood level of 0.05%. The behavior changes associated with alcohol and its effect on driving performance have been well established. Epidemiological studies have shown that 4060% of all fatally injured drivers had a BAC of 0.10 g dl1 or greater, and 3040% of those had a BAC > 0.15 g dl1. The cost of drink-related accidents has been estimated at $45 billion a year, with $70 billion lost in quality of life. In 1997, in the USA, just over 16 000 people were killed in crashes involving alcohol, nearly two-fifths of all traffic deaths. Mothers Against Drunk Driving (MADD) estimates that about 800 000 Americans are injured in alcoholrelated crashes every year, and that three of every 10 Americans will be involved in an alcohol-related traffic crash at some time in their lives. Comparison of the impacts of alcohol and epilepsy, the medical condition most commonly reported to driving-licencing authorities, reveals that, of every 10 000 individuals killed in motor vehicle accidents, 4000 deaths are due to excess alcohol, six to natural causes, and only one to epilepsy. It is strange that all 50 states in the USA carefully advise physicians to report to licencing authorities any driver with uncontrolled epilepsy, but none mandate reporting of
Table 1 The relative probability of having an accident by blood alcohol concentration (BAC) level
BAC level (g dl1)
Probability of having an accident
0.04 0.06 0.10 0.15
Drivers were as likely to have an accident as a sober driver Drivers were twice as likely as sober drivers to cause an accident Drivers were six times as likely as sober drivers to cause an accident Drivers were 25 times as likely as sober drivers to cause an accident
of the motion of the vehicle, such as weaving, signaling, speed, and the drivers response to the officers commands. Phase 2 is the officers direct contact with the driver. During the interview with the driver the officer evaluates the physical appearance, dexterity, breath odor, condition of the eyes, color of the face, and speech patterns. Phase 3 involves the administration of several psychomotor tests and the breath test. The three tests that constitute the standardized field sobriety test are the one-leg stand (OLS), the walk and turn (WAT), and the horizontal gaze nystagmus (HGN). The HGN is the most sensitive test to determine the impairing effects of alcohol. The specimen for DUI cases is the breath. Law enforcement prefers the breath test because collection and analysis are performed together. Blood specimens must be drawn by a trained healthcare professional, and urine must be collected under controlled and observed conditions. After the three phases the officer should be able to ascertain whether arrest or release of the driver is indicated. Sample collection among individuals of DUIA and DUID Specimens among living subjects should be collected from individuals suspected of being impaired by alcohol or other drugs. Blood samples are collected using the venepuncture technique. The disinfectant used to clean the arm should not contain ethanol, isopropanol, or any other volatile compound. Povidone iodine solutions are recommended. Samples used for alcohol determinations should contain blood collected in two 10-ml gray-top tubes of blood (e.g., Vacutainer Tubes), while urine should be collected in a plastic container. Samples used for alcohol and drug screens should contain at least two 10-ml gray-top tubes of blood, two 10-ml green-top tubes of blood, and one plastic container of urine. The urine specimens should be collected in a plastic container designed to prevent leakage during transport. The specimens should be collected while the subject is being observed. It is critical that a blood sample is submitted for all DUIA and DUID cases. A urine specimen by itself will only indicate recent ingestion. All specimens should be labeled, and put in a closed, sealed, and tamper-resistant package with: the name of defendant, specimen type, and the date and time specimen was obtained. The sample should be refrigerated and submitted as soon as possible after collection. Each specimen should contain a brief history, indicating any pertinent information or observations regarding the history, such as: medication taken that day, medical conditions, time of last drink, last meal, and drug history (such as history of drug abuse). In addition, document how
much time has elapsed between the time when the drug (or drugs) might have been taken and the time of sample collection. In postmortem cases of suspected cases of DUIA or DUID, the following biological samples should be collected. Blood should be collected from the heart blood, 60 ml in culture tube and 10 ml in a gray-top tube; femoral blood in two 10-ml gray-top tubes; and antemortem blood if available. Urine (3060 ml in culture tube), bile (30 ml in culture tube), and all vitreous fluid should also be collected. Samples of liver (60 g) and lung (10 g) and all contents of the stomach should be collected. In cases of suspected overdoses, package intact tablets separately and identify them as being found in the stomach contents. In suspected cases of inhalant, solvent abuse, or methane deaths submit lung samples (10 g) in an airtight and half-full container (use 40-ml volatile organic compound vials with a Teflon seal). All specimens must be labeled with autopsy number, name of deceased, date, and type of specimen. Each blood specimen must be labeled as to the anatomic site of origin (i.e., heart blood, chest blood). Antemortem blood samples must be labeled with the autopsy name, number, and the date and time of collection. Refrigerate samples prior to submission.
Drugs and Driving
The role of drugs of abuse other than alcohol has been recognized in an analysis of impaired driving performance. This insight led to the formation of the Drug Evaluation and Classification (DEC) program in the USA. Following several field validity studies by the NHTSA and the NIDA, the standards for training police officers as drug recognition experts (DREs) were established. The DRE drug evaluation has 12 components: (1) breath alcohol test; (2) interview of the arresting officer; (3) preliminary examination of the suspect; (4) examination of the eyes; (5) divided-attention psychophysical tests; (6) vital signs examination; (7) dark room examination; (8) examination of muscle tone; (9) examination for injection sites; (10) suspects statements and other observation; (11) opinion of the evaluator; and (12) toxicology examination. If it is the opinion of the DRE officer that the drivers impairment is caused by drugs, toxicological analyses are performed. In general, blood is the best specimen for analysis. Urine specimen is suitable for toxicology screen; however, no direct relationship can be ascertained between the urine concentration of a drug and impairment. Therefore, positive identification of a drug is only an indicator of

Table 2 Physiological features of various drugs used by the drug recognition evaluation (DRE)a
Drug recognition evaluation CNS depressant CNS stimulants
Hallucinogens
PCP
Narcotic
Inhalants
Cannnabis
Pupil size
Normal
Dilated
Dilated
Normal
Constricted
Normal
Reaction to light Horizontal gaze Vertical gaze Smooth convergence Pulse rate Blood pressure Body temperature Muscle tone Injection site
Slow Nystagmus present Nystagmus present Lacking Elevated or depressed Lowered Lowered Normal Not present
Slow Nystagmus not present Nystagmus not present Present Elevated Elevated Elevated Rigid Present
Normal Nystagmus not present Nystagmus not present Present Elevated Elevated Elevated Rigid Not present
Normal Nystagmus present Nystagmus present Lacking Elevated Elevated Elevated Rigid Not present
Normal Nystagmus not present Nystagmus not present Present Depressed Lowered Lowered Normal to flaccid Present
Slow Nystagmus present Nystagmus may be present Lacking Elevated Lowered Lowered or elevated Normal Not present
Normal/ slightly dilated Normal Nystagmus not present Nystagmus not present Lacking Elevated Elevated Normal Normal Not present
CNS, central nervous system; PCP, phencyclidine. a It should be noted that in many circumstances a mixed picture of drug and alcohol use has taken place rendering this information unsound.
exposure. It should also be noted that there is no wellestablished correlation between blood concentration and performance impairment for any drug other than alcohol. Table 2 shows physiological features of various drugs used by the DRE. Drivers under the influence of drugs are a significant problem outside the USA. The number of drivers under the influence has been increasing in the UK. This increase has resulted in the establishment of DEC programs in these countries. In the UK the Drug Recognition Training (DRT) and Field Impairment Testing (FIT) were developed. The DRT is used to identify the signs and symptoms associated with the effects of drugs. The effectiveness and interpretation of these testing methods is still widely debated as mis- or over-interpretation may occur. The FIT system was derived from the US sobriety testing that has been in use for over 20 years. The FIT used in non-US countries is very similar to the ones used in the US.
The Effects of Various Drugs on the Human Body
Drugs in this category result in a dose-related slowing of reflexes, loss of social inhibitions, impaired divided attention and judgment, increased risk-taking behavior, and emotional instability. CNS stimulants This class includes cocaine, and members of the amphetamine class such as methamphetamine. Acute use of the drugs in this category results in improved mood and a feeling of pleasure. Chronic use leads to paranoid behavior, psychosis, and violence. Hallucinogens This class includes lysergic acid diethylamide (LSD), 3,4-methylenedioxyamphetamine (MDA), and methylenedioxymethamphetamine (MDMA). Drugs in this category cause an altered or distorted perception of reality. Performance usually involves difficulty in remaining motivated and attending to a particular task. Phencyclidine (PCP) This class includes PCP and its structural analogs. PCP has anesthetic properties, hallucinogenic effects, and may act as either a CNS depressant or stimulant. Drivers under PCP experience disorientation, slurred speech, agitation, excitement, and altered perception of self, and typically have a fixed, blank stare.
Central nervous system (CNS) depressants This class includes alcohol, the most common CNS depressant. Other drugs include barbiturates, benzodiazepines, antidepressants, and antipsychotic drugs.
Narcotic analgesics This class includes natural opiates (heroin, morphine, and codeine), and synthetic opiates (hydromorphone, hydrocodone, fentanyl, methadone). The initial effects include a feeling of intense pleasure followed by dysphoria, nausea, and vomiting. Chronic use does not appear to interfere with intellectual or physical ability. Inhalants This class comprises the volatile organic solvents (e.g., toluene, gasoline), hydrocarbon gases (butane, freon, propane), anesthetic gases (halothane, nitrous oxide), and nitrites (isobutyl, amyl, and butyl nitrites). Inhalation of the fumes results in a feeling of euphoria, and CNS depression similar to the effects of alcohol. Abusers experience disorientation and confusion. Cannabis This class includes marijuana, hashish, hash oil, and n9-tetrahydrocannabinol (TCH) from the Cannabis sativa plant. At low doses these drugs cause a pleasurable high. Performance deficits from these drugs are primarily caused by a lack of motivation and an inability to attend to a task. Following use of marijuana performance on a standard field sobriety test is significantly impaired.
Drug Evidence with a Vehicle
Unsafe Driving Behavior: Not Drug-Related

The Drowsy Driver
The vehicle involved in a fatal injury is routinely searched for evidence of drug use. The most typical finds are cans of beer. On occasion drug paraphernalia is also located within the vehicle. Once drug evidence has been located, it should be collected and submitted for analysis. If vegetable-type matter is located or if the material appears to be freshly harvested marijuana it should be dried and packaged in a sealed suitable paper container prior to submission. Do not seal freshly cut suspected marijuana in plastic bags since such packaging promotes the growth of mold and the deterioration of the evidence. If moldy vegetable matter is encountered, the sample must be sealed in an airtight container. Evidence must be submitted in sealed packages. Use evidence tape or clear shipping tape to seal packages. Regular Scotch tape is not acceptable. All sealed packages must be initialed by the person who sealed the package and by the submitter. With small items, the sealed evidence package should be no larger than 13 18 cm (5 7 in.). For very large samples, such as suitcases, travel bags, or large plants, a sealed corrugated cardboard box is preferable to other types of paper. Evidence from different actors in the same case must be packaged in separate sealed containers and clearly marked with the actors name.
The NHTSA estimates that 13% of US highway crashes and 4% of fatal motor vehicle crashes are caused by driver sleepiness. Few attempts have been made to assess the total costs of drowsy driving, although a recent report from the NHTSA estimated them at $12.4 billion a year. Reports have shown that, when impairments in performance caused by alcohol and sleep deprivation were compared directly, sustained wakefulness for 17 h decreased performance about as much as a BAC of 0.05%. Fatigue is the leading cause of long-haul truck crashes. Rates of drowsy-driving crashes are highest among young people (especially men), shift workers, and people with untreated sleep conditions. NHTSA data show that males are five times more likely than females to be involved in drowsy-driving crashes. It has also been shown that male youths with the greatest extracurricular time commitments were most likely to report falling asleep at the wheel. The subgroup at greatest risk comprised the brightest, most energetic, and hardest-working teens. Experimental evidence has shown that sleeping less than 4 consolidated hours per night impairs performance of vigilance tasks. Individuals working rotating shifts lose 24 h with each shift. People who are restricted to 45 h sleep per night for 1 week need two full nights of sleep to recover vigilance, performance, and normal mood, according to one study. Although the relative risk for fall-asleep crashes has not been established, individuals who exhibit a sleep latency of less than 15 min on the maintenance of wakefulness test, a routine sleep lab study, are categorically too sleepy to drive a motor vehicle. Sleepiness and alcohol interact, with sleep restriction exacerbating the sedating effects of alcohol. A 1996 random survey of licenced drivers in New York state conducted by McCartt in order to determine the prevalence and circumstances of drowsy driving discovered that 54.6% of drivers had driven while drowsy within the past year; 22.6% had even fallen asleep at the wheel without having a crash; 2.8% had crashed when they fell asleep; and 1.9% had crashed when driving while drowsy. Of the reported crashes due to driving while drowsy or falling asleep at the wheel, 82.5% involved the driver alone in the vehicle, 60.0% occurred between 11:00 p.m. and 7:00 a.m.; 47.5% were drive-off-the-road crashes; and 40.0% occurred on a highway or expressway. Multiple regression analysis suggested that the following driver variables are predictive of
an increased frequency of driving drowsy: demographic characteristics (younger drivers, more education, and men); sleep patterns (fewer hours of sleep at night and greater frequency of trouble staying awake during the day); work patterns (greater frequency of driving for job and working rotating shifts); and driving patterns (greater distance driven annually and fewer number of hours a person can drive before becoming drowsy). Knowledge of specific risk factors for sleep-related crashes is an important first step in reducing the thousands of deaths and injuries each year in the USA attributed to drowsy driving.
Sleep-Related Deaths
Obstructive sleep apnea has been shown to be associated with an increased risk of road traffic accidents. Sleep apnea, as measured by the apneahypopnea index, has been associated with traffic accidents. As compared to those without sleep apnea, patients with an apneahypopnea index of 10 or higher had an odds ratio of 6.3 of having a traffic accident. In 1991 an expert panel of the Federal Highway Administration recommended that drivers with suspected or untreated sleep apnea not be medically qualified for commercial motor vehicle operation until the diagnosis has been eliminated or adequately treated. A 2003 population-based case-control study was carried out by Stutts to examine driver risk factors for sleep-related motor vehicle crashes. Cases included 312 drivers involved in recent North Carolina crashes and identified on police reports as being asleep at the time of the crash; 155 drivers were identified as fatigued. Controls were 529 drivers also involved in recent crashes but not identified as asleep or fatigued, and 407 drivers not involved in recent crashes. All drivers were contacted for brief telephone interviews. Results showed that drivers in sleep-related crashes were more likely to work multiple jobs, night shifts, or other unusual work schedules. They averaged fewer hours sleep per night, reported poorer-quality sleep, were less likely to feel they got enough sleep, were sleepier during the day, drove more often late at night, and had more previous instances of drowsy driving. Compared to drivers in nonsleep-related crashes, they had been driving for longer times, been awake more hours, slept fewer hours the night before, and were more likely to have used soporific medications.
Cell Phone Use and Driving
Epidemiological studies based on data obtained from insurance claims, police-reported collisions, cell phone companies, and violations have examined the risk of cell phone use and crashes. Drivers using cell phones had a higher risk of an at-fault crash than did nonusers. Cell phone users also had a higher proportion of rear-end collisions. The violation pattern of cell phone users suggests that they are, in general, riskier drivers. A study by Nabeau in 2003 showed the relative risk of all accidents and of accidents with injuries is higher for users of cell phones than for nonusers. The relative risk for injury from a collision was 38% higher among men than women cell phone users. However, this risk diminishes to 1.1 for men and 1.2 for women after controlling for other variables, such as the kilometers driven and driving habits. The most significant finding regarding cell phone use was the association of a doseresponse relationship between the frequency of cell phone use and crash risks. The adjusted relative risk for heavy users is at least twice that of those making minimal use of cell phones; the latter show similar collision rates as do the nonusers.
See Also
Road Traffic, Determination of Fitness To Drive: Sobriety Tests and Drug Recognition; General; Road Traffic, Global Overview of Drug and Alcohol Statistics
Further Reading
Beck KH, Rauch WJ, Baker EA, William AF (1999) Effects of ignition interlock license restrictions on drivers with multiple alcohol offenses: a randomized trial in Maryland. American Journal of Public Health 89: 16961700. Cherpitel CJ, Bond J (2003) DUI recidivism: a comparison of Mexican Americans and whites in a northern California county. Addictive Behavior 28: 963969. Harding PM, Laessig RH, Field PH (1990) Field performance of the Intoxilyer 5000: a comparison of blood- and breath-alcohol results in Wisconsin drivers. Journal of Forensic Science 35: 10221028. Krause KR, Howells GA, Bair HA, Bendick PJ, Glover JL (1998) Prosecution and conviction of the injured intoxicated driver. Journal of Trauma 45: 10691073. Laberge-Nadeau C, Maag U, Bellavance F, et al. (2003) Wireless telephones and the risk of road crashes. Accident Analysis and Prevention 35: 649660. Levine B (1999) Principles of Forensic Toxicology. USA: American Association for Clinical Chemistry. Marques PR, Tippetts AS, Voas RB, Beirness DJ (2001) Predicting repeat DUI offenses with the alcohol interlock recorder. Accident Analysis and Prevention 33: 609619.
The popularity and increased use of cell phones, especially while driving, has raised the concern that this behavior is a cause of many road crashes.
38 ROAD TRAFFIC, GLOBAL OVERVIEW OF DRUG AND ALCOHOL STATISTICS McCartt AT, Ribner SA, Pack AI, Hammer MC (1996) The scope and nature of the drowsy driving problem in New York State. Accident Analysis and Prevention 28: 511517. Rajalin S (1994) The connection between risky driving and involvement in fatal accidents. Accident Analysis and Prevention 26: 555562. Shope JT, Waller PF, Lang SW (1996) Alcohol-related predictors of adolescent driving: gender differences in crashes and offenses. Accident Analysis and Prevention 28: 755764. Stutts JC, Wilkins JW, Osberg J, Vaughn BV (2003) Driver risk factors for sleep-related crashes. Accident Analysis and Prevention 35: 321331. Turkington PM, Sircar M, Allgar V, Elliott MW (2001) Relationship between obstructive sleep apnoea, driving simulator performance, and risk of road traffic accidents. Thorax 56: 800805. Waller PF, Elliott MR, Shope JT, Raghunathan TE, Little RJ (2001) Changes in young adult offense and crash patterns over time. Accident Analysis and Prevention 33: 117128. Wilson J, Fang M, Wiggins S, Cooper P (2003) Collision and violation involvement of driver who use cellular telephones. Traffic Injury and Prevention 4: 4552. Vorona RD, Ware JC (2002) Sleep disordered breathing and driving risk. Current Opinion in Pulmonary Medicine 8: 506501.
ROAD TRAFFIC, GLOBAL OVERVIEW OF DRUG AND ALCOHOL STATISTICS

B Marc, Compiegne Hospital, Compiegne, France P Mura, Laboratoire Toxicology/Biochimic, France
Introduction
Most developed countries, including continental European countries, are concerned by the phenomenon of alcohol and drug abuse and its collateral effect, that is, driving under the influence of alcohol and drugs. This article will briefly present: (1) the legal aspects of driving under the influence, using European Community laws as an example, and (2) the most recent alcohol and drug statistics available for drivers. The use of illicit drugs is increasing, as is the combined use of drugs and alcohol. The under-26 age bracket particularly frequently reports driving under the influence of illicit drugs alone, while mixed use of drugs and alcohol is observed in the 2649-year age range; and alcohol on its own begins to increase after 50 years. In European penal laws, modifications have recently been introduced taking into account the importance of driving under the influence and its consequences for road safety and public health.
Aspects of European Laws Relating to Driving under Influence

With the increase in abuse of controlled drugs, there is concern over their effects and the reduction in ability to drive a motor vehicle safely under the influence of narcotic or hallucinogenic substances.
Although driving under the influence of alcohol is already established as an offense in all countries, drug abuse has not always been addressed, until recently. As an example of prevalence, one review, published in 1999, examined about 30 studies, estimating that in the general driving population the prevalence of illicit drug use would probably be 15% (mainly cannabis and opiates), whereas licit drug use would be 515% (mainly benzodiazepines). The European Union has legislated on the use or abuse of psychotropic substances that may affect physical and mental fitness to drive. Annex III of Council Directive 91/439/EEC, dated July 29, 1991, on driving licenses states that: Driving licences shall not be issued to or renewed for applicants or drivers who are dependent on psychotropic substances or who are not dependent on such substances but regularly abuse them. Under the European Union Action Plan 20002004 3.1.2.5, the Commission and member states are to undertake research into the effects of driving under the influence of illicit drugs and pharmaceuticals (roadside testing assessment or ROSITA program). However, problems with such testing include scientific discrepancies on the levels of drug concentration at which impairment is demonstrated, and the lack of suitable equipment for roadside testing. Examples below illustrate the regulations in different European countries.
Austria
In Austria, the law controlling drugs and driving is the Austrian Road Traffic Act. Under the Austrian Penal Code, it is a criminal offense punishable by up
ROAD TRAFFIC, GLOBAL OVERVIEW OF DRUG AND ALCOHOL STATISTICS 39
to 3 months in prison or 180 day-fines (180 days of general work as a fine) to endanger other people while under the influence of any substance. Under the influence of any substance, negligence resulting in death is a criminal offense punishable by up to 3 years in prison; if such negligence results in injury it is punishable by up to 6 months in prison or 360 dayfines. These rules also apply to driving under the influence of drugs. The police have the right to take a person to a doctor for drug testing and medical examination when suspected of driving under the influence of drugs. Since January 1, 2003, if it is suspected that drugs are affecting an individuals ability to drive, the examining doctor must take a blood sample.
Belgium
other than inebriation are suspected, the police may take the individual for a medical examination. A doctor will make a clinical study of the driver and take a blood sample for analysis looking for traces of alcohol, medicine, and drugs.
France
In Belgium, the law in force is the Reorganization of Traffic Police dated March 16, 1999. The substances targeted are the most common illicit drugs, e.g., traces of n9-tetrahydrocannabinol (THC), amphetamine, methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), morphine, cocaine, or benzoylecgonine. If any of these substances are detected, then the driver is considered guilty of an offense. If there is a criminal prosecution, the offender may be sentenced to imprisonment for 15 days to 6 months and/or a fine of E100010 000, or imprisonment for 1 month2 years. Those who may be subject to the test include anyone who is driving or about to drive in a public place, anyone presumed to be responsible for a car accident, or anyone who could have contributed to its cause.
Denmark
In France law 2003-87, dated February 3 2003, on driving under the influence of substances or plants classed as narcotics, has created a new crime of driving after using such substances. Testing may take place if the police have reason to suspect that the driver has taken drugs; testing is also standard in cases of death (Figures 1 and 2). The penalties are comparable to those for driving under the influence of alcohol 2 years in prison and a E4500 fine. If the offender drives after using narcotics and is under the influence of alcohol at the same time, the penalty rises to 3 years in prison and a E9000 fine. It is also possible to suspend or revoke the driving license for up to 3 years, and sentence to community service or day-fines. Before February 2003, driving under the influence of drugs was not subject to a specific sanction, as such a driver could always be charged for illicit use of drugs. An article was subsequently added to the law no. 99-505 of June 18, 1999 on road safety, allowing systematic drug testing for all drivers involved in a fatal accident. The decree 2001751 of August 27, 2001 defined a fatal accident as an accident having immediate fatal consequences, and established that urine drug tests should be carried out by a doctor, together with a clinical examination. Illicit drug metabolites tested in urine are: (1) benzoylecgonin (for cocaine); (2) THC; (3) morphine (for opiates); and (4) MDMA with defined cut-offs. If
In Denmark, according to the Road Traffic Act of August 2, 2001, driving is prohibited if the driver is incapable of driving in a fully reassuring way. The Road Traffic Act is defined as follows: A motordriven vehicle may not be driven or attempted to be driven by somebody, who because of illness, weakness, over-exertion, lack of sleep, influence of exhilarating or anaesthetic drugs or because of similar causes is found to be in such a condition, that he is incapable of driving the vehicle in a fully reassuring way. It can be seen that there is no distinction between specific drugs, and the act takes a clinical approach of the incapacity to drive . . . because of (drugs). Violation of this provision is a criminal offense. According to the Road Traffic Act, the police may hold someone in order to take blood and urine specimens for analysis, if there is cause to suspect such person of having committed an offense or if such person refuses or is unable to take a breath test. Additionally, if causes
Figure 1 Unexplained highway car crash resulting in two dead and one seriously injured. The driver and passengers were smoking cannabis.
40 ROAD TRAFFIC, GLOBAL OVERVIEW OF DRUG AND ALCOHOL STATISTICS
suspicion. Sanctions available to the authorities are up to 1 month imprisonment or a fine of E2601030, with suspension of the driving license for a period of 15 days to 3 months.
The Netherlands
Figure 2 Urine drug testing on drivers after a fatal car crash. The police officer fills in the judicial forms while the doctor carries out the urine screening test after sampling (left). A blood sample is taken (if urine testing is positive) and ready to be sent to the laboratory.
urine tests prove positive, then the blood sample is tested for these four illicit drugs. Law no. 2001-1062 of November 15, 2001, relating to daily security, envisaged the possibility for officers of the judicial police to test all drivers implicated in an accident, where injury was sustained, for drugs.
Germany
In Germany, two main provisions in the German Criminal Code addressing drugs and driving are: (1) Endangering road traffic, which prohibits driving while not in a condition to do so safely due to consumption of intoxicants, thereby endangering life, limb, or property of significant value; and (2i) Drunkenness in traffic, which prohibits driving while not in a condition to do so safely due to consumption of intoxicants. The police are permitted to check for drug use in any situation, even by random testing. These offenses give rise to a fine or up to 5 years imprisonment. This provision covers alcohol and the substances specified in the appendix, e.g. cannabis (THC), heroin, morphine, cocaine (benzoylecgonin), amphetamine, and MDMA. There are specified limits for the named substances, and over these limits the driver will be considered impaired.
Italy
In the Netherlands, according to the Road Traffic Law 1994, there are three criminal offenses: (1) causing a fatal traffic accident under the influence of drugs may be punished by a maximum imprisonment of 9 years or a maximum fine of E45 000; (2) causing an accident under the influence of drugs, which inflicted bodily harm, may be punished with a maximum imprisonment of 3 years or a maximum fine of E11 250; (3) if a person has driven a motor vehicle under the influence of drugs that affect the ability to drive or has the motor vehicle driven by someone who is under the influence of such drugs, then the driving license may be suspended for a maximum period of 5 years. Testing can take place if there is a presumption of driving under the influence of drugs, for instance, after causing a traffic accident or after bad driving. In the near future, it is proposed to penalize someone who is driving a motor vehicle under the influence of one or more drugs or medicines specified in the list if the concentration in that individuals blood is higher than the maximum limit indicated on the list. The drugs covered in the proposal include, among others, cannabis, heroin, and cocaine.
Spain
In Italy, article no. 187 of law 285/1992, the New Highway Code, makes it a criminal offense to be in an altered physical or mental condition related to the use of narcotic or psychotropic substances when driving. Roadblocks may be established for alcohol testing, but specific tests for drugs are made on the basis of
In Spain, the Organic Law 10/1995, of November 23, 1995, has modified Article 379 of the Penal Code: A driver under the influence of poisonous, narcotic or psychotropic substances or alcohol will be punished by the penalty of 812 weekend arrests for 38 months, and in any case, suspension of the driving license for one to four years. The offense may be either a criminal offense or an administrative infraction. Drivers may be tested at any time, for instance during traffic checks. Although both criminal offenses and administrative infractions deal with driving under the influence or under the effects, it is an administrative infraction when it is proven by positive analysis that the driver has taken drugs. It is a criminal offense if the drugs taken have some effect on road traffic, and put other drivers at risk.
The UK
In the UK, road traffic law governs this issue. Section 4 of the Road Traffic Act 1988 states: A person who, when driving or attempting to drive a motor vehicle
on a road or other public place, is unfit to drive through drink or drugs is guilty of an offence. Road traffic law does not distinguish between specific drugs. It simply deals with the impairment of driving. Penalties are the same as for driving under the influence of alcohol, and it is a criminal offense. These penalties are obligatory disqualification from driving for a minimum of 12 months (or 311 points license endorsement if exceptionally not disqualified); a fine of up to 5000 (approximately E7000); and a prison sentence of up to 6 months at the courts discretion. Drivers can be tested on police suspicion after poor driving or after an accident random stopping specifically for drug-testing purposes is not permitted. If they have sufficient grounds for suspicion, however, the police have the power of arrest and to take samples at a police station for formal assessment of breath, blood, or urine testing. The European Union has made major changes to its legislation in the past 5 years. Many factors are taken into account when establishing such laws, including the availability of practical and reliable drug testing and the impact of drugs and driving on public health. In some countries, such as Finland, a person found with traces of illicit drugs in the body during a test for drug driving may be prosecuted for illicit drug consumption; in other countries, such as Belgium and the UK, there are specific clauses in the road traffic law that prohibit the results of the tests being used for any other criminal charges. It remains difficult to prove scientifically that a person is actually under the influence at the time of driving, i.e., that his/her skills were affected. In addition, some laws provide for a driver to be adversely affected, whereas others may simply mention being under the influence this latter clause may lead to the punishment of a person who has taken a controlled substance in order to be well enough to drive a vehicle. Many countries do not specify what substance may be the cause of an offense. Austrias classification includes all except most benzodiazepines and barbiturates, Sweden and Finland exempt medical substances that the person has a right to use, France prohibits only narcotic substances, and Belgium specifies seven substances. But all the countries treat the combination of drugs and driving as a criminal offense. Nine European Union countries allow stopping for testing in any situation, such as random traffic checks, whereas six, including France, require some form of suspicion in order to carry out the test. Prison sentences (most severe in Germany), duration of license suspension (longest in Finland and the Netherlands), and levels of fines (greatest in Belgium and the UK) vary widely.
Worldwide Statistics on Driving under the Influence

Statistics show differences according to the dates of the studies, with an increasing proportion of drug use in drivers in more recent times, and according to the countries and type of studies cut-off levels (below which a result is considered negative) of drug levels also vary. Among early reports, an epidemiological report concerning drivers suspected of driving under the influence of drugs during the period 19821994 included 641 cases (86% men). The average age of the drivers was 27 7 years and the 1830-year age group was overrepresented (80%). Samples were taken after a traffic accident occurred in 254 (40%) of cases on 368 drivers suspected of driving under the influence of drugs (58%). In these cases, cannabinoids were found in 57%, opiates in 36%, ethanol in 36%, benzodiazepines in 15%, cocaine in 11%, methadone in 10%, and amphetamines in 4%. The majority (58%) of cases presented two or more drugs in biological samples, thus indicating a high incidence of potential interactions between drugs. During the 4-year study period from 1995 to 1998, a total of 752 biological samples from drivers suspected of driving under the influence of drinking and/ or drugs in Scotland were analyzed. Toxicological analyses revealed that cannabis was the most frequently encountered illegal drug, which was detected in 39% of all drug-positive blood samples. Benzodiazepines were detected in the majority of drug-positive samples, with 82% containing at least one member of this group. Polydrug use was prevalent, with the average number of drugs detected per sample increasing from 2.0 in 1995 to 3.1 in 1998. For comparison, the results of toxicological analyses from 151 fatally injured drivers tested positive for drugs in 19% and alcohol in 33%, showing that this was the main causative factor conducive to fatal road traffic accidents. From July 1, 1994 to June 30, 1995, a systematic drug and alcohol testing of blood and urine samples of drivers injured in weekend car crashes in Belgium was conducted. All injured weekend drivers admitted to emergency units were included in the study sample. Of the 211 injured drivers, 47.9% had positive test results for screenings for drugs or alcohol, 35.5% for alcohol alone, 6.6% for drugs alone, and 5.7% had positive results for both alcohol and drugs. Blood alcohol concentrations were 150190 mg dl1 in 25% of cases, and over 200 mg dl1 in 39%. For most of those with positive findings for alcohol alone or for drugs and alcohol (respectively, 72% and 78%), hospitalization in a general hospital unit or intensive care unit was necessary.
A study to determine the prevalence of opiates, cocaine metabolites, cannabinoids, and amphetamines in the urine of drivers injured in road traffic accidents was conducted in France in 1996, comprising 296 drivers aged 1835 years. Screening for drugs in urine was performed by fluorescence polarization immunoassays in each center and positive results were verified using gas chromatographymass spectrometer. Cannabinoids were found in 13.9% of drivers (16.0% of males and 8.3% of females, P < 0.05). Opiates were present in 10.5% of drivers urine samples. The prevalence of cocaine metabolites in drivers and patients was 1.0 and 1.1% while that of amphetamines was 1.4% and 2.5%, respectively. It seems that the high prevalence of cannabis and opiate use in young injured drivers has potential implications for road traffic safety in France. In 1996, blood samples from drivers suspected by the police of driving under the influence were collected in five Nordic countries (Denmark: n 255, Finland: n 270, Iceland: n 40, Sweden: n 86, Norway: n 149) and analyzed for alcohol and drugs (benzodiazepines, cannabinoids, amphetamines, cocaine, opiates, and a number of antidepressant drugs). Blood alcohol concentrations (BACs) below the legal limits were found in 32%, 18%, and 2% of the Norwegian, Icelandic, and Finnish cases, respectively (BAC < 0.05%), in 10% of the Danish cases (BAC < 0.08%) and in 20% of the Swedish cases (BAC < 0.02%). Drugs were most frequently found in the Norwegian and Swedish cases with no alcohol (8083%). Similar frequencies of drugs in samples with BACs above the legal limits (1922%)
were obtained for all countries showing combined use. Benzodiazepines, THC, and amphetamine represented the most commonly detected drugs. In South European countries, the phenomenon of driving under the influence of drugs is also widely observed. Samples were obtained for 5745 drivers killed in road accidents from January 1991 to December 2000. Of the samples, 91.7% represented males and 8.3% females, and 40.7% were under 30 years of age. Between 1991 and 2000, some type of psychoactive substance was detected in 50.1% of those drivers killed in road accidents, mainly alcohol (43.8%) and, less frequently, illicit drugs (8.8%). In all cases in which alcohol was detected, combined use with other substances accounted for only 12.5%, whilst in the case of BAC over 0.8 g l1 was recorded: cocaine (5.2%), opiates (3.2%), and cannabis (2.2%) were the three illicit drugs most frequently detected. The results showed the frequent presence of psychoactive substances, particularly alcohol, among Spanish motor vehicle users involved in fatal road accidents and pointed out that illicit and medicinal drugs in combination with other substances were a common feature. Far away from Europe, the incidence of alcohol and drugs in fatally injured drivers was determined in three Australian states for the period from 1990 to 1999. A total of 3398 driver fatalities were investigated, including 2609 car drivers, 650 motorcyclists, and 139 truck drivers (Figure 3). Alcohol at or over 0.05 g per 100 ml was present in 29.1% of all drivers. The highest prevalence was in car drivers (30.3%) and the lowest in truckers (8.6%). Almost 10% of
Figure 3 A garbage truck driver under the influence of drugs did not see his coworker behind him and reversed his truck over him.
cases involved both alcohol and drugs. Drugs (other than alcohol) were present in 26.7% of cases and psychotropic drugs in 23.5%. These drugs comprised cannabis (13.5%), opioids (4.9%), stimulants (4.1%), benzodiazepines (4.1%), and other psychotropic drugs (2.7%). The range of THC blood concentrations in drivers was 0.1228 ng ml1, with a median of 9 ng ml1. Opioids consisted mainly of morphine (n 84), codeine (n 89), and methadone (n 33), while stimulants consisted mainly of methamphetamine (n 51), MDMA (n 6), cocaine (n 5), and the ephedrines (n 61). The prevalence of drugs increased over the decade, particularly cannabis and opioids, while alcohol decreased. Cannabis had a larger prevalence in motorcyclists (22.2%), whereas stimulants had a much larger presence in truckers (23%). This study lends weight to the point of view that driving under the influence of drugs is at least as important as driving under the influence of alcohol (with frequent combined uses), especially in younger drivers. A more recent important study was conducted in France to determine the prevalence of alcohol, cannabinoids, opiates, cocaine metabolites, amphetamines, and therapeutic psychoactive drugs in blood samples from drivers injured in road accidents after 2001. The study included 900 drivers involved in a nonfatal accident who attended the emergency unit. BAC exceeding 0.5 g l1 (the legal French threshold) was found in 26%. In the 1827-year age range, alcohol was the only toxin found in blood samples of 17%. In all age groups, the main active substance of cannabis, THC, was found in 10% of drivers but in the under27-year group, THC (>1 ng ml1) alone was detected in the blood of 15.3%. THC was found alone in 60% of cases and associated with alcohol in 32% of cases. Morphine prevalence in drivers was 2.7% and the most frequently observed psychoactive therapeutic drugs were benzodiazepines in 9.4%. This study demonstrated a higher prevalence of opiates, alcohol, cannabinoids, and the combination of these last two compounds in blood samples from drivers involved in road accidents, suggesting a causal role for these compounds in road crashes.
Urine Drug Testing: How to Perform Roadside Testing?

Testing of drivers who are under the influence of drugs is mainly based on urine samples. Saliva and sweat, two methods appearing to be simpler and easier to apply, do not give accurate results. The specificity and sensibility of these methods are not
high enough to authorize their use for judicial procedures. A rapid urine test to identify reckless drivers who are under the influence of cocaine or marijuana is needed. However, intoxicated drivers show a broad range of effects and appearances. Nearly half the drivers intoxicated with cocaine perform normally on standard sobriety tests. In a 1993 US study, 150 subjects stopped for reckless driving provided urine samples for drug testing at the scene of arrest. Eightyeight (59%) tested positive: 20 (13%) for cocaine, 50 (33%) for marijuana, and 18 (12%) for both drugs. Ninety-four drivers were clinically considered to be intoxicated, and 80 of them (85%) tested positive for cocaine or marijuana. The intoxicated drivers showed a broad range of effects and appearances. In summary, over half of the reckless drivers who were not intoxicated with alcohol were found to be intoxicated with other drugs, indicating that toxicological testing at the scene is a practical means of identifying drivers under the influence of drugs (Figure 4). During the year 1996, 25 drivers who had died in road accidents and 38 injured drivers were tested by the emergency forensic physicians of the university teaching hospital at Jean Verdier near Paris. Their mean age was 24.3 4.2 and 26.5 3.9 years, respectively. Globally, the respective prevalence of positive drug testing for dead drivers and injured drivers was 40% (n 10/25) and 34% (n 13/38) for cannabinoids; 16% (n 4/25) and 3% (n 1/38) for opiates; and 8% (n 2/25) and 16% (n 6/38) for cocaine. The respective prevalence of alcohol level above the legal threshold value for drivers (0.5 g l1 in blood in France) was 44% (n 11/25) in dead drivers and 26% (n 10/38) in injured drivers (chi-square test: P < 0.008), indicating an influence of high alcohol level in cases of fatal road accidents. A positive result in urine for more than one substance or at least a substance and alcohol was found in 7 of 25 dead drivers (28%) and 8 of 38 injured drivers (21%). Positive detection of drug in urine represented, in dead and injured drivers, respectively, in the age groups: 37% (aged 1819), 33% (aged 2024), 55% (aged 2529), and 29% (aged 3034). A peak of drug use in victims (drivers) of road accidents was observed in the 2529-years group. The problem of driving under the influence of drugs and alcohol also concerns professional drivers. Among them, commercial tractortrailer drivers may endanger many people on the road if they operate their vehicles while under the influence of drugs. In Australia, a total of 822 drivers were tested for drugs. Anonymous urine specimens for drug analysis
Figure 4 A man hit on a zebra crossing by a heavy truck (44 tons). The body is under one of the truck middle wheels. The driver was under the influence of cannabis.
were requested, and 822 urine specimens were obtained in total. Overall, 21% of the urine specimens tested positive for illicit, prescription, and/or over-the-counter drugs, and 7% tested positive for more than one drug. The largest number of positive findings (9.5%) was for central nervous system stimulants, such as methamphetamine, amphetamine, ephedrine/pseudoephedrine, and cocaine. The second most frequently encountered drug class was the cannabinoids, with 4.3% of professional drivers testing positive for marijuana metabolites. Only 11 drivers (1.3%) were positive for alcohol. The results indicate that some tractortrailer drivers are taking illicit and other drugs with a potentially negative effect on their driving ability and which may be responsible for serious car crashes (on highways for example) or accidents (when driving a gas trailer, for example). Driving under the influence of alcohol or drugs now affects many age groups and both sexes, although women are underrepresented. Among them, the most frequent drugs in addition to alcohol are THC, benzodiazepines, and amphetamine. Problems related to illicit drugs have direct effects on fitness to drive, since drivers with illicit drugrelated problems are involved in road accidents three times more often than those without such problems, according to the most recent European studies. There is now enough information about the impact of drug use among drivers and on drivers impairment by drugs other than alcohol on road safety. Information on drivers drug use has come from tests on
people killed in crashes or hospitalized with crash injuries. Most studies have found drugs other than alcohol among 10% of fatally injured or hospitalized car drivers of all ages. These percentages are much higher in younger drivers and in weekend-injured drivers. Moreover, illicit drugs are not usually found alone but more often are found in combination with high BACs. Different drugs impair people differently. Any illegal drug may cause the following reactions: slowing of reaction time, alteration of depth perception, reduction of peripheral vision, confusion, drowsiness, and lack of awareness of surroundings. All these reactions may be useful or vital when driving. On the one hand, dangers of driving after using cannabis are due to longer response times to events or situations and possibly choosing an inappropriate response, the inability to think clearly and to pay attention to other road users, and blurred vision. On the other hand, ecstasy can cause blurred vision and distorts visual perception, making it difficult to judge distances. Ecstasy is a stimulant drug and gives a driver a false sense of confidence, energy, and power. It may impair judgment and increase risk-taking behavior, such as more aggressive driving, decreasing the ability to coordinate the appropriate reaction while driving. Last but not least, it must be remembered that alcohol is involved in a third to a half of all car crashes with fatally injured drivers on weekends, especially at nighttime. Changes in nighttime single-vehicle crashes are an accurate means of measuring the changing role of alcohol in road accidents and crash deaths.
See Also
Road Traffic, Determination of Fitness To Drive: Sobriety Tests and Drug Recognition; General; Driving Offense
Further Reading
Augsburger M, Rivier L (1997) Drugs and alcohol among suspected impaired drivers in Canton de Vaud (Switzerland). Forensic Science International 85: 95104. Carmen del Rio M, Gomez J, Sancho M, Alvarez FJ (2002) Alcohol, illicit drugs and medicinal drugs in fatally injured drivers in Spain between 1991 and 2000. Forensic Science International 127: 6370. Christophersen AS, Ceder G, Kristinsson J, Lillsunde P, Steentoft A (1999) Drugged driving in the Nordic countries a comparative study between five countries. Forensic Science International 106: 173190. Couper FJ, Pemberton M, Jarvis A, Hughes M, Logan BK (2002) Prevalence of drug use in commercial tractor-trailer drivers. Journal of Forensic Science 47: 562567. Drummer OH, Gerostamoulos J, Batziris H, et al. (2003) The incidence of drugs in drivers killed in Australian road traffic crashes. Forensic Science International 134: 154162. EMCDDA (1999) Literature Review on the Relation between Drug Use, Impaired Driving and Traffic Accidents, at http://www.emcdda.eu.int/multimedia/project_ reports/situation/drugsanddriving_report.pdf. EUs ROSITA project (Roadside Testing Assessment) reports at http://www.rosita.org
Longo MC, Hunter CE, Lokan RJ, White JM, White MA (2000) The prevalence of alcohol, cannabinoids, benzodiazepines and stimulants amongst injured drivers and their role in driver culpability. Part I: the prevalence of drug use in drive the drug-positive group. Accident Analysis and Prevention 32: 613622. Marc B, Bontemps V, Baudry F, et al. (2000) Drugs of abuse in urine of young adult drivers involved in road accidents in a Paris suburb (1996). Journal of Clinical and Forensic Medicine 7: 7781. Marquet P, Delpla PA, Kerguelen S, et al. (1998) Prevalence of drugs of abuse in urine of drivers involved in road accidents in France: a collaborative study. Journal of Forensic Science 43: 806811. Mura P, Kintz P, Ludes B, et al. (2003) Comparison of the prevalence of alcohol, cannabis and other drugs between 900 injured drivers and 900 control subjects: results of a French collaborative study. Forensic Science International 133: 7985. Schepens PJ, Pauwels A, Van Damme P, et al. (1998) Drugs of abuse and alcohol in weekend drivers involved in car crashes in Belgium. Annals of Emergency Medicine 31: 633637. Seymour A, Oliver JS (1999) Role of drugs and alcohol in impaired drivers and fatally injured drivers in the Strathclyde police region of Scotland, 19951998. Forensic Science International 103: 89100. Steinmeyer S, Ohr H, Maurer HJ, Moeller MR (2001) Practical aspects of roadside tests for administrative traffic offenses in Germany. Forensic Science International 121: 3336. Tomaszewski C, Kirk M, Bingham E, et al. (1996) Urine toxicology screens in drivers suspected of driving while impaired from drugs. Journal of Toxicology and Clinical Toxicology 34: 3744.
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SERIAL MURDER
R J Morton and J J McNamara, Serial Killer Unit, FBI Academy, Quantico, VA, USA
Published by Elsevier Ltd.
Definition
Law enforcement, mental health, and academic professionals have used a variety of definitions to describe serial homicide. Although a number of individuals have claimed to have invented the term serial murder, one of the earliest known references to that term was in a chapter titled The serial murderer, in the 1950 book, The Complete Detective: Being the Life and Strange and Exciting Cases of Raymond Schindler, Master Detective, by Rupert Hughes. The Federal Bureau of Investigations (FBI) Behavioral Science Unit first informally defined serial murder as a series of homicides, committed by a murderer who kills in 10 or more separate incidents. Over several years, the definition of serial homicide was refined by the FBI as a series of three or more homicides that are premeditated, planned, involve a fantasy component, and are separated by an emotional cooling-off period between the homicides that can last days, weeks, or months. According to this definition, it is the cooling-off period that separates serial offenders from other types of multiple murderers. In 1998, the US Congress passed legislation that defined serial killings as a series of three or more murders, having common characteristics to suggest that these crimes were committed by the same individual or individuals. Social scientists, law enforcement officers, mental health professionals, and academics have adopted different versions of serial murder that include a series of at least two or three murders committed as separate events by an individual or individuals, with a cooling-off period between offenses. Many definitions also include references to geography, themes of dominance, ritual, sadism, and sexual or fantasy elements. The variance of emphasis on the nuances of serial murder has led to multiple definitions. There is no consensus as to a single definition of serial murder. For the purposes of this article, the definition of serial murder will be three or more independent, planned murders committed by the same individual or individuals, and separated by a cooling-off period.
Introduction
In the realm of forensic science and law enforcement, the issue of serial homicide occupies a unique niche. There is a macabre attraction to the phenomenon of serial murder that draws an overabundance of attention from people within law enforcement, mental health, academia, the media, and the general public. Although serial homicides account for only a small portion of the total number of homicides committed every year, the resources required to investigate cases and identify and prosecute serial offenders can be staggering. Serial offenses, though rare, generate interest well beyond the proportion of the problem. The overall effect is to sensationalize a crime that requires the same detailed, methodical process required for any complex investigation. The difficulty for the medicolegal community lies within the nature of a serial offender, who for the most part, chooses victims with no apparent connection to himself. This lack of connection between offender and victim requires serial investigations to deviate from normally successful violent crime investigative strategies. Unknown relationship crimes are among the most difficult of crimes to investigate. This overview of serial murder acknowledges the perspective of a multitude of disciplines and definitions, examines attempts to classify serial murder into defined typologies, and reviews the epidemiology of serial murder. Finally, the authors employ their extensive case experience with actual serial murder cases in an attempt to ascertain any recognizable patterns of behavior and to define that behavior. The overall goal is to provide the medicolegal community with a broader understanding of serial murder that will ultimately provide assistance in the investigation of these types of cases.
48 SERIAL MURDER
The cooling-off period varies between offenders and can last hours, days, weeks, months, or even years, depending upon the particular circumstances in each offenders life. Planning is defined as any actions committed by an offender in preparation of a murder and involves the accumulation of items for use in the abduction, murder, and/or disposal and selection of a victim. Victim selection planning can range from simple observations to detailed surveillance of a victim or pool of victims.
Typologies
Academia, law enforcement, and the mental health communities have attempted to develop standardized typologies of serial murder and to reach a consensus regarding the definition of the term. The disadvantage of typologies is that they are blunt instruments used to measure very discrete data. They are label-driven, awkward to use, and attempt to provide a one size fits all explanation. Based upon the uniqueness and variances of human behavior, there are severe limitations in any specific serial murder typology.
generally more comprehensive and reliable than media accounts, are also secondary data, received from law enforcement investigators who use a collection form to record information about the crime, victim evidence, and suspect(s). Investigators levels of experience with and understanding of such offenses may vary widely since serial murder is a rare event. Broad-based, empirical studies of serial homicide are scarce because few researchers and/or academics have access to actual investigative case material. Some of these studies attempt to interpret very sensational but discrete and limited evidence, without having thoroughly reviewed case materials. To gain a comprehensive understanding of serial murder, researchers must review crime-scene photographs, police reports, laboratory reports, and victimology information, and must discuss the case with investigators or interview the offenders themselves (if possible).
Serial Murder
Many serial murder studies focus solely on sexually motivated murders and, indeed, include the sexual element as a necessary component of the definition. However, offenders may also commit three or more separate planned murders for other reasons or motivations. For instance, organized crime contract killings, drug/gang killings, or black widow killings can be motivated by revenge or profit. These types of serial killings involve victims who have a connection with criminal activity, or have a personal relationship with the offender. The motivation for serial killings in the healthcare setting involves perceived mercy or some unspecified intrinsic reason, for example, anger or appearing as the hero/rescuer. Angermotivated serial killings are often directed toward a targeted segment of the community, and the victims are chosen for their racial background, ethnic origin, gender, or sexual preferences. Product-tampering serial killing cases are extremely rare and involve a revenge or profit motivation. Thrill- or excitementmotivated serial killings are also very rare, and the victims are usually strangers. Motivation can be a synthesis of rationales, and could include combinations of anger, excitement, revenge, sex, or some other reason known only to the offender. Each discipline provides its own interpretation of the information, while this overview attempts to combine these into a multidisciplinary approach to a very complex issue. As noted earlier, for the purposes of this discussion, serial murder is defined as three or more independent, planned murders, committed by the same individual or individuals, and separated by a cooling-off period. This definition offers a broad, enveloping view of serial murder, instead of focusing
Epidemiological Perspective
Most serial murder studies rely upon information gleaned from media accounts of cases. These studies attempt to develop an empirical model of serial murderers crime scene behavior and to link crime scene behavior to the behavioral characteristics of the murderer. Data frequently include age, race, criminal history, marital status, employment status, cause of death, location and extent of trauma, weapon used, and manner and method of body disposal. Most such studies have found that the majority of the victims of serial murder were strangers to the offenders and were women or other vulnerable individuals. The studies are in agreement that the majority of serial murderers are male, have a criminal history, kill the victim for sexual motivations, kill by strangulation or stabbing, and dump the victims body in a remote location. Many crimes involve more than one crime scene or event site. Interpretation and generalization of many of the empirical studies are limited, particularly in those studies based primarily on media reports. Media accounts of crimes are secondary data and are often biased, fragmented, and limited in case information. Some research also uses the data contained in law enforcement databases, such as Washington States Homicide and Investigative Tracking System (HITS), the FBIs Violent Criminal Apprehension Program (ViCAP), and New York States Homicide and Lead Tracking (HALT) system. These sources, although
SERIAL MURDER 49
exclusively on one type of motivation, or other crime characteristic.
Serial Sexual Murder

The category of serial murder that elicits the most attention and encompasses a large percentage of serial murders is referred to as sexual homicide. For the purposes of this article, serial sexual homicide, or serial sexual murder, is defined as three or more independent, planned murders, committed by the same individual or individuals, separated by a cooling-off period, and having a sexual motivation. The overwhelming majority of serial sexual murders are committed by male offenders. Unlike other serial crimes, sexually motivated serial murderers overwhelmingly target victims who have no apparent connection to the offender, or who are complete strangers. The appearance of randomness in victim selection generates an overabundance of attention from the media and fear in the general public because of the perception that anyone could become the target of a serial sexual murderer. Serial sexual murders are rooted in fantasies that involve violent sexual themes. Offenders who commit serial sexual homicide have vivid, recurring, violent sexual fantasies that evolve over time. The existence of violent sexual fantasies is well documented in the literature, and there are commonalities in their origin and themes. The fantasies originate in childhood development and are a product of linking themes of violence and sex together. The sexually violent themes that offenders explore through their fantasies vary from individual to individual. The literature documents themes of sexual sadism, power and domination, necrophilia, and many others. The eroticized violent themes evolve over time and become more sophisticated and detailed until the offender acts out his violent sexual fantasy. The offenders violent sexual fantasy then meets the reality of his violent sexual acts. If part of the offenders fantasy acts is distasteful to him, he will adapt to avoid the portion of the act he found unappealing. If he discovers a part of the fantasy act that is pleasurable to him, he will spend more time exploring that act. The fantasy evolves as the offender commits more predatory offenses. This is the reason sexual behavior can appear to become increasingly more bizarre throughout a series of linked sexual homicides. An important factor in understanding the depth and breadth of violent sexual fantasies is recognizing how detailed and vivid these fantasy constructs become. Offenders constantly think about their fantasies and explore and relive them. One of the best examples of the vividness of a violent sexual fantasy
involved a case where photographs of a victim being tortured and sexually assaulted were discovered after the sexual murderer had been arrested and imprisoned for several months. After the photographs were found, the offender, while in his jail cell, constructed a series of drawings to explain the nature of the photographs, without having the photographs to refer to. A comparison of the drawings to the photographs revealed the detail to be almost identical. This was phenomenal considering the offender had not seen the location depicted in the photographs or the photographs themselves for several months (Figures 1 and 2). Serial sexual murderers have violent sexual fantasies and commit predatory violent sexual acts to fulfill those fantasies. The acts committed on a victim are the result of the offender acting out his fantasy. During the investigation of violent serial sexual murders, law enforcement or mental health professionals might attempt to identify specific motivations of the offender based upon an examination of the crime scene. Interpretation of specific fantasy themes through crime-scene analysis is very problematic. Similar to the general public, serial sexual murderers keep their sexual fantasies private and do not usually allow anyone to know the depths of their predilections. The privacy of such thoughts highlights the tremendous difficulties in identifying a specific fantasy based solely on a crime-scene interpretation, particularly when the offenders identity is unknown.
Figure 1 Polaroid photograph of the victim recovered several weeks after the offenders arrest, showing the victim bound and blindfolded.
50 SERIAL MURDER
Figure 2 Drawing made by the offender in his jail cell, after discovery of the Polaroid photographs. The drawings were an attempt to explain the purpose of the photographs.
Victim selection by serial sexual murderers is based upon three factors: (1) availability; (2) vulnerability; and (3) desirability. Availability deals with an offenders access to a particular victim, vulnerability highlights the victims risk level in becoming the victim, and desirability reflects how the victim corresponds to the offenders fantasy. High-risk victims can be described as individuals who, by occupation, activities, and/or lifestyle, are at high risk of becoming the victims of violent crime. Low-risk victims are individuals who, by occupation, activities, and/or lifestyle, are at low risk of becoming the victims of violent crime. The victim may be selected/targeted individually, or may be selected from a targeted pool of victims. Targeted victims are those who are singled out specifically by an offender as a potential target, while a targeted pool represents a group of potential victims from which the offender can select an individual. Targeted-victim pools are often groups of high-risk victims, such as prostitutes. Targeted victims are individuals whose risk levels range from low to high, depending upon occupation, activities, and/or lifestyle. Questions often arise in serial sexual murder investigations concerning why an offender will strike within a certain geographic area as opposed to another, apparently similar area. Serial sexual murderers are predators, and, just like predators from the animal kingdom, they hunt in areas they are very familiar with, and where desirable victims are
available. This is analogous to the waterhole theory, where predators go to the watering hole to look for prey, because that is where the prey are known to congregate. In examining the phenomenon of serial sexual murder, an important feature for the medicolegal investigator is identifying the different sites associated with the initial contact, assault, murder, and disposal of a victim by an offender. The initial contact site is the location the offender first makes contact with the victim. The assault site is the location where the offender sexually assaults the victim. The murder site is the location where the offender kills the victim. The disposal site is the location where the offender leaves the victims body. These can be separate sites, a combination of sites, or one single site, depending on the circumstances and the actions and/or motivations of the offender. The offenders initial contact with a victim will be one of the three universal approaches: con, surprise, or blitz. In the con or ruse approach, the offender uses his verbal skills to ingratiate himself with the victim, by designing a believable story. In the surprise approach, the offender capitalizes on circumstances, locations, and timing to gain control of a victim quickly. Once the surprise has been sprung, the offender employs verbal commands to guide the victim through the scenario. In the blitz approach, the offender forgoes any verbal interaction, and goes directly to a physical attack. Once the offender gains
SERIAL MURDER 51
control, there are a number of ways in which control is maintained over the victim, including bindings, isolation, physical and psychological threats, and display/use of weapons.
Body Disposal
There are two basic body disposal scenarios that apply, based upon whether or not the offender leaves the victim at the murder site or transports the victim away from the murder site. Each scenario can reflect the relationship between the offender and the victim. Within each of those scenarios, there are several avenues the offender can pursue. If the offender leaves the victim at the scene, the victims body can be left without any further action by the offender, in the position the offender committed the act. This is done as a function of utility. Second, in order to fulfill a portion of his fantasy, the offender may position or display the body in a bizarre or suggestive manner. Lastly, the offender may attempt to conceal the victim at the scene by covering and/or hiding the victims body. If the offender transports the victim away from the murder site, one of the three scenarios can occur: the victim will be dumped, concealed, or displayed. If the victims body is dumped, the offender is generally unconcerned whether the victim will be found. Offenders conceal victims bodies because they wish to delay or preclude discovery, in an attempt to prevent authorities from identifying the victim, to destroy physical evidence, and/or to distance themselves from contact with the victim. In rare instances, the body is concealed to allow the offender to return to the site to experiment with and/or indulge in sex with the corpse. If the victims body is concealed, the disposal can be simplistic or complicated depending upon the criminal sophistication and experience of the offender. Concealed body disposals would also include placing the body or dismembered body parts in dumpsters, hiding the body in a building, covering the body with brush or debris, wrapping the body in carpet or other coverings, or burning the body. A burial scenario could be considered simple or complex, depending upon the sophistication, time, and effort utilized by the offender. Surface deposit scenarios could also be considered simple or complex depending upon the location chosen, covering used, distance from a roadway, and remoteness of the site. The last scenario would involve a victim who is transported from the murder scene, but is left displayed, just as described earlier (Figure 3). The literature contains a plethora of information regarding method of operation (MO), ritual, and signature. For the purposes of this article, MO is described as the means used or necessary to commit the crime, commonly referred to as modus operandi. Rituals are the symbolic acts reflective of behavior committed by the offender during the course of the crime that are not necessary for the successful
Causes of Death
Studies of serial murderers have reported several specific causes of death employed by offenders, including strangulation (both manual and ligature), stabbing/ cutting, blunt-force trauma, and firearms. Strangulation and cutting/stabbing were found to be the most common cause of death in several studies. The primary reason cited for the predominance of those causes of death was the intimate aspect of a hands-on kill. It is also the opinion of the authors, based upon extensive case experience, that a close-quarters, manual type of death forms a large portion of the fantasy fulfillment of serial sexual murder.
Crime Scene
Many crime-scene indicators exhibited by serial offenders reflect unusual behavior that can be attributed to their fantasies. These include displaying or posing the victims body and taking possessions of the victim as souvenirs or trophies. Offenders often position victims in bizarre manners and take unusual items from the crime scene. These concepts can be confusing to medicolegal investigators when attempting to interpret offender actions at a crime scene. The literature contains a variety of definitions and theories concerning the display of the victims body. Some of these definitions are complex and create unwieldy parameters to define the display concept. The authors define display of a victim as a deliberate action by the offender to position the body of the victim, either for personal fulfillment of his fantasy, to provide a message concerning the offenders opinion of the victim or class of victims, or, in very rare instances, to shock the police or the general public. The literature also contains a number of definitions of the concepts of souvenirs and trophies. Most of the debate centers on the offenders perceived motive for taking the object. Offenders remove objects from crime scenes for a number of reasons, including destroying physical evidence, theft, and fulfillment of some fantasy aspect. As with other aspects of human behavior, there can be more than one motivation for any action, and definitively ascribing a single motivation to an individual act is conjecture at best. The terms souvenirs and trophies will be used generally to describe objects taken from a crime scene, regardless of the motivation.
52 SERIAL MURDER
Left As Is
Displayed
Left at murder site
Concealed Water Surface
Body disposal
Concealed
Deposit Buried
Transported from murder site
Dumped
Displayed
Figure 3 Possible body disposal scenarios.
completion of the crime. Both MO and ritual activities at crime scenes can evolve and change based upon the success of the offender in committing the offense, the interaction of the victim with the offender, and other outside influences. However, MO and ritual evolve along different lines. MO is driven to change by practicality, while ritual is driven to change by fantasy. Signature is defined as the unique combination of MO and ritual that allows one serial case to be linked to others. The issue of signature creates the most discord and disagreement within the literature. Various authors place different weight on the accuracy of a signature, ranging from probability to identical beyond any doubt. As in most aspects of human behavior, the line between MO and ritual and the resulting signature is very blurred, and finite conclusions are unlikely, and very suspect.
which they act. Interpretation of the unusual and unconventional activities of serial offenders is extremely difficult. The medicolegal community should seek the assistance of qualified, experienced professionals, who investigate and study these types of offenders, to ensure that serial murderers are identified and prosecuted.
See Also
Criminal Profiling; Dogs, Use In Police Investigations; Forensic Psychiatry and Forensic Psychology: Sex Offenders
Further Reading
Dietz PE (1986) Mass, serial and sensational homicides. Bulletin of the New York Academy of Medicine 62: 477491. Geberth VJ (1996) Practical Homicide Investigation, 3rd edn. Boca Raton, FL: CRC Press. Geberth VJ, Turco RN (1997) Antisocial personality disorder, sexual sadism, malignant narcissism, and serial murder. Journal of Forensic Science 42: 4960. Godwin GM (2000) Hunting Serial Predators: A Multivariate Classification Approach to Profiling Violent Behavior. Boca Raton, FL: CRC Press. Hughes R (1950) The Complete Detective: Being the Life and Strange and Exciting Cases of Raymond Schindler, Master Detective. New York: Sheridan House.
Summary
Serial murder is a rare and bizarre phenomenon. It creates immense difficulties for the medicolegal community in terms of resources required to investigate, identify, and prosecute a serial murderer. Most serial killers are males, who murder for sexual reasons, kill strangers, utilize strangulation or stabbing as the method of death, and have some history of arrest. Serial sexual murderers commit sexual homicide because they have vivid violent sexual fantasies on
SEROLOGY/Overview 53 Keppel RD (1997) Signature Killers. New York: Pocket Books. Keppel RD, Birnes WJ (2003) The Psychology of Serial Killer Investigations, The Grisly Business Unit. San Diego, CA: Academic Press. Malmquist CP (1996) Homicide: A Psychiatric Perspective. Washington, DC: American Psychiatric Press. Ochberg FM, Brantley AC, Hare RD, et al. (2003) Lethal predators: psychopathic, sadistic, and sane. International Journal of Emergency Mental Health 5: 121136. Ressler RK, Burgess AW, Douglas JE (1988) Sexual Homicide: Patterns and Motives. Lexington, MA: Lexington Books. Samenow SE (1984) Inside the Criminal Mind. New York: Time BooksRandom House. Schlesinger LB (ed.) (2000) Serial Offenders: Current Thoughts, Recent Findings. Boca Raton, FL: CRC Press. Schlesinger LB (2004) Sexual Murder: Catathymic and Compulsive Homicides. Boca Raton, FL: CRC Press. Smith MD, Zahn MA (eds.) (1999) Homicide: A Sourcebook of Social Research. Thousands Oaks, CA: Sage. Witte G (2000) A Comparative Analysis of Serial Homicide and Single Homicide Event Characteristics. Philadelphia, PA: MCP Hahnemann University and Villanova Law School.
SEROLOGY
Contents Overview Blood Identification Bloodstain Pattern Analysis
Overview
J Ballantyne, University of Central Florida, Orlando, FL, USA
2005, Elsevier Ltd. All Rights Reserved. This article is adapted from Serology: Overview in Encyclopedia of Forensic Sciences, pp. 13221331, 2000, Elsevier Ltd.
The Probative Significance of Biological Evidence Transfer

The perpetration of a violent crime often results in a number of different types of biological material being transferred in a unidirectional or bidirectional manner between the victim, the perpetrator, the crime scene, or the weapon (Figure 1). A genetic analysis of such biological material by the forensic biologist may yield important legal evidence that may associate or exclude a particular individual with the crime in question. Such analysis may also aid in the reconstruction of the sequence of events which occurred before, during, or after the commission of the crime. Based upon the circumstances of the case it is incumbent on the investigators (whether law enforcement officials or forensic scientists) to evaluate the potential probativeness of biological evidence which may have been transferred. By probativeness is meant the degree of meaningfulness of the potential information gleaned by examination of a particular piece of biological evidence as it relates to establishing a relevant fact which may be at issue. Examples of good probative evidence would include the finding of the presence of the perpetrators semen in the vagina of the rape victim or the presence of the deceaseds blood on the perpetrators clothing. Examples of evidence which would possess low or almost nonexistent probative value would include
Ethos
Serology is defined as the study of the composition and properties of the serum component of blood. Despite this inadequate description of what has colloquially become known as forensic serology, many individuals and laboratories use this rubric to describe a practice that more accurately could be described as forensic biology, forensic molecular genetics, or forensic biochemistry. Forensic serology, then, is the application of immunological and biochemical methods to identify the presence of a body fluid or tissue sample encountered in connection with the investigation of a crime, and the possible further genetic characterization of the sample with a view to determining possible donors thereof. For the purposes of this article the genetic characterization involves polymorphic cellular antigens and proteins (i.e., those that exhibit variable forms in the population) but does not include DNA genetic markers.
54 SEROLOGY/Overview
Figure 1 Directionality of biological evidence transfer. Reproduced from Ballantyne J. Serology: Overview. In Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
the finding of blood from a deceased in immediate proximity to the bloodied body itself or the finding of semen on the inside of a rape suspects underpants. The probative value of the evidence greatly increases if there is a demonstrated bidirectional transfer. An example of such transfer would be the transfer of the rape victims menstrual blood on to the rape perpetrators underwear concomitant with the assailants semen being deposited on the victim. In some circumstances the analysis of the nature and distribution of the stain is more important than the genetic characterization of it. A tiny spot of blood consistent with a low-velocity blood spatter pattern on an individuals clothing may belie his attempt to explicate the presence of the blood as a result of a good-Samaritan act. Thus it is important to evaluate the circumstances of each crime in order to make a rational judgment as to which evidence to remove for analysis.
The Role of Forensic Serology in the Post-DNA Era

It is now a matter of routine for the forensic scientist to obtain the (practically) unique genetic profile of an individual from DNA recovered from a biological stain deposited at the crime scene. Subsequent to a comparison between the crime-scene DNA sample and a known DNA sample from the individual in question, the person is included or excluded as a potential donor of the stain. Before attempting DNA analysis, it used to be standard practice to perform biochemical, serological, and immunological tests to identify the body fluid(s) comprising the biological stain. Increasingly, however, classical methods for body fluid identification are being supplanted by the facile and routine identification of human DNA in the sample extract. Proponents of this approach argue that demonstration of the presence of human DNA from a particular individual is sufficient and that the cell type (i.e., body fluid or tissue) from which the DNA originated is inconsequential.
While the ability to bypass conventional body fluid identification tests is appealing due to a perceived increase in operational efficiency, there are a number of case scenarios where body fluid identification per se could still provide important probative evidence. For example, consider a sexual assault involving vaginal intercourse whereby the female victim at the time of the assault is in menses. Blood is identified on the suspects clothing and, based upon DNA testing, is found to be consistent with having originated from the victim. The defense could argue that the blood came from the victims nose when she was punched by the suspect, and any sexual act is denied. However, the prosecution would argue that the blood was transferred as a direct result of the sexual assault. The ability to identify blood as menstrual in origin, as opposed to circulating peripheral blood, would be significant. In another case, the identification of vaginal secretions, for which no biochemical test currently exists, would assist the investigation. This example involves an alleged rape inside a vehicle in which the DNA of the victim is found on the car seat. The defense could argue that the DNA came from sweat or skin from the victims leg as she was sitting in the car. However, confirmation of the presence of her vaginal secretions would be incontrovertible evidence of sexual activity. In a third case, DNA from a victim is found on an implement that is believed to have been used in a sexual assault. The significance of this evidence would be enhanced by demonstrating that it originated from her vaginal secretions. The last example involves the sexual abuse of a young child by a person living in the same residence as the victim in which the suspects DNA is found on the childs clothing or bed linen. In many circumstances, it would be more difficult for the suspect to provide an innocent explanation for the presence of his semen versus traces of his saliva on these items. Since, as these cases illustrate, it can be important to identify the nature of the body fluid(s) present in a stain, the development of a body fluid identification system that is more compatible with current DNA typing technology is desirable.
The Importance of Communication between Law Enforcement and Laboratory Personnel

Communication of the circumstances of the case to the appropriate laboratory personnel is essential in order that an appropriate analytical scheme can be developed. Failure to do so could result in the inadvertent omission of certain tests that should have been conducted. An example of this would include an altercation that may have been precipitated as a result
SEROLOGY/Overview 55
of one individual spitting at another. If this information is not communicated to the laboratory, it is unlikely that testing for saliva would be performed and an important set of extenuating circumstances may not be corroborated. This is so because testing of clothing items for the presence of saliva is not normally performed in the forensic laboratory unless there is a specific reason to do so.
The Importance of Laboratory Search Activities

Evidence submitted to the laboratory must be processed and searched for the presence of probative physiological stains and for other trace materials. Searching takes place under a variety of lighting conditions, both with and without the aid of magnification. This general search phase is critical for locating materials of evidential value, recording information about the nature and location of these materials, and collecting and preserving them for later analysis. The general search phase often employs the use of a number of so-called presumptive chemical or biochemical tests for the presence of particular body fluids such as blood or semen. These preliminary tests allow the scientist to screen items efficiently prior to the use of more specific confirmatory tests.
Identification of Body Fluids and Tissues

Physiological material must first be identified as such before genetic analysis is performed. The most commonly encountered body fluids include blood, semen, saliva, and vaginal secretions, although there may be instances whereby the identification of fecal material, urine, and other physiological material may be necessary.
Blood
group is a nitrogenous planar structure, comprising a protoporphyrin IX ring and conjugated ferrous atom, which happens to possess an associated peroxidase activity (2H2O2 ! 2H2O O2). The peroxidaseinduced reduction of hydrogen peroxide can be coupled to the oxidation of a number of colorless (reduced) dyes such as phenolpthalein (Kastle-Meyer reagent), leuco-malachite green (LMG), o-toluidine, and tetramethyl benzidine to form their respective colored moieties. Alternatively, luminol (3-aminopthalhydrazide) can be oxidized to a product that luminesces and this is used to screen large areas for the presence of blood. In this case the area to be searched is sprayed with luminol reagent and the heme-induced luminescence is detected in the dark. Like luminol, fluorescein may be used to screen large areas for diluted blood stains but offers the advantage of being able to be used in a lighted environment. For convenience some laboratory tests employ commercially available clinical strips originally developed for occult blood determination (e.g., Hemastix, Bayer). These strips are embedded with peroxidase detecting reagents similar to those described above. The catalytic color tests are extremely sensitive to minute amounts of blood but can produce false-positive results in the presence of a number of substances, including chemical oxidants and catalysts and plant sources containing the enzyme peroxidase. The presence of chemical oxidants and catalysts can normally be excluded by performing a two-step test in which the colorless reduced dye is added first to check for the presence of heme-independent oxidation prior to the hydrogen peroxide substrate. Confirmatory tests Subsequent to a positive presumptive test, the presence of blood is confirmed by the immunological identification of Hb. Alternatively, a positive crystal test for the presence of certain heme derivatives or the demonstration of the characteristic visible absorption spectrum of Hb is regarded as conclusive proof of the existence of blood. The immunological identification of serum proteins is often employed to confirm the identification of blood as being of human (more strictly, primate) or animal origin. However, the latter is controversial in that the finding of a positive serum protein test could be due to the detection of homologous or identical proteins in a sample from a nonblood component (e.g., saliva or semen). Immunological identification of blood and determination of species origin The precipitin reaction occurs when a precipitating antibody combines with its conjugate antigen to produce an insoluble proteinaceous immune complex that can be detected
Blood consists of hematopoietic lineage cells (red blood cells, white blood cells, and platelets) in a proteinaceous fluid known as plasma. Serum is the fluid exuded from blood once it has clotted and thus comprises the plasma minus the proteins (principally fibrinogen and fibrin) responsible for the clotting process. Presumptive catalytic screening tests The principal function of blood is to transport oxygen to the tissues and remove carbon dioxide therefrom. The hemoglobin (Hb) molecule, which constitutes most of the protein content of the erythrocyte, or red blood cell, is principally responsible for this function and binding of the gas molecules takes place via the nonprotein prosthetic heme group of Hb. The heme
under appropriate oblique lighting conditions by the naked eye or by the use of general protein stains such as Coomassie blue or amido black. Polyclonal and monoclonal antibodies to serum proteins from humans and a range of domesticated animals are commercially available, as are antibodies to human Hb. The antibodyantigen reaction is either allowed to take place in an inert agar gel by diffusion of the antigen and antibody molecules toward one another (the Ouchterlony reaction or double diffusion in two dimensions) or is facilitated by an electric field (counterimmunoelectrophoresis or crossed-over electrophoresis). An immunochromatographic method initially developed for clinical use for occult blood is also in widespread use. In this method a dye-linked mobile monoclonal antibody to human Hb is allowed to react with the sample. If human Hb is present in the sample, it combines with the antibodydye complex and moves along a membrane until, in a reaction zone, it meets an immobilized polyclonal antibody to human Hb and is concentrated. A positive reaction is indicated by the formation of a dye front. A control zone consists of immobilized antiimmunoglobulin G that concentrates any unbound mobile monoclonal antibodydye complex and forms a dye front. Confirmatory crystal tests for the presence of blood The two main confirmatory crystal tests are the Teichmann and Takayama tests, named after their developers who initially described the reactions in 1853 and 1912, respectively. These tests rely on the formation of certain heme derivatives which are detected microscopically. The Teichmann test involves the formation of hematin (heme in which the ferrous ion has been oxidized to the ferric state) halide crystals, whereas the Takayama test induces the formation of salmon-pink pyridine hemochromogen crystals. Positive crystal tests, although specific for blood, provide no information regarding its species origin. Identification of blood by visible spectrophotometry The heme moiety of Hb has a characteristic absorption spectrum which, if present in a sample, is often regarded as conclusive evidence for the presence of blood. Although different heme derivatives produce different spectra, they all possess the Soret band at 400425 nm. Oxyhemoglobin produces two absorption bands at 538 and 575 nm and a shoulder peak at 610 nm, whereas hemochromogen displays a sharp peak at 550560 nm. This technique is confounded by the presence of a broad region of absorption at 500600 nm in blood stains that tends to obscure the diagnostic heme derivative peaks and, as a result, is not used routinely.
Fetal blood Normal adult Hb is a tetramer consisting primarily of two a and two b polypeptide chains (a2b2). However, during development of the embryo and the fetus, the e (embryo) and g (fetus) polypeptide chains are expressed instead of the b chain. Fetal blood can thus be distinguished from adult blood by the presence of the fetus-specific g subunit which is still detectable up to 6 months after birth. This can be accomplished immunologically with the use of antisera specific to fetal Hb (HbF) or by separation in an electrical field. Specificity problems with many antiHbF preparations for determining the Hb status in dried and aged stains have prevented its widespread use in forensic laboratories. Menstrual blood Menstrual blood may be transferred from a female victim of rape or assault to the assailant, and under certain circumstances the identification of it is of some investigative use. Menstrual flow consists of endometrial tissue, mucus, and blood. Usually not more than 5060 ml of blood is lost during the uterine cycle and it has the characteristic property of being unable to clot due to extensive degradation of the clotting factor fibrinogen (or its product fibrin). Fibrinogen degradation products are present in relatively high concentration in menstrual blood and can be detected immunologically and normalized against total protein to distinguish menstrual from venous blood. Alternatively, the isoenzymes of lactate dehydrogenase (LDH) can be used to distinguish venous from menstrual blood. Isoenzymes are structurally distinct forms of enzymes that have equivalent catalytic specificities. LDH is a tetrameric protein, the polypeptide chains of which can be of two types, H and M, thus giving rise to five possible isoenzymes, H4, H3M, H2M2, HM3, M4 or LDH 1, LDH 2, LDH 3, LDH 4, LDH 5. Venous blood consists primarily of the three isoenzymes LDH 1, LDH 2, and LDH 3, whereas menstrual blood additionally contains elevated levels of LDH 4 and LDH 5. Other tissues possess varying amounts of the LDH isoenzymes and, although the isoforms are readily separated by electrophoresis, difficulties with the presence of body fluid mixtures have limited the efficacy of this technique.
Semen
Semen principally comprises the germ cells (spermatozoa) suspended in a complex mixture of fluids secreted by various accessory glands of the male reproductive tract, including the prostate, seminal vesicles, Cowpers glands, and the glands of Littre. Spermatozoa make up 1025% of the volume of the semen and normal sperm density ranges from 60 to 100 million per ml. The ejaculate volume typically
ranges from 1 to 6 ml with an average of 3 ml and is dependent upon the time interval since the last ejaculation, the metabolic activity of the glands, and the presence of partial ductal obstruction. Screening tests Screening tests comprise the classical crystal tests for the presence of spermine (Barberio test) and choline (Florence test) or, more commonly, seminal acid phosphatase (SAP). The Barberio test relies on the formation of spermine phosphate or picrate crystals upon reaction of an appropriate extract from the suspected stain with appropriate anions. The Florence test detects the presence of choline periodide crytals when a semen extract is treated with a solution of iodine in potassium iodide. SAP is an enzyme present in high concentration in semen that, as a nonspecific orthophosphoric monoester phosphohydrolase, cleaves a variety of organic phosphates, including p-nitrophenyl-, a-napthyl-, and thymolphthalein monophosphates. As implied in its name, it is active at acid pH (4.95.5). Although SAP is a sensitive test, it is not specific for semen due to its presence in a number of other tissues, including, in particular, vaginal fluid. Confirmatory tests The presence of semen can be confirmed microscopically by the presence of spermatozoa or by the presence of the semen-specific protein p30. Spermatozoa Spermatozoa have a distinct and characteristic appearance as viewed under the microscope. They are 5060 mm in length and comprise a flattened ovoid head (4.6 2.6 1.5 mm) and a 50-mm tail. However, due to the lability of the tailhead junction, dried stains often possess sperm heads without tails. The head structure, which is principally composed of a nucleus surrounded by a thin layer of cytoplasm, contains at its anterior end a secretory vesicle known as the acrosome. This appears as a cap-like structure and can be differentially stained by standard histochemical stains such as hematoxylin and eosin or Christmas tree stain (nuclear-fast red and picroindigocarmine). The spermatozoa are the principal sources of DNA in semen. P30 protein P30 protein or prostate-specific antigen (PSA) is a protein that is synthesized in the prostate and is an important clinical indicator of malignancy. Its normal range in semen is 3004200 mg ml1 with a mean of 1200 mg ml1. However, it is found in breast, lung, and uterine cancers and it may function as an endogenous antiangiogenic protein. Commercial antibodies to PSA are readily available and standard immunochemical techniques can be applied to detect
it, including crossed-over electrophoresis, Ouchterlony double diffusion, immunochromatography, and enzyme-linked immunosorbent assay (ELISA). The immunochromatographic and ELISA techniques are sensitive to 1 in 105106 dilutions of semen (i.e., 1 ng ml1) and care must be taken in the interpretation of weak results. For example, it may be possible to get false-positive reactions from postejaculate urine, and urine from adult males, since PSA is present at a mean level of 260 ng ml1 therein. Other semen-specific proteins Other proteins that have been reported to be semen-specific include H-Y antigen and semen-specific vesicle-specific antigen (SVSA) but these tests are not in routine use due to sensitivity and specificity problems with their assays. Stability of semen components Dried seminal stains on clothing and bedding can generally exhibit some or all of the semen components months or even years after deposition. Washing will tend to remove any seminal material, although there have been reports of spermatozoa persistence after machine washing. However, persistence in the postcoital vaginal canal is a different matter and the differential stability of p30, SAP, and spermatozoa can be used to assess how much time has passed since the last act of sexual intercourse. Semen is lost from the vagina of the living victim due to drainage, dilution with vaginal fluid, and phagocytosis of spermatozoa by neutrophilic lymphocytes and mononuclear cells. However, significant levels of p30 tend to be lost within 24 h of deposition in the vaginal vault (as measured by immunodiffusion or crossed-over electrophoresis), SAP is normally lost 48 h postcoitus, and spermatozoa normally do not persist after 72 h. In deceased individuals these semen components can last for several days depending upon the environmental conditions and the rate of atrophy of the body tissues.
Vaginal Secretions
Although vaginal secretions are often encountered in postcoital vaginal swabs and stains, there is no definitive test for their presence. The squamous epithelial cells lining the vaginal tract are glycogen-rich, and some investigators have used staining with Lugols iodine to try and distinguish these from other epithelial cells such as those from the oral cavity. DNA extracts from stains containing a mixture of vaginal epithelial cells and spermatozoa can be differentially enriched for both components.
Saliva
Saliva is a secretion that acts as a digestive aid and it contains secretions from the salivary gland. There is
currently no definitive test for the positive identification of saliva, although there are a number of substances present in higher concentration in saliva than elsewhere. These include the inorganic anions thiocyanate and nitrite and the enzymes alkaline phosphatase and a-amylase. The presence of significant levels of a-amylase is strongly indicative of the presence of saliva and the detection of a-amylase is the most commonly used test for it. a-Amylase is produced by two different genetic loci, AMY1 and AMY2. The enzyme hydrolyzes the a(1,4) glycosidic bonds of glucose polymers such as glycogen or starch. AMY1 encodes the salivary form of the enzyme, which is found in saliva, breast milk, and perspiration, whereas AMY2 encodes the pancreatic isoform that is expressed in semen, vaginal secretions, urine, and feces. AMY1 and AMY2 can be distinguished by differential inhibition with wheat seed lectin (WSL) and kidney bean extract (KBE) in that WSL and KBE produce greater inhibitory effects on AMY1 and AMY2, respectively. The two most commonly used methods for a-amylase detection are radial immunodiffusion and dyed starch substrates. Radial diffusion A stain extract from a suspected saliva stain is placed into a well of an agar gel, which also has starch incorporated therein, and allowed to diffuse into the gel. If the extract contains saliva, the diffusing a-amylase will hydrolyze the starch and this can be detected by the classical starchiodine reaction. Starch will give a characteristic purple reaction with iodine, in contrast to a circular clear area where the starch polymer has been hydrolyzed by the a-amylase. A semilogarithmic relationship exists between the diameter of the clear circle and the amount of a-amylase present. Dyed starch substrates Starch is covalently linked to a dye such as Cibachron blue or Procion red to form an insoluble complex. Subsequent to a-amylase activity the dye is released into solution and can be measured by spectrophotometry. This forms the basis of the often-used Phadebas test which uses starch-Cibachron blue tablets as the substrate.
Urine
urine. Androgen metabolites such as 17-ketoacid conjugates are secreted into the urine in relatively high concentrations. Urea If the enzyme urease is added to a urine stain, it will catalyze the breakdown of any urea present and will produce ammonia, which can be detected using a variety of acidbase indicators. urease ! CO2 2NH3 Urea H2 O Uric acid The presence of uric acid can be confirmed by photometry subsequent to digestion of the sample with the enzyme uricase. This test appears to possess human specificity. Creatinine Urine gives a bright-red coloration in the presence of picric acid and a weak base, which is the basis of the Jaffe reaction for the presence of creatinine. Amines The general detection of amines is possible by reaction with p-dimethylaminocinnamaldehyde (DMAC), which gives a dark-pink/red coloration upon Schiffs base formation. 17-Ketoacid conjugates Particular combinations of these metabolites have been reported to be specific for human urine when detected by chromatographic methods such as gasliquid chromatography or high-performance liquid chromatography.
Fecal Material
Fecal material can be identified by a combination of microscopy and testing for the presence of urobilin (which gives feces its characteristic color). Microscopy Microscopic identification of fecal material relies on the presence of various undigested fibrous food residues such as meats, fish, and vegetables and Enterobacteriaceae such as Escherichia coli. Urobilin In a test known as the Edelman test, urobilinogen (a precursor of urobilin) is oxidized to urobilin by alcoholic mercuric chloride. Subsequent addition of alcoholic zinc chloride produces a green fluorescence due to the formation of a stable zinc urobilin complex.
Future Developments in Body Fluid Identification
Urine contains a variety of inorganic ions such as sulfate, phosphate, and chloride that can be identified by the formation of their barium, magnesium ammonium, and silver salts, respectively. However, urine also contains a significant number of amines, including urea, uric acid, and creatinine, and a positive chemical reaction for the presence of amines is regarded as presumptive evidence for the presence of
Current methods of body fluid identification use a variety of labor-intensive, technologically diverse techniques that are, with some exceptions, difficult to automate. Terminally differentiated cells, whether
they comprise blood monocytes or lymphocytes, ejaculated spermatozoa, epithelial cells lining the oral cavity, or epidermal cells from the skin, become such during a developmentally regulated program in which certain genes are turned off (i.e., are transcriptionally silent) and others are turned on (i.e., are actively transcribed and translated into protein). Thus, a pattern of gene expression that is unique to each cell type is not only evinced by the specific messenger RNAs (mRNAs) present but also their relative abundance. There are approximately 25 000 human genes and each cell type has a unique pattern of gene expression known as the transcriptome. Thus, if the type and abundance of mRNAs in a stain or tissue sample recovered at the crime scene could be determined, it would be possible to identify definitively the tissue or body fluid. Such RNA technology is in the process of being developed for this application.
moieties defining an antigenic specificity that can be detected with an appropriate antiserum. At least 30 different blood group loci exist but only a small subset of these have been successfully employed in forensic serology. These include the ABO, Rhesus, and Lewis systems. ABO blood groups In 1901 Landsteiner discovered that certain combinations of red blood cell suspensions from different people mixed with blood serum from other people reproducibly produced a cellclumping or agglutination reaction, whereas other combinations produced no such reaction. Individuals could be classified into four distinct groups, which were named A, B, O, and AB that occur with a frequency of 42%, 8%, 47%, and 3% respectively in the Caucasian population. The agglutination reaction takes place because there is recognition of the A or B agglutinogens (antigens) on the cell surface by corresponding isoagglutinins (antibodies). Uniquely, the ABO isoagglutinins are naturally occurring and found in all individuals who are type A (who possess B isoagglutinins), type B (who possess A isoagglutinins), and type O (who possess both A and B isoagglutinins). AB individuals possess neither A nor B agglutinins. A liquid blood sample is typed by firstly separating the red blood cells from the serum and then using commercially obtained monoclonal antiA and anti-B antisera to test for agglutination of the red blood cells. Confirmatory reverse typing is carried out by testing the sample serum for the presence of isoagglutinins by its reaction with A or B cells. Although the three common ABO alleles (A, B, and O) give rise to six different genotypes AA, AO, BB, BO, AB, OO, only the four types (A, B, O, and AB) are distinguishable by liquid typing due to genetic dominance effects of the A and B alleles over the O allele. Two common subtypes of A exist, namely A1 and A2. Hence, there are four common alleles at the ABO locus giving rise to 10 different genotypes: A1A1, A1A2, A2A2, A1O, A2O, BB, BO, A1B, A2B, and OO. Due to dominance effects of the A1, A2, and B alleles over the O, seven of the 10 genotypes can be distinguished by liquid typing. Secretors and nonsecretors The agglutinogens of red blood cells and the endothelial cells of the cardiovascular system consist of alcohol-soluble glycosphingolipids and, with rare exceptions, all individuals possess these. However, the mucous secretions from the gastrointestinal tract, vaginal secretions, and semen of certain individuals contain water-soluble glycoprotein blood group substances with the same antigenic specificity as their red blood cell
Genetic Marker Analysis

Classical genetic markers are inherited biochemical substances that exhibit variation (polymorphism) in the population. Questioned biological stains from the crime scene are typed in various genetic marker systems and compared to reference samples obtained from individuals who may be possible donors of the stain. Based upon the results obtained, it is possible either to exclude an individual as being the stain donor or to include that person as belonging to a class of individuals who cannot be excluded as having been the stain donor. Alternative forms of a particular genetic marker are known as alleles and polymorphic genetic loci are ones for which the most common allele frequency is <0.95 (or <0.99). At each of these genetic loci it is possible to assign each individual in the population to one of a small number of possible types, the frequency of which varies according to the alleles present and the subpopulation to which the individual belongs. If there are n alleles, then there are a possible n(n 1)/2 possible (geno)types. Classical genetic marker systems normally possess two, three, or four alleles, thus giving rise to three, six, or 10 subtypes respectively. Importantly, the more genetic markers tested in a particular crime scene sample, the smaller the proportion of individuals who would possess the constellation of alleles found and the more probative the evidence. Classical genetic markers can be classified into cellular antigens and extracellular proteins and intracellular isoenzymes.
Cellular Antigens
The classical blood groups comprise a diverse set of polymorphic cell surface molecules that are mostly erythrocyte-tethered glycolipids with carbohydrate
agglutinogens. These latter individuals are known as secretors and about 80% of the population belong to this group, whereas the remaining 20% of individuals who do not secrete blood group substances into their body fluids are classified as nonsecretors. The secretor/nonsecretor dichotomy has important forensic implications. For example, most nonblood body fluids recovered from a crime scene (80%) are expected to be able to be ABO-typed. In addition, nonsecretor individuals can be excluded as having been the body fluid donor even if the individuals ABO type is the same as that found in the stain, although aberrant secretors exist and each case needs to be examined on its own merits. ABO typing of stains Stains can be typed for the presence of ABO agglutinogens by absorption elution, absorptioninhibition, mixed agglutination or ELISA methods, or for isoagglutinins by the Lattes crust method. 1. Absorptionelution: blood-stained threads from a questioned stain are affixed by a suitable adhesive to three separate locations on a solid surface. A drop of anti-A is added to the first thread, antiB to the second thread, and anti-H is added to the third thread. If the cognate antigen is present in the blood stain the antibody (or lectin) will be bound (absorbed) to the stained thread, whereas if the antigen is absent no such absorption will take place. Upon heating to 56 C any absorbed antibody or lectin will be eluted and be available for agglutinating red blood cell suspensions of the appropriate type. 2. Absorptioninhibition: blood-stained threads are placed in separate testtubes and are able to absorb the cognate antisera as in the absorption elution method described above. An aliquot of each antisera supernatant is then removed and tested for its ability to agglutinate red blood cell suspensions of the appropriate type. A reduction in titer of the antisera due to absorption with its cognate antigen results in an inability to agglutinate the red blood cells. Thus inhibition of agglutination of a particular red blood cell type signals the presence of the cognate antigen in the blood stain. 3. Mixed agglutination: in this method the antibody is allowed to absorb on to blood-stained threads as before. Red blood cell suspensions of the cognate antigen are allowed to come into contact with the threads. Any absorbed antibody is detected microscopically by the presence of a layer of red blood cells coating the thread. 4. ELISA: in the direct ELISA technique, the ABO antigens in the stain are bound to a solid support and are detected by the binding of cognate primary
antibodies (such as anti-A or anti-B) via reporter molecules on secondary antibodies (that recognize the chemical structure of the bound primary antibody). The indirect format uses a solid-phase bound antibody (such as anti p84) to capture blood group substances from the physiological stain extract. The blood group substance specificity is determined by reaction with primary and secondary antibodies as before. 5. Lattes crust: separate portions of a blood-stained crust are allowed to react with A, B, and O red blood cell suspensions. Microscopical observation of agglutination indicates the presence of the cognate isoagglutinin. Lewis The Lewis system is most commonly used to confirm the secretor status of an individual. Individuals whose red blood cells are Le (ab) are secretors, whereas Le (ab) individuals are nonsecretors. The rarer Le (ab) type is noninformative with respect to secretor determination. Rhesus The clinically important Rhesus system consists of six antigens C, c, D, d, E, e, for which appropriate commercial antisera are readily available (except for the d antigen). Rhesus typing of blood stains can be performed using the absorptionelution methodology but this is less sensitive than the ABO system.
Extracellular Proteins and Intracellular Enzymes
Genetic variation in the structure of proteins, including enzymes, is mainly due to amino acid substitutions and at least a third of these are expected to result in charge differences in the protein. In the case of isoenzymes (enzymes that possess the same catalytic specificity but are structurally distinct), such variants are known as allozymes and they can be electrophoretically separated according to size and/or charge in an electrical field using sieving media such as starch, agarose, and polyacrylamide. After electrophoretic separation isoenzymes are detected using appropriate substrates which produce a color change due to the transfer of electrons from a donor such as NADPH or NADH to a dye such as MTT (methylthiazole tetrazolium) tetrazolium, thus forming a colored, insoluble complex. In the case of nonenzyme proteins the variants are detected postelectrophoretically using a variety of methods, including immunofixation with human protein-specific antibodies subsequent to capillary transfer of the separated proteins on to an inert membrane (Western blotting). A number of polymorphic isoenzymes and extracellular proteins have been commonly used for forensic purposes. The efficacy of genetic marker systems for individual discrimination can be mathematically ranked by comparing their
Table 1 Commonly used protein genetic markers
Genetic marker Protein type Discrimination potential (DP)
ACP1 ADA AK CAII ESD GLO1 PEPA GC HP AHSG Reproduced from
Isoenzyme Isoenzyme Isoenzyme Isoenzyme Isoenzyme Isoenzyme Isoenzyme Extracellular Extracellular Extracellular Ballantyne J.
0.67 0.06 0.25 0.25 0.27 0.57 0.28 0.69 0.62 0.54 Serology: Overview. In
Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J
Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
discriminatory potentials (DP). The DP of a genetic marker system is defined as the probability of discriminating two randomly chosen, biologically unrelated individuals. Mathematically, the DP 1 S Pi2, where Pi is the frequency of the ith genotype. Table 1 lists some commonly used genetic marker systems and their DP values for a US African-American population. An illustrative example of a genetic marker is the enzyme phosphoglucomutase 1 (PGM1), which is an important housekeeping enzyme involved in the metabolism of glucose. There are four common 2 alleles PGM12A(PGM2 1 ), PGM1 2B(PGM1 ), 1 1 PGM1 1A(PGM1 ), and PGM1 1B(PGM1 ) as well as at least 30 rare variants. The enzyme is detected by means of a substrate overlay (zymogram), as shown in Figure 2, where the underlined reagents are those that are added to the reaction mix. The allozymes are separated by isoelectric focusing; this is an electrophoretic technique in which separation is effected in a pH gradient according to differences in the proteins isoelectric points (the pH at which the net charge on the molecule is zero). The 10 common phenotypes are schematically depicted in the block diagram (Figure 3).
Figure 2 Pathway for phosphoglucomutase (PGM) reaction. Reproduced from Ballantyne J. Serology: Overview. In Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
Significance of Genetic Marker Typing Data

A typical case involves the genetic marker testing of a body fluid sample from a crime scene and reference samples from the victim(s) and suspect(s). Subsequent to the analysis, conclusions are drawn with respect to possible donor(s) of the identified body fluid. As an illustrative example, consider the following genetic marker data obtained from a violent assault whereby a blood stain found at the crime scene was typed, as were the victim and two suspects (Table 2). Note that it is not uncommon for some genetic markers to yield negative results, as can be seen for
the AHSG and HP genetic markers in this case. This can be due to a variety of factors such as sensitivity of the system and protein stability. Notwithstanding these negative results, what conclusions can be drawn from Table 2? First, the victim and suspect 1 are excluded as the source of the crime scene blood stain. Second, suspect 2 is included as a possible donor of the blood stain. What is the significance of this evidence? To evaluate this we ascertain the frequency of each genetic marker type in different population groups from look-up tables of genetic marker frequencies (Table 3). For example, the ACP1 B type occurs with a frequency of 39%, 57%, and 52% in the Caucasian, African-American, and Hispanic populations, respectively. The probability of obtaining the composite phenotype (i.e., ACP1 B, PGM1 1, ESD 1, GC 1S) is determined by using the product rule, simply multiplying together each systems phenotype frequency. The report would state that suspect 2 could not be excluded as the source of the crime scene blood stain and that approximately 1 in 29, 1 in 120, and 1 in 39 of the Caucasian, African-American, or Hispanic population cannot be excluded as possible donors. Both the victim and suspect 1 are excluded as possible sources of the blood.
Figure 3 Schematic representation of the IEF (isoelectric focusing) patterns obtained from the 10 common phosphoglucomutase 1 (PGM1) phenotypes. Reproduced from Ballantyne J. Serology: Overview. In Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
Table 2 Genetic marker data obtained from a violent assault: typing of blood stain, victim and two suspects
ACP1 PGM1 AHSG ESD HP GC
Victim Suspect 1 Suspect 2 Crime scene blood sample
BA B B B
1 21 1 1
21 1 21 No result
1 1 1 1
2 1 1 No result
21S 1S 1S 1S
ACP1 (acid phosphatase 1), PGM1 (phosphoglucomutase 1), phosphoglucomutase 1; AHSG (alpha-2-HS glycoprotein), ESD (esterase D), HP (haptoglobin), GC (group specific component). Reproduced from Ballantyne J. Serology: Overview. In Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
Table 3 Example of a look-up table of genetic marker frequency

Caucasian African-American Hispanic
ACP1 B PGM1 1 ESD 1 GC 1S Combined
0.39 0.36 0.79 0.31 0.034 or approximately 1 in 29
ACP1 B (acid phosphatase 1 type B), PGM1 1 (phosphoglucomutase 1 type 1), ESD 1 (esterase D type 1), GC 1S (group specific component type 1S). Reproduced from Ballantyne J. Serology: Overview. In Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
Sexual Assault Investigations

Conventional genetic marker analysis can aid sexual assault investigations but misinterpretation of the data, whether intentional or not, can occur and a discussion of the issues involved may be useful. A typical sexual assault case involves detection of semen stains on the victims vaginal samples taken from the victim shortly after the incident. Also, as a result of postcoital drainage, seminal stains are often found on the victims underpants and such stains can be a good source of seminal material. For the purposes of this exercise let us assume that a woman (victim, V) is raped by an individual (perpetrator, P) but shortly before this she has had consensual intercourse with her husband/boyfriend (B). This scenario must not be uncommon. Before consideration of the scientific data generated from the genetic marker results a number of mutually exclusive events may have in actuality occurred: 1. semen is present and only comes from P 2. semen is present and only comes from B 3. semen is present and comprises a mixture from P and B 4. no semen is present from either P or B. From this analysis it is clear that the absence of semen from P does not mean that P did not rape V (due to the possibility of events 2 and 4 above). Other factors may confound the analysis of genetic marker data. For example, semen stains on vaginal swabs (and often on underpants) will be mixed with vaginal epithelia or secretions and therefore testing will identify the genetic factors from V. Although sperm are lost from the vaginal vault (normally not present after 72 h) and seminal stains on underpants are stable (for months or years), the vaginal swab best represents semen deposited at time of rape. The genetic profiles of V, P, and B may have alleles in common and masking of one component by another is possible. There is often no scientifically reliable method of determining the number of semen donors using conventional methods. From the foregoing it should be obvious that the interpretation of conventional genetic marker testing data in sexual assault evidence is multifactorial and requires a case-by-case consideration of the meaning of the data generated. The use of highly discriminating DNA typing systems has helped alleviate some, but not all, of these problems. For example, it may be a facile matter to determine the number of semen donors in certain cases with the use of Y-chromosome STR markers.
See Also
Blood Grouping; Crime-scene Investigation and Examination: Collection and Chain of Evidence; Major Incident Scene Management; Underwater Crime Scene; Recovery of Human Remains; Suspicious Deaths; Crime-scene Management, Systems: Continental Europe; United Kingdom; United States of America; DNA: Basic Principles; Ethics of Forensic Applications and Databanks; Statistical Analysis; Risk of Contamination; Mitochondrial; Postmortem Analysis for Heritable Channelopathies and Selected Cardiomyopathies; Evidence, Rules of; Immunoassays, Forensic Applications; Serology: Blood Identification; Bloodstain Pattern Analysis; Sexual Offenses, Adult: Human Normal Sexual Response; Injuries and Findings after Sexual Contact
Further Reading
Baechtel S (1988) The identification and individualization of semen stains. In: Saferstein R (ed.) Forensic Science Handbook, vol. II. Engelwood Cliffs, NJ: Prentice Hall. Biology Methods Manual: Metropolitan Police Forensic Science Laboratory (1978) London: Commissioner of Police of the Metropolis. Culliford BJ (1971) The Examination and Typing of Bloodstains in the Crime Laboratory. US Department of Justice, Law Enforcement Administration, Superintendent of Documents. Washington, DC: US Government Printing Office. Divall GB (1985) The application of electrophoretic techniques in the field of criminology. Electrophoresis 6: 249258. Gaensslen RE (1983) Sourcebook in Forensic Serology, Immunology, and Biochemistry. US Department of Justice, National Institute of Justice, Superintendent of Documents. Washington, DC: US Government Printing Office. Harris H (1980) The Principles of Human Biochemical Genetics, 3rd edn. Amsterdam: Elsevier/North-Holland Biomedical Press. Harris H, Hopkinson DA (1976) Handbook of Electrophoresis in Human Genetics. Amsterdam: North-Holland. Juusola J, Ballantyne J (2003) Messenger RNA profiling: a prototype method to supplant conventional methods for body fluid identification. Forensic Science International 135: 8596. Lee H (1982) Identification and grouping of blood stains. In: Saferstein R (ed.) Forensic Science Handbook, vol. 1, pp. 267325. Englewood Cliffs, NJ: Prentice-Hall. Race RR, Sanger R (1975) Blood Groups in Man. 6th edn. Oxford, UK: Blackwell. Sensabaugh G (1982) Biochemical markers of individuality. In: Saferstein R (ed.) Forensic Science Handbook, vol. 1, pp. 338403. Englewood Cliffs, NJ: Prentice-Hall.
64 SEROLOGY/Blood Identification
Blood Identification
H C Lee and E M Pagliaro, Connecticut Forensic Science Laboratory, Meriden, CT, USA
Introduction
Blood stains are one type of serological evidence associated with various crimes against persons, including homicide, assault, domestic violence, child abuse, and sexual assault. In addition, many property crimes, such as burglaries, robberies, and arson, may be associated with the presence of blood at the scene, on weapons, or on tools. Since the 1990s, many criminal investigations have benefited from the ability of forensic scientists to individualize blood and body fluid stains through application of the various DNA technologies. Polymerase chain reaction analyses of autosomal and Y STR typing and mitochondrial DNA sequencing technology provide reliable results using minute quantities of DNA. Because DNA profiles can be generated from such small samples of blood as well as from trace amounts of semen, other body fluids, tissues, and skin cells, it is more important than ever to identify positively the source and nature of the biological material. Whenever possible, forensic scientists must answer the following questions: . Does the evidence sample contain blood? . Is the blood mixed with other biological material? Without the knowledge that blood or some other biological substance is present, it may be impossible for the scientist to offer a complete and accurate interpretation of the DNA profiles generated from that sample or to reconstruct the crime accurately. In addition to determining if blood is present, further classification of the biological materials should be conducted whenever possible. In the case of blood, classification means determining if the blood is human or from some other animal. It may also be necessary to determine if the blood sample is from menstrual blood or from a circulating source. Certain investigations may require that the determination of the species of origin be completed before further testing can be conducted. For example, if no other evidence is legally available to the investigator, the classification of a blood stain as human at a suspected primary scene could provide sufficient evidence to support a search warrant. Confirmation of human blood on a suspects person or clothing may also be necessary before a known sample can be obtained from that suspect for comparison purposes.
Blood can be identified by its physical, chemical, or biochemical characteristics. Many techniques have been developed to determine if a liquid or stain is, in fact, blood. Additional procedures are available if it is necessary to confirm that the blood is human. The ease with which this identification and classification is carried out depends on both the amount of blood present and the physical state of the blood. Figure 1 depicts the steps in the identification and classification of physical evidence suspected of containing blood. As shown in Figure 1, prior to any chemical or biological testing, the scientist must accurately document the physical characteristics of the possible blood stain, including size, shape, color, and physical state. Notations concerning clotting of the sample or separation of serum if the sample is liquid or semiliquid should also be made at this time. In many cases, a complete set of notes, diagrams, and photographs may be necessary to document the number and pattern of the possible blood stains. This documentation could prove vital in the subsequent reconstruction of the incident, estimating the time of death, or similar circumstance. Thus, documentation must be completed prior to any sampling and testing that could potentially alter the blood patterns. Documentation of physical characteristics is also important if the quantity of stain present precludes some of the identification tests. In these cases, preliminary observations of the color, texture, shape, and size of the stain, combined with subsequent DNA testing, may be the only information available to the forensic scientist. With sufficient preliminary data, however, the forensic
Figure 1 Stepwise examination of a questioned blood stain.
SEROLOGY/Blood Identification 65
biologist may be able to draw conclusions about the likelihood that a particular, minute sample is blood. After preliminary observations are completed, the identification of a sample as blood and its classification as human or some other animal may be necessary. Most of these tests are based on microscopic, chemical, or biological characteristics of the blood.
Human Blood
Human blood is a tissue composed of approximately 45% cellular components and 55% liquid plasma. The cells consist of erythrocytes or red blood cells (RBCs), various types of leukocytes or white blood cells (WBCs), and platelets. The number of RBCs in a normal adult is between 4.5 and 5.4 million cells per milliliter of blood. Mammalian red cells lose their nuclei prior to release into the circulatory system, resulting in their characteristic biconcave appearance. RBCs contain large quantities of the complex protein hemoglobin (Hb). It is the heme portion of the Hb molecule that imparts the characteristic red color to RBCs. The heme molecule serves as the basis of most tests for the identification of blood in an unknown sample. Leukocytes retain their nuclei. It is the nucleated WBCs (leukocytes) that provide the source of genetic information detected by nuclear DNA analysis. These cells may have lobed nuclei and contain granules that stain differentially (eosinophils, basophils, and neutrophils); other forms of white cells lymphocytes and monocytes have relatively large, unlobed nuclei. The normal adult human has only 400010 000 WBCs per milliliter. In addition, the cytoplasm of blood cells contains thousands of mitochondria. Mitochondria contain DNA distinct from the nucleus (mtDNA) and are the source of DNA information related to maternal linkage. RBCs and WBCs are so characteristic in appearance that they provide a simple method of sample identification when liquid blood is examined microscopically. Blood plasma serves as a carrier of all nutrients, proteins (primarily albumins and enzymes), immunochemicals, salts, cellular waste products, and other soluble materials in the body. As such, it is a complex mixture of variable composition. Because the chemicals in plasma are not unique to blood, identification of a sample as blood based on serum or plasma is limited in scope.
developed for the identification of blood. No matter what the method of choice, blood identification is based on the detection of a characteristic shape or component of blood. The specific component being identified may vary, as do the techniques to detect that component. Thus, there is variability in both the specificity and the sensitivity of the tests for blood. Which method should be used to identify a sample as blood is determined by the availability of equipment, reagents, and other resources. Whether the test is used as a field test or a laboratory test will also affect which test is employed. The size, age, and condition of the suspected blood stain are also considerations when choosing blood identification tests. In general, whatever test is used for the identification of blood, the scientist must use the smallest amount of sample necessary so that as much stain as possible is available for further laboratory testing.
Microscopic Identification of Blood Stains
Methods for the Identification of Blood

Blood identification is most often conducted using microscopic, biochemical, or immunological methods. Some instrumental techniques have also been
Liquid or freshly clotted blood located at a crime scene, on a weapon, on clothing, or on another object can be collected to facilitate identification of the sample as blood. When the blood is in a liquid or semiliquid state, a small portion of the liquid or clot may be removed to a sterile test tube or vial containing ethylenediaminetetraacetic acid (EDTA) or other suitable preservative. If necessary, a small amount of saline may also be added to the tube to suspend the clot. Collection of the sample in this manner will provide a medium that will preserve the cellular components intact. The sample should be refrigerated at 4 C and submitted to the laboratory as soon as possible. Microscopic identification of the RBCs from this type of sample is a straightforward process that can be carried out under a standard compound microscope at 4001000 magnification. Confirmation of blood may be based on the microscopic identification of RBCs on the unstained slide. If desired, a blood smear can be made and air-dried. The sample is subsequently stained with one of the common differential, biological stains. This method allows for the identification of both erythrocytes and leukocytes, which may be important information in the evaluation and reconstruction of genetic marker testing results. In addition, microscopic examination of the extract may reveal other potentially useful information, such as the identification of sickle RBCs or increased granulocytes. Staining may also be preferred in samples that contain a small number of cells so that the minimum amount of sample is used for the identification process. As blood dries, water from the blood cells will osmose from the cell into the surrounding environment. This dehydration process results in destruction
66 SEROLOGY/Blood Identification
of most of the blood cells, preventing identification by methods of microscopic examination. However, if the resulting blood stains are relatively fresh, it may be possible to reconstitute sufficient cells to conduct microscopic identification of blood cells. A number of techniques have been reported for extracting cells from stains. In general, these techniques involve reconstituting the blood cells with a solution containing albumin, glycerol, and saline (or similar composition) to restore the original appearance of the blood cells. Various factors affect the success of these techniques. Age, temperature, bacterial growth, and pH may have a deleterious effect on the ability to extract intact blood cells from stains. In addition, the procedures are time-consuming and usually provide little information beyond what would be supplied by faster, less cumbersome chemical or immunological methods.
Chemical Screening Tests for Blood (Presumptive Tests)
shown in Figure 2. By design, all presumptive tests for blood are highly sensitive (typically 1:1 million diluted blood) and require only minute quantities of blood to effect a visible reaction. However, because these tests are based on an oxidation process, all presumptive test reagents will yield positive results with some chemical substances other than blood, the so-called false-positives. Among those materials creating false-positive reactions are peroxidases, cytochromes, strong oxidizing agents, and some metallic salts. Because these other oxidation reactions may occur, a positive result with a chemical presumptive test for blood alone cannot support a definitive conclusion that blood is present in a questioned stain. Test procedures As noted previously, no tests should be conducted before documenting an unknown stain. Test procedures should limit alteration to the appearance or pattern of the stain as much as possible. Because the chemical tests for blood are very sensitive, and are preliminary screening tests, the amount of sample utilized should be minimal. If there is limited sample, this test may be eliminated in favor of a combined identificationclassification test, such as a test utilizing antihuman Hb. The screening test for blood should be conducted whenever possible with a small portion of stain removed by scraping or swabbing. The test procedure can be conducted to eliminate oxidizing agents as the source of false-positive results by the following two-step testing procedure: 1. Color reagent is added to the stain material on swab or in a clean plate. 2. If no color change is noted after 1530 s, a drop of 3% hydrogen peroxide is added. A resulting color change indicates that blood may be present. If the color change is noted before the addition of peroxide, the presence of a chemical oxidant is indicated. If the forensic scientist suspects blood may be present in the mixture that reacts without peroxide, alternative identification procedures that do not rely on the catalyst activity of heme must be conducted. A positive color test alone should not be interpreted as definitive evidence of blood because peroxidases and catalases cannot be eliminated as possible sources of the color change by this two-step method. Microscopic examination of a sample may eliminate tissues, pus, or similar materials as the source of the peroxidase activity, if necessary. If no color change occurs, the lack of a reaction may be interpreted as proof that blood is not present in detectable amounts, unless an inhibitor is suspected. If it is suspected that a strong inhibitor is in the sample,
As stated previously, when blood dries, the cells are dehydrated. During this process, the cellular contents are released to the surrounding environment. Among these contents is a protein, Hb, that is found in high concentration within the RBCs. The presence of this chemical substance serves as the basis for most of the blood identification procedures employed by forensic scientists. Although more than 100 variants of the Hb molecule have been described, all of the variants tested or their derivatives in blood stains have yielded identical reactions and positive results with these chemical tests. The presumptive tests for blood are based on a catalyzed oxidationreduction reaction. In this process, the heme in blood, because of its peroxidasetype activity, catalyzes the breakdown of an oxidizing agent such as hydrogen peroxide. The resulting oxygen subsequently reacts with a chemical compound that demonstrates a color change when it is oxidized. These two steps in the presumptive test for blood can be summarized as follows: 1. H2O2 Hb ! H2O 1=2 O2 2. O2 reduced reagent (color 1) ! oxidized reagent (color 2) Many compounds have been used as color reagents in this process, including such widely used chemicals as phenolphthalein, leucomalachite green, o-toluidine, and tetramethylbenzedine, which effect marked color changes upon oxidation. Other chemical substances, such as luminol and fluorescein, are used for their chemiluminescence upon oxidation. Reaction schemes for some common chemical reagents are
Reaction schemes for common presumptive tests for blood O HO C H COOH Phenolphthalin (colorless) N(CH3)2 H2O2 C H Leucomalchite green (yellow) N(CH3)2+Hb C N+(CH3)2 OH H2O2 C H+ O OHC O C O PINK C O Phenolphthalein (colorless) N(CH3)2 O HO OH
+ Hb
*
NH2
Oxidized malachite green (blue-green)
NH2
O NH H2O2 OH
O O O+ O
NH2
O O O O
Hb+ O
NH
Luminol
3-Aminophthalate* (*excited state)
3-Aminophthalate+h (ground state)
Figure 2 Reaction schemes for common presumptive tests for blood.
this possibility must also be considered when drawing a conclusion based on a presumptive test result. Because of the presumptive nature of the catalytic test, a confirmatory test is necessary when there is a positive presumptive test for blood results. Confirmation of the blood may take the form of additional microcrystal tests, instrumental analysis, electrophoretic methods, or immunological techniques. Identification of heme is also the basis of most confirmatory test procedures. Most laboratories conduct confirmation by chemical or immunological tests because these methods require the least amount of sample and no special equipment.
Crystal Tests
There are several crystal tests that may be used for the confirmation of blood in stains. Derivatives of heme, such as hemin and hemochromogen, are formed by the addition of reagent mixtures. These tests are among the oldest in forensic serology. For example, in 1853 Teichmann reported that on warming a
blood stain with acetic acid in the presence of salts, characteristic crystals were formed. These crystals are the result of ferriprotoporphyrin reacting with halogen salts. Half a century later, Takayama formed stable crystals, hemochromagen, by mixing blood with a pyridine reagent. These crystal tests have been shown to be highly specific and sensitive. As little as 0.1 mg Hb will suffice to cause a reaction that is detectable by microscopic examination. Studies combining microspectrophotometric analysis with traditional crystal tests have also enhanced the sensitivity of these procedures. The number of cases in which crystal tests are employed has been greatly reduced in recent years, often because of concerns about consuming portions of the sample for mere confirmation of blood. In addition, falsenegative results have been obtained on older blood stains and blood on materials such as tannic acidtreated leather. Thus, the failure to obtain a positive crystal reaction cannot be interpreted as proof that blood is not present in a stain.
68 SEROLOGY/Blood Identification Immunological Tests
Among the most commonly used confirmatory tests for blood are those employing immunological techniques. Antihuman Hb sera are readily available from commercial vendors. The highly specific reaction of a human blood stain extract with the antihuman Hb serum allows for the confirmation of blood by identifying the presence of human Hb in the stain. In addition, this test also determines the species of origin of the sample. This reaction can be demonstrated by several methods. A positive result with one of these techniques is absolute identification of blood and that the blood is human. However, it is vital to confirm that the specificity of the antiserum used for that interpretation of anti-Hb tests is appropriate. In addition, the blood from other primate species often reacts with antihuman Hb, but this is not usually a major concern in a forensic setting.
Spectrophotometric Methods
Spectrophotometric procedures are seldom used in current forensic practice. Spectrophotometric analysis to identify blood is based on identifying Hb or one of its derivatives through specific absorption spectra. This method was once considered to be one of the most conclusive tests for the identification of blood stains, and spectral data may be found in older case files. Near-ultraviolet and visible absorption spectra were used to confirm the presence of methemoglobin, oxyhemoglobin, and carboxyhemoglobin. Hb and its derivatives have a strong absorption band at 400425 nm. Studies indicate that porphyrin compounds from other animal and plant sources may also demonstrate similar spectral characteristics. Thus, the identification of blood cannot be made solely on the absorption spectrum.
techniques demonstrate the presence of an in vitro antibodyantigen (AbAg) reaction in a variety of ways. However, no matter what the method of choice, the reaction requires the use of an antiserum, a buffer system, and the blood stain extract (the antigen). Environmental factors such as temperature, pH, incubation time, salt concentration, and strength of the antiserum have a direct effect on the formation of the AbAg complex. The optimal conditions for any particular species antiserum are technique-specific. Antiserum specificity is the most important aspect of species determination. If an antiserum contains trace amounts of contaminating antibodies, falsepositive results may be obtained with a sample. Therefore, it is necessary for each lot of antiserum purchased to be thoroughly tested for specificity and sensitivity (titer). Specificity must be demonstrated by direct testing for cross-reactivity among other commonly encountered species. In the case of anti-Hb, specificity to blood must be shown if this test is to be used as confirmation of blood as well as a speciesdetermining test. Only through strict control can the laboratory offer conclusions to a reasonable degree of scientific certainty. The most commonly used techniques for demonstrating an AbAg complex in forensic species testing are double-diffusion (Ouchterlony), crossed-over electrophoresis, and rapid immunoassay. In addition, species-specific DNA testing is conducted. Figure 3 depicts examples of these test results.
Double-diffusion (Ouchterlony) Technique
Determination of Species of Origin

When a stain has been identified as blood, these results alone may not be sufficient for investigative or analytical purposes. It is often necessary to determine from what species the blood originates. If enough sample is present, the confirmation that blood is human may provide the basis of a warrant to obtain a known sample for comparison from a suspect in a case. Alternatively, the determination that a stain is not of human origin can prevent the waste of valuable laboratory or investigative resources. The first immunological precipitin test for medicolegal species determination was performed in 1901. Most methods for the determination of species of origin are still immunological in nature. These
Using the double-diffusion (Ouchterlony) method, precipitates may be visible when the AbAg complex forms. In 1949, Ouchterlony described the use of precipitating antisera and antigen solutions in wells of an agar gel. By this method, the two solutions diffuse into the gel from the well. If antibodies react with any antigens, a white precipitate will form at the reaction front. Precipitin bands provide considerable information concerning the diffusion coefficients and relative concentrations of the reactants. The Ouchterlony method also gives the scientist information concerning the identity, partial identity, or nonidentity of an AbAg product. Thus, issues of cross-reactivity can often be addressed in a relatively simple manner. Since passive diffusion is the basis for this test, little time is necessary to prepare test materials relative to the amount of information gained from the test. The double-diffusion test may lack sensitivity with some antisera because of the need to observe the precipitate. Staining with protein dyes and other techniques is sometimes employed to enhance visualization of the AbAg complex.
placed in the cathodic well and antiserum in the opposite well of a test pair. When current runs through the system, the antiserum (Ab) will travel toward the cathode, whereas the stain extract (Ag) will migrate toward the positive electrode. A precipitin band will form between the two wells at the point of AbAg complex formation. General protein stains are used to enhance the ability to visualize the results. Because antibodies and antigens travel in a specific direction, crossed-over electrophoresis is much more sensitive than the double-diffusion method. This technique also has the advantage of providing for the testing of multiple samples at the same time. However, no information can be gained concerning cross-reactivity or partial identity from crossed-over electrophoresis.
Rapid Immunoassay
Figure 3 Typical test results to determine species of origin. (A) Double-diffusion (Ouchterlony) plate showing white precipitin reactions with human blood and antihuman hemoglobin (center well). (B) Rapid immunoassay result from a blood stain extract diluted 1:1000. (C) DNA human-specific probe reactions with 10, 5, 2.5, 1.2, 0.63, 0.31, and 0.16 ng of control human DNA (17, respectively), positive human blood stain extract (8), negative control (9), and various stain extracts.
Crossed-over Electrophoresis
In crossed-over electrophoresis, precipitating antibodies and stain extracts containing antigens are forced together by use of an electric field. A precipitate will form at the point of interaction between the antigen and antibody. Typically, small wells are punched into an agar gel. Buffer is utilized so that stain extract is
Rapid immunoassay test strips are among the most common techniques employed by laboratories for the confirmation and classification of blood. This test is highly sensitive and requires little preparation time or sample. Most test strips are also highly specific for human Hb and, as such, can provide reliable information about the presence of human blood in a questioned sample. Immunoassay strips require extraction of antigens from the material being evaluated. After antigens are solubilized, they will react with monoclonal antibodies that are already present on the test strip. The monoclonal antibody has been combined with a dye complex at the time of manufacture. The AbAg complex will diffuse up the test strip to a point where a second immobilized antibody is present. The complex will react with this antibody and the dye present in the test area will become visible. Some assays also contain a built-in positive control area to confirm that the test is functioning correctly in the event of a negative test result. Rapid immunoassay test strips have a reported sensitivity of 0.05 mg Hb per milliliter. This test has yielded positive results in the range of 1:50 000100 000 diluted blood in many forensic laboratories. Thus, these tests provide a high degree of sensitivity that is useful with limited sample size, older stains, and stains that have been subject to environmental onslaught. Procedures have also been developed to use this test in conjunction with standard DNA extraction techniques. Because of their portability and the short extraction time necessary with fresh blood stains, rapid immunoassays have been used for screening purposes at some crime scenes by trained forensic scientists. One disadvantage of the rapid immunoassay strip is the high dosage effect that has been noted with concentrated samples; the presence of a high concentration of antigens can yield false-negative results.
70 SEROLOGY/Bloodstain Pattern Analysis
However, since Hb is a colored compound in the extract solution, an extract with a high concentration of Hb can be readily detected. Thus, a proper sample dilution can be made before the stain extract is applied to the test strip. Although the test strips are generally highly specific, positive reactions have been reported by a number of laboratories with blood from animals in the weasel family, particularly ferret blood. Any interpretation of positive results in case materials should consider this possibility.
Quantitation of Human DNA
Although confirmation of a sample as blood cannot be easily done by standard forensic DNA quantitation methods, the classification of a sample as human is easily accomplished by this process. Probes complementary to primate-specific DNA sequences are readily available. These analyses are used primarily in DNA testing to estimate the quantity of human DNA extracted from a stain being assessed before DNA analysis. Several methods to visualize the presence of the human DNA may be used. Typically, DNA from a sample is spotted on a membrane along with known concentrations of human DNA. After incubation, results from the questioned sample are compared to the intensity of the known standards. The amount of human DNA in the sample can be estimated in this manner. Instrumental methods for the detection of human DNA by chemiluminescence have recently been developed. The sensitivity of human DNA quantitation is commonly in the 0.1 0.2 ng range when using a color reagent system. Data show that this technique to determine human origin is extremely sensitive and requires only a few cells to yield a positive result. It must be emphasized that this technique will identify the presence of human DNA from any tissue or cell with a nucleus. Thus, it is not possible to confirm the presence of blood without employing one of the heme-based identification techniques previously described.
Hochmeister MS, Budowle B, Sparks R, et al. (1998) Validation studies of an immunochromatographic 1-step test for the forensic identification of human blood. Journal of Forensic Science 44: 597602. Inman K, Rudin N (1997) An Introduction to Forensic DNA Analysis. New York: CRC Press. Lee HC (1982) Blood stain identification and grouping. In: Saferstein R (ed.) Forensic Science Handbook, vol. 1. Englewood Cliffs, NJ: Prentice-Hall. Lee HC, Gaensslen RE (eds.) (1985) Advances in Forensic Science. vol. 1. Foster City, CA: Biomedical Publications. Lee HC, Pagliaro EM (2000) Blood stain identification. In: Siegel J, et al. (eds.) Encyclopedia of Forensic Sciences. London: Academic Press. Lee HC, Miller M, Palmbach T (2001) Henry Lees Crime Scene Handbook. London: Academic Press.
Bloodstain Pattern Analysis

T L Wolson, Crime Laboratory Bureau, Miami, FL, USA
2005, Elsevier Ltd. All Rights Reserved. This article is adapted from Serology: Bloodstain Pattern Analysis in Encyclopedia of Forensic Sciences, pp. 11381349, 2000, Elsevier Ltd.
Introduction
When violent crimes are committed, it is not unusual for the participants to be injured. If these injuries are accompanied by blood flow, distinctive blood stain patterns may result that can be used to provide investigative information about the activities that occurred during the commission of the crime. These distinctive blood stain patterns occur because of the physical properties of the blood and how it reacts when acted upon by physical forces. The analysis of these patterns can provide the investigator with information about the direction of travel of the blood, the level of force used to put the blood in flight, the location of the blood source which was acted upon to create the pattern, movements during bloodshed, movements after bloodshed, and activities during bloodshed. Blood stain pattern analysis studies how different forces and activities influence the creation and appearance of the blood stain patterns, so that they can be interpreted as part of the crime-scene investigation.
See Also
Blood Grouping; Crime-scene Investigation and Examination: Collection and Chain of Evidence; DNA: Basic Principles; Immunoassays, Forensic Applications; Pattern Evidence
Further Reading
Culliford BJ (1964) The Examination and Typing of Blood Stains in the Crime Laboratory. Washington, DC: US Department of Justice. Gaensslen RE (1984) Sourcebook in Forensic Serology, Immunology, and Biochemistry. Washington, DC: US Department of Justice.
History
In recent years, blood stain pattern analysis has been used on a frequent basis to assist in the investigation of violent crimes. Because of this, blood stain pattern
SEROLOGY/Bloodstain Pattern Analysis 71
analysis is perceived as a new forensic science. The roots of blood stain pattern analysis can be traced back more than 100 years. As the historian for the International Association of Blood stain Pattern Analysts (IABPA), Herbert Leon MacDonell has found literature references to bloodshed characteristics dating back to the 1500s. In 1895, Dr. Eduard Piotrowski published an article on experiments that he did to examine blood stain patterns resulting from head wounds. In 1939, Dr. Victor Balthazard presented a paper at the 22nd Congress of Forensic Medicine concerning research performed by himself and his associates in blood stain pattern analysis. In 1955, Dr. Paul Kirk of the University of California at Berkeley submitted an affidavit concerning his examination of the blood stain pattern evidence in the homicide case of the State of Ohio v. Samuel Sheppard. Dr. Sheppard, a prominent doctor in Bay Village, Ohio, was convicted of the beating to death of his wife Marilyn Sheppard. Dr. Kirk examined the blood stain patterns at the crime scene and did scientific research that he used to formulate his opinions concerning the blood stain patterns on the walls of the Sheppards bedroom. This is considered to be the beginning of blood stain pattern analysis as a forensic discipline. In 1966, Dr. Kirk testified as an expert for the defense during Dr. Sheppards second trial, in which he was acquitted of beating to death Marilyn Sheppard. In 1971, Herbert Leon MacDonells Flight Characteristics of Human Blood and Stain Patterns was published. This publication was a compilation of Mr. MacDonells research that was funded by a grant from the Law Enforcement Assistance Administration (LEAA). In 1973, Mr. MacDonell developed a training program and instructed the first of many blood stain institutes. In the years that followed, interest in blood stain pattern analysis grew rapidly. Many publications and books can be found concerning this forensic discipline and several professional associations have been created. The IABPA, founded in 1983, is dedicated to advancing blood stain pattern analysis as a forensic science. The IABPA publishes a quarterly newsletter and hosts an annual training conference that is attended by blood stain analysts from around the world. In 2002, the Federal Bureau of Investigation hosted the first meeting of the Scientific Working Group for Blood stain Pattern Analysis (SWGStain). SWGStain is tasked with addressing current issues that affect the forensic sciences and the impact of those issues on the discipline of blood stain pattern analysis. SWGStain has also been tasked with developing recommended guidelines for training, quality assurance, and research in blood stain pattern analysis.
Blood Stain Characteristics

Many factors affect the size and shape of the blood drops. Blood is composed of solids suspended in liquid. The major constituent of the solid portion of blood is the red blood cells. Red blood cells do not contain deoxyribonucleic acid (DNA), the genetic material that defines us. Also present in the solid portion are the white blood cells, which are the source of the DNA that is used for forensic analysis. The liquid portion of blood is slightly more than 50% of the whole blood volume. Plasma is the liquid portion of blood containing the clotting factors. The liquid that remains after the blood has clotted is called serum. When blood passively drips off a surface and falls on to a smooth hard horizontal surface, the resulting blood stain will be round. As the blood falls through the air, it takes the shape of an oscillating sphere. The blood droplets will not break up in the air as they fall due to gravitational force alone. Additional forces, however, can break the drops apart. The diameter of the blood stain is dependent upon the distance the drop falls to the horizontal surface, as well as the volume of the blood drop. As the distance of the fall increases, the diameter of the blood stain will increase until it reaches a maximum diameter. The maximum diameter for the blood stain occurs after the drop has fallen about 2.5 m (7 ft). The volume of the drop of blood also affects the diameter of the blood stain. As volume increases, so will the diameter of the resulting blood stain. Early research identified the average volume of passively falling drops of blood as 0.05 ml. Subsequent research determined that the average volume of passively falling drops of blood varies depending on the surface characteristics of the item from which the blood drips. Blood drops fall off a surface because its volume increases to the level where the pull of the earths gravity overcomes the viscosity of the blood and allows the surface tension to break. The shape and finish of the surface from which the blood falls affects the blood volume that is needed for the surface tension of the blood to break and allow it to fall. In addition to droplet volume, distance of fall, and the blood source surface characteristics, other factors affect the size, shape, and appearance of the blood stains. Droplet size is a factor of how much force was imparted on the blood source to put it in flight. The viscosity, specific gravity, and surface tension of blood make it resistant to being broken up into drops. When an external force is imparted on a static pool of blood, it causes some of the blood to react and be thrown in flight. The distance the drops of blood fly through the air is dependent upon how much force was used to create the drops, the size of the blood
Figure 1 (A)(C) The angles of impact for blood stains against a target surface. Reproduced from Wolfson TL. Serology: Bloodstain pattern analysis. In Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
drops, and air resistance. In low-force events (also referred to as low-velocity), the number of blood drops put in flight is low and the sizes of the droplets tend to be large. Most droplets will be larger than 3 mm in diameter, with very few having a diameter less than 3 mm. The distance these droplets travel from the blood source tends to be short. As the level of force or velocity increases, the number of blood drops put in flight and the distance they travel away from the blood source increases. The diameter of the drops decreases as force increases, with many of the blood drops being 1 mm in diameter. There will still be larger drops, but these drops tend to travel a greater distance away from the blood source than the smaller 1- and 2-mm diameter drops. Small drops of blood travel less distance, since they lack the physical weight to resist the air currents and friction, and the energy that put them in flight dissipates rapidly. Most small blood drops do not travel more than 0.9 m (3 ft) from the blood source. When the level of force becomes extremely high (also referred to as high-velocity), such as in spatter created by gunshot, many thousands of blood drops that are 1 mm and less in diameter will be put in flight. As distance from the blood source increases, the size of the droplets increases, but these droplets are small (2 and 3 mm) in comparison to the large drops created by a low-force bloodspatter event. Many of the larger drops that are created in these high-force events are the result of smaller blood drops colliding while in flight and combining into larger-volume drops of blood. Blood stain shape is determined by the angle between the flight path of the droplet and the surface that it impacts (Figure 1). When a drop of blood strikes a horizontal surface from the perpendicular
Figure 2 The shape of a drop of blood that impacted the target surface from an angle of 90 .
(at an angle of 90 , Figure 2), the resulting blood stain will be round. As the angle between the blood drops flight path and the target surface decreases, the length of the resulting blood stain increases and the width decreases; in other words, the blood stain becomes longer and narrower as the size of the angle decreases (Figure 3). A blood drop that has impacted a target surface from an angle of 12 will be long with a
narrow width (Figure 4). Also present on these long narrow stains is a tail (Figure 4). As the drop of blood impacts the target surface, the main body of the droplet will stick to the surface. A small portion of the blood drop will tear off from the top and continue in a forward direction. This secondary spatter has the appearance of a tail. The tail is an important tool when reconstructing blood stain patterns because it points in the direction the droplet was traveling in when it impacted on to the target surface. The shape of the blood stain is also important in the reconstructive process. When the blood drop is deposited on to a surface that does not distort or alter its shape, the width-to-length ratio can be used to calculate the angle of impact for the blood stain (Figure 5). The most frequently used formula for this calculation is: Impact angle arcsine stain width stain length The direction of travel for multiple blood stains in a pattern, when combined with the angle of impact determinations, is used to find the location of the blood source that was hit to create the pattern (Figure 6).
Surface effects on blood stain appearance are very important. If a blood drop is deposited on a smooth, hard, nonporous surface, the shape of the blood stain, as well as the width-to-length ratio, can be used for pattern reconstruction and interpretation (Figure 7). If the surface has characteristics which distort
Figure 6 Blood stain pattern reconstruction. Reproduced from Wolfson TL. Serology: Bloodstain pattern analysis. In Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
Figure 5 Measurement of the blood drop to determine angle of impact. Reproduced from Wolfson TL. Serology: Bloodstain pattern analysis. In Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
Figure 7 Blood dripped from a height of 1 m (3.28 ft) on to a nonporous smooth surface (glass plate).
the appearance of the blood stain or destroy its shape, then the stain will not be useful for a pattern reconstruction. Absorbent surfaces can also affect the appearance, shape, and size of the blood stain (Figure 8). The blood may soak into the absorbent surface unevenly, causing the blood stain shape, as well as the width-to-length ratios, to be altered. These alterations may result in an inaccurate angle of impact determination; this information could prevent an accurate pattern reconstruction for locating the pattern blood source. When a drop of blood strikes a surface that is very rough, it will cause the blood drop to break apart (Figure 9). Determining the angle of impact for these blood stains cannot be done because it is not possible to determine the width and length measurements of the blood stain accurately.
Impact Blood Stain Patterns

Impact blood stain patterns result when static pools of blood are hit. The energy of the impact is transferred to the blood, causing it to break up into droplets that are propelled through the air. If the droplets of blood hit an intermediate surface before the energy that put the blood in flight can dissipate to a level where the pull of the earths gravity overtakes it, distinctive blood patterns will result (Figure 10). The appearance of these blood patterns is affected by the forcefulness of the impact, the volume of blood impacted, the characteristics of the surface the impacted blood is on, the characteristics of the surface the spattered blood is deposited on, and what is impacting into the blood to put it in flight (Figure 11). When viewing an impact blood stain pattern, the distribution, size, and shape of the blood stains in the pattern can provide information concerning the location of the blood source that was hit. Very close to the blood source, the blood stains in the pattern will be more numerous round stains with smaller diameters than the blood stains that are deposited at the edges of the pattern. The blood stains at the
Figure 8 Blood dripped from a height of 1 m (3.28 ft) on to a porous rough surface (paper towel).
Figure 9 Blood dripped from a height of 1 m (3.28 ft) on to a nonporous rough surface.
Figure 10 A low-force impact pattern.
Figure 11 The characteristics of the blood stain droplets near the center of the impact pattern.
edges of the pattern will usually have larger diameters and be elongated. These blood stains will also show in which direction the blood drop was traveling when it impacted the target surface. These stain characteristics make it possible to reconstruct these patterns and determine the location of the pool of blood that was impacted. The number of stains in the pattern, as well as the size of the stains, depends on the forcefulness of the impact. The majority of the small stains will be close to the blood source, while the larger stains tend to be longer distances away from the blood source. The number of stains in the pattern is dependent on the volume of the blood pool and how hard it was hit. Patterns that result from low-force impacts have a low number of stains, most of which are large and have diameters greater than 3 mm. The patterns will cover a smaller surface area than patterns resulting from high-force impacts. High-force impact patterns have more blood stains in the pattern and most of the stains that are close to the blood source will have diameters of 1 mm or less. The size and shape of the blood stains and their distribution on the target surface make it possible to interpret blood stain patterns and determine, within a reasonable degree of scientific certainty, the level of force used to impact the blood source.
Cast-Off Blood Stain Patterns

When liquid blood coats the surface of an object that is being swung, the blood will be thrown off the objects surface due to the centrifugal force of the swing. If the blood is deposited on a target
surface, the resulting pattern is called a cast-off pattern (Figure 12). The blood stains in cast-off patterns line up with one another, giving the pattern a linear appearance. The blood stains in the pattern that are closest to the start of the swinging motion will be round, while the blood stains that are at the terminal end of the pattern (cast off at the end of the swinging motion) will be oval. If the pattern is deposited on multiple surfaces that are oriented different to one another, such as a corner where two walls meet, the shape of the stains in the pattern will be round wherever the arc of the swing was perpendicular to the target surfaces. The width of the cast-off pattern is a factor of the width of the surface from which the blood is forced. The general appearance of the pattern can be affected by the surface characteristics of the object, as well as by the motion and speed of the swing. Cast-off patterns usually only occur during the back swing away from the blood source. When a blood-coated object is swung forcefully, most of the blood will be cast off during the back swing. The effects of inertia as the swing switches direction will force any remaining blood to be cast off before the forward motion begins. Hitting a blood source several times can produce overlapping cast-off patterns. Since it is impossible for each swing to travel along the same arc, the overlapping patterns can be counted to indicate the number of hits after blood flow began. Cast-off patterns may exhibit a slight curvature along the length of the pattern. Under some conditions, this curvature can be used to indicate if the swing was left- or right-handed. Because it is easy to misinterpret cast-off patterns, it is
Figure 12 A cast-off blood stain pattern.
important to be cautious when evaluating these patterns for the number of hits or if the swing was rightor left-handed.
Projected Blood Stain Patterns

Projected blood stain patterns occur when the blood is propelled forward against a target surface, causing the blood to splash as a result of the impact into the surface (Figure 13). In this situation, the energy that put the blood in flight is traveling in the same direction as the blood, pushing it from behind. The action is similar to that of water squirted from a squirt gun. One or more large blood stains will characterize the area of the target surface where the blood strikes first. Radiating out from these blood stains will be hundreds of smaller blood stains. The velocity of the blood when it impacts into the target surface determines the shape, distribution, and quantity of the blood droplets that splash outward. The higher the velocity of the blood when it strikes the target surface, the more spatter that is generated and the more distinctive the shape of the blood stains. The commonest cause of these patterns is arterial injury. Blood flows through our bodies in a closed system of veins and arteries. When an artery is damaged, blood will be forced out of the injury with every beat of the heart. The blood exits the artery under high pressure. If the blood strikes a target surface while the pressure or force is still elevated, the resulting pattern will have
Figure 13 A projected blood stain pattern.
a very distinctive appearance. As the blood impacts into the target surface, the blood is broken up into hundreds of droplets that are splashed outward at an acute angle to the target surface, creating hundreds of secondary blood stains that are very long and spindly in appearance. With each successive beat of the heart, more blood will be pumped out of the breached artery, but the pressure at which it is forced out decreases due to blood loss. The patterns that occur later will not impact the target surface at a lower velocity, thus reducing the quantity of blood drops that splash out from the impact site and changing
their shape from long and spindly to round or oval. These lower-force projected patterns can also occur when the projected blood travels an extended distance from the blood source to the target surface. As the blood flies through the air, the energy that propels it forward will decrease until the speed the blood is traveling at has slowed down to the terminal velocity for that volume of blood.
Large Volumes of Falling Blood Patterns

Patterns that result from large volumes of falling blood will usually have a large central blood stain where the blood impacts the target surface, with numerous blood stains radiating out from the impact site (Figure 14). Blood stain patterns that result from large volumes of falling blood will vary in appearance due to differences in the distance the blood falls to the target surface. Large volumes of blood fall due to the pull of the earths gravity. As the blood falls, its velocity increases. The velocity of the falling blood will continue to increase until it reaches terminal velocity. Terminal velocity is achieved when the air resistance the blood experiences as it falls equals the downward pull of the earths gravity. The terminal velocity of the falling blood and the distance it must fall to reach
terminal velocity are related to its volume. Small volumes and droplets of blood will reach terminal velocity in shorter distances of fall than large volumes and droplets of blood. Studies done by MacDonell on 0.05-ml drops of falling blood showed that they achieved a terminal velocity of 7.6 m s1 (25 ft s1) after falling 7.6 m (25 ft). There is a rapid acceleration of the falling blood in the first 1.2 m (4 ft) of the fall, after which the acceleration is gradual until terminal velocity is reached. Blood that falls a short distance impacts into the target surface at a low velocity, causing a less forceful splash and less secondary spatter. As velocity increases, the blood will impact into the target surface more forcefully, the secondary spatter will be more numerous, and the blood stains may start to become long and spindly. It is possible for blood stain patterns from falling blood to be confused with projected blood stain patterns. Both patterns are the result of the blood splash that occurs when the blood impacts into a target surface. As the large volume of blood falls, its velocity increases until it impacts into a target surface or reaches terminal velocity and impacts into a surface. The velocity of projected blood decreases until it impacts into a surface or it reaches terminal velocity and impacts into a surface. If the distance traveled by the volumes of the blood is similar and the distances that the blood travels are long enough, both volumes of blood will be traveling at the same terminal velocity when they impact into the target surface and the resulting patterns may appear similar.
Contact Blood Stain Patterns

Contact or transfer patterns happen when a bloody object or surface comes into contact with an unstained object or surface. The blood on the object can be transferred to the surface, leaving a pattern. Contact patterns can be nondescript, lacking any characteristics that may reveal the origin of the pattern, or the pattern may exhibit some of the objects characteristics (Figure 15). These characteristics can be compared to the object for the purpose of identification. The most common occurrence of this situation is bloody latent prints. These patterns are very important, since they can be used to identify an individual and place him/her at the crime scene. They are also of importance when the latent print belongs to the subject and the blood the print is made from belongs to the victim. This situation indicates that there was some type of interaction between the subject and the victim after blood flow began. This type of comparison can also be done using bloody impressions from shoes, bare feet, or any object that has individualized characteristics. Some contact patterns
Figure 14 A large volume of falling blood pattern.
Figure 15 A transfer blood stain pattern that resulted from a blood-saturated mattress being leaned against a wall. Reproduced from Wolfson TL. Serology: Bloodstain pattern analysis. In Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
exhibit class characteristics such as the shape of the object. These patterns can be useful for identification of the object type. If the object is wrapped while bloody, or the bloody object comes into contact with another surface, it may transfer blood, creating a pattern in its shape. Even though a pattern may lack details that can identify a specific object, the pattern is useful for investigative purposes.
Blood Trails
When blood drips from an open wound or from a bloody object as it moves horizontally, a blood trail will occur. Blood trails are characterized by large blood drops in a linear pattern that has been deposited on a horizontal surface while dripping from the blood source. This linear characteristic is due to the horizontal movement of the blood source above the target surface while the blood drips due to the pull of gravity (Figure 16). The shape of the blood stains and the degree of secondary spatter associated with the stains will be affected by the distance the drops fall and the speed of horizontal movement for the source of the dripping blood. These patterns can provide information about movements during and after bloodshed. For example, stains in a blood trail may show the direction of the blood sources horizontal motion. If the direction of travel can be determined, the trail can be followed. This is extremely useful when an injured individual leaves the crime scene.
If nothing is done to obstruct the flow of blood, the trail may be followed to determine the location of the individual. Trails can also provide information concerning the sequence of events at a crime scene or assist in locating important evidence. In addition, trails can be characterized by drag marks rather than droplets of blood. When a blood-coated object is dragged over a surface or the object is dragged through blood on a horizontal surface, a trail of smeared blood will result. The direction of the horizontal motion can be determined by examining the fine detail of the pattern.
Blood Stain Drying Times

Blood stain pattern evidence drying times are affected by a number of environmental and physical factors. Blood volume is the main physical factor affecting the length of time required for the stains to dry. Large volumes of blood will dry slower than small volumes of blood when exposed to identical environmental assaults. Environmental factors such as temperature, humidity, surface characteristics, and airflow will affect the speed at which the blood stain patterns dry. Temperatures that are warm will facilitate drying and accelerate the speed at which the blood dries. Cool or very cold temperatures will usually retard blood stain drying times. Humidity also affects blood stain drying times. When equal volumes of liquid blood are
Figure 16 A blood trail. Reproduced from Wolfson TL. Serology: Bloodstain pattern analysis. In Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
deposited in environments with contrasting humidities, the blood that is in the high-humidity environment will dry slower than the blood in the lowhumidity environment. Drying occurs as the water in the stain evaporates into the surrounding air. In high-humidity environments, the air is saturated with water, retarding evaporation and increasing the length of time it takes for the stain to dry. The characteristics of the surface the blood is deposited on will also affect blood stain drying times. If the surface is one that protects the blood by limiting the amount of the blood stains surface that is exposed to the environment, drying of the stain will be retarded, resulting in longer drying times. When the blood stain is deposited on a surface that maximizes the amount of the stains surface that is exposed to the environment, the drying times will be shortened. Environments that allow a good airflow across the exposed surfaces of the blood stain decrease the length of time required for the stain to dry.
Documentation of Blood Stain Pattern Evidence

Documentation and reconstruction of the blood stain pattern evidence are very important aspects of this forensic analysis. When the evidence and reconstruction are poorly documented, the conclusions can become very subjective. There are many different
techniques that are currently in use for the documentation and reconstruction of the blood stain pattern evidence. Some blood stain pattern analysts use computer programs that evaluate data from the blood stain patterns and crime scene and determine the blood source locations. Many blood stain pattern analysts do a physical evaluation and reconstruction of the blood stain patterns at the crime scene while others may work from the crime scene notes, sketches, and photographs. Thorough and complete notes should accompany documentation and reconstruction of blood stain pattern evidence. The notes should contain all observations and data that the analyst used to evaluate the blood stain evidence. Contained in the notes may be police reports, crime scene reports, medical examiner reports, and other forensic evaluations that may have been reviewed prior to the development of the analysts conclusions. The photographic record should include a quality set of pictures that show the blood stain patterns evaluated and the reconstructions done. Prior to starting analysis or reconstruction, the patterns should be photographed and sketched. The camera should be positioned perpendicular to the surface on which the patterns are deposited. This limits distortion in the pictures and gives a truer representation of the appearance of the blood stain patterns. It may be necessary to use artificial lighting to illuminate
the blood stain patterns being photographed. The lights should be positioned to provide even lighting across the entire area of interest. This will avoid creating areas that are overlit (too bright) or underlit (too dark). It is recommended that a handheld photographic light meter be used to assist in positioning the lights. After the blood stain pattern evidence has been photographed in an unaltered state, measurement scales should be positioned around the pattern. Every picture should contain measurement scales that show the location of the pattern in relation to two fixed points. The measurement scales are also important to demonstrate blood stain size data used in the blood stain interpretation process. The blood stain patterns should be rephotographed, showing the patterns with the measurement scales in place. Both the aforementioned series of photographs should start with a general overview of the whole pattern(s) and then proceed to more specific pictures that show the details of the blood droplets in the patterns. After the patterns have been documented in photographs, sketches, and notes, the reconstruction may be performed. Each step of the pattern reconstruction should be photographed. Notes and sketches recording the data obtained should accompany the photographs from the reconstruction. Upon completion of this process, samples of the blood should be collected and submitted to a crime laboratory for analysis. Analysis of the blood samples may assist in the final interpretation of the patterns by helping the analyst connect the patterns to the individuals involved in the blood-spattering event.
See Also
Serology: Overview; Blood Identification
Further Reading
Bevel T, Gardner RM (1998) Blood Stain Pattern Analysis, With an Introduction to Crime Scene Reconstruction. Boca Raton, FL: CRC Press. Eckert WG, James SH (1989) Interpretation of Blood Stain Evidence at Crime Scenes. New York: Elsevier. James SH (ed.) (1998) Scientific and Legal Applications of Blood Stain Pattern Interpretation. Boca Raton, FL: CRC Press. James SH, Eckert WG (1998) Interpretation of Blood Stain Evidence at Crime Scenes. Boca Raton, FL: CRC Press. Laber TL, Epstein BP (1983) Experiments and Practical Exercises in Blood Stain Pattern Analysis. St. Paul, MN: Minnesota Bureau of Criminal Apprehension Forensic Science Laboratory. MacDonell HL (1982) Blood Stain Pattern Interpretation. Corning, NY: Laboratory of Forensic Science. MacDonell HL (1993) Blood Stain Patterns. Corning, NY: Laboratory of Forensic Science. MacDonell HL, Bialousa L (1971) Flight Characteristics and Stain Patterns of Human Blood. Washington, DC: United States Department of Justice, Law Enforcement Assistance Administration. Wolson TL (1995) Documentation of blood stain pattern evidence. Journal of Forensic Identification 45: 396408. Wolson TL (2001) DNA analysis and the interpretation of blood stain patterns. Canadian Society of Forensic Sciences Journal 34: 151157. Wonder AY (2001) Blood Dynamics. London: Academic Press.
Serology, Paternity Testing
See Parentage Testing
SEXUAL OFFENSES, ADULT/Human Normal Sexual Response 81
SEXUAL OFFENSES, ADULT

Contents Human Normal Sexual Response Injuries and Findings after Sexual Contact Evidential Sample Collection Management Postassault Male Sexual Assault Drug-Facilitated Sexual Assault Global Crime Figures and Statistics
Human Normal Sexual Response

R J Levin, University of Sheffield, Sheffield, UK
Introduction
Adult human sexual responses service two functions: procreation (reproduction) and recreation (pleasure). Modern contraception, especially the introduction of steroid contraception (the pill) in the USA in 1960 and in the UK in 1961, enabled the separation of procreation from recreation with near certainty, giving women especially a freedom to explore their sexuality free from the fear of an unwanted pregnancy unheralded in any previous era. However, the resurgence of the specter of venereal disease, especially that of human immunodeficiency virus/ acquired immunodeficiency syndrome (HIV/AIDS), has once again curtailed this freedom. This article describes the role of adult sexual response in both functions but focuses more on the recreational than the reproductive.
Modeling Human Sexual Responses

Simple graphical models depicting human sexual response as diagrammatic curves starting at a horizontal baseline of no arousal with an ascending slope of arousal reaching a peak at orgasm and then a rapid descent back to baseline were published in the mid twentieth century. This model, proposed by William Masters and Virginia Johnson, and based mainly on physiological body and genital changes, characterized arousal in heterosexuals, homosexuals, and bisexuals and for many years was the accepted standard and became almost iconic. The reason for this was mainly that no other laboratory in the world was able to undertake similar studies to verify the changes or their
sequence. Their model categorized human sexual responses into a linear, progressive, four-phased sequence. The phases were named the excitation (E) phase, during which arousal induced by sexual stimuli led to a plateau (P) phase, where the arousal became intensified and if high enough could activate the orgasmic (O) phase, when orgasm occurred, leading to the resolution (R) phase, where the sexual tensions were dissipated. If the induced arousal was not sufficient to achieve orgasm then the phase was bypassed and arousal took much longer to resolve. The acronym EPOR has been applied to this model. Its strengths were in its clinical utility as it encompassed what happened in both males and females and in its aid in treating sexual dysfunctions, but its weakness was that it did not include the psychological dimension of arousal. It became obvious to American sex therapists that they had patients, both male and female, who were not interested in being sexually aroused, even by their loved or significant others. This was interpreted as indicating the absence of a so-called desire (D) phase, which was suggested to occur normally before the E phase. It also became obvious that the so-called P phase of Masters and Johnson was misnamed, as arousal actually increased during this phase and did not plateau; it was really the late part of the E phase. These criticisms led to the modification of the EPOR into the DEOR (desire, excitation, orgasm, resolution) model, which seemed to resolve the major problems of the EPOR model. However, it became apparent from other studies that a large minority of women who were orgasmic claimed never to have experienced spontaneous desire for sexual arousal but when they were sexually aroused, they then had a desire to follow through. Thus, a further modification of the model was needed to separate the D phase, including the classic desire phase (D1) that arises spontaneously and prefaces the E phase as well as a second desire phase (D2) initiated by excitation in the E phase (Figure 1).
82 SEXUAL OFFENSES, ADULT/Human Normal Sexual Response Excitation
Excitation in humans is both central, namely in the brain, and peripheral. The arousal can occur by stimuli acting through sight, touch, sound, taste, smell, and fantasy. Central excitation Until the recent advent of brain imaging looking at the increased regional cerebral blood flow (rCBF) or oxygen utilization in specific regions and monitored either by blood oxygenation level-dependent (BOLD) positron emission tomography (PET) or by functional magnetic resonance imaging (fMRI), little was known about what areas of the brain were active during sexual arousal, ejaculation, and orgasm. Studies have now shown that many parts of the brain are activated during arousal (e.g., ventral tegmental areas, cerebellum, thalamic nuclei, zona incerta, lateral putamen) while some areas show a depressed activity (amygdala in males). While females have a similar pattern of brain activation during arousal there are differences during orgasm. Females show activation of the periaqueductal gray area while males do not and females do not show depression in the amygdala. At our present state of knowledge of rCBF, it is too early to interpret the complex functions and the interactions of all the activated and deactivated areas. Peripheral excitation This is mainly of the genitals (in males, penile tumescence and erection, scrotal contraction and elevation; in females, labial and clitoral tumescence, vaginal engorgement and lubrication) but nipple/areolae erection and increases in blood pressure, heart rate, respiration, perspiration, and myotonia also occur. Emission of sounds (sighs, moans, groans, loud exclamations) often occurs at high levels of excitement and pupil dilation (the cause of the preference for subdued lighting during arousal).
Figure 1 The development of the human sexual response model from the original excitation, plateau, orgasm, resolution (EPOR) concept of Masters and Johnson, through to the addition of the desire (D) phase and abandoning of the plateau (P phase) model of Kaplan (1979), to the current D1/D2EOR model. Adapted from Levin RJ (2001) Sexual desire and the Deconstruction and Reconstruction of the Human Female Sexual Response Model of Masters and Johnson. In: Everaerd, Laan, Both (eds.) Sexual Appetite, Desire and Motivation: Energetics of the Sexual System, p. 66. Amsterdam: Royal Netherlands Academy of Arts and Sciences.
It has even been controversially suggested that without a stimulus that activates arousal there will be no desire, claiming that processing of the emotional stimuli creates physiological changes that prepare the body for action, which in the case of sexual stimuli involve changes in the somatic motor system and specific genital changes that culminate in sexual behavior. Other therapists have suggested that womens desire for and activation of sexual arousal are not identical to mens, and that a different model is needed.
Hormones and Sexual Arousal
Hormones are involved directly and indirectly in sexual arousal in both sexes. The genital structures and functions are maintained by testosterone in males and by a combination of estrogen, progesterone, and androgens (adrenal) in females. Male and female libido (sexual drive) and arousal appear to be dependent on adequate levels of androgen in both sexes. A number of peptide hormones (prolactin, oxytocin, vasopressin) are involved in the neuroendocrine aspects of the sexual response, especially in relation to their release at orgasm. Despite numerous studies, the involvement of hormones in influencing female sexual desire at various stages of the menstrual cycle is still not fully resolved; controversy exists as to whether it peaks around ovulation and perimenstrually.
Male Genital Structures

The primary male genital structures involved in sexual arousal are externally the penis and scrotal sac and internally the testes, epididymis, vas deferens, seminal vesicles, prostate, bulbous and penile urethra, bulbourethral (Cowpers) glands, and the glands of Littre .
Sexual Arousal in the Male

Although the DEOR model applies to males, it is easier to appreciate how sexual arousal is activated by describing the four Es sequence of genital
arousal: excitation, erection, emission, and ejaculation (with orgasm).

Excitation
Males can be conditioned to respond sexually to practically any object or stimulus. Hence, sexual arousal can become linked to rubber and leather garments, female underwear and shoes, furs and female fabrics, the smell of female soiled underwear, material depicting sexually explicit images, sounds of female sexual arousal, and even to physical and mental punishment.
Erection
The flaccid or urinary penis is pendulous, approximately 8.510.5 cm long and 35 cm in diameter. It consists of three longitudinal erectile chambers arrayed around the urethra. The upper two are the paired corpora cavernosa arranged side-by-side above the urethra and consisting of spaces (lacunae) that can become filled with blood and are surrounded by a 2-mm-thick connective tissue membrane the tunica albuginea. The lower chamber is ventral to the corpora cavernosa and surrounds the urethra. At one end it enlarges to form the end or glans of the penis and at the other the penile bulb. During sexual arousal more blood flows initially into the erectile chambers of the penis than can drain away so that the organ first becomes tumescent or swollen but is still pliable. As even more enters, the pressure of the incoming blood rises rapidly against the inextensible tunica, occluding still further the venous drainage through the emissary veins that obliquely pierce the membrane (venoocclusive mechanism). The penis then becomes stiff and cannot be bent the true, full erection. A certain degree of stiffness is essential for penetration through the lips of the vagina (labia minora) into the cavity proper. The stiffness comes exclusively from the erect corpora cavernosa. The corpus spongiosum is filled with blood at a much lower pressure (one-third to one-half that of the cavernosae), creating a soft-ended penile glans that acts: (1) as a protective shock absorber during thrusting to the rigid end of the corpora cavernosa; (2) to protect the female genital tissues from trauma on thrusting; and (3) preventing the urethra from becoming totally occluded during erection and allowing the ejaculated semen to pass. Complete surgical removal of the spongiosum in patients with cancer of the penis does not prevent erection occurring. The long-term mechanisms keeping the unaroused or urinary penis flaccid are still not understood. Blood flow into the flaccid penis is limited by a high sympathetic tone that constricts the blood vessels and lacunae mediated by alpha-adrenergic transmission
(norepinephrine (noradrenaline)). Other constrictive neurotransmitters, such as endothelin-1, thromboxane A, and prostaglandin (PGF2) are also expected to play a part. On effective sexual stimuli the neural sympathetic tone is reduced and at the same time the neural nonadrenergic, noncholinergic parasympathetic innervation is activated to release neuropeptide vasoactive intestinal peptide (VIP) and the gaseous transmitter nitric oxide (NO), causing smooth-muscle relaxation of the penile blood vessels and arterial supply and thus vasodilatation. NO is the major vasodilator and is manufactured from arginine by the enzyme nitric oxide synthetase (NOS) located in penile nerves, smooth muscle, and the cells of the endothelial lining of the cavernous spaces. The NO activates the enzyme guanylate cyclase to form the compound cyclic guanosine monophosphate (GMP) that initiates smooth-muscle relaxation. It is catabolized by the enzyme phosphodiesterase 5, which can be inhibited by various agents such as sildenafil (Viagra), thus raising cyclic GMP levels, facilitating smooth-muscle relaxation, and augmenting penile blood flow. Taken by mouth, such compounds can greatly potentiate the smooth-muscle relaxation response and thus enhance erection in a variety of erectile dysfunctional states. They also reduce the duration of the refractory period in young adult males, suggesting their possible use as recreational performance enhancers. The bulbocavernosus and ischiocavernosus, two striated muscles surrounding the base of the penis, have often been claimed to create erection by contracting and closing off venous drainage. This proposal was first made by Varolius in 1573! However, careful laboratory studies monitoring their electrical myographic activity during erection have clearly shown that erections occur without any such contractile activity but some men use their voluntary contractions to aid or pump up their erections. Erections occur frequently at night during sleep, usually in periods of rapid eye movement (REM) sleep and often with erotic dreams, which can occasionally lead to orgasm and ejaculation (so-called wet dreams). It is thought that during REM sleep the sympathetic system is depressed, thus the vasoconstrictor control of penile blood vessels is relaxed, allowing dominance of proerectile neural innervation. The function of REM-sleep erections is probably to maintain good oxygenation of the penile muscular structures, as it is only then that they receive maximum oxygen supply.
Emission
Emission is activated in the late excitation phase. Secretions are moved into the male ducts due to the adrenergic-mediated contractions of the smooth
84 SEXUAL OFFENSES, ADULT/Human Normal Sexual Response
muscles in the capsules of the various glands (testes, epididymis, seminal vesicles, and prostate). The prostatic and seminal vesicle secretions together with smaller volumes from the testes and epididymis are moved into the prostatic urethra, causing a two- to threefold distension of the urethral bulb. This creates the conscious feeling of ejaculatory inevitability, an awareness that ejaculation is imminent. It is mediated by the pudendal and splanchnic nerves. Normally the sphincter of the bladder closes to prevent any retrograde influx of semen.
Ejaculation
the sperm), buffers, flavins, giving it a yellowy color, and enzymes that decoagulate the clotted semen. Interestingly, sperm do not survive long in seminal vesicle fluid and it has been claimed that ejaculating this fluid last into the vagina protects the sperm from competition from another males sperm if the female tries to cuckold her partner.
Orgasm in the Male
Within a second or two of the feeling of ejaculatory inevitability, the ejaculatory reflex is initiated and various striated pelvic muscles contract clonically, initially about every 0.8 s. These contractions, especially those of the bulbocavernosus, pump the semen along the penile urethra and expel it with force, creating a projectile ejaculation accompanied by throbbing ecstatic pleasure. Most of the ejaculate is expelled by the first few contractions. The importance of these muscles is highlighted if they become paralyzed; the ejaculation is then only mediated by the smooth-muscle contractions of the capsules and the peristalsis of the ducts, creating a dribbling ejaculation of little pleasure.
The Ejaculate
The human ejaculate is a complex, whitish-gray fluid with a characteristic odor (claimed to resemble that of fresh chestnuts and mainly caused by L-pyrolline) and a salty taste. It is an ordered, spurting-type ejaculate: ordered because it consists of a sequenced series of glandular secretions creating a final volume of 26 ml. The first, the pre-sperm fraction, comes from the bulbourethral (Cowpers) gland (sialoproteins) mixed with secretion from the glands of Littre (bicarbonate and protein) dispersed along the wall of the penile urethra. Their joint function is to neutralize any acid or alkaline urine remaining in the urethra and to act as a lubricant on the surface of the glans to ease the initial penetration through the labia minora into the vagina. The next secretion to be added is that of the prostate gland, representing some 30% of the total volume of the ejaculate. Prostatic fluid contains buffers and enzymes that are involved in coagulating the seminal proteins, creating a soft, gel-like structure in which the sperms are immobilized. The sperms are added in a little testicular and epididymal fluid, followed by the final secretion, that of the seminal vesicles, which represents about 60% of total volume. The seminal vesicle fluid contains a high concentration of fructose (presumed to be an energy source for
Because ejaculation and orgasm normally occur together, it is often thought that they are one and the same mechanism. In fact, there is good evidence to indicate that each is activated by a separate mechanism. Orgasm is the ultimate expression of sexual pleasure. It is said that it is the goal for most males if they undertake sexual arousal and that without attaining it they become frustrated with the sexual experience. The first orgasm is usually the most pleasurable; subsequent ones do not create the same ecstatic feelings. Young men can usually have orgasms with a relatively short interval between them but as the male ages the interval between orgasms (and thus ejaculations) gets progressively longer. This interval is called the refractory period and during it males cannot become erect or ejaculate. The specific neural site for the inhibition is not known for certain, but the release of prolactin at orgasm has been suggested as one possible source for the turnoff. The pleasure experienced during the first ejaculation/ orgasm is usually better than subsequent orgasms and the longer the sexual arousal lasts, the greater is the subsequent pleasure on its release. Although the occasional reference has been made to a typology of male orgasms, most assume taking their script from the Masters and Johnsons dictum that however it is generated, the physiological expression of the orgasm is always the same. There are anecdotal reports, however, that orgasms derived from stimulation of the prostate (per rectum) are different from those created by penile stimulation: the former are said to be deeper, more widespread and intense, and last longer than the latter. Unfortunately no laboratory studies have yet examined the two types.
Female Genital Structures Involved in Arousal

The external structures comprising the female genitalia are the outer and inner labia, the clitoris, and the periurethral glans.
Labia
The outer (majora) and the inner (minora) labia surround the vaginal entrance (introitus). There are very large variations in the size and appearance of the
minora; they can meet and close off the vaginal introitus or they can protrude and hang out of the outer labia. On arousal the inner labia become vasocongested, changing their color, and their size increases, adding 12 cm to the length of the vagina. As they act as the gate for entry to the vagina, they need to become lubricated either from the leaking vaginal secretions or possibly by the production of their own lubricative transudate. On engorgement they become quite sensitive to erotic caresses and are a source of sexual pleasure.
Clitoris
The exposed external clitoris represents only a small part of the total erotic clitoral tissue, most of which is internal and hidden. The superficial parts consist of the midline shaft (24 cm long, 12 cm wide) comprising the corpora cavernosa capped by the clitoral glans (23 mm long) at the normally exposed extremity. The shaft bifurcates internally into two curved crura (59 cm long) while on either side of the vagina are two vaginal (vestibular) bulbs (37 cm long) that are part of the corpus spongiosum of the clitoris. The triangular mucous membrane area surrounding the urethral meatus (extending from the upper margin of the introitus to just below the clitoral glans) has been called the periurethral glans. It is described as part of the female corpus spongiosum tissue and it actually has a strand that continues upwards toward the clitoris, ending as its glans. On effective sexual arousal the clitoral tissue becomes enlarged and engorged with blood, effected by the two neurotransmitters VIP and NO that dilate the blood supply to the organ. The enhanced blood flow and congestion make the shaft and especially the clitoral glans extremely sensitive to erotic caresses and these, when applied, give intense pleasure. How important the crura and vestibular bulbs are to the generation of coital sexual pleasure is not known. The internal genitalia consist of the vagina, uterus, and cervix and the anterior vaginal wall erotic complex (urethra, paraurethral glands (G-spot?), and Halbans fascia).
Vagina
membrane is usually ruptured by the first coital activity. Distally the vagina culminates in a cul-de-sac, the anterior wall of which is penetrated by the cervix. A basal fluid production keeps the walls just moist and prevents them adhering when they touch. This basal fluid is mainly produced by a transudation of the plasma leaking through the walls of the capillaries and then percolating between the cells of the epithelium on to its surface. While other fluids can enter the vagina (cervical and uterine fluid and possibly even fluid from the fallopian tubes), they make little contribution to the total volume of the basal fluid. The basal cells of the vaginal epithelium can actively transfer Na ions from the lumen into the interstitial tissue space and then back into the blood circulation. This ion transfer drives the reabsorption of the fluid by osmotic transfer so that the vaginal fluid is constantly being produced and reabsorbed, keeping the surface just moist. While preventing adhesion, this basal fluid is not sufficient lubrication for painless penile penetration and thrusting. Sexual arousal is needed to increase blood flow to the vagina by dilating the arteries through the release of the neurotransmitter VIP while venous drainage is probably constricted by release of the vasoconstrictor neuropeptide Y (NPY). The increased hydrostatic pressure of the blood in the peripheral vessels of the vagina facilitates the filtering of a protein-poor plasma from the capillaries into the interstitial space, creating a neurogenic transudate. This percolates between the epithelial cells, saturating their limited capacity to transfer Na and thus their ability to reabsorb all the fluid. The excess transudate passes between the cells on to the surface of the vagina, creating the lubrication fluid of arousal and allowing painless penile penetration and thrusting. On cessation of sexual arousal the lubrication fluid is slowly reabsorbed by the ionic transfer and the vagina is reset to the basal just moist state. It is often claimed that the female has very little erotic pleasure from simple penile stimulation of the vaginal walls but pressure stimulation of the anterior wall creates strong sexual arousal in many women. Moreover, the vaginal introitus is highly sensitive and pleasurable to the friction of the thrusting penile shaft.
Uterus and Cervix
The vagina is a potential space as when it is sexually quiescent its walls are normally collapsed. They consist of a squamous epithelium surrounded by smooth muscle. Longitudinally the vagina is like a stretched S-shape while its cross-section is H-shaped. It is set in a bed of powerful striated pelvic musculature. The introitus of the vagina is closed in the virgin by the hymenal membrane perforated with an aperture to let the menses and genital fluids escape. The
The involvement of the uterus and cervix in sexual arousal is still somewhat unclear. Masters and Johnson claimed that palpation indicated that the uterus was greatly enlarged during arousal presumably due to engorgement by blood, but MRI scans have not confirmed this enlargement. At orgasm, the
86 SEXUAL OFFENSES, ADULT/Human Normal Sexual Response
smooth muscle of the uterus contracts. The infolded epithelium of the cervix produces a mucoid secretion (sialoproteins) whose production is increased by estrogens but reduced by progesterone. Its secretion is probably released by VIP but it is not a significant part of lubrication during sexual arousal. The involvement of the cervix in the arousal process is even more controversial. It is acknowledged to have little or no sensory or afferent innervation; minor surgery can be carried out on the cervix without anesthesia but some authors think that penile buffeting of the cervix occurs during coitus, pushing the uterus against the peritoneal membrane, which supposedly causes pleasurable feelings. Others however think that this penilecervical contact occurs only rarely during coitus. One aspect of the uterocervix unit originally described by Masters and Johnson during arousal in the late E phase was the phenomenon of vaginal tenting and ballooning. At this time the uterus and cervix become elevated away from the posterior vaginal floor while the distal part of the vaginal cavity (posterior fornix) becomes enlarged. Apart from creating a reservoir for the ejaculated seminal fluid, no functional explanation for the uterocervix elevation and tenting has been forthcoming until recently. Levin has proposed that, by retracting the cervix away from the vaginal posterior wall, a delay in the transport of spermatozoa into the cervical canal and hence to the fallopian tubes is achieved, giving time for the ejaculate to liquefy, sperm motility and mobility to be initiated, and to begin the process of capacitation (making the sperm fertile). The uterine contractions at orgasm play little or no part in the normal transport of sperm during coitus as the cervix is retracted well away from the ejaculated pool of seminal fluid. In fact, the fastest sperm transport is actually in the unaroused woman. Some think that the contractions of the uterus signal the cessation of sexual arousal in the woman.
The Vaginal Anterior Wall Erotic Complex
Some claim that this area is also the site of the paraurethral glands, the remnant of the prostate gland in the female. However, most of the paraurethral glands are much further along the urethra near the vaginal introitus. A small amount of fluid can be secreted by the paraurethral glands during high sexual arousal and be emitted at orgasm, the so-called female ejaculation. Descriptions of large volumes of fluid being ejaculated suggest that urine is being spurted either directly or from a urethrocele. Halbans fascia The space above the anterior wall of the vagina between the trigone muscle of the bladder and the neck of the urethra is known as Halbans fascia and contains nerves and pseudocorpuscular nerve endings, and is rich in vascular tissue. When stimulated by strong pressure it gives rise to pleasurable feelings.
Female Orgasm
The urethra and paraurethral glands The urethra in the female is a short muscular tube approximately 34 cm long connecting the bladder base to the urethral meatus. It is embedded in the anterior vaginal wall and is invested with erectile tissue, which becomes engorged on sexual arousal. During coitus the thrusting penis buffets the base of the bladder, stretching the urethra and generating a pleasurable feeling. An area of the urethra around the junction with the base of the bladder is said to be the G-spot area that, when strongly massaged, can rapidly induce high sexual arousal and subsequent orgasm.
Ecstatic feelings often concurrent with genital and pelvic muscular contractions are common to both men and women at orgasm. Furthermore, written descriptions by men and women of orgasm with gender references removed cannot be distinguished from one another by male and female assessors. This suggests that the mental changes that occur at orgasm are similar in both sexes. There are, however, differences between male and female orgasms. Unlike males, females: (1) do not have a refractory period after orgasm so they can be serially multiorgasmic; (2) report that the pleasure experienced is better for subsequent orgasms compared to early ones; (3) can have their orgasms interrupted by extraneous mental or external stimuli or by cessation of the inducing stimulus; and (4) generally have longer orgasm (approximately 20 12 s, mean SD, n 26) than males. An intriguing question is: why do females have pelvic striated muscle contractions at orgasm? In males these muscles are important for creating projectile ejaculation but there is no such need in women who, if they ejaculate at all, are dealing with a few drops of paraurethral emission. Other functions claimed for the female pelvic contractions are: (1) to empty the vasocongested pelvic/genital tissues (but a single orgasm does not actually empty them); and (2) to create pleasure (but voluntary contractions of these striated muscles do not create pleasurable feelings). It is likely that the female contractions are vestigial in that they are initiated from a common male/female model (just like nipples) and as they do no harm there was no point in biological terms in using energy to get rid of them.
SEXUAL OFFENSES, ADULT/Injuries and Findings after Sexual Contact 87
Many women report that orgasms induced by clitoral stimulation feel different from those generated by coital activity. A controversial typology of orgasms has long been claimed for clitoral-induced orgasms compared to those generated by vaginal coitus/cervical buffeting. More recently, physiological recordings have indicated that orgasms induced by anterior vaginal wall stimulation (G-spot) gave a different balance of smooth to striated muscle contractions than those generated by clitoral stimulation but much further investigation of this area is needed.
Sexual Arousal and Orgasm by Forced or Nonconsensual Sexual Stimulation

In consensual sex the sexual arousal and possible induction of orgasm are normally the welcomed outcomes and it is tacitly assumed that a willingness to undertake and experience the activity is an important factor allowing arousal and orgasm to occur. What happens in the nonconsenting male or female forced to accept sexual stimulation? Can arousal and orgasm occur even though the victims of sexual aggression find the stimulation dreadful? A review of the sparse literature and a survey of various cases indicate that sexual arousal and indeed even orgasm can be induced in victims who presumably have strong excitatory but weak inhibitory control of their sexual responses. Evidence of arousal and orgasm should not be taken as evidence of consent to the enforced sexual stimulation.
Levin RJ (2002) The physiology of sexual arousal in the human female: a recreational and procreational synthesis. Archives of Sexual Behaviour 31: 405411. Levin RJ (2003a) The physiology of male and female sexual arousal. In: Payne-James J, Busuttil A, Smock W (eds.) Forensic Medicine: Clinical and Pathological Aspects, pp. 379389. London: Greenwich Medical Media. Levin RJ (2003b) The ins and outs of vaginal lubrication. Sexual and Relationship Therapy 18: 517521. Levin RJ (2004) An orgasm is . . . who defines what an orgasm is? Sexual and Relationship Therapy 19: 101107. Levin RJ, van Berlo W (2004) Sexual arousal and orgasm in subjects who experience forced or nonconsensual sexual stimulation a review. Journal of Clinical Forensic Medicine 11: 8288. Masters WH, Johnson V (1966) Human Sexual Response. Boston, MA: Little. Meuwissen J, Over R (1992) Sexual arousal across phases of the human menstrual cycle. Archives of Sexual Behaviour 21: 165173.
Injuries and Findings after Sexual Contact

C Bassindale, Lancashire Sexual Assault Forensic Examination Centre, Preston, UK J Payne-James, Forensic Healthcare Services Ltd, London, UK
See Also
Sexual Offenses, Adult: Injuries and Findings after Sexual Contact; Evidential Sample Collection; Management Postassault; Global Crime Figures and Statistics
Introduction
It is widely assumed outside the forensic medical arena that sexual assault of any nature will result in injury to the victim. This is not correct and sexual assault (including rape) may often occur without any visible physical injury genital or nongenital (extragenital). Conversely, consensual sexual activity (sexual activity between consenting adults) may result in injury. It is thus clear that the presence or absence of injuries in association with allegations of sexual assault do not necessarily indicate by themselves one way or another whether the particular activity was consensual or nonconsensual. It is the role of the forensic physician or other tasked with taking a history, undertaking an examination, and taking appropriate forensic specimens to ensure that their assessment will capture all relevant information that will allow courts and investigating authorities to come to an appropriate decision. The meticulousness of the examination should be the
Further Reading
Baker RR, Bellis MA (1995) Human Sperm Competition Copulation, Masturbation and Infidelity. London: Chapman Hall. Basson R (2003) The female sexual response; a different model. Journal of Sex and Marital Therapy 26: 5165. Holstege GG, Geiorgiadis JR, Paans AM, et al. (2003) Brain activation during human male ejaculation. Journal of Neuroscience 23: 91859189. Hutchinson KA (1995) Androgens and sexuality. American Journal of Medicine 98(suppl. 1A): S111S115. Kaplan HS (1979) Disorders of Sexual Desire. New York: Simon and Schuster. Levin RJ (1998) Sex and the human female reproductive tract what really happens during and after coitus? International Journal of Impotence Research 10 (suppl. 1): S14S21.
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same for both the complainant and the alleged perpetrator, and as an examiner an independent nonjudgmental stance should be taken when examining either individual. This article focuses on key principles to be aware of when considering injury related to sexual contact.
Table 1 Studies examining type and frequency of injury following clinical examination of complainants of sexual assault
Incidence of no genital injury Incidence of genital injury
Study
Availability of Data of Injury Following Sexual Contact

Any examination of a complainant or an alleged perpetrator of sexual assault should meticulously document injuries: (1) related to the genital, perineal, and anal regions; and (2) related to the rest of the body. A violent rape may leave no evident general injuries but injuries on limbs, head, and torso may well reflect accurately the assault from the account given. Therefore, any review of injuries following sexual activity must consider and comment on the presence or absence of both genital and nongenital injuries. There is however a relatively poor evidence base of case-controlled studies that have specifically explored patterns of injury following sexual assault compared with patterns of injury following consensual sexual activity, and thus there are few data to assist with the interpretation of injuries alleged to have occurred during a sexual assault. One of the reasons that this problem arises is the practical difficulty (if not impossibility) of matching subjects and sexual acts in research settings. The method of examination, which varies from both a country-by-country and region-by-region point of view, means that different methods of clinical examination are undertaken. The increasing use of colposcopes in examinations following alleged sexual assaults enables better visualization and documentation of micro injuries (e.g., bruises, abrasions) of the genitalia that may be present after assault. However, findings discovered in a clinical examination when a colposcope is used following an alleged sexual assault must be interpreted in the context of the very limited information regarding the prevalence and incidence of such examination findings following consensual sexual activity.
Riggs et al. (2000) Adams et al. (2000) Kerr et al. (2003) Islam (2003)
67% 39%
53% 79% 24% 39%
all the following, each of which may have differing influences at different times: age of the complainant, type of sexual activity, relative positions of the participants, previous sexual activity, and degree of intoxication of either or both of the participants. In addition to the activity/complainant/victim issues are factors such as the time of examination since assault and the methodology of examination. The incidence of injury found during examination of complainants of sexual assault varies markedly between studies, in part reflecting the differences described before. In the studies used here to illustrate, the incidence of genital injury varied between 24% and 79%.
Genital and Associated Injury
Nonconsensual Sexual Contact and Injury

A number of studies have been published that explore the type of injury seen and the frequency with which the injuries have been noted following clinical examination of complainants of sexual assault. Some of these are shown in Table 1. Factors that may influence the degree and severity of injury and the anatomical site of the injury include
The different types of sexual activity may give rise to different patterns of injury, when injury is present. It is therefore of the utmost importance to establish in detail what physical activity the alleged assault entailed so that the specific injuries that may be associated with the particular activity can be specifically looked for, documented if present, or recorded as such if not present. It must also be emphasized that each part of sexual activity may be undertaken by the complainant or suspect, either coerced or compliant, and thus appropriate examination of both parties with as much information as possible about the allegations will be required to maximize information that will be of use to the investigators and courts. Anilingus (rimming) is the kissing, licking, and sucking of the anus by a sexual partner. Cunnilingus is the kissing, licking, and sucking of a females genitalia by her partner. During anilingus and cunnilingus there may be repeated thrusting of the tongue over the mandibular incisors which may result in injury to the tongue or ulceration of the lingual frenulum. In digitalvaginal, penilevaginal, and object vaginal intercourse there may be friction or blunt trauma sustained as the digit, penis, or object penetrates through the labia majora, labia minora, and
SEXUAL OFFENSES, ADULT/Injuries and Findings after Sexual Contact 89
hymen into the vagina. It may be helpful to establish whether any form of lubrication was used or whether earlier consensual sexual activity may have assisted in lubrication at the time of assault. The digit, penis, or object may result in stretching or blunt trauma of the posterior fourchette. Thus, all forms of vaginal intercourse may result in bruises, abrasions, and lacerations of the labia majora, labia minora, hymen, and posterior fourchette. Published case reports following allegations of rape have highlighted that vaginal penetration can cause injury to the cervix. Cervical trauma may occur during penetrative vaginal intercourse as the penetrating item or bodily part collides with the cervix and this infrequently results in injuries to the cervix. Buggery is the lay term for penile penetration of the anus of a man, woman, or animal (in the latter case known as bestiality). In digitalanal, penileanal, and objectanal intercourse there may be friction or blunt trauma of the perianal skin, anal canal, and rectum which may result in bruises, abrasions, lacerations, and anal fissures of these sites. Anal fissures are longitudinal lacerations in the perianal skin and/or mucosa of the anal canal. Anal fissures may heal leaving a scar, skin tag, or no sign. Anal fissures have causes other than penetrative sexual activity, including the passage of hard stools and diarrhea. Fellatio (irrumination, penileoral penetration) is a sexual activity in which the penis is stimulated by the partners mouth. Nonconsensual fellatio may result in bruising (petechial and confluent) on the soft palate and at the junction between the hard and soft palates, lacerations of the frenula, and bruises and abrasions and of the lips. Holding the complainants face and neck forcibly may result in abrasions, scratches, and bruises.
Nongenital Injury
on the skin or abrasions or bruises. Suction may result in a petechial bruise or bruises. Being bitten can be extremely painful and the complainant may move away from the bite so that there is considerable movement and dragging of the teeth over the skin with a shearing action on the tissues which may distort the bite pattern. The investigation and interpretation of such bite marks particularly when issues of identification are an issue, as in allegations of stranger rape require the early involvement of a forensic odontologist.
Consensual Sexual Contact and Injury

There are very few data of the incidence and type of genital and nongenital injuries of females and males following consensual sexual activity. Consensual sexual activity has been shown to result in the full gamut of blunt-trauma injuries and consequently bruises, abrasions, and lacerations to genital and nongenital sites may be present. The severity and site of the injury vary according to many factors, including the type of sexual activity, position of participants, previous sexual activity, and intoxication of the participants. The accounts between two participants may differ substantially in the description of the degree of force used and the medical findings may add more weight to one account over the other. The factors that may influence the degree and severity of injury and the anatomical site of the injury are the same as for nonconsensual activity and thus may include some or all of the following, each of which may have differing influences at different times: age of the complainant, type of sexual activity, relative positions of the participants, previous sexual activity, and degree of intoxication of either or both of the participants.
Genital Injury
Many complainants of sexual assault have no injuries to their body surfaces and of those injured, most will have only minor injuries. If there was a struggle between the parties or if the complainant was physically assaulted, any type of injury at any site may result. The location or patterning of injuries may have forensic significance. For example, clusters of circular or oval bruises approximately 1 cm in diameter may result from the pressure of the fingertips as occurs in grabbing, grasping, or forcing the thighs apart. Abrasions and bruising of the ulnar borders of the forearms and hands (defense wounds) may occur as a complainant defends him/herself from offensive blows. Human bites may result in a characteristic broad U-shaped arch of broad, shallow indentation marks
Consensual insertion or attempts at insertion of a finger or fingers, penis, or any other object into the vagina may result in bruises, abrasions, and lacerations of the labia majora, labia minora, hymen, and posterior fourchette. Consensual digital vaginal penetration may result in accidental fingernail damage or injury to parts of the female genital tract which may not be noticed by either party. Death has been reported in a female who sustained such an injury during consensual sexual activity. Vaginal injuries may result in bleeding. If penilevaginal penetration follows the digital vaginal penetration then it seems likely that any injury or bleeding may be exacerbated. Cases have been reported where consensual vaginal sexual activity
90 SEXUAL OFFENSES, ADULT/Injuries and Findings after Sexual Contact
resulted in injury causing bleeding, which necessitated internal iliac artery ligation. Sexual intercourse causing bleeding from an inflamed or diseased cervix is mentioned in standard gynecology textbooks as an explanation for postcoital bleeding. It has been stated that the flaccid penis is protected by its mobility whereas the erect penis is an injury-prone organ. Direct blunt trauma to the penis may be caused when the penis accidentally slips out of the vagina and is thrust against the symphysis pubis or perineum or during other circumstances of an autoerotic nature. Such trauma may result in tears of the preputial skin or a rupture of the corpus cavernosum (known as a fracture of the penis). The latter may be associated with an audible crack and immediate hematoma formation, which requires early surgical exploration and evacuation to prevent organization of the hematoma with fibrous plaque formation, calcification, and formation of ectopic bone. It has been suggested that Peyronies disease, which results in a bent penis when erect, may be a result of the effects of shearing forces during strenuous intercourse. Consensual anoreceptive intercourse may cause blunt trauma to the anus and rectum which may result in bruises, abrasions, and lacerations. However, this is not commonly seen if adequate lubrication is used, and excess force is not applied.
Nongenital Injury
Table 2 Case reports highlighting severe life-threatening conditions resulting from consensual sexual activity
Condition Reference
Ruptured spleen Liver laceration Hematoperitoneum (as a result of laceration of the vaginal wall) Round-ligament laceration Ovary laceration Serous cystadenoma rupture
Mahmood (1970) Davidson et al. (1993) Bhagat (1996)
McGolgin et al. (1990) McGolgin et al. (1990) McGolgin et al. (1990)
Summary
Available data confirm that nonconsensual sexual activity does not necessarily cause injury and that consensual sexual activity can cause injuries. It is important to relate any injuries alleged to have occurred as a result of sexual contact to the precise activity stated to have been undertaken. Certain types of activity result in specific injury to both passive and active participants or assailant and victim. An awareness of these patterns will assist in interpreting significant positive and negative findings seen and recorded at examination.
See Also
Sexual Offenses, Adult: Human Normal Sexual Response; Evidential Sample Collection; Management Postassault; Global Crime Figures and Statistics
During consensual sexual activity, blunt trauma as a result of collision, friction, or grasping may result in bruises and abrasions on the surfaces of the body including the inner thighs. Consensual fellatio may result in bruising (petechial and confluent) on the soft palate and at the junction between the hard and soft palates. Love bites (hickeys) caused by sucking pressure result in petechial bruises. Published case reports highlight that severe lifethreatening conditions may result from sexual activity that was either stated or presumed to be consensual (that is, there was no complaint of sexual assault). Table 2 gives some examples. It appears that forces which may be exerted during vigorous sexual activity (not just penile penetration) can result in the type of accelerationdeceleration injuries that would normally be associated with more significant traumatic mechanisms (such as road traffic accidents and falls). Such forces are known to result in injuries to relatively fixed organs, such as the liver, spleen, and aorta. However, the variety of sexual activity and the incidence around the world suggest that such episodes are very rare.
Further Reading
Adams JA, Giardin B, Faugno D (2000) Signs of genital trauma on adolescent rape victims examined. Journal of Pediatric and Adolescent Gynecology 13: 88. Bhagat M (1996) Coital injury presenting in a 13 year old as abdominal pain and vaginal bleeding. Pediatric Emergency Care 12: 354355. Blandy J, Fowler C (1996) Urology. Oxford, UK: Blackwell Science. Bowyer L, Dalton ME (1997) Female victims of rape and their genital injuries. British Journal of Obstetrics and Gynaecology 104: 617620. Davidson PG, Ozuner G, Silich RJ (1993) Haematoperitoneum as a result of coital injury to the liver. A case report. Journal of Reproductive Medicine 31: 675677. Giardino AP, Datner EM, Asher JB (2003) Sexual Assault: Victimisation Across the Lifespan: A Clinical Guide. St. Louis, MI: GW Medical. Godec C, Reiser R, Logust A (1988) The erect penis injury prone organ. Journal of Trauma 28: 124126. Islam MN (2003) Retrospective study of alleged rape victims attended at Forensic Medicine Department of Dhaka
SEXUAL OFFENSES, ADULT/Evidential Sample Collection 91 Medical College, Bangladesh. Legal Medicine 5(suppl. 1): S351S353. Kerr E, Cottee C, Chowdhury R (2003) The Haven: a pilot referral centre in London for cases of serious sexual assault. British Journal of Obstetrics and Gynaecology 110: 267271. Kindermann G, Carsten PM, Maasen V (1996) Ano-genital injuries in female victims of sexual assault. Swiss Surgery 1: 1013. Mahmood A (1970) Coital rupture of the spleen. Journal of Obstetrics and Gynaecology of the British Commonwealth 77: 660. McGolgin WS, Williams LM, Sorrells TL, Morrison JC (1990) Haematoperitoneum as a result of coital injury without associated vaginal injury. American Journal of Obstetrics and Gynaecology 163: 15031505. Payne-James JJ (2003) Assault and injury in the living. In: Payne-James JJ, Busuttil A, Smock W (eds.) Forensic Medicine: Clinical and Pathological Aspects. London: Greenwich Medical Media. Riggs N, Houry D, Long G, Markovchick V, Feldhaus K (2000) Analysis of 1076 cases of sexual assault. Annals of Emergency Medicine 35: 358362. Rogers D, Newton M (2000) Sexual assault examination. In: Stark MM (ed.) A Physicians Guide to Clinical Forensic Medicine. Boca Raton, FL: Humana Press. Sadler DW, Pounder DJ (1998) Fatal air embolism during consensual intercourse in a non-pregnant female. Journal of Clinical Forensic Medicine 5: 7779. Sivalingham N, Rajesvaran D (1996) Coital injury requiring internal iliac artery ligation. Singapore Medical Journal 37: 547548. Slaughter L (1996) Patterns of genital injury in female sexual assault victims. American Journal of Obstetrics and Gynaecology 176: 609616. Slaughter L, Brown C (1991) Cervical findings in rape victims. American Journal of Obstetrics and Gynecology 164: 528529.
acceptable, yet it is difficult in the absence of an independent witness. Medical examination, investigation, and opinion may help to overcome this difficulty. The laws on rape have undergone transformations over the years. Many traditional definitions of rape have been reviewed and redefined. Today, the legal definition of rape and other sexual offenses varies from country to country.
Rape Laws and Interpretation

The word rape is probably derived from the Latin rapere, which means to snatch. Traditionally some form of violence or evidence of resistance is expected to be present on the victim before it is accepted that rape actually did take place. This evidence of resistance, justifying that there was no will on the part of the complainant, derives from early nineteenthcentury English common law. As a result, the court of law usually expects there to have been some form of physical violence to corroborate the allegation of rape. Some laws still include a section against her will in the definition of rape. However, this attitude is presently considered unfair. Many countries have reformed their rape laws to suit current need. According to English law on rape, a man commits rape if he has unlawful sexual intercourse with a woman who at the time of the intercourse does not consent to it; and at that time he knows that she does not consent to the intercourse or he is reckless as to whether she consents to it. The Criminal Justice and Public Order Act of 1994 has further amended the English law, replacing woman with person and defining sexual intercourse as penetration of the vagina or anus. At present in many countries the main issue pertaining to rape is the question of valid consent. The presence of injuries on the body of a victim suggestive of a struggle is supportive of an act against her will. However, due to various circumstances a woman may not be able to resist the rapist and therefore the absence of injuries does not necessarily mean that she was a willing partner. In the UK, Section 32 of the Criminal Justice and Public Order Act of 1994 granted the court power to use its discretion to decide on the question of corroborative evidence pertaining to sexual intercourse without the victims consent. In Malaysia, it is still a rule of law that the testimony of the complainant in a sexual offense case needs to be corroborated by an independent witnesss account such as that provided by medical evidence. Physical examination of the complainant is an essential part of the doctors clinical examination. If there are wounds suggestive of resistance or an attack by the assailant, then such findings will provide
Evidential Sample Collection

K Nadesan, University of Malaya, Kuala Lumpur, Malaysia
Introduction
Rape is said to be the fastest-growing violent crime in many parts of the world. As rape is a criminal offense in general terms, proof beyond reasonable doubt is necessary before guilt can be established. Independent corroboration may be necessary before the suspect can be found guilty. Even though in many countries uncorroborated testimony of the complainant is
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strong corroborative evidence. But, as already mentioned, in many instances there are no injuries present to suggest a struggle or physical assault.
Intercourse in Law
the hymen could be very loose, lax, and stretchable and hence will not tear during intercourse. Therefore, it is important to remember that an intact hymen is not necessarily proof of virginity and a torn or absent hymen does not necessarily mean that the woman was used to having intercourse.
Consent for Sexual Intercourse
Definitions vary but generally vaginal penetration by the penis is sufficient to constitute sexual intercourse for the offense of rape. The slightest degree of penetration is enough. Even the tip of the penis between the labia has been accepted as intercourse in law. If penetration cannot be satisfactorily proved, the defendant may be convicted of attempted rape, and if the intent is not proved he may be convicted of indecent assault. It is not necessary to prove the completion of sexual intercourse by orgasm or ejaculation of semen. In several countries rape laws are mainly related to unlawful sexual intercourse between a man and a woman. French law, for example, is a notable exception to this general principle. According to French law, rape is defined as any act of sexual penetration of any nature committed on another person by violence, constraint, threat, or surprise. According to this law, rape does not only relate to penile penetration of the vagina or an offense involving only a man and a woman. The Anti-Rape Law of Philippines, passed in 1997, is similar, and it includes as sexual assault inserting the penis into another persons mouth or anal orifice, or any instrument or object into the genital or anal orifice of another person without consent. In the USA many states have replaced the crime of rape and other traditional sex crimes with a series of gender-neutral and graded offenses with appropriate punishments. Even sexual penetrations have been redefined to include sexual intercourse, cunnilingus, fellatio, anal intercourse, or any other intrusions involving any part of a persons body or of any object into the genital or anal opening of another persons body. In a virgin, fresh injury to the hymen is suggestive of penile penetration but does not confirm it. Any other blunt object can cause laceration of the hymen. If seminal fluid or spermatozoa are detected in the vagina, this generally confirms penile penetration. An intact hymen and absence of semen do not necessarily rule out the possibility of penile penetration. The anatomy of the hymen is very variable. The hymen is generally a thin membranous structure found at the vaginal introitus: it has no definite function. The hymen is of many shapes: annular, marginal, septate, fimbriated, and occasionally imperforate. It is traditionally believed that the hymen ruptures on the first intercourse and in many communities this aspect has to be proven on the first night after marriage to prove that the bride was a virgin. However,
Consent for sexual intercourse has a very complex meaning. When given, consent should be free, voluntary, conscious, and informed. Further, the woman should be of consenting age and in a proper state of mental development and mental state to understand all the implications. There should not be any force, duress, or fraud while obtaining consent. English law on rape is very clear on this issue. It says that at a trial for a rape offense the jury has to consider whether the man believed that the woman was consenting to sexual intercourse; the presence or absence of reasonable grounds for such a belief is a matter to which the jury is to have regard, in conjunction with any other relevant matters, in considering whether he so believed. Consent for sexual intercourse is not an issue if the girl is below 16 years of age and therefore sexual intercourse with or without consent is considered as rape. Consensual sexual intercourse with a girl below 16 is referred to as statutory rape.
Examination of the Complaint

Valid consent should be obtained before examination. If the complainant is below 18, then consent has to be obtained from the parent or guardian. The examiner should direct attention to mental state, mental and physical development, the state of the clothing, and the general behavior of the victim. The weight, height, and apparent age should be noted. A detailed history should be obtained from the victim, covering the entire episode, including the actual sexual act. In addition, questions should be asked about the menstrual history, previous sexual exposures, surgical operations, childbirth, sexual intercourse with husband or boyfriend within the few days before the alleged rape, and the use of tampons. After carefully removing the clothing, the entire body should be examined for injuries. If the victim is examined shortly after the alleged offense, then she should be made to stand on a clean sheet of paper while undressing. Any trace materials falling from the clothing or body can be collected on the paper and sent to the forensic laboratory for analysis. Injuries to the genital area, state of the hymen, and the vaginal introitus need to be examined carefully under
SEXUAL OFFENSES, ADULT/Evidential Sample Collection 93
good lighting, which may provide evidence of vaginal penetration. Examination and interpretation of the findings in a hymen may be difficult at times. A particularly annular, fleshy, and deep-seated hymen may pose problems. It is also important that the survivor cooperates with the doctor so that a good examination can be carried out. In small children it may be necessary to carry out examination under anesthesia. Employing the Glaister-Keene rod will make it easier to examine the hymen although concerns are now expressed due to difficulties of ensuring sterility and decontamination of the rods. If any bite wounds are present then ideally a forensic odontologist should examine such wounds. The bite mark may be that of the assailant or, rarely, self-inflicted to implicate an innocent person or for any other reason, and hence an expert opinion may have to be sought. Collection of trace materials and other specimens from the victim, using correct techniques, appropriate instruments, and containers, is an important part of the medical examination. Contamination and crosscontamination should be avoided. Hence, the place where the victim is examined should be clean, instruments should be sterile, and the doctor should wear protective clothing. When oral sex or anal intercourse is alleged, then swabs must be obtained from the mouth and anus as well. To prove a case of rape, corroboration is important to the court, though not absolute. The doctors report and opinion will play an important role in providing independent and scientific corroborative evidence.
Examination of the Suspect

Appropriate examination of the suspect is as important as that of the complainant. Often the police will produce the suspect before a doctor for a medical examination. The protocol to be followed is the same as for the complainant. A valid consent for examination is essential. The doctor should be unbiased, as the person is a suspect, the offense is not proved, and the man may well be innocent. Complete privacy is essential and it may be appropriate during examination that police personnel are not allowed to remain in the examination room. There may be injuries to the suspect if there was a struggle. It is important to look for scratch abrasions caused by fingernails on the face, neck, back of chest, trunk, buttocks, and upper limbs. Very superficial abrasions, if they are fresh, may not be visible and if the person is examined again 24 h later, the injuries may become more visible due to drying and healing. There may be contusions on the suspect caused by fingertips pinching, punching, or kicking during the struggle. Faint bruises are easily detected in
fair-skinned individuals, but in dark-complexioned persons bruises may not be visible to the naked eye. With the aid of ultraviolet light, these latent bruises may be detected. Deep-seated bruises cannot be seen, but they can be detected during the clinical examination as tender areas. The color changes that occur in surface bruises may be important in establishing the age of the wound and may help to corroborate the approximate date of the alleged offense. If bite marks are present, whenever possible, the assistance of the forensic odontologist should be sought. Special attention has to be paid during examination of the male genitalia. The development of the penis, its size, whether it is circumcised or not, whether the prepuce is retractable or not, development of the testicles, evidence of vasectomy, and any peculiarities such as the presence of penile spheres should be looked for during the examination. In an uncircumcised person, retract the prepuce and carefully examine the frenulum, because this is an area that can be injured during intercourse. Foreign materials such as blood, seminal stains, vaginal secretions, vegetable matter, or mud stains sticking on the pubic area, thighs, buttocks, and knees should be looked for. Sometime the police may raise the issue of erectile dysfunction (impotence). A detailed investigation for this should be undertaken when the suspect claims that he has erectile dysfunction. Initial examination can establish if there are obvious anatomical abnormalities which may cause dysfunction or inherited genetic disorders or definite illnesses that may affect potency. Testing for impotence involves a physical examination, thorough clinical examination, and relevant laboratory and/or psychological investigations. An important cause of undiagnosed male erectile dysfunction is psychological causes. Hence, a clinical examination for male impotence usually involves a psychiatric opinion.
Collection of Specimens from the Complainant

If the complainant is produced immediately or shortly after the alleged attack, then it is useful to have her undress over a clean sheet of paper, provided in the rape kit. Any material such as hairs, cloth fibers, leaves from the complainant, or the location that may be sticking to the body may come loose and can be collected on the paper, providing excellent corroborative evidence. The examination procedure should be modified according to circumstances. If the offense took place shortly before the examination, then it may be better to proceed with an
94 SEXUAL OFFENSES, ADULT/Evidential Sample Collection
examination of the genital area and relevant evidential sample collection first. If some days have elapsed, then the examination may start with a general examination and then proceed to the genital area. In the latter situation there is no need to undress over a sheet of paper. The complainant lies in the lithotomy position before the swabs from the genital area are collected: 1. The first swab is taken from the vestibule. The labia are gently separated and two external swabs are obtained. 2. The next swab is taken from the perianal area (if ejaculation occurred, it is likely that seminal fluid would have leaked out of the vagina and contaminated the perianal area). If the perianal swab is positive for spermatozoa, this should not be taken as positive evidence for anal intercourse! 3. Two internal vaginal swabs are obtained, one from the low vaginal passage and the other from the upper vagina. The upper vagina should include the fornices. It is ideal to enclose the swab in a plastic sheath before introducing it into the upper vagina to obtain the high vaginal swab. Once the swab is obtained, it is withdrawn into the sheath before removing it from the vagina. This reduces the chance of a false-positive result. At least two swabs are obtained from each site. Note that if a few days have elapsed after the alleged assault, then the swabs are unlikely to be positive for semen or spermatozoa. However, it is reported that spermatozoa may be identified from the cervical os up to 7 days later (a vaginal speculum must be employed to obtain a swab from the cervical os). The swabs should be air-dried and packed in sterile tubes, not plastic bags. Do not dip the swabs in any transport media. Some laboratories entertain vaginal smears taken on slides in addition to swabs, and if the smear is found to be positive for spermatozoa then the swabs are used for DNA study. 1. If anal intercourse is alleged or suspected, then an anal swab must be obtained. Here too a low anal and a high anal swab are taken, if necessary with the aid of a proctoscope. 2. If oral sex is alleged or suspected, then an oral swab is obtained. 3. Visible dried stains in the form of crust seen on the body could be removed by scraping with a clean scalpel blade and collected into a clean bottle. Thin dried stains could be swabbed using a swab moistened in saline. Take a control swab from a nearby normal area.
4. If there are any bite marks then these should be examined by a forensic odontologist. If the bite is fresh, the area should be swabbed with a sterile swab to collect the saliva of the assailant for grouping. If the area is dried then use a swab moistened with saline. In addition, obtain a control swab on a normal area of the skin. Make sure to exclude self-inflicted bite marks. 1. The pubic area is combed with a clean comb (provided with the rape examination kit) to obtain loose hairs which may be from the victim, from the accused, or from both. The comb, together with the loose hairs, is placed in a clean plastic bag or envelope. Matted hair, if present, should be cut and collected separately. 1. The victims blood (510 ml) is collected in a plastic/glass bottle containing ethylenediaminetetraacetic acid (EDTA). This sample is used for DNA studies. 2. The victims blood (510 ml) is collected in a plastic/glass bottle containing sodium fluoride (NaF) for alcohol and other drug assays (if needed). 3. If necessary, saliva should also be collected in a clean container. No preservatives or additives are necessary. The saliva is used to study the victims secretor status and to look for the presence of spermatozoa in cases of oral sex. 1. Fingernail clippings could be obtained from the victim to look for the assailants tissues and blood which may be trapped under the nails. As an alternative, cocktail sticks or cotton buds may be used to scrape underneath the fingernails to collect tissues and blood. If the fingernails appear very clean without any trace of stains, then do not clip the nails (particularly in women). 1. Clothing worn by the victim at the time of the assault should be air-dried and packed separately in clean paper bags (particularly in tropical countries). Dried seminal stains on the clothing will give a starchy shiny appearance and feel like parchment. Semen fluoresces under ultraviolet light. Stained areas could be marked without touching them. 2. Any other tests that may be necessary, as determined by the nature of the allegation, e.g., alcohol,
SEXUAL OFFENSES, ADULT/Evidential Sample Collection 95
drugs, narcotic drugs, and sexually transmitted diseases, should be performed. These may be of particular relevance when considering drugs associated with drug-facilitated sexual assault. 3. For alcohol and other common drugs the blood is collected into a bottle containing NaF. 4. For human immunodeficiency virus (HIV), hepatitis A and B, and Venereal Disease Research Laboratory (VDRL), blood is collected in a clean plain bottle. To test for gonococcus, swabs are obtained from the cervical os and sent to the lab in a special transport medium (charcoal). Prophylactic contraception is at the discretion of the doctor. However, the complainant should be seen in the clinic after a month to exclude pregnancy and sexually transmitted diseases. A small number of complainants of sexual assault are males and the principles described above are applied appropriately.
Collection of Specimens from the Suspect

1. Any foreign material sticking to the body is collected into a clean plastic bag or bottle. 2. Stains on the skin are swabbed with a sterile swab. If the stain is dry, use a swab moistened with sterile water. 3. Comb the pubic area to locate loose hair, which may be from the victim. Collect the loose hair with the comb in a clean envelope. 4. Swab the glans penis after retracting the prepuce. Two smears are also made on microscope slides from the same area to look for the presence of vaginal epithelium. The swabs can be used to collect the vaginal epithelium for DNA studies. 1. Blood (510 ml) in a bottle containing EDTA for DNA studies. 2. Blood (510 ml) is collected for alcohol and drugs analysis. Preservative NaF should be used. 3. If necessary, saliva is collected in a clean container. No preservative or additives are needed. The saliva could be used to study the secretor status and grouping. 1. If necessary, fingernail clippings are obtained: as for the victim, this is to look for tissues and blood belonging to the victim. 2. Any other tests that may appear necessary are performed, such as blood for VDRL, HIV, urethral swab for gonorrhea. Use sterile cotton swabs.
Many countries do not use the rape examination kit. A rape kit is not an absolute necessity. Swabs, body fluids, and foreign materials can be effectively collected from the victim and the suspect, provided the facilities are available at hand in the examination room. The rape kit is expensive and often is not used fully, and unused items are discarded. It is very important that valid consent should be obtained from both the victim and the suspect before commencing examination. In the case of a minor or someone who is mentally handicapped, consent should be obtained from the parent or guardian. If consent is refused, do not proceed with the examination and inform the police accordingly. However, with a court order a person could be examined without consent. It is always preferable to take at least two swabs from each site. All bottles, tubes, and packages should be properly sealed and labeled. The date and time of examination, time of collection, identification of the victim/suspect, case number, place of examination, and name of the investigating police officer should be carefully recorded. Ensure that continuity of evidence is maintained through proper documentation. All materials collected must be refrigerated and submitted to the forensic laboratory as soon as possible.
Final Report
The complete exercise involves submitting a report to court and giving oral evidence if necessary. The details should be carefully and accurately documented in a chronological order. No report or oral evidence will be acceptable in a court of law unless it is based on documented materials. It is a matter for the court to decide whether rape or the alleged assault took place. The examiners responsibility is to document any injuries, the genital region, and to determine whether there was any evidence of sexual intercourse or whether the allegations are supported by the findings. It is important to emphasize that evidence of sexual intercourse does not necessarily mean that nonconsensual sexual contact took place. Conversely, totally negative findings do not exclude nonconsensual assault. The examiners role is to provide an independent, scientific, balanced, corroborative assessment, whenever possible, that may support various claims. It should be borne in mind that the medical evidence is only a part of the overall investigation and is used to corroborate other forms of evidence.
96 SEXUAL OFFENSES, ADULT/Management Postassault
See Also
Sexual Offenses, Adult: Injuries and Findings after Sexual Contact; Management Postassault; Global Crime Figures and Statistics
infection and support, the information being provided from a UK perspective, not being applicable globally.
Statistics Further Reading

Eugene JK (1994) False rape allegations. Archives of Sexual Behaviour 1: 8190. Girardin B, Faugno DK, Howitt J (2003) Adult sexual assault: practical management. In: Payne-James J, Bussutil A, Smock W (eds.) Forensic Medicine Clinical and Pathological Aspects, 1st edn., chapter 28. London: Greenwich Medical Media. Howitt J, Rogers D (1996) Adult sexual offenses and related matters. In: McLay WDS (ed.) Clinical Forensic Medicine, 2nd edn., chapter 11. London: Greenwich Medical Media. Laurent F, Patrice S, Pierre A, et al. (1999) False rape. A case report. American Journal of Forensic Medicine and Pathology 20: 374377. Nadesan K (1999) Management of rape survivors. Ceylon Medical Journal 44: 109113. Nadesan K (2001) Rape: an Asian perspective. Journal of Clinical and Forensic Medicine 8: 9398. Penal Code (Amendment) Act, No 22 of 1995. Penal Code of Sri Lanka, Sections 363 and 364 of Rape and Incest. Section 375 on Rape. Penal Code of Malaysia. Section 375, exception 2 on Rape. Penal Code of India. The Sexual Offenses (Amendment) Act 1976 of England, Chapter 82, 1(1).
Rape is common but underreported, with an estimated lifetime risk of up to one in four for women. The British Crime Survey in 2002 found that 0.4% of women aged 1659 in England and Wales said they had been raped in the preceding year and 4.9% had been sexually victimized since age 16. Only a minority of such assaults are reported; according to Home Office crime statistics, in England and Wales in the year ending March 2001 there were 20 301 cases of indecent assault and 8593 rapes.
Service Provision
Care available depends on local facilities and services; currently in the UK there is no consistency between regions, although in the 1990s a number of agencies have been striving to standardize and improve services available to those who have been sexually assaulted. Most areas have dedicated examination suites funded by the police. The St. Marys Centre in Manchester was the first dedicated specialist Sexual Assault Referral Centre (SARC) to open in the UK; others have since been developed to offer a comprehensive client-centered service to which clients may present as police or self-referrals. A Report on the Joint Inspection into the Investigation and Prosecution of cases involving Allegations of Rape was conducted by Her Majestys Inspectorate of Constabulary (HMIC) and Her Majestys Crown Prosecution Service Inspectorate (HMCPSI). Their recommendations about victim care, published in April 2003, should greatly influence future services.
Management Postassault
R Jawad and J Welch, Kings College Hospital, London, UK
Initial Management Definition

Sexual assault refers to any form of nonconsensual sexual activity. Rape is a legal term, the definition of which varies between countries; in England and Wales it is currently defined as nonconsensual vaginal or anal penetration of another person by a penis; the definition in the new Sexual Offences Bill (www. parliement.the-stationary-office.co.uk) also encompasses oral penetration. Forensic examination is covered elsewhere. This article aims to cover the clients other needs, including prevention of pregnancy and sexually transmitted Initial management following sexual assault depends on when, why, and where the client presents and when the assault took place. People who have been raped may present immediately or not for months or years. Of the approximately 750 people attending the Haven SARC in London each year, 80% are referred by the police but 20% attend as self-referrals. The latter may be willing to provide anonymous intelligence and samples, but many only wish to access support and other medical care. Rape is a disempowering experience, and giving people options about their management is important in supporting the process of recovery.
SEXUAL OFFENSES, ADULT/Management Postassault 97 Consent/Disclosure
A doctor (Sexual Offences Examiner, Forensic Medical Examiner) has a responsibility to consider the issue of informed consent before starting a forensic examination. In most such cases the purpose of the examination will have both forensic and therapeutic significance, and information from both initial examination and follow-up is likely to be disclosable. According to the General Medical Council, Patients must be given information, in a way that they understand, in order to enable them to exercise their right to make informed decisions about their care. The doctor must work in accordance with the presumption that every adult has the capacity to decide whether to consent to, or to refuse, proposed medical intervention, unless it is shown that they cannot understand information presented in a clear way. A patients capacity depends on their being able to comprehend, believe, and retain information that they have been provided with; they must then be able to consider the information and reach a decision. At present no individual can give or withhold consent to treatment on behalf of another adult unless health legislation applies.
Special Considerations
to consent to forensic examination, and should include psychiatrist, social worker/psychiatric nurse, carer, forensic physician, and the sexual offences investigating team police officer.
Relationship with Forensic Examination
The aim of forensic medical examination following sexual assault is to assess the client for physical injuries and to collect forensic evidence to support the justice process. It should be carried out as soon as feasible, but is less urgent than management of serious injuries.
Adolescents
Temporary loss of capacity due to intoxication In such cases a forensic examination should be deferred until the clients capacity has returned. The time needed by the client to be in a fit state to consent depends on the type, amount, and quantity of substance consumed. It is worth advising the client and the officer in the case that the client should not bath, shower, or wash during this time so that forensic evidence is not lost. Use of an early evidence kit, containing a mouth swab and urine-testing module, can prevent the loss of forensic evidence. Serious injury Patients who are seriously injured during sexual assault usually present to the Emergency Department by ambulance. There may be temporary or permanent loss of capacity, for example, resulting from a head injury. Decisions about any procedures should be taken using a multidisciplinary approach, with close liaison with the legal department and next of kin. Good documentation in the medical records is essential, as is informing the patient what has been done and why as soon as she or he has sufficiently recovered. Mental health problems A multidisciplinary team is also invaluable in assessing the patients capacity
Adolescents are extremely vulnerable to sexual victimization, and adolescent females are the most frequent victims of sexual assault. The physical and hormonal maturation of puberty heightens adolescents interest in sex, and occurs at a time when experimentation with alcohol and drugs, and other risk-taking behavior, is common. They also find it especially difficult to seek help, leaving them vulnerable to sequelae including unwanted pregnancy and sexually transmitted infection. Clients under the age of 16 who are able to fully understand what is proposed, and its implications, are competent to consent to medical treatment regardless of age (Fraser Ruling, often termed Gillick competence). If the young client is not Fraser competent, consent from the parent or carer with parental responsibility is necessary. Confidentiality is usually implicit when consent is given, though there are limits to confidentiality; for example, if sexual abuse or neglect has occurred because of parental neglect, the child protection team should be notified.
Elderly Persons
Sexual assault is a recognized form of elder abuse. The frequency of sexual assault of women over 50 years of age has been estimated as 23%, with examples including unwanted touching, fondling, and rape. The most common perpetrator of mistreatment against elders is a close relative such as the victims own child or spouse; the perpetrator may also be a substance misuser. Postmenopausal women who are sexually assaulted are more likely to sustain genital trauma than younger women.
Suspected Drug-Facilitated Sexual Assault
Drug-facilitated sexual assault (DFSA) has recently received extensive media coverage. The term is used to define offences in which victims are subjected to non consensual sexual acts while incapacitated or unconscious due to the effects of alcohol and/or
drugs, and are therefore prevented from resisting and/ or are unable to consent. The drugs most commonly implicated are: . Ethanol (alcohol): a central nervous system depressant with dose-related effects. Alcohol (selfadministered or mixed with drinks) is by far the most common drug associated with sexual assault. . Gamma hydroxyl butyrate (GHB): this drug can be prepared at home and is used as a recreational drug; its possession is not currently illegal. Its physical properties make it easier to administer, and it is undetectable, as it is a colorless, odourless liquid, powder, or capsule that is rapidly absorbed when taken orally. . Rohypnol (flunitrazepam): commonly associated with DFSA. . Ketamine: a commercially available anesthetic for intravenous and intramuscular use. It is available as a powder, tablet, and liquid, and can be smoked, sniffed, or injected. Alcohol is by far the most common substance found on toxicological testing of urine samples. The detection of a drug depends on when the client presents and has blood and urine collected. Early reporting and testing of clients, e.g., by the use of early evidence kits, could help detect other drugs before excretion from the body.
Males
Pregnancy
Domestic violence refers to the physical, sexual, or emotional, abuse, inflicted on a spouse or partner by the other. Pregnancy has been postulated as being an especially vulnerable time. McFarlane and coworkers in 1992 found that 17% of pregnant women reported physical or sexual abuse, and that these women were twice as likely to begin their antenatal care in the third trimester than nonabused women. Clinician awareness is important as pregnancy is one time in a womans life when she is likely to have frequent, regular contact with healthcare providers. The pregnant woman who has been sexually assaulted should receive the same medical care and forensic examination as other women with special regard to the gravid uterus. If the client is known to be pregnant at the time of the forensic examination, consultation with the obstetric team should be available. If necessary, the forensic examination should be done jointly with an obstetrician/gynecologist and the client reassured about the condition of the baby. Little is known about the acute effects of sexual assault on the pregnant victim and the subsequent outcome.
Medical Management
Acute
Although the lifetime risk of rape for men worldwide has been estimated at 3%, it remains a taboo subject for many, with men and boys who are sexually assaulted encountering attitudes similar to those experienced by women 20 years ago. Data on male sexual abuse are limited, in part due to the earlier narrow legal definition of rape in the English law, which until 1994 did not recognize rape of males. Males who have been raped are reluctant to tell the police and others about their experience, and the perceived and real barriers to reporting mean that the crime remains both underreported and undertreated. Sexual assualt has long been recognized as a problem in male institutions such as prisons, but only recently has awareness of the frequency of assaults affecting the general population developed. In a series of 92 men attending the Haven, 25 (27%) reported themselves as heterosexual and 28 (30%) as homosexual (data unavailable for the other cases). Women were involved as assailants in four cases. Male rape carries a high risk of sexually transmitted infections, including HIV, hepatitis B, and syphilis.
The patient can present acutely postsexual assault. This could be to a sexual health or Accident and Emergency service, or to a general practitioner.
Special Considerations
Care in accident and emergency Once the patient discloses that she/he has been sexually assaulted, care should be handed over to the person or team most suitable or appropriately trained to deal with such incident. Designated protocols should be followed, ensuring that forensic evidence is preserved. Good documentation of observations and procedures is crucial. All swabs used, any clothing removed, and any foreign debris recovered should be carefully packaged and preserved as forensic evidence. Forensics in the domiciliary setting (nursing homes, prisons, and psychiatric units) If circumstances preclude transportation of the client, police may request forensic examination to be conducted in a nursing home, psychiatric unit, or prison. Such situations are facilitated by close liaison between the forensic team and the unit where the client is lodged,
SEXUAL OFFENSES, ADULT/Management Postassault 99
and the ready availability of essential equipment. Security of staff is also an important consideration when doing outreach examinations; police support, e.g., by provision of a driver, is invaluable. Forensics in theater The patients condition may necessitate being taken to theater for examination under anesthesia, or major surgery under general or regional anesthesia. If possible a forensically trained practitioner should be involved from the start to collect evidence and document any injuries before and after the injured area is cleaned for surgical procedures or for catheterization, to avoid the loss of forensic evidence from sites including the vulva and perineum.
Infections found reflect those prevalent in the local community, and are often multiple. Common infections identified are Chlamydia trachomatis, gonorrhea, and trichomoniasis. The sequelae of chlamydia and gonorrhea include pelvic infection leading to infertility and ectopic pregnancy. Their incubation periods vary from days to weeks, and so it may be reasonable to defer their diagnosis and treatment until follow-up. Prophylaxis Prophylactic antibiotics at initial presentation should be considered; however, in situations where the client does not wish to return for follow-up or when default seems likely. The recommendations from national guidelines for prophylaxis of gonorrhea and chlamydia are: . ciprofloxacin 500 mg plus azithromycin 1 g stat . or ciprofloxacin 500 mg immediately plus doxycycline 100 mg bd for 7 days or (pregnant or breastfeeding) . amoxycillin 3 g immediately plus probenicid 1 g immediately plus erythromycin 500 mg bd for 14 days.
STIs and Evidence
Immediate Postforensic Care

Emergency Contraception
Consideration and provision of emergency contraception forms an important part of management following sexual assault. Emergency contraception provides women with a safe and effective means of preventing unwanted pregnancy following unprotected sexual intercourse or potential contraceptive failure. The most suitable method will depend on the individual woman and the time since the episode. Two methods of emergency contraception are currently recommended by the Faculty of Family Planning and Reproductive Health Care (UK). Oral progesterone is the only emergency contraception available on prescription as Levonelle-2 (two tablets each containing 750 mg of levonorgestrel). Its efficacy depends on how soon it is started after unprotected intercourse; recent evidence suggests that it is still effective up to 5 days later. One tablet should be given as soon as possible and repeated 12 h later, but in situations where client compliance is likely to be poor, the two tablets can be given together as a single dose of 1.5 mg of levonorgestrel. Copper-bearing intrauterine contraceptive devices can also be used for emergency contraception up to 5 days after the earliest expected date of ovulation. The use of prophylactic antibiotics to cover the insertion should be considered.
Prevention of Sexually Transmitted Infection
The finding of an STI is most likely to have medicolegal relevance when the victim or the orifice involved is sexually inexperienced, or at the extremes of age. In such circumstances samples should be handled using chain of evidence procedures, which should include laboratory arrangements to ensure that samples are handled appropriately, e.g., overseen by senior staff and frozen for long-term storage, and that additional tests for confirmation or typing are carried out. Laboratory investigations are neither 100% sensitive nor 100% specific; in medicolegal practice, it is crucial to confirm results, ideally with another sample, in a situation likely to have a major implication for the client or indeed the alleged assailant.
Prevention of HIV
The risk of acquiring a sexually transmitted infection (STI) following sexual assault is high, with reported rates ranging from 3.9% to 56%. The risks and concerns will depend on the circumstances, e.g., a different approach may be required for a woman who has been raped by her partner to that for an adolescent subjected to rape involving multiple assailants.
The risk of acquisition of human immunodeficiency virus (HIV) as the result of rape is small in the UK but much greater in high-prevalence areas (Table 1). Concerns about acquiring HIV are understandably common, however, and may be minimized by a reassuring discussion based on an individualized risk assessment (Table 2). Details and examples or how to assess this risk are given below. Postexposure prophylaxis following sexual exposure (PEPSE) should be considered if the risk of HIV is assessed as high. As PEPSE needs to be given within hours, services should if possible make arrangements in advance to avoid unnecessary delays, especially at night.

Table 1 Estimated prevalence of HIV in the UK
Population HIV prevalence
We would recommend that PEPSE is considered in the presence of one or more of the following: . . . . assailant known to have or at high risk of HIV anal rape trauma and bleeding multiple assailants.
Overall Injecting drug users Man from high prevalence area, e.g., sub-Saharan Africa Homosexual or bisexual man
1/3004000 1/3050 1/3060 1/85100 (depending on sample group)
Table 2 Risk of exposure

Source Risk of HIV acquisition
Needlestick injury Receptive vaginal intercoursea Receptive anal intercoursea

a
1/270300 1/6002000 1/30150
The risk from sexual exposure is increased by trauma and defloration.
Calculation of risk of HIV transmission The risk of a person contracting HIV following sexual exposure can be calculated by the following formula: risk of HIV transmission the risk that the source has HIV the risk of exposure Using the data for HIV prevalence given in Tables 1 and 2 this formula can be applied as shown in the following examples: 1. A woman is subjected to vaginal rape by an injecting drug user, without overt genital trauma. Her maximum risk would be: 1=30 his risk of HIV 1=600 risk of HIV acquisition 1=18 000 2. A man is subjected to anal rape by three men outside a gay club. His maximum risk would be: 1=10 chance of an assailant having HIV 1=30 risk of HIV acquisition 1=300 risk 3 number of assailants 3=300 i:e:;1=100 The risk would be increased by the presence of trauma, including that to the anal mucosa (may not be readily visualized). PEPSE HIV postexposure prophylaxis has been shown to be effective in occupational settings, reducing the risk by 80% following needlestick injury, but evidence following sexual exposure is very limited.
What is PEPSE? Antiretroviral drugs currently recommended for postexposure prophylaxis are a 4-week course (costing approximately 600) of Combivir (contains zidovudine 300 mg and lamivudine 150 mg) one tablet twice daily with food plus Nelfinavir (1250 mg) usually five tablets twice daily with food. If PEPSE is to be given, it should be started as soon as possible following the assault, ideally within hours. It is less likely to be effective after 72 h. Side-effects of the medication include headaches and gastrointestinal problems such as nausea, vomiting, and diarrhea; the efficacy of oral contraception may also be reduced. An HIV test should be recommended at baseline and offered at 3 and 6 months. It is usual to give a 35-day starter pack, which also contains antidiarrheals and antiemetics, and then review the client. At the Haven, 5% of clients accept PEPSE and fewer than half of these complete the 4-week course due to the toxic side effects and the requirement to take 12 tablets a day.
Hepatitis B
The risk of hepatitis B acquisition is significant following male rape but generally less for women. Risks will be increased if there were multiple assailants, or when an assailant is known to inject drugs or is from a high-prevalence area such as the Far East. Current national guidelines recommend offering vaccination following sexual assault; this is most likely to be effective if started within 72 h, although perhaps of value up to 3 weeks. In the accelerated course, injections are given at 0, 7, and 21 days with a booster at 12 months. In high-risk situations the vaccination should be started within 72 h and hepatitis B hyperimmune globulin considered in addition.
Follow-Up
People who have been sexually assaulted should be offered ongoing medical and psychosocial care. This usually includes a subsequent appointment to screen for sexually transmitted infections, and follow-up emergency contraception and any other medications and vaccinations given at the time of the forensic examination (bacterial prophylaxis, PEPSE). Tests for HIV, hepatitis B and C, and syphilis can be
SEXUAL OFFENSES, ADULT/Management Postassault 101
offered at later visits. Departments of genitourinary medicine and some family planning clinics can provide this care. Among rape victims, follow-up rates are generally low, but can be improved by proactive support.
Psychosocial Care
genitourinary medicine can either provide counseling or refer on for this or other interventions such as cognitive behavior therapy (CBT), and support is also available from a variety of other voluntary and statutory agencies. General practitioners are often invaluable in providing initial care and treatment and coordinating other services.
Psychological consequences following sexual assault can be acute/immediate or chronic/ongoing, with the severity varying from individual to individual. The reaction to trauma was described by Kardinger in 1941 and termed posttraumatic stress disorder (PTSD). PTSD has been defined as an anxiety disorder in which exposure to an extreme mental or physical stress is followed sometimes immediately, and sometimes not until 3 months or more after stress, by persistent re-experiencing general responsiveness, and manifestation of increased arousal. Over the years the diagnostic criterion has been refined and revised. It is associated with clinically important distress that transcends ordinary misery and unhappiness as well as with disruption and impairment of daily functioning. Acute PTSD usually lasts less than 3 months, while the duration of chronic PTSD can be 3 months or longer. Burgess and Holmstrom designed and conducted landmark research in the early 1970s to study and report the immediate and long-term effects of rape. Rape trauma syndrome refers to both the acute phase and a long-term reorganization process that results from either a forcible or attempted forcible rape. It is a clinical term and describes a clustering of biopsychosocial and cognitive symptoms exhibited by the victim. Female sexual abuse survivors, especially adolescents, are at increased risk for subsequent actingout behavior, sexual promiscuity, physical and sexual abuse, anxiety, depression, chronic sleep disturbance, dissociate disorders, eating disorders, suicidal intentions, and multiple associated psychiatric disorders. The mental health morbidity associated with sexual assault is profound, and clients require support, sensitive care, therapy, information, and follow-up services according to their needs and wishes. Those who are especially vulnerable, e.g., those with a previous history of mental health problems, self-harm, or substance misuse, should be offered referral to appropriate local mental health services. Victims of sexual assault should be offered immediate and ongoing psychosocial support to help with the well-recognized acute and chronic psychological consequences. SARCs and departments of
See Also
Children: Sexual Abuse, Epidemiology; Sexual Offenses, Adult: Injuries and Findings after Sexual Contact; Evidential Sample Collection; Male Sexual Assault; Drug-Facilitated Sexual Assault; Global Crime Figures and Statistics
Further Reading
British Medical Association, Law Society (1997) Assessment of Mental Capacity: Guidance for Doctors and Lawyers. London: BMA. Burgess AW, Holmstrom L (1974) Rape trauma syndrome. American Journal of Psychiatry 131(9): 981986. Clinical Effectiveness Group (Association of Genitourinary Medicine and the Medical Society for the Study of venereal Diseases) (2001) National guidelines on the management of adult victims of sexual assault. Available: www.mssvd.org.uk Drug and Therapeutics Bulletin Editorial (2002) Sexual assault in adults. Drug and Therapeutics Bulletin 40(1): 14. Faculty of Family Planning and Reproductive Health Care Clinical Effectiveness Unit (2003) Guidance emergency contraception. Journal of Family Planning and Reproductive Health Care 29(2): 916 and 29(3): 159. General Medical Council (1998) Seeking Patients Consent: the Ethical Considerations. London: GMC. Hindmarch I, ElSohly M, Gambles J, Salamone S (2001) Forensic urinalysis of drug use in cases of alleged sexual assault. Journal of Clinical Forensic Medicine 8: 197254. Jeffery RB, Jeffery LK (1991) Psychological aspects of sexual abuse in adolescents. Current Opinion Obstetrics and Gynecology 3: 825831. Johnson JK, Haider F, Ellis K, Hay DM, Lindow SW (2003) The prevalence of domestic violence in pregnant women. British Journal of Obstetrics and Gynaecology 110: 272275. Kerr E, Cottee C, Chowdhury R, Jawad R, Welch J (2003) The Haven: a pilot referral centre in London for cases of serious sexual assault. British Journal of Obstetric and Gynaecology 110: 267271. Lamba H, Murphy SM (2000) Sexual assault and sexually transmitted infections: an updated review. International Journal of STD and AIDS 11: 487491. Mein JK, Palmer CM, Shand MC, et al. (2003) Management of acute adult sexual assault. Medical Journal of Australia 178(5): 226230.
102 SEXUAL OFFENSES, ADULT/Male Sexual Assault Ramin S, Satin A, Stone I, Wendel G (1992) Sexual assault in postmenopausal women. Obstetrics and Gynecology 80(5): 860864. Satin AJ, Hemsell DL, Stone I, Theriot S, Wendel G (1991) Sexual assault in pregnancy. Obstetrics and Gynecology 77(5): 710714.
Male Sexual Assault

B Marc, Compiegne Hospital, Compiegne, France
Introduction
The recognition of male rape as a significant phenomenon has only occurred in recent years. Statistics vary from country to country depending on whether these assaults are committed by heterosexuals or by homosexual men assaulting other homosexual men. The act itself may not be defined in law; generally perpetrators are charged with either buggery or indecent sexual assault. In the French penal code, rape is characterized by the forcible entry of a penis or other object into the anus or the mouth. In order to achieve complete domination, humiliation, and control of the victim, the perpetrator often seeks to arouse the victim sexually, a process often culminating in ejaculation. This can leave the victim in a state of confusion about his own sexuality, questioning the extent to which he may have contributed to the assault in some way. In England and Wales, 27.6% of homosexual males reported sexual assault during their lifetime. They may be associated with an increased risk of trauma and sexually transmitted disease (STD). Sexual violence against men presents many of the same challenges to the medical profession as child sexual abuse did in the 1990s. Any case of perineal bruising or injury in a male should prompt the taking of a careful medical history, followed by physical examination, collection of appropriate samples, and screening for STD. The victim is often embarrassed and frightened about such incidents. In these circumstances men are little different to women and it is not surprising, therefore, that most male rapes and other sexual assaults are not reported. When disclosure does occur, however, the support needed by men is very similar to that needed by women. Male rape does not differentiate its victims based on their sexual orientation or position in society.
Similarly, perpetrators may be gay or straight and from any walk of life. Within our society men are portrayed as being intrinsically strong, as protectors. This model is shattered by the trauma of rape, and the victim frequently experiences feelings of disbelief, shame, and guilt. Nonconsensual sex in adulthood can be defined as when a person has sexual encounters with other persons without their consent with or without violence or other means of coercion. In Europe no clear epidemiological data are available on the prevalence of nonconsensual sex in men. Very few population studies on mens nonconsensual sexual experiences as adults are available. Of a sample of 1480 men in Los Angeles, CA, USA, 7% reported being pressured or forced to have sexual contact after the age of 16. A British study of 930 homosexual men reported that just over a quarter had been subjected to sex without consent in their lifetime and that 99 of these men had been raped. Another study on 2474 men (mean age 46 years) in England has shown that nonconsensual sexual experiences were associated with a greater prevalence of psychological problems, alcohol misuse, and self-harm. Almost 3% of men report nonconsensual sexual experiences as adults, often followed by psychological difficulties in men who have had such experiences. Nonconsensual sexual experience in childhood seems to be a significant predictor of nonconsensual sexual experience in adulthood. Sexually abused boys may often become perpetrators as adults, but child sexual abuse can also lead to further victimization as adults. Most men who reported nonconsensual sexual experiences with other men defined themselves as primarily heterosexual. However, men who reported having sex with other men were six times more likely to have had nonconsensual sex as an adult. Gay and bisexual men tend to have more sexual partners than do heterosexual men. Increasing numbers and anonymity of sexual partners may increase the risk of nonconsensual sex. These factors may explain why previous studies of gay men have found high rates of nonconsensual sex.
Definition of Male Sexual Assault

Almost all adult male rape victims are raped by other men and forced to submit to anal intercourse, oral sex, masturbation of the offender(s), and other sexual acts. Analysis of incidents of nonconsensual sexual activity among 930 homosexually active men living in England and Wales has revealed that 27.6% of them had been sexually assaulted at some point in their lives; one-third had been forced into
SEXUAL OFFENSES, ADULT/Male Sexual Assault 103
sexual activity usually anal intercourse by men with whom they had previously had consensual sexual activity. The recognition of male rape as a significant phenomenon has occurred only recently. For the purpose of this article, the term may be used to mean the forcible entry of the anus or the mouth by a penis or other object. In many cases this penetration will be accompanied by a level of violence far in excess of that which is needed for the rape to take place. For many men who have been raped, their self-image is clouded in doubt and confusion. It has been suggested that the stigmatization of sexual assault is greater in male rape victims because of social conditioning. The achievement of stability following an assault is, however, unusual, and victims more often experience a range of difficulties. These include alcohol problems, abuse of drug and other chemical substances, deliberate self-harm, getting into abusive relationships, or being unable to form and sustain satisfying relationships. Victims may be unable to hold down a job; they may get into trouble with the law. Aggression and fighting are not uncommon. Victims may have a problem expressing their anger and rage at what has happened to them and frequently turn it in on themselves rather than directing it towards the perpetrator. Self-esteem may disappear. Men with disabilities who live in a residential institution due to their physical, mental, and/or psychological disability are often exposed to sexual abuse. Approximately 50% of disabled males in certain institutions have indicated that they have been exploited sexually either by other residents or by carers.
injured during the violent physical attacks that sometimes accompany rape. There have been cases reported of human immunodeficiency virus (HIV) infection as a result of prison rape.
Physical Consequences of Male Sexual Abuse

The physical effects of a sexual assault vary according to its circumstances, e.g., associated assault, anal penetration, use of a lubricant. Male sexual assault often occurs as part of a more general physical assault and may be extremely violent. Males who suffer sexual abuse show a range of rape-related injuries which can include bruising, lacerations, and fractures, as a result of other forms of violence. Sexual assault of males remains an infrequently reported and a poorly understood phenomenon. Examiners, even in rape crisis centers, have little experience with the examinations of male victims but as the signs of sexual assault are not so different from those observed in other victims, the forensic examination should be similar, taking into account anatomical differences. Extreme violence as an element of rape is even more common with assaults involving more than one perpetrator. Male victims describe assaults involving, in many instances, more than two perpetrators, and sometimes even up to six or eight of them. The perpetrators typically take turns holding the victim down on the floor, or holding a weapon to him, while the others sexually assault him (Figure 1). Sometimes violence is not used, as it is easy enough for several men to overpower a single victim simply by holding him in place. Violent language and degrading insults are common, as well as threats to
Prevalence and Predictors of Nonconsensual Sex in Adulthood

In some studies, the mean age of the men at their first (or only) nonconsensual sexual experience is 20 (sd 5) years. Men who report having had sex with men are significantly more likely to report having had nonconsensual sex with men. Among male victims of sexual assault, one in five has been raped and only one in 15 reports the fact to the police. Significant predictors of reporting nonconsensual sexual experiences in adulthood are reporting male sexual partners, previous child sexual abuse, and age. Sexually transmitted infection may be associated with sexual molestation in adulthood.
Prison as a Special Risk for Nonconsensual Sex in Adulthood

Violence and sexual violence are the common law in inmates within a prison. Inmates can be seriously
Figure 1 Associative evidence of violence against a male rape victim assaulted by a male gang.
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kill the victim if he tells the authorities. Violence associated with male sexual abuse can even lead to killing during sexual assaults. The most common form of assault is anal intercourse (3/5), followed by forced oral penetration (2/5). Forced anal penetration may cause intense pain, bruising, abrasions, bleeding, in some cases fissures and lacerations, and tears of the anal canal and adjacent regions. Fecal incontinence can be present after recent or repeated anal intercourse (Figure 2). The risk of transmission of an STD is especially high during unprotected anal intercourse. Transmission of the HIV virus, which causes acquired immunodeficiency syndrome (AIDS) is a serious threat to victims of male rape. In prison, the threat of HIV transmission is particularly acute given the high prevalence of the virus among prisoners. In the USA, in 1997, an estimated 35 00047 000 prisoners were infected with HIV and another 8900 had AIDS. Exacerbating the danger of HIV transmission is the lack of preventive measures, with few risk-reduction devices available (such as condoms). Many other STDs can be encountered: hepatitis B, syphilis, condyloma acuminata, herpes progenitalis, Chlamydia, and gonorrhea. The diagnosis of STDs is important not only for the care of the victim but also in determining the fact of sexual contact. These infections may be important forensic markers as organisms become traceable between assailant and victim.
It is even possible in some cases to perform DNA typing of individual strains of microorganisms that can also be typed on the suspected perpetrator. In male sexual assault victims examined early enough after the rape, it is possible to provide appropriate disease prophylaxis to the victims. This may be of the first importance since data indicate that appropriate early HIV prophylaxis may influence the course of the infection. Nonconsensual sexual experiences are associated with a greater prevalence of psychological and alcohol problems and self-harm. Men who report sexual molestation in adulthood are twice as likely to experience a psychological disorder, but self-harm is the single most likely problem to occur. The short-term reaction to rape is characterized by a range of traumatic symptoms, including nightmares and other forms of sleep disturbance, intense fear, worry, suspicion, major depression, and impairment in social functioning. In the second stage, victims often experience depression and self-hatred, as well as social and sexual dysfunction. The long-term effects of rape, which may surface a year or more after the assault, often involve destructive or self-destructive behavior; common symptoms are anger, hypervigilance to danger, sexual dysfunction, and a diminished capacity to enjoy life. The literature also reveals that when men do seek help they may be treated poorly. Secondary victimization or sanctuary trauma results when there is a lack of empathy and understanding of the effect that rape can have on the survivor, such as rape-trauma syndrome.
Assessment of Sexual Assault of Male Adults

A full examination is a prerequisite to the appropriate assessment of the diagnosis and management of male victims. The physical and evidence examinations are conducted simultaneously. Diagnosis of male sexual abuse is assisted by collecting physical findings of violence and any sign of clear evidence of anal trauma, which can be linked to a history of penetration. As with female victims the individual should be able to make a choice as to the gender of the examining doctor. Signs of violence or restraint must be noted, reported (where appropriate) to schemes, and documented. Photography during the medical examination with consent is of great use. It can avoid further examination for the sexually abused male. X-rays for possible associated fractures may be required.
Figure 2 Fecal leakage in a 30-year-old disabled male after recent violent anal intercourse.
SEXUAL OFFENSES, ADULT/Male Sexual Assault 105
The extent and type of traumatic lesion may corroborate the accounts of the violent acts against the male victim and confirm the victims allegations. The conditions of the victims clothing and any signs of rips, tears, or other damage and other foreign materials should be noted in a victim seen shortly after the abuse. Scanning of the clothes with a Woods lamp for fluorescent exudates is very useful. Clothing (especially underwear) is collected and wrapped in a paper envelope. Abrasions, hematomas, and lacerations of the anus can be seen if the victim is examined shortly after the sexual assault with anal intercourse. Evidence of abrasions, bruises, bite marks, and restraint marks should be sought. There will be little evidence of injury after anal penetration in nonconsensual assault. Findings are often nonspecific. The presence of decreased tone and fissures may be corroborative of penetration. Anal lacerations, by contrast, have rarely been found in circumstances other than those of bluntforce penetrating trauma. Anal lesions are more evident if there is more than one perpetrator and if anal abuse is repeated. Anal fissures, lacerations, and changes in anal tone can be associated with traumatic or repeated anal penetration. Anal examination can be performed either in the lateral position or sometimes better in the kneechest or prone position. In 90% of cases, examinations of any other than very recently assaulted victims are
negative (normal). Any visible findings of trauma should be photographed using the proper technique. The presence of bruises around the anus (Figure 3), scars, anal tears (especially those that extend into the surrounding perianal skin), and anal dilation must be clearly described and noted. Photographs should be taken with the victims consent. Anal penetration results in trauma when there has been significant force or resistance. If lubrication has been used, the probability of seeing any evidence of trauma is largely reduced. Laxity of the sphincter, if present, should be noted (Figure 4). If there is any evidence of serious anorectal injury, an examination under anesthesia with proctoscopy and sigmoidoscopy may be necessary. Rarely, in violent rapes, extensive damage such as deep fissures or rupture of the sphincter will need surgical repair. At the time of repair, thought should be given to take appropriate forensic samples, including a search for DNA evidence. In an examination within 72 h of assault, the perianal area should be swabbed, followed by the anal canal and rectum, for the presence of semen and lubricants, which may require additional swabs for further forensic examination. Any oral trauma should be documented. If the victim reports fellatio, then the perioral area and the oropharynx need to be carefully examined for evidence of trauma. Any signs of petechial presence and tears of the frenulum need to be documented. If
Figure 3 Bruises around the anus after anal rape.
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referred to professionals who are trained in psychological trauma and posttraumatic disease.
See Also
Children: Sexual Abuse, Overview; Sexual Abuse, Epidemiology; Domestic Violence; Imaging: Radiology, Pediatric, Scintigraphy and Child Abuse; Sexual Offenses, Adult: Management Postassault; Drug-Facilitated Sexual Assault; Global Crime Figures and Statistics
Further Reading
Bartholomew BN, Doll LS, Joy D, et al. (1994) Emotional, behavioural and HIV risks associated with sexual abuse among adult homosexual and bisexual men. Child Abuse and Neglect 18: 747761. Coxell A, King M, Mezey G, Gordon D (1999) Lifetime prevalence, characteristics, and associated problems of non-consensual sex in men: cross sectional survey. British Medical Journal 318: 846850. Finkelhor D, Hotaling G, Lewis IA, Smith C (1990) Sexual abuse in a national survey of adult men and women: prevalence, characteristics, and risk factors. Child Abuse and Neglect 14: 1928. Follette VM, Polusny MA, Bechtle AE, Naugle AE (1996) Cumulative trauma: the impact of child sexual abuse, adult sexual assault and spouse abuse. Journal of Trauma and Stress 9: 2535. Freeman-Longo RE (1986) The impact of sexual victimization on males. Child Abuse and Neglect 10: 411414. Hickson FCI, Davies PM, Hunt AJ, et al. (1994) Gay men as victims of nonconsensual sex. Archives of Sexual Behavior 23: 281294. Hillman RJ, OMara N, Taylor-Robinson D, Harris JR (1990) Medical and social aspects of sexual assault of males: a survey of 100 victims. British Journal of General Practice 40: 502504. Hunter M (ed.) (1990) The Sexually Abused Male: Prevalence, Impact, and Treatment, vol. 1. Lexington, MA: Lexington Books. Hunter M (ed.) (1996) The Sexually Abused Male: Application of Treatment Strategies, vol. 2. Lexington, MA: Lexington Books. Keane FE, Young SM, Boyle HM, Curry KM (1995) Prior sexual assault reported by male attenders at a department of genitourinary medicine. International Journal of STD and AIDS 6: 95100. King M, Woollett E (1997) Sexually assaulted males: 115 men consulting a counseling service. Archives of Sexual Behavior 26: 579588. King M, Coxell A, Mezey G (2002) Sexual molestation of males: associations with psychological disturbance. British Journal of Psychiatry 181: 153157. Lisak D (1994) The psychological impact of sexual abuse: content analysis of interviews with male survivors. Journal of Traumatic Stress 7: 525548.
Figure 4 Wide anal opening after repeated anal sexual intercourse.
any oral penetration has occurred, the buccal mucosa will need to be swabbed, including the areas under the tongue and around the pillars of the fauces to the teeth. Swabs should be saved for examination under the microscope. The penis and the scrotum are also carefully examined for signs of trauma, abrasions of the glans, tears of the mucocutaneous junction of the meatus, lacerations, and evidence of bite marks. Evidential specimens of secretions and stains from blood, semen, and saliva need to be collected to send for analysis and search for spermatozoa, mainly using Papanicolaou and Christmas-tree staining. Dry sterile swabs are kept under frozen conditions in order to permit DNA identification later. Any foreign material or debris noted, in any site, including pubic hair, should be collected and placed in a sterile tube, which is then labeled and sealed with a proper indication of the anatomic site where it was found.
Conclusions
Medical professionals should be aware of the potential range of symptoms and signs found in men who suffer sexual assault experiences in adulthood. Training in this area is needed for the police, emergency department staff, clinical forensic practitioners, and community health services. It must be kept in mind that the aftermath of a male sexual assault can be devastating to the victim, so all victims should be
SEXUAL OFFENSES, ADULT/Drug-Facilitated Sexual Assault 107 Mezey GC, King MB (1992) Male Victims of Sexual Assault. Oxford, UK: Oxford University Press. Struckman-Johnson CJ, Struckman-Johnson D (1994) Men pressured and forced into sexual experience. Archives of Sexual Behavior 23: 93114. Turner CF, Ku L, Rogers SM, et al. (1998) Adolescent sexual behaviour, drug use and violence: increased reporting with computer survey technology. Science 280: 867873. Urquiza A, Capra M (1990) The impact of sexual abuse: initial and long-term effects. In: Hunter M (ed.) The Sexually Abused Male: Prevalence, Impact, and Treatment, vol. 1. Lexington, MA: Lexington Books. Urquiza A, Keating LM (1990) The prevalence of sexual victimization of males. In: Hunter M (ed.) The Sexually Abused Male: Prevalence, Impact, and Treatment, vol. 1. Lexinton, MA: Lexington Books.
Drug-Facilitated Sexual Assault

A Negrusz and R E Gaensslen, University of Illinois at Chicago, Chicago, IL, USA
Introduction and Basic Terms

This article gives a general overview of the drugfacilitated sexual assault (DFSA) phenomenon. Sexual assault, perpetrated on mainly women but also on men, while apparently incapacitated by so-called date-rape drugs, recently became the focus of many investigations conducted by law enforcement agencies in the USA and other countries. During the last decade an alarming increase has been observed in reports of this crime as well as in the number of scientific publications on the subject. The list of drugs associated with sexual assault is long and apart from alcohol among others includes flunitrazepam with other benzodiazepines such as diazepam, temazepam, clonazepam, oxazepam, as well as gamma-hydroxybutyrate (GHB), ketamine, and scopolamine. The most recent analytical developments in the toxicological investigation of drug-facilitated rape, designed to reveal drug presence and thus help successfully prosecute perpetrators, are also discussed. In a typical scenario, a sexual predator surreptitiously spikes the drink of an unsuspecting person with a sedative drug for the purpose of drugging and subsequently sexually assaulting the victim while under the influence of this substance. Victims usually report loss of memory during and after these incidents. They wake up in unfamiliar places, inappropriately dressed, and often with the sense but not the actual recollection of having had sex.
Sexual assault usually refers to a broad range of sexual offenses, from inappropriate touching or contact to actual penetration of intimate parts of a victims body without consent. The term includes a completed rape, i.e., vaginal, anal, and/or oral penetration in the case of a female victim (and oral and/or anal penetration in the case of a male victim) by penis, fingers, or objects. Sexual assault may be defined in different terms in the laws of different states (e.g., sexual battery, criminal sexual assault, rape). Rape is usually nonconsensual sexual intercourse, and in some states it refers only to penilevaginal penetration. Rape is often accomplished by a perpetrator using force or threat of force, but force or threat of force is not a required element. It has been established that 80% of all rapes are acquaintance rapes committed by a person known to the victim. Only 20% are stranger rapes when the victim has no previous relationship with the offender. The determining factor is consent. Absence of consent makes the sexual contact a sexual assault. DFSA means a completed rape perpetrated upon a victim, usually a woman, who is mentally and physically incapacitated by drugs given to her surreptitiously by another person(s), or as a result of voluntary consumption of alcohol and/or drugs and involuntary ingestion of another drug administered surreptitiously. In the third scenario, the victim is sexually assaulted after voluntary use of drugs and/or alcohol. There is some evidence too that some date-rape drugs may be used recreationally, and that sexual assaults can occur while a person is under their influence. These cases are also DFSAs, even though the drug may not have been surreptitiously administered to the victim by the perpetrator. It does not matter whether the victim was given the drugs unknowingly, or whether she/he was using the drugs recreationally. Club drugs mean drugs used recreationally by young people, often in conjunction with alcohol, at private parties and in clubs or bars. Club drugs include, but are not necessarily limited to methylenedioxymethamphetamine (MDMA: ecstasy), GHB and/or related compounds, Rohypnol, ketamine, methamphetamine, and lysergic acid diethylamide (LSD). Date-rape drugs are a sort of subclass of club drugs, and include any drug or substance that is known to be used in the mental and physical incapacitation of a person who is then sexually assaulted. The term usually applies to Rohypnol, clonazepam, occasionally other benzodiazepines (sometimes believed by users to be Rohypnol), GHB, and ketamine. Forcible rape is the term used by the Federal Bureau of Investigation (FBI) in its uniform crime reports
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(UCR) to mean actual completed rapes; by definition, the number of forcible rapes recorded in UCRs have been reported to the police. UCR is an annual, incident-based reporting system for several classes of violent (person) crime and several classes of property crime. UCR is a measure of crime reported to the police. The US National Crime Survey, conducted annually by the Bureau of Justice Statistics (BJS), is an estimate of total person and property crime and victimization, based on detailed, structured interviews with a fully ascertained, representative, sample of the US population. This survey is designed and intended to provide a measure of total crime, including incidents not reported to the police.
The Extent of the Problem

The number of reported sexual assaults in the USA, for example, according to FBI UCR, is presented in Figure 1. Both the number and the rate of reported rapes declined throughout most of the 1990s, reaching a low in 1999. It is also well known that the number of reported rapes is significantly lower than the actual number. In 1999, for example, the BJS estimated that there were over 141 000 cases of sexual assault, 58% more than the number actually reported to the police. At present, there are no reliable data or estimates of the fraction of sexual assaults actual or reported that involve drugs typically associated with sexual assault. The only published data directly relevant to the prevalence issue are based on the analysis of 1200 urine specimens from a random collection of cases submitted by forensic science or toxicology labs nationwide to the investigators, specifically in order to screen for and identify alcohol and date-rape and other drugs. Approximately 60% of all samples tested were positive for one or more drugs including
alcohol. GHB was detected in 4% of samples. About 8.2% of the specimens had confirmed benzodiazepines, but flunitrazepam was only seen in a few cases. A systematic study to estimate the prevalence of DFSA is currently being conducted at the University of Illinois at Chicago. The project is designed to gather preliminary data on DFSA practices in a representative sample of US jurisdictions. In this complicated but important protocol, 130 actual sexual assault complainants in five separate and widely scattered jurisdictions are recruited into the study to provide a urine specimen at the time they report the assault, and both urine and hair specimens approximately a week later. Results of analysis for relevant drugs in the volunteer subject population will be compared with results from a control population matched for age cohort, gender, and ethnic group. The victims remain anonymous to the investigators. All results are confidential.
Drugs Used to Facilitate Sexual Assault

The best known but by no means the only drug associated with sexual assault is flunitrazepam, manufactured by Roche under the name Rohypnol. Abuse of this drug in the USA was first reported in Florida to the Community Epidemiology Working Group in 1993. Because of the exposure and access to the Mexican border, the TexasFlorida Rohypnol Response Group was formed in New Orleans in 1994, and in 1995, it identified a flood of Roche products entering the USA at Laredo, TX. The problem was so widespread that the Group recommended closing the border. In addition, in 1995, Dade County, FL, initiated a flunitrazepam impairment detection program, and in 1996, US Customs, the Food and Drug Administration (FDA), and the Drug Enforcement Administration (DEA) banned the importation of flunitrazepam. President Bill Clinton mentioned flunitrazepam in his new federal drug strategy in April 1996. Flunitrazepam (Rohypnol: 5-(2-fluorophenyl)-1,3, dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2one) belongs to the 7-nitro group of benzodiazepines. Its hypnotic effect predominates over the sedative, anxiolytic, and muscle-relaxing effects of other compounds from the same pharmacological group. Flunitrazepam is available in oral tablets and in injectable form in 80 countries around the world. Flunitrazepam has much stronger affinity for the gamma-aminobutyric acid receptor than diazepam (Valium). In fact, it is 10 times as potent as diazepam. Flunitrazepam is readily (8090%) absorbed through the gastrointestinal tract and almost completely metabolized by the liver. Its metabolism includes reduction
Number of reported sexual assaults
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Figure 1 Number of reported sexual assaults, according to the Federal Bureau of Investigation uniform crime reports.
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SEXUAL OFFENSES, ADULT/Drug-Facilitated Sexual Assault 109
to 7-aminoflunitrazepam and then to the N-glucuronide, demethylation to the N-demethyl metabolite, hydrolysis to the 3-OH metabolite, and then to the O-glucuronide. Approximately 90% of its metabolites are excreted through the urine and 10% in the feces. Deaths involving flunitrazepam in conjunction with other central nervous system depressants, such as ethanol, but also due to overdose of flunitrazepam alone, have been reported. The first seizure of Rohypnol in the USA took place in 1989, and reports of the misuse of the drug have increased since then. Flunitrazepam is often used to enhance the effects of heroin, alcohol, or marijuana. Rohypnol tablets are smuggled into the USA (mainly from Mexico) and sold with street names like roofies, rophies, roopies, rib, rope, pappas, peanuts, pastas, forget pills, ro-shays, roaches, and roche 2. In the early 1990s, flunitrazepam was identified as the drug of choice in DFSA. As of 1996, the prescription, sale, and importation of flunitrazepam into the USA was banned. Other drugs that have been implicated in sexual assault include GHB and related compounds which are converted to GHB, such as gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD). GHB is sold on the streets under names such as salty water, scoop, soap, liquid X, natural sleep-500, and liquid ecstasy. It is used in date rape because it is rapidly effective, it is relatively easy to manufacture and obtain, and it is alleged to have aphrodisiac properties. Possession, sale, and clandestine manufacturing of GHB are illegal. Since July 2002, GHB is approved in the USA for the treatment of narcolepsy. The other drugs include ketamine, scopolamine, barbiturates, muscle relaxants such as carisoprodol, cyclobenzaprine, and meprobamate, diphenhydramine, clonazepam, and occasionally other benzodiazepines. Clonazepam is a benzodiazepine that expresses many of the characteristic pharmacological properties of this class of drug such as reduction of anxiety, induction of muscle weakness, and even hypnosis. It has also been shown to decrease seizure activity and is approved by the FDA only for use in the treatment of seizures. Clonazepam is available in tablets containing 0.5 mg, 1 mg, and 2 mg under the trade names Klonopin, Clonex, Iktorivil, and Rivotril. All drugs used in DFSA have depressant effects on their users. Symptoms reported by victims of alleged drug-facilitated rape include confusion, decreased heart rate, dizziness, drowsiness, impaired judgment, impaired memory, lack of muscle control, loss of consciousness, nausea, reduced blood pressure, and reduced inhibition. All these effects can be synergistically enhanced if the drug is taken with alcohol.
In addition, however, they induce amnesia, presumably the principal reason for their selection as date-rape drugs.
Specimens and Analytical Methods

In the mid-1990s, law enforcement agencies, Sexual Assault Nurse Examiner Sexual Assault Response Team (SANE-SART) facilities, and rape crisis centers in the USA recommended more sophisticated testing of specimens collected from alleged rape victims, and a nationwide urine-testing program was developed for drugs used in committing this crime. One of the most important issues that needs to be considered in DFSA investigation is the sensitivity of both screening and confirmatory techniques, since some of the compounds, e.g., benzodiazepines, are typically used in a single low dose. Preliminary screening techniques for drugs in urine include enzyme-multiplied immunoassay (EMIT), fluorescent polarization immunoassay (FPIA), Abuscreen OnTrak, and online immunoassays. Enzymatic hydrolysis followed by the extraction of benzodiazepines, including flunitrazepam and 7aminoflunitrazepam, is frequently performed in order to increase the sensitivity of the assay. Confirmatory methodologies include electron ionization with gas chromatographymass spectrometry (EI-GC-MS) and both positive (PCI-GC-MS) and negative (NCIGC-MS) chemical ionization detection. In developing background information for the construction and optimization of analytical methods for the drugs and their metabolites, one important component is a controlled, clinical dosing study with the drugs. In such a study, healthy volunteers are given single doses of a drug under careful medical supervision, then monitored for drug and metabolite concentrations in urine and hair for several days afterward. In recent years, substantial analytical progress was achieved in the USA and in France, allowing the detection of selected benzodiazepines and GHB in urine and hair after a single low dose for extended periods of time. This is important because DFSA victims often do not report the incident in a timely manner due to amnesia and doubt about what may have happened, and possibly other psychological reasons. It would not be unusual for a urine or blood analysis to provide a negative result when the drug had in fact been ingested because of the likelihood of a single low dose, urine volume, and the length of time since the drug was taken.
History and Legislation

Increased numbers of incidents of DFSA in the early 1990s, especially the illegal use of flunitrazepam to
110 SEXUAL OFFENSES, ADULT/Drug-Facilitated Sexual Assault
facilitate sexual assault, have prompted federal legislation known as the Drug-Induced Rape Prevention and Punishment Act of 1996 (21 U.S.C. Sec. 841(b) (7)). This important legislation provides criminal penalties of up to 20 years imprisonment for any person who distributes a controlled substance, such as Rohypnol, to a person with the intent to commit a crime of violence, including rape. On February 18, 2000 President Bill Clinton signed another very important piece of legislation, the Hillory J. Farias and Samantha Reid Date-Rape Drug Prohibition Act of 2000 (Public Law 106172), placing GHB on Schedule I of the Controlled Substances Act schedules, and requiring that the Secretary of Health and Human Services submit to Congress annual reports estimating the number of incidents of the abuse of date-rape drugs. This legislation was prompted and named after two teenage girls, Hillory and Samantha, who died after GHB was surreptitiously added to their sodas. In June 2000, a Drug-Facilitated Sexual Assault Forum took place in Washington, DC. This important meeting was organized by the Office for Victims of Crime, US Department of Justice. During the 2-day sessions, a representative group of professionals, including prosecutors, forensic nurses, investigators, forensic toxicologists, and victims, discussed from different perspectives the most important issues concerning the DFSA phenomenon. In 1998, during the Annual Meeting of the American Academy of Forensic Sciences in San Francisco, CA, the Drug-Facilitated Rape Committee was formed and chaired by Marc LeBeau from the FBI. Two years later, the Committee became one of the regular committees of the Society of Forensic Toxicologists. Very recently, during the 2002 Annual Meeting of the Society of Forensic Toxicologists in Dearborn, MI, three subcommittees were formed. One of the subcommittees is to work on recommendations for, and approaches to, toxicological investigations of DFSA. As a first step, the subcommittee identified all potential drugs and substances detected or suspected in biological specimens collected from victims. The compounds, in alphabetical order, are: alprazolam, amitriptyline (nortriptyline), amobarbital, amphetamine, butalbital, carisoprodol citalopram hydrobromide, chlopheniramine, chloral hydrate, chlordiazepoxide, clonazepam (7-aminoclonazepam), clonidine, cocaine (benzoylecgonine), codeine, cyclobenzaprine, dextromethorphan, diazepam (nordiazepam), diphenhydramine, doxepin, doxylamine, ethyl alcohol, flunitrazepam (7-aminoflunitrazepam), fluoxetine, GHB, 1,4-BD, hydrocodone, hydromorphone, imipramine (desipramine), ketamine, lorazepam, marijuana (9-carboxy-tetrahydrocannibinol: THC-COOH), MDMA, meprobamate, methadone,
methamphetamine, morphine, oxazepam, oxycodone, paroxetine, pentobarbital, phencyclidine (PCP), phenobarbital, scopolamine, secobarbital, sertraline, triazolam, valproic acid, and zolpidem.
Conclusion
Much has been made of the DFSA problem in the USA in the popular media and, to some extent, in the scientific literature. There is no doubt that the involvement in sexual assaults of flunitrazepam and benzodiazepines, ketamine, GHB, and some other drugs with similar pharmacological effects is a relatively new problem. The true extent of the problem is not yet known. The need for methods to detect these drugs in the body fluids and/or hair of complainants has drawn forensic toxicologists into the analysis of sexual assault evidence. This development has prompted considerable research in our laboratories and in others on the development of better, more sensitive methods of detection for the drugs and their metabolites. Controlled clinical studies on the time course of drug and metabolite elimination of some of the substances have also been done where feasible. Considerable progress has been made since the 1980s in the standardization of sexual assault evidence collection protocols and devices. These efforts have been coordinated in many places by groups with representation from police, prosecutors, clinicians, victim services advocates, and forensic laboratories. Until now, however, there has never been any need to consider or discuss the routine collection of urine and/ or hair for forensic toxicological analysis. To the extent that the date-rape drug phenomenon turns out to be a major problem, there will have to be significant changes in the initial response to complainants, in evidence collection kits, in the kind of forensic analysis done, and in follow-up procedures. Improvements in drug detection methodology and knowledge of drug elimination will help in designing those changes in order that they prove most useful in assisting victims, and identifying and convicting perpetrators of DFSA. Education in the use of alcohol and associated date-rape drugs is paramount and should be targeted at the populations of young people using them.
See Also
DNA: Hair Analysis; Forensic Psychiatry and Forensic Psychology: Sex Offenders; Sexual Offenses, Adult: Injuries and Findings after Sexual Contact; Management Postassault; Male Sexual Assault; Global Crime Figures and Statistics
SEXUAL OFFENSES, ADULT/Global Crime Figures and Statistics 111
Further Reading
LeBeau MA, Mozayani A (eds.) (2001) Drug-Facilitated Sexual Assault A Forensic Handbook, 1st edn. San Diego, CA: Academic Press. Public Law 106-172, February 18, 2000: the Hillory J. Farias and Samantha Reid Date-Rape Drug Prohibition Act of 2000 (http://lcweb2.loc.gov/law/usa/us060172.pdf). The Drug-Induced Rape Prevention and Punishment Act of 1996 (Act), 21 U.S.C. Sec. 841(b) (7) (http://www. usdoj.gov/ag/readingroom/drugcrime.htm).
The International Criminal Police Organization (Interpol)
Global Crime Figures and Statistics

P S L Beh, University of Hong Kong, Hong Kong, China
Introduction
This article will attempt to direct readers to the available statistical data on rape that are collected and published by international agencies. The sources of these data, such as local and national data on rape, must be viewed with an understanding of how this information is collected and the limitations and deficiencies of each of these data sets. It must also be appreciated that rape statistics are only a small portion of the entire spectrum of sexual violence. The term sexual violence has been adopted by the World Health Organization (WHO) amongst others and is understood to cover a broad spectrum of violence against women. Jewkes presented an elegant diagram in the shape of a pyramid which conceptualized the scope and breadth of the area of sexual violence.
ICPO, better known as Interpol, is an international organization based in Paris with 181 member countries. It claims to be the second biggest international organization, after the United Nations. It was formed with the aim of enhancing and facilitating cross-border criminal police cooperation. Amongst the data and publications it provides is a collection of international crime statistics, which are grouped by years. The data collected are those provided by member agencies and cover information on a standard list of crimes, including rape. The data also cover information on offenders who are detected or arrested. Data currently available on the website dates back as far as 1995. There is however no systematic attempt to validate such data or even to ensure that the data have been filed. Many countries submit incomplete data sets or neglect certain classes of crime. For instance, it is common for some countries not to submit data on rape or in some cases to submit data for a particular year but not for others. Table 1 collates the data that are currently available on the reported incidence of rape from members of Interpol. Interpol states categorically that the data are accepted as true and are published unchecked. Readers interested in the complete data sets on reported crime should visit their website.
The World Health Organization
Sources of International Data on Rape

Three international agencies that collect and publish data regularly on crime and on rape are described here: (1) the International Criminal Police Organization (ICPO); (2) WHO; and (3) the International Crime Victim Survey (ICVS). Their reasons for collecting such data and their focus are in many ways functions of the charter of these organizations. In order for the reader to understand the background of such data, a brief description is given of each organization and the data it publishes.
WHO has no interest in crime and its remit when first established was to monitor and promote international health. It has however accepted the challenge advocated initially by womens groups that sexual violence is now a matter of health concern and, in particular, that victims of sexual violence in its various forms carry a heavy economic, health, and social toll. In recognition of this, the WHO set up its Department for Injuries and Violence Prevention in March 2000. To its credit, this department has recently published a World Report on Violence and Health. This publication covers a broad spectrum of violence and there is an article on sexual violence. This document can be viewed on the website. Although commendable, it shows the appalling lack of information that is available on sexual violence, even to an agency such as the WHO. The source of WHO data appears to be a collection of published studies from researchers in different communities throughout the world. Individually, these publications are very informative for anyone interested in the study of rape and issues related to rape. However they are extremely difficult to use for comparative studies as the data are often the result of studies using different methodologies and
112 SEXUAL OFFENSES, ADULT/Global Crime Figures and Statistics

Table 1
Country
Data adapted from published material available from Interpol. Figures provided are rates per 100 000 inhabitants
1995 1996 1997 1998 1999 2000 2001 2002
Albania Algeria Andorra Angola Anguila Antigua and Barbuda Argentina Armenia Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bolivia Bosnia Herzegovina Botswana Brazil Brunei Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cayman Islands Chile China Colombia Cote dIvoire Croatia Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Savador Eritrea Estonia Ethiopia Fiji Finland Former Yugoslavic Republic of Macedonia France Gabon Gambia Georgia Germany Ghana
6.35 66.67 3.36 0.69 6.4 0.93 2.42 0.47 27.99 5.09 12.67 15.2 47.75
4.55 1.93 84.51 21.67 0.66 5.84 0.97 38.95 0.43
16.67 2.42
1.5 1.26 3.03 3.22
1.68 0.66 4.55
2.41 0.68 3.03
1.65 1.05
1.35
4.71 0.58 6.03 0.86 56.85 1.07 26.68 4.63 16.7 14.8 1.22
4.53 0.58 6.35 0.69 76.11 2.08 2.32 35.22 4.46 16.64 12.8 2.55 20.69
4.98 0.6
3.64
8.89 0.79 7.12 0.51
0.93
0.78 55.85
0.57
0.47
25.43 5.42
13.85 1.03
25.38 5.15 7.83
4.61
18.75
67.85 4.34 8.92
68.46 5 9.12 0.27 2 9.26 0.29 8.11 4.64 9.37 0.24 1.6 0.45 4.32 3.02 9.03 8.5 2.03 7
7.24
6.27
0.17 29.76 9.39 4.72 1.65 1.64 8.44
0.18 20 10.84 3.19 2.6 1.96 1.23 6.57 7.39 27.74 13.79 9.17
0.52
10.63 2.86 2.62 2.24 1.68 6.35 8.25 7 34.34 24.75 8.14 2.6 1.84 2.29 6.54 7.89 2.17 51.35 26.73 7.83 10.01
10.63
12.11 6.1
9.97
1.96 6.16 8.96 19.72 6.2
2.68 4.85 9.32
9.22
9.31
17.59 1.69 4.08 1.19 11.1 9.94 5.3 1.12 11.18
6.84 0.76 11.96 8.72 2.51
6.37 1.22 5.94 2
6.63 1.22 13.33 9.09 1.75
3.65 1.45 11.74 8.97 1.84
12.67 0.53 0.92 7.57
12.39 134.95 1.35 7.61 4.04
14.04
13.38
13.6
14.45
1.09 8.09 4.28
0.75 9.64 4.11
9.22 5.35
9.13 6.85
9.59 4.77
10.45

Table 1 Continued
Country 1995 1996 1997 1998 1999 2000 2001 2002
Gibraltar Greece Grenada Guyana Honduras Hong Kong Hungary Iceland India Indonesia Ireland Israel Italy Jamaica Japan Jordan Kazakhstan Kirghizistan Korea (Republic of) Kuwait Latvia Lebanon Lesotho Libya Lichenstein Lithuania Luxembourg Macau Madagascar Malaysia Maldives Mali Malta Mauritania Mauritius Moldova Monaco Mongolia Montserrat Mozambique Myanmar Namibia Nepal Netherlands New Zealand Nicaragua Niger Norway Oman Pakistan Panama Paraguay Peru Philippines Poland Portugal Puerto Rico Qatar Romania Russian Federation
3.33 2.28 17.28 0.27 1.66 4.06
6.67 1.78 70.53 15.3 1.36 4.14
2.08 60 15.79 1.14 3.85 16.35 1.6 0.6 7.27 13.46 34.27 1.31 2 10.79 7.8 4 0.73 4.8 1.11 1,353.29 13.42 1.17 1.35 3.41 14.53 0.57 8.05 14.31 34.46 1.48 1.75 7.96 4.38 0.2 3.38 1.88
3.33 2.33 15.94 1.33 3.28
3.33 2.29 15.75 1.53 2.93
6.67
1.41 3.2
2.89
0.64 5.43 9.36 30.68 1.19 1.01
5.11 12.96 37.4 1.18 1.42 12.95 3.98 0.54 5.17 1.5
0.63 6.01 16
0.62 11.06 10.11
1.47 2.14 7.13 4.51 5.29 1.7
1.78 8.69 4.86 6.94 2.33
1.75 9.72 4.29 5.11 2.05
3.98 6.25 2.05
6.06 5.41 11.22 4.42 10 2.8 5.43 3.2 2.67 1.8 3.54 7.2 0 14.24 4.37 6.22 1 6.6 4.37 10.62 1 6.94 0.46 2.16 3.06 4.29 3.33 14.87 18.18 3.7 2.3 2.88 6.14 3.33 15.21 3.24 0.88 2.07 0 3.17 2.26 5.92 0 5.92 6.76 6.89 5.04 5.67 8.78
5.12 2.76
5.78
3.73 6.06 0 16.51
5.2 0
5.64
1.72 50.46 0.66 9.16 32.26 11.23 34.96 0.67 11.7
0.98 45.87 9.8 19.67
0.5. 34.38 10.39
0.32 36.89 0.72
0.77
10.57 4.46 13.48 4.18
11.54 4.31
12.66 4.28
12.32 3.67
15.12 3.73 1.69 4.77 4.21 6.21 1.41 5.05
4.26
4.58 4.26 5.85 1.58 2.53 6.07 6.33
4.97 4.97 5.62 1.45 2.23 5.25 6.14
4.55
5.87 1.51 9 5.23 6.44 8.46
5.14 1.71 2.36 6.02
5.25 1.3 1.72 9.32 5.7
6.05 3.35
8.34 5.43
5.66
5.64 Continued
114 SEXUAL OFFENSES, ADULT/Global Crime Figures and Statistics

Table 1 Continued
Country 1995 1996 1997 1998 1999 2000 2001 2002
Rwanda Saudi Arabia Senegal Seychelles Singapore Slovakia Slovenia South Africa Spain Sri Lanka St Kitts and Nevis St Vincent and the Grenadines Swaziland Sweden Switzerland Syria Tanzania Thailand Tonga Trinidad and Tobago Tunisia Turkey Turks and Caicos Uganda UK (England and Wales) UK (Northern Ireland) UK (Scotland) Ukraine United Arab Emirates Uruguay USA Uzbekistan Venezuela Vietnam Yemen Zambia Zimbabwe
0.6
0.57 17.33 3.25 3.85 3.44 119.54 2.89 3.96 40 59.38 18.18 4.86 0.7 1.63 5.87
0.63
1.46 0 2.69 2.84 4.22 116.97 3.23 5.73 21.95 69.22 22.58 5.41 5.86
35.93 0.55
0.14 0 3.04 4.37 3.09 121.13 2.96
3.42 3.87 4.2 109.89 4.37 2.99
2.76 3.21 3.76 120.34 2.77 4.96 24.44 60.98 19.13 5.22 0.73 5.25 6.13 17.77 4.4 1.11 13.33 2.06 12.74
3.18 3.81 119.03 2.72 26 73.69 6.24 0.29 8.57 2.11
2.81 3.07
82.89 19 4.26 0.71 6.36
127.69 5.61 10.05
59.82 23.39 6.25
6.61
6.17 20.44 4.85 1.18 28 1.53 14.69 11.97 2.31 2.78 9.7 2.33
5.78 21.43 12.52
3.74
4.84 1.04 20.69 1.24 8.83 17.67 8.72 3.37 1.56 36.1 2.57 16.19 1.22 0.39 23.27
4.79 1.24 25 1.53
2.33
2.06
2.13 17.78
16.5 11.06 11.51 2.26 5.94 10.15 2.03 12.13 1.64 0.29 2.31 10.78 32.05 2.17
2.96 1.76 35.92 2.99 15.98 1.5 0.18 21.8
37.09
31.77 2.3
2.2
4.31 27.98
31.18
34.12
32.65
38.39
probably different definitions. In general the available data represent studies conducted by academics and/or local nongovernmental organizations (NGOs).
The International Crime Victim Survey
This is a study that is carried out under the auspices of the United Nations International Crime and Justice Research Institute. It is perhaps currently the most standardized data available for comparisons amongst countries. It uses a standardized sample survey instrument and looks at household experience with crime, policing, crime prevention, and feelings of unsafety. Indeed, the very reasons for setting up the ICVS were the problems in comparing crime between countries based on offenses recorded by the police and the absence of any standardized measure. The drawbacks
of these surveys are that they vary in scope amongst different countries at different times. During a particular year, the surveys may be carried out nationally in some countries but regionally or by towns and cities in others. Its other limitation is that, although each sample ranges from 1000 to 2000 respondents, it is distributed to household units and would therefore not sample those who do not have some semblance of a permanent abode, thus perhaps not sampling those at highest risk for crime victimization. The survey methodology was one of two types: computer-assisted telephone interviewing and face-to-face interviews. Each has its own setbacks: the first is limited to those who have a telephone while the second is subject to the myriad of problems associated with discussing sensitive subject material in a face-toface setting. It is however still a valuable source of
international crime victimization data, where the difference between the crime rates and the reported rates published by law enforcement agencies such as those available from Interpol can be seen and appreciated. It is also the only set of data where the focus is on victimization and therefore provides an estimate to researchers for the percentages of crime not reported to the police. It also attempts to explore the reasons for nonreporting for some of the crimes covered.
Other Useful Sources of Rape Statistics

The US Department of Justice, Office of Justice Programs through its Bureau of Justice Statistics maintains an excellent website where useful links and archival material are available for researchers. Raw international data sets can be downloaded and researched on a variety of topics, including rape. It also provides links to many countries official statistical websites.
incidence of rape reported by a country. Comparisons of such trends are even more problematic unless there is an indepth understanding of the culture, politics, social structures, religion, healthcare, and finally the criminal justice system of the countries being studied. Finally, increasing instability of political systems, civil unrest, and military conflict have profound impacts on the incidence of rape. Conflicts in the former Yugoslavia and civil unrest in Indonesia, to name a few, have seen the use of rape as a means of organized oppression of one party or faction by another. It is timely that there is a move to view such acts as war crimes and crimes against humanity, thus allowing the international criminal courts to pursue those behind such acts.
The Way Forward

Much is still unknown about rape, especially for a valid international comparison between countries. The few international bodies should perhaps gather their resources and those of their member countries to agree to a standardized protocol of collecting relevant rape data that cover the extent of victimization, the reasons for nonreporting, the number of reported cases, the extent of attrition of such reported cases, the judicial outcomes of such cases, and, of course, the short- and long-term medical and psychosocial effects on the victims and their families. Only then can we really make easy comparisons between countries and have an understanding of the effects of legal systems and of cultures on the incidence and prevention of rape.
Using International Rape Data

By now readers will have a sense of the limitations of using any of the data from the above sources. In this section, some of the more obvious and pertinent restrictions are described. First and foremost, the legal system varies from country to country. Over half of the countries in the world have legal systems that are the product of a civil-law tradition, followed by countries following the common-law tradition. There are also a substantial number of countries following Islamic law and/or various combinations of Islamic, civil, and common law. Second, the definition of rape varies between these legal systems and even between countries with similar legal systems. An example would be the difference between the definition of rape in Australia and Canada as compared with that in India or Hong Kong, although all have a common-law system of justice. Another example would be how marital rape is dealt with. Many jurisdictions still do not have specific legislations that recognize marital rape. Third is the difficulty in understanding the different variables that affect the likelihood of reporting by victims of rape in different countries. It is well recognized that even in a local context the attitudes of the victims, the care providers, and the police could on their own explain great fluctuations in the number of reported rapes from year to year. Ironically, where attitudes and services are improving, reported incidences initially rise. Extreme caution should therefore be exercised in attempting to describe trends in the
See Also
Sexual Offenses, Adult: Injuries and Findings after Sexual Contact; Drug-Facilitated Sexual Assault
Further Reading
Carillo R (1992) Battered Dreams: Violence against Women as an Obstacle to Development. New York: United Nations Fund for Women. Cook R (ed.) (1994) Human Rights of Women: National and International Perspectives. Philadelphia, PA: University of Pennsylvania Press. Davides M (ed.) (1994) Women and Violence: Realities and Responses Worldwide. London: Zed Books. France N (ed.) (1997) Elimination of Violence Against Women. Geneva, Switzerland: World Health Organization. Heise LL, Pitanguy J, Germain A (1994) Violence Against Women: the Hidden Health Burden. World Bank discussion paper no. 255. Washington, DC: World Bank.
116 SEXUAL OFFENSES, ADULT/Global Crime Figures and Statistics Jewkes R (2001) Understanding sexual violence: research challenges. Proceedings of the Fourth Meeting of The International Research Network on Violence Against Women 2224 January 2001, Johannesburg, South Africa. Pretoria, South Africa: Medical Research Council. Jewkes R, Ratsaka M, Gerber E (eds.) (2001) Proceedings of the Fourth Meeting of The International Research Network on Violence Against Women in Johannesburg South Africa. Pretoria, South Africa: Medical Research Council. Koss MP, Koss PG, Woodouff WJ, et al. (1991) Deleterious effects of criminal victimization on womens health and medical utilization. Archives of Internal Medicine 151: 342347. Krug EG, Dohlberg LL, Mercy JA, Zwi AB, Lozaro R (eds.) (2002) World Report on Violence and Health. Geneva, Switzerland: WHO. Swiss S, GillerSwiss J (1993) Rape as a crime of war: a medical perspective. Journal of the American Medical Association 270: 612615. Ward CA (1995) Attitudes toward Rape Feminist and Social Psychological Perspectives. London: Sage Publications. www.fbi.gov.ucr/96cius.htm www.Interpol.com www.ojp.usdoj.gov/bjs/ www.unicri.it/icvs/statistics/index_stats.htm www.who.int/health_topics/gender_based_violence/en/ Zvekic U (2000) Criminal Victimization Across the Globe. Resource material series no. 56. 112th International Training Course, United Nations, Asia, and Far East Institute for the Prevention of Crime and the Treatment of Offenders (UNAFEI).
Sexual Offenses, Children
See Children: Sexual Abuse, Overview; Sexual Abuse, Epidemiology
Sexual Offenses, Children, Diagnosis

Child Abuse
See Imaging: Radiology, Pediatric, Scintigraphy and
Sexual Offenses, Offenders
See Forensic Psychiatry and Forensic Psychology: Sex Offenders
Spousal Abuse
See Domestic Violence
Sudden Infant Death Syndrome, Autopsy Techniques and Findings

Findings: Sudden Infant Death Syndrome
See Autopsy,
SUDDEN INFANT DEATH SYNDROME, ETIOLOGY AND EPIDEMIOLOGY 117
SUDDEN INFANT DEATH SYNDROME, ETIOLOGY AND EPIDEMIOLOGY

T O Rognum, University of Oslo, Oslo, Norway R W Byard, Forensic Science Centre, Adelaide, SA, Australia
Of this unexplained cause Till the problem is solved by exclusion.
The Age Distribution

The first definition specified the age as an infant or young child. However, Beckwith and others observed a more narrow age distribution with a tall peak between the second and the fourth month (Figure 1). After campaigns for risk reducing were launched around 1990 and SIDS rates dropped dramatically in most industrialized countries, the age distribution became broader and the typical tall peak of small postneonatal infants became less significant (Figure 1). The SIDS epidemic started in the 1960s and the 1970s as the habit of putting babies to sleep prone was adopted. This was initiated because of the belief that infants would not aspirate and in addition would develop more rapidly when placed prone. There had been several observations that SIDS victims were often found dead in prone positions, but perhaps the first national organized campaign against the prone sleeping position was launched by de Jonge in the Netherlands in 1987. The effect of the riskreducing campaigns was dramatic in the indusrialized world (Figure 2), leading to up to 80% reduction in SIDS rates.
Etiology
Why do Some Babies Die Suddenly and Unexpectedly Without Explanation?
Since the cause of death in sudden infant death syndrome (SIDS) is by definition unexplained, the heading etiology is in a way contradictory. However, the strong association between the prone sleeping position and SIDS has led to the view that the cause of SIDS may have been found. Moreover, from an epidemiological point of view, risk factors for SIDS may be taken as etiological factors even if the fatal mechanisms are unknown. The understanding of the causal association between cholera and pollution of drinking water by sewage was well established 30 years before Vibrio cholerae was described as an infectious agent. In parallel, the risk factors for SIDS such as prone sleeping position, overheating, and cigarette smoke exposure may be looked upon as etiological factors. It is, however, important to remember that an overwhelming number of babies who have been sleeping prone or exposed to other risk factors have survived. The etiology of SIDS is probably multifactorial. According to the triple-risk hypothesis, death may occur when an infant is in a vulnerable developmental stage, has a predisposition to SIDS, and is exposed to a trigger event.
The First Definition of SIDS

The story of sudden infant death as a syndrome goes back to 1969 when Beckwith proposed a definition of SIDS. This original definition describes a fatal condition that excludes all known causes of death; i.e., it was the: sudden death of any infant or young child, which is unexpected by history, and in which a thorough postmortem examination fails to demonstrate an adequate cause for death. This definition by exclusion was immortalized by Sylvia Limerick in 1973:
When theories compete in profusion, Then the experts conclude, in confusion, Therell be flaws in all laws
Figure 1 Age distribution of SIDS victims before the back-tosleep period (19841989) and in the time thereafter (19902002).
118 SUDDEN INFANT DEATH SYNDROME, ETIOLOGY AND EPIDEMIOLOGY
Historical Developments
Sudden infant death is described in the Old Testament (I Kings 3:19: a womans son died in the night, because she lay on him). The belief that babies died because their parents had lain on them was commonly held for several thousands of years. Some of the main developments and theories of causes of sudden infant death are given below: . In ancient times: adults lay on their infants . 1830: status thymolymphaticus: cot death victims had enlarged thymus glands that pressed on their trachea, causing suffocation . 1950: viral inflammation of the airways . 1954: hypogammaglobulinemia . 1960: cows milk allergy
. 1967: hypoparathyroidism . 1969: first international definition of SIDS . 1971: SIDS World Health Organization International Classification of Disease (ICD) code in death statistics . 1972: triple-risk model: vulnerable developmental stage predisposition . trigger event . 19721982: repeated apnea widely accepted as a mechanism of death in SIDS . 1976: chronic hypoxemia/repeated hypoxic episodes precede death . 1985: prone sleeping position and other risk factors such as overheating and smoking . 1990s: fall in SIDS rates in many developed countries; fatal mechanisms still unsolved . 1995: increasing awareness of inflicted injury as a cause of sudden infant death . 2003: the phrase genetic risk factor introduced. Mothers convicted of infanticide were acquitted.
Recent Developments in Epidemiological Research

Risk Factors Prone Sleeping, Smoking, Overheating, Cosleeping
Most western countries experienced a SIDS epidemic during the 1970s and 1980s. In Norway the SIDS rate peaked in 1989 with 2.4 deaths per 1000 live births (Figure 2).
Prone Sleeping Position
Figure 2 SIDS rates in the Nordic countries 19772002.
After the first back-to-sleep campaign (Figure 3) in 19891990, the SIDS rate in Norway was halved in 1 year, and since 1993 it has been less than 0.5 deaths
Figure 3 Risk factors for SIDS: prone sleeping, smoking, and overheating.
per 1000 live births (Figure 2). Many authors have now shown that the drop in SIDS rates paralleled the reduction in the numbers of infants sleeping prone. When an infant has been placed prone to sleep, the odds ratio (OR) for death from SIDS is 13.9 when compared to supine sleeping (Table 1).
Face Right Down
more than 20 cigarettes per day (Table 5). The dose response if the father smokes is less significant.
Signs of Infection Before Death and Synergy of Risk Factors
The most dangerous situation is prone with the face toward a mattress compared to a supine position with the face up: the OR is 58.9 (95% confidence interval 25138) (Table 2).
Face Covered
Infectious symptoms before death are seen in half of SIDS victims, compared to 25% of normal live controls. Infectious symptoms, environmental smoking, and head covering are risk factors which, together with sleeping position, have more than an additive effect on the risk of SIDS (Table 6).
Breastfeeding
If the face was covered when an infant was found dead, the OR is 6.8, whereas if an infant was entangled in bed clothes, the OR is 2.9 (Table 3).
Parental Smoking
Breastfeeding has been claimed to be protective. The OR for not breastfeeding is 1.7, and 2.7 when age-adjusted, in the Nordic study. This was not supported, however, by data from the UK.
Bed Sharing Cosleeping
Maternal smoking varies among Nordic countries: 24% of controls were smokers in Sweden, compared to approximately 3536% in Norway and Denmark. In Norway as many as 72% of SIDS mothers smoke (Table 4). Adjusted according to the number of cigarettes per day, the increased risk of losing an infant to SIDS corresponds to an OR of 12.7 if the mother smokes
An adult sharing a bed with an infant increases the risk of SIDS/infant death with an OR of 1.7 (Table 7).
Table 4
Maternal smoking (Nordic Council 1997)

SIDS (%) Controls (%)
Nordic country
Denmark Norway Sweden
60 72 56
36 35 24
Table 1 Sleeping position and risk of SIDS (Nordic Council 1997)

Position placed to sleep the last time
Table 5
SIDS (%) Controls (%) Odds ratio
Parental smoking habits (Nordic Council 1997)

Mother odds ratio Father odds ratio
Number of cigarettes per day
Prone Side Supine
54 33 13
20 36 44
13.9 3.5 1.0
0 19 1019 20
1 2.4 5.3 12.7
1 0.65 2.2 2.1
Table 2
Position of face when found (Nordic Council 1997) Table 6 Combined factors (Nordic Council 1997)
Odds ratio SIDS (%) Controls (%) Odds ratio Factors
Position of infant
Towards mattress Side Upward
38 54 8
14 77 22
58.9 1.7 1.0
Infectious symptoms prone Head covered prone Environment smoking prone
29 17 8.1
Table 3 1997)
Face covered/entangled when found (Nordic Council
Table 7
Bed sharing (Nordic Council 1997)

SIDS (%) Controls (%) Odds ratio
Age of infant sharing a bed Position of infant SIDS (%) Controls (%) Odds ratio
21 Face covered Entangled in bedclothes 29 4.6 5 2 6.8 2.9 112 weeks 13 weeks
13
1.7 2.6 0.7
80
prone sleep position co-sleep SIDS rate Southeast Norway
2.5
Proportion of cases (%)
60
1.5 40 1.0 20 0.5
84 85 86 87 88 89 90 91 92 93 94 95 96 97 98
Figure 4 Usual mode of sleep within a control group compared to the SIDS rate for southeast Norway.
The risk of bed sharing is age-dependent; it is increased with an OR of 2.6 between 1 and 12 weeks, whereas no increased risk is seen in babies more than 13 weeks of age (Table 7). Given that some of these deaths will be due to accidental asphyxia and not to SIDS, separating out numbers and categories of deaths is not easy. Cosleeping has become increasingly popular in western countries: in southeast Norway 25% of all babies sleep in bed with parents (Figure 4) and 42% of all SIDS deaths now occur while an infant is in bed with an adult. It is also easy to imagine that a dangerous situation may occur if an infant is squeezed between the back of an adult and the back of a sofa (Figure 5), especially if the adult is intoxicated or tired and less able to react and respond to an infant. It seems that it is more dangerous to cosleep with a smoking mother than with a nonsmoking mother, and that younger infants are at most risk while bed sharing.
Large Geographical Variation in SIDS Rates

A Matter of Different Diagnostic Practices?
Figure 5 A dangerous situation: cosleeping on a sofa behind the back of an adult.
SIDS received its own ICD code in 1971, enabling comparisons of SIDS rates among different countries (Figure 6). It is unlikely, however, that the large variation in SIDS rates around the world is completely accurate, as it is probable that the variation will be influenced by different diagnostic cultures and habits; for example, figures from Japan, presented at the ESPID (European Society for the study and Prevention of Infant Death) conference in Jerusalem in June 1999,
showed that the increase in SIDS rates in Japan paralleled the decrease of deaths in infancy due to suffocation. The finding is suggestive of a diagnostic shift. Real differences between countries may occur, however. In the Nordic countries SIDS rates differed markedly during the1970s and the 1980s; Norway and Denmark had much higher rates than Finland
Number of cases per 1000
2.0

Deaths per 1000 live births 1997--2001
Netherlands Slovakia Israel Finland Denmark Hungary Norway Russia Greece Switzerland England Sweden Slovenia France Portugal Austria Scotland Belgium Ukraine Ireland Germany Canada USA Czechoslovakia Italy New Zealand Australia
0.2
0.4
0.6
0.8
1.2
Figure 6 SIDS rates in countries of the world. Source: World Health Organization (2001) World Health Statistics Annual. Geneva: World Health Organization.
and Sweden. These differences have been proved to be real in a multinational study involving 10 pathologists from different centers in the area.
SIDS Research
Possible Lethal Mechanisms in SIDS
SIDS A Diminishing Proportion of All Sudden Infant Deaths

Between 1984 and 1989 SIDS cases constituted 80% of all sudden unexpected deaths in infancy and small children in southeast Norway. In the period after 1990, the proportion of SIDS reduced to 56% (Figure 7).
More Gray-Area Cases

After the back-to-sleep campaigns, cases of neglect and child abuse became more prominent. It is, however, more likely that this is due to a relative increase in numbers due to a reduction in SIDS cases. The gray-area cases between SIDS and totally explained death seem to have become more frequent, a fact which is a challenge for forensic pathologists, and also underlines the necessity of cooperation with other experts (Figure 8). The exclusion of explained causes of death demands expertise in both forensic medicine as well as in pediatric pathology, neuropathology, radiology, pediatrics, microbiology, and toxicology.
Diagnostic accuracy is a prerequisite for research into SIDS. The history of SIDS research has been full of pitfalls: in addition to a lack of suitable controls, erroneous diagnoses have been the main obstacles. In 1972 Steinschneider described five infants who had periods of prolonged apnea during sleep. Two of these infants died suddenly and unexpectedly a few days after being discharged from hospital. This was the beginning of an era characterized by large research projects studying irregular breathing and SIDS. Later it turned out that the two deaths reported by Steinschneider were due to homicide. This tragedy provided the background for the large-scale selling of apnea monitors for home use. However, in spite of the failure of apnea monitors to prevent or predict infant deaths, irregular breathing causing hypoxemia may be an important factor in some SIDS deaths. Naeye described seven tissue markers for hypoxia in the SIDS case, including brainstem astrogliosis. Several authors have confirmed astrogliosis, although others have not been able to reproduce this finding. Problems with suitable controls may perhaps explain the discrepancy; e.g., since infections may also induce astrogliosis, infants dying from infections may not be suitable controls.
Figure 7 Distribution of types of sudden infant death in southeast Norway in two time periods: 19841989 and 19902000. SIDS was the dominant category in both periods, but in the latter period all other causes, when pooled, approached 50%.
SIDS
Disease Accidents Neglect Abuse Murder
Figure 8 The diagnosis of SIDS is difficult due to lack of positive criteria and potential overlap of findings.
Hypoxia
An episode of hypoxia has to be survived for several days before astrogliosis is visible. One therefore needs markers for hypoxia that can be measured in closer temporal association with the fatal episode. In 1988 elevated hypoxanthine levels in the vitreous humor of SIDS victims were reported (Figure 9). Hypoxanthine is a breakdown product in adenosine triphosphate catabolism and is accumulated in body tissue and body fluids in hypoxic states. It has been shown that SIDS infants and infants who died from infections have a similar hypoxanthine distribution in the vitreous humor, whereas infants and children who died from accidents have low levels. Chronic hypoxia
due to heart malformations or lung disease (respiratory distress syndrome (RDS)) assumes an intermediate position (Figure 9). Since animal experiments have shown that repeated episodes of hypoxia induce higher hypoxanthine levels in vitreous humor than chronic hypoxia, the latter is probably the situation for SIDS. Furthermore, it was found that a proportion of infants with apparent life-threatening events (ALTEs) had higher hypoxanthine secretion levels into the urine after an event than did controls. Studies of vascular endothelial growth factor (VEGF) in cerebrospinal fluid, vitreous humor, and the serum of SIDS infants also suggest that SIDS is preceded by prolonged hypoxia. VEGF is an important factor for neovascularization and is stimulated by hypoxia and downregulated by elevated oxygen levels. Thus a high level indicates preceding hypoxia in cerebrospinal fluid; mean VEGF was 3.6-fold higher in a SIDS group than in controls. These hypoxanthine and VEGF studies should prompt further research to identify possible triggering factors inducing hypoxia and the cascade of events leading to SIDS. Knowledge of such trigger factors may be the key to prevention.

18 SIDS No. 109 Median 239 mmol l1
12
0 6 Number of subjects RDS No. 22 Median 85 mmol l1
0 6 Heart malformation No. 20 Median 65 mmol l1
0 18 Sudden violent death No. 23 Median 0 mmol l1
12
0 0 200 400 Hypoxanthine (mmol l1) 600 800
Figure 9 Distribution of hypoxanthine concentrations in vitreous humor in cases of SIDS, respiratory distress syndrome (RDS), heart malformations, and sudden violent death. The concentrations of hypoxanthine in SIDS were significantly higher (P < 0.001) than those in sudden violent death, and also higher than concentrations in RDS (P < 0.01) and heart malformations (P < 0.01). Reproduced with permission from Rognum TO, Saugstad OD (1993) Biochemical and immunological studies in SIDS victims. Clues to the understanding of the death mechanism. Acta Paediatrica 389 (suppl.): 8285.
Repeated Episodes of Hypoxia in SIDS
Recently Poets et al., analyzed recordings from nine infants who suffered sudden infant death whilst on cardiorespiratory monitors. The primary cause of the monitor alarms was bradycardia in all but two infants. Gasping was already present at the time of the first alarm in three infants, and occurred within 3 min in four infants. The duration of gasping was several minutes if not interrupted by resuscitation. Since gasping only occurs if the PaO2 is <515 mmHg, it is most likely that the seven infants who gasped at, or shortly after the first alarm, were already severely hypoxemic at that time. This hypoxemia was apparently not caused by prolonged periods
with lack of breathing movements, as there was no apnea alarm before the development of gasping. The decrease in heart rate observed in seven of the infants was also suggestive of hypoxemia. The main purpose of gasping is to restore tissue oxygenation, i.e., autoresuscitation. Gasping will remain ineffective if there is circulatory failure and the increased oxygen levels in the pulmonary circulation will not reach the brainstem. Gasping will also remain ineffective if there is ongoing airway obstruction, or alveolar capillary block, e.g., due to severe pulmonary edema or airway collapse. Pulmonary edema is known to occur during asphyxia and is a characteristic finding in sudden infant death.
Failure of autoresuscitation may also be due to deficits in the medullary seretonergic network. A neurochemical imbalance in the medullary serotonergic network could put an infant at risk for sudden death during sleep as he/she passes through a critical period in autonomic and central control when confronting an exogenous stressor.
The Three-Hit Model
developmental stage; (2) predisposing factors; and (3) exogenous triggering events.
Vulnerable Developmental Stage
In 1972 Wedgewood proposed a triple-risk model for SIDS. The fatal triangle proposed by Rognum and Saugstad, the triple-risk model of Filiano and Kinney and the multifactorial model of Kahn are essentially the same (Figure 10). The model implies that an infant will only die from SIDS if three conditions are fulfilled simultaneously: (1) a vulnerable
The first postneonatal month is a critical period for homeostatic control. The infant goes through a period of reflex chaos in which fetal reflexes vanish and voluntary movements are not yet developed. In addition, the mucosal immune system undergoes rapid development (Figure 11).
Predisposing Factor
A certain genetic makeup may constitute a predisposition. Polymorphism in the IL-10 gene is a candidate. Other possibilities are mitochondrial DNA mutations. This heteroplasmy (only parts of
Critical developmental period
Vulnerable developmental stage of CNS and mucosal immunity
Maturational processes
Environmental factors
SIDS
Vulnerable infant Exogenous stressor(s)
Predisposing factors: Astrogliosis, genetic makeup
Trigger event: Overstimulation of the mucosal immune system?
Medical conditions
C The multifactorial model for SIDS
The triple risk model
The hypothesis of a "fatal triangle" in SIDS
Figure 10 Different versions of the triple-risk model that was first proposed by Wedgewood in 1972. SIDS, sudden infant death syndrome; CNS, central nervous system.
CSF: IL-6 Salivary gland: lgA, IgG, IgM HLA-DR CD45, CD3 Vitreous humor: Hypoxanthine, similar distribution in SIDS and infectious death
Larynx: IgA HLA-DR
Carina: IgM Urine: Hx/kreatinin ration Duodenum: IgA

Figure 11 Summary of the immunological and biochemical findings in material from the Institute of Forensic Medicine, University of Oslo. CSF, cerebrospiral fluid; SIDS, sudden infant death syndrome.
the mitochondrial DNA have the mutation) may cause impairment of adenosine triphosphate production, that may be fatal in stressful situations, e.g., the inability to turn a face-down head to the side due to muscle weakness. Under normal circumstances, such a mitochondropathy would not be recognized as pathological, but rather as part of normal variation.
Trigger Event
Increased SIDS rates in areas with endemic increases in infectious diseases are also recognized and half of SIDS victims have signs of mild infections in the days prior to death. A relationship between SIDS deaths and the month-to-month variation in Bordetella pertussis infection has also been shown. Moreover, in Norway during a whooping-cough epidemic a significant increase in SIDS rates was seen, and recently Bajanowski et al., found significantly more frequent RNA virus in lung tissue of SIDS victims than in non-SIDS victims.
SIDS and the Immune System

Paltauf in the late 1800s demonstrated mild inflammatory changes in the walls of the bronchioli in SIDS victims. Studies of immunoglobulins in pulmonary lavage fluid, and immunohistochemical examination of tracheal walls, intestinal mucosa, salivary glands, and tonsils have shown immune stimulation in SIDS (Figure 12). Within the central nervous system of certain SIDS infants increased levels of interleukin-6 (IL-6), a cytokine that induces fever, have been shown. Mild infections may be lethal if they affect infants at the time after birth when immunoglobulins in the blood are at their lowest level. However, it has been shown that infants who die from SIDS do not have lower gammaglobulin levels in blood than other infants. Several studies have demonstrated that the mucosal immune system undergoes a rapid development in the first weeks and months after birth. These observations point to a vulnerable period of life in the first weeks and months after birth (Figure 12). It is obvious that the downregulation of respiration that occurs in many SIDS victims is due to events in the central nervous system. In 1989 Guntheroth proposed that cytokines might constitute a link between the peripheral immune system and the central nervous system, and in 1995 Vege et al., demonstrated that half of SIDS victims had IL-6 levels in cerebrospinal fluid in the same range as infants who died from infections such as meningitis and septicemia.
Figure 12 The development of mucosal immunoglobulin A in salivary glands, tracheal wall, and duodenum mucosa. The age between the second and the fourth months is indicated by yellow columns.
Recently, the same researchers were able to demonstrate that SIDS victims with high IL-6 levels in the cerebrospinal fluid had also had slight signs of infection before death, and had increased number of immunoglobulin A cells and increased human leukocyte antigen (HLA)-DR expression in the epithelium of the laryngeal wall (Figure 13). Cytokines such as IL-1 are able to induce slow-wave sleep and fever in animals. Recently IL-10 has also been connected to SIDS. IL10 is an immunoregulatory cytokine that plays an important role in infectious disease. It downregulates the production of proinflammatory cytokines such
not only in their larynges but also, to a certain extent, in their tracheas. Staphylococcal toxins and endotoxins have also been suggested as a factor in SIDS. These toxins may induce shocklike reactions and fever.
SIDS and Laryngeal Vagal Reflexes

Animal experiments have shown that laryngeal stimulation may induce prolonged and even fatal apnea, as may stimulation of chemoreceptors and free nerve endings in the upper airways in human infants. Animal experiments have revealed that laryngeal stimulation in lambs infected with respiratory syncytial virus (RSV) has caused increased inhibition of minute ventilation and delayed recovery of regular breathing. RSV-infected infants also had a significantly reinforced reflex apnea response compared with noninfected infants. Other infectious agents may possibly act in the same way. In a study of children in day-care centers, nasal lavages were obtained in order to assess nasal cytokine production during acute upper respiratory infections. IL-1b, IL-8, IL-6, and tumor necrosis factor-a were markedly elevated during acute infection compared to baseline levels. Whether RSV was present or absent did not influence cytokine production, suggesting that cytokine release into nasal secretion is a general phenomenon in viral respiratory infection, rather than a response to specific pathogens. This view fits well with the observations of mucosal immune stimulation in the tracheal wall, the duodenal mucosa, the salivary glands, and the tonsils. Moreover, the relationship between clinical symptoms of infection before death, immune stimulation in the larynx, and IL-6 elevation in cerebrospinal fluid, may indicate an interplay between largyngeal reflexes and the immune system in SIDS (Figure 13). The finding fits well with the observation that a significant part of the reduction in SIDS cases in South East Norway was due to less victims with age between two and four months having had signs of infection prior to death.
Figure 13 Relationship between the immune response in laryngeal mucosa and the central nervous system in SIDS cases. Subjects with high interleukin-6 levels also showed an increased number of immunoglobulin A immunocytes and increased expression of human leukocyte antigen (HLA)-DR antigen in glandular epithelium.
as IL-6. Variability in IL-10 production has a hereditary component and IL-10 may also be inhibited by smoking.
SIDS and Infection

The relationship between the prone sleeping position and SIDS is well established. Furthermore, when analyzing the age distribution of the SIDS victims in southeast Norway before and after 1990, it was demonstrated that the most significant decrease was in small infants between 2 and 4 months of age who died in the prone position and had signs of infection before death (Figure 14). Seasonal variation in the two periods has not changed significantly: SIDS occurred more frequently during the winter both before and after the decline in rate. However, the number of deaths occurring outdoors was significantly reduced in the second period compared to the first (P < 0.01). From this Norwegian study it may be concluded that, after the riskreducing campaigns, there have been fewer deaths in young infants placed prone with signs of infection prior to death, sleeping outdoors during winter. This finding fits with the Nordic SIDS study which describes an OR of 29 when infectious symptoms were combined with prone sleeping position. Throughout the years SIDS has been linked to respiratory tract infections. It has been shown that healthy children carry potentially pathogenic bacteria
The Vicious Circle in SIDS

In cases of slight infection combined with prone position, a warm environment, and a vulnerable age period, a vicious circle leading to coma and death might be triggered (Figure 15). A slight respiratory infection in an infant placed prone may induce laryngeal immune stimulation which exaggerates vagal reflexes. Mucosal immune stimulation may induce IL-6 liberation in the central nervous system, giving rise to fever and thus hyperthermia. Because of a possible decreased threshold for
no infection infection
25
20
1984--89
15
10
5 Number of cases
0 <1 25 1 2 3 4 5 6 7 8 9 10 11 12 >12
20 1990--96 15
10
0 <1 1 2 3 4 5 6 7 8 9 10 11 12 >12
Months
Figure 14 Age distribution of SIDS with and without signs of infection before death in two time periods (19841989 and 19901996). Signs of infection were more frequent in infants between 2 and 4 months of age in the first period (P < 0.01). Note also the tall 24-months age peak in the first period compared to after the back-to-sleep campaign period.
vagal reflexes, bradycardia and irregular breathing may induce hypoxemia. In cases of inefficient gasping (autoresuscitation), the infant may develop severe hypoxia and finally coma and death. Failure of autoresuscitation may, in part, be due to deficits in the medullary serotonergic network. The vicious circle of SIDS is a model that can be further developed as new observations occur, e.g., decreased levels of IL-10, either due to genetic polymorphisms or due to secondary influences, i.e., smoking, which would facilitate IL-6 liberation. Animal experiments have shown that IL-1b counteracts autoresuscitation. The hypothesis that some infants overreact immunologically assumes that a slight infection may trigger the vicious circle which leads to depressed respiration, hypoxia, and death.
SIDS and Genetic Risk Factors

Carl Hunt recently used the expression genetic risk factors for SIDS. Polymorphisms in the IL-10 gene are interesting candidates for such a risk factor. Another possibility is the hypothesis of SIDS as a kind of mitochondropathy. Thus several independent researchers have shown that infants who later died from SIDS were more peaceful than agematched controls. They tended to sleep more and be less active, an observation which may be due to decreased adenosine triphosphate production. Santorelli et al., have demonstrated lesions in the mitochondrial DNA in SIDS victims, and Opdal et al., have demonstrated an elevation in the hypervariable D-loop region, and quite recently four specific mutations in mitochondrial DNA in four
. Vege. Figure 15 Vicious circle in SIDS showing lethal death mechanisms in some possible SIDS cases. Courtesy of Dr A
SIDS cases. Mutations in mitochondrial DNA may occur to different degrees in different organs in the same individual (heteroplasmia). One hypothesis is that SIDS may be due to a subclinical mitochondropathy. If the diaphragm or the heart muscles are affected, this may be of significance in a stressful situation with increased energy requirement. The finding of elevated hypoxanthine levels in the vitreous humor in SIDS victims further strengthens the theory of energy deficiency, since hypoxanthine is also a marker of adenosine triphosphate depletion. Familial clustering in occasional cases of SIDS also supports the hypothesis of a possible genetic disposition. A list of possible genetic risk factors for sudden infant death is given in Table 8. The reduction in serotonergic, kainate, and muscarinic cholinergic neurotransmitter receptors in a subset of SIDS cases also makes genetic changes in the serotonin transporter gene an interesting candidate. Partial deletions of the complement component C4 have been described in both German and Norwegian SIDS victims. In both studies an association between slight infections before death and part-deletion of either C4A or C4B gene was found. Long QT syndrome (LQTS) is an inherited cardiac disorder that causes syncope, seizures, and sudden death, usually in young otherwise healthy individuals. LQTS is caused by mutations in genes encoding for cardiac ion channels; these genes include KVLQT1, HERG, SNC5A, KCNE1, and KCNE2. Mutations in two of these genes have been identified in cases initially diagnosed as SIDS. Between 2% and
Table 8
Disorder
Genetic risk factors for sudden infant death

Frequency
MCAD Fatty acid oxidation Cardiac ion channels mtDNA Serotonin transporter Complement component C4 Interleukin-10 MCAD, medium-chain acyl-coenzyme deficiency; mtDNA, mitochondrial DNA. A
$1%? $3%? $3%? ? ? ? ? dehydrogenase
3% of cases until now recognized as SIDS, may be due to LQTS. Deficiencies of fatty acid metabolism have been extensively studied in cases of SIDS, and mediumchain acyl-coenzyme A dehydrogenase deficiency (MCAD) probably occurs in approximately 1% of cases initially diagnosed as SIDS. Defects in the genes involved in glucose metabolism, thermal regulation, and thrombosis, as well as the gene for HLA-DR have been investigated in SIDS victims, but there is no convincing evidence that these genes are involved.
Will the SIDS Enigma be Solved in Our Time?

Based on current knowledge it is reasonable to assume that a significant part of what is today named
SUDDEN INFANT DEATH SYNDROME, ETIOLOGY AND EPIDEMIOLOGY 129 Guntheroth WG, Spiers PS (2002) The triple risk hypothesis in sudden infant death syndrome. Pediatrics 110: e64: 170. Irgens LM, Markestad T, Baste V, et al. (1995) Sleeping position and sudden infant death syndrome in Norway 19671991. Archives of Diseases of Childhood 72: 478482. Kinney H, Filiano JJ, Harper RM (1992) The neuropathology of sudden infant death syndrome. A review. Neuropathology and Experimental Neurology 51: 115126. Kinney HC, Filiano JJ, White WF (2001) Medullary serotonergic network deficiency in the sudden infant death syndrome: review of a 15-year study of a single dataset. Journal of Neuropathology and Experimental Neurology 60: 228247. Mitchell EA, Brunt JM, Everard C (1994) Reduction in mortality from sudden infant death syndrome in New Zealand: 19861992. Archives of Diseases of Childhood 70: 291294. Nordic Council of Ministers (1997) Sudden infant death in Nordic countries. Tema Nord 600. Copenhagen, Denmark: Nordisk Ministerrad. Opdal SH, Rognum TO, Vege A, Stave AK, Dupuy BM, Egeland T (1998) Increased number of substitution in the D-loop of mtDNA in the sudden infant death syndrome. Acta Paediatrica 87: 10391044. Opdal SH, Rognum TO (2004) The sudden infant death gene: does it exist? Pediatrics 114(4): 506512. Poets CF, Meny RG, Cohobanian MR, Bonofiglo RE (1999) Gasping and other cardiorespiratory patterns during sudden infant deaths. Paediatr Res 45: 350354. Ponsonby AL, Dwyer T, Gibbons LE, Cochrane JA, Wang Y-G (1993) Factors potentiate risk of sudden infant death syndrome associated with the prone position. New England Journal of Medicine 329: 377382. Rognum TO, Saugstad OD (1993) Biochemical and immunological studies in SIDS victims. Clues to the understanding of the death mechanism. Acta Paediatrica 389(suppl.): 8285. Santorelli FM, Schlessel JS, Slonim AE, DiMauro S (1996) Novel mutation in the mitochondrial DNA tRNA glycine gene associated with sudden unexpected death. Pediat Neurol 15: 145149. Vege A, Rognum TO, Scott H, Aasen AO, Saugstad OD (1995) SIDS cases have increased levels of interleukin6 in cerebrospinal fluid. Acta Paediatrica 84: 193196. , Rognum TO, Opdal SH (1998) SIDS changes Vege A in the epidemiological pattern in eastern Norway 19841996. Forensic Science International 93: 155166.
Figure 16 Possible causes of sudden infant death syndrome. MCAD, medium-chain acyl CoA dehydrogenase deficiency; FAO, fatty acid oxidation deficiency; LQTS, long QT syndrome; mtDNA, mitochondrial DNA; SIDS, sudden infant death syndrome.
SIDS will be eventually attributed to identifiable diseases and conditions and will be separated from genuine SIDS cases (Figure 16). The remaining cases of SIDS (more than 50%) may be explained by the three-hit model. The age distribution of classical SIDS cases from the period before the back-to-sleep campaign, with a peak between the second and the fourth month after birth, favors the hypothesis of a vulnerable developmental stage, predisposing endogenous factors, and an exogenous trigger event occurring simultaneously.
See Also
Autopsy, Findings: Sudden Infant Death Syndrome; Children: Sudden Natural Infant and Childhood Death
Further Reading
Bajanowski T, Rolf B, Jorch G, Brinkmann B (2003) Detection of RNA viruses in sudden infant death (SID). International Journal of Legal Medicine 117: 237240. Byard RW, Krous HF (2001) Sudden Infant Death Syndrome Problems, Progress and Possibilities. London: Arnold.
130 STARVATION
STARVATION
S P Allison, Queens Medical Centre, Nottingham, UK
Introduction
The significance of starvation in clinical, forensic, or medicolegal terms depends upon the degree of malnutrition or metabolic derangements induced. These, in turn, depend upon the severity and duration of starvation and whether it is associated with exacerbating factors such as disease. In the developing world, starvation may be the primary factor responsible for malnutrition, although this increases susceptibility to infections and infestations, which are common in famine conditions. In the developed world, however, malnutrition is usually the consequence of diseases, which influence food intake, metabolism, or both. Indeed, using anthropometric criteria, between 10% and 40% of hospital admissions have been found to be undernourished and to suffer further nutritional deterioration during hospital stay, due mainly to underrecognition and undertreatment of the condition. Malnutrition in the sense of undernutrition has been defined as: a state of nutrition in which a deficiency or imbalance of energy, protein, and other nutrients causes measurable adverse effects on body composition and function, and on clinical outcome from disease. Clinically important malnutrition may also be defined in therapeutic terms as: a sufficiently severe state of undernutrition that measurable improvements in function and clinical outcome result from nutritional intervention by natural or artificial means. We are well adapted to cope with short periods of fasting, but, after a few days without food, and with loss of 5% of body weight, there are detectable impairments of mental and physical function. These changes assume major clinical importance after 1015% weight loss, by which time, in clinical practice, nutritional intervention should have been undertaken. More than 35% weight loss is life-threatening. These considerations assume a normal premorbid weight, and are not applicable to the controlled and gradual weight loss in obese individuals, eating a diet reduced in energy but adequate in protein and other nutrients, which allows a preferential loss of adipose tissue, with only a modest reduction in lean mass, particularly when combined with an exercise program. Although 23 months total starvation is usually fatal in individuals of previously normal weight,
obese subjects can survive for much longer periods due to their greater energy reserves. Conversely, thin individuals, who start with lower reserves, survive for less time. Smaller body stores in childhood mean that, while a normal adult may survive 70 days of starvation, a full-term baby can only survive 32 days, and a premature infant only 5 days. While total starvation is obvious, partial starvation may be less so, immediately, unless actual intake is measured and compared with estimated needs.
Normal Nutritional Requirements

Energy
To maintain body composition at a stable level energy intake, in the form of carbohydrate (4 kcal g1), fat (9 kcal g1), and protein (4 kcal g1), needs to equal energy expenditure. Total energy expenditure (TEE) is the sum of resting energy expenditure (REE), required to maintain the body at rest (2025 kcal g1 body weight), plus the additional expenditure from physical activity (usually 5070% of REE) and dietinduced thermogenesis (10% of REE). Adipose tissue has a relatively low metabolic rate, so that REE depends mainly upon the size of the lean mass, which is lower in women, and reduces by up to 50% between the ages of 30 and 78 years. These considerations mean that, to maintain energy balance, most normally active and normal-weight young to middle-aged adults need to ingest between 2000 and 3000 kcal day1, or 1.51.8 REE, depending on age, lean body mass, and activity. Those participating in prolonged and intense exertion, such as the Tour de France cycle race, or hauling a sledge across the Antarctic, need to consume 60008000 kcal day1 to maintain body composition.
Protein
To maintain the mass and function of lean tissue, including the major organs, requires not only fulfillment of energy needs, but a minimum daily protein intake of 0.8 g kg1 body weight, although, in the presence of disease, this requirement may rise to 1 g kg1 body weight or more. Weight loss due to a combination of protein and energy deficiency is known as proteinenergy malnutrition.
Other Nutrients
Normal tissue function also depends on an adequate intake of water, electrolytes, minerals, trace elements, and vitamins. Specific nutrient deficiencies, e.g., for
STARVATION 131
individual vitamins, may occur in isolation or as multiple deficiencies, often associated with concomitant proteinenergy malnutrition. The characteristics of such deficiency states are beyond the scope of this article, which will focus mainly upon global malnutrition secondary to total or partial starvation.
Disease-Associated Malnutrition
Acute or chronic disease exacerbates the problem of starvation, by increasing metabolic requirements and diminishing appetite or the capacity to swallow and digest food, so-called disease-associated malnutrition. Figure 1 shows the rates of weight loss, with time, in three different circumstances. The first, more gradual slope is derived from the studies of Keys and coworkers on normal young male volunteers who underwent semistarvation for a period of 24 weeks. The second, steeper slope describes the weight changes in the Irish Republican Army (IRA) hunger strikers who subjected themselves to total starvation for 70 days, by which time they had lost 38% of their body weight, and one-third had died from malnutrition. The third and steepest slope defines the effect of starvation combined with critical illness, when the time taken to reach a functionally significant or fatal weight loss may be halved.
but thereafter, essential glucose is provided by new glucose derived from conversion of protein, lactate, and glycerol (gluconeogenesis). The brain, which normally derives its energy from glucose, adapts to metabolize ketones from liver fat metabolism, thereby reducing the necessity to convert protein to glucose. With longer periods of starvation metabolic rate falls further, pari passu with loss of lean mass. These adaptive mechanisms are overridden in the presence of acute illness or injury, which is characterized by increased metabolic rate and protein catabolism. Such short periods of starvation result in less than 5% reduction in body weight, but identifiable, if small, reductions in function. Vasoconstriction to conserve heat is reduced, thereby impairing heat conservation in the body, an important consideration in cold environments. Mild sensations of cold, irritability, and loss of energy may be experienced. Reduced glycogen stores in liver and muscle also impair athletic performance. Short periods of starvation have also been shown to be important in patients undergoing surgery, in whom avoidance of starvation for more than 2 h preoperatively, and for more than a few hours postoperatively, has been shown to improve outcome and the rate of recovery from operation.
Partial or Complete Starvation >5 days with 5% Weight Loss
Degrees of Starvation
Fasting up to 72 h
This induces physiological adaptations designed to conserve protein, and hence the mass and function of essential tissues and organs, while mobilizing reserves of fat. REE, after an initial rise, falls by 10%. Initially glucose is released from liver glycogen,
This results not only in the adaptive responses described above, but also in further impairment of mental and physical function. Individuals react by reducing their physical activity and hence TEE. Mood and muscle strength also deteriorate. If, however, sufficient food is reintroduced to maintain weight at its new level, the individual adapts to the new lower weight and function returns. However, if food intake continues to be inadequate, resulting in further weight loss, then clinically important reductions in function become apparent. It has been recommended by both American and European authorities that surgical patients should not be allowed to starve for more than 7 days postoperatively without feeding by natural or artificial means.
Starvation >7 days and Weight Loss >10%
Figure 1 Percentage weight loss during semistarvation, total starvation, and disease-associated starvation. Reproduced from Allison SP (1992) The uses and limitations of nutritional support. Clinical Nutrition 11: 319330. 1992. With permission from Elsevier.
With this degree of malnutrition or greater, a number of significant functional changes occur. Some of these are illustrated in Figures 2 and 3, taken from the studies of Keys and coworkers on young male volunteers who underwent 24 weeks of semistarvation, followed by a further 24 weeks of controlled refeeding. Expressing changes in body composition (Figure 2) and changes in function (Figure 3) as a percentage of their starting value, it can be seen that
132 STARVATION
Figure 2 Body compositional changes (% starting value) in 12 male volunteers during 24 weeks of semistarvation, followed by 24 weeks of controlled refeeding. Adapted from the data of Keys et al. (1950) by Allison SP (1992) The uses and limitations of nutritional support. Clinical Nutrition 11: 319330. 1992. With permission of Elsevier.
Figure 3 Changes (% starting value) in weight, depression score, hand muscle strength, and fitness score in 12 male volunteers during 24 weeks of semistarvation followed by 24 weeks of controlled refeeding. Adapted from the data of Keys et al. (1950) by Allison SP (1992) The uses and limitations of nutritional support. Clinical Nutrition 11: 319330. 1992. With permission of Elsevier.
there is a progressive deterioration in mental and physical function as semistarvation continues and tissue is lost. With refeeding, restoration of fat mass is faster than that of lean mass, and there is a correspondingly slow return of mental and physical function over many weeks. A large amount of detailed data have accrued in the literature concerning functional change due to starvation.
Growth and Development
Muscle Function
Muscle strength diminishes progressively, not only through reduced mass but also through metabolic effects, independent of change in mass. These changes affect particularly the type 2 muscle fibers prevalent in the diaphragm, so that respiratory capacity is impaired, causing reduced exercise tolerance and increasing the risk of respiratory complications of illness or surgery.
Immune Function
In children, growth and development are retarded, with reduced height for age (stunting) and weight for height (wasting), compared with normal values for the population. Growth velocity also slows compared with premorbid values. Puberty and normal sexual development are delayed and bone age is retarded. Intellectual and cognitive attainment may also be permanently affected by prolonged infant malnutrition. Malnutrition during fetal and neonatal life, paradoxically, also predisposes to chronic diseases in later life such as obesity, diabetes, heart disease, and stroke.
Lymphocyte count, white cell function, and immune responses are reduced, predisposing to invasive infection.
Wound Healing
This appears to be particularly sensitive to recent food intake. A combination of previous weight loss and inadequate food intake, therefore, renders patients vulnerable to failure of wound healing, as well as to other complications of surgery. Malnutrition is also a
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risk factor for pressure sores in the elderly and impairs their healing.
Thermoregulation
Starvation for more than 48 h reduces heat conservation by cutaneous vasoconstriction. Severe weight loss also impairs the increase in metabolic rate due to a cold stimulus. Both these physiological defense mechanisms to maintain normal body core temperature are therefore reduced in thin, undernourished individuals, rendering them prone to hypothermia in a cold environment. Since a reduction in core temperature of as little as 12 C reduces coordination, cognitive function, and muscle strength, such individuals are prone to injury and death in cold conditions. In the studies of severe malnutrition, with weight loss in excess of 30%, carried out by Jewish physicians in the Warsaw ghetto in 1942, low body temperatures were noted, as well as the lack of fever in response to intercurrent infections with typhoid, tuberculosis, and pneumonia.
Gastrointestinal Function
resistance, and high levels of the catabolic hormones, catecholamines, glucogen, and cortisol, explaining at least in part the overriding of the adaptive response to starvation by the catabolic response to injury. Gonadotropin and sex hormone (testosterone and estrogen) levels fall. Menstruation ceases below a body mass index (BMI) of 17, in anorectic girls, and resumes as BMI is restored above this level.
Fluid and Electrolytes
The study of Keys and coworkers showed that, as lean and fat mass decrease during starvation, the extracellular fluid volume shrinks more slowly and actually increases as a percentage of body weight. This is associated with a decreased capacity to excrete a salt and water load, a phenomenon that is further exacerbated by the response to injury and disease. Such starved individuals may therefore suffer from famine edema, depending on their intake of salt and water. Too-rapid refeeding may worsen edema and cause death from pulmonary edema.
Clinical Outcome and Treatment
With very low levels of body weight secondary to malnutrition, pancreatic enzyme secretion is impaired and the small-bowel mucosa may show atrophic changes. Gastric acid secretion is also blunted. In severe famines, diarrhea is also a feature, exacerbated by too-rapid refeeding, which may cause fatal fluid and electrolyte imbalance.
Cardiovascular System
Malnutrition results in loss of cardiac muscle and impaired cardiovascular reserve. Bradycardia, hypotension, a 45% reduction in cardiac output, and electrocardiographic abnormalities, including prolongation of QT interval, were observed in the semistarvation studies conducted by Keys and coworkers. Similar changes have been described in other studies, with weight loss ranging from 15% to 30%. These changes also pose risks for refeeding with its sudden increase in metabolic demand, reloading with salt and water, and falls in serum potassium, phosphate, and magnesium concentrations (refeeding syndrome). Heart failure, and even death, may be precipitated by aggressive and rapid feeding of such individuals.
Endocrine Function
With progressive starvation alone, insulin levels fall, allowing lipolysis, ketosis, and the primary use of fat as fuel. Sympathoadrenal activity is also reduced. These changes are overridden by injury, which is characterized by high insulin levels with insulin
Mortality and morbidity rates from prolonged starvation, with or without injury, disease, or surgery, are increased in proportion to the degree of undernutrition. In those who survive, convalescence and rehabilitation are prolonged and quality of life is reduced. Early identification of nutritional risk and appropriate nutritional support by natural or artificial means improves function, even before any regain of lean mass, reflecting the immediate impact of nutrition on cell and tissue function. Appropriate feeding of the sick also reduces complications and mortality, and shortens rehabilitation and length of hospital stay. In a review of 166 controlled trials (7630 patients) of oral food supplements in addition to normal food, there was an average reduction in mortality of 24%, with the greatest reduction among those who were underweight (BMI < 20 kg m2); complications were reduced from 45% to 21%; length of hospital stay was reduced by 13 days, with financial savings of between 352 and 179 per patient. A review of 121 trials (4090 patients) of artificial tube feeding by the enteral route showed mortality reduction from 23% to 11%, with complications (particularly infections) reduced from 48% to 33%. Artificial feeding by the intravenous (parenteral) route may be life-saving in conditions causing prolonged gastrointestinal failure. All artificial feeding techniques, by the enteral or parenteral route, have their own inherent risks in inexpert hands and in each case these risks must be weighed against the potential benefits of treatment. In expert hands,
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however (and most major hospitals should have an expert team), the risks are low. Excessive complication rates resulting from techniques of nutritional support reflect upon the standard of care provided and raise questions concerning the competence of the institution concerned to provide such care. There is sufficient evidence to support the view that failure to detect nutritional risk and to treat accordingly (subject to ethical and clinical considerations) constitutes substandard medical management. In terminal cancer and late-stage Alzheimer disease, for example, the risks of treatment usually outweigh the likely benefits. In many other medical and surgical conditions, however, nutritional support is highly beneficial. It is axiomatic that appropriate nutritional treatment (as with any other form of treatment) cannot be given unless the problem is first identified and defined.
Current weight should be compared with remembered weight. An involuntary weight loss of >5% over 3 months due to illness is regarded as significant, and >10% definitely so. Food intake and disease severity Enquiry should be made concerning any recent decrease in food intake, whether due to lack of availability or secondary to disease. These simple measurements may be combined in a simple scoring system, which has been validated to detect nutritional risk and the need for intervention. Those found to be at risk may need more detailed assessment before an appropriate plan can be developed and a clinical decision made as to the most appropriate method and route of administration.
More Detailed Assessment
Detection of Nutritional Risk

In community and hospital medical practice, rapid screening followed by more detailed assessment of patients found to be at risk should be part of routine protocols. These techniques have also been used in public health surveys and under famine conditions.
Nutrition Screening
Height, weight, and body mass index Height (or length in infants) and weight have long been used by pediatricians to plot serial changes in weight for age, weight for height, and growth velocity, all of which are very sensitive to the adequacy of nutritional intake. In adults, the BMI (weight in kilograms divided by height in meters squared) is the most commonly used measure of an individuals current nutritional status. In assessing BMI, racial characteristics should be taken into account. There are many thin but perfectly healthy individuals in India, for example, although with diminished reserves in the face of disease or sudden famine. The figures in Table 1 apply to a UK population.
Table 1 Body mass index correlated with risk level for a UK population
Body mass index Risk level
<11 (men) <10 (women) <18.5 18.520 2026 3040 >40
High risk of death High risk of death Undernourished (increased risks, decreased function) Possibly undernourished Normal range Obese Morbidly obese
Anthropometric measurements, such as mid upperarm circumference (MAC) and triceps skin fold (TSF) thickness, are not only surrogates for weight when compared with reference tables for age and sex, but also give a measure of body composition or the proportions of residual fat and muscle. Functional assessment can be obtained from a history of mental and physical performance and observation during simple physical tasks, such as rising from a chair or climbing stairs. Current appetite and the ability to chew, swallow, and digest food will determine which route and method of feeding are most appropriate. A number of simple tests are useful in clinical practice: hand dynamometry for muscle strength; expiratory flow for respiratory function; mood score and cognitive tests for mental function; food intake can also be assessed formally by 57-day food diaries or by a recording observer; and disease severity and likely impact of this on subsequent nutritional status should be recorded. Metabolic rate and nutritional requirements can be calculated from standard formulae or tables based on age, sex, weight, and height. Allowances can then be made for activity and the catabolic effects of disease. Laboratory tests include hematological tests for anemia secondary to deficiency of iron, folate or vitamin B12, or to disease. Lymphocyte count may be reduced in undernutrition. Biochemical tests include serum albumin, which reflects inflammation and dilution with fluid rather than protein deficiency; levels of minerals, e.g., calcium, magnesium, and zinc, and, in some cases, levels of vitamins and micronutrients, although most of these are only available in specialist laboratories. Blood and urine urea values reflect protein turnover, as well as renal function, and are reduced in starvation. Blood and urinary
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creatinine levels are not only tests of renal function but are proportional to muscle mass and are low in malnutrition.
Autopsy Findings
The reports of autopsies carried out in the Warsaw ghetto provide graphic accounts of the pathological changes in extreme starvation, with >30% weight loss. Length, weight, and BMI should always be reported in those dying from or with malnutrition. Calculation of BMI will, of course, be affected by the elements of edema or dehydration, which should be noted. The body appears cachectic with loss of subcutaneous fat and atrophy of muscle. The epidermis is thin with increased cornification and pigmentation due to melanin with, in severe cases, pressure sores. Dependent edema may also be present, with effusions into the pericardial, pleural, and peritoneal cavities. The organs, apart from the brain, appear atrophic. The heart weight is decreased, with brown atrophy. The spleen, liver, and kidneys may also be atrophied. The adrenals, though of normal size, have a narrow cortex. The lungs often show features of terminal bronchopneumonia. It is easy to overlook the features of malnutrition in ascribing death to the agonal event, which may be bronchopneumonia, intestinal infection, or heart failure, secondary to starvation and weight loss.
Ethical and Legal Aspects of Difficult Clinical Problems Involving Feeding

These have been reviewed in detail by Lennard-Jones in a report for the British Association for Parenteral and Enteral Nutrition, and can only be summarized briefly here. All clinical decision-making, including the provision of adequate amounts of food and drink, is governed by ethical and legal as well as clinical considerations. The ethical principles of autonomy (patient decides), beneficence (does treatment benefit the patient?), nonmalfeasance (do no harm), and justice (equal treatment for all), are well known and have already been mentioned in relation to nutritional support in a number of clinical circumstances. These principles also underlie the law under which doctors and other carers practice. The highest judicial authorities in the USA and UK have ruled that, whereas normal feeding and drinking by mouth are parts of basic care, artificial feeding by tube into the gastrointestinal tract or into a vein is medical treatment and should be governed by the same sort of considerations as other medical treatments. Additionally, in ethics
and in law, there is no difference in principle between deciding not to start treatment or to withdraw it. The patient is entitled to refuse food and drink, and this must be respected unless he/she is legally incompetent to decide or is suffering from a psychiatric condition, e.g., anorexia nervosa, within the meaning of the Mental Health Act. One may contrast the voluntary action of political hunger strikers, in whom no attempt was made at artificial feeding, with the tube feeding of a murderer undergoing a life sentence. The latter was fed, not because he was on hunger strike, but because he was deemed to be suffering from a psychiatric illness. In general, although carers are obliged by the law concerning duty of care, and also under the European Law on Human Rights, to offer food and drink and to do their best to help patients to consume it, they are not obliged to force-feed or to give artificial feeding where consequent suffering or harm exceeds any likely benefit. Such decisions are sensitive and should only be taken after careful consultation with all those involved, although at present, in the UK, relatives or a nominated proxy cannot make a decision on behalf of an adult patient. The situation with minors is different. A legal judgment has been quoted by Ashby and Stofell that expresses this concept of the role and limitation of medicine: Medical science and technology has advanced for a fundamental purpose: the purpose of benefiting the life and health of those who turn to medicine to be healed. It surely was never intended that it be used to prolong biological life in patients bereft of the prospect of returning to an even limited exercise of human life. Although there are some situations, e.g., stroke, where it is appropriate to undertake a therapeutic trial of artificial feeding for an agreed period, followed by withdrawal if the treatment appears futile or harmful, there are other, more difficult circumstances in which the patient is incompetent to decide for him/herself and where the help of the courts may need to be sought. The classic example, following the Bland case in the UK, is that of severe brain damage, causing a persistent vegetative state, in which the highest legal authorities gave permission for withdrawal of tube feeding if, in the doctors opinion, it was in the patients best interests. Assessment of whether the care of any individual, in respect of food and fluid, falls below acceptable standards, is unethical or unlawful, or is negligent, requires very careful consideration of all the facts and circumstances, and whether intervention would have been beneficial, futile, harmful, ethical, or lawful. Important forensic considerations, particularly in the case of a young child or elderly and infirm person, are whether the individual was intentionally
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starved of food or was neglected by those with a legal duty of care. Starvation may also be a consequence of accidental entrapment, e.g., in tunnels, or kidnapping and unlawful imprisonment. In these conditions, death may occur early from dehydration or hypothermia before significant malnutrition can develop. The course of starvation in these situations may be contrasted with the slow deterioration seen in the long course of deliberate self-starvation for political ends, in which fluid intake is usually adequate, and in which survival of up to 3 months is possible, or even longer in those who were initially overweight. It should be remembered that the dying process from old age or from disease is associated with decreased appetite and thirst. Suffering should not be increased by well-meaning attempts to press unwanted nourishment during the final phase of life.
See Also
Consent: Treatment Without Consent; Medical Malpractice: Nursing Issues
Further Reading
Airedale NHS Trust v. Bland: Judgements of Family Division, Court of Appeal (Civil Division) and House of Lords (1993) In: Fennell P, Harpwood V, Hohnson H, Ngwena C (eds.) Butterworth Medico-Legal Reports vol. 12, pp. 64143. Allison SP (1997) Impaired thermoregulation in malnutrition. In: Kinney JHM, Tucker HN (eds.) Physiology, Stress and Malnutrition. Functional Correlates, Nutritional Intervention, pp. 571593. Philadelphia, PA: Lippincott-Raven. Ashby M, Stofell (1995) Artificial hydration and alimentation at the end of life: a reply to Craig. Journal of Medical Ethics 21: 135140. Bursztein S, Elwyn DH, Askanazi J, Kinney JM (1989) Energy Metabolism, Indirect Calorimetry, and Nutrition. Baltimore, MD: Williams and Wilkins. Elia M (1997) Tissue distribution and energetics in weight loss and undernutrition. In: Kinney JM, Tucker HN
(eds.) Physiology, Stress and Malnutrition. Functional Correlates Nutritional Intervention, pp. 383412. New York: Raven Press. Elia M, Lunn PG (1996) Biological markers of proteinenergy malnutrition. Clinical Nutrition 16: 146. Gibson RS (1990) Principles of Nutritional Assessment. New York: Oxford Univeristy Press. Gillick M (2000) Rethinking the role of tube feeding in patients with advanced dementia. New England Journal of Medicine 342: 206210. Hill GL (1992) Disorders of Nutrition and Metabolism in Clinical Surgery. Edinburgh, UK: Churchill Livingstone. James WPT, Ferro-Luzzi A, Waterlow JC (1988) Definition of chronic energy deficiency in adults. European Journal of Clinical Nutrition 42: 969981. Lennard-Jones JE (1998) Ethical and Legal Aspects of Clinical Hydration and Nutritional Support. Maidenhead, UK: British Association for Parenteral and Enteral Nutrition. Morgan JB, Dickerson JWT (eds.) (2003) Nutrition in Early Life. Chichester, UK: Wiley. Paris JJ (1993) Ethical issues in withholding or withdrawal of nutrition and fluids. Clinical Nutrition 12(suppl.): S12S15. Payne-James J, Grimble G, Silk DBA (eds.) (2001) Artificial Nutrition Support in Clinical Practice. London: Greenwich Medical Media. Rosenberg IH, Sastre A (eds.) (2002) Nutrition and Aging. Nestle Nutrition Workshop Series, Clinical and Performance Program, vol. 6. Basel, Switzerland: Karger. Royal College of Physicians Report (2002) Nutrition and Medicine: a Doctors Responsibility. London: Royal College of Physicians. Shils ME, Olson JA, Shike M, Ross AC (eds.) (1999) Modern Nutrition in Health and Disease, 9th edn. Philadelphia, PA: Lippincott/Williams and Wilkins. Stratton RJ, Green CJ, Elia M (2003) Disease-Related Malnutrition: An Evidence-Based Approach to Treatment. Wallingford, UK: CABI Publishing. Tanner JM, Whitehouse RH, Takaishi M (1965) Standards from birth to maturity for height, weight, height velocity and weight velocity: British children. Archives of Diseases in Childhood 41: 613635.
SUBSTANCE MISUSE/Medical Effects 137
SUBSTANCE MISUSE
Contents Medical Effects Cocaine and Other Stimulants Herbal Medicine Heroin Substitution Drugs Sedatives Miscellaneous Drugs Urine Analysis Hair Analysis Alternative Body Fluids Analysis Patterns and Statistics Crime
Medical Effects
M M Stark, St. Georges Hospital Medical School, Epsom, UK
History and Examination

Substance Misuse History
Introduction
Substance misuse can result in medical and health complications that may be specific to the particular drug of use, or may be generic, in that they are caused by the manner of substance misuse. Medical complications resulting from substance misuse may be the method of presentation of an underlying problem without any current symptoms and signs of specific drugs. Findings from the British Crime Survey 2002/2003 show that, of all 1659-year-olds, 12% had taken an illicit drug and 3% had used a class A drug (lysergic acid diethylamide (LSD), cocaine, crack, ecstasy, heroin, magic mushrooms, and methadone) in the last year. This equates to about 4 million illicit drug users and around 1 million class A drug users. Cannabis is the most frequently used illicit drug around 3 million 1659-year-olds have used it in the last year. Levels of drug use in the UK have remained stable since 2001/2002. In this article the medical effects of substance misuse will be summarized, including the infective, vascular, pulmonary, psychiatric, and noninfective complications. The importance of a comprehensive substance misuse history and full physical and mental state examination will be stressed, and guidance outlined regarding reducing the harm resulting from substance misuse.
In the custodial environment the medical history should concentrate on current drug use and in particular the type(s) of substance(s) misused; the duration of substance misuse; the quantity taken per day on an average/typical day, and/or amount spent on substances; the frequency of use; the route of administration (noting sites of any injection); the amount used in the last 2448 h; the time of the last dose(s); use of alcohol; and whether any substitution treatment is being prescribed. A specific enquiry regarding the concomitant use of other substances, including those legitimately prescribed, and alcohol should be made. Alcohol dependence is often not recognized or reported by substance misusers. Alcohol withdrawal may complicate other presenting symptoms and signs and carries a significant morbidity and mortality. Current and relevant past medical and psychiatric history should also be noted.
Physical Examination
The examination should concentrate on whether there are any physical signs of intoxication, withdrawal, or evidence of dependence. Physical signs will depend on the substances used but consideration should be given to documentation of the conscious level, blood pressure and pulse, temperature, pupil size, eye movements, and tests for coordination. General physical examination may give clues to illicit substance misuse with evidence of neglect, poor nutritional state, dental caries, and weight
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loss. The presence of fresh needle marks and other skin stigmata of intravenous drug misuse, including fresh abscesses, older healed abscesses, and track marks due to scarring and hyperpigmentation of the skin over the veins, may be seen. Atrophic scarring may occur from injecting subcutaneously skin popping. Evidence of muscle wasting and obliteration of the normal anatomical landmarks of the hands due to lymphedema may occur. Tattoos may be used to hide evidence of drug injection and may have a drug theme.
Polydrug Use and Tolerance
Misuse of more than one drug polydrug use is increasingly common and the result is that the expected symptoms, signs, and effects of misused substances are more difficult to predict. Drug combinations may result in additive or synergistic effects, or antagonism may occur. Findings on examination will vary with the substances misused and the method of administration. Tolerance occurs with regular use of a drug, resulting in the drug being metabolized more quickly and the duration and peak intensity of the desired effect reduced, for example, as occurs with alcohol. Metabolic cross-tolerance may occur where the chronic use of one drug reduces the pharmacological effect of a second drug, for example, alcohol and benzodiazepines. Central nervous system (CNS) tolerance occurs when the CNS adapts gradually to the action of a given drug as the original dose of the drug used has a reduced effect, e.g., opiates. However, CNS tolerance to different effects of a drug does not necessarily develop at the same rate or may not develop to all the effects. For example, tolerance develops rapidly to the sedative/hypnotic effects of the benzodiazepines but not to the respiratory-depressant effects.
Clinical Syndromes
Harmful use is a pattern of psychoactive substance use that is causing damage to health. The damage may be physical (e.g., hepatitis following injection of drugs) or mental (e.g., depressive episode secondary to heavy alcohol intake). Dependence syndrome is a cluster of behavioral, cognitive, and physiological phenomena that may develop after repeated substance use. Typically these phenomena include a strong desire to take the drug, impaired control over its use, persistent use despite harmful consequences, a high priority given to drug use rather than to other activities and obligations, increased tolerance, and a physical withdrawal reaction when drug use is discontinued. Withdrawal syndrome is a group of symptoms of variable clustering and degree of severity, which occur on cessation or reduction of use of a psychoactive substance that has been taken repeatedly, usually for a prolonged period, and/or in high doses. The symptoms may be accompanied by signs of physiological disturbance. Withdrawal can be complicated by delirium, as seen with alcohol.
Infective Complications of Injection

Injection carries a high risk of infection: needles and syringes are often used on more than one occasion and works (needles, syringes, spoons, etc.) shared with others. Resulting infection may be local or systemic (hepatitis and human immunodeficiency virus (HIV)). Drugs themselves may on occasions be contaminated with bacteria such as Clostridium. Local infections such as cellulitis and abscesses may occur at the site of skin popping or mainlining. The majority of bacteria isolated from injection sites are Staphylococcus aureus and 20% are Streptococcus species. Anaerobes such as Bacteroides and Clostridium species, including Clostridium botulinum, have also been reported. The risk of infective complications is greater when cocaine is injected simultaneously as this encourages anaerobic conditions. Areas of infection may be complicated by local thrombophlebitis and the general irritant effect of injected drugs. Nectrotizing fasciitis may also occur. Treatment includes rest and elevation, cleaning and dressing any wounds, and incising abscesses as appropriate. Swabs should be taken for bacteriological culture and sensitivity, and antibiotic treatment should be initiated. Admission to hospital should be considered if the infection is severe or if the individual is toxic. Endocarditis may occur in substance misusers with normal hearts, often with a more unusual organism, including Staphylococcus aureus, Pseudomonas, or Candida. Characteristic skin manifestations may
Clinical states that may occur following substance use include, for example, acute intoxication, harmful use, dependence syndrome, and withdrawal syndrome. Intoxication is a condition that follows the administration of a psychoactive substance and results in disturbance in the level of consciousness, cognition, perception, judgment, affect or behavior, or other psychophysiological functions and responses. The disturbances are related to the acute pharmacological effects of, and learned responses to, the substance and resolve with time with complete recovery, except where tissue damage or other complications have arisen. Intoxication is highly dependent on the type and dose of drug and is influenced by an individuals level of tolerance and other factors.
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be seen, such as splinter hemorrhages. This should be suspected in any misuser who has pyrexia and a changing heart murmur. Substance misusers may also present with septic arthritis, osteomyelitis (hematogenous) with septic emboli seen in vertebrae, nephritis, bacterial pneumonia, and septicemia.
Bloodborne Viruses
Noninfective Complications
A variety of noninfective complications may occur: . Amyloidosis is a possible complication of chronic skin infection associated with subcutaneous injection (skin popping). . Anaphylaxis may occur as an acute allergic response to a drug or its contaminants. . The patient may experience constipation from chronic opiate use. . There may be dental decay, especially with methadone mixture. . Malnutrition may be linked to a generally chaotic lifestyle or lack of money. Opiates and amphetamines result in anorexia and drugs such as volatile substances can cause nausea and vomiting. Alcohol can produce intestinal change, impeding the absorption of nutrients; gastritis and peptic ulceration may occur. Chronically alcohol consumption is associated with deficiencies in thiamine, folate, pyridoxine, vitamin B12, magnesium, and zinc. . Accidental overdose may occur and early recognition and appropriate treatment may help to reduce deaths from overdose. . Kidney failure may result from an immunological reaction or damage to blood vessels. It can also be secondary to rhabdomyolysis seen in relation to raised body temperature caused by drugs such as cocaine and related methylated amphetamines, including 3,4-methylene-dioxymethamphetamine (ecstasy).
The prevalence of HIV in intravenous drug users in the UK is 1% overall and up to 3.5% in London. This results from the sharing of injecting equipment and sexual contact, particularly drug users who turn to prostitution to fund their habit. The prevalence of hepatitis B in intravenous drug users in the UK is 1015% and of hepatitis C up to 80%. Transmission of hepatitis B can occur via shared injection equipment, by saliva, sexual contact, and vertically from mother to child. Delta virus infection may be superimposed on hepatitis B infection. Several large outbreaks of hepatitis A have occurred in intravenous drug users. Transmission occurs percutaneously in the viremic phase through needle sharing and via the fecaloral route. Chronic hepatitis, chronic persistent hepatitis (which is relatively benign), chronic active hepatitis (which is progressive), cirrhosis, and primary hepatocellular carcinoma may result.
Vascular Complications
Vascular complications may occur when injection is accidentally made into an artery, which may result in vascular spasm with ischemia. Gangrene and amputation may follow accidental injection into an artery and prolonged arterial spasm. False aneurysms may develop. Deep-vein thrombosis may complicate intravenous injection and pulmonary embolus may occur as well as localized superficial thrombophlebitis. Chronically, complications include limb swelling resulting from lymphedema and postphlebitic changes, varicose eczema, and varicose ulcers.
Mental Health
Comorbidity (dual diagnosis) of substance misuse and severe mental illness is common and the risk of deliberate self-harm is increased in those with a history of dependence. A brief mental state assessment should be performed on detainees with substance misuse problems in general, and in particular, on any acutely disturbed patient. This should cover general behavior, speech, mood, abnormal beliefs and/or experiences, and cognitive state. It may be that a mental state examination needs to be deferred until a detainee is no longer acutely intoxicated. This may lead to the identification of a coexistent psychiatric illness, such as schizophrenia, which needs treatment. Identification of a mental illness or the presence of a psychotic state may affect responsibility for an offense and fitness to be interviewed by the police. Substance misuse may also be associated with a psychotic state through a number of mechanisms, including intoxication (e.g., with cannabis and stimulants) and withdrawal (alcohol and benzodiazepines).
Pulmonary Complications
Pulmonary complications are common in substance misusers who inject, from introduction of particulate matter in the form of crushed tablets or adulterants of illicit drugs. Microemboli occur in the lungs, resulting in pulmonary infarction. Pneumothorax may occur after the forced inhalation of drugs such as cocaine. Noninfective respiratory wheeze occurs with opiate withdrawal. The prevalence of tuberculosis is increased, and is associated with poor living conditions, malnutrition, and immunological suppression.
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The psychotic state will be characterized by hallucinations and delusions with a clear consciousness. Thought disorders may be present and the individual may lack insight into the condition. Panic reactions may occur with fear and agitation or an organic mental state with confusion and clouding of mental functioning. Individuals are often perplexed and frightened and perceptual disorders such as hallucinations and illusions are present. A physical examination with documentation of pulse, blood pressure, and temperature should be recorded, and urinalysis for drugs of abuse sent for toxicological analysis, if possible. Individuals with acute behavioral disturbance should not be taken to a custody suite but directly to an emergency department. Occasionally, forensic physicians may be asked to attend a custody suite and give advice on the management of these detainees. Reassurance should be given to these patients that the unpleasant effects are drug-related and will improve as the drug is metabolized and eliminated from the body.
Rapid Tranquilization
Drug-Related Deaths
It should be remembered that deaths may occur from immediate use of a drug and chronic diseases resulting from, for example, virus infections. Death from drugs may result from a variety of toxic effects, including the nature of the drug itself, the dose, and the purity of the drug. Changes in purity of a drug supply may be responsible for some accidental deaths, and substance misusers have minimal control over dosage and content of illicit substances taken. Loss of tolerance may lead to death from overdose, as may occur soon after release from prison. Impurities may be present in street drugs that may also lead to untoward effects. As mentioned previously, drug use is rarely confined to a single substance and combinations of drugs often result in additive effects that are potentially more life-threatening. The simultaneous consumption of opiates and benzodiazepines, opiates and alcohol, and alcohol and benzodiazepines are all dangerous combinations. Fatalities may occur due to accidents and other risky behavior secondary to impairment in mental functioning. Many drugs alone or in combination impair reaction time and coordination and impair judgment. Violence related to drug dealing, domestic violence, and homicide may occur.
Occasionally consideration may have to be given to rapid tranquilization if other approaches have failed to de-escalate the acutely disturbed behavior. The forensic physician may decide that the detainee needs to be transferred to hospital and sedation is required to facilitate that transfer, and to reduce suffering for the detainee prior to further assessment, or appropriate disposal. The use of medication for rapid tranquilization in the police station is a serious step because of the possibility of oversedation and loss of consciousness. This is particularly so because detainees may have taken other drugs which interact with those used for rapid tranquilization, leading to serious additive effects in terms of CNS depression. Therefore, extreme caution is needed before sedating any such patient and adequate safeguards must be in place to ensure the individuals safety. The presence of paramedics should be considered, as the skills and equipment required for cardiopulmonary resuscitation need to be available. The use of oral treatment is preferred and has been shown to be as effective as parenteral medication. Lorazepam 12 mg and/or either olanzapine 10 mg or risperidone 12 mg may be used. Rarely, intramuscular treatment may have to be considered. Consideration should be given to seeking specialist advice and the legal status of the detainee. The ongoing monitoring of the detainee will need to be ensured.
Harm Reduction
Substance misusers should receive advice on a number of issues when the opportunity arises. Treatment should be given for any current medical problems and consideration of referral to local agencies and/or drug arrest referral schemes. Education on the risk of overdose (including loss of tolerance and multiple drug use) and sexual health issues (including contraception and sexually transmitted diseases) should be provided. Advice can be given to reduce the harm of injecting practices. It is better to smoke rather than inject, and to inject into veins and avoid muscle or skin if possible. Only a small amount of citric acid should be used to dissolve the heroin as the citric acid can damage muscle and other tissue under the skin, giving the bacteria a better chance to grow. Different sites should be used for injecting different drugs and clean needles and syringes obtained, avoiding sharing any drug paraphernalia. Medical help should be sought if there is any redness or pain at the injection site or pus collecting under the skin. General awareness of bloodborne viruses should be increased and hepatitis B vaccine offered.
SUBSTANCE MISUSE/Cocaine and Other Stimulants 141
Special Investigations
Special investigations may contribute to the overall assessment of a detainee. A full blood count may reveal anemia; folate and vitamin B deficiency (raised mean corpuscular volume (MCV)) resulting from alcohol misuse; raised white cell count associated with injecting and infection; a low white count may occur from bone marrow depression from solvent misuse. Raised liver enzymes suggest liver damage, which may occur from hepatitis associated with alcohol misuse and injecting. A raised urea level suggests kidney damage from solvent misuse; nephrotic syndrome and renal damage also occur with misuse of minor analgesics. Wassermann reaction and Treponema pallidum hemagglutination (TPHA) test that are positive for syphilis and hepatitis B and C, and HIV antibody test, indicate hepatitis B, C and HIV infection. Chest X-ray may reveal undiagnosed pathology with evidence of pulmonary embolism, infarction, or hypertension. Pneumonia and tuberculosis may occur, or aspiration pneumonia in those misusers who may have been unconscious following overdose. Urine testing may reveal the presence of the parent drug or of metabolites. Such tests give qualitative rather than quantitative results and confirm whether a substance has been used rather than the actual amount used. Any on-site rapid urine-testing kit will give a proportion of false-positives and -negatives and results should be interpreted in the light of a full clinical assessment.
of the Association of Forensic Physicians (available from www.afpweb.org.uk). Stark MM (2003) Substance misuse. In: Payne-James JJ, Busuttil A, Smock W (eds.) Forensic Medicine: Clinical and Pathological Aspects, pp. 513524. London: Greenwich Medical Media. Stark MM, Norfolk G (2000) Substance misuse. In: Stark MM (ed.) A Physicians Guide to Clinical Forensic Medicine, pp. 179219. Totowa, NJ: Humana Press. Stark MM, Payne-James JJ (2003) Symptoms and Signs of Substance Misuse. London: Greenwich Medical Media. World Health Organization (1994) Lexicon of Alcohol and Drug Terms. Geneva: World Health Organization.
Cocaine and Other Stimulants

F J Couper, Office of the Chief Medical Examiner, Washington, DC, USA
Introduction
Cocaine and methamphetamine are highly addictive central nervous system (CNS) stimulants, and are among the worlds most frequently abused illicit drugs (Table 1). Prescription medications such as amphetamine and methylphenidate (Table 2) are also abused for their stimulant properties. Historically used to treat asthma and other respiratory problems, these prescription drugs are now largely indicated for the treatment of obesity, narcolepsy, and neurological disorders. Ephedrine is another popular stimulant drug available in a variety of dietary and herbal supplements. A large factor in the popularity of stimulant drugs is their widespread availability and relatively low cost. They are abused by addicts for their intense euphoric and stimulant effects; by teenagers and adults (particularly females) to suppress appetite; by athletes to improve physical performance; by truck drivers and students for their ability to keep the user awake; and are commonly administered with club drugs at dance clubs and parties. 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) and other designer amphetamine drugs also have mild stimulant properties.
See Also
Substance Misuse: Miscellaneous Drugs; Patterns and Statistics; Crime
Further Reading
Association of Police Surgeons, Royal College of Psychiatrists (2000) Substance Misuse Detainees in Police Custody. Guidelines for Clinical Management, 2nd edn. Report of a Medical Working Group. Council Report CR81. London: Royal College of Psychiatrists. Ghodse H (2002) Drugs and Addictive Behaviour. A Guide to Treatment, 3rd edn. Cambridge, UK: Cambridge University Press. Home Office (2000) A Report by The Advisory Council on the Misuse of Drugs. Reducing Drug-Related Deaths. London: The Stationery Office. Norfolk GA, Stark MM (2003) Acute Behavioural Disturbance. Guidelines on Management in Police Custody. East Kilbride, UK: Education and Research Committee
Cocaine
Cocaine is a naturally derived CNS stimulant extracted and refined from the leaves of the coca plant (Erythroxylon coca). Such plants are grown primarily in the Andean region of South America
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Table 1 Common illicit stimulant drugs
Stimulant Common street name
Cocaine hydrochloride Cocaine base Methamphetamine Amphetamine
Blow, caine, coke, dust, flake, lady, nose candy, shake, snow, stardust, toot, white Crack, free-base, rock Chalk, chrissy, crank, crystal, glass, go, hydro, ice, meth, rock candy, speed, whiz Crank, dex, speed
Table 2 Commonly misused prescription and over-the-counter stimulant drugs

Stimulant Common or brand name Indication for use
Methamphetamine Amphetamine Methylphenidate Ephedrine
Desoxyn Adderall, Benzedrine, Biphetamine, Dexedrine, DextroStat, Gradumet Ritalin Ephedra, ma huang, desert tea, and many others
Narcolepsy, ADD, ADHD Narcolepsy, ADD, ADHD, weight control ADHD Herbal supplement, diet aid
ADD, attention deficit disorder; ADHD, attention deficit hyperactivity disorder.
and, to a lesser extent, in India, Africa, and Indonesia. For over 2000 years, the coca leaves have traditionally been chewed or brewed into a tea and used in religious ceremonies, as a refreshment, and to relieve fatigue. The coca leaves can also be dried and crushed as part of the process to extract the alkaloid, resulting in coca paste which is eventually used to produce cocaine hydrochloride. This form of cocaine is a white to light-brown crystalline powder with a bitter, numbing taste. Cocaine hydrochloride is typically injected or snorted by the user rather than smoked. The hydrochloride salt tends to burn rather than vaporize; hence smoking is an inefficient method of drug ingestion. Crack is the street name given to cocaine that has been processed from cocaine hydrochloride. This form of cocaine can be smoked and produces a distinctive crackling sound when smoked. It is prepared by adding baking soda to aqueous cocaine hydrochloride and heating it until the freebase cocaine precipitates into small pellets. The mixture is cooled and filtered, and then the rocks are smoked in a crack pipe. Cocaine is a controlled substance throughout the world (e.g., schedule II in the USA; schedule 2/class A in the UK; schedule I in Canada). It does have a legitimate yet minor medical use as a topical local anesthetic for ear, nose, and throat surgery; however, it is illegal to possess and sell in most countries. Recreationally, cocaine is used for its intense euphoric effects, to increase alertness, to relieve fatigue, and to make the user feel stronger and more decisive. Depending on the demographic region, street purity of cocaine hydrochloride can range from 20 to 95%, while that of crack cocaine is 2080%. The hydrochloride powder is often diluted or cut with a
variety of substances such as sugars (e.g., lactose, sucrose, inositol, mannitol), other mild CNS stimulants (e.g., caffeine, ephedrine, phenylpropanolamine), or other local anesthetics (e.g., lidocaine, procaine, benzocaine). Cocaine is also frequently used in combination with other drugs. It is commonly injected with heroin (speedball); smoked with phencyclidine (tick); smoked in marijuana blunts (turbo); or taken with alcohol to reduce irritability. Cocaine interferes with the reabsorption process of dopamine, a neurotransmitter associated with pleasure and movement. Cocaine prevents the reuptake of dopamine by blocking the dopamine transporter. This leads to increased extracellular dopamine levels, resulting in chronic stimulation of postsynaptic dopamine receptors. This chronic stimulation is what results in the euphoric rush. The user will often experience a dysphoric crash when this dopamine level subsequently falls back below previous levels. Similarly, cocaine also interferes with the uptake of norepinephrine (noradrenaline) and serotonin (5-HT), leading to accumulation of these neurotransmitters at postsynaptic receptors. As a local anesthetic, cocaine reversibly blocks the initiation and conduction of nerve impulses. Commonly abused doses of cocaine range from 10 to 120 mg. In general, the faster the absorption of cocaine, the more intense and rapid the high, but the shorter the duration of action. Smoking or snorting cocaine produces an almost immediate intense response and the resulting high lasts up to 15 min with smoking, and up to 30 min with snorting. Injecting cocaine will also produce an effect within 1530 s, while the onset of effects following oral ingestion can be 1 h. The effects of cocaine will persist for 12 h
SUBSTANCE MISUSE/Cocaine and Other Stimulants 143
depending on the dose, and repeated doses are frequently administered to avoid the crash that follows the period of euphoria. This pattern of repeated use may last from hours to days, often terminating only when supplies of the drug run out. During the initial phase of cocaine effects, the user will experience intense euphoria, excitation, feelings of well-being, self-confidence, increased sexual excitement, increased focus and alertness, self-absorption, increased talkativeness, motor restlessness, and loss of appetite. Other effects may include an increase in heart rate and blood pressure, an increase in body temperature, constriction of peripheral blood vessels, difficulty in focusing, dilated pupils, an increased sensitivity to light, blurred vision, tremors, nausea, and vomiting. In higher doses or following acute intoxication, users may exhibit a pattern of psychosis with confused and disoriented behavior, irritability, fear, paranoia, antisocial behavior, aggressiveness, delusions, and hallucinations. Other overdose symptoms may include tachycardia, convulsions, seizures, respiratory dysfunction, unconsciousness, stroke, and heart failure. The crash following binge use can last up to several days and may consist of intense dysphoria, depression, inattention, irritability, nervousness, fatigue and prolonged sleep or, insomnia leading to hypersomnolence, and initial drug craving. Cocaineexcited delirium is a syndrome caused by excessive cocaine use, and is associated with a dissociative state, exaggerated strength, extreme hostility and violence, hyperthermia, cardiorespiratory arrest, and sudden death. Chronic use of cocaine may also lead to personality changes, malnutrition, renal failure, acute myocardial infarction, and worsening of preexisting heart disease. Users who habitually smoke cocaine may suffer from acute respiratory problems including cough, shortness of breath, and severe chest pains with lung trauma and bleeding. Prolonged cocaine snorting can result in ulceration of the mucous membrane of the nose. Burnt lips and fingers from crack pipes are frequently seen, as are rashes and skin reddening from scratching. The combined use of cocaine and ethanol forms cocaethylene in the body, which is as equipotent to cocaine in blocking dopamine reuptake. Although less pharmacologically active than cocaine, cocaethylene intensifies cocaines euphoric effects and possibly increases the risk of sudden death. Cocaine is a powerfully addictive drug of abuse. Its short duration of effects is one reason leading to the probability of addiction, particularly if snorting or smoking is preferred and repeated doses are frequently readministered. An initial acute tolerance to the euphoric high may develop with binge use,
although this tolerance appears to level off during any period of abstinence. Withdrawal symptoms can typically last several weeks and may consist of alternating low and high drug craving, low to high anxiety, paranoia, dysphoria, depression, apathy, irritability, disorientation, hunger, fatigue, and long periods of sleep.
Methamphetamine
Due to its high potential for abuse and dependence, d-methamphetamine is a controlled substance with limited therapeutic use (e.g., schedule II in the USA; schedule III in Canada). Medicinally, it is used in the treatment of narcolepsy, attention deficit disorder (ADD), and attention deficit hyperactivity disorder (ADHD). Typical doses are 1040 mg daily, and a course of greater than 6 weeks is not recommended. Methamphetamine is also infrequently used in the treatment of obesity, overeating disorders, and weight loss. Methamphetamine hydrochloride is a white to light-brown crystalline powder or clear chunky crystals resembling ice. The majority of street methamphetamine is produced in clandestine laboratories and there are currently two common methods of illicit manufacture: reduction of l-ephedrine or d-pseudoephedrine over red phosphorus with hydroiodic acid, or reduction with sodium or lithium in condensed liquid ammonia. The purity of street methamphetamine in the USA is currently very high, at approximately 6090%. Common abused doses of methamphetamine are in the order of 1001000 mg day1, but can range up to 5000 mg day1 during chronic binge use. Initially, users often begin with oral use or snorting before progressing to intravenous use. In contrast to cocaine, the hydrochloride salt of methamphetamine can itself be effectively smoked; however, this is not the route of choice for most users. Alcohol and marijuana are commonly coadministered with methamphetamine, particularly during the drugs withdrawal phase. Methamphetamine increases synaptic levels of the neurotransmitters dopamine, 5-HT, and norepinephrine, and has a- and b-adrenergic agonist effects. An increase in dopamine corresponds to methamphetamines locomotor effects, psychosis, and perception disturbances; norepinephrine is responsible for its alerting, anorectic, locomotor, and sympathomimetic effects; and 5-HT is responsible for the delusions and psychosis. The effects of methamphetamine are similar to cocaine, but its onset of action is slower and the duration is longer. Onset of effects is rapid following intravenous use and smoking, with peak subjective effects occurring at 1520 min. The onset of effects
144 SUBSTANCE MISUSE/Cocaine and Other Stimulants

Table 3 Phases of binge methamphetamine use
Approximate duration
Phase
Common manifestations
Rush Shoulder Binge Tweaking Crash Normal Withdrawal
5 min 1h 15 days 424 h 13 days 27 days
Intense euphoria, rapid flight of ideas, high energy, compulsive behavior, thought-blending Less intense euphoria, hyperactivity, rapid flight of ideas, compulsive behavior, thought-blending Drug is frequently readministered to maintain the euphoric high Dysphoria, scattered thoughts, intense craving, anxiety, irritability, paranoia, hallucinations, delusions Intense fatigue, uncontrollable sleepiness, drug craving Return to normalcy, drug craving may appear particularly in presence of cues Exhaustion, periods of intense craving, depression, hypersomnolence
occurs more slowly following oral use and the effects are less intense. Overall effects typically last 48 h and residual effects can last up to 12 h. Tolerance may develop and users can quickly become addicted to methamphetamine, using it with increasing frequency and in increasing doses. The clinical appearance and duration of chronic binge use are summarized in Table 3. The desired effects following methamphetamine use include euphoria, exhilaration, excitation, increased libido, reduced fatigue, increased alertness, feelings of well-being, and feelings of increased strength. The user may also experience rapid flight of ideas, rapid speech, restlessness, irritability, insomnia, anxiety, obsessive-compulsive behavior, paranoia, hallucinations, delusions, and psychosis. Physiological effects include increased heart rate, blood pressure, and body temperature; increased sensitivity to light, tremors, abdominal cramps, appetite suppression, and twitching. With an overdose, symptoms may include hyperthermia, tachycardia, severe hypertension, convulsions, chest pains, stroke, cardiovascular collapse, and possible death. The crash phase is often characterized by intense dysphoria, residual stimulation, agitation, paranoia, violence, aggression, delusions, psychosis, extreme fatigue, and drug craving. Abrupt discontinuation following binge use can produce extreme fatigue, mental depression, apathy, long periods of sleep, irritability, and disorientation. Chronic abuse of methamphetamine generally produces a psychosis that resembles schizophrenia and is characterized by paranoia, picking and scratching of the skin, preoccupation with ones own thoughts, and auditory and visual hallucinations. Aggression and violent, erratic, and irrational behavior are frequently seen among chronic abusers. Prolonged use can also result in septicemia, abscesses, collapsed blood vessels, and malnutrition. Over time, methamphetamine appears to cause reduced levels of dopamine, which can result in Parkinson-like symptoms.
Amphetamine
Amphetamine is also a controlled substance (e.g., schedule II in the USA; schedule III in Canada; schedule 2/class B in the UK), and is medically available as the sulfate salt of the d-isomer, as the racemic mixture, or a mixture of the two. Amphetamine is used medicinally in the treatment of ADD and ADHD, narcolepsy, and weight control. Recreationally, amphetamine is abused to increase alertness, relieve fatigue, control weight, and for its euphoric and mood-elevating effects. Amphetamine has similar chemical and pharmacological properties to methamphetamine but is somewhat less potent. It increases feelings of well-being and confidence, increases talkativeness, and reduces appetite. Other common effects include an increase in heart rate, blood pressure, and body temperature; blurred vision, dry and itching skin, twitching, tremors, restlessness, anxiety, paranoia, and aggressiveness. Long-term use of amphetamine can lead to weight loss, malnutrition, vitamin deficiency, skin disorders, and depression; while overdose can result in confusion, nausea, vomiting, diarrhea, abdominal cramps, aggression, panic states, hallucinations, arrhythmias, circulatory collapse, and convulsions.
Methylphenidate
Methylphenidate is a mild CNS stimulant available in tablet form by prescription only. In children and adults, methylphenidate can increase attention span, improve concentration, and has an overall calming effect, making it the drug of choice in the treatment of ADHD. In adults, it is also medicinally used for the treatment of narcolepsy and mild depression. In recent years, both adolescents and adults have misused methylphenidate for its stimulant and euphoric effects, and for its ability to decrease fatigue, increase mental alertness, and reduce appetite.
SUBSTANCE MISUSE/Herbal Medicine 145
In prescribed doses, methylphenidate use is not habit-forming; however, tolerance and dependence could develop in recreationally abused doses. With an overdose, frequent symptoms include nausea, vomiting, tremors, sweating, flushing of the skin, twitching, delirium, hallucinations, tachycardia, arrhythmias, convulsions, and coma.
Ephedrine
Ephedrine is structurally related to methamphetamine but has far less CNS potency. It occurs naturally in a number of Ephedra plant species but it is also synthetically manufactured, and until recently, was available over-the-counter throughout the world. The sale of ephedrine and ephedrine-containing products has been regulated, as it is a precursor drug in the illicit manufacturer of methamphetamine. Additionally, in 2003 the US Food and Drug Administration (FDA) issued a consumer alert warning that dietary supplements containing ephedra present an unreasonable risk of illness or injury, and should not be consumed. In 2004, the FDA prohibited the sale of dietary supplements containing the ephedrine alkaloid, ephedra. Ephedrine stimulates a- and b-receptors, causing a release of norepinephrine, and has mild central stimulant and pronounced peripheral effects. It is most commonly used as a nasal decongestant and bronchodilator, and is contained in a number of dietary supplements that are sold as energizers, for weight loss, and for enhanced sport performance. In frequent or high doses, ephedrine is capable of causing dizziness, headache, nervousness, agitation, tremors, insomnia, hypertension, tachycardia, and cardiac arrhythmias. Similar to many stimulant drugs, ephedrine overdose is characterized by increased heart rate, blood pressure, and body temperature; aggressiveness, sweating, paranoid delusions, and hallucinations.
Higgins ST, Katz JL (eds.) (1998) Cocaine Abuse: Behavior, Pharmacology, and Clinical Applications. San Diego, CA: Academic Press. Isenschmid DS (2002) Cocaine effects on human performance and behavior. Forensic Science Review 14: 61100. Johanson C-E (1992) Cocaine: A New Epidemic, 2nd edn. London: Burke. Karch SB (1998) A Brief History of Cocaine. Boca Raton, FL: CRC Press. Logan BK (2001) Amphetamines: an update on forensic issues. Journal of Analytical Toxicology 25: 400404. Logan BK (2002) Methamphetamine effects on human performance and behavior. Forensic Science Review 14: 133151. Lukas SE (1985) The Encyclopedia of Psychoactive Drugs. Amphetamines: Danger in the Fast Lane. New York: Chelsea House. Shulgin A, Shulgin A (2000) PIHKAL: A Chemical Love Story, 5th edn. Berkeley, CA: Transform Press.
Herbal Medicine
S B Karch, Berkeley, CA, USA
Overview
Herbal remedies have always been used for health maintenance and preventing disease. Traditional Chinese and ayurvedic medicines are the best examples of this. However, until very recently, western users of herbal products have usually taken them for the very same reasons as any other over-the-counter remedy: for the treatment of minor medical problems, such as colds and stomach upset. Increasingly, herbal products are now taken with hopes of preventing disease. A rapidly proliferating number of obscure agents are now used to promote wellness, not treating any specific disease. There is no reliable way of calculating either the number of products or the number of users, but even by the most conservative estimates, there are tens of millions of regular users, yet reports of toxicity are rare. The reason why episodes of toxicity seem so uncommon is partly the benign nature of the most popular herbs. Table 1 lists the products most often sold in the USA in 2002 and 1998. Except for stomach upset, it is difficult even to imagine what sort of toxicity the number-one seller, garlic, might exert. Another factor acting to limit the toxicity of herbal products is, at least in the USA, the laws under which herbal products are produced and marketed; herbal products cannot be fortified. Concentrations of the
See Also
Pharmacology of Legal and Illicit Drugs; Substance Misuse: Substitution Drugs; Sedatives; Miscellaneous Drugs; Toxicology: Methods of Analysis, Antemortem; Methods of Analysis, Postmortem
Further Reading
Couper FJ, Logan BK (2004) Drugs and Human Performance Fact Sheets. NHTSA technical report no. DOT HS 809 725. Washington, DC: US Department of Transportation.
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Table 1 Most widely used herbal supplements sold in the USA during 2002. Rankings based upon sales in major retail outlets, not including figures for traditional Chinese remedies
2002 1998
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Garlic Ginkgo biloba Echinacea Soy Saw palmetto Ginseng St. Johns wort Black cohosh Cranberry Valerian
Echinacea St. Johns wort Ginkgo biloba Garlic Saw palmetto Ginseng Goldenseal Aloe Siberian ginseng Valerian
studies are available, but are of little help in establishing causality in specific cases. Rarely, a herb may induce specific anatomic lesions (such as pyrrozolidine alkaloids), or a specific complex of symptoms (such as digitalis or anticholinergic poisoning), or produce measurable electrophysiologic changes (such as quinine-induced torsades des pointes), allowing a cause-and-effect relationship to be established with a high degree of certainty. Issues of product adulteration, drug interaction, and poor manufacturing practice are also of concern and are increasingly the subject of forensic investigation. It is only in this last area that modern techniques of forensic science have been applied with any vigor.
active ingredients in the finished product must be comparable to concentrations in the plant itself. In most cases, the amount of active ingredient present in the plants is very small, amounting to less than 1%. If pure plant material is ingested, concentrations of the active ingredient will remain more or less as in the plant itself. Short of massive overdose, the average consumer is unlikely ever to be exposed to a high enough concentration to cause harm. Problems only arise when extracts or tinctures are produced. Under US law, standardization of these products is not required. However, even though fortification is against the law, alcohol-based tinctures can, as the fluid evaporates, become quite concentrated. A completely separate issue is raised by the ready importation of products from other countries where concentration is, indeed, permitted. When herbal toxicity does occur, the pattern of side-effects is probably dose-related, and similar to the effects observed with prescription medications used to treat the same problems. However, at least in the case of prescription medications, the active ingredient, or ingredients, responsible for producing the undesirable side-effect is known. It is only within the last few years that modern analytical techniques have been systematically applied to the identification of the active principles in crude plant extracts, and few of these compounds have ever been studied in randomized clinical trials. The peer-reviewed literature discussing herbal product toxicity consists mainly of individual case reports, computerized literature searches summarizing the case reports, and review papers summarizing earlier review papers. Piling literature summary on literature summary adds very little useful information, but it falsely inflates the significance of the original case reports. Controlled clinical measurements of herbal pharmacokinetics, toxicokinetics, and bioavailability are nearly nonexistent. Limited data from tissue culture
Determining Causation
Litigation against herbal product manufacturers is increasingly common in the USA and often mediadriven. The number of adverse event reports made to the Food and Drug Administration about ephedracontaining products, for example, used to increase whenever a television news program carried a feature on an alleged case of ephedrine toxicity. The same phenomenon can, no doubt, occur with any herbal product. Forensic toxicologists and pathologists consulted about herbal issues quickly learn that courts and medical journals use different standards for determining causation. No serious scientist would ever suggest that a passively collected anecdotal case report has the same value in determining causation as a double-blind control trial, or a controlled laboratory study, but a jury might reach exactly that conclusion, and judges are unlikely to put things right by explaining the weight of different kinds of scientific evidence to the jury. Application of the Bradford-Hill criteria for causation, originally devised for use in the case of occupational exposures, can sometimes be helpful, at least to make things clear in the mind of the investigator, if not the jury. In Bradford-Hills original publication, nine separate criteria for causation were suggested. All of the criteria need not be met in order to prove scientific causation, but the more criteria fulfilled, the greater the likelihood that a causeand-effect relationship actually exists. The criteria most often mentioned include: (1) temporal relationship; (2) specificity; (3) biological plausibility; and (4) coherence. Attempts at applying those criteria are likely to run foul of one very big problem: lack of specificity. What is to be concluded from a series of two or three case reports describing the occurrence of a common event, such as myocardial infarction or stroke, in ginseng, ginkgo, or ephedra users? Millions of people consume

Table 2 Naranjo algorithm
Sample Naranjo calculation Score
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Are there previous conclusive reports on this reaction? Did the adverse event appear after the suspected drug was given? Did the adverse reaction improve when the drug was discontinued or a specific antagonist was administered? Did the adverse reaction reappear when the drug was readministered? Are there alternative causes (other than the drug) that could on their own have caused the reaction? Did the reaction reappear when a placebo was given? Was the drug detected in the blood (or other fluids) in concentrations known to be toxic? Was the reaction more severe when the dose was increased, or less severe when the dose was decreased? Did the patient have a similar reaction to the same or similar drug in any previous exposure? Was the adverse event confirmed by any objective evidence?
The Naranjo algorithm assigns a score of 1 for every positive answer, and a score of 1 for every negative answer. No points are accorded if the answer is not known. Events are classified as definitely (total score 912), probably (total score 58), possibly (total score 14), or doubtfully (total score 2 to 0) drug-related.
these products, and a significant number would be expected to have become ill, no matter whether they had used the herb or not. In addition, three case reports describing the occurrence of some rare disease, such as Wegeners granulomatosis, or Stevens Johnson syndrome, in users of one particular product, would be cause for very great concern. The issue of ginkgo biloba-related clotting disorder provides a good illustration of the problem. Since the 1980s, billions of doses have been sold. Exactly one case of spontaneous hyphema has been reported during that time, and this case is cited in nearly all of the more than 100 review papers that have been written on ginkgo. Whether ginkgo ingestion really has any relationship with hyphema, or bleeding disorders in general, is impossible to say, but the notion is now so ingrained in the literature that it would probably be considered malpractice for a physician to recommended ginkgo to someone taking regular doses of aspirin. If not all the Bradford-Hill criteria are given equal weight, the results can be very misleading. A causeand-effect relationship may be biologically plausible, but plausibility does not eliminate the need for adequate differential diagnosis. Suppose, for example, that someone with several days symptoms of an upper respiratory infection dies suddenly after taking one pseudoephedrine tablet. A pseudoephedrine concentration of 30 ng ml1 is found in right heart blood, and microscopic examination of the heart discloses no obvious abnormality. Pseudoephedrine is classified as a sympathomimetic agent, and overdose with drugs in this category is known to be associated with arrhythmia. Would it be reasonable to conclude that pseudoephedrine was the cause of death? Perhaps, but only if alternative causes of death have been excluded. There is, of course, the obvious question of the doseresponse relationship is it reasonable to suggest that a 30-mg dose can produce
the same arrhythmic effects as 300 mg? Common sense dictates not, but an even more compelling reason for not inferring a cause-and-effect relationship is that several important, and reasonably common, causes of sudden death cannot be ruled out by microscopic examination alone. Patients with several genetically distinct types of hypertrophic cardiomyopathy may die suddenly, even when hypertrophy is not apparent. If no medical history is available, the presence of heritable long QT syndromes, Brugada syndrome, and other channelopathies can only be determined by DNA testing, which is not likely to be done. More confusing still, recent DNA studies show that viral infection, particularly with parvovirus, can cause an acute coronary syndrome, even in the absence of microscopic changes diagnostic for myocarditis. An algorithm based upon the original BradfordHill criteria has been developed by Naranjo and coworkers and is reproduced in Table 2. The algorithm was designed for use with hospital patients. In most alleged episodes of herbal-related toxicity, there simply is not enough information available to allow the algorithm to be completed.
Terms and Definitions

The same herb may be sold formulated as a pill, elixir, tincture, or extract. It may also be sold in bulk in the form of crushed leaves or stems. Powdered plant materials may be placed inside a gelatin capsule or dissolved in a health drink. In the USA, nothing requires manufacturers of herbal remedies (regulated under a law called the Drug Supplement Health and Education Act or DSHEA) to standardize any of these products. An extract sold by one company may contain twice as much, or half as much, active ingredient as a similarly named product from another manufacturer.
Some of the terms used to describe these products are archaic, and unlikely to be understood by either their users or by healthcare professionals treating the users. Even forensic scientists are unlikely to know what, precisely, is meant by the term decoction, let alone how a decoction is produced. The one common feature of all these dosage forms is that the amount of active ingredient contained in them is unknown. Products from large supplement makers are generally manufactured following standardized procedures; individual dosage units are unlikely to contain very much more, or very much less, than what is written on the label. With most unprocessed herbal products, content variations of as much as 30% are unlikely to have a significant impact on health. A simple consideration of the numbers shows why. The active principles of valerian, whichever they may be, are though to be contained in a volatile oil that constitutes 0.41.4% of the root. A 500-mg capsule of valerian root can be expected to contain, at most, 1.4% of the volatile oil, equivalent to 7 mg. If the content of a particular batch contained 30% more than stated, the same 500-mg capsule would then contain 9.1 mg of active ingredient. Presuming that sesquiterpenoids have a moderate volume of distribution on the order of 3 l kg1 (which would not be unreasonable), a 7-mg dose would be expected to provide a peak plasma concentration of 33 ng ml1. If the dose were increased to 9.1 mg, the plasma concentration would increase to 43 ng ml1. Statistically the increase would be very significant. Clinically, it is hard to imagine how the additional 10 ng ml1 of seqsquiterpenoids would have much impact. Of much more concern are small producers, largely unregulated and inexperienced in proper manufacturing practice; there can be extreme variation in the final composition of the product. However, even the most rigid adherence to rigid manufacturing standards provided no guarantee of effectiveness, because the active ingredient or ingredients in most herbal products are usually not known. St. Johns wort, for example, is standardized for its hypericin content, but whether hypericin, or some other molecule completely unrelated to hypericin, is responsible for the plants therapeutic effect is not known. The seventeenth-century term galenicals is still used by some to describe the different way that plants can be processed. Extracts are classified as decoctions, infusions, fluid extracts, tinctures, pilular extracts, semisolid extracts, or powdered extracts.
Infusions
soaking varies from producer to producer. Accordingly, the concentration of active ingredient found in the infusion, whatever that ingredient might be, will depend on how long the herb has been allowed to steep and at what temperature. Some products are packaged in tea bags containing a fixed amount of dried herb, allowing consumers to make their own infusion. The final concentration of active ingredients in home brews is a function of both the amount of product in the tea bag, and the length of time the user allowed it to steep. If the active ingredient in the herb is not water-soluble, as is the case with chamomile, then almost none of the active ingredients (in the case of chamomile, a weak benzodiazepine receptor agonist) will be present in the infusion.
Decoction
This term is no longer used in modern pharmacy. If a plants active ingredient is only found in the stem or bark (the exception, not the rule), the woody part of the plant may be boiled to extract the active components. If it is heat-stable, the stems or bark may be boiled in water for 15 min, then cooled and strained into cold water. In the mid-1800s, quinine was administered as a decoction prepared from Jesuits bark. Even if a standardized amount of bark was used to prepare the decoction, the amount of quinine given would have depended on both the quinine content of the bark (which is highly variable) and the efficiency of the extraction process.
Tinctures
These are no longer used in traditional medicine and are no longer even mentioned in modern textbooks. In the past, pharmaceutical manufacturers preparing very potent medications (like digitalis) would dissolve 10 g of plant material in 100 ml of alcohol, or an alcohol/water mixture. If the drug prepared is less potent, double the amount of plant material would be used. In practice, plant material is soaked in alcohol for 35 days and the mixture is then strained or percolated. It was considered good manufacturing practice to standardize tinctures, either by diluting or concentrating the liquid to yield a predictable amount of drug. Herbal tinctures are not standardized. Of course, the whole notion of standardization makes very little sense when, as is the case for most herbal remedies, the active ingredient is not known.
Fluid Extracts
Theses remedies are made by soaking dried herbs in water. The water may be cold or hot and the length of
This term is used to describe products that contain alcohol as either a solvent or a preservative. They are compounded in such a way that 1 ml of the final product will contain the active ingredients found in
1 g of herb. Fluid extracts made by pharmaceutical companies (rarely done today) are tested to ensure that some standard concentration is contained in the final product. Herbal remedies may or may not be standardized, but even if they are, there is no assurance that different producers have standardized them to the same concentration. As with tinctures, the whole notion of standardization loses much of its meaning when the active ingredient, or ingredients, are not known.
Specific Syndromes
Toxic reactions involving the liver, kidneys, heart, and brain have all been reported, but rarely. The existence of pathognomonic lesions is rarer still.
Hepatotoxicity
Herbal medicinal products have been alleged to cause a broad spectrum of liver disease, ranging from transient elevations of liver enzyme levels to fulminant liver failure. The incidence of these disorders is not really known and, with a few prominent exceptions, definite evidence of causation has never been provided. Pyrrozolidine alkaloids toxicity is one of the very few exceptions. The pyrrolizidine alkaloids are mainly found in members of the family Boraginaceae: Senecio jacobaea, Symphytum officinale (comfrey), Pteridium aquilinum (bracken fern), and Heliotropium (eichwaldi in India, lasiocarpium in China, europaeum in India and Greece, indicum in Africa and South America) are all hepatotoxic. Occasional case reports have described the sporadic occurrence of venoocclusive disease (BuddChiari syndrome), in chronic users of comfrey-based remedies. Exposure to the alkaloids of these plants results in portal hypertension due to obliteration of the smaller hepatic venules. The pattern of hepatic injury observed in experimental animals chronically exposed to Russian comfrey is similar in pattern to that observed in humans, and is dose-dependent. Comfrey accounts for a minute fraction of herbal sales, and heliotrope is not used at all. Except for the rare case of agricultural poisoning, herbal product users are unlikely ever to be exposed to these toxins. Hepatotoxicity secondary to the use of the anxiolytic kava appears to be more common. Reports of liver toxicity, first from Switzerland and then from the rest of Europe, led to the withdrawal of kava from most markets in 2002. The active components of kava are thought to be kavalactones. Products containing kava usually specify a kavalactone content on the label, but there is no standard laboratory method
for making this measurement, and a wealth of anecdotal reports suggest that the actual lactone content of commercial products may differ quite dramatically from the amount specified on the label. Kavalactone concentrations have been measured in traditional kava preparations, but the results of these studies have not been replicated, or compared with those in commercial extracts. It is believed that alcohol or acetone extracts with a high content of kavalactones accounted for most of the reactions, though this issue still remains controversial. Water extracts of kava are considered safe, and are still allowed in some countries such as Australia. The total number of reported cases of kava toxicity is less than 30. A detailed analysis of 19 cases by a German government agency concluded that in all but one of the reported cases (a patient having just recovered from a bout of apparently kava-related hepatotoxicity became ill after accidentally taking kava a second time) there were insufficient data to allow any conclusion. Germander (Teucrium chamaedrys) use has been linked to sporadic cases of hepatic failure, leading French authorities to ban its use. Germander, which is still promoted by some as a slimming aid, contains a diterpenoid called teucrin A. The furan ring of the diterpenoid is oxidized by CYP3A4 to form a reactive epoxide that, in turn, reacts with proteins such as CYP3A. Damage to the P450 system raises concern for herbal toxicity secondary to herbdrug interaction; however, definitive evidence for such interactions remains elusive. Of more concern would be confusion of germander with skullcap or even valerian.
Renal Toxicity
Chinese herb nephropathy was first described in a group of women who had been given diet pills made from powdered extracts of the Chinese herb Stephania tetrandra, in combination with an assortment of other agents, including fenfluramine. Renal failure occurred in many of those treated with the extract, and a high percentage went on to dialysis and/or transplantation. Biopsies of the removed kidneys showed interstitial fibrosis leading to severe atrophy of the proximal tubules. In nearly one-half of the cases where tissue was examined, there was evidence of urethral carcinoma. Chemical analysis of removed tissues disclosed the presence of aristocholic acid (AA)-related DNA adducts, which are specific markers for previous exposure to AA. They are also known carcinogens. Analysis of the pills taken by the women confirmed the presence of AA instead of tetrandrine, proving that a medication error had occurred, with the traditional Chinese medication
Hanfang ji having been replaced by Aristolochia fangchi. The substitution of Aristolochia for Stephania was a result of confusion on the part of the physicians who compounded the pills, leading to the mistaken inclusion of the wrong plant. This problem also affects Mu tong, which, in the past, was often used in herbal prescriptions for skin conditions, as were Akebia quinata, Clematis armandii, or Aristolochia manshuriensis. As a consequence, AA nephropathy may occur in patients who have used Chinese herbal medicine for skin conditions.
Cardiac
The use of ephedrine-containing herbal supplements is allegedly a frequent cause of cardiovascular toxicity, but the handful of published case reports meet so few of the Bradford-Hill criteria that it is difficult to see how any connection between ephedra and cardiovascular disease could even be considered biologically plausible, let alone established in any individual case. Oral ephedrine, in the amounts provided by most herbal supplements (less than 150 mg day1), as opposed to the intravenous ephedrine used in surgery, has little measurable effect on cardiovascular function. One possible mechanism for ephedrine-related toxicity might be chronic catecholamine toxicity. Myocardial fibrosis and small-vessel disease are recognized consequences of chronic catecholamine excess, and this pattern of injury is commonly observed in cocaine and methamphetamine users. Catecholamine concentrations have never been measured in herbal supplement users, but two case reports describing catecholamine cardiomyopathy have been published. Both were secondary to the ingestion of thousands of milligrams of ephedrine per day over many years. Extracts made from the peel Citrus aurantium L., also known as bitter orange, contain adrenergic amines (dl-octopamine, dl-synephrine, and tyramine) that, taken in sufficient concentrations, can raise blood pressure and possibly cardiac arrhythmias. When prescribed by herbalists (mainly to treat stomach upset) the dosage is 45 g day1. When added to herbal weight loss supplements, the dosage is usually only a few milligrams. Analysis of juice extracts has shown that the mean synephrine content of the juices is 57 mg ml1. An 8-oz. (250-cc/250 ml) glass of Seville orange juice contains a total of 15 mg of synepherine, and has no measurable impact on cardiovascular function. Theoretically, the juice might exert toxicity via interaction with a large new family of G protein-coupled receptors, some of which bind and are activated by octopamine and synephrine. Traces of these amines are normally detectable in
plasma and platelets of healthy people, although baseline plasma levels of octopamine, tyramine, or synephrine seem to vary widely among healthy individuals. It follows that detection of any of these amines would not constitute proof of ingestion. Most of the herbal supplements sold in the USA contain only a few milligrams of the peel extract. An entirely different type of cardiotoxicity is sometimes seen in the users of traditional Asian remedies made from dried toad skin. Toad venom poisoning is, in fact, similar to digitalis toxicity and carries a high mortality. The venom gland of cane toad (Bufo marinus) contains large quantities of cardiac glycosides, as do some plants. Poisoning victims are bradycardic and usually complain of oral numbness, as well as vomiting and diarrhea. No distinctive myocardial lesions are produced, but the electrocardiogram is diagnostic for digitalis poisoning: paroxysmal atrial tachycardia with atrioventricular block. Serum analysis by means of high-performance liquid chromatography (HPLC) will reveal the presence of active digitoxin metabolites, but no parent drug. When the diagnosis of cardioactive steroid poisoning is suspected on clinical grounds, laboratory analysis can confirm the presence of cardioactive steroids by using immunoassays of varying specificity. If ingestion results in death, great caution must be exercised in postmortem testing, because digitalis-like molecules are produced by the putrefaction. The rootstocks of aconitum plants, which contain aconite alkaloids, have been common components of Chinese herbal recipes since antiquity. Western herbalists occasionally use the root as an antiinflammatory, but reports of toxicity are still very rare. Patients with aconite toxicity develop symptoms within 2 h of herb ingestion, and mostly arrhythmias, including conduction block and ventricular arrhythmias. The mechanism of aconitine-induced arrhythmia has not been established directly, but increasingly appears to be ion channel related.
Contamination and Adulteration

In the past, commercially produced traditional Chinese remedies were very likely to be adulterated or contaminated, or both. One study from Taiwan found that 24% of all samples were contaminated with at least one conventional pharmacological compound. Products intended to treat arthritic symptoms were being fortified with butazoladine or indometacin. Products intended to calm the nerves were enhanced with potent tranquilizers, and products designed to promote weight loss might contain any combination of thyroid extract, aspirin, and a diuretic. Unsuspecting users subject to workplace drug testing may test
positive and never even suspect the cause of the positive. Whether the problem continues is not known, since there have been no recent surveys or studies. Herbal remedies from the Indian subcontinent have occasionally been found to have high concentrations of heavy metals. The incidence of heavy-metal contamination in Indian remedies is not known, but one study showed that 64% of samples collected in India contained significant amounts of lead (64% mercury, 41% arsenic, and 9% cadmium). A number of case reports and case series have been published. The presence of arsenic and lead in these products is probably a consequence of the use of contaminated well water in the manufacturing process. Ground water in the Bengal plain is massively contaminated (concentrations >3400 mg l1 have been recorded). Arsenic exerts its toxicity by inactivating hundreds of different enzyme systems. Acute arsenic poisoning is initially associated with nausea, vomiting, abdominal pain, and severe diarrhea. Encephalopathy and peripheral neuropathy are consequences of prolonged exposure, as is malignancy. Arsenic-induced torsades des pointes is a worrisome complication that has only recently been recognized. Tissue culture studies have shown that arsenic blocks both IKr and IKs channels and, at the same time, activates IKATP channels. The effects of arsenic on the various channels appear to cancel each other out, and in most patients cardiac repolarization is undisturbed. QT interval prolongation and the ventricular arrhythmias arise when the blocking and activating effects are out of balance, as would occur when a gastrointestinal upset causes minor electrolyte shifts. As illustrated by the outbreak of AA nephropathy, plant misidentification is an issue of concern, especially when an individual or small company compounds the herbal remedy. In the USA, bulk purchases of individual herbs must be accompanied by certificates of authenticity, which, on repeat testing, are often found to be inaccurate. Such certificates do not accompany small purchases, and small manufacturers do not routinely reanalyze their starting ingredients. Within the last few years techniques for plant DNA analysis have improved sufficiently so that the species and variety of most herbs could be established with relative ease. The technology may not be of great interest to manufacturers, but could have great forensic utility, especially in cases of alleged product liability. For example, if toxicology testing disclosed low concentrations of phenylpropanolamine in a patient with alleged ephedrine toxicity, it would be a relatively simple matter for manufacturers to show that the taxon of ephedra used to make their product was one that did not produce phenylpropanolamine (most taxa do not).
There are several different ways in which plant products can be chemically profiled or genetically fingerprinted. Of the two, chemical profiling is a more cumbersome and time-consuming approach. After HPLC separation, liquid chromatography mass spectrometry analysis can be performed for the flavonoid content, and the flavonoid profiles of different samples can be compared. The alternative is DNA fingerprinting (amplified fragment length polymorphisms (AFLP)). This approach is already being used to identify the provenance of opium, coca, and marijuana plants. There is every reason to suppose it would work equally with other herbal products.
Drug Interactions
A handful of case reports have suggested that drugherb interactions can result in unexpected concentrations of therapeutic drugs, causing lower plasma concentrations of ciclosporin, theophylline, and digoxin. Clinically significant interactions have been identified when St. Johns wort was taken together with prescription medications including warfarin, ciclosporin, human immunodeficiency virus (HIV) protease inhibitors, theophylline, digoxin, and oral contraceptives. In every case the interaction resulted in a decrease in plasma drug concentration or decreased effect of the medicines. These interactions are probably due to the induction of cytochrome P450 isoenzymes CYP3A4, CYP2C9, CYP1A2, and possibly to interactions with the transport protein P-glycoprotein by constituents. However, the degree of interaction and clinical effects are extremely unpredictable, and not common. One reason for the unpredictability may simply be the unpredictable composition of the different St. Johns wort products. The risks of using ephedra and St. Johns wort with monoamine oxidase inhibitors have been widely publicized, even though there are few anecdotal data, and no data from controlled trials, suggesting that clinically relevant herbalmonoamine oxidase inhibitor interactions occur. Some of the evidence suggests otherwise. For example, there are no reports of pseudoephedrine or ephedrine interacting with selegeline, a potent monoamine oxidase inhibitor.
Drug Testing
Several reports have been published showing that standard screening immunoassays for methamphetamine cross-react with ephedrine and its isomers. The problem, however, appears to be largely confined to ephedra; there is no evidence that any of the other commonly used herbs are capable of causing falsepositive tests for drugs of abuse.
152 SUBSTANCE MISUSE/Heroin
See Also
Drug-Induced Injury, Accidental and Iatrogenic; Drugs, Prescribed: Licencing and Registration; Product Liability
Heroin
O H Drummer and J Gerostamoulos, Victorian Institute of Forensic Medicine, Southbank, VIC, Australia
Further Reading
Bradford-Hill A (1965) The environment and disease: association or causation? Presidents address. Proceedings of the Royal Society of Medicine 9: 295300. Chauvin P, Dillon JC, et al. (1994) [An outbreak of heliotrope food poisoning, Tadjikistan, November 1992March 1993.] Sante 4: 263268. Currie BJ, Clough AR (2003) Kava hepatotoxicity with western herbal products: does it occur with traditional kava use? Medical Journal of Australia 178: 421422. Ernst E (2002) Adulteration of Chinese herbal medicines with synthetic drugs: a systematic review. Journal of Internal Medicine 252: 107113. Gowda RM, Cohen RA, et al. (2003) Toad venom poisoning: resemblance to digoxin toxicity and therapeutic implications. Heart 89: e14. Henderson L, Yue QY, et al. (2002) St Johns wort (Hypericum perforatum): drug interactions and clinical outcomes. British Journal of Clinical Pharmacology 54: 349356. Johnson EL, Saunders JA, et al. (2003) Identification of Erythroxylum taxa by AFLP DNA analysis. Phytochemistry 64: 187197. Kalman D, Incledon T, et al. (2002) An acute clinical trial evaluating the cardiovascular effects of an herbal ephedra-caffeine weight loss product in healthy overweight adults. International Journal of Obesity Related Metabolic Disorders 26: 13631366. Lunetta P, Levo A, et al. (2003) Molecular screening of selected long QT syndrome (LQTS) mutations in 165 consecutive bodies found in water. International Journal of Legal Medicine 117: 115117. McRae CA, Agarwal K, et al. (2002) Hepatitis associated with Chinese herbs. European Journal of Gastroenterology and Hepatology 14: 559562. Naranjo CA, Busto U, et al. (1981) A method for estimating the probability of adverse drug reactions. Clinical Pharmacological Therapy 30: 239245. Nortier JL, Vanherweghem JL (2002) Renal interstitial fibrosis and urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). Toxicology 181182: 577580. Pankuweit S, Moll R, et al. (2003) Prevalence of the parvovirus B19 genome in endomyocardial biopsy specimens. Human Pathology 34: 497503. Penzak SR, Jann MW, et al. (2001) Seville (sour) orange juice: synephrine content and cardiovascular effects in normotensive adults. Journal of Clinical Pharmacology 41: 10591063. Yeong ML, Clark SP, et al. (1991) The effects of comfrey derived pyrrolizidine alkaloids on rat liver. Pathology 23: 3538.
Introduction
The sticky gum or milky exudate of the opium poppy (Papaver somniferum) is known as opium and is the source of most of the illicit heroin. This gum contains many alkaloids, of which morphine content at 421% is the most important. Small and variable amounts of other opioids such as codeine (0.23.0%) are also present. Opium has been known to humans for more than 2000 years as a sleep-inducing and pain-relieving substance. The name morphine derives from Morpheus, the Greek god of dreams. Heroin is one of the most widely used illicit drugs. Heroin or diacetylmorphine has little or no medical use in most countries, hence its supply and use in those countries are illegal. Heroin is also one of the most dangerous drugs, capable of severe drugdependence problems as well as giving rise to a high mortality rate. This article reviews the source and physiological properties of heroin and factors that determine its response in humans and consequent health risks relevant to forensic and legal medicine.
Worldwide Usage
The use of opioids (drugs related to morphine) such as heroin for recreational reasons is widespread. Estimates suggest that there are 8 million users of heroin worldwide and that 5 million kg of opium are produced each year, largely from South America and Southeast Asia, of which large amounts are converted into injectable heroin. This has the potential to produce 2050 million doses of heroin. Health surveys in the USA show 34% of fulltime college students used illicit drugs in the year 2003, of which 4.7% used heroin and other opioids. Household surveys in the USA show that heroin was used by at least 0.1% of the population. Similar use of drugs probably exists in other developed countries, and increasingly in other parts of the world. In Australia, the annual mortality is about 3 per 100 000 population, and attendance by emergency medical care occurs at a rate some 10 times the death rate.
SUBSTANCE MISUSE/Heroin 153
Manufacture and Forms

Illegal sources of the opium poppy come from the tropical highlands of Southeast Asia (Laos, Myanmar, Thailand, Vietnam, and Yunnan province of China) and in central and southern Asia (Afghanistan, India, Pakistan, Turkey) as well as Colombia and Mexico. These first two regions are called the Golden Crescent and Golden Triangle, respectively. Heroin is prepared from opium by acetylation and purification. The final product varies considerably in color and form. Colors can range from crystalline white, off-white, and beige, to dark brown. Generally, the white or off-white forms have the highest morphine content, generally greater than 70%, unless it has been cut with excipients. The grades of heroin available on the street range from No. 4, a white crystalline powder often produced in Southeast Asia, to No. 3, a discolored product (tan to black) often used in smoking, to No. 1 and No. 2, which are largely unprocessed raw heroin. The various forms of heroin will vary not only in the purity of heroin, but also in the content of acetylcodeine (formed from codeine by acetylation), 6acetylmorphine (6-AM) (monoacetylated morphine also produced from heroin by hydrolysis), narcotine, and papaverine. Typically, acetylcodeine and papaverine content ranges up to 45%, although narcotine and papaverine are not always present in purified heroin. In some countries (e.g., New Zealand), codeine is demethylated in clandestine laboratories to morphine (homebake procedure). Acetylation and formation of the hydrochloride salt yield a white crystalline powder. This powder is cut with inert sugars such as glucose and lactose and is sold on the street as heroin. Occasionally, other substances are found laced with the heroin that will modify the pharmacology and toxicology of the drug. These include lidocaine (lignocaine), quinine, strychnine, and acetaminophen (paracetamol). Street purities of heroin vary from less than 5% to over 70%. Crude extracts, such as Mexican black, are also a significant source of heroin.
increasingly common routes for the use of heroin, particularly with high purity and in the nonsalt form (free base). Smoking allows drug to be efficiently and quickly absorbed, although a good technique is required to ensure that most of the drug is vaporized and little pyrolysis occurs. Skin-popping is also used to introduce heroin to the body.
Metabolism and Excretion

Heroin is rapidly converted to morphine (within minutes) through the intermediate 6-AM. This conversion occurs in most parts of the body, including blood, whereas conjugation of morphine to the 3and 6-glucuronides occurs mainly in the liver. All species are active pharmacologically, although both heroin and 6-AM are only present in blood and tissues for a relatively short period. Morphine is the dominant active species after several minutes and is removed from the body by either metabolism to 3- and 6-glucuronides or by excretion as unchanged drug in urine and bile. Morphine is rapidly excreted in urine as glucuronides, with up to 85% of the dose recovered in urine within 24 h. Only small amounts of morphine are excreted unchanged (210%). The presence of 6-AM in urine distinguishes heroin use from morphine. Small amounts of codeine are also present in the urine of heroin users because of the presence of acetylcodeine in the heroin. Small amounts of normorphine are formed following oral administration of morphine.
Pharmacological Effects
Heroin can produce depression of the respiratory centers in the brain, leading to a decrease in rate and depth of breathing. The depressant effect is associated with a decrease in the sensitivity of the respiratory center to carbon dioxide. All strong opioids produce this effect without causing significant depression of the brain regions (medulla), which control cardiovascular function. Other drugs that act as central nervous system depressants usually exhibit nonspecific depression of the medullary centers, for example, barbiturates, benzodiazepines, alcohol, and, if present, will exacerbate the effects of opioids on respiration. Respiratory depression can occur at low doses unless tolerance has developed. This respiratory depression is affected by the conscious state. Persons awake and in pain are less likely to develop respiratory depression than those asleep. Pneumonia and chronic obstructive airways disease, such as emphysema, increase the risk of adverse effects to heroin and other related opioids.
Route of Administration
The absorption and resultant bioavailability (amount of drug available for action that has not been metabolized in the first passage through the liver) of heroin depends very much on the route of administration. The highest absorption will occur when the drug is taken intravenously, by snorting, or through smoking. Intranasal routes, or snorting, and smoking (chasing the dragon and ack ack) are now
Heroin also produces sedation and narcosis. Drowsiness leading to sleep is one of the typical effects of a heroin user, although the sleep is not usually deep. Conscious state is often clouded, leading to a diminution of mental state. Apathy, reduced visual acuity, reduced physical activity, and lethargy are also common. The user is more likely to be in a drugged or stoned state, although there is a component of paradoxical excitement.
Heroin users will exhibit abstinence symptoms within 610 h that become maximal at 3648 h. Symptoms gradually subside over 1 week. The opioid receptor antagonists (naloxone, naltrexone, etc.), or mixed agonist/antagonists (e.g., buprenorphine, pentazocine) will often produce abstinence symptoms in heroin-dependent persons. These symptoms can be severe if a person has developed a significant tolerance.
Dependence and Toxicity

There is limited medical use of heroin (or diamorphine) in countries such as the UK. Doses in adults are 2.510 mg intravenously, intramuscularly, subcutaneously, or 2.55 mg by epidural. Nontoxic concentrations of heroin vary widely depending on the degree of tolerance an individual has developed and of course this also depends on the purity of the street heroin. While plasma concentrations of some drugs have been defined for optimal therapeutic use, there is no safe therapeutic concentration for heroin (usually measured as morphine). A blood concentration of morphine, which can produce a therapeutic response (i.e., analgesia), can equally well cause respiratory depression. Therefore, therapeutic concentrations of morphine overlap completely with toxic (fatal) concentrations. The additional use of sedatives such as benzodiazepines can result in enhanced sedation and drowsiness. Mixing heroin with alcohol will also exacerbate any adverse effects. An intravenous 20 mg dose of heroin can kill an opiate-naive person, whereas daily doses of over 1000 mg (1 g) can be tolerated in a person accustomed to the drug. This tolerance can develop quite rapidly, within days to weeks in persons constantly consuming heroin. In practice, illicit drug users tend to use heroin sporadically, resulting in high and low blood concentrations with relatively long intervals between doses. In this situation drug tolerance and physiological dependence may not develop to any significant degree. Abstinence symptoms in tolerant persons abstaining from heroin are characteristic, and include anxiety, chills, diarrhea, gooseflesh, hostility, hyperthermia, muscular aches, rhinorrhea, sweating, and vomiting. As with all drug-withdrawal symptoms the time of onset, the intensity, and duration of symptoms will depend on the route of administration and the degree of established tolerance and dependence. Neonates from opiate-dependent women may develop a potentially fatal withdrawal symptom.
Behavioral Changes
Most of the physiological manifestations of heroin use and abuse derive from its effects as a strong analgesic, narcotic, and euphoric drug. In drivers of motor vehicles, reduced vigilance and hypersomnolence are significant risk factors for impaired road control and a possible enhanced crash risk. Adverse effects on direct psychomotor control mechanisms tend not to be severe with controlled heroin use; however the strong sedative effects of heroin misuse in occasional users together with the high risk of polydrug use lead to a serious risk of impaired decision-making.
Morbidity and Mortality

Heroin users often start at an early age and may continue until at least middle age. While the median age of heroin deaths is often in the late 20s, the annual mortality rate may range from 1% to 3% per year, which is 620 times those of nondrug users. This mortality is associated with both a significant risk of an adverse drug effect (i.e., overdose) and an increased incidence of serious diseases. Intravenous drug abuse of heroin can lead to a number of potentially life-threatening adverse effects. These include noninfectious neurological disorders such as arterial hypotension, venous congestion, and cerebral edema. Spongiform encephalopathy is a disorder that can occur following the smoking of heroin. Transverse myelopathy has also been reported in addicts who reuse heroin following a long period of abstinence (34 months). Symptoms include flaccid paralysis and complete sensory loss from the lower extremities to thoracic or even cervical levels. Other complications in heroin addicts include necrotizing angiitis resulting from unsterile injections, elevated compartmental pressure, and prolonged hypoxia. Stroke due to thromboembolism, hypotension, and positional vascular compression can also result from heroin abuse. Endocarditis has been found to be associated with heroin abuse. Gastrointestinal disorders that affect heroin users include enlargement of lymph nodes, inflammation
SUBSTANCE MISUSE/Heroin 155
of the portal tracts, and chronic hepatitis. Chronic intravenous heroin use can cause kidney disease, though factors determining individual susceptibility remain poorly understood. Kidney disease is also relatively common in heroin users. Acute renal failure can be secondary to rhabdomyolysis. Amyloidosis and focal glomerulosclerosis both induce heavy proteinuria and nephrotic syndrome. The amyloidosis is attributed to the chronic skin suppuration. The focal glomerulosclerosis resembles the idiopathic form and that seen with other conditions, and has a similar tendency to progress to end-stage renal failure. Heroin users show a high susceptibility to infections and other diseases due to the impairment of their immune systems from multiple causes caused by nutritional deficiencies and breach of skin defenses. The manifestation of infectious diseases in intravenous drug users plays a critical role in lifethreatening complications for addicts. The risk factors include needle sharing, unsafe sexual practices, undernourishment, poor hygiene, focal breaches of the skin barrier, and the injection of nonsterile substances into the body. These factors contribute to their diminished immune function and increase the risk of acquired immune deficiency syndrome (AIDS), viral hepatitis, pneumonia, and tuberculosis. Further complications derived from infections include endocarditis, septicemia, liver cirrhosis, meningitis, and tetanus. Foreign-body granulomas, complications of phlebitis, and formation of abcesses usually occur because of repeated injections of particulate material. Aspiration and fungal pneumonia also afflict heroin users more than the normal population. Noncardiogenic pulmonary edema and aspiration pneumonia are also known.
Definition of a Heroin Death

Deaths attributed to heroin use are not necessarily easy to define or classify. Deaths attributed to heroin can be defined as a case in which heroin use has been a substantial direct cause of death. This may occur even when other drugs are present that may have a significant toxic effect in their own right. This includes alcohol, benzodiazepines, sedating antidepressants, and sedating antipsychotic agents. The use of a speed ball through co-administration of an amphetamine or cocaine is a particularly dangerous habit. Heroin use can either be confirmed by the recent mention of heroin use in the circumstances (including presence in syringes) and/or the presence of 6-AM in the urine. Rarely is heroin or 6-AM detected in blood or other tissues. The association with needle track
marks, pinpoint pupils, decreased level of consciousness, and decreased respiratory rate and depth mark a person suffering from heroin toxicity. It is best to view a heroin death as a situation in which heroin use has precipitated a series of physiological events that lead to premature death. Persons may collapse within moments of an injection and die with the needle in their arm and have little if any morphine or 6-AM in their urine, but have relatively large amounts of morphine in their blood, or lapse into a coma and die slowly over a period of several hours. At the point of death in these delayed cases, their morphine concentration in blood is often relatively low, with significant amounts of morphine in urine. Rarely, anaphylactic reactions to heroin or dislodgement of an injected solid particle cause death from an embolism. However, pulmonary embolism from deep-vein thrombosis is much more common. There are certain findings at autopsy that can be used to distinguish heroin users. An external examination at autopsy frequently reveals the presence of injection sites, usually in the antecubital fossa, on the front of the elbow, or into one of the prominent veins in the forearms or dorsum of the hand. Old injection sites can show bruising and the veins may show overlying fibrosis where phlebitis has occurred, or old venous thrombosis with firm cord-like vessels under the skin. Tissue scars, which are sometimes pigmented and hypertrophied, result from nonsterile injection and can be present at any place where there are veins, including the neck and lower extremities. In longer-term users injection sites can occur in the femoral veins of both groins. Tattoos are another common finding and can conceal old scars or fresh injection sites. Inflammation, subcutaneous abscesses, and uneven induration of the skin are usually indicative of skin popping. These findings are common in women and older male addicts who may find it difficult to locate veins for intravenous injection. Internal findings at autopsy can include gross pulmonary edema. This can also be seen externally with an abundance of white frothy material oozing from the nostrils or mouth. Initially this froth is gray-white, but it may become blood-tinged as tissue autolysis progresses. Pulmonary edema is a consistent feature in chronic heroin users. Microscopic examination often reveals the presence of foreign materials in the scar tissues, such as fragments of cloth, cotton, talc, or other unidentifiable matter. Foreign-body giant-cell reactions are common in skin poppers, as is thrombosis in intravenous heroin users. Long-term use of heroin can also result in enlarged lymph nodes near the liver and other organs. Viral hepatitis type B and C can also
be transmitted by intravenous or oral ingestion of contaminated material and can often be found in heroin users. In some situations viral hepatitis can lead to liver cirrhosis.
Demographics of a Heroin User

Heroin users tend to be young, typically in the 2030year age group. Most are occasional users rather than regular or dependent users. Occasional use, most typically, involves sharing a quantity of heroin with a group of friends once a month. Social use may also include the consumption of alcohol. By contrast, those with strong physical dependence to heroin may administer the drug 510 times a day, depending on their resources. They may finance their use either from legitimate sources, or more usually engage in illegal activities such as dealing, theft, and prostitution to support their habit (Table 1). The majority of heroin deaths occur in the home, whereas nonfatal heroin overdoses more often occur in public places (e.g., shopping centers, toilets, street). The majority of heroin users are usually unemployed.
Presence of Other Drugs

An overwhelming majority of heroin-related deaths involves the use of other drugs. Alcohol is also typically detected in heroin users. In over 25% of deaths attributed to heroin, the blood alcohol concentration is over 0.10 g per 100 ml (1 g l1). In these cases the fatal dose of heroin is decreased significantly. In some jurisdictions benzodiazepines are detected in over 30% of fatal cases. Benzodiazepines are used to minimize withdrawal symptoms, but are also likely to increase the risk of death, particularly if misused. These sedatives enhance the respiratorydepressant effects of heroin, but also may relax the muscles controlling the upper airway, causing respiratory obstruction. Drugs such as the sedating antihistamines can prolong morphine metabolism leading to increased respiratory depression. Phenothiazines, including promethazine and chlorpromazine, are also known to potentiate opioids by interfering with the metabolism of morphine. Other opioids, such as methadone, have also been reported to cause death in heroin users because of an accumulation of methadone from one dose to another, with the final dose too much for their developed tolerance to opioids.
Treatment of Heroin Users

The abrupt withdrawal of heroin from persons physically dependent on the drug precipitates a withdrawal syndrome, the severity of which depends on the individual, the strength of heroin used, the size, and frequency of the dose, and the duration of drug use. The onset and duration of withdrawal symptoms also vary according to the duration of action of the drug. Withdrawal symptoms may be terminated by a suitable dose of morphine or another opioid. Methadone is currently the most widely used
Table 1 Characteristics of heroin users suffering from overdose

Characteristic Statistic
Mode of administration Age of victim Gender of victim Location of overdose Peak time of day Time of onset of toxicity Morphine blood concentration (free) Morphine urine concentration (total) Other contributing drugs (in loose order of priority)
Other contributing conditions
Most often intravenous Mean age about 2535 years Predominantly male Indoors > private dwelling > public places Early-morning hours and afternoon/evening Varies depending on posture, time of day, rate of injection, and use of other drugs: may be delayed some hours Median 0.20.3 mg l1, but toxicity can occur at much lower and much higher concentrations Sudden acute deaths often <1 mg l1 Others usually well above 1 mg l1 Benzodiazepines Alcohol Other opioids (e.g., codeine, methadone) Cocaine Amphetamines Antidepressants Antipsychotics Infections: HIV, HCV, TB, pneumonias Endocarditis, coronary artery disease, foreign-body granuloma, vascular diseases, stroke, cerebral edema, spongiform encephalopathy, kidney disease
HIV, human immunodeficiency virus; HCV, hepatitis C virus; TB, tuberculosis.
SUBSTANCE MISUSE/Substitution Drugs 157
pharmacotherapeutic agent for maintenance treatment of heroin addicts. Methadone is effective in the suppression of withdrawal symptoms and in the reduction or elimination of an addicts compulsion to take heroin. The major objective of the methadone maintenance program is to achieve long-lasting stabilization of the addicts drug dependence by providing methadone indefinitely in doses large enough to produce a level of cross-tolerance that is sufficient to block the effects of ordinary doses of heroin. Newer alternatives such as buprenorphine are now also common treatments of heroin dependence in some countries. Benzodiazepines are often used to treat anxiety and sleeplessness associated with the dependence. Clonidine is also used for the symptomatic treatment of opioid withdrawal. In some situations pharmacological agents are used to wean a person off opiates altogether.
See Also
Pharmacology of Legal and Illicit Drugs; Poisoning, Overview and Statistics; Toxicology: Overview
Further Reading
Baselt RH (2000) Disposition of Toxic Drugs and Chemicals in Man, 5th edn. Foster City, CA: Year Book Medical. Bedford KR, Nolan SL, Ohrusy R, Siegers JD (1987) The illicit preparation of morphine and heroin from pharmaceutical products containing codeine: homebake laboratories in New Zealand. Forensic Science International 34: 197204. Drummer OH, Odell M (2001) The Forensic Pharmacology of Drugs of Abuse. London: Arnolds. Ellenhorn MJ, Schonwald S, Ordog G, Wassrerberger J (eds.) (1997) Ellenhorns Medical Toxicology, 2nd edn. Baltimore, MD: Williams & Wilkins. Goodman, Gilmans (2001) The Pharmacological Basis of Therapeutics, 10th edn. Hardman JG, Limbird LI, Gilman AG (eds.). New York: McGraw Hill. Karch S (1998) Drug Abuse Handbook. Roca Baton, FL: CRC Press. Marcelline B (ed.) (2003) Medical-Legal Aspects of Drugs. Tucson, AZ: Lawyers & Judges. Shesser R, Jotte R, Olskhaker J (1991) The contribution of impurities to the acute morbidity of illegal drug use. American Journal of Emergency Medicine 9: 336342.
Interpretation of Toxicology Testing Results

Toxicology laboratories usually target morphine in the blood (or plasma) and urine; however some laboratories will target a combined total of morphine and the two glucuronide conjugates. This sum of the principal morphine species is known as total morphine. The major morphine glucuronide is the 3-metabolite, although the 6-glucuronide is also pharmacologically active. Morphine concentrations in blood in deaths attributed to heroin can typically vary from less than 0.1 to over 1 mg l1, although a median concentration is about 0.20.3 mg l1. Total morphine concentrations range to over 2 mg l1, although the median is about 0.30.6 mg l1. The absence of morphine in urine or concentrations less than 1 mg l1 strongly suggests that death has occurred shortly after injection, since no significant amounts of morphine have been excreted, and the deceased had not used heroin within 2 days of the fatal dose. Occasional users of heroin are unlikely to develop tolerance, hence are most at risk of a fatal overdose. In most cases other drugs will be present that will increase the inherent toxicity of heroin. This includes in particular, alcohol, benzodiazepines, cocaine, and amphetamines. Whatever the circumstances, it will be impossible to interpret the significance of a morphine concentration alone. While heroin can easily cause sudden and unexpected death, other relevant factors need to be excluded (i.e., natural disease and injuries) before arriving at a conclusion of a probable heroin death.
Substitution Drugs
K Wolff, Kings College, London, UK
Introduction
Substance misuse is often considered to be an unpopular subject with many doctors, partly because of the frequent relapses experienced by addicts and partly because of the behavioral problems that can occur when drug users interact with substance misuse treatment services. Many clinical drug treatment services are dominated by the prescribing of methadone to those dependent on heroin (diacetylmorphine). Methadone maintenance treatment (MMT) has been the most rapidly expanded treatment for heroin dependence since the 1970s, with increasingly large numbers of countries providing such treatment for extensive treatment populations. Even more recently buprenorphine, a partial agonist, has been introduced into drug treatment services and has provided an
158 SUBSTANCE MISUSE/Substitution Drugs
alternative to methadone. Both compounds will be discussed in detail as follows.
Methadone
As the number of heroin users and treatment services has grown worldwide, for a number of social, medical, and political reasons, methadone has become the orthodox prescribing response. Methadone prescribing in the UK, for instance, increased fourfold from 1988 to 1995. Substitution therapy with methadone has grown on the back of the identification that good MMT programs facilitate several positive outcomes for the addict. These include a reduction in the consumption of illicit heroin and in criminal behavior; and an improvement in the physiological, psychological, and social stabilization of addicts. Some of these efforts are largely evident even within the first month of once-daily treatment with a fixed dose of the drug. Similar benefits have been demonstrated in Australia and the USA where it has also been reported that MMT helps to reduce human immunodeficiency virus (HIV) and hepatitis B/C transmission.
Pharmacokinetics
Methadone is an unusual opioid in that it is orally effective and is well absorbed from the gastrointestinal tract, particularly the small intestine. The fraction of the oral dose that reaches the bloodstream is very high (bioavailability 7095%) compared to other opiates such as morphine (oral bioavailability 40 50%). However, methadone is highly lipophilic and so is sequestered into the tissues with continued dosing. It is also highly bound to plasma proteins (mainly a1-acid glycoprotein) so that the free (unbound) pharmacologically active fraction of the drug is very small, ranging from 6% to 14%. Hence, plasma methadone levels in the general circulation are therefore usually quite low. After oral administration it takes about 4 h in opiate addicts for the methadone concentration in blood to reach a peak (range 16 h). Unlike other opioids, methadone is also a very longacting drug whose action is prolonged because there is little significant first-pass effect (extraction rate (ER) from the liver 0.089) as is observed with morphine (ER 0.7). The half-life most commonly ascribed to methadone is conveniently about 24 h. However, in truth the elimination kinetics of the drug are highly complex and subject to wide variation between patients, depending on a number of key factors, some of which have yet to be fully characterized.
Overdose
Symptoms of intoxication may include confusion, light-headedness, sedation, sweating, headache,
constipation, and pruritus. However, such events (as well as dry mouth, drowsiness, and blurred vision) were reduced or had disappeared in opioid addicts within 6 months of beginning treatment with methadone. The incidence of adverse effects seems to vary amongst individuals and may be peculiar to the racemic form that is predominantly prescribed for heroin dependence. True overdose has been described as the consumption of a quantity of methadone in excess of an individuals current tolerance. Methadone death, on the other hand, is a term that has been used with various and confusing definitions and is often inclusive of complicating disease or pathological condition. More recently, methadone-related death has been used to refer to those cases in which methadone is considered the primary factor in the death but it is recognized that other drugs or underlying health factors may have contributed. Few published investigations have looked specifically into the circumstances of methadone-related deaths. However, it may be significant that the majority of methadone deaths occur at nighttime when sleep may augment the adverse effects (respiratory depression) of the drug. There does not appear to be a unique fatal dose of methadone, nor a plasma concentration above which, if the individual were untreated, death would occur. This is because it is possible for addicts to tolerate different quantities of methadone depending upon the degree of previous exposure to opioid-type drugs. Consequently, blood concentrations that cause toxicity in some are safe and effective in others. There is much uncertainty regarding a patients tolerance, and it remains difficulty to determine objectively the degree of tolerance in an addict presenting for treatment, such that the rate at which tolerance to methadone is developed or lost is not certain. Nevertheless, a lethal dose for a nontolerant adult could be as little as 25 mg (less if taken with alcohol or benzodiazepines). In children, if untreated, as little as 10 mg can be fatal. Most opiate addicts have experienced an overdose and many have witnessed it in others. Lack of awareness of the long-acting nature of methadone and uncertain effects following combination drug use (especially benzodiazepines, alcohol, and opioids) and generalized poor health make the opiate addict population a group vulnerable to both intentional and accidental overdose. Polydrug users who embark on a methadone maintenance program are also at risk of pharmacokinetic interactions occurring between methadone and other drugs. Accident and emergency personnel should be aware that an apparently collapsed adult presenting respiratory arrest with a pulse may be suggestive of opioid overdose.
Signs suggestive of an opioid overdose are as follows: . pinpoint pupils unreactive to light (not universally seen in children) . drowsiness with a variable degree of reduced consciousness/coma . respiratory depression with a decreased respiratory rate/depth (rate <8 min1) . bradycardic and hypotensive (this is usually mild except in severe cases).
Drug Interactions
Coadministration of other prescribed drugs is common practice for the addict population in treatment and can present clinical problems. Although the response produced by each drug may be known and thus predictable, that produced by the combination may be less certain. In some circumstances where patients self-administer either prescribed or illicit drugs, the response may be unpredictable and potentially problematic. Drugdrug interactions are expected to be graded and changes in the action of a drug vary continuously in relation to the plasma concentration of the interacting drug(s) and hence with time. Indeed, given in sufficiently high doses, almost any drug can interact with another. Thus, the incidence of drug interactions is likely to be very high on occasions when there is: 1. the use of substances in excess of recommended dosing regimes 2. binge-style consumption 3. polysubstance use. Drug interactions often involve a change in pharmacokinetics. Some drugs inhibit metabolizing enzymes and slow elimination: drugs that inhibit activity of certain cytochrome P450 liver enzymes (CYP3A4) have the potential to increase the concentration of methadone in blood. However, individuals will respond differently to combinations of drugs. The timeframe over which inhibitors exert their maximum effect is generally in the order of days, and therefore should not incur significant adverse effects. Theoretically complete inhibition of CYP3A4 could halve methadone clearance, with significant repercussions for the drugs pharmacological effects. For instance, serotonin uptake inhibitors such as sertraline variously inhibit isoenzymes responsible for the metabolism of methadone. It is recommended that clinicians should consider monitoring serum methadone levels when treating depressed or anxious methadone patients with second-generation antidepressants.
Inhibition of methadone clearance is most probable with strong liver enzyme inhibitors such as erythromycin and diazepam. The transient increase in plasma methadone levels and the positive subjective opiate effects that occur are likely to be the reason in the latter case (with diazepam) that benzodiazepines are commonly consumed by those prescribed methadone. Sedation and nausea are the most common clinical indications of toxicity, although at the onset of methadone treatment patients may also run the risk of the onset of respiratory depression. Ciprofloxacin caused profound sedation, confusion, and respiratory depression in a patient who had been previously stable on methadone for 6 years. Coadministration of the following drugs with methadone may cause adverse (though transient) effects in some susceptible patients, such as opioid-na ve individuals about to begin methadone therapy, pregnant opioid users, and those with end-stage liver disease: . calcium channel antagonists verapamil, nifedipine, diltiazem . protease inhibitors used in the treatment of HIV infection, e.g., ritonavir, zidovudine . antidepressants desipramine (raised plasma levels of desipramine) . antibiotics erythryomycin . histamine H2-antagonists (cimetidine and ranitidine) . antibacterials clotrimazole, ketoconazole . anxiolytics barbiturates like secobarbital, amobarbital . hormones progesterone, ethinylestradiol . selective serotonin reuptake inhibitors (SSRIs, e.g., sertraline, fluvoxamine, fluoxetine) . miscellaneous isoniazid, disulfiram, allopurinol, ciclosporin, quinidine, bromocriptine. Other drugs stimulate drug-metabolizing enzymes (induction) and hasten drug loss from the body. Those that induce activity of the liver enzyme CYP3A4 may decrease the plasma level of methadone and precipitate the onset of withdrawal symptoms. For instance, doubling the activity of the enzyme CYP3A4 could increase the clearance of methadone by up to 50%. The timeframe over which inducers exert their maximum effect is 23 weeks. In order to prevent treatment failure, dosages of methadone may need to be increased as a result of comedication with strong enzyme inducers. This should not be attempted until after the onset of withdrawal symptoms and should be undertaken in an incremental fashion. Moreover, methadone dosing for patients already on medications that inhibit or induce CYP3A4 should err toward caution.
Otherwise the onset of unexpected withdrawal symptoms may initiate use of illicit substances or methadone obtained illegally. Potent enzyme inducers include: . antiepileptics: carbamazepine, phenobarbital, phenytoin . antituberculosis: rifampicin, rifabutin confounded by isoniazid . steroids: dexamethasone . diuretic: spironolactone . nonnucleoside reverse transciptase inhibitors: nevirapine, efavirenz . nucleoside reverse transciptase inhibitors: abacavir . protease inhibitor: amprenavir.
Methadone Measurement
and forensic toxicology, fluorescence polarization immunoassay (FPIA) for whole blood has been utilized. Interestingly, immunohistochemical detection of methadone is possible and the intake of this medicament can now be proven morphologically.
Methadone Monitoring
A variety of increasingly sophisticated techniques have been used to detect methadone in biological samples. Qualitative analysis using automated immunoassay tests such as Emit (Roche, cut-off level 300 mg l1) is commonly used for urine drug-screening purposes by drug treatment services that prescribe methadone for opioid dependence. More recent developments include immunoassay for the primary metabolite of methadone, 2-ethylidene-1,5-dimethyl3,3-diphenyl pyrrolidine (EDDP, Microgenics CEDIA) cut-off level 100 mg l1. Urinalysis is expected to be unable to convey with any degree of accuracy compliance with methadone prescribing since methadone excretion is pH-dependent and the urinary ratio between methadone:EDDP is variable. Innovations in the field have seen the development of noninvasive tests involving the collection of oral fluid (Cozart) and oral mucosal transudate (OMT, Altrix) for on-site methadone screening. However, scientific scrutiny of the validity and efficacy of such tests is limited. Quantitative determination of methadone in biological fluids has been successfully undertaken using high-performance liquid chromatography (HPLC) with ultraviolet detection. However, sample preparation has often been the rate-limiting step; because of its lipophilic nature, methadone is difficult to extract from blood or plasma. A variety of preparation procedures have been reported, including nonaqueous electrophoresis-mass spectrometry and solid-phase microextraction (SPME). Unless provision is made for the supervised consumption of methadone by drug addicts, plasma methadone monitoring is recommended to monitor compliance. Research interest in the stereoisometry of methadone in order to investigate the kinetic profile of the different enantiomers has seen chiral chromatography developed for this purpose, whilst in clinical
To date, clinicians rely largely on clinical acumen when prescribing methadone. There is a need to take greater account of the individual patient, particularly during dosage induction, with regard to methadone compliance and individual tolerance to opioid drugs. It has been argued that the inadequate doses of methadone will encourage patients experiencing withdrawal symptoms to top up the prescribed dose of methadone with heroin, benzodiazepines, or illicit methadone, whilst doses that are too high may result in toxicity and overdose. There is a need to find a balance between effective dosing while minimizing the risk of therapeutic failure as stable methadone plasma concentrations are reached. However, although data consistently demonstrate the overall benefit of methadone treatment, even in the best-managed programs a considerable number of patients fail to follow their prescriptions. The size and composition of this group of addicts who fail remains largely undocumented. Various reasons have been proposed to explain why some patients do not fare well on methadone. The importance of the adequacy of dose has been highlighted by the recognition that suboptimal dosing is more likely to be associated with the continuation of, or return to, use of illicit opiates. Earlier reports found that insufficient dose (inadequate for the prevention of withdrawal symptoms for the total duration of the dosing interval 24 h) was the reason patients gave when questioned about their poor methadone compliance. More recently, it has been shown that the clearance of methadone is slower at the onset of treatment than at steady state and that for susceptible individuals methadone accumulation is a risk during dosage induction and may lead to overdose. One of the major benefits of quantitative measurements of methadone in plasma is the ability to monitor compliance. International studies of treatment response of those with opiate dependence have shown that patients who comply with the recommended course of treatment have longer-lasting posttreatment benefits. Thus, it is discouraging for many practitioners that opiate addicts are frequently poorly or noncompliant subjects and subsequently resume substance use. Unfortunately, it is probably for this reason, in conjunction with the difficulty of blood collection in this population, that
plasma measurements have not been widely used. However, evidence-based reports indicate growing evidence for such procedures as a useful clinical tool for methadone treatment, and dosage alterations based on interpretation of plasma measurements may help more patients do well on methadone.
Buprenorphine
Buprenorphine is a partial opiate agonist that is 2550 times more potent than morphine as an analgesic and has recently been registered in Europe, Australia, and various Asian countries for the management of opiate dependence. Buprenorphine has gained popularity in recent years after research suggested the drug to be comparable to MMT when used in equivalent doses. Buprenorphine has been reported to be more effective than symptomatic medications (such as clonidine and benzodiazepines) in individuals undergoing short-term detoxification from heroin. The registered product for treating opiate dependence, Subutex, is available in 0.4, 2, and 8 mg sublingual tablets. Standard therapeutic doses as a maintenance agent are in the order of 824 mg day1. However, the most effective buprenorphine induction procedure for individuals maintained on methadone has not been universally agreed. It does appear, however, that a gradual reduction of methadone dosage along with stable buprenorphine administration does not result in a greater attenuation of withdrawal signs and symptoms. Current clinical experience seems to suggest that subjects maintained on 30 mg methadone per day could be effectively transferred to buprenorphine over 510 days.
Pharmacokinetics
Conventional approaches to maintenance substitution treatment, such as oral methadone and sublingual buprenorphine, have been demonstrated to be effective for most clients entering treatment. Buprenorphine has a range of pharmacological properties that make it potentially well suited to treatment of heroin dependence. Buprenorphine has a long duration of action (40 48 h) when given sublingually in high doses, allowing once-a-day dosing for clients, and a considerable proportion of clients (approximately two-thirds) can be maintained on one dose every 2 or 3 days. Unlike methadone, buprenorphine has an active n-methylated metabolite known commonly as nor-buprenorphine. Buprenorphine considerably reduces (or blocks) the effects of coadministered heroin or other opioids due to its high affinity for opiate receptors (ability to
bind to the site of action) and its efficacy (ability to initiate effects once at the site of action). However, despite this pharmacological property, most efficacy outcome studies indicate that similar proportions of clients in buprenorphine and methadone treatment use additional heroin. This suggests that there may be a proportion of clients in treatment who continue to inject heroin for factors other than the pharmacological effects of their drug use (such as behavioral or social reasons), and several authors have identified the phenomenon of needle fixation. Buprenorphine acting predominantly as a partial agonist has a high affinity for m- and somewhat lower affinity for k-opioid receptor subtypes. It seems that buprenorphine acts competitively at the m-receptor in methadone-maintained subjects but noncompetitively in abstinent addicts. Therefore, when substituted for high-dose heroin, morphine, or methadone regimes, m-antagonistic actions predominate and this may precipitate opioid withdrawal symptom complaints because full agonists are being replaced by a compound which cannot activate m-receptors to the same extent. For instance, buprenorphine (28 mg) precipitated opioid withdrawal symptoms more prominently in patients maintained on 60 mg methadone per day than in those receiving 30 mg methadone per day. Additionally there are anecdotal reports from clinicians and patients that suggest that buprenorphine produces a low-intensity withdrawal syndrome after cessation of the drug. This is likely to be related to the saturation of receptor sites and the very slow dissociation of the drug from opioid receptors. Indeed, this maintenance of homeostasis may help to counter the development of an overt withdrawal syndrome commonly seen after the abrupt cessation of methadone (cold-turkey effect). It has been reported that withdrawal symptoms first appear 23 days after the last dose of buprenorphine and the intensity of symptoms peaks after about 2 weeks, lasting about 810 days in a similar fashion to methadone. It is also of importance that buprenorphine is not orally effective (undergoing extensive first-pass metabolism) and its low oral bioavailability makes this route of administration impractical and costly. Currently, the usual route of administration is sublingual. Sublingual dosing usually requires patients to be observed for a longer period of time than following oral administration in order to deter illicit diversion.
Misuse
There already exists a culture of injecting buprenorphine among some groups of drug users. Misuse of
buprenorphine tablets by injection has been widely reported in settings with limited or no supervision of medications. It has recently been reported in a sample of French injectors attending needle exchanges that 58% had injected buprenorphine tablets within the preceding 6 months, whilst of those who had been in buprenorphine treatment, 71% had injected their tablets during the previous 6 months. This high frequency of injecting occurred despite the harms associated with injecting buprenorphine tablets (local inflammation or infection at injecting sites, systemic infection, and bloodborne diseases such as hepatitis and HIV). Recently, a combination sublingual tablet of buprenorphine and naloxone has been formulated as a possible solution to problems with parenteral misuse, i.e., the unsanctioned injection of buprenorphine tablets. When the combination tablet is taken sublingually as intended, only a small proportion (approximately 10%) of naloxone is absorbed, with few discernible effects. However, if the combination sublingual dose of buprenorphine and naloxone is dissolved and injected, the naloxone will be fully absorbed and this will precipitate a brief, uncomfortable withdrawal reaction in a heroin user. The marketed combination product (Suboxone) has a 4:1 ratio of buprenorphine to naloxone.
Overdose
analytical difficulty because of the low doses that were consumed (0.02 and 0.04 mg tablets) and this drug was rarely identified during a routine drug screen. This difficulty remains and as a lipophilic drug, buprenorphine does not lend itself easily to enzyme immunoassay. Urine samples are most frequently tested for the presence of buprenorphine using radioimmunoassay (RIA), and quantitative measurements are restricted to chromatographic techniques. New techniques such as saliva testing have been suggested as alternative matrices but have yet to be tested rigorously. The primary factor influencing the effectiveness of buprenorphine may be different for different individuals. For some, the maximum morphine-like effects obtainable from buprenorphine will be the most important consideration. For others, the blockade of effects from exogenously administered opiates or the number and degree of withdrawal symptoms accompanying buprenorphine dosage reduction may be paramount. Regardless of which factor is most important, the evidence reported thus far indicates that buprenorphine deserves its place as a substitute treatment for opioid dependence, given its safety and pharmacological profile.
See Also
Buprenorphine, as a partial agonist, has an unusual doseresponse curve that is bell-shaped so that increasing dosage does not increase the magnitude of pharmacological effect. Clinically this is manifest by the observation that some effects such as respiratory depression appear to reach a plateau beyond which further dosage increments produce no additional response. Thus, even very high sublingual doses are tolerated by opiate-naive individuals, without the problems associated with other opioids (methadone, heroin) such as severe respiratory depression, coma, and death. However, individuals do demonstrate a high degree of variability for opioid responsiveness, and susceptible individuals may conceivably develop respiratory problems, especially when consuming concurrently alcohol and benzodiazepines. Once established at m-receptor sites, there is some evidence that buprenorphine has been difficult to antagonize with naloxone.
Buprenorphine Measurement Pharmacology of Legal and Illicit Drugs; Substance Misuse: Medical Effects; Cocaine and Other Stimulants; Sedatives; Patterns and Statistics; Crime
Further Reading
Cowan A, Lewis JW (1995) Buprenorphine: Combating Drug Abuse with a Unique Opioid. Chichester, UK: Wiley-Liss. Editorial (1996) Addiction. Lancet 347: 373376. Rostami-Hodjegan A, Wolff K, Hay AWM, Raistrick D, Calvert R, Tucker GT (1999) Population pharmacokinetics in opiate users: characterisation of time-dependent changes. British Journal of Clinical Pharmacology 47: 974986. Seivewright N (2000) Community Treatment of Drug Misuse: More Than Methadone. Cambridge, UK: Cambridge University Press. Strang J, Tober G (2003) Methadone Matters (Evolving Community Methadone Treatment of Opiate Addiction). London: Martin Dunitz. Wolff K (2002) Characterisation of methadone overdose: Clinical considerations and the scientific evidence. Therapeutic Drug Monitoring 4: 457470. Wolff K, Farrell M, Marsden J, Monteiro RA, Welch S, Strang J (1999) A review of biological indicators of illicit drug misuse, practical considerations and clinical usefulness. Addiction 94: 12791298.
In the 1980s, buprenorphine was not used as a substitute drug for the treatment of opioid dependence but was misused as a drug formulated for analgesia. This misuse of Temgesic, as it was known, presented
SUBSTANCE MISUSE/Sedatives 163
Sedatives
Introduction
Sedative and hypnotic drugs are among the most commonly prescribed and most commonly misused medications throughout the world. Often referred to as tranquilizers and sleeping pills, examples of these drugs include the benzodiazepines, barbiturates, and muscle relaxants. They are primarily used in the treatment of insomnia, sleep disorders, muscle pain and spasms, and anxiety; and are also used as preoperative anesthetics and to prevent seizures. Misuse and abuse of these medications commonly occur when patients self-administer increasing dosages or continue to use the drugs long after the insomnia, anxiety, or pain has lessened, and become reliant on the drugs to cope with life. Tolerance to these medications is common and patients are often unaware of the abuse potential of these drugs. These classes of drugs are also recreationally used for their sedative and intoxicating effects. Cocaine and heroin users may use benzodiazepines to enhance the effects of these illicit drugs and to help ease the withdrawal phase and induce sleep. Both patients and recreational drug users will obtain prescriptions from several doctors and forge prescriptions in order to maintain their supply. Due to their sedative and memory-impairing effects, these drugs can also be used to facilitate sexual assaults. Although the benzodiazepine Rohypnol is the best-known date-rape drug, other benzodiazepines and muscle relaxants have been used for this purpose.
Benzodiazepines
Benzodiazepines are among the most frequently prescribed therapeutic drugs in many countries. They are legally available in tablet and liquid form by prescription only, and the most common benzodiazepines are listed in Table 1. Benzodiazepines are further classified by their duration of action and halflives. Short-acting benzodiazepines have half-lives of less than 12 h, mid-acting benzodiazepines from about 12 to 40 h, and long-acting benzodiazepines have half-lives up to 200 h. This class of drug works by enhancing the action of the major inhibitory neurotransmitter gammaaminobutyric acid (GABA), and they primarily affect
a persons emotional reactions, memory, thinking, control of consciousness, muscle tone, and coordination. Therapeutically, benzodiazepines are used in the management of anxiety disorders, panic disorders, and stress; for the treatment of insomnia; as an adjunct for the relief of muscular pain and headaches; as anticonvulsants in status epilepticus; and as minor tranquilizers or sedatives. They are also used clinically to reduce the effects of acute alcohol withdrawal. Benzodiazepines such as diazepam and alprazolam are used recreationally as sedatives, and to enhance the effects of other drugs such as alcohol, methadone, and opioids. They can be used by cocaine users to increase seizure threshold and by heroin and cocaine users to reduce the impact of withdrawal symptoms between doses. The tablets are usually orally ingested but can be crushed and intravenously injected. The effects of benzodiazepines are usually dosedependent. At low doses, benzodiazepines are moderate sedatives causing sleepiness, drowsiness, confusion, and some loss of anterograde memory. At higher doses, disinhibition, severe sedation, and effects on respiration can occur. A state of intoxication similar to that of alcohol can be observed following large doses and the user may experience slurred speech, disorientation, and lack of balance and coordination. These effects are dramatically increased when benzodiazepines are administered concurrently with other central nervous system (CNS) depressants such as alcohol, narcotic analgesics, muscle relaxants, and barbiturates. Side-effects are common and include blurred or double vision, headache, vertigo, nausea and vomiting, tremor, and depression. Elderly patients are more likely to develop significant adverse effects. In overdose, users may experience paradoxical reactions such as anxiety, insomnia, stimulation, and hallucinations. Shallow breathing, clammy skin, weak and rapid pulse, coma, and death are possible, particularly when other CNS depressants have been consumed. Abrupt withdrawal from benzodiazepines can produce excitement, restlessness, dysphoria, anxiety, headache, muscle stiffness, tremors, insomnia, vomiting, abdominal cramps, delirium, panic attacks, and occasionally seizures or convulsions. Since the benzodiazepines do not address the underlying cause of the insomnia, anxiety, and/or muscle pain, these drugs should only be prescribed for short periods of time. Depending on the dose and frequency of use, tolerance may take several weeks or months to develop; however, the potential for drug dependency increases with long-term or chronic use.
164 SUBSTANCE MISUSE/Sedatives

Table 1 Commonly prescribed benzodiazepines and their primary therapeutic indications
Benzodiazepines Short- to mid-acting Common trade names Primary indication for use
Alprazolam Flunitrazepam Lorazepam Midazolam Nitrazepam Oxazepam Temazepam Triazolam

Mid- to long-acting
Xanax Rohypnol Ativan, Lorapam, Lorzem Versed Mogadon, Insoma, Nitrados Serepax, Serenid, Serax Normison, Euhypnos Halcion, Tricam Librium Klonopin, Rivotril Valium Dalmane
Anxiety and panic disorders Insomnia, sedative, preanesthetic Anxiety disorders, preanesthetic Anticonvulsant, sedative, preanesthetic Insomnia Anxiety disorders, alcohol withdrawal Insomnia Insomnia Anxiety disorders, muscle spasms, alcohol withdrawal Anticonvulsant Anxiety disorders, preanesthetic, anticonvulsant, alcohol withdrawal Insomnia
Chlordiazepoxide Clonazepam Diazepam Flurazepam
Nonbenzodiazepine Sedative Hypnotics

The nonbenzodiazepine sedative hypnotics are a newer class of sedative drugs and include zolpidem (e.g., Ambien), zaleplon (e.g., Sonata), and zopiclone (e.g., Imovane). They are primarily indicated for the short-term (4-week) treatment of insomnia. When taken as prescribed, immediately before bedtime, the main effects of zaleplon and zolpidem last between 2 and 5 h (dose-dependent) and there are generally no residual sedative effects the next morning. Zopiclone has a longer duration of action and its sedative effects can often be experienced during the morning after a nighttime dose. Similar to the benzodiazepines, this class of drug is commonly used in conjunction with other medications such as antidepressants, narcotic analgesics, and muscle relaxants. In addition to their sleep-inducing effects, the nonbenzodiazepine sedatives may also induce dizziness, lightheadedness, confusion, double vision, and memory impairment. Other side-effects include nausea, ataxia, slurred speech, slow reflexes, loss of balance and coordination, and vertigo. In overdose, patients may experience somnolence and drowsiness, varying degrees of consciousness, respiratory depression, and in extreme cases, coma and respiratory failure. Withdrawal following abrupt discontinuation may include mild dysphoria and insomnia, fatigue, vomiting, abdominal and muscle cramps, sweating, tremors, convulsions, and panic attacks. Tolerance to the nonbenzodiazepine sedatives and physical dependency are not typically observed following the recommended 4 weeks of therapeutic use; however, tolerance may develop following chronic administration and continued misuse.
Barbiturates
Barbiturates were commonly prescribed for several decades for the treatment of insomnia, anxiety disorders, and epileptic seizures. They were also recreationally used as downers, particularly to counteract large doses of cocaine, amphetamine, or methamphetamine, and their potential for abuse was high. Barbiturates are far less frequently prescribed nowadays and have largely been replaced by other sedativehypnotic drugs such as the benzodiazepines. However, they are still administered in hospitals as anticonvulsants and for the relief of anxiety prior to surgery, and for the short-term treatment of insomnia. Examples of barbiturates include amobarbital, barbital, butabarbital, pentobarbital, phenobarbital, and secobarbital. Similar to many of the sedativehypnotic drugs, patients may also experience slurred speech, somnolence, intoxication and feelings of drunkenness, memory impairment, and loss of balance and coordination. Tolerance to barbiturates develops rapidly, and long-term use can result in chronic tiredness, slowed reflexes, vision problems, sexual dysfunction, breathing disorders, and emotional instability. On abrupt withdrawal, disorientation, vomiting, sleep disorders, eating disorders, and hallucinations can occur.
Muscle Relaxants
Carisoprodol (Soma, Sodol, Soprodol, Soridol) is a centrally acting skeletal muscle relaxant commonly prescribed for the treatment of acute musculoskeletal pain. It is available in tablet form either on its own or in combination with aspirin and/or codeine. Meprobamate is the primary metabolite of carisoprodol;
SUBSTANCE MISUSE/Miscellaneous Drugs 165
however, it is also a CNS depressant in its own right (Miltown, Equanil) and is indicated for the management of anxiety disorders and for short-term treatment of anxiety symptoms. Both carisoprodol and meprobamate are frequently prescribed with other drugs such as opiates and benzodiazepines to control chronic pain. Following therapeutic use, the effects of carisoprodol begin within 30 min and last for up to 46 h. Meprobamate has a much longer duration of effect and drug accumulation may occur during chronic therapy. Unwanted effects are common with both drugs and include dizziness, drowsiness, disorientation, unsteadiness, slurred speech, ataxia, and tremor. Patients also have a tendency to doze off or fall asleep. In higher doses, patients may experience intoxication or drunken behavior, loss of balance and coordination, weakness, agitation, disorientation to place and time, and sleep disturbances. In abuse or overdose, patients may be consistently sedated and even become comatose. Overdose symptoms can include shallow breathing, clammy skin, weak and rapid pulse, paradoxical insomnia, convulsions, severe respiratory depression, and possibly death. Following chronic use of either drug, development of abuse and moderate physical and psychological dependence can occur. Abrupt discontinuation after long-term use can result in mild withdrawal symptoms such as anxiety, abdominal cramps, insomnia, vomiting, muscle twitching, confusion, and occasionally chills, convulsions, and hallucinations.
Holm KJ, Goa KL (2000) Zolpidem: an update of its pharmacology, therapeutic efficacy and tolerability in the treatment of insomnia. Drugs 59: 865889. Reeves RR, Carter OS, Pinkofsky HB, Struve FA, Bennett DM (1999) Carisoprodol (soma): abuse potential and physician unawareness. Journal of Addictive Diseases 18: 5156. Robertson MD, Marinetti LJ (2003) Carisoprodol effects on human performance and behavior. Forensic Science Review 15: 110. Salamone S (ed.) (2001) Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press.
Miscellaneous Drugs
Introduction
While drugs such as marijuana, cocaine, and heroin remain some of the most commonly abused substances throughout the world, drugs such as hallucinogens, inhalants, club drugs, and designer amphetamines appear to be gaining in popularity. Many users believe that these drugs are less dangerous and less addictive compared to drugs such as cocaine and heroin. While it is true that relatively few deaths are directly due to toxicity of hallucinogens, inhalants, and club drugs alone, their use is often associated with fatal accidents and violent or bizarre behavior. Hallucinogenic drugs such as lysergic acid diethylamide (LSD) and phencyclidine (PCP) were once popular in the 19601970s and are now showing a resurgence in use in many parts of the world. Inhalants are most frequently abused by a younger population of users due to their ease of availability and low cost. Recreational use of club drugs such as g-hydroxybutyrate (GHB) and 3,4-methylenedioxymethamphetamine (MDMA) has gained increasing popularity since the 1980s. In general, however, it is often difficult to estimate the true prevalence of these drugs in different populations as they are not routinely tested for in hospitals, emergency rooms, arrestees, and medical examiners or coroners offices, unless their use is suspected. Estimates are often based on anecdotal reports and user surveys. There is an incredible array of other psychedelic and/or designer amphetamine drugs that are less frequently used at clubs, parties, and in other social settings. These drugs include mescaline/peyote,
See Also
Pharmacology of Legal and Illicit Drugs; Substance Misuse: Cocaine and Other Stimulants; Substitution Drugs; Miscellaneous Drugs; Toxicology: Methods of Analysis, Antemortem; Methods of Analysis, Postmortem
Further Reading
American Psychiatric Association (1990) Benzodiazepine Dependence, Toxicity and Abuse. A Task Force Report of the American Psychiatric Association. Washington, DC: American Psychiatric Association. Couper FJ, Logan BK (2004) Drugs and Human Performance Fact Sheets. NHTSA Technical Report no. DOT HS 809 725. Washington, DC: US Department of Transportation. Drummer OH (2002) Benzodiazepines effects on human performance and behavior. Forensic Science Review 14: 114. Henningfield JE (1992) Barbiturates: Sleeping Potion or Intoxicant? 2nd edn. Broomall, PA: Chelsea House.
166 SUBSTANCE MISUSE/Miscellaneous Drugs
cathinone (khat), 4-methyl-2,5-dimethoxy-amphetamine (DOM), N,N-dimethyltryptamine (DMT), 3,4-methylenedioxyethylamphetamine (MDEA), 5-methoxy-di-isopropyltryptamine (5-MeO-DiPT; foxy), 2-bromo-2,5-dimethoxy-phenethylamine (2C-B; nexus), 4-propylthio-2,5-dimethoxyphenethylamine (2C-T-7), and a variety of anticholinergic drugs such as atropine and benztropine mesylate. These less frequently used substances are not included in any detail in this article; suffice to say that they share many of the same psychological and physiological effects as the better-known hallucinogens and club drugs. MDMA has both mild hallucinogenic and mild stimulant properties and is discussed in the club drug section, as it is most commonly used in such settings.
accidents, suicides, and violent and bizarre behavior have occurred during or shortly after intoxication.
Lysergic Acid Diethylamide
Hallucinogens and Dissociative Anesthetics

Hallucinogenic or psychedelic drugs are substances that cause profound perceptual distortions such as illusions, disorders of thought and mood, and hallucinations. Users will often see images, hear sounds, and feel sensations that seem real to them but do not exist in reality. The most commonly used hallucinogenic drugs throughout the world include LSD, PCP, ketamine, and psilocybin-containing mushrooms (Table 1). PCP and ketamine are also classed as dissociative anesthetics: with these substances, in an anesthetized state, the subject remains conscious with a staring gaze, flat facies, and rigid muscles. The effects of hallucinogenic drugs are often unpredictable and will depend largely on the dose ingested, the users personality and mood, the users expectations and the surroundings. Physically or psychologically unsettling events in the days before a trip can develop into more serious distress and trauma while tripping. There is also evidence that chronic use of psychedelic drugs is associated with the development of persistent psychotic disorders. Toxic fatalities from hallucinogenic drugs are rare; however, fatal
LSD is manufactured from lysergic acid, which occurs naturally in the ergot fungus that grows on wheat and rye. LSD is the model hallucinogen and is used recreationally for its ability to alter human perception and mood. It is a controlled substance throughout the world (e.g., schedule I in the USA; schedule I class A in the UK; schedule III in Canada). LSD is available in a clear, colorless liquid, a white powder, tablets (microdots), and capsule form. The liquid is often applied to small (0.5 cm or 1=4 in.) squares of blotter paper (frequently with colorful designs), stickers, sugar cubes, candy, drinks, or soda crackers. LSD is also available in small dropper bottles or in the form of gelatin sheets or shapes (window panes). The primary route of administration is oral, but LSD can be inhaled, injected, or transdermally applied. It is the most potent of hallucinogens, with doses as little as 2050 mg producing significant psychedelic effects. Nowadays, the strength of LSD typically ranges from 20 to 80 mg per dose, which is considerably less than doses reported during the 1960s and 1970s of 100200 mg or higher per unit. Experienced users typically administer 100200 mg to obtain a good high. Psychological effects of LSD include hallucinations, increased color perception, altered mental status, thought disorders, temporary psychosis, delusions, trance-like state, body image changes, and impaired depth, time, and space perceptions. Users may feel several emotions at once or swing rapidly from one emotion to another. Bad trips may consist of severe, terrifying thoughts and feelings; fear of losing control; despair and paranoia. Physiological and adverse effects include tachycardia, hypertension, elevated body temperature, dilated pupils, sweating, loss of appetite, sleeplessness, dry mouth, body tremors, speech difficulties, and piloerection. Other unwanted effects include rhabdomyolysis, renal failure,
Table 1 Examples of common hallucinogenic drugs and their street names

Drug name Common or street names
Lysergic acid diethylamide (LSD) Phencyclidine (PCP) Ketamine Psilocybin/psilocin (mushrooms) Dextromethorphan (DXM)
Acid, animal, barrels, beast, blotter or paper acid, cid, dots, kool aid, microdots, panes, Sandoz, tabs, trips, window pane Amp, angel dust, dips, elephant, fry, hog, peace pill, sherms, super kools, TicTac, tranq Ketalar, Ketaject, bump, cat valium, jet, K, lady K, special K, special LA coke, super acid, super K, vit K Cubes, liberty caps, magic mushrooms, mushies, psilocybes, shrooms Robitussin, Robbo tripping
prolonged mania, panic, and impairment in color discrimination. Following oral ingestion, the onset of the first effects is experienced in 2030 min, and peaks at 24 h. The main effects gradually diminish over 68 h; however, residual visual effects may last longer. Flashbacks may occur suddenly, often without warning, and may occur within a few days or more than a year after use. LSD users may also manifest relatively long-lasting psychoses similar to schizophrenia, or severe depression. Frequent and/or repeated doses of LSD are unusual, and as such, tolerance is not commonly observed. Tolerance may develop to the behavioral effects after 34 daily doses, but no withdrawal syndrome has been described. Cross-tolerance with mescaline and psilocybin has been demonstrated in animal models. Overall, LSD is not considered an addictive drug since it does not produce compulsive drug-seeking behavior.
Phencyclidine
PCP is a synthetic chemical made in clandestine laboratories, or it is diverted from veterinary sources. It is a controlled substance throughout the world (e.g., schedule II in the USA; schedule II class A in the UK; schedule I in Canada). PCP is available as either a clear yellowish liquid or white crystalline powder. It is often sold as a liquid in small shaker bottles, but can be mixed with dyes and sold in a variety of tablets, capsules, and colored powders. PCP analogs are also available and tend to be similar to or more toxic than PCP. Analogs include cyclohexamine (PCE), phenylcyclohexylpyrrolidine (PHP), phenylcyclopentylpiperidine (PCPP), and thienylcyclohexylpiperidine (TCP). PCP was originally developed as a surgical anesthetic in the 1950s but was later abandoned due to a high frequency of postoperative delirium with hallucinations. It became a popular drug of abuse in the 1960s, first in oral form then in smoked form. A light dose of PCP typically consists of 35 mg; a common dose is 510 mg; while a strong dose is often greater than 10 mg. Lighter doses are usually smoked, intravenously or intranasally administered, while heavier doses are commonly ingested orally. The liquid is most commonly sprinkled on tobacco, marijuana, parsley or mint leaves then smoked, or the cigarettes or joints themselves can be dipped in PCP solution. The resulting PCP dose can therefore vary widely. PCP is often administered or mixed with other drugs such as crack cocaine (beam me up), cocaine hydrochloride (lovelies), and marijuana (crystal supergrass, donk, killer joints, sherms, wacky weed, and wicky stick).
The onset of effects is very rapid when PCP is smoked or injected (15 min) and effects generally peak within 1530 min. The onset of effects is delayed when PCP is orally ingested (30 min). There is a gradual decline of major effects over 46 h, although a return to normal may take up to 24 h. Psychological effects are usually dose-dependent. Effects include euphoria, calmness, feelings of strength and invulnerability, lethargy, disorientation, drowsiness, loss of coordination, distinct changes in body awareness, distorted sensory perception, impaired concentration, disordered thinking, illusions and hallucinations, agitation, combativeness or violence, bizarre behavior, memory loss, and sedation. Physiological effects include a rise in blood pressure and heart rate, flushing, profuse sweating, generalized numbness of extremities, lack of response to painful stimuli, double or blurred vision, grimacing facial expression, speech difficulties, ataxia, muscular incoordination, marked analgesia, and anesthesia. In the anesthetized state, the subject remains conscious with a staring gaze and rigid muscles. Other adverse effects include nausea, vomiting, severe anxiety, paranoia, flashbacks, seizures, and coma. PCP can simulate schizophrenic-like symptomatology such as flattened affect, dissociative thought disorder, depersonalization, and catatonic states. Most PCP users administer the drug intermittently, although daily use has been reported and tolerance may develop. PCP can be addicting and use can lead to psychological dependence, craving, and drug-seeking behavior. Upon abrupt discontinuation, physical distress, lack of energy, and depression have been reported. Extended periods of use may lead to memory loss, difficulties with speech and thinking, depression, weight loss, liver function abnormalities, and rhabdomyolysis. These effects can last up to a year after cessation of use.
Ketamine
Ketamine is structurally related to PCP and is a white, crystalline powder or clear liquid. In many countries, it is legal to possess ketamine but illegal to sell or distribute it. In the USA it is currently a schedule III controlled substance and is classed as a dissociative anesthetic for animal and human use. In humans it is used as an anesthetic induction agent for diagnostic and surgical procedures, before the administration of general anesthetics. Ketamine is recreationally used as a psychedelic and for its dissociative effects. It is difficult to synthesize clandestinely and is usually stolen from veterinarian offices or diverted from legitimate pharmaceutical sources in liquid form. This liquid can be gently heated to evaporate the
water, leaving a white powder (ketamine hydrochloride), which can be snorted or orally ingested. Similar to PCP, ketamine can be added to cigarettes or marijuana and smoked. Psychological effects of ketamine are generally dose-related and include a decreased awareness of the general environment, drowsiness, sedation, dreamlike state, vivid dreams, feelings of invulnerability, increased distractibility, disorientation, and subjects are generally uncommunicative. Users can experience intense visual or polysensual hallucinations, impaired thought processes, out-of-body experiences, and changes in perception of body, surroundings, time, and sounds. Overall, users have likened the physical effects of ketamine to those of PCP, and the visual effects similar to LSD. Physiological effects of ketamine include a profound insensitivity to pain, anesthesia, cataplexy, immobility, increased heart rate and blood pressure, hypersalivation, increased urinary output, amnesia, slurred speech, and lack of coordination. There is a high incidence of adverse effects following ketamine use including anxiety, paranoia, chest pain, vomiting, palpitations, seizures, rhabdomyolysis, delirium, psychosis, and schizophrenic-like symptoms. Following long-term exposure to ketamine, high tolerance, drug craving, and flashbacks have been described. The onset of effects is within seconds if smoked, 15 min if injected, 515 min if snorted, and within 1030 min if ingested orally. Effects typically last only 3045 min if injected, 4560 min if snorted, and 12 h if taken orally. Subsequently, ketamine is often readministered due to this relatively short duration of action. Some subjects may experience dreams 24 h after drug administration.
Psilocybin
awareness, realizations about past feelings, quickly changing emotions, increased emotional sensitivity, and open- and closed-eye visuals. Unwanted effects can include nervousness, confusion, paranoia, anxiety, mild nausea, and frightening thoughts and visions. Psilocybin mushrooms are neither physically addicting nor likely to cause psychological dependence. In fact, many users find that their desire to use mushrooms lessens for a period of time after use. There is a short period of tolerance after mushroom use using mushrooms 2 days in a row can often lead to a diminished experience the second day.
Dextromethorphan (DXM)
DXM has recently become a popular recreational drug in younger users as it is legal and readily available. DXM is available in numerous prescriptions and over-the-counter cough and cold medications, often in combination with drugs such as pseudoephedrine, codeine, acetaminophen (paracetamol), guaifenesin, and chlorpheniramine. At recommended doses (60120 mg daily) dextromethorphan produces little or no central nervous system (CNS) depression. Recreationally, however, DXM is used in large doses (2001500 mg) for effects ranging from euphoria, mild stimulation and intoxication, to creative dreamlike experiences, and dissociation of mind from body. Side-effects can be serious if very large doses of the combined preparations are ingested. For example, chlorpheniramine and DXM can cause seizures, loss of consciousness, and bleeding.
Inhalants
Inhalants consist of any gas or fume inhaled for the purpose of getting high, and include volatile solvents, aerosols, and anesthetic gases (Table 2). Their recreational use is most common among younger adolescents, primarily because they are readily available, inexpensive, and legal. Two of the most commonly abused inhalants, toluene and nitrous oxide, are discussed in this section. The onset of inhalant effects is immediate, and overall effects of most inhalants include euphoria, grandiosity, floating sensation, inebriation similar to alcohol intoxication, CNS depression, numbness, confusion, nausea, vomiting, distorted perception of time and distance, possible hallucinations, and bizarre thoughts. Aerosols and anesthetic gases have a much shorter duration of action (minutes) compared to volatile solvents (hours). Characteristic indicators of inhalant use include a strong odor of solvent or chemical on the subjects breath or clothes; residue of substance around nose,
Psilocybin-containing mushrooms grow wild in many countries around the world; however, most of the recreationally used mushrooms are cultivated rather than picked wild. Psilocybin mushrooms can be grown indoors or outdoors and are brown or tan in color with a golden crown. A distinguishable feature of most psilocybin-containing mushrooms is that they bruise blue when handled. The mushrooms are most commonly swallowed, and recreational doses range from 1 to 5 g of dry mushrooms, depending on the species. Dosages for fresh mushrooms are about 10 times higher. The onset of effects is usually within 2060 min and effects generally last 36 h. Effects of psilocybin mushrooms often include an initial feeling described as anxiousness, feeling of energy and contentment, mental stimulation, feelings of insight or spiritual

Table 2 Examples of different types of inhalant and their sources
Inhalant type Examples Examples of source
Volatile solvents Aerosols Anesthetic gases
Acetone, benzene, ethyl acetate, toluene, mineral spirits, xylene Fluorocarbon propellants, freon, helium, insecticides Amyl nitrate, butyl nitrate, chloroform, enflurane, ether, halothane, isoflurane, nitrous oxide
Model airplane glue, paint, paint thinner, gasoline, kerosene, propane, correction fluid, nail polish remover Chemicals discharged from pressurized containers: furniture polish, hairspray, air fresheners Dental offices, whipped-cream dispensers. Medically used to produce analgesia
mouth, and hands; slurred speech and general intoxication. Frequent side-effects include nausea, vomiting, intense headache, bloodshot or watery eyes, lack of muscle control, and unconsciousness. There is also a risk of suffocation when the bag, mask, or balloon used to inhale these substances stays on the persons face as he or she loses consciousness.
Toluene
blood pressure. More severe intoxication can lead to arrhythmias, respiratory depression, convulsions, severe organ damage, coma, and death. Long-term toluene exposure can result in paranoid psychosis, temporal lobe epilepsy, attention deficits, visual impairment, and brain, liver, and kidney damage. Toluene has the potential to produce physical and psychological dependence, and signs of physical dependence are observed on withdrawal.
Nitrous Oxide
Toluene is a colorless, flammable liquid with a sweet pungent odor. It occurs naturally in crude oil and in the tolu tree. Toluene is also produced during the process of making gasoline and other fuels from crude oil, in making coke from coal, and as a byproduct in the manufacture of styrene. Toluene has numerous commercial and industrial applications: it is a solvent in paints, lacquers, thinners, glues, correction fluid, and nail polish remover, and is used in the printing and leather tanning processes. Acute and chronic accidental exposure to toluene can occur, particularly in work environments; however, toluene is frequently abused for its intoxicating effects. Since recreational use is common among younger adolescents, many jurisdictions have placed restrictions on the sale of toluene-containing products to minors. The main route of administration is via the inhalation of toluene vapor. It may be sniffed directly from on open container, or huffed from a rag soaked in the substance and held to the face. Alternatively, the open container or soaked rag can be placed in a bag where the vapors can concentrate before being inhaled. Toluene is rapidly absorbed and is detectable in the arterial blood within about 10 s of inhalation exposure. The effects of toluene generally last several hours and include euphoria, grandiosity, reduced inhibitions, feelings of inebriation, floating sensation, drowsiness, sedation, reduced ability to concentrate, distorted perception of time and distance, weakness, lethargy, fatigue, memory loss, delusions, and possibly hallucinations. Frequent physiological effects include irritation to the nose, throat, and eyes, headache, slurred speech, ataxia, impairment of coordination, nausea, vomiting, and elevated heart rate and
The two most commonly used anesthetic gases at clubs and parties are nitrous oxide and amyl nitrate. Nitrous oxide is a clear gas used in dentistry, and is known as nitrous, N2O, laughing gas, and hippy crack. The full effects of nitrous oxide are reached within a few seconds and last for several minutes only. It is obtained from clinics and hospitals, and purchased from retailers, most commonly in the form of whipped-cream charges. These charges are cracked into a balloon for inhalation. A single cartridge typically represents between one and three lungsfull of gas. This is generally enough for a short nitrousexperience, although users often choose to inhale many cartridges over a period of time. Nitrous oxide causes rapid analgesia, euphoria, mild sedation, laughing, and sometimes psychedelic and dissociative effects. Although nitrous oxide is typically unscheduled, its sale is often restricted to minors.
Club Drugs
Club drugs is a general term used for drugs that are popular at nightclubs and all-night dance parties (trances and raves). Included in this section are the mild stimulanthallucinogen MDMA, and GHB and its precursor drugs (Table 3). Methamphetamine, ketamine, nitrous oxide, and LSD are other popular club drugs but are discussed above. The use of club drugs appears to be widespread throughout the world, not only at dance parties and clubs, but also in normal recreational and social settings. Many users tend to experiment or regularly use a variety of club drugs in combination. MDMA and GHB are

Table 3 Examples of club drugs and their common street names
Club drug Common street name
3,4-Methylenedioxymethamphetamine (MDMA) Gamma-hydroxybutyrate (GHB) Gamma-butyrolactone (GBL) 1,4-Butanediol (1,4-BD)
Adam, candy canes, disco biscuit, doves, E, eckie, ecstasy, essence, hug drug, love drug, M&M, roll, X, XTC Degreaser lye, everclear, G, G-caps, gamma-OH, Georgia home boy, grievous bodily harm, liquid X, liquid XTC, salt water, scoop, soap, somatomax, vitaG, water Blue nitro, G3, invigorate, jolt, reactive, REMforce, renewtrient, resteze, revitalize, revivarant, verve, V35 Amino flex, enliven, FX, GHRE, innerG, NRG3, pine needle extract, revitalize, serenity, somatopro, thunder nectar, TMG, zen
both frequently taken in combination with ethanol, marijuana, methamphetamine, designer amphetamines, cocaine, nitrous oxide, and LSD. There have been numerous reports of subjects driving while under the influence of either GHB or MDMA, and of GHB being used as a date-rape drug because of its sedative properties.
Methylenedioxymethamphetamine (MDMA; ecstasy)
MDMA is a phenethylamine that has mild stimulant and psychedelic effects. MDMA is the methylenedioxy derivative of methamphetamine and is commonly available in tablet forms of various colors, carrying distinctive markings on one side such as a dove, E, yin/yang symbol, and Mitsubishi symbol. It is a controlled substance throughout the world (e.g., schedule I in the USA; schedule I class A in the UK; schedule III in Canada). MDMA was originally patented as an appetite suppressant and used as a possible adjunct to psychotherapy (to enhance insight and self-knowledge); however, there is currently no legitimate medical use for MDMA. Potency of street samples is highly variable, and tablets sold as ecstasy may contain little or no MDMA. Instead they may contain caffeine, ephedrine, 3,4-methylenedioxyamphetamine (MDA), phenylpropanolamine, paramethoxyamphetamine (PMA), dextromethorphan, amphetamine, methamphetamine, and ketamine. A single ecstasy tablet can contain anywhere from 10 to 150 mg of MDMA. User surveys report a range of doses between 50 and 700 mg in a session, with an average of 120 mg. A common pattern of use is binge consumption at all-night rave or dance parties. The onset of desired effects is within 2030 min and effects peak around 13 h, depending on dose. Residual and unwanted effects are generally gone within 2 h, although confusion, depression, and anxiety may last several days to weeks. Low-to-moderate doses (50200 mg) of MDMA produce psychological effects such as mild intoxication, relaxation, euphoria, an excited calm or peace,
feelings of well-being, increase in physical and emotional energy, increased sociability and closeness, increased responsiveness to touch, changes in perception, and empathy. At higher doses, agitation, panic attacks, and illusory or hallucinatory experiences may occur. Side-effects are relatively common and include blurred or double vision, sweating, muscle tension, involuntary jaw clenching, depression, fatigue, attentional dysfunction, hyperthermia, tachycardia, and convulsions. Persistent neurological deficits may occur, including serotonergic neuron damage, decreased serotonin production, poor memory recall, psychosis, and depersonalization. Tolerance to MDMA does develop; however, the occurrence of physical and/or psychological dependence is unknown.
GHB, g-butyrolactone (GBL), and 1,4-butanediol (1,4-BD)
GHB is a naturally occurring compound present in both mammalian CNS and peripheral tissue. It is also a minor metabolite and precursor of the major inhibitory neurotransmitter g-aminobutyric acid (GABA). GHB is classed as a CNS depressant and was first used clinically as an anesthetic in the 1960s. Its use was soon discontinued as it lacked analgesic properties and had an unpredictable duration of action. GHB is now used recreationally for its intoxicating, euphoric, sedative, and supposed muscle-enhancing properties. The precursor drugs g-butyrolactone (GBL) and 1,4-butanediol (BD) rapidly convert into GHB in the body and are subsequently used as GHB substitutes. GHB can be clandestinely made and street purity is often unknown. GBL and 1,4-BD are commercially available as industrial solvents and are used as ingredients in cleaners, solvents, paint removers, and engine degreasers. They are also sold as natural supplements and nontoxic dietary supplements over the internet, and in some health food stores and gymnasiums. Despite GHB being used for its reported muscle-enhancing effects, there is no evidence of actual increase in body mass.
SUBSTANCE MISUSE/Urine Analysis 171
In some European countries, GHB is still used as an anesthetic adjunct and hypnotic agent, to treat narcolepsy, and to suppress symptoms of alcohol dependence and opiate withdrawal syndrome. In the USA, medically formulated sodium oxybate (Xyrem) has been approved as a schedule III controlled substance for the treatment of cataplexy. Apart from this specific medical use, GHB is a schedule I controlled substance in the USA. At low doses, the psychological effects of GHB are similar to those seen with alcohol. Effects include relaxation, reduced inhibitions, euphoria, confusion, dizziness, drowsiness, sedation, and inebriation. Higher doses can result in agitation, combativeness, nausea, vomiting, profuse sweating, visual disturbances, incontinence, somnolence, uncontrolled shaking or seizures, bradycardia, hypothermia, suppression of gag reflex, severe respiratory depression, mild acute respiratory acidosis, and transient or unarousable unconsciousness. Deaths have been reported following overdose from GHB, GBL, and 1,4-BD alone, and in combination with other drugs. Caution must be exercised when interpreting GHB-related fatalities as GHB can be endogenously produced postmortem. The onset of effects following GHB use occurs within 1020 min and effects generally last 25 h. Tolerance can develop to some effects with chronic abuse, and cross-tolerance does exist between GHB and ethanol. Severe physical and psychological addiction can also occur with chronic abuse, and a withdrawal syndrome can start as early as 12 h after the last dose in addicted individuals.
Jacobs MR (1987) MDMA (ecstasy; 3,4-methylenedioxymethamphetamine). In: Jacobs MR (ed.) Drugs and Drug Abuse, 2nd edn., pp. 337343. Toronto, Canada: Addiction Research Foundation. Logan BK, Couper FJ (2003) 3,4-methylenedioxymethamphetamine effects on human performance and behavior. Forensic Science Review 15: 1128. Marinetti LJ (2001) g-Hydroxybutyric acid and its analogs, g-butyrolactone and 1,4 butanediol. In: Salamone S (ed.) Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press. Mozayani A (2002) Ketamine effects on human performance and behavior. Forensic Science Review 14: 123131. Mozayani A (2003) Phencyclidine effects on human performance and behavior. Forensic Science Review 15: 6173. Shulgin A, Shulgin A (2000) PIHKAL: A Chemical Love Story. Berkeley, CA: Transform Press.
Urine Analysis
A K Chaturvedi, Civil Aerospace Medical Institute, Oklahoma City, OK, USA R H Liu, Fooyin University, Kaohsiung Msien, Taiwan
Published by Elsevier Ltd. This article is adapted from Drugs of Abuse: Urine in Encyclopedia of Forensic Sciences, pp. 651662, 2000, Elsevier Ltd.
Introduction
Misuse of chemical substances for ameliorating social stresses is growing with the increasing complexities of modern societies. However, the majority of these substances have the potential for abuse, and their analyses in biological specimens have primarily been associated with death investigations and criminal prosecutions of those individuals accused of driving under the influence of alcohol and drugs. Recent emphases (especially in the USA) in adopting drug testing as a proactive approach in combating drug abuse in the criminal justice system, military, and workplace, including aviation and other transportation industries have dramatically increased drug testing using urine as the specimen of choice.
See Also
Sexual Offenses, Adult: Drug-Facilitated Sexual Assault; Substance Misuse: Cocaine and Other Stimulants; Sedatives; Toxicology: Methods of Analysis, Antemortem; Methods of Analysis, Postmortem
Further Reading
Balster R (1998) Neural basis of inhalant abuse. Drug and Alcohol Dependency 51: 207214. Burns M, Page T, Leikin J (1998) Drug Information Handbook for the Criminal Justice Professional. Hudson, OH: Lexi-Comp. Cohen RS (1998) The Love Drug: Marching to the Beat of Ecstasy. Binghamton, NY: Haworth Medical Press. Couper FJ, Logan BK (2004) Drugs and Human Performance Fact Sheets. National Highway Safety Administration. DOT HS 809 725. April 2004. Couper FJ, Marinetti L (2002) g-Hydroxybutyrate (GHB) effects on human performance and behavior. Forensic Science Review 14: 101121.
The views, opinions, and assertions contained herein are those of the authors and are not to be construed as official or reflecting the views of the United States (US) Government. The US Government assumes no liability for the contents or use thereof and does not endorse manufacturers or products referenced in this article.
172 SUBSTANCE MISUSE/Urine Analysis

Table 1 Immunoassay and gas chromatographymass spectrometry (GCMS) test cut-offs adopted by the US certification programs
Immunoassay (ng ml 1)a Drug category or drug Analyte targeted DoD HHS GCMS (ng ml 1)a Analyte targeted DoD HHS
Amphetamines
Barbiturates
Amphetamines Amphetamine Methamphetamine Secobarbital
500 500 200
1000
Cocaine Marijuana Opiates
Benzoylecgonine D9-THC-COOH Morphine
150 50 300
300 15 300
Phencyclidine LSD
Phencyclidine LSD
25 0.5
25
Amphetamine Methamphetamine Amobarbital Butalbital Pentobarbital Secobarbital Benzoylecgonine D9-THC-COOH Codeine Morphine 6-MAM Phencyclidine LSD
500 500 200 200 200 200 100 50 2000 4000 10 25 0.2
500 500b 150 15 2000 2000c 10c 25
Notes: DoD, US Department of Defense drug-testing program; HHS, US Department of Health and Human Services, National Laboratory Certification Program; D9-THC-COOH, 11-nor-D9-tetrahydrocannabinol-9-carboxylic acid; 6-MAM, 6-monoacetylmorphine; LSD, lysergic acid diethylamide. a For administrative purposes, a specimen is considered negative if the concentration of a target analyte is lower than the listed cut-off value. b A common practice is that a specimen is only considered positive if ! 200 ng ml1 amphetamine is also present. c Analysis of 6-MAM is only required when the concentration of morphine is ! 2000 ng ml1. Courtesy of Liu RH (1995) Evaluation of common immunoassay kits for effective workplace drug testing. In: Liu RH, Goldberger BA (eds.) Handbooks of Workplace Drug Testing. p. 70. Washington, DC: AACC Press. Courtesy of the American Association for Clinical Chemistry.
The Mandatory Guidelines for Federal Workplace Drug Testing Program published by the US Department of Health and Human Services formulated the mechanisms by which the National Laboratory Certification Program oversees civilian drug-testing activities in the USA. These guidelines and previously established military directives adopt urine for testing amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, lysergic acid diethylamide, methadone, methaqualone, opiates, phencyclidine, and propoxyphene. However, no random urine drug-testing program included all of these drugs or drug categories. Test methodologies normally include an immunoassay screening, preliminary, or initial test followed by gas chromatographymass spectrometry (GC-MS) confirmatory/quantitative test of the drug found positive by the immunoassay. In a workplace drug-testing program, screening test results within the laboratory are initially considered presumptive positive or negative terms not holding the same meanings as commonly defined in the laboratory for scientific measurements. Universal administrative cut-off values, rather than scientific and statistical detection limit data established by individual laboratories, are used as the basis for determining whether a specimen is presumptive positive or negative. Those considered positive are analyzed using a GC-MS protocol, having a universal
administrative cut-off concentration of the targeted analyte as the basis for deciding a specimen to be positive. Cut-off values adopted by the US workplace and the military drug-testing programs are shown in Table 1.
Urine Specimen Characteristics and Integrity

Characteristics
Compared with blood, urine is relatively free of protein, thus making it possible for direct extraction. Urine also contains high concentrations of metabolites and provides a longer detection time for most drugs. Since certain drugs may not be detected in urine, urine screening alone may not be sufficient for systematic toxicological evaluation. Blood is a better specimen for toxicological assessment, as blood drug concentrations can be well correlated with biological responses. Urine drug-testing results depend on factors, such as time lapse between specimen collection and drug intake and urine pH. Diet that changes urine pH may significantly alter excretion of drugs. Thus, basic drugs are more efficiently excreted in acidic urine, while acidic drugs are more efficiently excreted in alkaline urine.
SUBSTANCE MISUSE/Urine Analysis 173 Integrity Immunoassays in Urinalysis
Factors that may compromise specimen integrity include substitution of a nonurine liquid or urine from a different person, dilution or adulteration rendering the specimen unsuitable for certain methodologies, or the presence of certain characteristics associated with the specimen container or storage conditions. Origin identification Analysis of blood group antigens and polymorphic proteins may help exclude a specific person as the specimen donor, but these approaches are often ineffective due to their low discrimination power and the large sample size requirement. Squamous and transitional epithelial cells from the urinary tract generally provide adequate DNA for specimen individualization by polymerase chain reaction (PCR). Various PCR kits are commercially available to establish sequence (PMDQA1) and length (D1S80, short tandem repeats, and gender identification) polymorphism-based genotyping with a high discrimination power. Alteration and evaluation parameters Specimens can be altered in vivo by using diuretics, a large volume of liquid, pH-altering liquids, or test-interfering substances. Most widely reported in vitro alteration is achieved by using household products that often affect immunoassay results. Some products may actually destroy analytes, resulting in negative GC-MS results. It is difficult to distinguish between an altered urine sample and a genuine one that responds marginally toward tests implemented to monitor parameters specific gravity, pH, and creatinine level indicative of alteration. Selecting appropriate cut-off values of these parameters, which can identify presumptive positive altered specimens for further confirmatory identification of an adulterant, is no trivial matter. Other indicative parameters include temperature, color, and smell, and contents of additional substances, including diuretics and chemical species, such as glutaraldehyde, nitrite, chromium (VI), iodide, and peroxide, reportedly being specifically formulated for urine adulteration. Analyte stability Postcollection stability of analytes may affect the quantitative data and the interpretation of these results. Important factors affecting analyte stability include pH variations caused by intrinsic and extrinsic specimen characteristics; container properties and other storage conditions, such as light and temperature; and the presence of oxygen, preservatives, and other exogenous substances.
Immunoassays are adopted as the official preliminary test method in workplace urine drug-testing programs because they are sensitive, do not require pretreatment, can be automated, and are based on an underlying principle that is different from the confirmatory GC-MS methods.
Common Immunoassays
Most immunoassays adopt the competitive binding principle, wherein the antibody is allowed to react with a mixture of labeled (control) and unlabeled (sample) drugs. The presence of a drug in the sample is established based on the quantities of the labeled drug in the reacted or unreacted forms. The control drugs are labeled in different ways, each requiring different methods of detection and quantification. An immunoassay is considered heterogeneous if a phase-separation step is needed prior to detection. The process is designed to measure the extent of the labeled antigen linked (directly or indirectly) to the antibody, thus reflecting the amount of the test drug (unlabeled antigen) in the sample. Methodologies based on the measurement of radioactivity are heterogeneous because the detecting device cannot differentiate the source of the radioactivity (free or bound labeled antigen). Therefore, a separation step is required. Optical intensity-based immunoassays, not requiring a separation step, are considered homogeneous. In such assays, optical properties are modified through the substrates linkage (directly or indirectly) to the antibody.
Interference and Cross-Reactivity
Interference can be defined as the cause for a test result that does not provide the intended diagnostic finding reflecting the true status of the specimen. The following conditions may generate test results leading to incorrect interpretation of the specimen status: . the presence of the targeted analyte derived from sources other than the targeted drugs . the presence of cross-reacting compounds with known/unknown structures . specimen conditions that cause nonspecific binding or interfere with the assays detection mechanism . the presence of adulterants that degrade the analytes or alter their interacting characteristics. Targeted analytes from legitimate sources Some analytes targeted as indicators of drug abuse may derive from unintended exposure, food consumption, or licit medication. For example, morphine and
codeine may be observed in urine from individuals consuming food items with poppy seeds or prescriptions containing morphine and codeine. Methamphetamine and amphetamine can derive from the use of Vicks nasal inhaler and many other licit drugs. Cross-reacting compounds Such compounds are widely reported and many are listed in reagent inserts provided by the manufacturers. Identities of most reported cross-reacting compounds are known, while others are not. For example, structurally related compounds and unknown metabolites of chlorpromazine, brompheniramine, and labetalol cause the enzyme-multiplied immunoassay technique (EMIT) d.a.u. (drug abuse wine) monoclonal amphetamine/methamphetamine assay to generate falsepositive results. Metabolites of these drugs are believed to be responsible for the cross-reaction because such drugs were prescribed for the urine donors and were present in the urine specimens; and studies on control samples with various concentrations of the parent drugs alone failed to generate a positive result. Since reference metabolites of these drugs are not available, their exact cross-reacting cannot be established. Nonspecific binding Many postmortem urine specimens reportedly produced absorbance change values lower than those resulting from negative calibrators and specimens collected from healthy persons. Such ambiguity is attributed to the presence of nonspecific interacting materials, giving a higher initial absorbance value. Detection mechanism Enzyme immunoassays are most likely to suffer spectrometric interference caused by other substances. For example, . p-nitrophenol (a parathion metabolite), and tolmetin and its metabolites can absorb strongly in the 340-nm region at pH 8.0 . metronidazole or mefenamic acid causes excessively high initial absorbance values . salicyluric acid (the principal aspirin metabolite) reduces the absorptivity of NADH at 340 nm. Adulterants Adulterants with oxidizing ability may actually destroy the targeted drugs, thus rendering the specimen truly negative, while most adulterants cause nonspecific binding or create interference to the targeted antibodyantigen reaction or the detection mechanism. Many products are known to affect the responses of common immunoassays (Tables 2 and 3). Most interference studies did not compare the effects of adulterants on various immunoassays under the same
conditions; thus, it is difficult to make general statements concerning the robustness of one methodology over the others. It seems to be clear, however, that cannabinoid assays are more susceptible to the interfering effects of adulterants, particularly oxidants. Although numerous mechanisms have been proposed to account for the interference, exact causes are generally unknown. For example, bleach and chromium (VI) actually cause the degradation of D9THC-COOH (11-mor-D9-tetrahydrocannabinol-9carboxylic acid); and Visine was believed to increase the adhesion of D9-THC-COOH to the borosilicate glass containers, thereby reducing the availability of D9-THC-COOH in antibody-based assays.
GC-MS in Urinalysis
Confirmatory test procedures for drugs of abuse in biological media often include acidic, basic, or enzymatic hydrolysis; liquidliquid or solid-phase extraction; and often derivatization. Selective ion monitoring (SIM) GC-MS protocols are commonly used for the analysis of the limited number of drugs/metabolites targeted by workplace drug-testing programs.
Specimen Pretreatment
Many drugs and their metabolites have strong affinity to proteins, whereas most of their conjugates are highly hydrophilic and not amenable to organic solvent extraction. Thus, pretreatment procedures generally include the removal of the binding proteins, the hydrolysis of drug conjugates, and the extraction of the analytes from the resulting reaction mixture. Since urine has limited protein content, protein removal is not necessary. Drug conjugate hydrolysis Acidic and enzymatic hydrolyses have their merits. For example: . b-Glucuronidase releases intact benzodiazepines from their glucuronides without converting to their corresponding benzophenones, which is a typical product of acid hydrolysis. . Compared to b-glucuronidase, acid hydrolysis of morphine glucuronide is less time-consuming and can achieve a higher recovery rate. However, this process tends to cause the decomposition of acidlabile compounds in the matrix, leaving a dirty reaction mixture. Enzymatic hydrolysis may be preferred when the analyte is acid-labile and high recovery is not an important factor. Extraction This step typically removes interfering materials and concentrates the analyte.
Table 2 Effects of various adulterants on immunoassays for drugs of abuse

Adulterant Amphetamines Barbiturates Benzodiazepines Cocaine Opiates Phencyclidine Marijuana
Ammonia Ascorbate Bicarbonate Bleach Detergent Drano Golden seal Hand soap Joy Lime Peroxide Phosphate Salt (NaCl) Vanish Vinegar Visine
R R R R; E; F; C C E; C C F F R R C F; C E; C F F E; C C E; C F E R; E; F E; F E R E E R; F E F E R R E E R E; F R; E; C C F; C R; E; F; C E R; E; F; C C E; C F R; E; F; C C C E; F; C R; E; C R; E; C R; E R; E; F R
E R
Notes: Adulterant reduces () or increases () response to drug listed by methodology: R, radioimmunoassay; E, enzyme-multiplied immunoassay technique; F, fluorescence polarization immunoassay; C, cloned enzyme donor immunoassay. Courtesy of Dr Alan HB Wu and Forensic Science Review. With permission.
Table 3 Effects of various designer adulterants on immunoassays for drugs of abuse (Information is gathered from various literature reports.)
Designer adulterant Active content
a
Affected immunoassay drug category Product trade name Amphetamines Barbiturates Benzodiazepines Cocaine Opiates Phencyclidine Marijuana
Chromium (VI) Glutaraldehydeb Nitrite Peroxide
Urine Luck Urinaid Klear, Whizzies Stealth
E; P E P
E E
E E
E; P E P; D
All E P P; D
Notes: Adulterant reduces () or increases () response to drug listed by methodology: P, online particle immunoassay; D, CEDIA (cloned enzyme donor immunoassay) enzyme immunoassay; E, Syva enzyme-multiplied immunoassay technique; All, all immunoassays (gas chromatographymass spectrometry was used for this study and the analyte was found to be reduced or lost; thus, all immunoassays will presumably be affected). a The same designer product may have different contents when manufactured at different dates. The same active ingredient may be found in designer products bearing different names. b Effect on concentrations ranges from 0.75 to 2.00% (v/v) of glutaraldehyde in urine.
Liquidliquid extraction systems are designed to have the analyte partition, preferably into the organic phase in its unionized form or as an ion pair. The addition of a proper counter ion or pH adjustment of the sample may be used to facilitate a favorable partitioning of the drug. The analyte may also be salted out of the aqueous phase with high ionic strength of the medium. High concentrations of electrolytes are used to generate the ionic strength of the medium in salting-out approaches. In a solid-phase extraction process, separation is performed with a solid additive or column material using hydrophilic, hydrophobic, or ionic groups attached to silica gels. Over conventional liquidliquid procedures, solid-phase extraction approaches offer the advantages of less organic solvent usage, no foaming problems, shorter sample preparation time, and ease of incorporation into an automatic operation process. Solid-phase extraction procedures widely adopted for the drug urinalyses include four steps: (1) conditioning; (2) loading; (3) rinsing; and (4) eluting. The first conditioning solvent should be as strong as, or stronger than the elution solvent. The second conditioning solvent should be the same as or as close to the strength of the loading solvent as possible. The loading solvent should be as weak as possible to result in the tightest or narrowest band of adsorbed sample on the sorbent. A solvent that is slightly stronger or the same strength as the loading solvent is used as the rinse solvent. The rinse will elute unwanted sample components that are not as strongly retained as the analytes and also wash down small droplets of loading solvent adhering to the walls of the tube to ensure that all sample comes in contact with the sorbent. An ideal eluting solvent should elute the analytes within 510 bed volumes. The optimal amount of solvent to elute the analytes from a 500-mg cartridge is about 0.61.2 ml. Using a too-strong solvent will cause the elution of unnecessary sample components that are more strongly retained than the analytes, whereas a too-weak solvent will cause excessive elution solvent volumes. Sometimes, a desired solvent strength may be obtained by blending appropriate amounts of miscible solvents. If a water-immiscible eluant is selected and the analysis is to be performed with the GC, a drying procedure should be applied between the rinsing and the eluting steps. The combination of vacuum and a small amount of methanol can produce a dry eluate without causing a substantial loss of drugs.
Derivatization
chromatographic environment or to maximize their chromatographic separation and detection efficiencies. Specifically, derivatizations are carried out to: (1) improve the analytes volatility; (2) eliminate active functional groups that may cause undesired interactions with the chromatographic components resulting in peak loss (due to irreversible adsorption) or peak tailing (caused by reversible adsorption); and (3) achieve resolution of enantiomers. Derivatization is also an effective approach to facilitate analyte structure elucidation. In GC-MS applications, mass shifts in the spectra produced by different derivatizing agents can reveal valuable information concerning the functional groups in the analyte.
Qualitative Analysis
Serving as a chromatograph detector, a master spectrometer (MS) provides valuable fingerprint information by resolving and displaying charged particles originated from chromatograph eluates. Together with the chromatographic retention data, MS detection provides results that are normally considered conclusive for analyte identifications. MS detector also facilitates adopting an isotopic analog of the analyte as the internal standard. Serving as internal standard, an isotopic analog incorporated at the very early stage of the analysis serves as a model compound which, through its detection at the final step, provides a mechanism to prove successful completion of the entire analytical process. Verifying a successful protocol is essential when the targeted analyte is not detected in the test sample. Internal standards also provide intrasample retention time and ion intensity data that help in analyte identification and quantification. Generally, fully credible qualitative analysis, as opposed to target compound analysis, requires operating the MS in full-scan mode. The resulting spectra are then compared with those in the database or with an in-house standard; together with the GC retention data, analyte identification is often conclusive. Data collection using SIM mode can provide enhanced sensitivity and is commonly used as an integral part of a well-designed target-compound analysis (qualitative and quantitative) scheme. Without the benefits of complete spectra, the use of SIM data for qualitative determination purposes should be carefully scrutinized. For example: . As many ions as are characteristic of the analyte should be selected. Ideally, the molecular ion should be used if it exists with a reasonable intensity. If the analyte is derivatized with a derivatizing reagent prior to the GC-MS analysis, at least one of the
Many drugs/metabolites are derivatized to bring the analytes to the forms that are compatible with the
ions selected should include the complete or a characteristic moiety of the analyte. The exclusive use of only ions that are derived from the derivatizing reagent is not acceptable. . The intensity ratios of the selected ions should be closely monitored and compared with the corresponding ratios obtained from a standard that is analyzed under identical conditions. . The retention times of all ions monitored for the analyte should be coincidental. Additionally, the retention time and ion-intensity ratios of the internal standard should be compared with the corresponding data of the analyte. This intrasample information further improves the certainty of identification. . This approach should only be applied to well-studied systems wherein isotopic analogs of the analytes are normally available and incorporated in the analytical process. Furthermore, GC operation conditions should be optimized so that closely related compounds are chromatographed with distinguishable retention data. Given the fact that the identified analyte has also survived the chemical processes designed for the targeted analyte and proven effective for the internal standard, the above identification criteria should not reach an incorrect conclusion.
Quantitative Determination
analyte that are relatively free of cross-contribution by the internal standard. If these requirements are not met, quantitative results and the ion-intensity ratio data may become unreliable. Calibration A typical quantitative GC-MS protocol involves monitoring several selected ions from the analyte and the isotopic analog. Quantification is achieved by comparing a selected analyte-to-isotopic analog ion intensity ratio observed from the test specimen and the same ratio observed from the calibration standard. The calibration standard contains the same amount of the internal standard and a known amount of the analyte, and it is processed in parallel with the test specimen. The analyte concentration in the test specimen can be calculated using a one-point calibration approach (Figure 1). Alternatively, the ion-intensity ratio data can be used to determine the responses of a set of standards, from which a calibration curve is established and used for analyte concentration determination in a test specimen. Multiple-point calibration approaches can be implemented with different regression models, including linear or nonlinear; weighted or unweighted; and whether or not to force the regression through the point of origin. Multiple-point nonlinear calibration can provide a wider calibration range. Factors that should be carefully considered include: (1) cross-contribution of quantification ions selected for the analyte and the internal standard; and (2) selection of an appropriate calibration model to take into account the crosscontribution interference. Instrumentation SIM GC-MS parameters, such as instrument resolution, ion-monitoring position, threshold setting, and dwell time, must be carefully considered. Instrument drift from the peak center and the fluctuations in intensities of the selected ion beams will affect measurement precision, mainly because of the greater variation in the intensities of the weaker signals detected. Improper threshold settings will also affect the weaker signals to a greater extent. To achieve the best results, the signal level of the internal standard should be comparable with that of the analyte. Problems associated with differences in ion residence time in the ion source must also be addressed.
Although MS, by itself, is not necessarily the most quantitative detector for a chromatographic system, the use of an isotopic analog as the internal standard alleviates the effects of many variations in the analytical process. Therefore, this approach often provides the best overall quantitative result. Internal standard Deuterated analogs of the analytes are now commonly used internal standards for the quantification of drugs in biological matrices. However, not all deuterium-labeled isotopic analogs of the analyte are effective. Since the analyte and the internal standard are rarely separated adequately, the proposed isotopic analog must generate at least one ion (preferably two or three ions) that are relatively free of cross-contribution by the analyte. There must also be at least three ions designated for the
Figure 1 Formula for calculating analyte concentrations using a one-point calibration protocol. Reproduced from Liu RH. Elements and
Practice in Forensic Drug Urinalysis. Taipei, Taiwan: Central Police University Press. 1994.

H
O
CH2CHCH3
CH2CHCH3
NHR
O R2 R1 Butalbital: Secobarbital: Amobarbital: Pentobarbital:
N N O
NHR O Amphetamine: R = H; Methamphetamine and MDMA: R = CH3
H R2 = CH2CH(CH3)CH3 R2 = CH(CH3)C3H7 R2 = C4H9 R2 = CH(CH3)C3H7
Phosphate buffer (pH 5--7) Condition the column with methanol and phosphate buffer (pH 6) Bond Elut Certify Wash the loaded column with acetic acid and methanol Elute with 2% NH4OH (in ethyl acetate) Evaporate to dryness (40 8C) NaOH 1-Chlorobutane Aqueous (Waste) Organic Dimethylaminopyridine/acetone Trichloroacetic anhydride (5060 8C) Carbonate buffer (pH 9.5) NaOH Aqueous (Waste) Organic
O R1 = Cl3CC O CH2CHCH3 NRR1 O CH2CHCH3 NRR1
R1 = CH2CH=CH2; R1 = CH2CH=CH2; R1 = C2H5; R1 = C2H5;
Acetate buffer (pH 7) Condition the column with methanol and acetate buffer Bond Elut Certify II Wash the loaded column with acetate buffer and hexane/ethyl acetate (95:5) Elute with hexane/ethyl acetate (75:25) Evaporate to dryness Tetramethylammonium hydroxide/ DMSO (1:20) Iodomethane HCl; Isooctane Aqueous (Waste) O R2 R1 Organic CH3 N N O CH3 O
(A)
CH3 N C=O CHOH C=N COOH
(B)
Cl
OH
Oxazepam (metabolite of several benzodiazopines) -Glucuronidase 45% NH4OH Wash with water Du Pont Prep Type W Cartridge Elute with methanol/acetone/ methylene chloride (10:2:30)
O 9 11-Nor- -tetrahydrocannabinol-9-carboxylic acid (marijuana metabolite) 45% KOH (50--60 8C; 15 min) Carbonate buffer (pH 9.0--9.5) Wash the loaded column with 0.01 M NH4OH ( pH 9.5D10.2) and methanol Elute with ethyl acetate/methanol/ acetic acid (90:10:2) Evaporate to dryness Tetramethylammonium hydroxide/ DMSO (1:20) Iodomethane HCl; Isooctane Aqueous Organic COOCH3 OCH3
DuPont Prep Cartridge Aqueous (Waste) Methylene chloride Type A Organic Evaporate to dryness Methyl iodide Tetrahexylammonium hydrogen sulfate Aqueous (Waste)
Organic Evaporate to dryness Silver sulfate (saturated; hot) Toluene Aqueous Organic
(Waste)
Cl
CH3 N C=O CHOCH3 C=N
(Waste)
(C)
(D)
Figure 2 Specimen pretreatment procedures for gas chromatographymass spectrometry analysis of selected drugs in urine. (A) Amphetamines; (B) barbiturates; (C) oxazepam; (D) 11-nor-D9-tetrahydrocannabinol-9-carboxylic acid; (E) benzoylecgonine; (F) phencyclidine; (G) methadone; (H) opiates EDDP, 2-ethylidene-1,5-dimethyl-3,3-diphenyl-pyrzolidine. Adapted from Liu RH. Elements and Practice in Forensic Drug Urinalysis. Taipei, Taiwan: Central Police University Press. 1994.

O C OH
O C O
CH3 N
N Phencyclidine
Benzoylecgonine (cocaine metabolite) KOH, 3 M Wash the loaded column with water
DuPont Prep Cartridge Type W
Elute with acetone/ethyl acetate (50:50) Evaporate to dryness Tetramethylammonium hydroxide/ trimethylphenylammonium hydroxide/DMSO (1:40:200) Iodopropane (5055 8C) H2SO4 (0.3 N) Ethyl acetate Dichloromethane Aqueous (Waste) Aqueous (Waste)
NaOH Isooctaane Organic HCl Aqueous Organic

(Waste)
NaOH Carbonate buffer (pH 910) Isooctane Aqueous (Waste)
Aqueous
Organic (Waste)
Organic
Organic O CH3 N C OC3H7 O C

O
(E)
CHCH3 N CH3 CH3 Methadone EDDP Carbonate buffer (pH 9.09.2) 1-Chlorobutane Aqueous (Waste) Aqueous Carbonate buffer (pH 9.09.2) 1-Chlorobutane Aqueous Organic Organic
Acetate buffer (pH 12)
(F)
RO O N CH3 HO Morphine: R = H; Codeine: R = CH3
HCl/Autoclave (121 8C) KOH Carbonate buffer (pH 9.5) 10% Isobutanol/dichloromethane
CH3 C2H5COCCH2CHN(CH3)2
Aqueous (Waste)
Organic Sodium acetate (pH 1.0) Aqueous Organic (Waste) Organic

Pyridine/acetic anhydride Acetone (5060 8C) Methylcyclohexane Carbonate buffer (pH 9.5)
Organic (Waste) Carbonate buffer (pH 99.5) 10% Isobutanol/dichloromethane Aqueous (Waste)
(Waste) CH3 C2H5COCCH2CHN(CH3)2 CHCH3 N CH3 CH3 Methadone EDDP
Aqueous (Waste)
Organic RO O
O CH3C--O
N CH3
(G)
Figure 2 (continued)
(H)
Table 4 Important parameters for selective ion monitoring gas chromatographymass spectrometry analysis of targeted drugs
Drug category and druga Amphetamines Reconstitution solvent and approximate volume Oven temperature range (C) Ions monitored (m/z)b analyte; ISc Ion ratios monitored Cut-off (ng ml 1)d
Ethyl acetate 40100 ml
150200 118, 188, 190; 123, 194 91, 202, 204; 209, 211 204, 162, 202; 164, 208 237; 241 237; 241 251; 258 251; 258 181, 195, 196; 171, 169, 184, 185; 171, 169, 184, 185; 171, 181, 195, 196; 171,
189 189 189 189
Amphetamine Methamphetamine MDMA ()-Amphetamine ()-Amphetamine ()-Methamphetamine ()-Methamphetamine

Barbiturates
118/190, 188/190; 123/194 91/204, 202/204; 211/209 204/162, 202/162; 208/164
10 ml
100250
500 500 500d 500
20 ml
140190 181/196, 195/196; 171/189 184/169, 185/169; 171/189 184/169, 185/169; 171/189 153/168, 195/168; 171/189 313/372, 357/372; 360/375 210/331, 226/331; 213/334 229/341, 282/341; 232/344 310/369, 327/369; 372/330 186/243, 200/243; 205/248 255/271, 314/271; 276/319 223/294, 295/294; 226/297 200 200 200 200 15 150 2000 2000 25 300 300
Butalbital Amobarbital Pentobarbital Secobarbital

Cannabis
Cyclohexane 20 ml 20 ml Ethyl acetate 20 ml
220270 313, 357, 372; 360, 375 190240

210, 226, 331; 213, 334
D9-THC-COOH
Cocaine
Benzoylecgonine
Opiates
200270 229, 282, 341; 232, 344 310, 327, 369; 330, 372 186, 200, 243; 205, 248 255, 271, 314; 276, 319 223, 294, 295; 226, 297
Codeine Morphine
Phencyclidine Oxazepam Methadone
Methanol 20 ml Cyclohexane 20 ml Ethyl acetate 20 ml
170210
a Some of these drugs/metabolites were analyzed as derivatives using methodologies shown in Figure 2. (S)-()-N-(Trifluoroacetyl)prolyl chloride was used for stereochemical (enantiomeric) composition analyses of amphetamines. b Italic ions are used for quantification. c IS, Internal standard. 1-Phenyl-2-aminopropane-1,2,3,3,3-d5, 1-phenyl-2-(methyl-d3-amino)propane-1,1,2,3,3,3-d6, 1-(3,4-methylenedioxy)phenyl-2-(methylamino)propane-1,2,3,3,3-d5, pentobarbital-5-ethyl-d5, 11-nor-D9-tetrahydrocannabinol-9-carboxylic acid-50 -d3, benzoylecgonine-N-methyl-d3, codeine-N-methyl-d3, morphine-N-methyl-d3, phencyclidine-phenyld5,oxazepam-phenyl-d5, and methadone-1,1,1-d3 are used as the IS for respective analytes. MDMA, 3,4-methylenedioxymethamphetamine. D9-THC-COOH, 11-mor-D9tetrahydrocannabinol-9-carboxylic acid. d For administrative purposes, a sample is considered negative if the concentration of the target analyte is lower than the listed cut-off value. It is also common practice for a sample to be considered positive only if ! 200 ng ml1 amphetamine is also present. Reprinted with permission from Liu RH, Gadzala DE Handbook of Drug Analysis Applications in Forensic and Clinical Laboratories. Washington, DC: American Chemical Society. Copyright 1997.
To assure adequate accuracy, the number of data points that define an ion chromatographic peak must be sufficient about 20. Because ions are sequentially monitored, the number of data points for a GC peak depends not only on the chromatographic peak width but also on the ion-monitoring cycle time. The cycle time depends on the number of ions monitored, the time spent on monitoring each ion (dwell time), and the overhead time needed by the system for effective switches.
cut-off level adopted for the immunoassay. Immunoassay cut-offs that best correspond to a specific GC-MS cut-off vary with the type, the manufacturer, and the lot of the adopted immunoassay.
Interpretation
Application Examples
The implementation of workplace testing programs prompted the development of many robust extractionderivatization GC-MS procedures for routine and large-scale analysis of targeted drugs in urine (Figure 2). Important GC-MS parameters for targeted drugs are given in Table 4.
Immunoassay and GC-MS Result Correlation

Conventional immunoassays are typically not very specific, but cross-reactivity to drugs with similar structures can be advantageous. However, there is a significant disadvantage when used in workplace drug-testing programs. Under such programs, a positive result is only reported if the GC-MS result of a targeted drug/metabolite is at or above a cut-off concentration, and the immunoassay result is also at or above an identical or higher cut-off level. Thus, manufacturers often strive to reduce a reagents crossreacting characteristics and improve the detection mechanism so that immunoassay results can be more comparable with those of GC-MS. The ideal situation is that all samples screened positive are confirmed for the target drug/metabolite at or above the GC-MS cutoff, while those screened negative contain no, or below GC-MS cut-off, targeted drug/metabolite. Despite the lack of absolute specificity, it is anticipated for an immunoassay to respond sensitively toward variations of the analyte content, especially in the vicinity of the selected cut-offs. Furthermore, the immunoassay responses should correlate reasonably with the GC-MS results. The appropriate relationship between the cut-offs set for these two tests depends on the distribution pattern of drug metabolites and the cross-reactivity characteristics of the immunoassay. Testing for marijuana use serves as an excellent example to illustrate the importance of cut-off selection when using an immunoassay as the preliminary test for GC-MS analysis. With a specific cut-off adopted for the GC-MS test, the overall positive rate varies with the
Urine specimens tested positive for opiates and amphetamines could actually be caused by the use of licit medication or food items. For the opiate category, it is possible to confirm heroin use if 6monoacetylmorphine is detected. Concentrations of morphine and codeine and their ratio could provide useful, but often inconclusive, information. Detection of methamphetamine as an analytical artifact has been attributed to the presence of high level of ephedrine/pseudoephedrine in urine specimens. Therefore, a urine specimen cannot be reported positive for methamphetamine without the presence of amphetamine. Amphetamine and methamphetamine may derive from the use of Vicks nasal inhaler and other medicines. Amphetamine and methamphetamine may also be present as metabolites of other drugs. Since amphetamine and methamphetamine derived from such drugs have certain enantiomeric composition characteristics, enantiomeric analysis can often provide valuable information, but not always with definite conclusions. Unintended passive inhalation of marijuana and cocaine can result in the detection of the metabolites normally monitored to indicate the abuse of these drugs. The detection of cocaine metabolite has been attributed to drinking Health Inca Tea, handling of cocaine-contaminated currency, and skin absorption for those exposed to cocaine at their work environment. Analyte concentrations resulting from such drug exposure means are generally low. Therefore, claims should be carefully evaluated on a case-bycase basis. Opinions are often offered, but definite conclusions are not always achievable based on test results alone.
See Also
Substance Misuse: Herbal Medicine; Miscellaneous Drugs; Alternative Body Fluids Analysis; Patterns and Statistics
Further Reading
Department of Health and Human Services, Substance Abuse and Mental Health Services Administration (1994) Mandatory guidelines for federal workplace drug testing programs: notice. Federal Register 59: 2990829931.
SUBSTANCE MISUSE/Hair Analysis 183 Liu RH (1994) Elements and Practice in Forensic Drug Urinalysis. Taipei, Taiwan: Central Police University Press. Liu RH, Gadzala D (1997) Handbook of Drug Analysis: Application in Forensic and Clinical Laboratories. Washington, DC: American Chemical Society. Liu RH, Goldberger BA (1995) Handbooks of Workplace Drug Testing. Washington, DC: American Association for Clinical Chemistry. Wu AHB (1998) Integrity of urine specimens for toxicological analysis: adulteration, mechanism of action, and laboratory detection. Forensic Science Review 10: 4765.
Hair Analysis
T Mieczkowski, University of South Florida, Tampa, FL, USA
USA hair specimen analysis for poisoning was first introduced in court in 1882 in a homicide case in Wisconsin. The detection of psychoactive drugs in hair dates back more than 50 years, with the identification of barbiturates in animal hair first being reported in the early 1950s by Goldblum. Hair analysis has undergone intense development in the last two decades and has been rapidly applied to detection of the major illicit drugs of abuse, especially cannabis, cocaine, various opiates, phencyclidine, and amphetamines. Since the 1990s, American courts have generally accepted hair analysis for psychoactive drugs when introduced as evidence, and hair analysis is now quite commonly used as a drug-screening protocol for workplace and security monitoring. Commercial hair analysis services are now well developed and readily available. In 2000, the US Federal Food and Drug Administration issued its first approval to a commercial laboratory providing hair analysis for a commonly abused psychoactive drug.
Hair as a Drug-Assay Medium Introduction

There are a wide variety of legal and professional circumstances that call for an assessment of the presence of psychoactive drugs in biological specimens. Forensic scientists, medical practitioners, clinical workers in other helping professions, criminologists, and epidemiologists are among the specialists who seek to determine accurately and reliably types and intensities of psychoactive drug use. In recent years, there has been rapid development of relatively low-cost, dependable drug detection technologies, which has made it costeffective to evaluate drug use via biospecimen analysis. This is primarily due to the development of immunochemical drug assays. The most widely used of these applications is urinalysis. However, over the past decade the use of a variety of specimens has been considered. Attention has been given to saliva, sweat, and hair as suitable targets for analysis. Of these three, hair has been the most extensively developed and used. In this article, the development and use of hair analysis, and its application in detecting the presence of psychoactive, and mostly illegal, drugs are reviewed. Hair analysis offers several unique attributes when compared to other specimens for the purposes of drug detection, and this is reviewed in detail. While the application of hair analysis to the detection of psychoactive drugs is relatively new, the use of hair as a forensic specimen is itself rather old. Hair specimen analysis in Europe dates from the 1850s Casper, for example, reported the detection of arsenic in the hair of an exhumed cadaver in 1857. In the Hair analysis offers several unique attributes in comparison with more traditional specimens such as urine and blood. Blood is the least frequently employed drug identification method excluding, of course, postmortem examinations, largely because of its invasive nature, painful collection by hypodermic syringe, and the need to be collected under the supervision of a physician. Moreover, while blood is an excellent specimen to determine immediate intoxication status, it will not reveal historic drug use. Drugs are rapidly cleared from plasma, typically within a few hours of ingestion. Urinalysis, which offers several advantages over blood, has emerged over the last 20 years as the most popular specimen for drug assessment in routine monitoring circumstances. While its collection can be viewed as invasive of privacy, urinalysis is not biologically invasive. Generally, urine can be conveniently collected and does not require the supervision of a physician. Drugs remain in the urine longer than in the plasma for the commonly abused psychoactives, so it provides a better historic view than blood. Hair analysis offers several enhancements relative to urinalysis. The most critical of these is the enhancement of retrospective capacity the ability to look backward at historic drug use over a longer period. This is critically important in raising the likelihood of detection of the rapidly excreted and commonly abused drugs cocaine, amphetamines, and opiates most notably heroin. Table 1 compares hair-based drug testing to urinalysis along several commonly considered dimensions of utility and application.
184 SUBSTANCE MISUSE/Hair Analysis

Table 1 Comparing hair and urine specimens: selected properties
Urine specimens Hair specimens
Time window Dosage estimations Assay replication Evasion potential Storage/handling

a
23 days Not claimed Not comparable for repeat sample Moderate to high Somewhat difficult: refrigeration required, possible sepsis
Months or longer Possible ordinal ranking Comparable for repeat sample Low Simple storage under most conditions
With the exception of cannabinoids.
As noted in Table 1, since drugs are generally excreted quickly via the urine, but trapped indefinitely in the hair, the time limitations restricting urinalysis are improved by using hair specimens. This is the most prominent advantage of hair specimens. Urinalysis cannot be used for dosage estimations. Hair, however, can be used in limited ways to assess apparent relative intensity of use, although this aspect of hair analysis interpretation is more controversial. The general principle is that the amount of drug recovered from the hair bears a relationship to the amount recovered by the hair assay. However, because of individual biovariability, and a host of contextual, drug-consumption issues related to drug purity, concomitant consumption of fluids and foods, and other variations, the assessment of amount of drug use is recognized as restricted, at best, to ordinal rankings. It has been frequently reported that hair assays reveal greater concentrations of drug in the hair in individuals who use large amounts of drug when contrasted with those who use drugs sparingly. Likewise, it has been shown that in other bio-linked contexts (e.g., drug-using mothers and their neonates) there is a positive correlation between concentration values. Nevertheless, the absolute assay values cannot be tied to specific drug doses. Hair can be used to look at the relative changes within a single person by repeated samples collected over time and/or sequencing of a single sufficiently long hair sample. In many circumstances, hair assays have been shown to be approximately correlated to ordinal levels of use. In these circumstances, for example, a person typically functions as his/her own control, and relative changes in concentration in their hair can be tracked over time and reflect changes in drug consumption patterns. This is often seen in clinical settings, such as drug treatment programs that rely on hair analysis to monitor client compliance. A specific example of this effect will be presented later in this section.
The Basis of Hair Assays

The conceptual basis of hair analysis is that drugs and their metabolites ingested by an individual are
subsequently carried to and invade the follicle via the circulatory system. These materials are incorporated into the keratinaceous matrix of the hair shaft during hair protein synthesis. In the shaft, these materials form a stable drug bolus that remains embedded in the hair matrix. The bolus is not sharply defined, but does have a regional locus. With sufficiently long samples of hair, an approximate point in time can be inferred from the locus, provided the orientation of the sample (i.e., knowing which end is the scalp or proximal end) is maintained and an ordered sectioning of the hair sample is done. For particular categories of drugs, it appears that the embedded material is very stable, depending on the drug and the environment to which the hair is exposed. For example, several researchers have reported recovery of cocaine and opiates from hair samples that range from hundreds to thousands of years old. The research literature has reported the recovery of cocaine from mummified hair that was around two millennia old. Drugs and drug metabolites enter the hair shaft while it is subdermal, when the forming shaft is undergoing keratinization. As the hair emerges above the scalp, the embedded material is retained in the protein matrix of the hair. Figure 1 provides a very simplified illustration of this principle. Hair analysis begins with collection of the specimen. A hair sample, typically consisting of about 60 strands of hair, is removed by cutting from the scalp at the base of hair, normally from the posterior vertex of the head. In some circumstances, hair is collected from other body regions. (While body hair as well as scalp hair can be used to assay for drugs, the timelines that are applicable to head hair are different because body hair has a different growth/dormancy pattern.) The collected specimen is then examined to determine the condition of the hair, and to assess the degree to which the hair may be porous, damaged by harsh cosmetic treatment, or exhibit other characteristics that would warrant special caution in its use or the interpretation of the results of its analysis. If the hair is suitable for analysis, it is then subjected to a series of washes to remove external contaminants. The washes are analyzed to identify and quantify
SUBSTANCE MISUSE/Hair Analysis 185
Figure 1 Illustration of hair entrapment of drug materials. Psychemedics Corporation. Reproduced with permission.
the amount (if any) of drug contamination that may be present on the hair from environmental sources. The hair is then subjected to digestion that is used to liberate the sequestered analytes. Digestion of the hair sample, which can be accomplished with enzymes, acids, or bases, liquefies the specimens and prepares it for extraction. The resulting liquefied material is then subject to an initial screen by immunoassay to detect the materials of interest. Immunoassays are typically the method of choice for screening samples, and a variety of different immunoassay techniques have been used on hair samples, including radioimmunoassay, enzyme-multiplied immunoassay, and similar technologies. Confirmation of immunoassay results is usually carried out by gas chromatography/ mass spectrometry, or similar procedures. However, if desired, the material can be subject to direct mass spectrometric examination. Since immunoassay detection is, however, relatively rapid and certainly less costly than chromatographic and spectrometric methods in most commercial applications, immunoassay methods are used to screen out the negative samples, with chromatographic/spectrometric methods used to quantify and confirm samples that are screened as positive.
such as cannabinoids, appear to be weakly taken up or retained in the hair. There have been a variety of speculations regarding the bonding mechanism by which these materials are retained in the hair. Furthermore, since hair is a heterogeneous material, they appear to be bound to different components of the hair. Thus, it is widely accepted that several different mechanisms are responsible for the retention effect, and the relative preponderance of particular bonding types is substance-dependent. Under ordinary circumstances drugs which are deposited on the surface of the hair are not bound as tightly to hair as internally deposited material, and this material can be substantially removed by a series of initial ethanol or isopropyl alcohol washes followed by phosphate buffer washes. Criteria that determine the sufficiency of the washes to remove contaminants are based on analysis of the wash products themselves. By analyzing and comparing the analyte concentrations recovered from the washes to the recovered analyte from the hair matrix, a determination can be made distinguishing passive or environmental contaminates from internally deposited material. Figure 2 illustrates the effect of the wash procedures removal of materials that are superficially deposited and loosely bound to the hair surface, and the diminishing yields of contaminants as washes are repeated. The wash procedure is continued until no (or extremely small) quantities of drug are yielded in the wash analysis. The criteria for determining that analytes originate from ingested material and not externally deposited drug rest on specific wash ratio criteria, primarily developed by Baumgartner and Hill. Additionally, the presence of endogenous metabolites and in some cases unique endogenous metabolites (in addition to parent drug) is also a criterion for distinguishing contaminants from ingested drug. A number of commonly abused drugs yield rare or unique endogenous metabolites, such as cocaethylene, or ecgonine methylester for cocaine,
180
Wash/digest ratio
120
Sequestration of Drugs in Hair

Analytes of different drugs vary in their affinity for sequestration in hair. It appears that certain substances, e.g., cocaine, amphetamine, and opiates, are tightly bound in the hair, and once bound to the hair are very stable over long periods. Other materials,
60
0 1st 2nd 3rd 4th 5th 6th Wash
7th Digest
Figure 2 Idealized wash kinetics curve and specimen digest.
or 6-monoacetylmorphine for heroin. The detection of these materials, or the detection of these materials in concentrations of sufficient magnitude, indicates that the drug was ingested and metabolized by the body and not just superficially deposited on the external surface. For example, it is generally accepted that a benzoylecgonine concentration which is !5% of the parent cocaine value is indicative of use. It is important to bear in mind that the ratios of metabolite to parent drug found in hair are not necessarily the same as those found in plasma, sweat, or urine.
Repeated Assays, Sequential Assays, and the Quantitative Value of Assays in Relation to Dose
The DoseAssay Relationship
The use of hair analysis also offers the potential of utilizing the hair shaft as a type of approximating dosimeter. The mechanism of entrapment of endogenously deposited materials suggests that there should be a general pharmacological relationship between the amount of ingested drug and the amount of drug or drug metabolite recovered from the hair. Several researchers have reported such a relationship. Figure 3 indicates that the relationship between the selfreported use of cocaine and the recovery of cocaine from the hair has a positive linear relationship with a high correlation value (r 0:619; P 0:000). These data come from Baumgartners study of 43 selfreporting cocaine users who estimated their weekly consumption of cocaine and the simultaneous collection and analysis of their hair specimens. Similar correlations have been reported by several different
40.0 Cocaine in hair (ng/mg) 30.0
20.0
10.0
0.0 0.0 1.0 2.0 3.0 4.0 Weekly cocaine use (g) 5.0 6.0
Figure 3 Relationship between cocaine in hair and selfreported intensity of cocaine use (Baumgartner, personal communication).
researchers between cocaine-positive head hair from delivering mothers and their neonates. One should note, however, that not all reported doseassay results are consistent with these findings. Thus, the interpretation of doseassay conjectures should be conservative. One corollary of this dosimetric phenomenon is that the use of discrete sequential hair assays, based on specimen collection over a regular time interval, provides a way to track compliance to the requirement to abstain from drug use while in drug treatment. Figure 4 provides an example of this application and represents data from a psychiatric patient who entered treatment for cocaine and morphine abuse. The patient was subject to regular hair analysis as part of the therapeutic regimen. As the bar graph indicates, the patients reduction or cessation of use and subsequent relapse are reflected in the pattern of assay values over time. In this case, in the initial stages of treatment the patient continued to use both substances, but after approximately 18 months entered a period of markedly reduced use. The resulting hair assays indicated a diminution in the concentration of both substances. However, the patient left the immediate care of the physician to go on holiday, and during that time relapsed into both cocaine and opiate use. The pattern of the behavior is well represented by the hair analysis results. The sequential relationship illustrated in Figure 4 has been applied to examination of compliance for medicinals, as well. Williams, in his work in England, has shown similar patterns of hair analysis outcomes when assessing patient compliance with antiepileptic medication regimens. For example, Williams found correlation values for dose assay correlations that ranged from r 0:3 to r 0:8. One limitation of this interpretive aspect of hair analysis is that it does not allow the determination of an estimated dose as an interpolation of the assay value itself. Those who have attempted to fit a regression equation in order to estimate such a value have not been successful. It is problematic if one wishes to know the specific doseassay concentration, because little is known about the range of interpersonal biovariability of analytes in hair, and it appears that a number of variables can affect the final concentrations recovered from hair. However, the general pharmacological principle of the greater concentration consumed, the greater the concentration in the hair, seems to hold based on a variety of laboratory and field studies. As Figure 4 illustrates, the utilization of the quantitative assay values derived across time for the same individual is a useful way of measuring an individuals general change with both cocaine and some other categories of drugs.

Monthly hair analysis: single subject "N" Cocaine & Morphine
Concentration ng/mg
20 15 10 5 0
Jan Apr Sep Oct Nov Dec Jan Feb Mar Apr May June July Aug Sep Oct Nov Dec Jan Feb Mar Apr May 93 94 95
Cocaine Morphine
July 1993May 1995
Figure 4 Sequential sample results from a patient undergoing treatment for cocaine and morphine abuse.
Hair shaft
Growth direction Venous and arterial blood
Medulla
Cuticle Drug bolus Cortex
Follicle Embedded drug

Figure 5 Time and sequential sectioning of a hair sample.
Sequential Segmentation of a Single Hair Sample
A hair sample collected from a single individual can also be oriented from root to distal end and be sequentially sectioned, preserving the proximal to distal orientation of the hair shafts. Each section can then be analyzed individually, resulting in a timeexposure profile. This principle is illustrated in Figure 5. Drugs enter the hair via the circulating plasma, and since the plasma concentration attains a peak and then falls to zero over a relatively short interval, the drug and its metabolites constitute a bolus. Over time, that bolus moves from the scalp or proximal end toward the distal end of the hair as the hair elongates. This occurs at the rate of roughly 11.5 cm every 30 days. It is generally estimated that it takes approximately 57 days before a drug that was ingested will be detectable in the hair shaft that is accessible above the epidermis. In contrast, ingested drugs appear very rapidly in the urine. This means that the 4872 h of detectability (the urine
memory) make it an appropriate specimen for incidence testing, to determine if immediately after an event a person had been exposed to drugs within this short time span. Alternatively, hair analysis, by examining a much wider time window, can provide information of the long-term drug use history of an individual. This is the single most compelling advantage of hair analysis. A number of researchers have reported on the outcome of these sequential segmentary analyses. Hair samples have been analyzed by sequential analysis of a specimen involving known doses of cocaine, antiepileptic medicinals, nicotine, poisons, amphetamines, and opiates. The dosing pattern is typically quite consistently and appropriately represented in the sequential hair assay values. However, there have been a few reports on the hair reflecting an inconsistent pattern of sequential values. The potential utility of sequential assays to track the hair
100 Post-dose
Overdose event
75
50 Pre-dose 25
0 Proximal end Segment Direction of growth

Figure 6 Analysis of hair sample segments in a fatal cocaine overdose.
Distal end
concentration changes of an analyte of interest over time is very appealing. Figure 6 represents the sequential analysis of a hair sample collected postmortem from a case of cocaine overdose. In this case, a person unknowingly drank a bottle of liquid refreshment that had been adulterated with approximately 40 000 mg of cocaine as part of a smuggling attempt. A large portion of a shipment of a commercial beverage had high concentrations of cocaine dissolved in the liquid, which was then resealed into normal-looking containers. The intent of the smugglers was to extract the cocaine from the material after it had passed through customs. Unfortunately, a person unloading the stocks of material pilfered one of the bottles and drank it. In short order, the person suffered from seizures, and then lapsed into a coma. The individual was admitted to a hospital, but died after approximately 24 days. A 2.5-cm sample of hair was recovered from the cadaver and sequentially sectioned into five 0.5-cm segments. Each segment was analyzed for the presence of cocaine. Figure 6 shows the concentration values of the segments on the y-axis (in ng mg1 of hair), and the corresponding segment on the x-axis. The analysts concluded that the person had been a recreational user of cocaine before the event. The middle segment (no. 3) corresponds to the ingestionevent itself, and the relative diminished concentrations are consistent with growth and no further cocaine consumption while comatose.
Handbuch der gerichlichen Medizin the identification of arsenic in human hair recovered from a cadaver exhumed after more than a decade of internment, and American courts first accepted testimony on hair analysis as a forensic entity in the early 1880s. Since the early 1970s toxicological research work has focused great attention on illicit psychoactives and has demonstrated the deposition of various substances, including psychoactive drugs, in skin, saliva, hair, urine, apocrine excretia, and menstrual blood. In the late 1970s work has increasingly focused on human hair analysis for illicit psychoactives and medicinals. As a result a great many papers have been published on hair analysis using experimental models (involving both animal and human subjects) including: a number of in vitro experiments using human hair in various laboratory scenarios; papers which have looked at very large sample sizes and examined the epidemiological patterns of hair and urinalysis outcomes compared; and a number of papers focusing on specific questions related to the interpretation of hair analysis outcomes. Among these questions has been the doseassay relationship, the issue of passive contamination, and the potential effects of hair color, and in some cases ethnicity or race, on the interpretation of hair analysis data.
DoseAssay Relationship
Hair Analysis: Discussion and Summary

As noted earlier, the use of hair as a forensic medium for determining the presence of toxic agents is not, as commonly believed, a recent innovation. More than 130 years ago J L Casper reported in Praktisches
The basic nature of the doseassay relationship has already been discussed in an earlier section. In summary, the relationship between dose and assay values seems to follow the general pharmacological principle of the greater the material ingested, the greater the degree of concentration in the specimen and hence the higher the reported standardized concentration values. This basic principle has been affirmed in a number of studies, but the experience of researchers
has shown that there is substantial variability in assay outcomes, even under reasonably controlled conditions. In part this is probably due to the variety of techniques employed in the early phase of development of the assay protocol. There is reasonable consistency when we compare the doseassay relationship within a single competently executed assay technique, which indicates that the procedure is useful for a rank-order level of measurement. There is likely an intrinsic limitation on the utility of this aspect of the assay due to normal biovariability, and the fact that the drugsomatic body interaction is a highly complex one which is dependent on a number of variables, not all of them understood or recognized. However, as the example material presented has shown, reasonable interpretations of the correlation between intake and output, and especially so with relative changes within the individual, seem robust. It also appears, based on research reports from clinical settings, that on an aggregate level the dose assay relationship exhibits a rational, positive correlation. For example, researchers have reported that in clinical settings where persons are entering drug treatment programs, the intensity of drug use they report in the period leading up to their admission to treatment correlates well with the value of hair assays on a rank-order scale.
Passive Contamination
hair, which is uniquely metabolically associated with the use of heroin. Additionally, a metabolite may be present as a trace contaminant of a parent drug as a result of processes that the parent drug has undergone during manufacture, transport, or consumption. For example, benzoylecgonine is a major metabolite of cocaine, but can also be produced by the hydrolysis of cocaine outside the body. In these circumstances one can use a proportionality criteria. The amount of contaminant benzoylecgonine can be differentiated from metabolic benzoylecgonine by the preponderance of benzoylecgonine in the specimen. Currently, for example, it is generally accepted that benzoylecgonine present in a concentration which attains 5% of the value of the parent drug is due to metabolism.
Microingestion
Because hair is exposed to the environment, the issue of passive contamination of the hair from environmental sources is an issue of concern. Research has shown that hair can be contaminated by drugs from sources such as smoke, airborne contamination, and similar sources. If hair is unwashed and improperly prepared for analysis, then passive contamination will confound the results of a hair assay. Generally, the issue of passive contamination is handled by appropriate washing, examination of the wash products to assess the degree of external contaminants, and a comparison between the yield of the washes and the yield of the digested hair. An additional criterion useful in assessing the problem of contamination versus ingestion is the examination of the specimen for metabolites. In ideal circumstances, the drug may produce a unique endogenous metabolite, which can reasonably arise only from internal metabolic chemistry. For example, if cocaine and ethanol are consumed simultaneously, the metabolite cocaethylene is produced. While it is not impossible to produce cocaethylene in vitro, its appearance in hair is almost certainly due to the consumption of cocaine and ethanol. Another example is the identification of 6-monoacetylmorphine in
A related problem to passive contamination is the issue of microingestion of drugs. This issue is not uniquely related to hair analysis, but is a problem with any bioassay. If drugs are in the environment as a contaminant they can also be inhaled, inadvertently ingested, and thus detected in an assay procedure. Since we look to the specimen analysis to make a reasonable inference about drug use, this inference implies some knowing or willful consumption of the drug. A decision tree, illustrating the logical process of inference from assay illustrates this issue. Figure 7 identifies the logical pathway by which one may account for the appearance of drugs in an analytic specimen. There is no assay, nor any specimen type, which in and of itself can produce a result that will identify the intentions of the user and determine whether or not the individual is an active user or someone who has ingested unknowingly. However, there are two issues which bear upon the inferences an investigator might make in reaching a judgment regarding the potential conclusions represented by the lower-right corner box in the decision tree (Figure 7). If the results are below the clinically utilized threshold, the investigator can conclude that the individual likely had unknown environmental contact, and ingested the drug unknowingly. This will account for a specimen value which must lie between the limit of detection and the agreed-upon threshold. If the specimen value exceeds the threshold, then the explanation of microingestion is rejected as implausible. When considering acutely psychoactive drugs (i.e., drugs whose psychoactive properties have a quick and determined onset), it is unlikely that a person could experience substantial levels of dose without noticing the effects of the drug. However, there may be some circumstances in which an investigator would find such an
Active, knowingly Deny use. They may have . . .
Contamination arises from exposure
Exposure can be
Admit use
Inquire and investigate. The person may . . .
Passive, innocent 1. Ingested drug unknowingly 2. Had unknown environmental contact 3. Experienced both events 4. Misrepresented their drug use
Figure 7 Decision tree for passive exposure/active use analysis.
Ingested drug dose
Hair color/melanin content
Assay concentration value
Figure 8 Hypothesized relationship of hair color to hair assay outcome.
explanation plausible. In the event of an accounting for a postive result (above the threshold) based on the explanation of large-scale unknowing consumption, the investigator would be forced to rely on information other than that which can be revealed by a specimen analysis.
Color Effects
Several researchers have suggested that the utilization of hair analysis is burdened with a result bias. This bias is predicated on a hypothesized relationship between hair color and assay outcome, such that hair color acts as an intervening variable mediating the concentration of the analyte of interest. The path diagram given in Figure 8 can represent the simple model. The hypothesized relationship is that, as hair color is darker, i.e., more heavily pigmented, the hair assay value for cocaine will be greater for an equivalent dose of the analyte. While this conjecture has been called a bias, it is more appropriate to call it an effect. Furthermore, the observation has been sensationalized to some degree by the suggestion that this, in effect, means that hair analysis may be racially biased. This implication is generally based upon the erroneous belief that hair color is a phenotypic and distinctive expression of a racial type. It has also been suggested that some other unidentified race effect may be important, but such a conjecture has never been seriously developed in the literature. The literature describing the bias hypothesis has almost exclusively focused on cocaine, with a smaller literature examining opiates. The data in support of
the race effect have been weak and the association of race and hair color has been obscure and anecdotal. In some circumstances, the two concepts of race and hair color have been so intermingled that the determination of the exact independent variable being assessed in the research has been impossible to identify. The earliest studies suggested race bias, with the implication that race is a covariate of hair color. This linkage has been challenged, and some of its early proponents have modified their hypotheses regarding this potential race/color effect. For example, one research team that promoted a melanin bias theory could not duplicate their own findings, leading them to conclude that differences in melanin content are an unlikely explanation for variance in concentrations found among their subjects. In a recent evaluation of hair color, racial identity, and drug binding across several studies, the reported findings were determined to be not logically consistent with such an effect. In a series of statistical analyses on existing data and original data, a number of authors have not been able to identify a statistically meaningful color or race effect. Large population studies directly comparing the results of hair and urine tests have found no race/ color effect. Some work has identified a melanin effect for codeine, but the size of the effect appears to be very small. There are good data to show that some commonly abused drugs bind to melanin, and therefore, hair containing high amounts of melanin will exhibit higher concentrations of drug. However, it has also been clearly shown that drugs bind to hair in the absence of melanin, so melanin only accounts for a portion of the drug fragment contained in hair.
Furthermore, the nature of the effect is drug-dependent and so cannot be assumed across all categories of drugs. In cases where melanin concentration is a cause for concern several different technical solutions have been proposed. One is to remove the melanin fragment from the hair digest by centrifugation. Analyses of specimens that have undergone such a demelanization have not shown a statistically significant melanin effect. An alternative which has been suggested for controlling for a potential melanin effect is to standardize the assay by measuring melanin and reporting the drug concentration as a standardized unit per melanin weight. Lastly, there is nothing to preclude the use of hair analysis if such an effect were demonstrated, since it has already been suggested that one would simply need to weight the interpretation of the assay values to reflect any such effect. Indeed, it has been known for a long time that such effects exist for other specimens, but their magnitude is not sufficient to raise a concern regarding their basic utility. For example, renal clearance rates are a function of age the body slows in its ability to clear toxins from the blood as it ages. However, there has been no demonstration that this has adversely affected the use of urine specimens. Likewise, there is no general standardization of drug analysis for body weights. A fixed drug dose taken by two subjects of significantly different weight and size can hypothetically lead to a biased outcome because the smaller person will have a higher concentration of the drug. However, one has not seen a serious proposal that may need the thresholds of assays to be adjusted to accommodate these individual variations. Generally, these effects are considered negligible, affect the assay interpretation in a conservative direction, or they are so highly variable between subjects that they do not evidence a systematic level of effect.
use of this technique for monitoring the drugs, and the development of the potential of this technology for other related uses, such as measuring compliance to medicinal regimens, exposure to complex and novel toxins, and similar forensic and investigative challenges.
See Also
DNA: Hair Analysis; Substance Misuse: Cocaine and Other Stimulants; Heroin; Miscellaneous Drugs; Alternative Body Fluids Analysis; Patterns and Statistics
Further Reading
Baumgartner W, Hill V (1992) Hair analysis for drugs of abuse: decontamination issues. In: Sunshine I (ed.) Recent Developments in Therapeutic Drug Monitoring and Clinical Toxicology, pp. 577598. New York: Marcel Dekker. Baumgartner W, Hill V (1996) Hair analysis for organic analytes: methodology, reliability issues, and field studies. In: Kintz P (ed.) Drug Testing in Hair, pp. 223266. Boca Raton, FL: CRC Press. Chatt A, Katz S (1988) Hair Analysis: Applications in the Biomedical and Environmental Sciences. New York: VCH. Graham K, Koren G, Klein J, Schneiderman J, Greenwald M (1989) Determination of gestational cocaine exposure by hair analysis. Journal of the American Medical Association 262: 33283330. Grant T, Brown Z, Callahan C, Barr H, Streissguth A (1994) Cocaine exposure during pregnancy: improving assessment with radioimmunoassay of maternal hair. Obstetrics and Gynecology 83: 524531. Hoffman BH (1999) Analysis of race effects on drug-test results. Journal of Occupational and Environmental Medicine 41: 612614. Jehuda Y (1995) Forensic Applications of Mass Spectrometry. Boca Raton, FL: CRC Press. Kintz P (ed.) (1996) Drug Testing in Hair. Boca Raton, FL: CRC Press. Kintz P (2004) Hair analysis. In: Moffat A, Osselton M, Widdop B (eds.) Clarkes Analysis of Drugs and Poisons 2004, pp. 124133. London: Pharmaceutical Press. Koren G, Klein J, Forman R, Graham K (1992) Hair analysis of cocaine: differentiation between systemic exposure and external contamination. Journal of Clinical Pharmacology 32: 671675. Mieczkowski T (2000) Drug Testing Technologies: Field Applications and Assessments. Boca Raton, FL: CRC Press. Mieczkowski T (2001) Drug screening technologies: a review of capacities, limits, and issues influencing interpretation of drug tests in clinical and field settings. In: Coombs R (ed.) Addiction Recovery Tools: A Practitioners Handbook, pp. 111126. Newbury Park, CA: Sage Publications.
Conclusion
In spite of the popular conception that hair analysis is a novel technique, it is actually over a century old. The detection of poisons in hair is a longestablished forensic investigative tool. What is notable is the rapidity of development of hair analysis for the detection of illicit psychoactive drugs over the last 20 years. Hair analysis has successfully applied immunoassay chemistry and sophisticated mass spectrometric technology to the identification of many classes of drugs. This has created an extended capability to look back for relatively long periods of time in determining the history of drug use and exposure. Because hair is a stable and easyto-collect matrix, one can expect to see an increasing
192 SUBSTANCE MISUSE/Alternative Body Fluids Analysis Mieczkowski T, Newel R (1995) An evaluation of patterns of race and sex bias in cocaine assays of human hair. In: de Zeeuw R, Al Hosani I, Munthiri S, Maqbool A (eds.) Proceedings of the International Conference on Hair Analysis in Forensic Toxicology, pp. 90107. Abu Dhabi: Royal Government of the United Arab Emirates. Rook A (1975) Racial and other genetic variations in hair form. British Journal of Dermatology 92: 599. Wang W, Cone E (1995) Testing human hair for drugs of abuse. IV. Environmental cocaine contamination and washing effects. Forensic Science International 70: 3951.
Alternative Body Fluids Analysis

S Kerrigan, Houston, TX, USA B A Goldberger, University of Florida College of Medicine, Gainesville, FL, USA
2005, Elsevier Ltd. All Rights Reserved. This article is adapted from Drugs of Abuse: Body Fluids in Encyclopedia of Forensic Sciences, pp. 616626, 2000, Elsevier Ltd.
Drugs of abuse are frequently self-administered by oral, intranasal, intravenous, or smoked routes, although passive smoke inhalation and ingestion of certain foodstuffs may produce detectable amounts of drug or metabolite. Unconventional drug exposure, such as that which occurs in utero or in nursing mothers, has also necessitated the use of alternative biological specimens. Our discussion of these unconventional samples is limited to amniotic fluid, breast milk, saliva, semen, and sweat. The growing concern regarding the effects of drugs on health and human performance has resulted in an explosion of interest in alternative body fluid analysis in multiple forums: law enforcement, probation, parole, drug compliance and abstinence programs, employment, health, and insurance among others. The relative expectations, limitations, and interpretation vary widely between these different applications. Selection of the most appropriate biological fluid is critical, as each may provide unique chemical and pharmacologic information. Factors that influence specimen collection are listed in Table 1 and the interpretive value, advantages, and disadvantages of different biological fluids are summarized in Table 2.
Table 1 Factors influencing the choice of biofluid
Introduction
Blood and urine have long been the dominant matrices for the identification of substance misuse. Incorporation of drugs into these body fluids is well understood, and the analysis and interpretation of these findings have become routine for many commonly abused drugs. More recently, interest has shifted toward alternative specimens that may offer distinct advantages over conventional body fluids. These benefits may include long-term, cumulative information on drug use, or the convenience of noninvasive sample collection. Following absorption of a drug, distribution, metabolism, and excretion pathways account for the sequential appearance of drug and metabolite in different tissues and fluids. Physicochemical characteristics of the drug and biological fluid can be used to rationalize or predict the appearance of drug in a particular fluid or compartment of the body. The pKa, lipid-solubility, protein-binding, and body fluid composition determine the extent to which the drug is present. Transfer of drug from the circulating blood plasma (pH 7.4) to another biological fluid involves transport across membranes, which are an effective barrier against ionized, highly polar compounds. Following penetration of the membrane and transfer into the biofluid, the pH differential may result in ionization of the drug, restricting further mobility. Accumulation of the drug in this way is commonly referred to as ion trapping.
Sample collection
Invasiveness Risk of infection, complication, hazards Protection of privacy Ease and speed of collection Training of personnel (medical/nonmedical) Likelihood of adulteration Contamination Volume of specimen
Analysis
Qualitative or quantitative Window of detection Drug concentration/accumulation in biofluid Parent drug or metabolite(s) Stability of drug(s) Biofluid storage requirements Pretreatment of specimen Limitations of the matrix Likelihood of interferences Inter- and intrasubject variability of the matrix Use of existing analytical procedures Speed of analysis Personnel training requirements Appropriate cut-off concentrations
Interpretation
Pharmacologic effects Behavioral effects Indicator of recent drug use (h) Short-term drug exposure (days) Long-term drug exposure (weeks) Forensic defensibility Reproduced from Kerrigan S and Goldberger BA: Drugs of Abuse: Body Fluids. In: Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
SUBSTANCE MISUSE/Alternative Body Fluids Analysis 193

Table 2 Advantages and disadvantages of sampling of body fluids
Biofluid Advantages Disadvantages
Amniotic fluid
Breast milk
Minimal sample preparation Amenable to most analytical techniques Relatively few interferences Useful in determining in utero exposure at an early stage of development (1620 weeks) Many drugs determined Maternal and neonatal drug exposure can be determined
Highly invasive sampling procedure Requires local anesthetic, ultrasound scan, and highly trained personnel Risk of complication associated with sampling High lipid content may interfere with analysis Additional extraction steps may be required Disposition of drug varies with milk composition Matrix variability between individuals and in one feed Inconvenient specimen collection (requires pump) Invasion of privacy Low concentration of drug relative to urine Drug concentration varies with saliva flow rate and pH Sample collection may influence drug disposition Small sample volume (15 ml) Short drug detection time (similar to blood) Unsuitable matrix for determining drug history Possibility of sample adulteration by mouth Contamination of saliva after smoking or orally ingested drug Drug instability/transformation
Saliva
Semen
Noninvasive sample collection Readily accessible Rapid and economical collection Minimal sample preparation Few interferences Amenable to most analytical techniques Many drugs determined Parent drug present Correlation with free drug concentration in blood Pharmacologic interpretation possible Indicates recent drug use Minimal sample preparation Amenable to most analytical techniques Noninvasive specimen collection Easily accessible biofluid Rapid specimen collection (skin wipe) Convenient long-term collection device (patch) Patch may be worn for up to 14 days Many drugs determined Parent drug present Gives a cumulative estimate of drug exposure Useful in determining individual drug history Less frequent drug-testing compared to urine Adulteration unlikely
Sweat
Invasion of privacy Heterogeneous composition of fluid (intra- and intersubject variation) Small sample volume Volume of sample may be unknown Requires extraction prior to analysis High rates of noncompliance Skin irritation or discomfort possible Patches must be worn for extended period (days) Drug stability/degradation in sweat patch Low concentration of drug Generally short window of detection in skin wipes Drug disposition varies with flow rate and pH Volume excreted varies between individuals, emotional state, temperature, exercise Unequal distribution of sweat glands Drug concentration unlikely to correlate with blood Pharmacologic interpretation unlikely No correlation with impairment
Reproduced from Kerrigan S and Goldberger BA: Drugs of Abuse: Body Fluids. In: Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
Amniotic Fluid
Introduction
of neonates tested positive for drugs. Of these, 30.5% tested positive for cocaine, 20.2% for opiates, and 11.4% for cannabinoids.
Anatomy and Physiology
Increasing use of illegal drugs by expectant mothers has led to an increase in the need for prenatal toxicological testing. Exposure to drugs of abuse may result in higher rates of congenital anomalies and neonatal complications. Identification of gestational drug exposure may benefit the newborn in terms of increased vigilance and monitoring of the infant by medical and social services. Cocaine, heroin, amphetamines, and nicotine have been associated with impaired fetal growth and neonatal abstinence syndrome. In a 1997 study, in which gestational drug exposure was measured in almost 3000 newborns, as many as 44%
Amniotic fluid, which is produced by cells that line the innermost membrane of the amniotic sac (amnion), is the liquid that surrounds and protects the embryo during pregnancy. This fluid cushions the fetus against pressure from internal organs and from the movements of the mother. Production of fluid commences the first week after conception and increases steadily until the 10th week, after which the volume of fluid rapidly increases. Amniotic fluid, which may total about 1.5 l at nine months, contains cells and fat
194 SUBSTANCE MISUSE/Alternative Body Fluids Analysis
which may give the liquid a slightly cloudy appearance. Amniotic fluid is constantly circulated, being swallowed by the fetus, processed, absorbed, and excreted by the fetal kidneys as urine at rates as high as 50 ml h1. This circulation of fluid continuously exposes the fetus to compounds that may absorb in the gut or diffuse through fetal skin in the early stage of development. The encapsulation of the fetus in this fluid may prolong exposure to harmful drugs or metabolites. The pharmacokinetics of drug disposition in utero varies from drug to drug, and the acute and chronic effects that may result are the topic of continuing research.
Sample Collection and Analysis
Table 3 Methods of analysis of drugs in body fluids

Purification
Liquidliquid extraction Solid-phase extraction Supercritical fluid extraction

Drug detection by immunochemical techniques
Cloned enzyme donor immunoassay (CEDIA) Enzyme-linked immunosorbent assay (ELISA) Enzyme-multiplied immunoassay technique (EMIT) Fluorescence polarization immunoassay (FPIA) Kinetic interaction of microparticles in solution (KIMS) Radioimmunoassay (RIA)
Drug identification by chromatographic techniques
The collection of amniotic fluid (amniocentesis) usually takes place between the 16th and 20th week of pregnancy. The liquid is usually collected to test for fetal abnormalities or to learn the sex of the child. The presence of illicit drugs or their metabolites in amniotic fluid suggests that the fetus has been exposed to these substances via maternal blood circulation. A maternal serum sample taken at the same time as the test may provide complementary toxicological data and help assess the relative risk to the fetus. Amniocentesis is an invasive procedure. Prior to the test an ultrasound scan is used to determine the position of the fetus. After receiving a local anesthetic, a needle is inserted through the abdomen into the womb where there is the least chance of touching the placenta or the fetus. Although complications are rare, miscarriage occurs in approximately 1% of women. Typically 530 ml of amniotic fluid is removed. The pH of amniotic fluid decreases from slightly alkaline to near-neutral pH at full term due to fetal urination. Amniotic fluid, which is 99% water, contains dilute plasma components, cells, and lipids. Following amniocentesis, the fluid may be centrifuged and the supernatant layer frozen, prior to the drug test. Drugs present in amniotic fluid can be analyzed using well-established techniques, which are routinely used for blood, urine, or serum (Table 3). A few interferences are encountered with amniotic fluid due to its high water content. Sample pretreatment may not be necessary prior to an immunoassay screening test. However, confirmation of presumptive positive results by gas chromatographymass spectrometry may require isolation of the drug using solid-phase or liquidliquid extraction techniques.
Interpretation
Capillary electrophoresis Gas chromatography Gas chromatographymass spectrometry Gas chromatographymass spectrometrymass spectrometry High-performance liquid chromatography Liquid chromatography/mass spectrometry Thin-layer chromatography Reproduced from Kerrigan S and Goldberger BA: Drugs of Abuse: Body Fluids. In: Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
A number of maternal, fetal, and placental factors have been documented to affect fetal drug exposure. Of these, binding to serum proteins in the maternal and fetal circulation and fetal elimination are
particularly important. Conjugated drug metabolites, which tend to be highly water-soluble, may accumulate in the fetus or amniotic fluid due to limited placental transfer. Small lipid-soluble drugs can rapidly diffuse across the placental barrier, producing similar drug concentrations in amniotic fluid and fetal plasma. Larger, water-soluble compounds, which are transferred more slowly, are incorporated into the amniotic fluid from fetal urine. Basic drugs may accumulate in the amnion due to ion trapping, resulting in drug concentrations in excess of those found in fetal or maternal plasma. Cocaine abuse has been associated with spontaneous abortion, premature labor, precipitous labor, stillbirth, fetal malformations, cardiopulmonary effects, neurobehavioral sequelae, and placental abruption. Concentrations of cocaine in amniotic fluid have been reported at concentrations up to 250 mg l1 and its major metabolite, benzoylecgonine, has been reported in excess of 5000 mg l1. After crossing the placental barrier by simple diffusion, the drug distributes between fetal and maternal blood. The amniotic sac and its contents serve as a deep compartment with restricted, slow equilibrium between adjacent compartments. As a result, amniotic fluid inside this protective sac may expose the fetus to potentially harmful drugs or metabolites. Ion trapping and underdeveloped renal function may result in an accumulation of the drug in fetal blood, thus compounding the risk. Narcotic analgesics are reported to cross the placental barrier rapidly. Heroin use during pregnancy has been associated with low birth weight,

Table 4 Drugs and metabolites detected in body fluids
Biofluid Drug/drug metabolite
Amniotic fluid Breast milk
Saliva
Semen Sweat
Benzodiazepines, benzoylecgonine, cocaethylene, cocaine, ecgonine methyl ester, meperidine, methadone Amphetamine, benzoylecgonine, chloral hydrate, cocaethylene, cocaine, codeine, diazepam, dothiepin, fentanyl, fluoxetine, 11-hydroxy-THC, methadone, morphine, nordiazepam, oxycodone, temazepam, THC, THC-COOH 7-aminoflunitrazepam, 6-monoacetylmorphine, anhydroecgonine methylester, amphetamine, amobarbital, barbital, benzoylecgonine, buprenorphine, chloral hydrate, chlordiazepoxide, clonazepam, cocaethylene, cocaine, codeine, N-desmethyldiazepam, diazepam, ecgonine methyl ester, EDDP, ephedrine, flunitrazepam, gammahydroxybutyrate, heroin, hexobarbital, hydrocodone, hydromorphone, MDA, MDMA, meperidine, methadone, methamphetamine, methaqualone, morphine, nitrazepam, oxycodone, PCP, phenobarbital, phenylpropanolamine, phentermine, pholcodine, secobarbital, THC, THC-COOH Amphetamine, benzoylecgonine, cocaine, methadone, phenobarbital 6-monoacetylmorphine, anhydroecgonine methylester, amphetamine, benzoylecgonine, buprenorphine, cocaethylene, cocaine, codeine, diazepam, dimethylamphetamine, ecgonine methylester, heroin, methadone, methamphetamine, MDA, MDEA, morphine, nordiazepam, oxazepam, PCP, phenobarbital, THC
of prenatal drug exposure are limited and many consequences of fetal drug exposure are still unknown. Despite adequate understanding of the maternal consequences of drug abuse, fetal consequences for many drugs are poorly understood and this is a challenging area of maternalfetal medicine.
Breast Milk
Introduction
The prevalence of drug abuse among pregnant women throughout urban USA is reported between 0.4% and 27%, depending on geographical location. This is accompanied by a near threefold increase in the number of women who breastfeed their infants. These factors combined significantly increase the likelihood of infantile drug exposure.
THC, D-9-tetrahydrocannabinol; THC-COOH, 11-nor-9-carboxy-D9-tetrahydrocannabinol; EDDP, 2-ethylidine-3,3-diphenylpyrrolidine; MDA, methylenedioxyamphetamine; MDMA, methylenedioxymethamphetamine; MDEA, methylenedioxyethylamphetamine; PCP, phencyclidine. Reproduced from Kerrigan S and Goldberger BA: Drugs of Abuse: Body Fluids. In: Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
The female breast consists of 1520 lobes of milksecreting glands, embedded in the fatty tissue. During pregnancy, estrogen and progesterone, secreted in the ovary and placenta, cause the milk-producing glands to develop and become active. The ducts of these glands have their outlet in the nipple and by midpregnancy the mammary glands are prepared for secretion. Colostrum, a creamy-white to yellow premilk fluid, may be expressed from the nipples during the last trimester of pregnancy. This fluid, which is a rich source of protein, fat, carbohydrate, and antibodies, is replaced with breast milk within 3 days of delivery of the fetus and placenta. Proteins, sugar, and lipids in the milk provide initial nourishment for the newborn infant. The production of between 600 and 1000 ml of milk per day by the milk-secreting cells is stimulated by the pituitary hormone, prolactin. Contraction of the myoepithelial cells in the alveoli express the milk into the duct system.
miscarriage, prematurity, microcephaly, and intrauterine growth retardation. At physiological pH, narcotic analgesics tend to be charged. As a result the concentration of the drug in the amniotic fluid is expected to be lower than that of the maternal plasma. Benzodiazepines readily cross the placenta due to their high lipid-solubility and lack of ionization. However, drug concentrations in the amniotic fluid remain low due to extensive protein-binding in the maternal plasma and minimal renal excretion by the fetus. Table 4 summarizes drugs and metabolites that have been detected in amniotic fluid and other alternative biological fluids. Interpretation of toxicological findings is complicated because drug dose, route, and time of administration are usually unknown. Long-term implications
Fluid is collected using a special device such as a breast milk pump, after which established analytical techniques may be used to detect drugs of abuse. Breast milk, which contains protein (1%), lipid (4%), lactose (7%), and water (88%), varies in pH between 6.35 and 7.35. However, the high lipid content of milk may interfere or decrease the extraction efficiency or recovery of drug. Additional washing with nonpolar solvents such as hexane may be necessary to remove excess lipids prior to chromatographic analyses. The effect of natural emulsifying agents, which have detergent-like activity, may interfere with antibodyantigen reactions that take place in immunoassay screening tests. The daily variation of breast milk composition, combined with drug dose and time of administration relative to the
expression of milk, is likely to affect the amount of drug present and the effect on the infant. The concentration of drug found in the breast milk is subject to both within- and between-subject variations, further confounding attempts to generalize infant risk assessment. The lipid content of the milk varies not only daily, but also during a single feed; the latter portion of expressed milk may contain a several-fold increase in fat, which in turn may increase or decrease the concentration of a particular drug.
Interpretation
The transfer of drug into the milk depends on metabolism, protein-binding, and the circulation of blood in the mammary tissue. Passive diffusion transports the drug across the mammary epithelium into the milk. The mildly acidic pH of breast milk tends to trap weakly basic drugs, particularly those of low molecular weight, which can diffuse fairly rapidly through small pores in the semipermeable membrane. Although drugs that are extensively protein-bound may not readily pass into the milk, emulsified fats serve to concentrate lipid-soluble drugs such as cannabinoids and phencyclidine (PCP). For this reason, PCP was detected in breast milk for as long as 41 days following cessation of maternal drug use. Notall lipophilic drugs produce deleterious effects in the nursing infant. Fentanyl, which was found to concentrate in lipid-rich colostrum at much higher concentration than maternal serum, has a low oral bioavailability, somewhat minimizing the risk to the child. However, inactive conjugated metabolites in breast milk may undergo reactivation by deconjugation in the gastrointestinal tract of the infant. Opiate addiction and withdrawal symptoms have been reported in infants receiving milk from substance-abusing mothers. Low oral doses of morphine to nursing mothers may produce drug concentrations in milk as high as 100 mg l1. Methadone maintenance (50 mg day1) in a drug-dependent nursing mother produced breast milk concentrations between 20 and 120 mg l1 in the first 24 h after the dose, substantially lower than maternal plasma concentration. Benzodiazepines, which are excreted in the milk, can accumulate in the infant due to underdeveloped metabolic and excretory function. Watersoluble drugs appear least likely to partition into the milk and are less likely to accumulate. However, stimulants such as amphetamine have been detected in milk at concentrations 37 times higher than those found in maternal plasma due to ion trapping of basic drugs. Cocaine is also believed to partition preferentially into milk, thus increasing the likelihood of infant intoxication.
Despite the fact that as many as 34% of pregnant women are reported to have used marijuana, the effect of this drug on the infant is not yet definitively understood. The concentration of the primary active ingredient, D-9-tetrahydrocannabinol (THC), is reported to be as much as eightfold higher in breast milk than maternal plasma. Metabolites of THC and the parent drug were measured in breast milk at concentrations as high as 340 mg l1 in a chronic marijuana smoker. The direct impact of specific drugs on the newborn child is difficult to evaluate. Many substance-abusing women use multiple drugs, receive inadequate healthcare, and may be predisposed to other health problems that can impact both neonatal and maternal outcomes.
Saliva
Introduction
Saliva, which can be collected conveniently, and without invasion of privacy, is perhaps one of the most appropriate body fluids for on-site drug testing. The principal psychoactive component of marijuana (THC) was detected in the saliva of 9% of motorists who displayed erratic driving behavior. Law enforcement agencies are particularly interested in saliva as a complementary tool to identify impaired drivers using roadside drug-testing devices. This approach, which has already received widespread use for employment, health, and insurance drug testing, is rapidly gaining momentum.
Saliva is the clear viscous fluid that is secreted by salivary glands and mucous membranes that line the mouth. It serves to lubricate the oral cavity, assists in the swallowing of food, and facilitates our sense of taste. This biofluid, which may be secreted at rates of 1.5 l day1, has an average pH of about 6.8 and is comprised of 99% water and 0.3% protein. The remainder is made up of electrolytes, mucin, urea, lipids, digestive enzymes, white blood cells, and debris from the lining of the mouth. Three pairs of glands secrete saliva via ducts in the mouth. Each gland consists of thousands of saliva-secreting sacs and a network of canals that transport the fluid into the main ducts in the mouth. The parotid glands, which are the largest of the salivary glands, lie inside the cheek, just below and in front of the ear. These glands secrete serous fluid derived from blood plasma. Serous fluid and mucin are secreted by the sublingual glands, located on the floor of the mouth beneath the tongue and by the submandibular glands, just below the jaw on the front of the neck.
Mixed saliva is mostly comprised of submandibular secretions (71%). Parotid and sublingual glands are responsible for 25% and 4% of the remaining volume.
Mixed saliva is collected noninvasively by expectoration, aspiration by vacuum or by saturation of an absorbent swab. Secretions from a specific gland may be collected using a special device or by cannulation, but this is uncommon. Chewing an inert substance, such as Teflon tape or a rubber band, may increase salivation for the purpose of specimen collection. It is necessary to ensure that no adsorption takes place between the drug and the chewed substance. Acidic candy or citric acid has also been used to stimulate glandular secretions. Care must be taken that residual food or drink in the mouth does not interfere with the analysis. It is possible that interfering substances could be placed in the mouth to adulterate the saliva, but this has not yet been reported. Saliva is relatively free from common interferences and is amenable to most types of toxicological analyses. It is possible that endogenous enzymes in saliva could interfere with colorimetric or fluorescence immunoassays which detect drug indirectly from the activity of a labeled enzyme. If saliva is collected by expectoration or free flow, sample pretreatment may not be necessary prior to immunochemical testing. Dilution of the sample with buffer may be sufficient, although centrifugation may be used to remove any solid debris. Solid-phase or liquidliquid extraction is necessary prior to chromatographic analyses, in a manner analogous to other body fluids.
Interpretation
Drug detection times in saliva are relatively short compared to urine. Although saliva does not provide a history or long-term profile of substance misuse, parent drug may be detected for several hours following drug use at concentrations proportional to those measured in plasma. Saliva, which is an ultrafiltrate of interstitial fluid, contains the unbound fraction of drug, which is pharmacologically active. As a result, saliva tests may allow pharmacologic interpretation of results. Salivary ducts in the mouth are separated from the systemic circulation by a layer of epithelial cells. Transfer of drug from the plasma into saliva requires transport across the lipid membrane of these cells. Passive diffusion is perhaps the most important route of passage for most drugs, although ultrafiltration and active secretion from the blood may also occur. Size, charge, and macromolecular binding
restrict transfer across cell membranes. Therefore, the pH of the saliva, pKa of the drug, and plasma protein-binding of the drug strictly control the passage of drug into this body fluid. At fixed salivary pH (6.8), theoretical estimates of the partition of a drug between the saliva and plasma (S/P ratios) can be predicted from the HendersonHasselbalch equation. Increasing the saliva flow rate can increase pH from 5.5 to 7.9, greatly affecting the disposition of drugs that are ionized at normal plasma pH. Stimulation of saliva flow by chewing waxed film or sour candy may decrease the concentration of weakly basic drugs, such as cocaine (pKa 8.7) several-fold. This weakens the reliability of saliva testing for pharmacologic interpretation and accounts for discrepancies in S/P ratios between authors. Although saliva pH is the principal determining factor for ionizable drugs, compounds that are uncharged in plasma are unaffected. In contrast to cocaine, the concentration of zwitterionic metabolite, benzoylecgonine (pKa 2.3, 11.2), is unchanged by saliva pH. Passive diffusion through lipid membranes requires the drug to be in a lipid-soluble form. Glucuronides or polar metabolites may be too hydrophilic to cross the membranes. Saliva has a minimal protein-binding capacity compared to plasma. In order to be retained in saliva, the drug must be water-soluble, a property largely augmented by ionization of the drug. This transformation prevents back-diffusion of the drug into the plasma. Drugs of abuse that are strongly basic in nature may be preferentially distributed into saliva, as is the case with amphetamine. Saliva concentrations may exceed those measured in plasma by as much as two- to threefold, which may increase the detection time for several days. Following a single dose of methylenedioxymethamphetamine (MDMA), peak salivary concentrations were 17296511 mg l1. Because the range of saliva pH is typically much narrower (6.57.2) than that of urine (4.58.0), it may be of diagnostic value for drugs whose excretion is heavily dependent on urinary pH, such as the amphetamines or PCP. Numerous other drugs have been measured in saliva, including a number of opioids. Concentrations of morphine and codeine in saliva samples taken from individuals with a history of intravenous opiate use ranged as high as 208 and 428 mg l1, respectively. Salivary methadone concentrations were shown to correlate well with plasma concentrations. Phenobarbital, amobarbital, and other barbiturates have been detected in saliva, typically with S/P ratios of about 0.3. Other sedative drugs, methaqualone and meprobamate, had S/P ratios of 0.1 and 1, respectively. Due to their widespread abuse, a number of benzodiazepines, including diazepam, have been investigated.
S/P ratios were typically low (0.04 or less), which is very much lower than predicted. This is likely the result of the extensive plasma protein-binding which takes place with these compounds. Drug transformation and instability have been reported for certain drugs, including some of the benzodiazepines, which may undergo reduction of the nitro group in saliva. Cocaine concentrations in saliva have been shown to correlate well with plasma concentrations and behavioral effects. Metabolites of cocaine are present in very low concentration in saliva. Inconsistencies in S/P ratios have been attributed to contamination of saliva following oral and smoked routes of administration. Peak cocaine concentrations in saliva increased from 4281927 mg l1 following a single oral dose to between 15 000 and >500 000 mg l1 after smoking. Contamination of the oral cavity following these types of exposure precludes pharmacologic or behavioral interpretation of results. However, these results may indicate recent exposure to the drug, which could be of equal forensic importance. Elevated THC concentration (501000 mg l1) after smoking marijuana is also the result of oral contamination. Shortly after exposure, the concentration rapidly declines in a dose-dependent manner similar to that of plasma. However, some cannabinoids can be detected in saliva for longer periods than plasma, suggesting that some drugs are actually sequestered in the buccal cavity during smoking.
Seminiferous tubules of the testes contribute less than 5% of the seminal fluid volume, which is typically between 3 and 5 ml. Paired seminal vesicles, which are thin-walled, pear-shaped structures, secrete a thick, slightly alkaline fluid that mixes with the sperm as they pass into the ejaculatory ducts and urethra. These secretions, which are expelled when the seminal vesicles contract during orgasm, constitute about 60% of the seminal fluid volume. This secretion is rich in fructose, a sugar which stimulates the sperm to become mobile. The prostate gland, which sits just below the bladder, secretes a thin milk-colored fluid that accounts for about 30% of the total volume. This fluid helps activate sperm and maintain motility. Bulbourethal glands, located below the prostate, produce mucus-like secretions that lubricate the terminal portion of the urethra, contributing about 5% of the total volume.
Semen
Introduction
Following ejaculation, seminal fluid can be analyzed for drugs of abuse using techniques that are widely used for serum and other body fluids. Diluted seminal fluid may be used in immunoassay screening tests and chromatographic analyses may be performed following extraction of the drug using conventional techniques. Semen pH typically ranges between 7.3 and 7.8, depending on the differential contribution of fluids. The overall alkalinity of the fluid helps protect spermatozoa from the acidic environment of the female reproductive tract.
Interpretation
Analysis of semen for drugs of abuse has not been widely adopted. Privacy issues surrounding collection of this body fluid restrict its widespread use. Despite limited reports of drug detection in semen, it is known that certain drugs, such as cocaine, can influence the characteristics of the spermatozoa, causing decreased motility and anatomical abnormalities. It has also been shown that cocaine binds to sperm with high affinity, suggesting a unique mode of transport to the ovum. Although the concentration of drug in semen is not sufficient to elicit a response in a sexual partner, it has been suggested that insemination of drug-laden sperm into the egg could result in abnormal development.
Semen is the viscous fluid released from the male upon ejaculation. The fluid contains spermatozoa as well as auxiliary sex gland secretions. Two seminal vesicles, the prostate gland and the bulbourethral glands, contribute 95% of the gelatinous secretion.
Lipid-solubility and pKa of the drug play an important role in the transport of drugs of abuse into seminal fluid. Ion trapping may be responsible for the transport of certain drugs from the seminal plasma to the genitourinary tract. Drug ionization depends on the pH difference between plasma (pH 7.4) and prostatic fluid (pH 6.6); prostatic fluid can trap basic drugs in the prostate. In contrast, the vesicular fluid, which is more alkaline in nature, is likely to contain much lower concentrations of these drugs. Cocaine was detected in semen at concentrations typically 6080% of those measured in plasma, independent of route of administration. Following a 25-mg dose of cocaine, parent drug and benzoylecgonine concentrations in semen were 45 and 81 mg l1, respectively at 24 h. One study involving opioidmaintained individuals indicated that methadone was present in semen at concentrations in excess of those found in blood. Amphetamine concentrations in semen were reported to correlate well with wholeblood concentration following drug exposure.
However, the disposition of drugs of abuse in this body fluid is widely variable due to the heterogeneous nature of the seminal fluid.
Sweat
Introduction
Sweat analysis is becoming increasingly popular in drug compliance programs, such as rehabilitation, probation, or parole, due to noninvasive, convenient specimen collection, and less frequent testing. Although pharmacologic interpretation of drugs in sweat is not possible, the presence and quantity of drug present in a sweat sample are indicators of exposure.
Parts of the bodys surface are also bathed in sebum, an oily secretion of the sebaceous glands. Composed of keratin, fat, and cellular debris, sebum mixes with sweat to form a moist, acidic film on the surface of the skin, protecting it from drying. This waxy lubricant, which consists mostly of fatty acids, maintains a pH of about 5 and is mildly harmful to bacteria and fungus, providing additional protection against infection.
About 3 million tiny structures deep within the skin are responsible for the elimination of fluid between 300 and 700 ml in a 24-h period. These glands secrete sweat, which is then transported through narrow passageways to the surface of the skin, whereupon evaporation has a cooling effect that helps maintain body temperature. The glands themselves are controlled by the autonomic nervous system, which is responsible for increased rates of secretion during times of anxiety or fear. Elimination of this body fluid, which occurs during normal breathing, is known as insensible sweat. Sensible sweat, which refers to perspiration that is actively excreted during stress, exercise, or extreme temperature, may be eliminated at rates of 24 l h1. About half of the total volume of sweat is eliminated from the trunk of the body. The remaining fluid is lost from the legs or upper extremities and head in approximately equal amounts. The fluid consists of water (99%), sodium chloride, phosphate, protein, urea, ammonia, and other waste products. The average pH of sweat is about 5.8, but increased flow rates increase the pH to between 6.1 and 6.7 in a manner analogous to saliva. Sweat is produced by two types of gland: eccrine and apocrine. The former are coiled, tube-like structures that are located throughout the skin. These glands, which are concentrated in the palms of the hands and soles of the feet, open up directly to the surface through tiny pores in the skin. Apocrine glands, which become active only after puberty, are large, deep glands in the axillae (armpit), pubic, and mammary regions. These produce cellular material as well as sweat, which results in the secretion of a more viscous fluid with characteristic odor. Apocrine glands often open up into hair follicles before reaching the surface of the skin. Contamination of the exterior surface of the hair has been demonstrated as a result of this exchange.
Sweat is usually collected using an adhesive absorbent patch, which is placed on the surface of clean skin or by wiping the skin with a swab or gauze. Careful preparation of the skin is necessary prior to placement of a sweat patch to minimize external drug contamination or bacterial degradation of the drug once it has been retained. Occlusive sweat collection devices typically consist of an absorbent pad with an adhesive polyurethane exterior, similar to a waterproof bandage. These allow sweat to diffuse into the patch but prevent water or compounds from the environment from penetrating the device. In some instances, discomfort and inconvenience led to high rates of noncompliance among sweat-patch users as a result of tampering, loss of the patch, or refusal to wear. Due to the relatively small volume (microliters) of insensible sweat secreted from a small absorbent area (typically 3 5 cm), patches are typically worn for several days on the outer portion of the upper arm or back. Sweating may be induced by occlusive wrapping or by diaphoretic treatment, but these efforts, which are more invasive, are not routinely used. Occlusive bandages have been replaced by more advanced technology which improves user comfort. Use of a semipermeable membrane to cover the absorbent pad prevents nonvolatile components in the environment from penetrating the pad externally, but allows oxygen, water, and carbon dioxide to diffuse through. This helps maintain healthy skin, improves user comfort, and increases the likelihood of compliance. Salts, solids, and drugs that pass through the skin are trapped in the absorbent pad, where they are temporarily stored in situ, until the patch is removed. Most skin wipes and patches contain a mixture of both sweat and sebum, both of which are secreted from the surface of the skin. Most reports of drugs of abuse in sweat actually refer to the collection of the mixed matrix. As yet, there have been relatively few reports of drugs of abuse in sebum alone. This biofluid is typically collected from the forehead, which is rich in sebaceous glands, as are the face and scalp. Unlike sweat, which is predominantly water, fat-soluble drugs can be sequestered in sebum due to the high lipid content of this fluid.
Surface secretions of sweat and sebum must be extracted prior to even a preliminary drug screen. Drugs that are present in the absorbent collection material are generally extracted with alcohol, buffer, or a combination of both. Recovery of commonly abused drugs during this process is typically quite high (80% or more) and limits of detection by gas chromatographymass spectrometry are generally less than 1 ng per patch. The increased work necessary to analyze sweat patches is counteracted by the relative ease of sample collection and its ability to determine cumulative drug exposure over an extended period.
Interpretation
Quantitative analysis of drugs of abuse in sweat is rarely attempted because the volume of biofluid collected is generally uncertain. If an occlusive collection device is used, the volume of sweat can be estimated from the increased weight of the patch. However, newer nonocclusive devices that can be worn for longer periods give no indication of specimen volume. However, it has been suggested that the sample volume could be estimated indirectly from the concentration of sodium or lactate in the patch, both of which are excreted in sweat at relatively constant rates. One of the principal advantages of sweat analysis is that it can provide information on long-term continuous exposure to drugs of abuse. As most drugs are eliminated in the urine within 23 days of a single exposure, effective drug monitoring necessitates urinalysis every few days, which is inconvenient and labor-intensive. On the other hand sweat patches can be worn for as long as 2 weeks, are less likely to be adulterated, and require drug testing to be performed only once, when the patch is removed. Small, lipid-soluble compounds favor incorporation of drugs into sweat by transdermal migration or passive diffusion. Drugs which are highly bound to plasma proteins, such as benzodiazepines, are present in sweat at low concentrations. Basic drugs with high partition coefficients and pKa values close to sweat appear to be maximally excreted. The patch itself operates as an ion trap toward weakly basic drugs, which ionize as a result of the pH differential between plasma (pH 7.4) and sweat (pH 56). The predominant analyte in sweat appears to be the parent drug, which is generally less polar than the metabolites commonly found in urine. However, relative amounts of parent drug and metabolite vary between drugs and subjects, and this may be attributed to differences in skin enzymes or excretory pathways. Unlike many other body fluids, heroin, which is metabolized very rapidly by the body, is excreted in the sweat together
with 6-monoacetylmorphine. In another study, sweat samples collected from the forehead of injured drivers gave THC concentrations of 4152 ng per pad. Using a sweat patch, one-time exposure to cocaine can be detected for up to 7 days. Cocaine concentrations greater than 100 mg l1 were detected in sweat 72 h following a 2 mg kg1 intranasal dose. Appearance of the drug in sweat occurs within 12 h of exposure and peaks within 24 h. Ion trapping may increase the detection window of certain basic drugs in sweat compared to urine. In one study, methamphetamine was detected in sweat for up to 140 h following a 10-mg dose, compared to 96 h in urine. Individual skin wipes obtained from methamphetamine users indicated nanogram quantities of both methamphetamine (20164 ng) and amphetamine (313 ng) on the surface of the skin. Adulteration of patches is rare. Adulterants that are commonly used for urinalysis are difficult to apply without causing noticeable disturbance to the patch. Introduction beneath the adhesive layer using a hypodermic needle is possible at the risk of causing substantial irritation to the skin, due to the reactive or caustic nature of many adulterants. Once patches are sealed, the skin is free from further environmental drug contamination. However, studies have shown that external deposition of drug on the surface of the skin may result in detectable amounts of drug for several hours following normal hygiene practices. Cleaning the skin with alcohol prior to placement of a sweat patch may not sufficiently remove residual drug in these instances. In situ storage of excreted drugs in the sweat patch prior to removal makes drug stability in this biofluid an important consideration. Presence of drug metabolites in sweat may not reliably indicate in vivo drug exposure. Sweat contains esterases and other enzymes that may degrade or transform drug on the surface of the skin. Hydrolysis of drugs such as cocaine and heroin to benzoylecgonine and 6-monoacetyl morphine may take place inside the sweat patch.
Conclusion
Scientific and technical developments in body fluid analysis have advanced rapidly and have overtaken some of the regulatory and policy-level decisionmaking that is needed. Although drug testing is often performed in accordance with local, state, and federal guidelines, the use of alternative biofluids is rarely described. Relatively few countries have statutes that specifically address the role of these matrices in the forum of workplace drug testing, abstinence, and clinical or forensic science. The US Department of Health and Human Services is
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evaluating the use of these samples in federally regulated programs. Recently the European Unions roadside testing assessment (ROSITA) project investigated the functionality and reliability of alternative biological fluids to enforce administrative traffic offenses. These investigations, and others like them, will enhance our understanding of drug use in society, and encourage more widespread utilization of alternative biofluids in a variety of applications ranging from gestational drug exposure to traffic safety.
See Also
Substance Misuse: Urine Analysis; Hair Analysis; Patterns and Statistics
Further Reading
Cone EJ (2001) Legal, workplace and treatment drug testing with alternate biological matrices on a global scale. Forensic Science International 121: 715. Cone EJ, Jenkins AJ (1997) Saliva Drug Analysis. Handbook of Therapeutic Drug Monitoring and Toxicology. Boca Raton, FL: CRC Press. Huestis MA, Cone EJ (1998) Alternative Testing Matrices. Drug Abuse Handbook. Boca Raton, FL: CRC Press. Huestis MA, Choo RE (2002) Drug abuses smallest victims: in utero drug exposure. Journal of Forensic Sciences 128: 2030. Kidwell DA, Holland JC, Athanaselis S (1998) Testing for drugs of abuse in saliva and sweat. Journal of Chromatography B 713: 111135. Schramm W, Smith RH, Craig PA (1992) Drugs of abuse in saliva: a review. Journal of Analytical Toxicology 16: 19. Skopp G, Potsch L (1999) Perspiration versus saliva basic aspects concerning their use in roadside drug testing. International Journal of Legal Medicine 112: 213221. Sunshine I, Sutliff JP (1997) Sweat It Out. Handbook of Therapeutic Drug Monitoring and Toxicology. Boca Raton, FL: CRC Press.
and data of seizures of illicit substances by law enforcement agencies. These data provide evidence of use, but patterns may vary over time and also be dependent on the way information is recorded. With fatal drug misuse an analysis of death certificates will provide evidence of patterns of drug-related death but will also depend on how the pathologist incorporates toxicological data into the cause of death. Furthermore, in deaths from trauma, toxicological data may not be recorded in the death certificate, and unless there are mechanisms for recording these data separately, the role of drugs in such incidents as vehicular collisions, suicides, and accidents will be underestimated. Alcohol and smoking are significant substances of abuse. Cannabis is also a widely misused substance, though not directly associated with acute deaths.
Opiates
Opiates are commonly misused and an important group of drugs in drug-related deaths. Use of opium dates back at least to the ancient Greeks. Socrates died from a combination of opium and hemlock. Laudanum, another mixture containing opium, was used from the Renaissance for a variety of ailments. Morphine was isolated at the start of the nineteenth century, and opium smoking was so popular among the Chinese that it caused concerns over the economic effects of its importation. Following the ban in 1839 the UK went to war with China to maintain the trade and opium addiction remained a major problem in China until the 1960s. In 1874, diamorphine was synthesized at St Marys Hospital in London. The hypodermic syringe had been invented almost 20 years earlier. Diamorphine, more popularly known as heroin, became popular at the start of the twentieth century, and enjoyed a resurgence of use from the 1960s. Heroin is now one of the most important drugs used recreationally. It is commonly injected, but may also be taken by smoking or inhalation chasing the dragon, also known as tooting in the UK. Snorting is also said to be increasing in popularity. Smoking, snorting, and inhalation at least avoid the potential dangers of injection, which include viral and other infections. Subcutaneous injection, known as skin popping, has been a relatively popular method of administration and may be associated with infections; outbreaks of botulism have been associated with this habit. Heroin is illicitly manufactured in a number of areas in the world. Half of all illicitly produced heroin derives from the golden triangle of Myanmar. Other sites in Southeast Asia and Southwestern Asia are also important areas of production. In the western
Patterns and Statistics

C M Milroy, University of Sheffield, Sheffield, UK
Introduction
Drug misuse is common, and substances have been used by humans for pleasure and to alter perception for millennia. The identification of patterns of drug misuse depends on a number of factors, including analysis of clinical samples, postmortem toxicology,
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hemisphere Colombia and Mexico are the important producers. The heroin that is produced in the latter areas is known as black tar heroin because of its appearance. The purity of heroin varies, and may vary from 0% to over 50%. The lack of purity probably accounts for the continued administration via injection, as the bioavailability of intravenous heroin is much higher than for other routes of administration. Illicit heroin contains a number of other agents such as noscapine, allowing the differentiation from medically produced heroin. Most of the substances with which heroin is diluted (cut) are nontoxic. Heroin remains the most important opiate drug in drug misuse deaths, accounting for over 40% of such deaths in the drug abuse warning network (DAWN) in the USA in 1998. Whilst diamorphine is available for clinical use in the UK, the heroin that is encountered in the UK is illicitly manufactured and not diverted pharmaceutical preparations. Whilst heroin has been the most popular of the opiates to be abused, other opiates are subject to misuse. Morphine preparations are used in the clinical setting, including slow-release preparations for pain relief. They are rarely subject to abuse, though like other medicinal preparations, those who have access to them, typically physicians and nurses, may abuse them. Deaths associated with heroin use have shown a steady increase in the 1990s. In a study published in 2001 of UK dance-scene drug users, where 96% admitted using ecstasy, 12% admitted using heroin at some time. After heroin, the most important opiate drug causing death in western society has been methadone. This synthetic opiate is used in the treatment of opiate addiction, and also as a painkiller in terminal cases. Methadone is also subject to abuse via diversion from those in methadone maintenance programs. Methadone is available in oral, tablet, and injection formulations. It has a long half-life and does not produce the euphoria of heroin. The longer half-life, that is of benefit as a painkiller and allows a single daily dose, may also mean that naive abusers will use a dangerous quantity as the effects of the drug are not rapid, as with heroin. The oral preparation can be attractive to the naive user, as it does not require injection. The effects are not immediate and it is easy to ingest a fatal dose. The progression is then into coma, when the other people present think the individual has simply gone to sleep, and the opiate-induced unconsciousness is not recognized. These victims often have an inhalational pneumonitis/pneumonia seen on microscopy, indicating the compromised airway. Methadone poisoning is often seen in association with heroin use and other substances, such as alcohol. The postmortem blood
concentrations of methadone seen in fatal cases frequently overlap with those seen in patients on methadone maintenance programs, illustrating the problems of interpretation of postmortem toxicology, as well as the issues of tolerance and dealing with potentially different populations. Deaths related to methadone showed an increase in the UK during the early 1990s before reaching a peak and then declining slightly. This may have been due to better prescribing controls. Injectors of opiates, as with any intravenous drug misuse, carry the risks of their injection habit, as well as the risk of acute poisoning. The obvious risks include viral hepatitis and human immunodeficiency virus (HIV) transmission. In additional local abscess formation, septicemia, and endocarditis add to the morbidity and mortality from an injecting habit. Needle exchange programs help to reduce these complications. Other opiates that may be encountered include dextropropoxyphene, though in the UK this is more commonly encountered in self-harm episodes from prescribed painkillers, dihydrocodeine, used as a painkiller as well as in the treatment of opiate withdrawal, pethidine, another synthetic opiate, codeine, hydrocodone, and fentanyl. Fentanyl is a synthetic drug structurally related to meperidine. It has potent opiate action and is used in clinical practice, but is also subject to abuse. Fentanyl has been manufactured in clandestine laboratories; pharmaceutically manufactured patches and intravenous preparations are also used. Oxycodone has been encountered in deaths in the USA, but is rarely encountered in the UK. Nalbupane has been subject to abuse and has been popular with body builders. Buprenorphine is a synthetic opiate with partial agonist and antagonist action. It is a potent opiate. It can be administered sublingually and is used as a painkiller. It has also been used in France as an alternative to methadone in opiate addiction programs, where it has been associated with fewer deaths than methadone. It has also been subject to abuse, when tablets are crushed and then injected. Postmortem toxicology in opiate abusers, as with other drugs, must be considered in the context of the whole of the autopsy findings. Tolerance is a significant factor with opiate misusers and a history of recent abstinence is important. One common scenario with opiate misusers is death soon after release from custody. Not all opiate drugs are detected on routine screening and a discussion with the toxicologist is necessary where an unusual opiate is suspected. In some rapid heroin deaths the urine screen for opiates may be negative and it is important in these cases that the toxicologist analyzes blood as well as urine. With
heroin deaths the reporting of heroin metabolites is an important indicator of heroin use. Heroin is rapidly converted to morphine, which is the substance measured in the blood. Pure morphine is rarely abused, though those who have access to medicinal morphine, typically healthcare professionals, may misuse it. The metabolite 6-monoacetylmorphine provides evidence that heroin had been used, though it is a labile substance and its absence does not exclude heroin. Codeine may be present in urine as a byproduct of heroin manufacture, but may also result from direct proprietary codeine products. When morphine is reported in the blood, it is typically derived from heroin. The reporting of the death as due to morphine poisoning may result in an underestimation of the use of heroin in drug-related deaths.
Cocaine
Cocaine is a naturally occurring synthetic stimulant derived from two closely related species, Erythroxylum coca Lam and E. novogranatense Hieron, native to South America. Native South Americans chewed the leaves whilst early European explorers noted its use and it was not until the latter part of the nineteenth century that it gained popularity as a potential medicine. Cocaine-containing wines had been produced in the 1860s, but it was with the discovery of the local anesthetic effects of cocaine and the promulgation of cocaine by Freud in the 1880s that cocaine for medicinal purposes became popular. Early explorers to South America had noticed problems with its use, but chewing the leaf only provided small amounts of cocaine. The wines also had relatively low concentrations and it was the production of purified cocaine that released the potential for significant abuse and addiction. The production of freebase cocaine provided a further development that allowed for more rapid administration of cocaine, which was superseded by the use of crack cocaine. The coca plant was transplanted to Java, India, Sri Lanka, and Taiwan for production, but today cocaine is derived from the region of the Andes in South America. Colombia has been the principal producer, with Peru and Bolivia important sources. Cocaine is extracted from the leaves and turned into a crude cocaine paste, which is then dried. The paste is usually further purified, though it can be smoked. Cocaine seizures indicate typically high concentrations of cocaine, over 80%, which is then diluted to produce a product, which may have between less than 50% and 80% cocaine. Synthetic cocaine can be produced, but does not appear to be a common activity.
Coca leaves have been chewed for thousands of years, and may be turned into a tea. With purified cocaine, inhalation through the nose became the popular method of administration. Snorting allows rapid administration of the drug, though as it is a vasoconstrictor it also acts to inhibit its own absorption. The absorption of cocaine through mucous membranes is the medical basis of cocaine as a local anesthetic. Cocaine may be combined with epinephrine (adrenaline) as a local anesthetic agent. Complications may arise from this, including the development of myocardial infarction. Cocaine may also be injected. The hit from cocaine requires multiple injections, in contrast to opiate abusers, thus increasing the morbidity associated with intravenous misuse. In the 1980s the practice of smoking freebase cocaine, sometimes called freebasing, was introduced. To achieve this, freebase cocaine had to be heated with ether; a clearly hazardous procedure, and freebasing gave way to smoking crack cocaine. Crack cocaine is produced by mixing cocaine with sodium bicarbonate. Drug concentrations are similar between crack cocaine users and snorters. Gastrointestinal absorption of cocaine is important and people caught with cocaine may try and swallow it. The absorption of crack cocaine will depend on how much sodium bicarbonate is present and how it reacts with the gastric acid. Another important situation in which gastrointestinal absorption may be encountered is in so-called body packers or mules, where there is an attempt to smuggle cocaine in condoms or similar material. If a package ruptures, large quantities of cocaine may be released. In these deaths high concentrations of cocaine are detected. With body packers, small amounts of cocaine may be detected in the urine in the absence of rupture of a packet, allowing detection of suspected carriers by law enforcement agencies. However, not all body packers will give a positive urine test for cocaine and urinalysis in body packers must be treated with caution. Cocaine misuse is a major cause of drug-related morbidity and mortality. It has been the most common drug detected in drug-related deaths in the USA and in 1999 it was estimated that 1.5 million Americans were users of cocaine. A study of use of drugs in 35year-olds showed 6% of men and 3% of women had used cocaine in the previous year. It has been less of a problem in Europe, partly presumably because it is produced in South America, whereas opiates are produced in a number of regions in the world. However in the 1990s its use in the UK increased significantly and cocaine-related deaths are
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becoming more common, and its presence in toxicology samples is now frequent. The number of recorded deaths from cocaine in the UK rose from just 12 in 1993 to 88 by 1999. Cocaine use among the UK dance scene is common, with 75% admitting use at some time; 13% have used crack cocaine. As with opiates, cocaine concentrations must be interpreted with caution. Very high concentrations of cocaine have been encountered in trauma victims, where death was clearly not associated with direct cocaine toxicity. Cocaine may be taken in combination with alcohol. This may result in the formation of cocaethylene, which is a toxic substance, though its role in human toxicity is unclear. One scenario where cocaine may play an important role is in deaths in custody. A number of reports have appeared detailing the role of cocaine toxicity in deaths associated with restraint. Cocaine is associated with the syndrome of excited delirium. The role of cocaine poisoning in comparison with the position in which the detained person has been restrained has been debated. It may well be that, whilst positional asphyxia is important in many cases, in others cocaine may be the principal factor, and some victims may actually be dying when they are arrested and restrained because of their violent conduct. In these cases careful analysis of all the evidence is required before a determination of the cause and manner of death is given. Cocaine use is associated with significant cardiovascular morbidity and mortality. It may cause acute myocardial infarction, cardiac arrhythmias, and symptomatic and silent myocardial ischemia. Atherosclerosis can be accelerated and hypertension, aortic dissection, myocarditis, endocarditis, and hypertrophic and dilated cardiomyopathy may result from its use.
has hallucinogenic effects. It was popular in the nineteeth century and was immortalized by the French impressionist painters. Absinthe drinks are produced in Europe and contain high concentrations of ethanol (70%). Absinthe use is currently enjoying a resurgence in the UK.
Amphetamines
Amphetamine was first manufactured in 1887 and it a synthetic stimulant. A Japanese chemist first manufactured methamphetamine. Amphetamines were used medicinally as nasal decongestants and were also proposed for a wide variety of other disorders, including schizophrenia. Amphetamines are now recognized to induce psychosis. Deaths from amphetamines were reported in the 1950s, though reports were unusual until the production of ice, a pure form of ()-methamphetamine that was smoked. It was estimated that in 1997 over 4 million Americans had tried methamphetamine, though many had tried it in the 1960s and 1970s. There has been a resurgence in its use. The first ice laboratories producing illicit methamphetamine were encountered in Japan, then in Korea and other parts of Southeast Asia, before production started on the west coast of the USA. Its use remains unusual in the UK, and no significant problem is associated with methamphetamine use, though amphetamines are commonly used in the UK and occasional deaths are encountered. The usual route of administration of methamphetamine is via injection, smoking, snorting, or swallowing. In the UK amphetamines are typically swallowed or injected. Methylphenidate (Ritalin) is a commercially produced amphetamine used in the treatment of attention deficit hyperactivity disorder (ADHD). Diverted methylphenidate is now encountered as a drug of misuse; the tablets are crushed and injected.
Other Natural Stimulants

As well as cocaine a number of other naturally occurring stimulants may be encountered. Caffeine is the most commonly encountered stimulant, and is also used in some pharmaceutical products, but serious toxicity is rare. Ephedrine is used in a number of commercial products and is also a precursor for methamphetamine production. Khat is a native plant of East Africa and is grown extensively in Yemen. Its active compound is cathinone. It is illegal in the USA, but can currently be lawfully imported into the UK. The leaves are chewed. Occasional cases of khat-induced psychosis are encountered in the UK. Absinthe is a naturally occurring stimulant derived from wormwood. Absinthe also contains extracts of anise, angelica, calamus, and marjoram. Calamus
Ecstasy and Other Dance-Scene Drugs

Ecstasy is the commonest street name for the drug 3,4-methylenedioxymethylamphetamine (MDMA). It was first manufactured at the start of the twentieth century. It was tested by the US army in the 1950s but was not used recreationally until the 1960s. It was then used on college campuses, but it was not until the rave scene developed in Europe in the late 1980s that its popularity grew. A survey of university students in the UK revealed that 13% had tried ecstasy and among dance-scene attendees, 96% had used it. A similar pattern has been seen in Australia, where 6.1% of Australians 1429 years of age admitted ecstasy use, and 2.9% reported recent use.
Occasional deaths had been recorded from the USA, but few were directly related to the drugs pharmacological effects. In the UK, in the early 1990s, reports of deaths appeared and had a different pattern to the deaths in the USA. MDMA and related substances have both stimulant and hallucinogenic properties. The rave and dance-scene use was associated with prolonged physical activity. Deaths were reported from hyperpyrexia, with some victims having body temperatures above 44 C. These deaths were followed by deaths from water intoxication. These victims had low sodium concentrations and the deaths could be related both to the inappropriate antidiuretic hormone production and the consumption of large quantities of water. Following further advice to dancers to drink carefully and use isotonic drinks rather than water, the number of cases of water intoxication appears to have fallen. At the same time, in the UK and other parts of Europe, a number of deaths associated with liver failure were encountered, requiring liver transplantation or resulting in death from fulminant liver failure. This appears to be an idiosyncratic response to MDMA. Biopsy-proven hepatitis has been seen following ecstasy use in these cases. MDMA use continues to be popular, and occasional deaths are encountered. As well as MDMA the chemically similar 3,4-methylenedioxyethylamphetamine (MDEA) and MBDB (N-methyl-1-3,4 methylenedioxyphenyl-2-butanamine) have occasionally been encountered, but are apparently not as popular with users. In the UK (population 57 million) during the 1990s, between 11 and 28 deaths per year were recorded as being due to MDMA or MDEA. The long-term morbidity of MDMA remains unclear, but in view of the known pharmacological activity and animal data, concerns about neurotoxicity and cardiovascular effects remain. The typical route of administration of MDMA is by oral ingestion, but occasional users have tried injecting and snorting it, and a few have even tried it as a suppository. As well as MDMA and similar drugs, other chemically unrelated drugs, including ketamine and gamma-hydroxybutyrate (GHB), are used. GHB is commonly known as liquid ecstasy, though it is not a stimulant. In the UK it was lawfully available until 2003. It is normally ingested. Because of its actions and its liquid form, it has been used as a date rape drug. Users of GHB often present clinically as an emergency in a deeply unconscious state. After a period of unconsciousness they rapidly gain consciousness and are able to walk out of hospital. Deaths are typically associated with alcohol use. Postmortem blood concentrations of GHB must be interpreted carefully as postmortem production occurs.
Ketamine is manufactured as an anesthetic for both human and animal use. It is structurally related to phencyclidine (PCP). PCP has been commonly encountered in the USA, with recreational use reported in California in the 1960s. It was associated with violent behavior and its popularity declined. The same pharmacological problems prevented its use as an anesthetic agent. Its use has declined from the 1970s and 1980s. PCP use never became popular in the UK. Ketamine has become a popular drug in the dance scene and at ketamine parties, where it is often called special K. Clinically, ketamine has a wide range of safety and it is rarely reported in deaths, though its use in the UK is increasing. It may modify behavior, and like PCP, its use may result in violent conduct. Tablets that are sold as MDMA may contain other substances or no pharmacologically active substance. Many tablets contain logos of commercial products, but this is no guarantee of the source of the tablet, as other illicit manufacturers may copy a popular tablet.
Volatile Substance Misuse

Solvent abuse remains an important cause of death and tends to occur in a younger age group than with other drugs. Whilst often known as glue-sniffing, because of misuse of toluene-based adhesives, the commonest substance causing death in the UK is butane and related gases. Harm reduction programs such as the regulation of butane-containing products, the reformulation of paper correction substances that previously contained 1,1,1-trichloroethane, and the removal of commercially available fire-extinguishers containing bromochlorofluormethane, have all helped to reduce the number of volatile substance abuse deaths in the UK from a peak in 1990.
Polydrug Use
It is increasingly recognized that drug misusers will take a variety of substances. This may be because of the pattern of recreational use or as a result of a deliberate attempt at trying to reverse the effects of one drug with another. Thus some users of MDMA will try and come down off their party high by using alcohol or cannabis and even heroin occasionally. Friends of a collapsed heroin injector may try and revive him/her with amphetamine or another stimulant. It is now typical to see mixed patterns of use. Benzodiazepines are a common accompaniment to heroin use, and increasingly the pathologist and toxicologist are faced with interpreting a large number of drugs in a single victim. One view is to include all drugs found as the combination of effects is
206 SUBSTANCE MISUSE/Crime
unpredictable. This will result in some drugs being included in the death certificate that have doubtful or nontoxic effects. Another view is that drugs that have similar effects should be included. Therefore, respiratory depressants such as alcohol and benzodiazepines should be included in deaths where heroin is the principal toxic substance. Both schools of thought have some justification. What seems reasonable is that trivial substances, such as the presence of cannabis, should not be included.
Rodgers J, Ashton CH, Gilvarry E, Young AH (2004) Liquid ecstasy: a new kid on the dance floor. British Journal of Psychiatry 184: 104106. Winstock AS, Griffiths P, Stewart D (2001) Drugs and the dance music scene: a survey of current drug use patterns among a sample of dance music enthusiasts in the UK. Drug and Alcohol Dependence 64: 917.
Conclusion
The patterns of drug-related deaths continue to evolve with the changing in popularity and availability of available drugs. In any drug-related death, the toxicological data should be considered in combination with the pathological findings and the clinical information.
Crime
J Payne-James, Forensic Healthcare Services Ltd, London, UK
Introduction
The relationship between substance misuse and crime is one of ever-increasing importance on a worldwide basis. This article will explore the generality of these two issues from the perspective of England and Wales. The implications are similar in any country or region with problems of substance misuse, although the extent of the problems will be modified by local economics, police response to crime, legal penalties for drug offenses and drug-related crime, and political will. Terminology and definitions within the field of substance misuse are variable, and without clarification can be misconstrued. The term substance misuse will be used here to refer to drug taking which is unsanctioned by professional and cultural standards and may be hazardous or harmful the definition used by the Task Force to Review Services for Drug Misusers in 1996. The same report defined a problem drug-taker as any person who experiences social, psychological, physical, or legal problems related to intoxication and/or regular excessive consumption and/or dependence, as a consequence of his or her use of drugs or other chemical substances (excluding alcohol and tobacco). The exclusion of alcohol and tobacco from this definition is because (in general) the use is not prohibited by law (although there are statutory situations such as within the UK Road Traffic Act 1988 when alcohol may be relevant) even though in health terms they are the two most harmful substances regularly used. The third term which must be defined is drug (or substance) dependency. The World Health Organization defines drug dependence as:
See Also
Substance Misuse: Medical Effects; Cocaine and Other Stimulants; Heroin; Miscellaneous Drugs; Substitution Drugs; Urine Analysis
Further Reading
Degenhardt LI, Barker B, Topp L (2004) Patterns of ecstasy use in Australia: findings from a national household survey. Addiction 99: 187195. Drummer O, Odell M (2001) The Forensic Pharmacology of Drugs of Abuse. London: Arnold. Flannagan RJ, Rooney C (2002) Recording acute poisoning deaths. Forensic Science International 128: 319. Goldfrank LR, Flomebaum NE, Lewin NA, et al. (2002) Goldfranks Toxicologic Emergencies. London: McGraw-Hill. Karch SB (1998) A Brief History of Cocaine. London: CRC Press. Karch SB (2002) Karchs Pathology of Drug Abuse. London: CRC Press. Lange RA, Hillis D (2001) Medical progress: cardiovascular complications of cocaine use. New England Journal of Medicine 345: 351358. Merlene AC, OMalley PM, Schulenberg JE, et al. (2004) Substance use among adults 35 years of age: prevalence, adulthood, predictors, and impact of adolescent substance use among adults 35 years of age. American Journal of Public Health 94: 96102. Milroy CM (1999) Ten years of ecstasy. Journal of the Royal Society of Medicine 92: 6872. Milroy CM, Forrest ARW (2000) Methadone deaths a toxicological analysis. Journal of Clinical Pathology 53: 277281.
SUBSTANCE MISUSE/Crime 207 a cluster of physiological, behavioral, and cognitive phenomena of variable intensity, in which the use of a psychoactive drug (or drugs) takes on a high priority. The necessary descriptive characteristics are preoccupation with a desire to obtain and take the drug and persistent drug-seeking behavior. Determinants and the problematic consequences of drug dependence may be biological, psychological, or social and usually interact.
Recreational drug misuse is the final definition required and this refers to drug taking on an occasional or infrequent basis as part of personal and social recreation. There is obvious potential overlap between drug dependence and recreational drug misuse, and a recreational drug misuser may move into the category of drug dependence, dependent on the type, quantity, and frequency of the drug being used. Substance misuse and the crime it brings with it impacts on the legal system by virtue of the fact that certain substances are themselves illegal (e.g., to possess or supply), and secondly because drugs are a cause of crime either because crime needs to be committed to get access to drugs or because the drugs themselves alter the individuals behavior so that he or she behaves outside the norms of society or the law. This categorization is simplistic but enables views to be taken about the effects of substance misuse on the legal system. This type of categorization has been further classified into drug-defined offenses that are defined by law in terms of the illegal use of a specific substance in various ways, including possession, supply, and importation; drug-inspired offenses, including such offenses committed to finance the purchase of drugs (such as shoplifting, theft, and burglary), and drug-induced offenses which occur as a result of the effect of the substance on a persons behavior.
Legal Framework
Reference here will be limited to the laws of England and Wales. The gradual development of statutes to control drug use originated in the nineteenth century with western concern about the use of opiates in China. Opium was used to induce stupefaction, but no restriction in its distribution was present until the Pharmacy Act 1868 regulated its sale. In 1909, the Shanghai Conference, with 13 countries present, introduced the idea of control, and in 1912 the International Convention of Opium limited manufacture, trade, and sale. In the UK, the Defence of the Realm Act 1916 introduced controls on cocaine, and the Dangerous Drugs Act 1920 codified previous regulations and made the possession of opium and
cocaine for personal consumption illegal. Subsequently the Dangerous Drugs Act 1925 put controls on the possession and use of cannabis. In the 1960s possession of lysergic acid diethylamide (LSD) and amphetamines was restricted by the Drugs (Prevention of Misuse) Act 1964 and the Dangerous Drugs Act 1965, respectively. The Misuse of Drugs Act 1971 was enacted with a view to controlling the importation, distribution, and use of substances and products considered by the government of the day to be capable of having harmful effects likely to constitute a social problem. It had six broad aims: (1) to control the use, production, and distribution of all drugs recognized to be medically or socially harmful; (2) to create a body comprising experts in the field of science and social science to advise the government; (3) to use research to understand more fully the problems of drug misuse; (4) to enforce the law by criminal sanction when relevant; (5) to facilitate the treatment of those with drug dependency; and (6) to educate the public. The Act prohibits the nonmedical use of certain drugs and places them in different classes, lays down the penalties for the particular drugs at issue, and identifies the various unlawful acts of possessing, manufacturing, and trafficking controlled drugs. Under the Act it is an offense to allow anyone on ones premises to produce, give away, or sell illegal drugs or even to offer to supply a controlled drug free of charge. The Act provides the legal framework for the control of drugs and details the specific requirements for the prescription, safe custody, record-keeping, and the offenses relating to production, cultivation, supply, and possession of most drugs. Penalties for contravention of sections of the Misuse of Drugs statutes and regulations can be severe, including life imprisonment for supplying (selling or giving away) a class A drug. The Drug Trafficking Offences Act and Part III of the Criminal Justice (International Cooperation) Act 1990 allowed for the destruction of drugs seized by the authorities and for the confiscation of any profit derived from drug dealing or importation. It also amended the 1971 Act, making it an offense to sell or supply drug paraphernalia (those items excluding syringes and needles used for the illicit consumption of drugs). Import and export of drugs controlled under these Acts is within the jurisdiction of HM Customs and Excise under the Customs & Excise Management Act 1979. The Misuse of Drugs Act 1971 also controls how legally produced drugs which are included under the Act may be prescribed in certain circumstances.
Under the Misuse of Drugs (Supply to Addicts) Regulations 1997 a registered medical practitioner is prohibited from administering, supplying, or prescribing certain controlled drugs to a person considered to be, or reasonably suspected of being, a drug addict except under a license issued by the Secretary of State, although such drugs can be prescribed for organic disease or injury. These drugs include cocaine, diamorphine (heroin), and dipipanone. The Misuse of Drugs (Notification of and Supply to Addicts) Regulations 1973 state that a person is to be regarded as being addicted to a drug if he or she has, as a result of repeated administration, become so dependent on the drug that he or she has an overpowering desire for the administration of it to be continued. When prescribing controlled drugs certain regulations apply. The prescription should be in ink and hand-written with the address of the prescriber, signed, and dated. The name and address of the patient stating the drug, the form, strength (where appropriate), dose, number of dosage units, or the total quantity given in words and figures must be supplied. The Misuse of Drugs Regulations 1985 provide schedules which define certain classes of persons who may possess, produce, supply, prescribe, or administer certain drugs in the practice of their professions. There are a number of other Acts which have direct relevance to, or provision for, substance misuse. The Health & Safety at Work Act 1974 places responsibilities on both employers, to ensure the health, safety, and welfare of their employees as far as is reasonably practical, and employees, who have a responsibility to take care of their own safety and that of fellow employees. Clearly, the use of drugs or alcohol by employees, or knowledge by the employer of such use, could mean that either or both are not fulfilling their duties under the Act. There has been increasing recognition of this fact and preemployment screening or workplace testing programs are becoming more common. The Road Traffic Act has a number of provisions relating to the use of either alcohol or drugs or both. Section 5 (1) (a) of the Act states that a person commits an offense if he or she drives or attempts to drive a motor vehicle on a road or other public place when his or her alcohol level exceeds the limits prescribed. Section 4 (1) of the Road Traffic Act 1988 as amended by section 4 of the Road Traffic Act 1991 states that a person commits an offense if he/she drives or attempts to drive a mechanically propelled vehicle on a road or other public place when unfit through drink or drugs. Section 4 (2) of the Road Traffic Act, as amended by s4 of the Road Traffic
Act 1991, states that a person commits an offense if he/she is in charge of a mechanically propelled vehicle on a road or other public place when unfit through drink or drugs. The assessment of individuals who have been arrested for such offenses is complex and ambiguous, in both medical and legal terms. Section 27 (1) of the Transport and Works Act 1992 states that it is an offense for any of the following persons to carry out their work while unfit through drink or drugs, namely a train or tram driver, guard, conductor, or signalman or anybody who works on a transport system in which he can control or affect the movement of a vehicle or works in a maintenance capacity or as a supervisor or lookout for persons working in a maintenance capacity. Under section 27 (2) of the same Act it is an offense for these persons to carry out their work after having consumed more alcohol than the prescribed limit. The Intoxicating Substances [Supply] Act 1985 applies to England and Wales, and makes it an offense for a person to supply or to offer to supply to someone under the age of 18 substances which are not controlled drugs if the supplier knows or has reason to believe that the substance or the fumes from that substance will be used to achieve intoxication. Whilst the former may relate to drug-defined offenses, other statutes may relate to drug-inspired or drug-induced offenses. Examples include the Offences Against the Person Act 1861, The Theft Act 1968, and the Criminal Damage Act 1971. In England and Wales, the Police and Criminal Evidence (PACE) Act 1984 is a wide-ranging statute delineating the powers and limitations of the police during criminal investigations and the rights of suspected and arrested persons and makes particular reference to the medical care of detained suspects and prisoners. Special reference is made with regard to fitness to interview and the Codes of Practice state: No person who is unfit through drink or drugs to the extent that he is unable to appreciate the significance of questions put to him and his answers may be questioned about an alleged offence in that condition except in accordance with Annex C. It is thus recognized in PACE that the effects of drug misuse may affect due process of the law. There are thus a number of different ways in which substance misuse can impact on the legal system. The increasing use of drugs throughout society means that year after year, larger numbers of individuals will be arrested for either specific drug offenses, or other criminal offenses as a result of either drug dependence or acute intoxication with drugs. The outcome of such arrests may itself be dependent on the individuals particular form of substance misuse.
SUBSTANCE MISUSE/Crime 209
Crime Statistics
The link between substance misuse and crime is well established. What is less clear is whether the crime is always as a direct result of the drug use, or whether the individual concerned would have been an offender even without drugs. Goldstein has distinguished three ways in which drugs and crime are connected the first way is by what he terms the psychopharmacological link, whereby the effect of the substance produces criminality per se; the second way is by the economic link when the crime is committed to further a habit; and in the third way, the systemic link, crime is intrinsic to the system of drug distribution. Whatever model is used and whatever the causality proposed, the links between drugs and crime are strong. An Audit Commission Report (1996) showed that the pattern of offending may start at an early age: heavy use of alcohol and drugs is one of the main predictors of children who are more likely to become offenders when they grow up. Seventy percent of young offenders who were on supervision orders admitted to some form of drug use and 9% had used heroin at least once. Cannabis was most commonly used (by over 60% of offenders). Almost a quarter felt their offending had sometimes been influenced by the need to take drugs. It seems likely that this figure is an underestimate, particularly as half of the same group admitted that they got drunk at least once a week. Fifteen percent of sentenced youths had problems with drugs and/or alcohol. The use of large quantities of alcohol or hard drugs (cocaine, heroin) is associated with a greater likelihood of reoffending. The amount of crime related to substance misuse is vast. One study showed that 70 000 crimes had been committed in the 3 months preceding entry into the study. Both males and females were engaged in criminal activity, although males were in the clear majority. Males were more likely to commit crimes such as supplying drugs, burglary, robbery, and theft whilst the females were more likely to shoplift, undertake fraud, or solicit. In our 1992 study of 150 drug misusers in police custody, the average spent on drugs per day was 100, irrespective of whether the individual was receiving methadone as part of a treatment program. Thus, the annual financial turnover for these 150 users would be 5.475 million (150 100 365) per annum. This represented a small sample from a small central area of London almost a decade ago; this analysis has recently been repeated and, although daily costs are now between 100 and 200, the percentage of those seen with drug problems has risen from 11% to 30%.
The effects of drugs on other (nonproperty) offenses is also marked. A study of blood and urine analyses of those arrested for possible drug driving in the Lothian and Borders area of Scotland showed that 86.7% cases had drugs confirmed, and of those, 9.3% had multiple drugs present. Benzodiazepines were the most frequently found (40%), with cannabinoids present in 24% of samples. It is of particular interest that 47.2% of drivers had previous convictions for drug-related offenses. Recent statistics from England and Wales that relate specifically to drugs and drugs and crime show the following key points: 1. Around 10% of arrests in England and Wales in 20022003 were for drug offenses (predominantly possession or supply). 2. In a study of drug screening/testing in pilot sites across England and Wales, of almost 18 000 tests undertaken on prisoners arrested for various crimes, about 50% tested positive for cocaine, heroin, or both. 3. The most common offenses for which the individuals being tested had been arrested were theft and burglary and it is likely that those who are using cocaine and/or heroin are carrying out these type of offenses to pay for their substance misuse. 4. Theft, robbery, and burglary accounted for 43% of arrests in England and Wales in 20022003, and by implication from the drug-screening program half of these i.e., 21.5% of total arrests would be related to substance misuse. 5. In 20022003 12% of all 1659-year-olds had taken an illicit drug and of those, 3% had used a class A drug in the previous year this equates to around 4 million illicit drug users and around 1 million class A drug users. These data confirm that a large minority perhaps one-third of the workload of criminal justice system relates to substance misuse.
Conclusions
The adverse effects of all types of substance misuse on our society over and above those simply of health are only really just being recognized by the general population. The ability to control or substantially reduce substance misuse has not yet been achieved. The relatively recent awareness of how strongly drugs are implicated in crime and social disorder in the UK has highlighted the gravity of the problem. Government appears to recognize the extent of the problem but it is
not evident that attempting to deal with it is high on the political agenda. The implications of substance misuse and its criminal burden on an already overstretched and underfunded legal system are so great that any failure to check current trends could prove to be devastating, not only for substance misusers and the legal systems within the England and Wales, but for the community as a whole. These problems are present globally and intergovernmental cooperation is essential to minimize the movement and supply of drugs.
See Also
Substance Misuse: Substitution Drugs; Patterns and Statistics
Further Reading
Adamson SJ, Sellman JD (1998) The pattern of intravenous drug use and associated criminal activity in patients on a methadone treatment waiting list. Drugs and Alcohol Review 17: 159166. Audit Commission (1996) Misspent Youth Young People and Crime. London: Audit Commission Publications. Ayres M, Murray L, Fiti R (2003) Arrests for Notifiable Offenses and the Operation of Certain Police Powers under PACE. England and Wales 2002/2003. London: National Statistics. Department of Health (1999) Drug Misuse Statistics for 6 Months Ending March 1998. London: Department of Health. Edgar K, ODonnell I (1998) Mandatory Drug Testing in Prisons. The Relationship between MDT and the Level and Nature of Drug Misuse. Home Office Research Study 189. London: Home Office Research and Statistics Directorate. Gossop M, Marsden J, Stewarts D (1998) The National Treatment Outcome Research Study. Changes in
Substance Use, Health and Criminal Behaviour One Year after Intake. London: Department of Health. Graham J, Bowling B (1995) Young People and Crime. London: Home Office Research and Planning Unit, Home Office. Home Office Development and Practice Report (2004) OnCharge Drug Testing: Evaluation of Drug Testing in the Criminal Justice System. London: Home Office. Home Office Findings 229 (2003) Prevalence of Drug Use: Key Findings from the 2002/2003 British Crime Survey. London: Home Office. Ledingham D (1999) Drugs and driving: a retrospective study of the analyses of blood and urine specimens submitted to the Lothian and Borders police forensic laboratory. Journal of Clinical Forensic Medicine 6: 133140. Payne-James JJ, Dean PJ, Keys DW (1994) Drug misusers in police custody: a prospective survey. Journal of the Royal Society of Medicine 87: 1314. Payne-James JJ, Bailey C, Wall I (2005) Drug misusers in police custody 2003: A prospective survey. Journal of Clinical Forensic Medicine (in press). Povey D, Cotton J (2000) Recorded Crime Statistics. England and Wales October 1998September 1999. London: Home Office Research Development and Statistics Directorate. Ramsay M, Partridge S (1999) Drug Misuse Declared in 1998: Results from the British Crime Survey. Home Office research study no. 197. London: Home Office. Sidwell C, Best D, Strang J (1999) Cost of drug use and criminal involvement before and during methadone treatment. Journal of Clinical Forensic Medicine 6: 224227. The United Kingdom Anti-Drugs Coordinator (1999) First Annual Report and National Plan. London: Central Office of Information. Turnbull PJ, McSweeney T, Webster R, Edmunds M, Hough M (2000) Drug Treatment and Testing Orders: Final Evaluation Report. London: Home Office Research, Developments and Statistics Directorate.
Substance Misuse, Alcohol See Alcohol: Breath Alcohol Analysis; Blood and Body Fluid Analysis; Acute and Chronic Use, Postmortem Findings
Substance Misuse: Back-tracking Calculations
See Back-tracking Calculations
SUDDEN NATURAL DEATH/Cardiovascular 211
SUDDEN NATURAL DEATH

Contents Cardiovascular Central Nervous System and Miscellaneous Causes Infectious Diseases
Cardiovascular
A Burke and R Virmani, Armed Forces Institute of Pathology, Washington, DC, USA
Introduction
Incidence
Sudden cardiac death occurs in 300 000400 000 individuals annually in the USA, with an incidence of 100200/100 000 per year. In adults 40 years of age or younger, the incidence is far lower. For example, in Olmsted County, Minnesota, the incidence of sudden death in young adults has been estimated to be 510/100 000 population per year.
Definition
study, 62% of all coronary heart disease deaths were sudden in men aged 4554 years, whereas in the 55 64-year and 6574-year age groups, the percentage of sudden death declined to 58% and 42%, respectively. There was a 3.8-fold higher incidence of sudden cardiac death in men than in women. The excess relative risk in men peaked at 5564 years, reflected in a maleto-female ratio of 6.75:1; this ratio decreased to 2.17:1 in the 6574-year age group. Racial differences in the incidence of sudden cardiac death have also been noted: blacks have an increased risk compared to whites. Hereditary factors are important in a variety of causes of sudden cardiac death, including atherosclerosis, cardiomyopathies, and channel diseases.
Causes of Sudden Cardiac Death
Sudden cardiac death is natural, nonviolent, unexpected, and occurs within a short time of the onset of acute symptoms (usually 1 h, for purposes of definition). When the definition of death is less than 2 h after onset of symptoms, 12% of deaths are sudden and 88% are due to cardiac causes. When applying a symptom duration of less than 24 h, 32% of deaths are sudden and cardiac causes of death decline to 75%.
Epidemiology
The ages at which sudden death is most prevalent are birth to 6 months (sudden infant death syndrome) and between 45 and 75 years. Only 19% of sudden natural deaths in children between 1 and 13 years of age are cardiac in origin, whereas in the 1421-yearold age range 30% are cardiac. In the adult population, the most common cause of sudden death is coronary heart disease, with various forms of cardiomyopathies the second most common cause. The proportion of deaths from heart disease that are sudden declines with advancing age. In the Framingham
The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Department of the Army, the Department of the Air Force, or the Department of Defense.
Virtually any pathologic process that involves the heart may result in sudden death by virtue of the wide variety of mechanisms that may result in terminal arrhythmias. Acute ischemia, infiltrative diseases (primarily scars or inflammation), cardiac hypertrophy, and cardiac failure are the most common anatomic substrates of ventricular arrhythmias and may have a variety of interrelated causes (Table 1). In developed countries, coronary atherosclerosis is by far the most common finding in cases of sudden cardiac death in patients older than 3035 years. Coronary atherosclerosis may result in sudden death by acute ischemia, arrhythmias secondary to healed infarcts, cardiac rupture, and acute heart failure. The second most common cause of sudden death is intrinsic myocardial diseases, which may be classified as hypertrophic cardiomyopathy, dilated cardiomyopathy, hypertensive cardiomyopathy, and idiopathic left ventricular hypertrophy. The third most common cause of death is valvular disease, especially mitral valve prolapse and aortic stenosis. Congenital heart diseases that may result in sudden death include coronary artery anomalies, forms of hypertrophic cardiomyopathy, and forms of aortic stenosis; these are an especially important cause of death in men and women younger than 35 years of age. In adolescents and young adults, myocarditis, cardiomyopathies (right ventricular dysplasia and hypertrophic and idiopathic left ventricular hypertrophy),
212 SUDDEN NATURAL DEATH/Cardiovascular

Table 1 Causes and mechanisms of sudden cardiac death
Immediate cause Underlying causes Mechanisms
Acute ischemia
Coronary atherosclerosis Nonatherosclerotic coronary diseases Aortic stenosis Inflammatory (myocarditis) Scars (healed infarcts, cardiomyopathy) Hypertrophic cardiomyopathy Systemic hypertension Idiopathic concentric left ventricular hypertrophy Aortic stenosis Dilated cardiomyopathy Chronic ischemia Systemic hypertension Aortic insufficiency Mitral insufficiency Ruptured myocardial infarct Aortic rupture Pulmonary embolism Mitral stenosis Left atrial myxoma Severe ischemic heart disease Aortic stenosis Pulmonary embolism Massive myocardial infarct Ruptured papillary muscle Chordal or leaflet rupture Pulmonary stenosis Pulmonary hypertension Neuromuscular diseases Accessory pathways Congenital and acquired states Atrioventricular nodal scarring, inflammation, tumor
Infiltrative diseases Cardiac hypertrophy
Ventricular fibrillation Bradycardia Electromechanical dissociation (usually end-stage or postresuscitation) Ventricular fibrillation Bradyarrhythmias (uncommona) Ventricular fibrillation Bradyarrhythmias (uncommon)
Cardiac dilatation (congestive failure)
Ventricular fibrillation Bradyarrhythmias (uncommon)
Tamponade Disruption of blood flow
Pulseless electrical activity Pulseless electrical activity Ventricular fibrillation Baroreflex stimulation with bradyarrhythmias Ventricular tachyarrhythmias Pulseless electrical activity Ventricular fibrillation Bradyarrhythmias Baroreflex stimulation with bradycardia Atrial fibrillation ! ventricular fibrillation Ventricular fibrillation (torsade de pointes) Bradycardia ! ventricular fibrillation
Global myocardial hypoxia
Acute heart failure
Systemic hypoxia Vasovagal Preexcitation Long QT Heart block
Especially in the presence of infiltrative processes involving the conduction system. Reproduced with permission from Virmani R, Burke A, Farb A, and Atkinson JB (eds.) Cardiovascular Pathology, p. 342. Philadelphia, PA: WB Saunders. 2001.
and coronary artery anomalies are the most common causes of sudden cardiac death in individuals with structural heart disease (Tables 24). The most common identifiable causes of sudden death in young children are myocarditis and congenital heart disease, including coronary artery anomalies and hypertrophic cardiomyopathy. Up to 50% of cardiac causes in children who die during exercise are idiopathic arrhythmias with apparently normal heart at autopsy. For children and young adults, in cases of apparent sudden cardiac death with no morphologic cardiac abnormalities at autopsy, genetic abnormalities of ion channels or calcium signaling should be considered.
Degrees of Certainty and Causes of Death
Table 2 Causes of sudden cardiac death in infants and children

01 years (n 20) 121 years (n 50)
Anatomic findings
Coronary artery anomalies Myocarditis No finding Other findings Hypertrophic cardiomyopathy
10 (50%) 0 7 (35%) 2 (10%) 1 (5%)
12 (24%) 14 (28%) 10 (20%) 8 (16%) 6 (12%)
Reproduced with permission from Virmani R, Burke A, Farb A, and Atkinson JB (eds.) Cardiovascular Pathology, p. 342. Philadelphia, PA: WB Saunders. 2001.
The underlying substrates for ventricular arrhythmias may be chronic or subacute conditions, leading to
difficulties in assessing a precise cause of death. Occasionally, there may be more than one anatomic abnormality that may lead to a lethal arrhythmia, and the exact cause of the terminal event may be difficult

Table 3 Causes of death, ages 2130
Cause of death
Atherosclerosis No findinga Idiopathic left ventricular hypertrophy Hypertrophic cardiomyopathy Myocarditis Anomalous coronary artery Dilated cardiomyopathy Tunnel coronary artery Aortic dissection Rheumatic mitral stenosis Complex congenital heart disease Hypertensive left ventricular hypertrophy Endocarditis Sarcoidosis Aortic stenosis Floppy mitral valve Right ventricular cardiomyopathy Coronary aneurysm (congenital) Amyloid Pericarditis Total
a
64 (28%) 49 (21%) 27 (12%) 16 (7%) 14 (6%) 9 (4%) 7 (3%) 7 (3%) 7 (3%) 6 (3%) 5 (2%) 4 (2%) 4 (2%) 3 (1%) 3 (1%) 2 (1%) 2 (1%) 1 (0.4%) 1 (0.4%) 1 (0.4%) 229
to determine. Definite causes of death are those that result in cardiac tamponade, cardiac rupture, and acute coronary thrombi. Other causes, such as stable atherosclerotic plaque, left ventricular hypertrophy, ventricular scars, focal myocarditis, and cardiomyopathy, should be only considered when other potential conditions have been excluded.
Coronary Atherosclerosis
Coronary Morphology in Sudden Cardiac Death due to Atherosclerosis
The proportion of these cases caused by channel disorders is unknown. Due to rounding totals are more than 100%. Reproduced with permission from Virmani R, Burke A, Farb A, and Atkinson JB (eds.) Cardiovascular Pathology, p. 342. Philadelphia, PA: WB Saunders. 2001.
Table 4 Causes of death, ages 3140

Cause of death n (%)
Atherosclerosis No finding Hypertensive left ventricular hypertrophy Idiopathic left ventricular hypertrophy Dilated cardiomyopathy Hypertrophic cardiomyopathy Myocarditis Sarcoidosis Aortic stenosis Aortic dissection Endocarditis Floppy mitral valve Tunnel coronary artery Right ventricular dysplasia Rheumatic mitral stenosis Anomalous coronary artery Coronary artery dissection Congenital heart disease Lipomatous hypertrophy, atrial septum Total
258 (60%) 38 (9%) 26 (6%) 18 (4%) 16 (4%) 13 (3%) 12 (3%) 10 (2%) 9 (2%) 8 (2%) 6 (1%) 6 (1%) 3 (1%) 3 (1%) 3 (1%) 2 (0.5%) 2 (0.4%) 1 (0.2%) 1 (0.2%) 432
Based on autopsy studies comparing the degree of luminal narrowing of coronary arteries between patients dying suddenly with those dying of other causes, it has been determined that 7580% of cross-sectional luminal narrowing is a useful figure for separating critical stenosis that may result in acute myocardial ischemia from noncritical stenosis. However, any decision that death is due to coronary atherosclerosis, especially in the presence of a stable plaque, must be supported by rigorous exclusion of other noncardiac causes of death. The frequency of coronary thrombosis in sudden coronary death varies from 20% to 70%. The time interval between onset of symptoms and death, the presence of concurrent conditions that may cause arrhythmias (scars and ventricular hypertrophy), and the type of prodromal symptom (stable angina, unstable angina, or no apparent symptoms) all affect the incidence of thrombi in coronary sudden cardiac death. Coronary thrombosis may occur over two major substrates: rupture of thin-cap fibroatheroma (Figure 1) and plaque erosion (Figure 2). Plaque erosion occurs in men and women younger than age 50 and is less common, whereas plaque rupture is more common, occurs at all ages in adults, and is associated with hypercholesterolemia.
Myocardial Findings in Sudden Coronary Death
Due to rounding totals are more than 100%. Reproduced with permission from Virmani R, Burke A, Farb A, and Atkinson JB (eds.) Cardiovascular Pathology, p. 342. Philadelphia, PA: WB Saunders. 2001.
The likelihood of discovering an acute infarction in autopsied cases of sudden coronary death is more than 50% in hospital-based studies of sudden death. In out-of-hospital deaths, and cases of instantaneous sudden death with no symptoms, or symptoms lasting less than 1 h, acute infarcts are unusual, and are found in less than 25% of cases. The incidence of healed infarcts in out-of-hospital sudden coronary deaths is greater than that of acute infarcts. The rate of healed infarcts is greater in the elderly and patients with diabetes mellitus. Postinfarction cardiac rupture, when it involves the free wall, is almost uniformly fatal. The incidence of rupture is highest in the elderly, women, patients
Figure 1 Coronary artery thrombosis secondary to plaque rupture. (A) A cross-section of the left anterior descending coronary artery severely narrowed by lipid-rich atherosclerotic plaque. The lumen (center) is filled with thrombus. (B) A higher magnification of plaque rupture with cholesterol clefts at the site of rupture of the fibrous cap. Movat pentachrome stain.
myocardial infarction is increased in patients with anterior-wall infarctions and bundle-branch block.
Congenital Coronary Artery Anomalies

Anomalous Left Main Coronary Artery
Figure 2 Coronary artery thrombosis secondary to plaque erosion. The left anterior descending coronary artery demonstrates moderately severe narrowing by fibrous plaque with luminal thrombus that is nearly occlusive. The cap is rich in proteoglycans (green staining with alcian blue, Movat pentachrome stain) and there is no cap rupture, as in plaque rupture.
without previous infarction, and in patients with hypertension. The underlying acute infarct is generally transmural, involving at least 20% of the left ventricle. The time interval between infarct and rupture is usually 14 days after infarction but can range between 1 day and 3 weeks.
Mechanisms and Underlying Conditions
The mechanism of sudden death in most cases of ischemic heart disease is ventricular fibrillation; 2030% of patients die with bradyarrhythmias, and a minority of patients have diffuse myocardial damage resulting in acute heart failure or pulseless electrical activity. The mechanisms of ischemia-induced ventricular arrhythmias are most likely related to reentry phenomena. The incidence of ventricular fibrillation during the first 30 days after acute
The most common coronary anomaly resulting in sudden death is an aberrant left main arising in the right coronary sinus of Valsalva. There is a male-tofemale ratio of 4:1 to 9:1. Sudden death occurs in up to two-thirds of individuals with this anomaly, 75% of which occur during exercise. Most patients are adolescents or young adults, although death may occur as young as 1 month of age. There are often premonitory symptoms of syncope or chest pain, but stress electrocardiograms and stress echocardiograms are often negative. Pathologically, there are several variants to this anomaly. The common feature is the presence of the left main ostium within the right sinus (Figure 3). This ostium is typically near the commissure, and in some cases it actually lies above the commissure between the right and left sinuses. Often, the ostium is somewhat malformed and slitlike, and an ostial ridge is present. The proximal artery lies within the aortic media and traverses between the aorta and pulmonary trunk. The pathophysiology of sudden death in patients with aberrant left main coronary artery may be related to compression of the left main by the pulmonary trunk and aorta, diastolic compression of the vessel lying within the aortic media, and poor filling during diastole because of ostial ridges or slitlike ostia.
Anomalous Right Coronary Artery
In contrast to anomalous left main coronary artery, anomalous right from the left sinus is usually an incidental finding, although up to one-third of patients may die suddenly. Approximately 50% of these deaths are exercise-related, and most deaths occur in young and middle-aged adults younger than age 35.
a tunnel greater than 5 mm deep may be considered a potential cause of a lethal arrhythmia.
Other Nonatherosclerotic Coronary Causes of Sudden Death

Spontaneous Coronary Dissection
Figure 3 Anomalous left coronary artery arising in the right aortic sinus. Note the ostial valve-like ridge (double arrow) of the left main coronary artery. The ostium of the right coronary artery (single arrow) likewise arises in the right (R) sinus of Valsalva. The noncoronary cusp (NC) and left (L) cusp are shown to the right and left of the right sinus of Valsalva.
Grossly, there are two ostia located in the left sinus of Valsalva. The ostium supplying the right coronary artery may have similar features as anomalous left ostia located in the right sinus. Namely, there may be upward displacement, location near the commissure, and slitlike ostia with ostial ridges. The proximal anomalous right coronary generally also courses between the aorta and pulmonary trunk. The pathophysiology of sudden death is similar to that of anomalous left coronary artery, and, like that anomaly, evidence of acute or remote ischemia in the ventricular myocardium is not often found.
Origin from Pulmonary Trunk
Coronary artery dissection accounts for approximately 0.5% of sudden deaths in patients 3040 years old (Table 3). Most patients are young women, and sometimes death occurs in the postpartum period. In autopsy studies of coronary dissections that result in sudden death, more than 90% of cases involve the left anterior descending coronary artery. Histologically, the dissection plane is in the outer media, with infiltrates of eosinophils, lymphocytes, neutrophils, and macrophages in the adventitia. The inflammatory infiltrate is believed to be secondary to the dissection and not a vasculitis. The etiology and genetics of spontaneous coronary dissection are unknown.
Small-Vessel Disease
The left main coronary artery arises from the pulmonary trunk in 1/50 000 to 1/300 000 autopsies. Most cases are identified in the first year of life, and sudden death occurs in about 40% of cases. Sudden death usually occurs at rest, but it may arise after strenuous activity in older children. Pathologically, the aberrant artery arises in the left pulmonary sinus in 95% of cases. Typically, the artery appears thin-walled and veinlike, and the right coronary artery, although normal in location, is tortuous.
Tunnel Coronary Arteries
Narrowing of the small arteries supplying the sinoatrial and atrioventricular nodes has been associated with sudden death. The etiology of the narrowing in a majority of these cases is a form of arterial dysplasia. Small-vessel dysplasia has also been associated with catecholamine-induced sudden death, hypertrophic cardiomyopathy, sickle-cell disease, and mitral valve prolapse. Although most cases of small-vessel disease and sudden death have involved arteries supplying the specialized conduction system of the heart, thickened arteries within the wall of the ventricular septum have also been implicated in sudden cardiac death.
Cardiomyopathies
Assessment of Cardiomegaly
A tunnel coronary artery is formed by a myocardial bridge that results in a focally intramural coronary artery that is flanked by epicardial segments. The most common location is the middle third of the left anterior descending coronary artery. Tunneled segments of the left anterior descending coronary artery are found in about 30% of hearts at autopsy. In cases of sudden death without other apparent cause,
Most cases of cardiomyopathy result in cardiac hypertrophy. Normal heart weight varies with body weight, which must be taken into consideration before assessing the degree of cardiomegaly. Ninety-five percent confidence intervals of normal heart weight, as based on body weight and body surface area (kg m2), are readily available and of extreme importance in the assessment of cardiac hypertrophy. Normal heart weight is about 0.45% of body weight in men.
Hypertrophic Cardiomyopathy
Sudden death is the mode of presentation for more than 50% of patients with hypertrophic cardiomyopathy. Patients at risk for sudden death are those with a
family history of sudden death and those with a history of syncope or presyncope. In children with hypertrophic cardiomyopathy, coexistent tunneling of the left anterior descending coronary artery may predispose to sudden death. Familial forms of the disease account for approximately half of the cases and are inherited as an autosomal dominant trait. Genetic defects in familial cases involve structural proteins of the sarcomere, most commonly the beta-myosin heavy chain. Asymmetric left ventricular hypertrophy (predominantly septal), small left ventricular chamber cavity, left atrial dilatation, thickening of the anterior leaflet of the mitral valve, and evidence of left ventricular outflow tract obstruction (left ventricular outflow tract plaque) are all gross features of hypertrophic cardiomyopathy (Figure 4). Histologic features include myofiber disarray with hypertrophy and intramural myocardial artery thickening. Myofiber disarray may be accompanied by significant interstitial fibrosis, especially in advanced stages of disease. There are several potential mechanisms of sudden cardiac death in patients with hypertrophic cardiomyopathy. The major possible mechanisms include acute ischemia secondary to subaortic stenosis, ventricular arrhythmias secondary to disordered muscle bundles in the ventricular septum, myocardial ischemia secondary to small-vessel coronary disease,
altered autonomic vascular control, and myocardial hypertrophy. An increase in the collagen network of the interstitium has been implicated in sudden death due to hypertrophic cardiomyopathy.
Hypertensive Cardiomyopathy
Left ventricular hypertrophy of any cause is associated with ventricular ectopy and increased risk for ventricular tachyarrhythmias. Patients with hypertension and left ventricular hypertrophy have an increased risk of sudden death. As for other causes of cardiomegaly, the diagnosis of concentric left ventricular hypertrophy requires demonstration of increased heart weight as a function of body weight and height.
Idiopathic Concentric Left Ventricular Hypertrophy
In 1040% of sudden deaths in young individuals, especially athletes, concentric left ventricular hypertrophy, as determined by body weight and height, is the only pathologic finding at autopsy. Some cases of idiopathic concentric left ventricular hypertrophy may represent forms of hypertrophic cardiomyopathy, lacking typical morphologic expressions of the disease, especially in patients with a family history of cardiomyopathy. The diagnosis of idiopathic concentric left ventricular hypertrophy assumes the absence
Figure 4 Hypertrophic cardiomyopathy. (A) A long-axis cut of the heart demonstrates a markedly thickened ventricular septum as well as right ventricular hypertrophy. (B) A histologic section of the ventricular septum shows myofiber disarray (Masson trichrome stain). (C) A thickened intramural coronary artery present in the ventricular septum in a patient with hypertrophic cardiomyopathy.
of systemic hypertension, as determined by history or examination of renal microvasculature.

Dilated Cardiomyopathy
Regardless of etiology, the failing heart is prone to ventricular arrhythmias, which may potentially result in sudden death. Ambulatory Holter monitoring in patients with idiopathic dilated cardiomyopathy often demonstrates ventricular arrhythmias, including nonsustained ventricular tachycardia. Although patients with dilated cardiomyopathy frequently die sudden arrhythmic deaths, death is generally not unexpected because illness is often chronic and progressive. The autopsy diagnosis of dilated cardiomyopathy rests on the identification of cardiac dilatation in the absence of significant atherosclerotic and valvular disease. The heart is moderately to significantly enlarged, there is four-chamber dilatation (ventricles more pronounced than atria), and the left ventricular wall is of normal thickness or thinned. The ventricular cavity is generally >4 cm at the level of the papillary muscles. Histologic sections are required to rule out specific causes of cardiomyopathy.
Cardiomyopathy of Obesity
proportion to body weight and myocardial hypertrophy. The most common causes of death are dilated cardiomyopathy, severe coronary atherosclerosis, and concentric left ventricular hypertrophy without left ventricular dilatation. When death occurs during sleep in patients who are obese, concomitant sleep apnea, as determined by history, may be a contributing factor.
Arrhythmogenic Right Ventricular DysplasiaCardiomyopathy
The association of obesity and sudden death has been known since ancient times, as illustrated by Hippocrates adage that sudden death is more common in those who are naturally fat than in the lean. In a study in which morbid obesity was defined as being more than 100% or 100 lb (about 45 kg) over desired body weight, the annual sudden cardiac death mortality rate was 65/100 000 versus 1.6/100 000 in normal-weight women. Autopsy studies of sudden death in the massively obese have shown an increase in heart weight in
Arrhythmogenic right ventricular dysplasia accounts for less than 5% of sudden cardiac deaths but is a relatively common cause of exertional death. Arrhythmogenic right ventricular dysplasia is familial in up to 50% of cases, in which case the mode of inheritance is autosomal dominant with variable penetrance. Most patients are younger than 40 years at the time of death, and some deaths occur in children. Pathologically, the right ventricle is often dilated, with focal thinning (Figure 5). Biventricular scars are seen in the majority of hearts from patients dying suddenly. Histologically, the right ventricle demonstrates areas of scarring and fatty infiltrates; in the left ventricle, these findings are distinctly subepicardial in location.
Right Ventricular Hypertrophy and Pulmonary Hypertension
Patients with idiopathic pulmonary hypertension are at an increased risk for sudden death, especially those with a history of syncope. Syncopal episodes and sudden death generally occur at rest but may be triggered by catheterization procedures and exercise. The mechanism of sudden death in patients with pulmonary hypertension is most likely multifactorial,
Figure 5 Arrhythmogenic right ventricular dysplasiacardiomyopathy. (A) The right ventricle demonstrates focal fat infiltration (bright yellow). (B) The corresponding histologic section shows fat infiltration within the myocardium. (C) A Masson trichrome stain demonstrates fibrosis (blue) in addition to the fat.
including the arrhythmogenic effects of the hypertrophied right ventricle complicated by anoxia-induced bradycardia.
Myocarditis
Lymphocytic Myocarditis
Usually a sequela of viral infection, lymphocytic myocarditis is the cause of sudden cardiac death in 1520% of children and young adolescents and less in young adults. At autopsy, a pericardial effusion is often found. Histologically, there is myocyte necrosis with an accompanying lymphocytic infiltrate. The degree of infiltration may be especially marked in infants and young children, and there may be scattered neutrophils and histiocytes, in addition to lymphocytes. Areas of scarring are not uncommon, and are indicative of chronicity and healing. Large areas of granulation tissue may be present in cases of extensive myocarditis. Serologic and molecular studies suggest that many cases of lymphocytic myocarditis are caused by enteroviruses, especially coxsackievirus type B3, and adenoviruses, although a variety of other viruses have been implicated in isolated cases.
Giant-Cell Myocarditis
suddenly with sarcoid, one-third have no previous medical history, one-third have a history of cardiac symptoms not attributed to sarcoid, and one-third have a previous diagnosis of sarcoidosis. Sarcoidosis affects the heart in 30% of patients with symptomatic pulmonary sarcoidosis, and it may result in ventricular premature beats, ventricular tachycardia, and heart block. The left ventricle is involved in all cases with cardiac involvement, and the interventricular septum is involved in 95% of cases (Figure 6).
Idiopathic Left Ventricular Scars
Occasionally, the only cardiac finding in cases of sudden cardiac death is ventricular scarring, in the absence of significant coronary artery disease or sarcoidosis. Diffuse ventricular scars are likely related to healed myocarditis; subepicardial scars in the left ventricle are frequent in cases of right ventricular dysplasia and may also be present in cases of chronic myocardial emboli. Chronic abuse of cocaine and other drugs may result in ventricular fibrosis in the absence of coronary disease.
Valvular Heart Disease

Mitral Valve Prolapse
A myocardial inflammation that is an especially aggressive form of myocarditis, giant-cell myocarditis is characterized by chronic inflammation with numerous giant cells, widespread myocardial necrosis, and scarring. Sudden death may occur secondary to ventricular arrhythmias or acute heart failure. The differential diagnosis is sarcoidosis, which generally involves mediastinal lymph nodes, lacks myocyte necrosis, and demonstrates well-formed granulomas.
Sarcoidosis
Approximately 2% of sudden deaths in young adults are caused by sarcoidosis. Of patients that die
The lifetime risk of sudden cardiac death in patients with mitral valve prolapse is 13%. The rate of sudden death in patients with mitral valve prolapse is greater if mitral regurgitation is present. The pathophysiology of sudden cardiac death in mitral valve prolapse and competent valves is poorly understood. Vectorcardiograms suggest that the majority of ventricular arrhythmias in patients with mitral valve prolapse arise in the posterior basilar septum of the left ventricle. Autopsy studies have provided several theories for sudden death, including endocardial friction lesions resulting in ventricular arrhythmias, traction of an abnormally inserted valve on the conduction system, deposition of proteoglycans within the
Figure 6 Cardiac sarcoidosis. (A) The heart from a man who died suddenly, without prior history, shows focal epicardial plaquing (arrows), seen more clearly in (B), a photograph of the ventricular apex. (C) Cut sections of the myocardium show multifocal infiltrates and scars, typical of sarcoidosis.
Figure 7 Mitral valve prolapse. (A) The left atrium shown from above, demonstrating the mitral valve, with characteristic billowing and redundancy of leaflets. (B) A histologic section (Movat pentachrome stain) of the atrioventricular septum posterior to the atrioventricular node shows increased proteoglycans (green) as well as a dysplastic, thickened branch of the atrioventricular nodal artery (arrow).
autonomic nerve supply to the heart, and small-vessel dysplasia at the base of the heart (Figure 7).
Aortic Stenosis
Myocardial Rupture
The incidence of sudden death due to aortic stenosis has decreased with the introduction of valve replacement. The principal mechanism of sudden death in aortic stenosis appears to be activation of left ventricular baroreceptors, which causes reflex bradycardia and cardiac arrhythmias. Myocardial ischemia may also contribute to terminal arrhythmias in patients with aortic stenosis via diastolic compression of intramural coronary arteries. Aortic stenosis may be the result of a variety of morphologic valve defects. The most common are calcified bicuspid aortic valves and nodular calcification in normal, trileaflet valves. Asymptomatic patients with aortic stenosis have excellent survival and prognosis. However, after angina or syncope occur, the average survival is 13 years. Aortic valve replacement greatly reduces the risk for sudden death but does not eliminate it: about 20% of deaths in patients with stenotic aortic valve replacement are sudden. Overall, the rate of sudden death is low, estimated to be 0.3% per year. The indications for aortic valve replacement in patients with aortic stenosis are the degree of symptoms, degree of gradient, concomitant coronary disease, degree of left ventricular dysfunction, the presence of arrhythmias, and valve area.
Cardiac rupture generally results from acute myocardial infarction. The infarct almost always involves the left ventricular myocardium, although the epicardial rupture site may be located over the right ventricle. Rarely, cardiac rupture may result as a complication of cardiac abscess. A case of isolated ventricular rupture has been reported in the absence of myocardial necrosis, possibly precipitated by fatty infiltration. Direct cardiac rupture secondary to trauma occurs primarily from gunshot wounds and stab wounds, and it usually involves the anterior wall of the right or left ventricle. In contrast, blunt trauma results from cardiac compression and affects all four chambers of the heart with equal frequency and less commonly results in perforation by rib fracture. Because traumatic deaths are not natural, they are not considered in the spectrum of sudden unexpected cardiac death and will not be discussed further. Iatrogenic forms of traumatic cardiac rupture may result from catheterization procedures, including insertion of pacemakers, and tamponade may be a delayed event. Puncture of the left ventricle or atrium may occur during transvenous approaches to valvoplasty and is often fatal.
Rupture of the Aorta
Cardiac Tamponade
Acute cardiac tamponade occurs when there is sudden hemorrhage into the pericardial space, resulting in impaired ventricular filling and reduced cardiac output. When massive, such as secondary to rupture of the heart, aorta, or coronary artery, electromechanical dissociation and sudden cardiac death occur.
The most common cause of death from type I and II aortic dissections is cardiac tamponade, because the site of rupture of the false lumen is generally within the pericardial reflection. Less commonly, type III dissections (those with the intimal tear in the descending thoracic aorta) will rupture into the pericardial space; the majority of type III dissections rupture into the left hemothorax.
Sudden Death due to Abnormalities in the Conduction System

Cystic Tumor of the Atrioventricular Node
A developmental rest originally believed to be of mesothelial origin, cystic tumor of the atrioventricular node is a collection of endodermal-derived glands in the region of the atrioventricular node (Figure 8). The condition is congenital and results in heart block from birth in most patients. Sudden death may occur at any age, from young childhood to late adulthood; in most patients, a clinical diagnosis of congenital heart block is known.
Heart Block
Cystic tumor of the atrioventricular node is a rare cause of heart block. More commonly, the condition is the result of fibrosis with interruption of the atrioventricular nodal pathways. Congenital heart block is often the result of maternal lupus autoantibodies, and inflammation and scarring, often with calcification, occur in utero. Acquired inflammation and scarring may occur in children and adults without known predisposing cause. The risk of sudden death in patients with congenital or acquired heart block is small, and the need for implantable defibrillators is controversial.
communication (the bypass tract avoiding the atrioventricular node) between either atrium and ventricle. The most common arrhythmias are benign, but sudden death may occur. The incidence of sudden death in patients with the WolffParkinsonWhite syndrome is estimated to be less than 1 per 100 patient-years follow-up; 70% of patients who experience ventricular tachyarrhythmias have a previous history of symptoms. In symptomatic patients, curative ablative therapy prevents recurrent arrhythmias, including atrial fibrillation. In cases of sudden death in patients with known WolffParkinsonWhite syndrome, histologic confirmation of the bypass tract is difficult, and the most important task facing the forensic pathologist is the exclusion of other potential causes of death.
Ion Channel Disorders
Sudden Death in the Absence of Morphologic Findings

Preexcitation Syndromes
The WolffParkinsonWhite syndrome results from preexcitation caused by an abnormal muscular
Mutations resulting in an inactivation of the cardiac potassium channel subunits (encoded by KCNQ1, KCNH2, KCNE1, and KCNE2) cause electrocardiographic prolongation of the QT interval, ventricular tachyarrhythmias, syncope, and sudden death. A ventricular tachyarrhythmia characteristic of the long QT syndrome is torsade de pointes. KCNQ1 and KCNE1 encode for alpha and beta subunits of the slow delayed rectifier potassium current (KvLQT1 and minK); KCNH2 and KCNE2 encode for alpha and beta subunits of the rapid delayed rectifier potassium current (HERG and MiRP1). HERG and MiRP1 are alpha and beta subunits of the same channel protein; likewise for KCNQ1 and minK, respectively. Mutations in the KCNQ1, or LQT1 (long
Figure 8 Cystic tumor of the atrioventricular node. (A) An uncommon cause of congenital heart block and sudden death, atrioventricular nodal tumors are occasionally grossly visible. (B) A histologic section of a different tumor, in which the cystic spaces are of microscopic size.
QT-1), gene have been identified as the cause of RomanoWard syndrome, an autosomal dominant condition characterized by familial premature sudden death. There are several long QT syndromes; the KCNH2 (HERG) gene corresponds to LQT2, KCNE1 (minK) corresponds to LQT5, and KCNE2 (MiRP1) corresponds to LQT6. Mutations in any of these genes may cause ventricular arrhythmias and sudden death. The genes are on different chromosomes (with the exception of minK and MiRP, which share sequence identity) and are composed of multiple exons. Homozygous mutations in the KCNQ1 gene are the cause of the Jervell and LangeNielsen syndrome, an autosomal recessive disorder characterized by marked prolongation of the QT interval, sudden death, and sensorineural deafness. Mutations resulting in activation (as opposed to inactivation) of the cardiac sodium channel gene (SCN5A, or the LQT3 gene) also cause long QT syndrome, torsade de pointes, and sudden cardiac death. There are some differences in typical clinical presentation according to the type of long QT syndrome (Table 5). The Brugada syndrome is characterized by electrocardiographic findings of right bundle-branch block with ST segment elevation in leads V1V3, ventricular arrhythmias, syncope, and sudden death. The syndrome is related to sudden unexpected nocturnal death syndrome in Southeast Asia and Japan, where it has many synonyms, including bangungut, nonlaitai, laitai, and pokkuri. Most cases are autosomal dominant. There have been reports of mutations in the SCN5A gene, the gene responsible for LQT3, with
decreased, instead of increased, activity of the sodium current. A relationship between Brugada syndrome and arrhythmogenic right ventricular dysplasia has been proposed, but is questionable. Mutations of the cardiac ryanodine receptor (RyR2) gene result in familial polymorphic ventricular tachycardia, an autosomal dominant syndrome characterized by ventricular arrhythmias, slight prolongation of the QT interval, and sudden death. Cardiac events, including sudden death, are often precipitated by exertion or adrenergic stimuli (Table 5). The autopsy diagnosis of channel diseases may be accomplished by genetic analysis with sequencing of potential culprit genes, especially the KVLQT1 gene. In selected cases with a strong suspicion, such as unexplained drowning deaths or patients with a family history of unexplained sudden death or LQT syndrome, sequencing of the KVLQT1 or other candidate genes may be possible.
Pulmonary Embolism
Incidence
The incidence of pulmonary embolism is from 23 to more than 200 per 100 000 population annually, and it is the cause of death in 0.25% of people. Approximately 10% of sudden deaths due to cardiovascular causes are due to pulmonary emboli, and about 5% of cardiac arrests are due to pulmonary embolus. The major risk factors for pulmonary embolism are deep venous thrombosis, trauma, postoperative state
Table 5 Characteristics of selected channel disorders that may result in sudden cardiac death without morphologic abnormalities
Events by age 40 (%) Lethality of event (%) Median age at first event (years)
Syndromea
Chromosome
Gene KCNQ1 (KV LQT1) KCNH2 (HERG) SCN5A KCNE1 (MinK protein) KCNE2 (MiRP1 protein) KCNQ1 (KV LQT1) SCN5A RyR2
Current
Triggers
LQT1 LQT2 LQT3 LQT5 LQT6 JLN1 Brugada FPVT
11p 15.5 7q 3536 3p 2124 21q 22.122.2 21q 22.122.2 11p 15.5 3p 2124 1q 4243
+IKs +IKR *INa +IKs +IKR ++IKs +INa *Cab
Exertion, near drowning Auditory stimuli Rest, sleep
62 46 18
4 4 20
9 12 16
Exertion Sleep Exertion, adrenergic stimuli
75 64
50 10
6 35 25
All are autosomal dominant, with the exception of JLN (autosomal recessive). Mutations associated with FPVT result in increased sensitivity of calcium-induced activation of the calcium-release channel complex (L-type calcium channel). LQT, long QT; HERG, human ether-a-gogo related gene; IKs, slowly activating component of delayed rectifier potassium current; IKR, rapidly activating component of delayed rectifier potassium current; *INa, sodium current; JLN, Jervell and LangeNielsen syndrome; MiRP1, MinK-related peptide 1; SCN5a, cardiac voltage-dependent sodium channel gene; FPVT, familial polymorphic ventricular tachycardia; RyR2, cardiac ryanodine receptor. Blank fields indicate insufficient data.
b
(accounting for approximately 25% of hospital deaths due to pulmonary embolism), obesity, malignancy, old age, female gender, and chronic heart disease. After surgery, death from pulmonary embolism may occur within 24 h of the procedure and up to 30 days thereafter. Deficiencies in protein C and S may be first diagnosed in patients who present with pulmonary embolism at a young age, often postoperatively. Affected members of families with protein S deficiency suffer pulmonary embolism at a high rate, from 7% to 26%, depending on other genetic factors. A large study from a medical examiner did not show an increased frequency of factor V Leiden in a series of patients who died with unexpected pulmonary embolism, and neither did a retrospective study of medical autopsies. The lack of association between pulmonary embolism and factor V Leiden is perplexing, given the established increased risk for deep venous thrombosis. Other thrombogenic factors that have been implicated in pulmonary embolism include a polymorphism of plasminogen activator inhibitor-1, which may increase the risk of pulmonary embolism in protein S-deficient individuals, and polymorphism for factor II (prothrombin G20210A polymorphism).
Pathologic Findings
embolism, partly because these patients are treated with anticoagulation.
See Also
Children: Sudden Natural Infant and Childhood Death; Sudden Natural Death: Central Nervous System and Miscellaneous Causes; Infectious Diseases
Further Reading
Ackerman MJ, Tester DJ, Porter CJ, Edwards WD (1999) Molecular diagnosis of the inherited long-QT syndrome in a woman who died after near-drowning. New England Journal of Medicine 341: 11211125. Burke AP, Farb A, Virmani R, Goodin J, Smialek JE (1991) Sports-related and non-sports-related sudden death in young adults. American Heart Journal 121: 568575. Burke AP, Subramanian R, Smialek J, Virmani R (1993) Nonatherosclerotic narrowing of the atrioventricular node artery and sudden death. Journal of the American College of Cardiology 21: 117122. Burke AP, Farb A, Tang A, Smialek J, Virmani R (1997) Fibromuscular dysplasia of small coronary arteries and fibrosis in the basilar ventricular septum in mitral valve prolapse. American Heart Journal 134: 282291. Chiang CE, Roden DM (2000) The long QT syndromes: genetic basis and clinical implications. Journal of the American College of Cardiology 36: 112. Davies MJ (1992) Anatomic features in victims of sudden coronary death: coronary artery pathology. Circulation 85(suppl. I): I19I24. Farb A, Tang AL, Burke AP, et al. (1995) Sudden coronary death. Frequency of active coronary lesions, inactive coronary lesions, and myocardial infarction. Circulation 92: 17011709. Kelly KL, Titus JL, Edwards JE (1993) Pathology of sudden apparent cardiac death in the young. Legal Medicine 42: 4986. Kullo IJ, Edwards WD, Seward JB (1995) Right ventricular dysplasia: the Mayo Clinic experience. Mayo Clinic Proceedings 70: 541548. Kurkciyan I, Meron G, Sterz F, et al. (2000) Pulmonary embolism as a cause of cardiac arrest: presentation and outcome. Archives of Internal Medicine 160: 15291535. Marks AR (2002) Clinical implications of cardiac ryanodine receptor/calcium release channel mutations linked to sudden cardiac death. Circulation 106: 810. Schatzkin A, Cupples A, Heeren T, Morelock S, Kannel WB (1984) Sudden death in the Framingham heart study. Differences in incidence and risk factors by sex and coronary disease status. American Journal of Epidemiology 120: 888899. Shen WK, Edwards WD, Hammill SC, et al. (1995) Sudden unexpected nontraumatic death in 54 young adults: a 30-year population-based study. American Journal of Cardiology 76: 148152. Thiene G, Nava A, Corrado D, Rossi L, Pennelli N (1988) Right ventricular cardiomyopathy and sudden death in
The point of origin is usually in the lower veins (legs and abdomen). In a large series, 60% of thrombi were located in the lower venous tree, 12% in the upper venous tree, and no source could be detected in 28% of cases. The originating thrombi may be overlooked in an attempt to prevent disfigurement of the body, or the entire clot may have dislodged or lysed. Although saddle emboli are invariably fatal, pulmonary emboli in cases of sudden death may be segmental, only involving muscular arteries. Often, a fatal embolus is relatively small but hardly tolerated because of the underlying cardiopulmonary situation. There is a wide variety of patterns of pulmonary embolism, but there is a predisposition to the right lung and lower lobes, and multiple emboli are the rule. Because of the dual blood supply of the lungs, infarction only occurs if there is associated heart disease, especially mitral stenosis. Pulmonary infarction occurs in approximately 15% of cases, is more common in females, and is rare in patients without underlying cardiac diseases. Of pulmonary emboli found at autopsy, 3040% are considered the cause of death, 25% contribute to death, and the remaining are incidental. Symptomatic deep-vein thrombosis or pulmonary embolism is uncommon prior to autopsy-documented pulmonary
SUDDEN NATURAL DEATH/Central Nervous System and Miscellaneous Causes 223 young people. New England Journal of Medicine 318: 129133. Towbin JA (2001) Molecular genetic basis of sudden cardiac death. Cardiovascular Pathology 10: 283295. Veinot JP, Johnston B (1998) Cardiac sarcoidosis an occult cause of sudden death: a case report and literature review. Journal of Forensic Science 43: 715717. Virmani R, Forman MB (1989) Coronary artery dissections. In: Virmani R, Forman MB (eds.) Nonatherosclerotic Ischemic Heart Disease, pp. 325354. New York: Raven Press. Virmani R, Roberts WC (1987) Sudden cardiac death. Human Pathology 18: 485492. Virmani R, Rogan K, Cheitlin MD (1989) Congenital coronary artery anomalies: pathologic aspects. In: Virmani R, Forman MB (eds.) Nonatherosclerotic Ischemic Heart Disease, p. 153. New York: Raven Press. Wagenvoort CA (1995) Pathology of pulmonary thromboembolism. Chest 107: 10S17S.
symptoms or when the immediate clinical history is unknown.
Systems
Central Nervous System
The optimum investigation of deaths resulting from intracranial pathology involves formalin fixation of the brain and examination by a neuropathologist. Unfortunately this level of investigation is becoming available only at specialist institutions. A further significant issue of relevance to neuropathological examination is organ retention. However, with sensitive and open discussion with the deceaseds family and by using rapid fixation techniques, these problems can be addressed. The forensic and general pathologist can facilitate later expert review of a particular case if generous labeled sections are taken for histology along with adequate notation and photographs. Intracranial hemorrhage Sudden and unexpected death attributable to the central nervous system usually occurs as a consequence of intracranial hemorrhage. The two common natural anatomical sites of intracranial hemorrhage are intraparenchymal hemorrhage and subarachnoid hemorrhage. Less commonly, the hemorrhage may involve the extradural or subdural spaces or the ventricular system. The site of the hemorrhage will tend to vary with respect to the deceaseds age and the underlying pathology. Intraparenchymal hemorrhage Intraparenchymal hemorrhage incorporates intracerebral and brainstem hemorrhages. The vast majority of cases are associated with systemic hypertension. The common sites for hypertensive intraparenchymal hemorrhage are basal ganglia, thalamus, the hemispheres, pons, and cerebellum (Figure 1). The clinical evolution of intraparenchymal hemorrhage tends to be sudden with rapid decline in neurological function. The clinical symptoms range from sudden onset of headache to immediate loss of consciousness in pontine hemorrhage. Supratentorial hematomas within the rigid confines of the skull will displace the brain in a predictable way. The volume of blood within the brain required to cause critical brain compression is 75100 ml. After the ventricles are compressed there will be subfalcine, transtentorial, and finally cerebellar tonsillar herniation. Cerebellar hemorrhage may result in headache, ataxia, and vomiting with loss of consciousness occurring due to brainstem compression. Pathological examination of the brain may reveal lipohyalinotic degeneration of blood vessels in sites of predilection for hemorrhage. It has
Central Nervous System and Miscellaneous Causes

M P Burke, Victorian Institute of Forensic Medicine, Southbank, VIC, Australia
Introduction
The investigation of sudden natural death occupies a significant proportion of the workload of the forensic pathologist. Sudden natural death as investigated by a coroner or medical examiner may have significant medicolegal ramifications in addition to providing valuable information to the deceaseds immediate family and the community as a whole. Cardiovascular disease and, in particular, coronary artery atherosclerosis is the most common cause of sudden and unexpected natural death in western societies. This review will concentrate on the important causes of noncardiac death, with particular emphasis on the central nervous system. Meningoencephalitis has been discussed elsewhere.
Definition
The definition of sudden natural death varies between organizations and jurisdictions. Although the World Health Organization defines sudden death as occurring within 24 h of the onset of symptoms, many forensic pathologists would only include cases where the death has occurred within hours of signs and
224 SUDDEN NATURAL DEATH/Central Nervous System and Miscellaneous Causes
Figure 1 Hypertensive brain hemorrhage.
been recently reported that an acute vascular lesion in intracerebral hemorrhage is fibrinoid necrosis of arterioles. In general, individuals who die from a hypertensive hemorrhage will have a clinical history of longstanding hypertension. The postmortem examination may show systemic effects of the disease including concentric left ventricular hypertrophy and benign nephrosclerosis. The brain may also show evidence of old lacunar infarcts within the basal ganglia. Cerebral amyloid angiopathy causes about 12% of primary nontraumatic intracerebral hemorrhage. The disorder occurs as the result of the deposition of amyloid protein within small- and medium-sized cortical arteries and results in often multifocal peripheral and lobar hemorrhage. The deposition of amyloid into the vessel walls renders them leaky. Cerebral amyloid angiopathy is seen in elderly, normotensive individuals and is associated with both Alzheimer disease and Down syndrome. Unusual anatomical sites of hemorrhage may suggest an underlying vascular malformation. The most frequent of these lesions is the arteriovenous malformation, a collection of tangled arteries, veins, and vascular channels that commonly occur over the cerebral hemispheres but also deep within the basal ganglia and thalamus. Arteriovenous malformations may cause both subarachnoid and intraparenchymal hemorrhage. Other less common causes of intraparenchymal hemorrhage include bacterial endocarditis, vasculitides, connective tissue disorders, blood dyscrasias, and tumors. In young adults the presence of an intraparenchymal hemorrhage should raise the possibility of an association with recent use of illicit drugs, including amphetamines and cocaine.
Figure 2 Aneurysms within the circle of Willis.
Subarachnoid hemorrhage Nontraumatic subarachnoid hemorrhage arises primarily from berry aneurysms arising from bifurcation points within the circle of Willis at the base of the brain (Figure 2). Berry aneurysms are believed to originate from a congenital defect in the media of the artery at a branching point. The elastic lamina and muscularis of the artery terminates at the neck of the aneurysm with the wall of the aneurysmal sac formed by thickened hyalinized intima and adventitial tissue. It is believed that the most critical factor leading to rupture of an aneurysm is its size, with diameters greater than 1 cm at significant risk of rupture and subsequent death. The rupture of such an aneurysm is more likely to occur during the day and may be associated with acute stress causing an elevation of blood pressure. The rupture is usually from the tip of the aneurysm and results in blood entering the subarachnoid space and manifests as sudden onset of severe headache or collapse. It is not uncommon for the deceased individual to have complained of symptoms including severe and persistent headache during the weeks leading to death and this is due to the aneurysm leaking. The ruptured aneurysm results in extensive basal subarachnoid hemorrhage and may be associated with intraventricular hemorrhage, and sometimes intracerebral hemorrhage if the aneurysm ruptures directly into the brain parenchyma.
SUDDEN NATURAL DEATH/Central Nervous System and Miscellaneous Causes 225
Figure 3 Arteriovenous malformation of the brain.
Figure 4 Hydrocephalus from colloid cyst of third ventricle.
At the postmortem examination it is imperative to examine the brain before fixation. The arachnoid is gently removed with fine forceps and the blood displaced with a gentle stream of running water. Removal of the blood may be facilitated by a dampened swab. In most cases the aneurysm can be identified; however, in some cases, no aneurysm can be detected and one assumes the rupture has completely destroyed a small aneurysm. Rupture of an arteriovenous malformation causes approximately 10% of subarachnoid hemorrhage and this is more often associated with intraparenchymal and intraventricular extension (Figure 3).
Sudden and Unexpected Death in Epilepsy
Sudden and unexpected death in epilepsy (SUDEP) may be defined as a death occurring in an individual with a documented clinical history of epilepsy, not associated with trauma, drowning, or status epilepticus, and associated with a normal complete postmortem examination with toxicological examination. Most of these deaths occur in the 2040-years age group with a slight male preponderance. Whilst witnessed deaths occur, including those following a seizure, most affected individuals are found deceased in bed. Evidence of seizure activity such as tongue injuries and incontinence are relatively nonspecific and may also occur following terminal seizure activity in deaths from other causes. Risk factors for SUDEP include early onset of seizures, poor seizure control, and generalized tonic/clonic seizures. The weight of evidence would suggest that the deaths may be a result of seizure-related apnea and cardiac arrhythmias. The identification of pathological processes within the central nervous system varies with the level of neuropathological investigation. In one prospective
study of 50 cases of SUDEP with formal neuropathological examination, no structural cause of epilepsy was found in 28 cases. Old head injury accounted for eight cases. Mesial temporal sclerosis was identified in eight cases. The remaining cases showed arteriovenous malformations, ectopic gray matter, cortical dysplasia, SturgeWeber syndrome, and multicystic encephalopathy. Temporal sclerosis is believed to be a consequence of seizure activity rather than the underlying cause. Toxicological examination may show therapeutic or subtherapeutic levels of anticonvulsant medications with conflicting reports presented in regard to the incidence of subtherapeutic levels of anticonvulsant therapies in SUDEP. These discrepancies may also relate to postmortem drug redistribution that occurs with many therapeutic drugs, including anticonvulsants, in the postmortem period. Tumors and tumor-like conditions In rare circumstances an individual may die suddenly and unexpectedly from an undiagnosed central nervous system tumor. When this occurs, it is most commonly associated with hemorrhage into the tumor or sudden obstruction to cerebrospinal fluid, resulting in acute hydrocephalus. Hydrocephalus may also be seen in association with the rare colloid cyst of the third ventricle which may cause sudden death in young individuals (Figure 4).
Respiratory System
Sudden death from asthma is well described in the forensic and respiratory medicine literature. Uncommon causes of sudden death include acute epiglottitis, pneumonia, massive pulmonary hemorrhage, and pulmonary hypertension.
Sudden death in asthma Individuals with asthma may suffer sudden and unexpected death not associated with status asthmaticus. The death rate increases with age. The true incidence is difficult to determine as the presence of other diseases, especially ischemic heart disease and chronic obstructive airways disease, may cause a falsely reduced reporting of acute asthma on death certificates. In general, individuals who die from asthma have a history of significant disease with multiple hospital admissions, low FEV1 (forced expiratory volume in one second), peripheral blood eosinophilia, and a high degree of irreversibility of bronchospasm with a bronchodilator, all factors which suggest severe or uncontrolled asthma. There is a weak association with prior use of oral corticosteroids. However, a significant proportion of the deaths occur in individuals whose asthma has been clinically stable. An acute asthmatic attack results in airway obstruction by mucus and bronchospasm with subsequent ventilationperfusion imbalance, leading to hypoxia and hypercapnia. It is believed that death is ultimately related to a cardiac arrhythmia, most probably occurring in the setting of hypoxia and acidosis in a myocardium sensitized by catecholamines. Postmortem radiology may reveal pneumothorax and mediastinal emphysema reflecting severe obstruction with raised intrathoracic pressures. Macroscopic examination of the lungs reveals voluminous lungs with mucus plugs in bronchi and bronchioles (Figure 5). There may be regions of collapse. Microscopic examination of the lung tissue shows a thickened basement membrane within bronchi, smooth-muscle hyperplasia, and an infiltrate of inflammatory cells, including neutrophils and eosinophils. Eosinophils are prominent within the mucosa and within the bronchial lumen. Some studies have suggested the presence of numerous neutrophils as a marker for an acute attack. Rarely one may see desquamated mucosal epithelium (Curschmann spirals) within the bronchus. Occasionally, the initial diagnosis of asthma will be made at the postmortem examination. More commonly, information from the scene may include a bronchodilator in close proximity, the presence of cigarettes at the scene, and other medications such as aspirin or beta-blocking medications that could potentially precipitate an acute attack. Acute epiglottitis Acute epiglottitis is an acute infection of the epiglottis that is well recognized in children but which may also occur in adults. The causative organism is usually Haemophilus influenzae. Despite immunization with the H. influenzae type B (HiB) vaccine, isolated cases are still
Figure 5 Mucus plugs within bronchi in asthma.
Figure 6 Purulent exudative epiglottitis in an adult with only moderate edema.
recorded. The disease is characterized clinically by high fever, severe sore throat, and painful dysphagia. Death results from acute upper-airway obstruction. The postmortem examination shows edematous mucosa with a pronounced acute inflammatory infiltrate (Figure 6). Pneumonia In developed countries most individuals with significant lower respiratory tract infections will consult their medical practitioner and receive appropriate care. However, individuals who live a marginal existence, or those with significant underlying natural disease, may succumb to pneumonia before a diagnosis is established and thus be referred to the coroner. The most common cause of community-acquired pneumonia is Streptococcus pneumoniae. Infections
SUDDEN NATURAL DEATH/Central Nervous System and Miscellaneous Causes 227
with organisms such as Legionella pneumophila may result in sporadic deaths in addition to occasional outbreaks. Massive pulmonary hemorrhage Massive pulmonary hemorrhage leads to death as a consequence of profound hypoxemia secondary to upper-airway obstruction. The most common cause is erosion of a large artery by a lung malignancy. Rarely vasculitides, infectious, and other inflammatory disorders may be the underlying cause. Pulmonary hypertension Pulmonary hypertension is usually a secondary manifestation of primary myocardial or cardiac valve diseases, underlying pulmonary disease, or chronic pulmonary thromboembolism. Sudden and unexpected death is seen in primary pulmonary hypertension, a rare progressive disorder characterized by the presence of intimal fibrosis, medial hypertrophy, microthrombosis, and plexiform lesions in precapillary pulmonary arteries. The disease is twice as common in females and usually presents in the third decade of life.
Gastrointestinal Tract
Figure 7 Peptic ulcers within the duodenum.
Sudden and unexpected death attributable to the gastrointestinal tract often involves a catastrophic complication of an underlying chronic disease process. Massive gastrointestinal hemorrhage, perforated viscus, hemoperitoneum, and pancreatitis are the more common causes of death. Gastrointestinal hemorrhage The etiological factors in gastrointestinal hemorrhage are protean and include esophageal varices, peptic erosions and ulceration, angiodysplasia, diverticular disease, ischemic colitis, and tumors. Hemorrhage arising from the upper gastrointestinal tract may result in hematemesis, the vomiting of frank blood. Blood acted upon by gastric acid becomes a sticky black stool called melena. The scene of death in such cases may demonstrate a large volume of fresh blood and/or show melena stool. The hemorrhage may be entirely internal with no significant scene findings. Individuals with cirrhosis of the liver from any cause may develop varices of submucosal esophageal veins, which are prone to trauma and sudden massive hemorrhage. The concomitant liver disease results in coagulation abnormalities, which exacerbate the hemorrhage. The postmortem examination may not show any macroscopic abnormality in the esophagus as the varices will collapse with the absence of blood pressure. Blind sections for histology should demonstrate dilated submucosal veins.
Peptic ulceration is often associated with the colonization of the stomach with the bacterium Helicobacter pylori. Ulceration also occurs with ingestion of alcohol and therapeutic medications, including nonsteroidal antiinflammatory drugs (Figure 7). Torrential hemorrhage can occur if there is erosion of a submucosal artery. Widespread gastric erosions are seen in severe stress of any cause and is believed to relate to increased circulating glucocorticosteroids. Rarely, both benign and malignant gastrointestinal tumors may cause fatal hemorrhage. Meckel diverticulum in the small bowel may contain acid-secreting gastric mucosa and develop ulceration. Angiodysplasia and other vascular disorders have been described in the stomach and more commonly in the right colon. The source of the bleeding can be extremely difficult to define at the postmortem examination. Angiographic techniques have shown success in identifying the abnormal vessels. Microscopic examination shows dilated mucosal capillaries with associated dilated submucosal capillaries and venules. Ischemic colitis leads to shock from a combination of hemorrhage and sepsis related to the ischemic mucosa, and is well recognized in elderly individuals with generalized atherosclerosis. The condition may also occur acutely when emboli from the heart or aorta occlude the superior mesenteric artery. Peritonitis Perforation of a viscus is most commonly seen from full-thickness ulceration in the stomach or duodenum. Occasionally a perforated appendix, diverticulum, or tumor can cause death from generalized peritonitis. Spontaneous bacterial peritonitis is a serious complication of ascites in individuals with chronic liver disease. Spontaneous hemoperitoneum Spontaneous hemoperitoneum is a rare condition with a number of etiologies. The intraperitoneal hemorrhage may
occur from rupture of the spleen, liver, or from dysplasias and inflammatory disorders of the splanchnic arteries. Infectious mononucleosis and lymphoid malignancies of the spleen have been associated with rupture, as have adenomas and sarcomas of the liver. Arterial dysplasia and vasculitides such as polyarteritis nodosa may result in splanchnic artery rupture. Pancreatitis Acute and chronic pancreatitis is most commonly related to the presence of gallstones or excessive alcohol intake but is also seen in hyperlipoproteinemia, the vasculitidies, and other inflammatory conditions. The severe end of the spectrum of acute inflammation, hemorrhagic pancreatitis, can lead to death due to gross metabolic disturbance and multiple-system failure induced by systemic inflammatory mediators in the systemic inflammatory response syndrome.
Endocrine System
In the undiagnosed case histological sections may reveal granulomas in tuberculosis, or lymphocytic inflammation in autoimmune disease. Serological examination can confirm the presence of autoantibodies and biochemical analysis can measure adrenocorticotropic hormone and cortisol levels.
Metabolic and Inherited Causes of Sudden Death
Sudden and unexpected death attributable to the endocrine system mainly involves metabolic complications of diabetes mellitus and, rarely, adrenocortical insufficiency. Diabetes mellitus Diabetes is a major risk factor for atherosclerosis and subsequently acute myocardial infarction and cerebrovascular events. Furthermore, diabetes mellitus may cause sudden and unexpected death in young individuals from profound metabolic disturbance associated with the presence of marked hyperglycemia. Diabetes mellitus may lead to sudden unexpected death as a consequence of diabetic ketoacidosis or, rarely, nonketotic hyperosmolar hyperglycemia. Often in retrospect there may have been a history of polydipsia and polyuria, weight loss, and a sense of being generally unwell. Postmortem toxicological examination can reveal a raised glucose concentration within the vitreous humor of the eye. This will be associated with a markedly raised acetone level in blood in cases of ketoacidosis. Microscopic examination of the kidney in cases of diabetic ketoacidosis may show vacuolization of the tubules (ArmanniEbstein lesion). Adrenocortical insufficiency Adrenocortical insufficiency refers to adrenal gland cortical failure. Patients with clinically stable adrenocortical insufficiency may succumb to an Addisonian crisis from acute illness. Rarely an individual with undiagnosed adrenocortical insufficiency may die suddenly and be referred for coronial postmortem examination. In the first instance the examination is tailored to identify any acute illness that could have precipitated the death.
Disorders of connective tissue are a group of uncommon and rare genetically determined diseases that may present as sudden unexpected death. Marfan syndrome is an autosomal dominant disorder of connective tissue with high penetrance and variable severity which affects multiple organ systems. The common clinical findings are bilateral subluxation or dislocation of the lens of the eye, a tall thin stature with arachnodactyly, with 90% of affected individuals having cardiovascular involvement, including mitral valve regurgitation and mitral valve prolapse. Dissection and rupture of the aortic root are the most common causes of sudden death. The underlying changes in connective tissue are caused by mutations in extracellular matrix glycoprotein fibrillin-1, which is encoded at chromosome 15. EhlersDanlos syndrome (EDS) is a heterogeneous group of rare autosomal dominant inherited disorders of connective tissue caused by mutations in the gene encoding type III collagen. The more common clinical findings are tissue fragility with easy bruising, excessive skin elasticity, and joint hypermobility. Eleven types of EDS have been described. In type IV EDS vascular involvement can lead to fatal vascular, intestinal, and obstetric complications. Arterial rupture is the most common cause of sudden unexpected death. Inborn errors of metabolism encompass a wide range of inherited disorders, including the organic acidemias, urea cycle defects, and disorders of amino acid metabolism. These disorders typically present in the infant with lethargy, poor feeding, recurrent vomiting, and failure to thrive. Metabolic acidosis and hypoglycemia are common clinical findings in many of these conditions. Clinical investigation in the infant suspected of having an inborn error of metabolism includes blood-gas analysis, serum, urea and electrolytes, blood glucose, urinary reducing substances and ketones, plasma and urine amino acids, and urine organic acid analysis. Further investigations include liver biopsy, skin biopsy with fibroblast culture, enzyme assay, and molecular analysis.
See Also
Sudden Natural Death: Cardiovascular; Infectious Diseases
SUDDEN NATURAL DEATH/Infectious Diseases 229
Further Reading
Black M, Graham D (2002) Sudden unexpected death in adults caused by intracranial pathology. Journal of Clinical Pathology 55: 4450. Bounds BC, Friedman LS (2003) Lower gastrointestinal bleeding. Gastroenterology Clinics of North America 32: 11071125. Burke MP, Opeskin K (1999) Adrenocortical insufficiency. American Journal of Forensic Medicine and Pathology 20: 6065. Lammie GA (2002) Hypertensive cerebral vessel small vessel disease and stroke. Brain Pathology 12: 358370. Opeskin K, Berkovic SF (2003) Risk factors for sudden unexpected death in epilepsy: a controlled prospective study based on coroners cases. Seizure 12: 456464. Sidebotham HJ, Roche WR (2003) Asthma deaths: persistent and preventable mortality. Histopathology 43: 105117.
such as immunosuppression caused by the infection and adverse reactions to therapeutic drugs. Sudden death due to infectious disease may be classified by organ system involvement (e.g., cardiac myocarditis; nervous system meningitis and encephalitis) or according to the etiological agent (e.g., viral, chlamydial, bacterial, fungal, protozoal, or helminthic). The common infectious causes of sudden death by organ system are listed in Table 1. The morphological findings at autopsy will depend on the type of organism, the site involved, and the hosts response to the organism. Microbiological demonstration of an organism does not equate to disease, as a host may be colonized by bacteria or the patient may have an asymptomatic viral infection. The exquisite sensitivity of molecular tests, e.g., polymerase chain reaction, may exacerbate this problem if the results are not correlated with the pathological findings at autopsy.
Infectious Causes of Sudden Death
Infectious Diseases
M A Dada and N G Lazarus, PathCare, Durban, South Africa
Categories of human pathogens include prions; viruses; chlamydiae, rickettsiae, and mycoplasmas;
Table 1 Common infectious causes of sudden death
Introduction
A wide range of deaths from natural causes is encountered in the field of forensic medicine. Despite the advances in the diagnosis and treatment of infectious diseases, a substantial number of sudden and unexpected deaths are caused by infections. In most medicolegal systems these deaths are subject to a forensic investigation. The World Health Organization defines sudden death as that occurring within 24 h of the onset of symptoms. Some authors variably define sudden death as that occurring within 1, 6, and 12 h of the onset of symptoms. Forensic pathologists should be aware of the importance of infectious causes of sudden death in the present era of bioterrorism and emergent and reemergent diseases. Genetic engineering has led to the development of highly infectious and virulent strains of microorganisms (e.g., anthrax). Emerging infectious diseases are infections whose incidence has increased in recent years and/or threatens to increase in the near future. Reemergence refers to the reappearance of a known infection after a period of disappearance or decline. Death from infectious agents may occur as a direct consequence of the infection or from complications
Cardiovascular system
Myocarditis
Coxsackie A and B
Chlamydia pneumoniae Corynebacterium diphtheriae, Neisseria meningitidis, Borrelia burgdorferi, Mycobacterium tuberculosis Chagas disease (Trypanosoma cruzi ) Hydatid disease (Echinococcus granulosus) Staphylococcus, Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella, Candida Haemophilus influenzae
Infective endocarditis
Respiratory system
Acute epiglottitis Pneumonia
Respiratory syncytial virus, parainfluenza virus, adenovirus, influenza A and B, severe acute respiratory syndrome (SARS), Streptococcus pneumoniae, staphylococci, H. influenzae, Pseudomonas aeruginosa, coliform bacteria, Legionella
pneumophila, Pneumocystis carinii
Central nervous system Meningitis H. influenzae, S. pneumoniae, N. meningitides, Cryptococcus
Encephalitis
Herpes simplex virus-1 Toxoplasmosis, malaria
Gastrointestinal system Peptic ulcer Helicobacter pylori Enterocolitis Vibrio cholerae, Clostridium perfringens, Salmonella, Shigella, enteroinvasive Escherichia coli, Entamoeba histolytica
230 SUDDEN NATURAL DEATH/Infectious Diseases
bacteria; fungi; protozoans; and helminths. Infection by prions, rickettsiae, and mycoplasmas is not normally associated with sudden and unexpected death.
Viral Causes of Sudden Death
Viruses are ubiquitous and cause a spectrum of disease in humans. These may range from asymptomatic infection, severe debilitating illness, to sudden death. Viral infections causing sudden death usually involve the cardiac, respiratory, or the central nervous system. Morphologic findings in viral infections may include intranuclear and/or intracytoplasmic inclusions, multinucleate giant cells, and tissue necrosis (cytopathic effect). In many cases the diagnosis can only be made on special investigations, e.g., culture, electron microscopy, serology, or molecular testing. Viral hemorrhagic fevers such as Marburg, Lassa, and Ebola virus may cause sudden death in children. If there is any suspicion of a viral hemorrhagic fever, special care must be taken to avoid unwarranted exposure to health workers. The local public health officials must be informed and consideration given to limited autopsy examination in consultation with a virologist (e.g., postmortem blood sampling and liver biopsy). Viral infections of the cardiovascular system Cardiac involvement usually takes the form of myocarditis. Although many viruses may cause myocarditis (Table 2), coxsackie A and B are responsible for most cases. Fulminant coxsackievirus infection may also cause leptomeningitis, florid interstitial pneumonitis, pancreatitis, and focal hepatic necrosis. Coxsackie B viruses should also be considered as a cause of sudden infant death. At autopsy, the myocardium is usually mottled and flabby. Histology reveals focal infiltrates of inflammatory cells (neutrophils and/or lymphocytes, plasma cells, and macrophages). At least two foci of individual myofiber necrosis associated with 510
inflammatory cells are required for the histological diagnosis of myocarditis. Focal aggregates of lymphocytes not associated with necrosis may be seen in elderly patients and are not diagnostic of myocarditis. Myocardial involvement may be patchy. For adequate histological sampling, it is recommended that at least six sections be taken from various areas of the myocardium, including the left ventricle and nodal tissue. Indirect damage to the myocardium may occur as an allergic response to a viral infection and eosinophilia, e.g., in eosinophilic myocarditis. This is a rare cause of sudden death in apparently healthy children due to the cardiac toxicity of eosinophils. Studies have shown that persons undergoing severe mental or physical stress may have reduced immunity to viral infections. In the investigation of sudden death in athletes, the diagnosis of viral myocarditis must be considered. Enteroviral infection may also play an important role in coronary plaque instability and may precipitate coronary thrombosis, leading to ventricular tachyarrhythmias and sudden death. Viral infections of the respiratory system Sudden death due to viral involvement of the respiratory system may be due to fulminant viral pneumonitis or bacterial pneumonia complicating an initial viral pneumonitis. Viruses implicated include respiratory syncytial virus, human herpesvirus-6, and parainfluenza virus in children, and adenovirus and influenza A and B in adults. Microscopically, the findings of a viral pneumonitis are usually nonspecific and include edema and widening of the interstitial septa with a mononuclear cell infiltrate. In some cases, diagnostic viral inclusions may be demonstrated. Emergent diseases such as severe acute respiratory syndrome (SARS) have a high mortality and may cause death within hours. SARS refers to an acute respiratory illness caused by infection with a novel coronavirus currently known as the SARS virus. Postmortem histopathological evaluations of lung tissue show diffuse alveolar damage consistent with the pathologic manifestations of acute respiratory distress syndrome. There is usually mild interstitial inflammation with scattered alveolar pneumocytes showing cytomegaly, and enlarged nuclei with prominent nucleoli. When faced with the finding of diffuse alveolar damage at autopsy, the pathologist should consider other infective causes such as influenza, para influenza, respiratory syncytial, and adenoviruses, Chlamydia, Mycoplasma, Pneumococcus, Legionella, and Pneumocystis.
Table 2 Viral causes of myocarditis Adenovirus Cytomegalovirus EpsteinBarr virus Herpes simplex virus 1 and 2 Human immunodeficiency virus 1 (HIV-1) Influenza A and influenza B Parvovirus Picornavirus (e.g., enterovirus and coxsackievirus A and B) Respiratory syncytial virus Rotavirus Varicella-zoster virus
Viral infections of the central nervous system Sudden death may occur due to direct infection of the nervous system or a complication of a viral infection such as toxoplasmosis in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Herpes simplex virus-1 encephalitis is usually due to reactivation of latent infection. Commonly affected sites include the temporal lobe(s) (medial before lateral), the inferior frontal lobe(s), and the Sylvian cortex(es). At autopsy there is widespread and asymmetrical necrosis. In fulminant cases there is prominent hemorrhage and swelling with raised intracranial pressure and brain herniation. Histological findings include perivascular cuffing by mononuclear cells (Figure 1) and, in a small number of cases, intranuclear inclusions may be seen in astrocytes and neurons. In adult HIV infections, sudden death from infective causes may be due to opportunistic infections (e.g., toxoplasmosis) or rupture of mycotic aneurysms. In viral central nervous system infections the brain may appear macroscopically normal, especially in very young, elderly, debilitated, and immunocompromised individuals. Specimens should be taken for microbiology and histology. Serum and cerebrospinal fluid (CSF) should be sent for antibody studies. Tissue for histological examination should be taken from normal, obviously abnormal, and transition areas. Routine sections should be taken from the cerebral cortex (all four lobes), thalamus, basal ganglia, hippocampus, brainstem, and cerebellum. As poliomyelitis has been described as a cause of sudden death in infants, autopsy protocols in sudden death should include histological examination of spinal cord and dorsal root ganglia.
Chlamydial Causes of Sudden Death
Chlamydia pneumoniae may be associated with myocarditis and sudden unexpected death.
Bacterial Causes of Sudden Death
Bacterial infections are responsible for sudden unexpected death in adults and children. In the pediatric population bacterial infections of the respiratory, gastrointestinal, and central nervous system account for the majority of cases of sudden death. Bacterial infections of the cardiovascular system Bacterial causes of myocarditis include Corynebacterium diphtheriae, Neisseria meningitidis, and Borrelia burgdorferi. In B. burgdorferi, cardiac involvement occurs in 18% of cases and death may occur as a result of conduction disturbances. In diphtheritic myocarditis myocardial damage is caused by the release of toxins. Bartonella-induced silent myocarditis has been described as a cause of sudden unexpected cardiac death in athletes. Granulomatous myocarditis may also lead to sudden death (Table 3). The mechanism of death includes arrhythmias, cardiac rupture, coronary occlusion, obstruction to pulmonary blood flow leading to fatal hemorrhage, and impaired myocardial contractility. Cardiac tuberculosis is usually an autopsy diagnosis. Histological examination of the myocardium shows a nodular, miliary, or diffuse infiltrative pattern. The coronary arteries may show narrowing or complete occlusion due to an intimal or diffuse tuberculous arteritis. It is uncommon to demonstrate acid-fast bacilli within the lesions. Molecular tests such as the ligase chain reaction (LCR) and polymerase chain reaction (PCR) may be used to demonstrate the organism.
Table 3 Differential diagnosis of granulomatous myocarditis
Disease Histological features
Giant-cell/ Fiedlers myocarditis Tuberculosis Sarcoidosis
Noncaseating granulomas with adjacent muscle necrosis giant cells Caseous necrosis with Langhans giant cells Noncaseating granulomas with myocardial fibrosis Schaumann and asteroid bodies Calcium oxalate crystals within giant cells Gummata with necrosis Sparse epithelioid cells Myocardial abscesses and endocarditis Tuberculoid granulomas Granulomas with or without necrosis Hyphae and yeasts
Syphilis Brucellosis Tularemia Fungi
Figure 1 Viral meningoencephalitis. Insert: perivascular cuffing by lymphocytes.
Sudden death in infective endocarditis occurs as a result of perforation of a free-wall myocardial abscess or rupture of a valve leaflet. Staphylococcus aureus is responsible for 1020% of cases and is the major cause in intravenous drug abusers. Other bacterial causes include Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella (HACEK group). Negative bacterial cultures may be found in
10% of cases as a result of prior antibiotic therapy. The most common sites of infection are the aortic and mitral valves, except in intravenous drug abusers, where the right-sided valves are primarily affected. Tertiary syphilis causing aortitis may cause sudden death from rupture of aortic aneurysms with aortic dissection. The mechanism of death is either blood loss with hypovolemic shock or a fatal cardiac tamponade from intrapericardial rupture. Bacterial infections of the respiratory system Sudden death from acute epiglottitis occurs from respiratory obstruction caused by swelling of the epiglottic folds, uvula, and vocal cords. The most common cause of acute epiglottitis in developing countries is Haemophilus influenzae type B. In countries with established immunization programs, the incidence of H. influenzae epiglottitis has decreased and other bacteria, such as streptococcus, staphylococcus, and pneumococcus, have been implicated as possible causes. Postmortem blood cultures are positive in 5075% of cases. Lobar pneumonia (Figure 2) and confluent bronchopneumonia are the most frequent cause of sudden death from acute pulmonary disease. Some 9095% of lobar pneumonia is due to Streptococcus pneumoniae type 3. Bronchopneumonia is caused by staphylococci, streptococci, H. influenzae, Pseudomonas aeruginosa, and coliform bacteria. Pulmonary tuberculosis may result in hemoptysis, which can cause hypovolemic shock and sudden death. Histologically, caseating granulomas are found. Acid-fast bacilli are demonstrated using the ZiehlNeelsen stain (Figure 3).
Figure 2 Lobar pneumonia. Left lung, showing consolidation of the lower lobe. Insert: alveolar spaces filled with acute inflammatory exudate.
Figure 3 Tuberculosis. Acid-fast bacilli demonstrated using a ZiehlNeelsen stain.
Corynebacterium diphtheriae produces a gray pseudomembrane from the pharynx to the larynx, and this may lead to respiratory obstruction and sudden death. Legionnaires disease is associated with outbreaks of sudden death. The disease is caused by Legionella pneumophila, a facultative intracellular organism. It causes severe pneumonia in the elderly, in smokers, and in immunocompromised patients. The organisms may be transmitted via droplet spread from contaminated air-conditioning units and water coolers. The organism may be demonstrated by a modified silver stain (Dieterle stain) or by immunofluorescence and culture. Bacterial infections of the central nervous system Pyogenic meningitis may cause sudden death. The causative organism varies according to the age of the patient (Table 4). The location of the exudates depends on the organism. In H. influenzae it is basally located. In pneumococcal meningitis it occurs over the convexities
of the brain in the parasagittal region (Figure 4). Microscopic examination reveals neutrophils filling the subarachnoid space with extension of the inflammation into the leptomeningeal veins in fulminant cases. Blood spread is the most common means of entry; however other routes of infection include local extension of infection, e.g., paranasal sinusitis, osteomyelitis, direct implantation, and via the peripheral nervous system. Diffuse bacterial meningitis may follow rupture of a brain abscess, which may lead to sudden death. The organisms may be demonstrated by microbiological culture of the CSF and examination of Gram stains of the CSF and brain tissue. Bacterial urogenital tract infections Fulminant acute bacterial pyelonephritis may lead to septicemia, causing sudden death. At autopsy, the kidneys show tubular necrosis with interstitial suppurative inflammation. Renal papillary necrosis may also be present. Bacterial infections of the gastrointestinal tract Severe bacterial enterocolitis may lead to sudden death, especially in the young. The pathogenesis of the diarrhea depends on the cause. Vibrio cholerae and Clostridium perfringens cause diarrhea by ingestion of a preformed toxin that is present in contaminated foods. Enteroinvasive organisms such as Salmonella, Shigella, and enteroinvasive Escherichia coli invade and destroy mucosal epithelial cells. Death occurs as a result of dehydration and electrolyte imbalance. Bleeding peptic ulcers that are caused by Helicobacter pylori may be the first indication of an ulcer and account for 25% of ulcer deaths, many of which are sudden and unexpected.
Table 4 Bacterial causes of acute meningitis according to age group

Age group Organisms Escherichia coli
Neonates
Streptococci Children Adults Elderly

Listeria monocytogenes Haemophilus influenzae Neisseria meningitidis Neisseria meningitidis Streptococcus pneumoniae Streptococcus pneumoniae Listeria monocytogenes
Figure 4 Bacterial meningitis. Exudate demonstrated over convexities and base of the brain.
Fulminant bacterial peritonitis secondary to acute appendicitis, acute salpingitis, ruptured peptic ulcer, diverticulitis, strangulated bowel, and cholecystitis may cause sudden death. Primary peritonitis may occur postsplenectomy and in patients with splenic hypoplasia. Patients with sickle-cell disease may have anatomical or functional asplenia. The former is due to repeated bouts of infarction leading to autosplenectomy. The latter is due to a defect in opsonization of encapsulated bacteria. Massive bilateral adrenal hemorrhage with adrenocortical insufficiency may occur as a result of septicemic shock from overwhelming bacterial infection (WaterhouseFriderichsen syndrome). The most common association is with Neisseria meningitidis septicemia; however, other virulent organisms, e.g., H. influenzae and Pseudomonas species, may also lead to this syndrome.
Fungal Causes of Sudden Death
cells. Small perivascular inflammatory foci called malarial or Du rcks granulomas may be present. Sudden death in malaria may also be due to rupture of an enlarged spleen. An enlarged spleen is fragile and more vulnerable to rupture. Other infections that may lead to splenic rupture and sudden death are infectious mononucleosis and typhoid. Sudden death due to cardiac involvement in Chagas disease (Trypanosoma cruzi) occurs in 510% of acute cases. The damage to the myocardium causes fatal ventricular tachycardia. Histological examination shows myofiber necrosis with an acute inflammatory reaction. Clusters of organisms may be found within dilated myofibers, resulting in intracellular pseudocysts.
Helminthic Causes of Sudden Death
Sudden death due to fungal infection may occur in an immunocompromised host such as in HIV/AIDS. Organisms include Cryptococcus (meningitis or disseminated disease) and Pneumocystis carinii (pneumonia). Intravenous drug abusers are susceptible to endocarditis due to fungi such as Candida. These patients are prone to fungal thromboembolism, leading to sudden death. Sudden death may also be due to a complication of fungal diseases such as fatal subarachnoid hemorrhage complicating actinomycotic meningitis or fatal hemoptysis complicating pulmonary mucormycosis. Diagnostic modalities include culture of the organism and the histological demonstration of the organisms in tissue. This may be facilitated by special stains such as the periodic acidSchiff (PAS) or Grocotts methenamine silver stain.
Protozoal Causes of Sudden Death
Clinically occult helminthic diseases such as hydatid disease (Echinococcus granulosus) and neurocysticercosis (Taenia solium) may cause sudden death. In neurocysticercosis death may occur due to epilepsy or raised intracranial pressure. Parasitic cysts containing scolices are present, especially in the subarachnoid space, cortical sulci, and cortical gray matter. Large multilocular cysts (racemose cysts) may be present in the basilar cisterns near the cerebellopontine angle (Figure 5). Isolated cardiac hydatid cyst is an uncommon manifestation and accounts for fewer than 3% of all hydatid disease. Sudden death may be the initial manifestation of the disease. Death may be due to involvement of the left ventricular myocardium or to massive pulmonary embolism.
Autopsy in Cases of Sudden Death due to Infectious Causes

All autopsies must be approached using universal precautionary principles. In sudden deaths complete autopsy examination is recommended with appropriate tissue and body fluid sampling for special investigations. Autopsy sampling for microbiological investigations is indicated in the following circumstances: sudden unexpected deaths in children and adults, deaths in immunocompromised patients, deaths in patients with clinically suspected infections, and deaths with organ changes of infection. The problems encountered with autopsy microbiological testing are contamination during procurement of the sample because of poor technique or due to the postmortem spread of commensals. To prevent false-positive postmortem blood cultures the following should be observed: the body should be refrigerated as soon as possible; and movement of
Fatal cardiac tamponade may occur with intrapericardial rupture of an amebic liver abscess due to Entamoeba histolytica. Fatal amebic meningoencephalitis may be caused by Naegleria fowleri. The organism enters the arachnoid space through the cribriform plate of the nose. There is meningeal hemorrhage with fibrinoid necrosis of blood vessels. Cerebral malaria does not usually cause sudden death. However, it may be the primary cause of sudden death in nonimmune persons. Susceptible individuals are tourists, business travelers, and sailors. At autopsy, the brain is swollen and may have a slate gray color due to the brown-black malarial pigment called hemozoin. Histology reveals petechial hemorrhages as well as intravascular parasitized red
Figure 5 Hydrocephalus with basal obliterative, granulomatous cysticercus meningitis. Courtesy of Professor RH Hewlett, University of Stellenbosch.
the body should be limited to decrease the possibility of postmortem bacterial spread. An aseptic technique should be used to collect the sample, which should be stored and transported in the correct medium and temperature. Close liaison with the microbiology and virology laboratories is important to guide collection, preservation, transport, and evaluation of specimens. This is particularly important in cases where there are positive cultures with negative histological findings. Sampling at multiple sites and determining the antibiotic sensitivities may be helpful in determining the significance of positive cultures. The finding of a pure as opposed to mixed culture helps to determine the significance of the findings. The type of organism in relation to the site where it was cultured also helps to differentiate contaminants from significant positive cultures. Relevant special techniques should be used by the pathologist in order to improve the diagnostic yield in infectious diseases (Table 5). In a small group of cases (so-called negative autopsies) no obvious cause of death is apparent after detailed initial external and internal examination. The incidence of negative autopsies is 5%10%; this figure improves to about 5% when special tests such as postmortem chemistry and microbiology are carried out.
Table 5 Special techniques used to demonstrate infectious agents

Organism Special technique Comment
Viruses
Chlamydia
Hematoxylin & eosin, antibody probes, culture and DNA probes Giemsa, culture
Bacteria
Fungi
Protozoans
Helminths
Gram stain, silver stain, acid-fast stain, culture, DNA probes Periodic acidSchiff, silver stain, Giemsa, culture Giemsa, periodic acidSchiff, DNA probes Modified acid-fast stain
Intranuclear and/or cytoplasmic inclusions, giant cells Necrotizing granulomas with stellate abscesses Polymerase chain reaction and ligase chain reaction for mycobacteria Mucicarmine for capsule of cryptococcus
In bilharzia, acid-fastness is concentrated in the spine of the egg
changes, investigation of appropriate autopsy samples by recently developed laboratory techniques may prove invaluable and shed light on the cause of death.
Conclusion
Infectious agents are not a common cause of sudden death. Even in cases with little or no morphological
See Also
Children: Sudden Natural Infant and Childhood Death; Sudden Natural Death: Cardiovascular; Central Nervous System and Miscellaneous Causes
236 SUICIDE/Etiology, Methods and Statistics
Further Reading
Adams JH, Graham DI (1988) An Introduction to Neuropathology, pp. 83117. Edinburgh, UK: Churchill Livingstone. Di Maio VJM, Dana SE (1998) Forensic Pathology, pp. 3563. Austin, TX: Landes. Lazarus NG, Dada MA (2001) Sudden unexpected deaths. In: Dada MA, McQuoid-Mason DJ (eds.) Introduction to
Medico-Legal Practice, pp. 365376. Durban, South Africa: Butterworths. Samuelson J (2003) General pathology of infectious diseases. In: Kumar V, Cotran RS, Robbins SL (eds.) Basic Pathology, 7th edn., pp. 307322. Philadelphia, PA: Saunders. Winn WC Jr. (2000) Demonstration of infectious agents in tissue. Current Diagnostic Pathology 6: 8492.
SUICIDE
Contents Etiology, Methods and Statistics Parasuicide Youth Suicide
Etiology, Methods and Statistics

B Marc, Compiegne Hospital, Compiegne, France
Introduction
In the year 2000 an estimated 815 000 people died from suicide around the world. This represents an annual global mortality rate of 14.5 per 100 000 population. According to the World Health Organization (WHO), suicide is the 13th leading cause of death worldwide. It leads among violent causes of death (e.g., suicide, homicide, traffic deaths). Among those aged between 15 and 44 years, suicide is the fourth leading cause of death, and violence against the self is the sixth leading cause of disability. Suicidal behavior ranges in degree from merely thinking about ending ones life, through developing a plan to commit suicide and obtaining the means to do so, attempting to kill oneself, to finally carrying out the act of completed suicide. The term suicide is based on the Latin words sui (of oneself) and caedere (to kill). The Encyclopaedia Britannica defines suicide as: the human act of self-inflicting ones own life cessation. However, it is often difficult to reconstruct the thoughts of people who commit suicide unless they have made clear statements before their death since all suicidal deaths are not clearly planned. In many legal systems, a death is certified
as suicide if murder, accidental death, and natural causes can all be ruled out and if the circumstances are consistent with suicide. This article deals with fatal suicidal behavior. This is the term proposed for suicidal acts that result in death and that directly concern forensic medicine; it does not cover nonfatal suicidal behavior, attempted suicide, or deliberate self-harm, i.e., suicidal actions that do not result in death and which may be referred to psychiatrists. Even if it is not always clearly planned, suicide is a result of an act deliberately initiated and performed by a person in expectation of its fatal outcome. Suicide is also now a major public health problem, as evidenced by epidemiologic data. According to WHO, taken as an average for 53 countries for which complete data are available, the age-standardized suicide rate for 2000 was 14.5 per 100 000. The rate for males was 22.9 per 100 000 and for females 6.8 per 100 000. The rate of suicide is almost universally higher among men compared to women by an aggregate ratio of 3.5 to 1. For some countries the most recent data are shown in Table 1. Over nearly 30 years (19701996), for 39 countries for which complete data are available, the suicide rates seem to have remained quite stable. Geographically, changes in suicide rates vary considerably. According to the French National Institute on Demographic Studies (INED; Institut National des Etudes De mographiques), which provides reliable information on suicide mortality, the rates range from 40.1 per 100 000 in the Russian Federation to 31.6 per 100 000 in Hungary, 25.1 per 100 000 in Japan,
SUICIDE/Etiology, Methods and Statistics 237

Table 1 Suicide rates (per 100 000) in various countries
Country Year (1998 and over) Males Females
Australia Austria Belarus Bulgaria Canada China (selected rural and urban areas) Croatia Czech Republic Denmark Estonia Finland France Georgia Germany Greece Hungary India Ireland Italy Japan Latvia Lithuania Luxembourg Malta Mauritius The Netherlands New Zealand Norway Poland Portugal Republic of Korea Romania Russian Federation Singapore Slovakia Slovenia Spain Sweden Switzerland Ukraine United Kingdom United States of America
01 02 01 02 00 99 02 01 99 02 02 99 00 01 99 02 98 00 00 00 02 02 02 02 00 00 00 01 01 00 01 02 02 01 01 02 00 01 00 00 99 00
20.1 30.5 60.3 25.6 18.4 13.0 30.2 26.0 21.4 47.7 32.3 26.1 4.8 20.4 5.7 45.5 12.2 20.3 10.9 35.2 48.4 80.7 28.6 5.6 18.8 12.7 19.8 18.4 26.7 8.5 20.3 23.9 69.3 11.5 22.2 44.4 13.1 18.9 27.8 52.1 11.8 17.1
5.3 18.7 9.3 8.3 5.2 14.8 10.0 6.3 7.4 9.8 10.2 9.4 1.2 7.0 1.6 12.2 9.1 4.3 3.5 13.4 11.8 13.1 10.2 4.0 5.2 6.2 4.2 6.0 4.3 2.0 8.6 4.7 11.9 6.9 4.0 10.5 4.0 8.1 10.8 10.0 3.3 4.0
17.5 per 100 000 in France, 11.3 per 100 000 in the USA, and 8.2 per 100 000 in Italy. Socioeconomic reasons are often suggested as a factor contributing to an increase in suicide rates. A flat evolution of suicide rates may hide an increase in mens rates statistically compensated for by a decrease in womens rates (as occurred, for example, in Australia, Chile, Cuba, Japan, and Spain); the same would apply to extreme age groups, such as adolescents and the elderly (e.g., in New Zealand). It has been shown that an increase in unemployment rates is usually, but not always, accompanied by a decrease in suicide rates of the general population (e.g., in Finland), but by an increase in suicide rates
of elderly and retired people (e.g., in Switzerland). Other factors such as alcohol consumption (e.g., in the Baltic States and the Russian Federation) and easy access to some toxic substances (e.g., in China, India, and Sri Lanka) and to firearms (e.g., in the USA) seem to be positively correlated with suicide rates across countries included in the study, whether industrialized or developing. Suicide is a leading cause of death among young adults. It is the first or second leading cause of death for both sexes in the population aged between 15 and 34 years. The curve is almost flat in the 4070year age group, and reaches a peak in the oldest population.
The precise explanation for variations in suicide rates must always be considered in a local context. There is a pressing need for epidemiological surveillance and appropriate local research to contribute to a better understanding of this major public health problem and improve the possibilities of prevention.
Etiology of Suicide
A variety of factors determine the prevalence, onset, and course of mental and behavioral disorders that may lead to the suicide. These include social and economic factors, demographic factors such as sex and age, serious threats such as conflicts, the presence of major physical diseases, and the family environment, which may have an impact on mental health and lead to suicide attempts.
Social and Economic Factors
disorders. Among the reasons for the sex differences in common mental disorders is the high rate of domestic and sexual violence to which women are exposed. Among women, suicide can be a consequence of intimate-partner violence. In contrast, almost all the studies show that substance-use disorders and antisocial personality disorders are much more common among men than among women.
Age
Poverty and unemployment, low educational level, deprivation and homelessness are not only widespread in poor countries, but also affect a large minority of rich countries. In the USA, children from the poorest families were found to be at increased risk of disorders in the ratio of 2:1 for behavioral disorders, including suicidal behavior, with respect to children from the general population. Similar results have been reported by the WHO International Consortium of Psychiatric Epidemiology from recent studies carried out in North America, Latin America, and Europe. The course of disorders is determined by the socioeconomic status of the individual, because either resources for mental health care are often unavailable to the poorer segments of society, or lack of insurance coverage, lower levels of education, unemployment, and racial, ethnic, and language minority status create insurmountable barriers to care. Moreover, behavioral disorders may be added to those related to alcohol use, and the vicious cycle of poverty and mental disorders at the family level may lead to suicide.
Psychological Factors
Age is an important determinant of mental disorders. A high prevalence of disorders is seen in the elderly. Besides Alzheimers disease, the prevalence of some mental and behavioral disorders tends to rise with age. Depressive disorder is common among elderly people: recent studies on community samples of people over 65 years of age found depression among 1125% of this population (Figure 1). Depression is more common among older people with physical disabilities. Depressive disorders among the elderly go undetected even more often than among younger adults because they are often considered as a part of the aging process suicide often leads to a retrospective diagnosis of depression of the elderly.
Posttraumatic Stress Disorder
Posttraumatic stress disorder (PTSD), often along with depressive or anxiety disorders, arises after a
In developed (and also developing) countries, anxiety and depressive disorders are more common among women, while substance-use disorders and antisocial personality disorders are more common among men. Sex differences in rates of depression seem to be strongly age-related; the greatest differences occur in adult life, with no reported differences in childhood and few occurrences among the elderly. Psychological and social factors are, however, also significant for the gender difference in depressive and anxiety
Figure 1 Suicide by hanging of an old woman.
Figure 2 Suicide by hanging of a terminally ill man (cancer).
stressful event of an exceptionally threatening nature and is characterized by intrusive memories, avoidance of circumstances associated with the stressor, sleep disturbances, irritability and anger, lack of concentration, and excessive vigilance. The point prevalence of PTSD in the general population is 0.37%. The specific diagnosis of PTSD has been questioned as being culture-specific but, even if the suitability of this specific diagnosis is uncertain, the overall significance of mental morbidity among individuals exposed to severe trauma is generally accepted. Victims of violence and victims of natural disasters have shown a high rate of mental disorders that might encourage suicide.
Major Physical Diseases
Figure 3 Suicide by hanging (complete) of a middle-aged man having lost his job, at his workplace.
The presence of major physical diseases affects the mental health of individuals. Most of the seriously disabling or life-threatening diseases, including cancer, acquired immunodeficiency syndrome (AIDS), or spinal cord injury in both men and women have this impact. Patients with organic disease who make serious attempts to commit suicide are characterized by high psychiatric morbidity, with a predominance in the diagnosis of severe depression (Figure 2). Hopelessness is thought to be more closely correlated with suicidal ideation than with the level of depression. For this reason, suicide ideation concerns more patients with terminal illness as well as the elderly patients. A physical condition in these complex situations can lead to psychosocial consequences at individual and family levels and may determine their full impact on mental health and on suicidal behaviors.
Life and Social Factors
that there is an accumulation of life events immediately before onset of mental disorders and suicide attempts (Figure 3). Studies suggest that all significant events in life act as stressors and, added to several interacting factors (such as genetic predisposition and personality), predispose the individual to mental disorders and to a number of physical diseases, e.g., myocardial infarction. Individuals at a higher risk because of experiencing major life events in quick succession (e.g., loss of job, loss of spouse, and change of residence) have a higher risk of onset of mental disorders. Notable among these is suicide (Figure 4).
Suicide Rates
Geographically, changes in suicide rates vary considerably. According to more recent data, suicide rates range from 3.4 per 100 000 in Mexico to 14.0 per 100 000 in China and 34.0 per 100 000 in the Russian Federation. Chosen data on suicide rates (per 100 000), by country, year, and gender, obtained from the most recent year available as of June 2004, are shown in Table 1. Very high rates of suicide are observed in Europe in former Soviet Bloc countries that recently entered into the European Union, such as Hungary, Latvia, and Lithuania, as well as the Russian Federation and Ukraine. Existential factors may play a leading role in
Mental disorders and suicide behaviors are rooted in the individuals social environment. People go through a series of significant undesirable events in life such as bereavement or business failure. It has been observed
100 000 for the same dates. These changes in suicide rates may hide an increase in mens rates that is statistically compensated for by a decrease in womens rates; the same would apply to extreme age groups, such as adolescents and the elderly and retired people.
Methods of Suicide
Methods of suicide do not differ greatly from one country to another. Violent suicides (hanging, use of a firearm) seem to be slightly more frequent in males than in females. Women attempting suicide often jump from a height or throw themselves in front of a train. For example, according to the US Centers of Disease Control, the US suicide rate has followed the following pattern (19791994): 7 deaths per 100 000 persons per year by means of guns; more than 1.5 by means of asphyxia (hanging or suffocation in a plastic bag in rare cases); 1.2 by means of drugs; 0.18 by means of cuts and stabs; 0.15 by means of drowning; 0.3 by means of jumping from a height. In countries where guns are restricted, statistics obviously differ. In the Russian Federation, as well as in other neighboring countries of Central and Eastern Europe, alcohol consumption has increased precipitously in recent years, and has been linked to an increase in rates of suicide and alcohol poisoning. Deliberate self-poisoning with nonopiate analgesics, especially acetaminophen (paracetamol), is common in the UK, resulting in a substantial number of deaths each year. After legislation restricting pack sizes of acetaminophen and salicylates was introduced in the UK, a substantial decrease in mortality associated with self-poisoning using these drugs was observed (Figure 5). Moreover, the prescription of psychotropic medicines is higher among women. These drugs include antianxiety, antidepressant, sedative, hypnotic, and antipsychotic drugs. The higher use of drugs is also linked to a greater use of these drugs in womens suicide. The ingestion of toxic substances, such as pesticides, herbicides, or medication, is the preferred method for committing suicide in rural areas and in developing countries. For example, in Western Samoa in 1982, the ingestion of paraquat, a widespread herbicide, had become the predominant method of suicide. It is well known that availability of means to commit suicide has a major impact on actual suicides in any region. It has been clearly established that firearm availability is linked to high mortality by suicide among individuals who had bought firearms in the recent past. A clear example is given by the fact that, among individuals who died from firearm
Figure 4 Suicide by hanging shortly after a divorce: pictures of family and children are tied to the body.
explaining the phenomenon, as well as cultural factors in countries having lost free religious practice during their communist rule. At worst, depression can lead to suicide, a tragic fatality associated with the loss of about 850 000 lives every year. Depression was the fourth leading cause of disability in the year 2000. Today, depression is already the second leading contributor to the global burden of overall disease in the 1544-year age group for both sexes combined. Depression can be reliably diagnosed and treated in primary care. Antidepressant medications and brief, structured forms of psychotherapy are effective for 6080% of those affected. Fewer than 25% of those affected have access to effective treatments. Barriers to effective care include the lack of resources, lack of trained providers, and the social stigma associated with mental disorders including depression. This may explain the discrepancies in suicide rates observed between the developing and the developed countries. The evolution of suicide rates has been rather flat in the 19602000 period. Rates have decreased in Germany from 20.9 per 100 000 in 1960 to 14.2 per 100 000 in 2000, and in Sweden from 17.4 per 100 000 to 14.2 per 100 000 for the same dates. Rates have slightly increased in France from 15.9 per 100 000 in 1960 to 17.5 per 100 000 in 2000, in Japan from 21.6 per 100 000 to 25.1 per 100 000, and in the USA from 10.6 per 100 000 to 11.3 per
Figure 5 Anticoagulant injections administered after a massive ingestion of acetaminophen (paracetamol) in a man with a liver disease.
Figure 7 Suicide by shotgun: entrance wound in the mouth and facial major lesions.
Figure 6 Suicide by shotgun: entrance wound in the chest.
injuries in the USA in 1997, a total of 54% died by suicide (Figures 68). Several studies have shown an association between the possession of handguns at home and suicide rates. Legislation restricting access to handguns has already shown a beneficial effect in the USA, where the restriction of the selling and purchasing of handguns was associated with lower firearm-related suicide rates. Currently, the most frequent method for suicide remains hanging, mainly used in older people attempting suicide. This method can be considered among violent suicidal methods, such as drowning, jumping from a height, throwing oneself in front of a train or self-stabbing (Figure 9). Very simple methods can
Figure 8 Suicide by plastic bullet still in the entrance wound: death by intracranial hemorrhage and temporal skull fractures.
have fatal effects, and there is no doubt that those wanting to kill themselves can imagine and find useful means of attempting suicide. Another example is suicide linked to the confinement of vulnerable
Figure 9 Self-stabbing of the throat in an elderly woman.
groups (thus, exposed to the increased risk of suicide), e.g., prisoners and detainees.
Suicide, Murder, or Accident?

Whether the death is accidental, suicidal, or homicidal is one of the main questions asked of the forensic physician at the death scene. Some criteria may help to distinguish between these three types of death. By order of frequency, differential diagnosis of suicide by firearms, hanging, poisoning, and self-stabbing are detailed in the following. Suicidal deaths due to guns are characterized by a distance of the discharge beyond arms length. If a pistol can be held easily by the victim to shoot him/ herself in the head, mouth, neck, and front of the chest, measurements must be made on a longbarreled weapon to see if the length of the arm could physically reach the trigger. Of course, if no weapon is present at the scene of death, then suicide is almost exc1uded, unless someone else removed the gun. Moreover, suicide attempters always try to reach vital sites on their body to kill themselves with guns. These include the temples, the mouth, and thorax over the heart. Right-handed people shoot themselves more frequently in the right temple, but there are many exceptions. Laboratory atomic testing of hands to seek propellant residues indicating that a gun was held by the deceased is of great interest. Moreover, a gunshot is not always instantly fatal and the suicide attempter can fire more than once in rather quick succession, especially when the weapon used is of a small caliber (22 LR). Suicidal use of weapons is much more frequent in men, especially if they own guns or if they are familiar with their use (policemen, soldiers, hunters). Automatic weapons are not frequently used in suicidal deaths, but they may also cause more than one entrance wound, since more than one bullet can be automatically fired at once. Where gunshot wounds
are inflicted on an inaccessible part of the body, or in a part where the shot is not sure to be lethal, accident or murder can be highly suspected. Asphyxial deaths can pose considerable difficulties for the forensic physician and investigator to distinguish between accident, suicide, or homicide. Hanging is almost always suicidal. Although it is more common in men, it is not unusual in women. Homicidal hanging of an adult is very rare and, unless the victim is drugged or drunk, cannot be accomplished in a resisting conscious adult without restraint. Homicidal hanging has been reported in dyadic suicide, where, for example, a father kills his own children before hanging himself. Typical hanging lesions consist of an oblique ligature mark to the place where the knot is situated, reaching the jaw angles, generally leaving a gap of the skin mark where the rope leaves the body surface to tend to the knot. Sexual hangings (masochism, sexual games) can accidentally lead to suffocation hanging, especially if the hanged person is alone or if his frightened partner leaves the scene as quickly as possible. Strangulation is usually homicidal, but self-strangulation by ligature is not uncommon and the victims are able to tighten several turns of rope around their neck, even using a tourniquet system. In such cases, a psychiatric background is not rare in adults. In ligature strangulation, whether murder or suicide, the mark is a generally horizontal course (complete), which may not reach the angles of the jaw. Small children may be accidentally hanged by curtain cords or restraint harnesses, but suffocation is much more frequent. Accidental suffocation is caused by obstruction by a small object swallowed or mechanical suffocation (pillows, cushions, and plastic bags) in young children able to move. Homicidal suffocation in babies and very young children can be observed in the context of childrens mistreatment or in single-parent families with a very young or psychiatrically ill mother. Autopsy brings many elements for differential diagnosis, which can also reveal a sudden-death syndrome of the very young child. Suicidal stabbings are often observed in people who pull aside the clothing first, a feature which is evidence of the motive. Many suicidal stabbings take place in bathrooms. Obviously, the death scene is often prepared and in order. Suicidal stab wounds take place on wrists and arms or on the inner surface of the throat, sometimes on a vascular access (hemodialysis). Stab wounds in suicide are repeated, usually parallel, and close together. Tentative or trial incisions are next to the deeper ones, reaching a major vessel or larynx. Abdominal suicidal stab wounds (hara-kiri) are not usual in occidental countries. In contrast, homicidal stab wounds have no particular
character, they are often associated with a violent crime scene, and only close together when the victim has been injured by many knife wounds before finally dying under the killers knife. Drowning poses the same questions: accident, death, or murder? Knowledge of circumstances is very useful. Accidental drownings may have been seen by witnesses, even if the body is retrieved after only a few days in quiet or sea water. Alcohol-related accidental drowning is not infrequent, as is hydrocution with thermic shock in cold water after a long stay under the summer heat. In adults, drownings in bathrooms may be accidental (cardiac or neurologic illness) or suicidal, usually associated with toxic ingestion (tranquillizers or alcohol). Drowning of young children remains suspect until the autopsy is performed (homicide? neglect?). In suicidal attempts by drowning, the suicidal attempter often leaves behind a letter or a phone call before departing to jump into the water. Examination of a cadaver after drowning is never simple and autopsy must carefully search for suspect lesions and wounds that may occur in homicidal drownings. Moreover, a dead body can be thrown into the water. Autopsy will find both the absence of submersion syndrome and causes of death. Poisoning assessed by blood and urine samples analyzed with reference methods (gas chromatography with mass spectrometry) cannot explain if toxic substances were accidentally or voluntarily consumed. Circumstances will give important elements to determine the suicidal use. In very young children and disabled persons, the spectrum of homicidal poisoning is present. Although poisoning, especially with heavy metals, was widely used in the past as a homicidal means, it seems to be less and less frequent in western countries, following progresses in drug detection.
Conclusion
Currently, suicide is the most severe complication of major depressive disorders in both developed and developing countries. Major depressive disorders account for 2035% of all deaths by suicide. From the forensic experience, it is known that a completed suicide is more common among those with more severe and/or psychotic symptoms, with late-onset, coexisting mental and addictive disorders, as well as among those who have experienced stressful life events, who have medical illnesses, and/or who have a family history of suicidal behavior. In industrially developed countries, men complete suicide three to four times as often as women, but women attempt suicide four times as frequently as do men. Suicide is not only a topic for forensic medicine but it also represents a serious public health problem.
The rate of suicide per 100 000 is higher than the rate of homicide: 10 times higher in the UK, 15 times higher in Germany, 25 times higher in France, and 30 times higher in Japan, countries where homicide rates are low or very low. The suicide rate is almost double the homicide rate in the USA (11.3), where the homicide rate is rather high (6.2). Knowledge of suicide is necessary for forensic physicians and scientists, as well as psychiatrists. The suicide rate in adolescents and young adults has almost tripled since the early 1950s in most developed countries, but older persons (65 years and above) have the highest suicide rates of any age group. The suicide rate for individuals aged 85 and older is the highest, and trends from 1980 to 1992 reveal that suicide rates are increasing among more cohorts of older persons. Thus, forensic practice will experience these problems more frequently. Accurate guidelines to differentiate suicide from murder, accidental death, and natural death must be kept in mind. Suicide cannot be established without arguing that the circumstances are consistent with suicide (Figure 10), whatever the type and method of suicide. Specific illnesses, such as AIDS, cancers of the brain and nervous system, and multiple sclerosis, are associated with an increased risk of suicide in the medically ill. When medical illness becomes terminal, difficult end-of-life decisions may be encountered. The suicide problem is, therefore, also linked to the ethics of end-of-life decision-making, and the terminally ill patients right to refuse life-sustaining treatments or to have death hastened. Euthanasia, physician-assisted suicide, and other end-of-life decisions have greatly contributed to the debate about the role of such practices in modern healthcare. In the Netherlands, the continuing debate about whether and when physician-assisted dying is acceptable seems to be resulting in a gradual stabilization of
Figure 10 Letters and photographs left as suicide testimony.
244 SUICIDE/Parasuicide
end-of-life practices. Since 1995, the demand for physician-assisted death has not risen among patients (0.3% of all deaths in the Netherlands), and physicians seem to have become somewhat more reluctant in their attitude towards this practice. Even if assisted suicides are not so frequent, 57% of all medical doctors in the Netherlands have performed euthanasia or physician-assisted suicide since the law was implemented. How this phenomenon can be considered according to the ethical code of medical doctors is a major ethical debate, now widely discussed in many developed countries.
Marzuk PM, Leon AC, Tardiff K, et al. (1992) The effect of access to lethal methods of injury on suicide rates. Archives of General Psychiatry 49: 451458. Onwuteaka-Philipsen BD, Van der Heide A, Koper D, et al. (2001) Euthanasia and other end-of-life decisions in the Netherlands in 1990, 1995, and 2001. Lancet 362: 395399. Sainsbury P (1986) The epidemiology of suicide. In: Roy A (ed.) Suicide, pp. 1740. Baltimore, MD: Williams and Wilkins. Shah A, Hoxey K, Mayadunne V (2000) Suicidal ideation in acutely medically ill elderly inpatients: prevalence, correlates and longitudinal stability. International Journal of Geriatric Psychiatry 15: 162169.
See Also
Autoerotic Death; Deliberate Self-Harm, Patterns; Forensic Psychiatry and Forensic Psychology: Suicide Predictors and Statistics; MurderSuicide; Suicide: Parasuicide; Youth Suicide
Parasuicide
R Nathan, Merseyside Forensic Psychiatry Service, St Helens, UK K J B Rix, Leeds Mental Health Teaching Trust, Leeds, UK
Further Reading
Charlton J, Kelly S, Dunnell K, Evans B, Jenkins R (1993) Suicide deaths in England and Wales: trends in factors associated with suicide deaths. Popuation Trends 71: 3442. Chesnais J-C (2003) Les morts violentes dans le monde. [Violent deaths in the world.] Population et Socie te s 395: 14. De Leo D, Scocco P, Marietta P, et al. (1999) Physical illness and parasuicide: evidence from the European Parasuicide Study Interview Schedule (EPSIS/WHO-EURO). International Journal of Psychiatry and Medicine 29: 149163. DeVivo MJ, Black KJ, Richards JS, Stover SL (1991) Suicide following spinal cord injury. Paraplegia 29: 620627. Hawton K (2000) Gender differences in suicidal behaviour. British Journal of Psychiatry 177: 546550. Hepple J, Quinton C (1997) One hundred cases of attempted suicide in the elderly. British Journal of Psychiatry 171: 4246. Kleespies PM, Hughes DH, Gallacher FP (2000) Suicide in the medically and terminally ill: psychological and ethical considerations. Journal of Clinical Psychology 56: 11531171. Knight B (1991) Murder, suicide or accident? In: Arnold E (ed.) Simpsons Forensic Medicine, 10th edn., pp. 117 127. London. Kreitman N, Carstairs V, Duffy J (1991) Association of age and social class with suicide among men in Great Britain. Journal of Epidemiology and Community Health 45: 195202. Lewis G (1998) Suicide, deprivation, and unemployment: record linkage study. British Medical Journal 317: 12831286. Marc B, Baudry F, Zerrouki L, Ghaiath A, Garnier M (2000) Suicidal incised wound of a fistula for hemodialysis access in an elderly woman. American Journal of Forensic Medicine and Pathology 21: 270272.
Introduction
The term parasuicide embraces an enormous variety of behaviors. Between 1 and 5% of respondents to community surveys in the USA and Europe have deliberately harmed themselves, although higher rates have been reported. The problem of parasuicide is especially pressing in forensic populations. Rates among offenders are significantly elevated and the management of parasuicide in forensic settings poses particular difficulties. Furthermore, courts may be more likely to seek the evidence of an expert witness when the proceedings relate to an individual with a history of parasuicide.
Definition
The clinical judgment as to whether an event such as a deliberate overdose or self-laceration represents parasuicide is usually straightforward. However, given the different types of actions and intentions, a single descriptive term that can be applied universally has proved elusive. Attempted suicide suggests suicidal intent, which cannot be assumed. Suicidal behavior covers suicide and attempted suicide, but is often used more broadly to describe all fatal and nonfatal deliberate self-harm. Although deliberate self-harm does not refer to suicidal intent, it implies harm, which is not a necessary condition. A deliberate overdose should not be excluded from consideration because either the individual unwittingly took too low a dose
SUICIDE/Parasuicide 245
to cause harm, or medical intervention prevented harm. Parasuicide has the advantage of not being bound to a specific intention or outcome. However it may encourage the view that suicide and parasuicide are alike in all respects apart from the outcome. Although it is no longer accepted that there is a clear distinction between suicide and parasuicide, there are important differences in the age and gender distributions between these two groups. In this article no distinction is made between the terms parasuicide and deliberate self-harm. While a standardized definition is essential for research, in order to account for the enormous variations of actions and intentions, such definitions are cumbersome. The World Health Organization/European Study on Parasuicide referred to an act with nonfatal outcome, in which an individual deliberately initiates a nonhabitual behavior that, without intervention from others, will cause self-harm, or deliberately ingests a substance in excess of the prescribed or generally recognized therapeutic dosage, and which is aimed at realizing changes which the subject desired via the actual or expected physical consequences. Other terms refer to specific forms of parasuicide such as self-poisoning and self-laceration (albeit that a laceration is a full-thickness skin wound caused by blunt force and, as the term is meant to apply to wounds caused by sharp cutting instruments, the term ought to be self-cutting). Self-injury is sometimes used to describe acts of deliberate selfharm other than poisoning. This term is commonly used for learning-disabled people where the deliberate self-harm is classified under the heading challenging behavior. Self-mutilation is often used to refer to the behavior of personality-disordered individuals who engage in frequent repeated self-injury in an attempt to relieve tension. However self-mutilation is sometimes restricted to self-injury driven by psychotic symptoms. The behavior may be bizarre and extreme, for example, eye enucleation or penis amputation.
in the USA are more representative of the general population, but less detail is available. Parasuicide can take many forms, but in the west over three-quarters of cases involve drug poisoning, usually with analgesic or psychotropic medication. Self-laceration is generally the next most common method, although the order varies between countries. For instance, in Hungary the use of pesticides and other agricultural chemicals is about three times as common as cutting. The use of agricultural chemicals is also prevalent in Asia. Self-poisoning with alcohol is found more commonly in Scandinavian countries. Geographical variation in part reflects differences in the availability of methods. Other methods include poisoning with other substances, burning, hanging, gas inhalation, drowning, stabbing, shooting, jumping from a height, and throwing oneself in front of a moving object. In a significant minority of cases a combination of methods is used. Some methods are associated with particular groups. Thus patients with emotionally unstable personality disorder sometimes insert objects into their body. Learning-disabled people are more likely to resort to head-banging or biting. Rates of parasuicide are highest among women in their teens to early 20s and men in their mid-20s to early 30s. In general, rates are higher among women than men, although again there are geographical variations. Within Europe, for example, the rate of parasuicide by men has been increasing in the UK and the gender difference has reversed in Finland. Although in any one country the overall order of methods of deliberate self-harm is similar between the sexes, there are important differences in the frequencies. Women are more likely than men to take overdoses, and men are more likely to use cutting, solvents, pesticides, hanging, jumping, and throwing oneself in front of a moving object.
Framework of Assessment
The following description provides a framework on which to base the assessment of parasuicide. In order to make sense of an act of parasuicide in a way that can be communicated clearly to others, it is usually necessary to consider a number of variables separately. First, one can consider the immediate factors that have a relatively direct causal link to the act of parasuicide. Thus the impulse to harm oneself arises in a particular state of mind, which is often evoked by identifiable proximal triggers. Particular attention should be paid to motive. Second, the broader emotional and environmental context should be assessed. There is often background emotional disturbance, which sometimes represents a mental disorder. Certain personality variables are associated with
Epidemiology
When taking an international perspective on parasuicide, direct comparisons between countries are difficult due to the use of different nomenclature and different interpretations of the same terms. Multicenter research using standardized assessments allows meaningful comparisons. The World Health Organization/European Study on Parasuicide produces detailed data relating to episodes of parasuicide that have come to the attention of medical staff in 16 centers across Europe. Results from population surveys such as the National Comorbidity Study
parasuicide and there are commonly salient social factors. Early life experiences may be relevant. Third, an account should be produced that acknowledges the continuous interplay between these factors, which in reality are changing over time.
Immediate Factors
the individual may isolate him/herself, choose a time and a place which reduce the chance of discovery, and not seek help after the act. Writing a note, planning the act, and making arrangements in anticipation of death, such as preparing a will, also point to high suicidal intent. There is evidence that greater suicidal intent is likely to accompany parasuicide by men.
The Broader Context
The emotional disturbance at the time of deliberate self-harm can be characterized by type and degree. Parasuicide does not have a particular association with any one state of mind, but emotions commonly reported correspond to sadness, despair, hopelessness, anger, frustration, shame, low self-esteem, humiliation, and powerlessness. There is often a pattern of increasing emotional arousal, reaching its peak at the point of self-harm. The possible triggers are countless and in any one case can be multiple. However, there is frequently evidence of interpersonal conflict such as an argument or separation. Other potential triggers include loss, especially through bereavement, and financial, social, and legal problems. By detailing the individuals internal and external experiences it is possible to gain some understanding of the behavior. However, it is more difficult to determine definitively what the subject hoped to achieve. The individual is usually very emotionally aroused and in up to half of cases alcohol has been consumed in the hours before the act. Although motives may be multiple, confused, and changing, certain common themes emerge from accounts of deliberate self-harm. The act of parasuicide is often a desperate attempt to communicate disturbed emotions by an individual who is unable to express him/herself adaptively in that instance or more generally. The display of emotions in this way may also be motivated by an urge to relieve distress or terminate an unpleasant experience. In some more emotionally disturbed individuals, the resulting shortterm relief encourages a pattern of repeated deliberate self-harm, often by self-laceration. A sense of being unable to escape from an unbearable situation, whether emotional or environmental, has been described as entrapment. The experience of entrapment may contribute to a sense of hopelessness, a cognitive variable associated with parasuicide. Of course, death may have been the intended outcome. Although there is sometimes clear evidence that the individual was driven by a strong impulse to end life, it would be a mistake to consider suicidal intent as either present or absent. In reality suicidal intent varies by degree and persistence and can coexist with other motives. The presence of high suicidal intent is supported by evidence of steps taken to avoid discovery and extensive premeditation. To avoid discovery
As well as determining the more immediate factors, it is important to assess the broader emotional and environmental circumstances. There is usually a history of emotional disturbance, which predates the act of parasuicide. This may have been manifest in previous parasuicide. The emotional disturbance often amounts to a mental disorder according to diagnostic conventions. These disorders can be broadly divided into mental illness, personality disorder, substance misuse, and learning disability. Clinical depression is the commonest mental illness among individuals who have deliberately harmed themselves. This is not surprising given some of the core symptoms of this illness, notably persistent low mood, reduced self-regard, and hopelessness. Parasuicide may accompany psychotic symptoms, especially self-destructive auditory hallucinations and persecutory or nihilistic delusions in schizophrenia or psychotic depression. Anxiety disorder, panic disorder, posttraumatic stress disorder, obsessive-compulsive disorder, eating disorders, and phobic disorder have also been associated with this behavior. An adjustment disorder, which is a temporary emotional disturbance in response to stressful circumstances, is also commonly diagnosed, but in practice it is not always easy to distinguish clearly this condition from milder forms of depression. Parasuicide patients commonly have a history of alcohol abuse. Rates of drug abuse are also elevated, but not to the same degree. The presence of substance abuse increases the risk of both repeated parasuicide and eventual suicide. Rates of parasuicide are significantly increased among individuals with personality disorder. Moreover personality disorder is commonly diagnosed among individuals who have deliberately harmed themselves. Although this behavior is not confined to any one personality disorder diagnosis, self-harming preoccupations and actions have diagnostic significance in borderline personality disorder. The World Health Organization diagnostic criteria for the borderline variant of emotionally unstable personality disorder refer to suicidal threats or acts of self-harm. The equivalent diagnosis in the American Psychiatric Association classification, borderline personality
disorder, includes the criteria of recurrent suicidal behavior, gestures, or threats, or self-mutilating behavior. This disorder is also characterized by impulsiveness, affective instability, and significant interpersonal dysfunction. Although there are fewer relevant studies concerning other personality disorders, parasuicide has been found to be associated with anxious/ avoidant, dependent, paranoid, dissocial/antisocial, and obsessive-compulsive personality disorders. While parasuicide is more common among people with learning disability, rates vary depending on the sample surveyed. Ten to 20 percent of those in institutions and up to 10% of community samples display self-injurious behavior. A consistent finding across these surveys is the association between deliberate self-harm and the degree of intellectual impairment. Some 8090% of those who deliberately harm themselves have profound or severe learning disability, that is, an IQ less than 35. In common with other groups, deliberate self-harm by an individual with learning disability serves as a means of emotional expression and communication. However, specific genetic syndromes are associated with deliberate self-harm. Patients with LeschNyan syndrome, an X-linked recessive disorder, have severe learning disability and self-injure by biting their lips and fingers and hitting themselves. Repeated skin picking occurs in PraderWilli syndrome, which is caused by a chromosomal abnormality. In people with severe learning disability there is a strong association between deliberate self-harm and violence. It is clear that parasuicide is found in many different mental disorders. Certain cognitive and emotional variables, which can be considered independently of psychiatric diagnoses, have been implicated in the etiology of parasuicide. Parasuicide is associated with particular styles of thinking and feeling such as impulsiveness and hopelessness. Problem-solving difficulties have also been examined. Patients with a history of parasuicide tend both to generate fewer helpful solutions to problems and depend on others for solutions. Patients are also less able to think of positive events in the future. This may account for the relationship between hopelessness and parasuicide. Enquiry about the individuals social circumstances is important. Although the overrepresentation of single and divorced men and women among parasuicide patients is a robust research finding, many of these people are found not to be living alone. The major risk factor in this area is likely to be interpersonal problems, of which being single or divorced is a manifestation. Studies have also consistently found an association between parasuicide and unemployment and while the relationship is complex, there is some
evidence that unemployment has a causal role. Parasuicide is more common in lower social classes. It is important not to ignore the more distal risk factors. Childhood experiences may contribute to the risk of parasuicide in later life. Such experiences include early loss of parents and poor parenting, especially abuse, neglect, and overprotection. There is evidence that childhood adversities have an enduring impact on interpersonal functioning, which increases the vulnerability to parasuicide. Twin and adoption studies provide support for a genetic susceptibility to parasuicide. It has been suggested that the genetic influence acts through impulsiveness and aggression possibly via abnormalities in the metabolism of the neurotransmitter serotonin. There is strong evidence of an association between parasuicide and serotonergic abnormalities, especially where the act was violent or with high suicidal intent. Abnormalities of other neurotransmitters, hormones, and cholesterol have been implicated, but the evidence is less convincing.
Formulation
In considering the above variables separately there is a risk of producing a static account. The final step in the assessment involves drawing together the relevant proximal and distal factors with reference to the dynamic interactions between these factors. For example, an act of parasuicide may have been an alcohol-fueled response by a generally impulsive person to an argument in the context of an emotionally distant relationship against a background of childhood abuse. The childhood experiences are likely to be relevant to both the individuals general interpersonal functioning and his/her response to this conflict. The tendency to resort to alcohol at times of stress may affect the nature of the partner relationship and contribute to the likelihood of parasuicide on this occasion. Thus, as well as precipitating parasuicide, mental disorder and environmental factors may influence the impact of precipitants. The most notable example is alcohol intoxication, which can increase impulsiveness and reduce consideration of the consequences of actions.
Repetition
Parasuicide is a major risk factor for future suicide. Between a quarter and two-thirds of patients who commit suicide have previously deliberately harmed themselves. A history of recent parasuicide is associated with a significantly elevated risk of suicide. A recent British study found that the risk of suicide in the first 12 months following parasuicide was 66
times the annual population risk. Despite this clear association, given the low base rate of suicide it remains difficult to predict. Factors that are associated with fatal repetition include a medically serious act of parasuicide with precautions against discovery, substance misuse, especially alcohol dependence, and a history of mood disorder or psychosis. Older age and male gender are also risk factors for subsequent suicide. A total of 3060% of parasuicide patients have a history of previous parasuicide. Of particular relevance in forensic populations is the finding that a history of offending or violence predicts nonfatal repetition. Other predictors include personality disorder, drug and alcohol abuse, unemployment and low social class, all variables that are common in offender groups. Some individuals, referred to briefly above, with a pervasive emotional disturbance who display features of borderline personality disorder deliberately harm themselves with alarming frequency. This type of behavior occurs more commonly in institutions, including prisons. The self-harm may take a number of forms, but a particular pattern often develops in relation to self-injury, such as cutting or burning. In some cases individuals insert objects into wounds or body orifices. Typically there is an experience of rising tension accompanied by a strong urge to self-harm, which becomes overwhelming. There may be no identifiable trigger or it may be trivial. Analgesia or a sense of unreality is often reported at the time of self-harm, but pain may develop subsequently. The act of self-harm leads to a sudden release of the tension, which may be pleasurable. The sight of blood can be important to the individual in this process. The immediate relief from distress reinforces this behavior. However, subsequent consideration of the behavior and the often unsympathetic response of others disrupts the individuals already fragile self-esteem and undermines emotional stability, increasing the risk of further deliberate self-harm. In some cases the behavior can be understood in terms of self-punishment by individuals whose dislike of themselves physically and emotionally can be traced to childhood abuse. Although this behavior occurs with little suicidal intent, the act may be serious and individuals also experience suicidal urges. Thus there is a significant risk of suicide. While they form a small proportion of the parasuicide population, such patients attract a disproportionate amount of emergency care and mental health resources.
Respectively, 20% and 30% of sentenced male and female inmates had a history of parasuicide. Among remand inmates the rates were 7% higher for both men and women. The rate of parasuicide is increased among offenders, largely due to the prevalence of risk factors for deliberate self-harm in this group. Thus offenders are more likely to suffer from mental disorder, experience social and relationship problems, and come from disturbed backgrounds. In the case of inmates who deliberately harm themselves whilst in custody the impact of their detention needs to be considered. Access to their social network is severely limited. Relationships are likely to be strained by the detention of one party. The prospect of a lengthy period of imprisonment may be difficult to contemplate. Inmates who deliberately harm themselves may report victimization and intimidation and legal proceedings are an additional source of stress. The commonest methods of parasuicide in custody are cutting and hanging. Although inmates do not have immediate access to large doses of medication, vulnerable inmates may store prescribed medication with the intention of taking an overdose. Parasuicide may be linked more specifically to a criminal act, but there is still usually evidence of more general psychological problems. A particular emotional state such as jealousy or anger may contribute to both the self-harming and offending behavior. Aggression to others and self-directed aggression in the form of parasuicide may occur during the same highly emotionally charged period. A more general association between parasuicide and aggression is supported by the finding that psychiatric patients who deliberately self-harm are more likely to have a history of aggression. This association may be mediated by impulsiveness, either as a general personality trait or a state produced by emotional disturbance and/or alcohol intoxication. Contemplation of offense behavior by the perpetrator may lead to a frame of mind, such as shame, guilt, or hopelessness, in which parasuicide is more likely. Some offenses, such as sexual offenses and offenses against children, are considered by society in general and other offenders in particular to be especially repugnant. Offenders responsible for such acts often face intimidation, threats, and assaults and these experiences may increase their vulnerability to parasuicide. Finally, offending behavior such as arson and reckless or dangerous driving may be an act of parasuicide.
Parasuicide and Offending

A recent representative survey of correctional facilities in the UK revealed high rates of parasuicide.
Management
Comprehensive prevention programs have been shown to reduce parasuicide significantly in correctional
facilities. These programs involve the screening of all inmates on arrival for risk factors such as suicidal thoughts, and a history of parasuicide, mental disorder, or substance misuse. For inmates considered to be at an increased risk of parasuicide certain steps should be considered. Treatment should be offered for any treatable mental disorder. It may be necessary to transfer the patient to healthcare facilities within the prison if available or to a hospital. While in custody precautions can be taken, such as removing belts and laces, and avoiding housing the inmate in a single cell. Various levels of supervision can be applied. Continuous monitoring either by video surveillance or direct sight is used in cases of imminent serious risk. Prisons in the UK employ a policy, at the center of which is the F2052SH procedure. This procedure is activated for prisoners considered to be at risk and comprises a case review, assessment by healthcare staff and medical officer, and documented observations of the prisoner. Similarly, it may be necessary to increase the degree of supervision for high-risk individuals in police custody. Following parasuicide medical intervention is often indicated. However, the patient may refuse treatment. Clinicians should be familiar with the law relating to refusal of consent for the jurisdiction in which they practice. Although the following section is based on the law in England and Wales, the same principles apply in many other jurisdictions. The fundamental rights of self-determination and individual autonomy underpin the principle that every persons body is inviolate. The principle of sanctity of life, while central to medical practice, is not absolute and must yield to the patients right to self-determination. Consent must be given voluntarily and without duress or undue influence and on the basis of information about the nature, risks, and consequences of the treatment being offered. This position is no different for a patient who is also a prisoner. Treating patients without their consent, even if it is deemed to be in their best interest, is potentially both a crime of battery and a tort of trespass. There is a presumption that patients have the capacity to consent to or refuse medical treatment unless the contrary has been demonstrated. A patient is considered to lack capacity if he/she is unable to comprehend and retain information that is material to the decision, and/or he/she is unable to use and weigh this information as part of the decision-making process. It is not always possible to assess capacity, for example, in an unconscious patient or highly disturbed inmate. In the absence of an advanced directive he/she should receive essential treatment in his/her best interests. As well as attending to the patients physical health, priority should be given to managing any
ongoing risk the patient may present to him/herself. It may not be appropriate to conduct a detailed psychiatric assessment in the first instance. However, information obtained during the initial stages, such as that referring to the method used, the means by which the episode came to the attention of others, and the response to the offer of treatment, often proves useful later. When the patients physical health allows, an assessment of his/her mental health should be conducted. Given that the individual may not have had a clear motive, recollection may be impaired and he/she may not feel able to discuss intentions; his/her account of the motive may be unreliable. For this reason it essential to collate information from as many sources as possible. Management of parasuicide patients should address social, psychiatric, and psychological factors. For individuals in custody probation officers may help with social problems, such as those relating to accommodation following release. The management of many mental disorders includes pharmacological treatment. Given the evidence of serotonergic abnormalities in deliberate self-harm patients, the potential therapeutic value of selective serotonin reuptake inhibitors has been considered. Although improvement in mood symptoms is reported, it remains to be determined whether this group of drugs specifically reduces repetition. A number of psychological interventions recommended for individuals who are at risk of parasuicide share cognitive behavioral principles. Cognitive behavioral therapy, dialectical behavior therapy, and problem-solving therapy focus on the present rather than the past and require active and explicit collaboration between the patient and the therapist with homework tasks for the patient. Problem-solving therapy is a brief psychotherapy in which the patient is helped to identify the current problems, understand the relationship between these problems and his/her emotional difficulties, and develop and apply adaptive skills to solve specific problems. Although parasuicide is associated with problem-solving difficulties, and problem-solving therapy improves depression, hopelessness, and problems for parasuicide patients, the evidence that this intervention reduces repetition of parasuicide is limited. The results from studies of dialectical behavior therapy are more promising. This treatment is targeted at patients with borderline personality disorder, among whom it has been shown to reduce the rate of parasuicide. Dialectical behavior therapy comprises four components: (1) individual therapy sessions typically held weekly; (2) a weekly skills training group; (3) the opportunity for the patient to telephone the therapist between sessions; and
250 SUICIDE/Youth Suicide
(4) a weekly consultation group for therapists. The aim of the individual therapy is to improve motivation to continue treatment and change maladaptive behavior. Group work aims to enhance emotional regulation, interpersonal effectiveness, and self-acceptance.
Youth Suicide
R W Byard, Forensic Science Centre, Adelaide, SA, Australia
Conclusion
Patients with a history of parasuicide are overrepresented among forensic populations. An episode of parasuicide has implications for the risk that the individual presents to him/herself, and is likely to be a marker of more pervasive psychological difficulties. A psychological or psychiatric assessment may be requested to inform the management of such patients in forensic settings or to assist the court in its deliberations. While bearing in mind the general correlates of parasuicide, the assessment should also cover specific factors relevant to offenders.
Introduction
Suicides represent a substantial proportion of unnatural deaths, accounting for more fatalities than motor vehicle accidents and homicides in many communities. Methods of suicide vary among countries and between regions influenced by the availability of materials required for the fatal episode and ideas of what constitutes an appropriate and effective lethal technique. The latter perceptions may be influenced by the age and sex of victims. While suicide rates have remained relatively stable in a number of western countries, there have been marked changes in rates in different age groups. For example, a decline in numbers of victims over the age of 65 has been counterbalanced by an increase in numbers of suicides in young adult males since the 1960s. This change has been noted in the USA, Canada, Australasia, and in parts of Europe. Male suicide rates are generally higher than female rates, except in countries such as China and Macedonia (Table 1).
See Also
Consent: Treatment Without Consent; Deliberate SelfHarm, Patterns; Detainees: Care in Prison Custody, United Kingdom; Forensic Psychiatry and Forensic Psychology: Suicide Predictors and Statistics; Medical Malpractice: Psychiatry; MurderSuicide; Suicide: Etiology, Methods and Statistics; Youth Suicide
Further Reading
Comtois KA (2002) A review of interventions to reduce the prevalence of parasuicide. Psychiatric Services 53: 11381144. Department of Health (1999) Safer Services. National Confidential Inquiry into Suicide and Homicide by People with Mental Illness. London: Department of Health. Hawton K, van Heeringen K (eds.) (2000) The International Handbook of Suicide and Attempted Suicide. Chichester, UK: John Wiley. Hawton K, Zahl D, Weatherall R (2003) Suicide following deliberate self-harm: long-term follow-up of patients who presented to a general hospital. British Journal of Psychiatry 182: 537542. Swenson C, Torrey W, Koerner K (2002) Implementing dialectical behavior therapy. Psychiatric Services 53: 171178. van Heeringen K (ed.) (2001) Understanding Suicidal Behaviour: The Suicidal Process Approach to Research, Treatment and Prevention. Chichester, UK: John Wiley. Williams M (1997) Cry of Pain: Understanding Suicide and Self-harm. London: Penguin Books.
Methods of Self-Destruction
Self-inflicted injuries may be lethal or nonlethal. The characteristics of nonlethal self-inflicted wounds are described elsewhere in this encyclopedia. Lethal events are most often due to hanging, carbon monoxide toxicity, drug overdose, shooting, cutting or stabbing, drowning, suffocation, vehicle or train-related trauma, jumping from heights, electrocution, or burning. Preferred methods of suicide change over time and vary from community to community. For example, hanging has become more common in females in Australia and the UK in recent years, whereas self-immolation and ingestion of caustic substances, methods favored in certain other countries, are relatively rare in western communities. Changes in methods may reflect substitution of a more available method for another, for example, hanging instead of shooting, if guns become less accessible due to stricter gun control legislation. Similarly, the decline in deaths due to drug overdose may have been influenced by reduced prescribing of barbiturates and tricyclic antidepressants, with substitution
SUICIDE/Youth Suicide 251

Table 1 Selected national suicide rates for 1519-year-olds per 100 000 population
Country Male rate Female rate
Macedonia Greece China Tajikistan Netherlands United Kingdom France Denmark Sweden Belgium Kyrgyzstan United States of America Australia Austria Canada Lithuania Kazakhstan New Zealand Russian Federation
1.8 2.3 3.9 4.4 5.9 6.3 7.6 8.7 9.4 14.6 14.7 14.9 17.5 18.6 19.1 28.5 30.7 33.2 34.5
3.7 0.5 6.4 1.8 2.9 2.0 2.9 2.0 3.4 3.5 5.0 3.2 5.4 4.9 4.9 10.3 10.3 17.1 8.5
suicides at very young ages. Conversely, accidental deaths occurring in young males during autoerotic asphyxial activities have in the past been incorrectly ascribed to suicide. Courts have been shown to consistently underestimate the true number of suicides with a gender bias, in that verdicts of suicide are more likely in cases involving females. For this reason, careful evaluation of cases is important prior to assigning a particular manner of death.
Youth Suicide
Suicide in the young has received considerable media attention in recent years; however, there has been a lack of clarification of terminology. For example youth has been used to refer not only to adolescents, but also to young adults, extending in some studies up to 29 years. The rates of suicide and predisposing factors in individuals aged between 25 and 29 years are different from rates and characteristics in the 1519-year-old age group. Thus, grouping these two quite disparate populations has confused interpretation of data. Results of studies examining numbers and rates of suicide in adolescence are detailed below. Characteristics of suicide in the young include male gender, mental illness with a history of mental health care, substance abuse, exposure to childhood sexual abuse, poor parental relationship, prior suicide attempts, low educational level, and stressful life events. Higher rates are often found in white populations with a history of risk-taking behavior, such as delinquency, playing with firearms, and reckless motorcycle riding. Suicides in the young often occur in and around the home. Precipitating factors are different in the elderly, for whom issues such as chronic illness, debility, social isolation and spousal loss are of greater significance.
Data from Pelkonen M, Marttunen M (2003) Child and adolescent suicide: epidemiology, risk factors, and approaches to prevention. Paediatric Drugs 5: 243265.
was replaced by less toxic natural gas in the UK, there was an associated fall in suicide rates from gassing. Methods that are chosen to terminate life also differ between the sexes, with females traditionally opting for less violent means such as drug or poison ingestion or carbon monoxide inhalation. This contrasts with males, who have tended to adopt more violent means of self-destruction, such as shooting and hanging. This has also been observed in murdersuicides involving parents and their children, with fathers more likely to kill not only their children, but other children, their spouse, and even family pets. The term family annihilator has been coined for such individuals. When mothers have murdered their children and then committed suicide, methods used are often less violent with sedation of children before the lethal event.
Study Results
Results of a study comparing the characteristics of suicides under 17 years in San Diego (USA) and South Australia are summarized in Tables 2 and 3. The 70 cases of suicide in San Diego county accounted for only 1.6% of the total number of suicides (4492) over the study period from 1985 to 1997. The average age of the 48 males and 22 females was 14 years 8 months, with deaths due to gunshot wounds, hanging, drug toxicity, and falls/jumps from heights (Table 2). The 48 cases of suicide in South Australia accounted for a similar low percentage (2%) of the total number of suicides (2251). The average age of the 34 males and 14 females was 15 years 4 months, with deaths due to hanging, gunshot wounds, train-related trauma, drug
Pathological Problems
Determination of the manner of death in certain cases of possible suicide may be difficult, resulting in misreporting in official data. For example, falls from heights may be accidental or intentional, or even homicidal if others were present. Drowning and heroin overdoses may represent accidents or suicides. Single-occupant vehicle crashes may be accidents or suicides, and deaths on train tracks or in fires may be suspicious. There may also be underreporting of
252 SUICIDE/Youth Suicide

Table 2 Breakdown of suicide by methods used and sex of victims in 70 cases under 17 years of age (San Diego CA, USA)
Method Male Female Combined
Gunshot Hanging Overdose Jumping Total
31 14 1 2 48
10 7 5 0 22
41 (59%) 21 (30%) 6 (9%) 2 (3%) 70
Reprinted from Journal of Clinical and Forensic Medicine, Vol 7, Byard RW, Markopolous D, Prasad D, Eitzen D, James RA, Blackbourne B and Krous MF. Early addescent suicide: a comparative study, pp. 69, 2000. With permission from Elsevier and AFP.
Table 3 Breakdown of suicide by methods used and sex of victims in 48 cases under 17 years of age (South Australia, Australia)
Method Male Female Combined
Figure 1 Number of suicides for males and females under the age of 17 years in South Australia (Australia) from January 1985 to July 2003, demonstrating an older male predominance (n 60).
Hanging Gunshot Train Overdose Jumping Self-immolation Carbon monoxide poisoning Electrocution Total
19 6 3 1 2 1 2 0 34
3 0 2 3 2 2 1 1 14
22 (46%) 6 (13%) 5 (10%) 4 (8%) 4 (8%) 3 (6%) 3 (6%) 1 (2%) 48
Reprinted from Journal of Clinical and Forensic Medicine, Vol 7, Byard RW, Markopolous D, Prasad D, Eitzen D, James RA, Blackbourne B and Krous MF. Early addescent suicide: a comparative study, pp. 69, 2000. With permission from Elsevier and AFP.
toxicity, falls/jumps from heights, self-immolation, carbon monoxide inhalation, and electrocution (Table 3). Suicides under the age of 17 years were rare in both populations, with no increase in numbers over the 13 years of the study. Self-destructive methods were different in the two populations with significantly more gunshot suicides in San Diego county compared to South Australia. Differences were also found in the methods used in South Australia among the young compared to older populations, with deaths involving firearms and inhalation of carbon monoxide less common in the younger age group, and more deaths due to hanging, falls/jumps, and self-immolation. The study demonstrated that the number of suicides in individuals under the age of 17 years in South Australia and San Diego over the past decade had been small, with no appreciable changes, despite reports of increases in suicide rates in 1524-year-old males over the past 30 years in a number of communities. The steady rate of suicides in younger victims is not a universal finding, however, with studies in other populations showing an increase in rates in younger
age groups. The significance of these apparently disparate findings is that suicide rates are subject to local social and cultural influences and thus it should not be a surprise to find different trends in different populations. However, recent mean worldwide annual rates of suicide in the 514-year-old age group have been cited as 0.5 per 100 000 for girls and 0.9 for boys, compared to 12 per 100 000 for females aged 1524 years and 14.2 for males in that age range. Further data from South Australia for the years 1998 and 1999 have also shown that only 1.4% of all unnatural deaths (15/1080) were due to suicides under the age of 20 years compared to 27.6% of deaths due to suicides between the ages of 20 and 49 years (298/1080). The rates of suicide per 100 000 of the population in this study were 7.5 in the 1019-year-old age group and 49 in the 2029-year-old group, again confirming lower rates in the young. Rates of suicide steadily increase through adolescence with a preponderance of 16-year-old male victims in cases under 17 years (Figure 1). Looking more closely at Australian data demonstrates that there has also been no appreciable increase in suicide rates for males or females in the under-14-year-old age groups in that country for over 100 years. For example, the suicide rate for boys per 100 000 of the Australian population was 0.5 between 1891 and 1910, 0.2 in 1964, 0.6 in 1986, 0.3 in 1990, and less than 0.5 in 1995. Similarly, for girls the rates were 0.4 between 1891 and 1910, 0.2 in 1964, 0.1 in 1986, 0.2 in 1990, and 0.6 in 1995. This contrasts with a report from the Centers for Disease Control that showed a 120% increase in suicide rate in 1014-year-olds between 1980 and 1992 in the USA.
SUICIDE/Youth Suicide 253
It has been asserted that the choice of method of suicide is not influenced by the age of the victim. However, this is incorrect. For example, drowning suicides are much less common in younger than older women. Carbon monoxide inhalation, shooting, and drug overdose are less common in certain adolescent populations compared to the general adult population, whereas trauma related to trains, jumping from buildings, and self-immolation may be higher. Geographic variability also occurs, with shooting being much more common in San Diego county than in South Australia. Reasons for the variability in preferred methods of suicide among different populations and ages remain conjectural; however, accessibility to injurious agents and perception of the effects of certain actions are probably involved. In North America, gunshotrelated deaths are far more common than in countries such as Australia and the UK. It is difficult to dismiss the possibility that the widespread availability of firearms in the USA is the reason for the extremely high rate of gunshot trauma. American studies have shown that firearms used by children in suicide attempts have generally been stolen or borrowed from a member of the family. In other parts of the world, firearm suicides are more common in rural areas, a finding again attributed to the greater availability of firearms on farms compared to urban areas. Failure to understand the requirements for setting up a lethal environment in a car for carbon monoxide inhalation may explain the lower numbers of deaths at younger ages. This may also be contributed to by a lack of car ownership at this age. Overdose of drugs may be less frequent in younger age groups, as psychotropic drug prescription is lower in adolescents, and there may be a lack of understanding of the amount required for a fatal outcome. On the other hand, the effects of self-immolation, standing in front of a train, or jumping from a height are obvious, and matches, train tracks, and tall buildings are all easily accessible. Suicidal drownings are more common in populations living next to the sea or large inland lakes, and jumping from a height is the most common method used in youth suicide in large cities, such as Singapore.
age group among countries can be seen in Table 1. Although youth suicide may be increasing in some groups, this is not a general phenomenon as the trends in, and method of, youth suicide may vary considerably from community to community. To be effective, strategies to deal with suicide should therefore not rely upon pooled data, but should examine particular features of specific populations with analysis of subgroups based on sex, age, and other local sociodemographic features.
See Also
Deliberate Self-Harm, Patterns
Further Reading
Beautrais AL (2003) Suicide and serious suicide attempts in youth: a multiple group comparison study. American Journal of Psychiatry 160: 10931099. Bell CC, Clark DC (1998) Adolescent suicide. Pediatric Clinics of North America 45: 365380. Byard RW, Knight D, James RA, Gilbert J (1999) Murdersuicides involving children: a 29-year study. American Journal of Forensic Medicine and Pathology 20: 323327. Byard RW, Eitzen D, James RA (2000) Suicide trends: adolescence and beyond (letter). Medical Journal of Australia 172: 461462. Byard RW, Markopoulos D, Prasad D, et al. (2000) Early adolescent suicide: a comparative study. Journal of Clinical Forensic Medicine 7: 69. Byard RW, Houldsworth G, James RA, Gilbert JD (2001) Characteristic features of suicidal drownings: a 20-year study. American Journal of Forensic Medicine and Pathology 22: 134138. Cantor CH, Leenaars AA, Lester D, et al. (1996) Suicide trends in eight predominantly English-speaking countries 19601989. Social Psychiatry and Psychiatric Epidemiology 31: 364373. Dudley M, Kelk N, Florio T, et al. (1997) Suicide among young rural Australians 19641993: a comparison with metropolitan trends. Social Psychiatry and Psychiatric Epidemiology 32: 251260. Goldney RD (1993) Suicide in the young. Journal of Paediatrics and Child Health 29(Supplement 1): S50S52. Gould MS, Greenberg T, Velting DM, Shaffer D (2003) Youth suicide risk and preventive interventions: a review of the past 10 years. Journal of the American Academy of Child and Adolescent Psychiatry 42: 386405. Kosky RJ, Eshkevari HS, Goldney RD, Hassan R (eds.) (1998) Suicide Prevention: The Global Context. New York: Plenum Press. Lee CJ, Collins KA, Burgess SE (1999) Suicide under the age of eighteen: a 10-year retrospective study. American Journal of Forensic Medicine and Pathology 20: 2730. Pelkonen M, Marttunen M (2003) Child and adolescent suicide: epidemiology, risk factors, and approaches to prevention. Paediatric Drugs 5: 243265.
Conclusion
Despite media assertions to the contrary, suicide rates in adolescence are low when compared to rates among people in their thirties and forties. Methods of suicide in the young also vary among populations and are likely to be influenced by the availability and access to agents of self-destruction. The great variability in rates of suicides in the 1519-year-old
254 SUICIDE/Youth Suicide Pritchard C (1996) New patterns of suicide by age and gender in the United Kingdom and the western world 19741992: an indicator of social change. Social Psychiatry and Psychiatric Epidemiology 31: 364373. Roesler J (1997) The incidence of child suicide in Minnesota. Minnesota Medicine 80: 4547. Ung EK (2003) Youth suicide and parasuicide in Singapore. Annals of the Academy of Medicine Singapore 32: 1218. Weinberger LE, Sreenivasan S, Sathyavagiswaran L, Markowitz E (2001) Child and adolescent suicide in a large, urban area: psychological, demographic, and situational factors. Journal of Forensic Sciences 46: 902907.
Suicide, Dyadic Death
See MurderSuicide
Suicide, Predictors and Statistics

Predictors and Statistics
See Forensic Psychiatry and Forensic Psychology: Suicide
Suicide Bombing
See Terrorism: Suicide Bombing, Investigation
T
TACTICAL MEDICINE
W S Smock, University of Louisville Hospital, Louisville, KY, USA J S Vayer, University of the Health Sciences, Bethesda, MD, USA
The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Department of the Army, the Department of the Air Force, or the Department of Defense.
Introduction: Defining TEMS

When most people hear the term tactical emergency medicine, they picture the combat medic holding an intravenous bag aloft, supporting a patient, all the while dodging enemy fire. But modern tactical emergency medical support (TEMS) is much more. It is a subspecialty of emergency medicine that involves an individual or team of professional and paraprofessional healthcare providers delivering a full spectrum of care. The tactical medical officers responsibility goes far beyond the acute management of trauma under fire. TEMS primary roles in mission support include injury control, the provision of preventive medicine and health promotion, nutrition, hydration and fitness, and the minimization of performance decrements. It is precisely because this practice is a comprehensive approach that the term tactical emergency medical support is preferred over the term tactical emergency medical services. TEMS medical officers buttress law enforcement and special operations in order to enhance the probability of mission success.
USA, the National Tactical Officers Association and the Counter Narcotics and Terrorism Operational Medical Support (CONTOMS) program developed by the Casualty Care Research Center of the Uniformed Services University were the first organizations to develop national training programs. Fortunately, within the USA there are multiple organizations that offer state-of-the-art training for tactical medical officers (Table 1). There is also a considerable growth in international acceptance of the TEMS concept for civilian law enforcement, especially in the UK. In law enforcement, special operations denote those tasks that are too complicated, too dangerous, or too technical to be handled by patrol units. Instead, those tasks are assigned to special, highly trained and well-equipped teams of officers who constantly operate at the edge of the safety envelope. These teams, referred to as special weapons and tactics (SWAT) or emergency response teams (ERTs), are able to bring improved technology and training to bear on the resolution of the crisis situation. Tactical medicine is just one of the tools they may use to conclude the mission successfully.
Benefits of TEMS
Contributing to the success of the primary law enforcement mission is the principal goal of TEMS; there are other significant benefits concomitant with the employment of a tactical medical program. First, it is likely to decrease mortality and morbidity among law enforcement personnel, perpetrators, and innocent third parties. Second, a TEMS program that includes preventive medicine and injury control strategies will also reduce line-of-duty injury and disability costs for public safety agencies. Since highly trained, difficult-to-replace human assets are the most precious resource of any special operations team, the reduction of lost work time for these operators is the third major benefit of tactical medicine. Special operations team members usually have skills and certifications acquired through long-term training and testing, and lesser-trained officers cannot
Development of TEMS
The use of TEMS has grown rapidly since its conception in the late 1980s, gaining widespread acceptance in the field of prehospital emergency medicine and within the law enforcement community as well. In the
256 TACTICAL MEDICINE

Table 1 Tactical emergency medicine support/training programs Casualty Care Research Center Department of Military and Emergency Medicine Uniformed Services University 4301 Jones Bridge Road Bethesda MD 20814-4799 USA Tel: 301-295-6263 Website: www.casualtycareresearchcenter.org International Tactical EMS Association (ITEMS) PO Box 504 Farmington MI 48322-0504 USA Tel: 248-476-9077 Website: www.TEMS.org Heckler & Koch, USA, Inc. International Training Division 21480 Pacific Boulevard Sterling VA 20166-8903 USA Tel: 703-450-1900 Website: www.tacticalmedicine.com National Tactical Officer Association (NTOA) PO Box 797 Doylestown PA 18901 USA Tel: 800-279-9127 Website: www.ntoa.org
Figure 1 Tactical officers operate in dangerous environments and are at risk for serious injury. The presence of a tactical medical officer provides a high level of medical care at the incident scene and increases the probability of mission success.
Figure 2 Tactical medical officers should be integrated and trained as part of the tactical team. Such training will facilitate tactically appropriate responses in the midst of an emergency.
provide any countermeasure to the risk created, may incur liability for the law enforcement agency.
temporarily replace them. Fourth, the provision of TEMS has a positive effect on the overall morale of the team. Tactical operators are expected to take enormous risks in very dangerous situations (Figure 1). Their willingness to engage fully in the mission, at a time when life-and-death decisions must be made by their commanders and colleagues in fractions of a second, is enhanced by the knowledge that management has assured the availability of the best possible medical care should they be injured. Finally, tactical operations are, by their very nature, liability-prone circumstances and the provision of tactical medicine to bridge the gap from point of injury to appropriate entry into the healthcare system can significantly enhance agency posture. The actions of the tactical team invariably contribute to the creation of some degree of hazard, even if the ultimate objective is to reduce a greater potential hazard. To create such risk and recognize that people might be harmed, yet fail to
The Daily Routine Doctrine

The daily routine doctrine is a term coined to describe a basic tenet of disaster and multicasualty response. It states that the activities in which one engages on a regular basis will be performed reasonably well during a time of crisis, while those activities that are done only in response to the crisis will be performed relatively poorly. This concept has application in tactical medicine. Since the actions of a tactical team are carefully choreographed and highly dependent on each operators knowledge of how each other operator is likely to respond in an emergency, it follows that tactical medics should train on a regular basis with the team they support and be fully integrated into all team activities (Figure 2). This facilitates effective utilization of tactical medical assets in mission accomplishment and keeps the medical component from becoming a burden to the team.
TACTICAL MEDICINE 257
Emergency Medical Services and TEMS: Major Differences in Medical Care

The principal difference between TEMS and everyday prehospital emergency medical services (EMS) is not the specific treatment procedures that are utilized, but rather the context in which treatment decisions are made. For example, the physiology of controlling hemorrhage does not change when the patient is in an operational environment: direct pressure, elevation, and pressure points are still options for stemming life-threatening bleeding. However, the tactical medic might be more inclined to move rapidly to a tourniquet since he/she may not be able to monitor the effectiveness of the pressure dressing during an extraction and the patient could bleed out over that time period (Figure 3). Tactical medics, based upon current military protocols, will elect to infuse crystalloid only when a patients blood pressure drops to a level that affects brain perfusion, whereas traditional EMS providers would start two large-bore intravenous infusions and pour intravenous fluids in to the patient. Such treatment with large amounts of intravenous fluids can dilute the patients clotting factors and cause increased blood loss.
Figure 3 Tactical medical officers monitor a suspects gunshot wound to the thigh. Exsanguinating injuries in the tactical environment may require the application of tourniquets if transport is delayed until the scene is secure.
Due to the multidisciplinary and comprehensive approach to the practice of tactical medicine, the tactical medic requires an expanded scope of practice that includes injury control, preventive medicine, field sanitation and hygiene, nutrition, sports-injury assessment and management, sick call, and selected specialty skills, such as managing dental injury without narcotic analgesia. In addition to the modified decision-making process, some treatment protocols should be modified for application in the tactical environment while other skills are unique to the practice of TEMS. Although management of the airway remains an important basic skill, airway compromise is a relatively rare occurrence in the tactical setting. Patients who cannot manage their own airway usually have penetrating wounds to the central nervous system that portend a poor outcome regardless of airway intervention. As reported in the CONTOMS database, an airway adjunct of any kind was used in only 2% of all treatments rendered, and only onethird of these casualties survived to arrival at the hospital. Digital intubation is an alternative airway technique that is practiced by tactical medics because only a tube and stylet are needed, intubation can be accomplished with minimal head and neck movement from a low-profile position, and it does not require the use of white light associated with a laryngoscope. Of course, the patient must be fully unconscious to reduce the likelihood of bite injury to the caregiver. Although patients may ventilate adequately on their own after establishment of a patent airway, an extender tube should be used if a bag-valve mask device is employed. The extender tube allows movement between the endotracheal tube and the bag without dislodging the tube during patient extraction. The bag-valve mask must have an exhalation valve that can be removed from the bag and placed on the downstream side of the extender tube, that is, the end closest to the endotracheal tube. This prevents the extender tube from becoming dead space that traps exhaled air during resuscitation. Cardiopulmonary resuscitation (CPR) has limited value in the tactical setting. Performing CPR in this environment is likely to subject the provider(s) to increased risk for longer periods of time and may divert scarce resources from other mission essential tasks. Generally, there is no role for CPR or artificial ventilation in the warm or hot zone of the tactical environment. The successful resuscitation rate from cardiac arrest secondary to trauma is so low, and the risk to the provider of performing this procedure so high, that it cannot be justified. Given the added complications of an austere, resource-poor environment, extended evacuation times, and the
absence of a rigid, wheeled litter on which to perform CPR, it should only be considered under unusual circumstances. However, in those situations where arrest is secondary to primary respiratory embarrassment, short periods of CPR may restore normal function and can be considered if resources are sufficient. These situations include near drowning, hypothermia, toxic exposure, electrocution, and lightning injury. Proper immobilization of the cervical spine requires a significant amount of time and personnel at least two. Prehospital personnel are traditionally taught to immobilize the spine if there is the slightest possibility of spinal column injury and this is not unreasonable given the devastating consequences of an occult, unstable fracture that results in spinal cord damage. However, evidence indicates that immobilization does not contribute significantly to an improved outcome in cases of penetrating injury to the neck and it is probably reasonable to extrapolate this evidence to all penetrating injuries, but not to blunt trauma. Generally, the projectile either passes through the cord or it does not, but it rarely creates an unstable fracture. Therefore, it is probably inappropriate automatically to immobilize the spine in the hot or warm zone of the tactical environment. The providers increased exposure to threats and hazards in a hot zone is unacceptable when weighed against the low probability of an unstable fracture that would benefit from immobilization. For penetrating trauma, immobilization should be delayed until the patient is in a safe area. Traditional teaching in prehospital care is to treat all chest wounds as if they were a sucking chest wound and to seal them with an occlusive dressing. However, in the TEMS environment, the medic is often unable to monitor the patient closely after initial contact due to rapidly changing tactical circumstances, limited staffing levels, and difficult extractions, and may not have the opportunity to recognize a tension pneumothorax created by the seal itself. Although most training advocates the placement of a three-sided seal that will act as a one-way valve (permitting trapped high-pressure air to exit the chest, but preventing air from preferentially entering the chest via the wound on inspiration), these one-way valves rarely function as intended. Since most chest wounds are not truly sucking chest wounds, and since many patients will do well for a short period of time with a small open pneumothorax, it is suggested that a chest wound not be sealed unless the patient is in extremis, in which case the wound may be sealed, needle thoracentesis performed, and the patient must be closely monitored for continuing respiratory distress.
TEMS Models
Across the USA and Europe tactical medical support for civilian law enforcement is provided through a variety of approaches based upon the local assets, resources, and foresight of community leaders. The two most common vehicles for rendering care in the tactical environment are with tactically trained emergency medical teams (EMTs) or paramedics via a firebased or third-service emergency medical service. Some models include the training of a tactical team member as an EMT while other programs look to the local medical community and train paramedics, nurses, or physicians as a member of the law enforcement team. No matter what model a tactical team chooses to employ, it is imperative to have some level of medical care readily available during training as well as call-outs. Placing an ambulance on stand-by some distance away from the scene is an inadequate method of addressing tactical operational medical support and puts the well-being of team members at risk secondary to the inevitable delay distance imparts. There are an estimated 5000 tactical medical providers in the USA. Data from the Casualty Care Research Center (CCRC) indicate that 86% of the medical care provided in the tactical environment is rendered by tactical EMTs and paramedics. Seven percent of the on-scene tactical medical care is provided by physicians and less than 1% by nurses. A 1999 survey of tactical physicians in the USA revealed that 100% of the physicians were male, with an average age of 43. Seventy percent of the physicians were emergency medicine-trained but also included other specialties: family medicine, general surgery, critical care, and dermatology. The same survey found that 66% of the tactical physicians carried a firearm and 53% were sworn law enforcement officers. Seventy-seven percent of the physicians were armed for defensive purposes (i.e., defending a patient), while 23% of the physicians were armed as members of the tactical entry team, including one physician who was also trained as a sniper. Based upon training, departmental policies, sworn versus nonsworn, and armed versus unarmed, tactical medical officers will operate in different zones of care. The cold zone is defined as the area away from the threat or target where there is no immediate tactical threat or danger to the medical officer or patient. The command post is traditionally located within the cold zone away from the risk or threat. A warm zone is an area between the hot and cold zones, not directly in the line of fire with cover and concealment, but with some element of a threat. The hot zone is the area closest to the threat or hazard. Tactical medicine
may be practiced in all three zones, although, to reduce the risk to officers, medics, and patients, only lifesaving measures should be applied in a hot zone: more extensive evaluations should wait until the patient can be removed to a warm or cold zone.
Responsibilities of the Tactical Medical Officer

The tactical medical officer, from EMT to physician, is responsible for the medical well-being of the tactical team. These responsibilities include preventive medical services, determination of fitness for duty, medical risk assessments associated with a particular mission, providing the SWAT and on-scene commanders with medical intelligence involving a particular threat, hazard, medication, or patient condition, providing care to and evaluating team members during prolonged operations, and rendering life-saving care under fire. The success or failure of any tactical mission ultimately rests with the commander. By helping to ensure the physical well-being of the law enforcement team, the tactical medical officer increases the probability of mission success.
Preventive Medicine
to assist the team commander in addressing a particular officers fitness for duty and determining team work/rest cycles and hydration/nutrition requirements based upon environmental conditions. Tactical medical officers must also have the ability to remove officers from the mission if, based upon medical evidence or observation, they pose a risk to themselves or the team.
Medical Threat Assessments
Every tactical mission, whether a training session, a high-risk warrant, a barricaded gunman, a hostage rescue, a clandestine drug laboratory raid, a terrorist incident response, a hazardous device, or dignitary protection event, should include a medical threat assessment as part of mission preparation (Figures 4 and 5). The medical officers mission hazard assessment will include an evaluation of: . environmental conditions and hazards weather (heat, cold, humidity, rain, snow, ice), shelter, terrain, water, animals (guard dogs, farm animals), poisonous plants or venomous reptiles, and insect/ parasite activity . technical hazards lab chemicals, nerve agents, biological or radiological material, booby traps, explosives, or special weaponry (Figure 6) . medical facilities location of and distance to closest hospital, trauma, and burn centers . location of ambulance and aviation LZ . availability of hydration and nutritional support . sanitation, hygiene, and sleeping facilities for extended operations. The tactical medical officer should make recommendations to the unit commander based upon the
Some of the most important work the tactical medical officer can perform is preventive medicine. Preventive medical issues include: monitoring immunization status, ensuring each member has the appropriate protective gear (such as eye and ear protection) during call-outs and training, providing predeployment and deployment hydration management, and ensuring appropriate dress for the environmental conditions. The medical officer should make certain all team members have up-to-date immunizations, including tetanus/ diphtheria and hepatitis B. Additional immunizations may be required depending upon the location and nature of the operations. Recently, some tactical teams have offered smallpox and anthrax vaccinations to members who would respond to a terrorist event.
Fitness for Duty
The tactical or SWAT operator must be physically and mentally capable of responding to a life-threatening situation, operate in austere environmental conditions, perform at peak levels for extended periods of time, and make split-second decisions involving the use of firearms with mental clarity and focus. Tactical operators who are unable to perform these duties for whatever reason jeopardize their own life and the lives of other team members and civilians as well as mission success. The medical officer must be ready
Figure 4 Unexpected hazards may await the tactical officer upon entry into an unknown clandestine drug laboratory. Medical preplanning as part of the medical threat assessment will facilitate a rapid and appropriate response.
Figure 6 Methamphetamine laboratories are potential toxic time bombs. Chemicals on site, including hydrochloric acid, can inflict career-ending and life-threatening injuries to unsuspecting tactical officers. Special protective clothing and self-contained breathing apparatus may be required for a tactical entry.
Figure 5 Dignitary protection details require a medical threat assessment that includes medical information on the health of the protectee. This would include knowledge of the dignitarys current medical conditions, medications, and drug allergies. Predetermined routes to local hospitals and trauma centers from anywhere along the detail are obligatory.
Tactical teams are increasingly called to missions involving potential terrorists, terrorist cells, and clandestine laboratories. These operations, in potentially hazardous environments, require that the tactical medic have advanced training and skills to operate safely and provide care at a contaminated scene. These advanced skills include: (1) recognition of cutaneous manifestations associated with class A biological agents (Figure 7); (2) recognition of symptoms associated with nerve agent toxicity and treatment (Figure 8); (3) ability to recognize and survey patients for the presence of radioactivity (Figure 9) and provide appropriate decontamination; and (4) knowledge of how to locate and attain hard-to-find antidotes for specific radiologic isotopes (Figure 10).
Medical Intelligence
specific needs and threats associated with a particular mission. The earlier the medical assessment is completed, the more time the commander will have to evaluate the recommendations and obtain the needed support.
On-scene SWAT and hostage negotiator commanders will rely on the tactical medical officer for ongoing medical information during the mission. This may include information on medications, interpretation of medical histories and conditions, evaluation of a barricaded subjects or hostages medical condition based upon a distant visual observation, or remote assessment via phone line. Medical intelligence also includes providing the commander with ongoing
Figure 7 The ability to recognize smallpox lesions on a terrorist suspect is an advanced level of training that tactical medical officers should acquire. An unrecognized human biologic vector poses a very grave threat to public health.
Figure 9 Tactical medical officers must be familiar with the use of survey meters so they can determine whether tactical officers have been exposed to radioactive material.
Figure 8 Atropine and pralidoxime chloride, antidotes for some nerve agents, should be part of the tactical medical officers pharmacopeia. Rapid injection of these medications is required after exposure to certain chemical nerve agents. The mark 1 nerve antidote kit (above) is carried by a number of tactical teams.
Figure 10 Treatment of inhaled or ingested radioactive material requires the identification of the specific isotope for appropriate care. Tactical medical officers should have knowledge of where to obtain specific antidotes, like calcium disodium versenate, once the isotope is identified.
assessments of the officers and observations regarding performance decrements based upon the effects of time, heat, cold, hydration, and nutrition.
Care under Fire
The tactical medical officer must decide, based upon the severity of injuries and safety considerations, when a patient needs emergent evacuation for a lifethreatening injury. If a patient, officer, or civilian has an obviously fatal and nonsurvivable injury, there is no need to risk additional injuries to others in order to evacuate a corpse. There are however situations where life-saving care, rendered within seconds or minutes, will determine if an officer or civilian
survives. Securing the airway and the control of exsanguinating hemorrhage are the two situations that require immediate attention by the tactical medical officer. Patients may require rapid extraction without medical care from the hot zone to a warm zone for evaluation and treatment before being transported to a medical facility for care. The medical officer is responsible for advising the tactical commander of the nature of injury and whether, based upon the severity of the injury, immediate extraction is necessary or if the patient can tolerate some delay in removal to the cold zone.
Clearance for Incarceration
Upon completion of the mission, there may be suspects who have been injured and require medical
clearance for incarceration. The ability to clear a suspect for incarceration is dependent upon a number of variables but foremost is the level of medical training, that is, EMT versus medical doctor. If a suspect has any change or alteration in mental status, whether from intoxication, chemical impairment, or head injury, it is obligatory that he/she must be medically cleared by a physician within a medical facility. Other cases may not be so obvious. A nonimpaired suspect with a contusion for a less lethal kinetic device (Figure 11) may or may not require physician clearance. Less lethal impacts to the chest and abdomen (Figure 12) could induce injury to underlying organs and would require observation and computed tomography or ultrasound evaluation, whereas impacts to extremities, without bony pain, may be able to proceed
directly to jail. If the tactical medical officer is in doubt, the prudent action would be to send the suspect for an additional medical evaluation.
Post-9/11 TEMS Response
Although tactical medicine was originally conceived as a support function for police tactical teams and counterdrug missions, it also has application in support of a counterterrorism investigation or event. Law enforcement investigation and interdiction of terrorist activities are carried out in a low-profile manner that protects operators, sources of intelligence, and pending actions, and avoids unnecessary interruption of essential infrastructure or commerce. These operations are conducted under strict operational security guidelines. Special operations medical providers should already have the requisite background investigations and security clearances, training in security practices, and needed technology, such as encrypted radios, to implement operational and communications security procedures. TEMS providers must now be trained in the evaluation and treatment of nerve agents. TEMS operators should be supplied with and trained to administer antidotes: atropine, 2PAM chloride, and Valium to victims of a nerve agent exposure. Knowledge of other toxic materials of terrorism, including blister agents, radiation dispersion devices, and biological pathogens, is now part of the tactical medics mission.
Figure 11 This sock round is a less lethal kinetic device, fired from a 12-gauge shotgun. The round, designed to incapacitate a suspect through pain compliance, is capable of inflicting serious injury to internal organs.
Summary
TEMS is an established subspecialty of prehospital emergency medicine designed to support civilian law enforcement in high-risk special operations. Utilization of professional and paraprofessional healthcare providers to address injury prevention, acute trauma care, nutrition and fitness, and special hazards will ensure tactical team well-being. In the current law enforcement environment, tactical teams must not compromise the safety of their officers by failing to apply TEMS but must realize that TEMS is an indispensable asset and an integral component of mission success. Post-9/11 TEMS is now required to expand beyond its traditional support of SWAT to support of domestic counterterrorism operations involving potential weapons of mass destruction.
See Also
Figure 12 Pattern contusions on the lateral abdomen of a suspect from sock rounds and pepper balls. Patients with less lethal impacts to the head, neck, groin, chest, or abdomen require medical clearance before incarceration.
Chemical Crowd Control Agents; Injuries and Deaths During Police Operations: Shootings During Police Stops and Arrests; Special Weapons and Training Teams; Occupational Health: Police; Restraint Techniques, Injuries and Death
TATTOOS, MEDICO-LEGAL SIGNIFICANCE 263
Further Reading
Carmona RH (2003) The history and evolution of tactical emergency medical support and its impact on public safety. Topics in Emergency Medicine 25: 277281. CONTOMS Database System (2004) Bethesda, MD: Uniformed Services University of the Health Sciences. De Lorenzo RA, Porter RS (1999) Tactical Emergency Care. Upper Saddle River, NJ: Prentice-Hall. Emergency Medical Technician Tactical Course Manual, 14th edn. (1995) Bethesda, MD: Uniformed Services University of the Health Sciences. Federal Response Plan, Terrorism Incident Annex (2003) Federal Emergency Management Agency. Available online at: http://www.fema.gov/pdf/rrr/frp/frp2003.pdf. Hardwick WC, Bluhm D (1984) Digital intubation. Journal of Emergency Medicine 1: 317320. Heiskell LE (1996) SWAT medical teams. Law and Order 7074. Heiskell LE, Carmona RH (1994) Tactical emergency medical services: an emerging subspecialty of emergency medicine. Annals of Emergency Medicine 23: 778785. Jones JS, et al. (1996) Into the fray: integration of emergency medical services and special weapons and tactics (SWAT) teams. Prehospital Disaster Medicine 11: 202206. Kanable R (1999) Peak performance. Law Enforcement Technology 7882. Llewellyn CH (2003) The antecedents of tactical emergency medical support. Topics in Emergency Medicine 25: 274276.
Macintyre AG, Christopher GW, Eitzen E, et al. (2000) Weapons of mass destruction events with contaminated casualties. Journal of the American Medical Association 283: 242249. McArdle DQ, Rasumoff D, Kolman J (1992) Integration of emergency medical services and special weapons and tactics team: the emergence of the tactically trained medic. Prehospital Disaster Medicine 7: 285288. Olds MA, Grande CM (1995) When Minutes can Mean a Lifetime. Counter terrorism and Security Reports, pp. 2628. Quinn M (1987) Into the fray: the search and rescue role with special weapons teams. Response 6: 1820. Rooker N (1993) The San Francisco shootings. JEMS 7481. Smock WS, Hamm M, Krista M (1999) Physicians in Tactical Emergency Medicine, 1999. American College of Emergency Physicians Research Forum. Annals of Emergency Medicine 34(suppl.): 4. Stein M, Hirshberg A (1999) Trauma care in the new millennium: medical consequences of terrorism the conventional weapon threat. Surgical Clinics of North America 79: 15381552. Stewart RD (1984) Tactile orotracheal intubation. Annals of Emergency Medicine 13: 175178. Vayer JS, Schwartz RB (2003) Developing a tactical emergency medical support program. Topics in Emergency Medicine 25: 282298. Vayer JS, Ten Eyck RP, Cowan ML (1986) New concepts in triage. Annals of Emergency Medicine 15: 927930.
TATTOOS, MEDICO-LEGAL SIGNIFICANCE

N E I Langlois and D Little, Westmead Hospital, Wentworthville, NSW, Australia
Tattoos can be categorized into: (1) flat; (2) traditional; and (3) fine-line. The images used in the figures in this article are illustrations based on real examples.
Flat Tattoos
Background
In the past a tattoo was symbolic of commitment to a group, of strength, or of having passed a significant event in life. Now tattoos are mainly adopted as body decoration and as a means of self-expression. The word tattoo was invented by Captain Cook, around 1770, based on the Polynesian word tattaw for describing the practice of permanently decorating the skin. The process of producing a permanent tattoo requires implanting a pigment into the dermis of the skin. Usually, the tattooist will apply a stencil to the skin and the areas to be colored will be filled in using a machine that pushes the ink into the dermis using needle(s) that are vibrated up and down many times a second.
Tribal tattoos are examples of flat tattoos. These tattoos lack detail. They include the facial decoration of Maoris (Moko), or the Pea tattoos of Samoans, which are distributed from the waist to just below the knees (Figure 1). The Celtic style (Figure 2), which may include intricate line designs termed knotwork, would also be regarded as flat.
Traditional Tattoos
Traditional (and the more elaborate neotraditional)style tattoos emerged in western society in the late nineteenth century. These tattoos comprise stylized representations in thick outlines and solid blocks of color. Designs typically incorporate daggers, hearts,
264 TATTOOS, MEDICO-LEGAL SIGNIFICANCE
Figure 3 A variation on the traditional/neotraditional style of tattoo comprising a Buddha that incorporates the owners umbilicus. Figure 1 Samoan tattoo of flat design comprising solid blocks of ink, in this example covering the waist to the thighs. This is also a characteristic cultural tattoo.
Figure 4 This tattoo attempts to create the illusion that ghouls are emerging from within.
Figure 2 A Celtic cross tattoo (a commonly encountered type of flat-style tattoo).
panthers, and other symbols that traditionally have intrinsic meaning. For example, a panther symbolizes spiritual and sexual power; a skeleton in a lifelike stance represents life after death; a cobweb means the wearer killed someone; the tiger is associated with anger and cruelty. However, it is unlikely that many who wear tattoos have given thought to the underlying meaning of their chosen design. Variations on the themes of traditional or neotraditional designs may incorporate anatomical features (Figure 3) or
attempt to create illusions, such as creatures emerging from within the body (Figure 4).
Fine-line Tattoos
The Pathophysiology of Tattoos

Immediately after being made, the tattoo is crisp in appearance (Figure 7), due to the presence of the pigment in the epidermis as well as in the dermis. A weal-and-flare reaction will occur. Within a day, there is a burn-like response. Blistering does not occur, because of the puncturing of the epidermis by the needles; however, the epidermis is shed and regeneration occurs from the basal epidermis. Over the next few days, sloughing of the epidermis occurs, often as small flakes that can make the design indistinct. However, the colors are usually vibrant around this early stage. Induration will be apparent from around 57 days, with erythema around the edge of the tattoo and fine crusts of exudate on the surface, and over the needle punctures. After about 1014 days the healing process subsides. The restoration of the epidermal layer from around 2 weeks causes a slight loss of the striking color and clarity of the initial tattoo. Pigment granules persist in the dermis where they are phagocytosed by macrophages over time, resulting in a gradual diffusing and fading of the tattoo over the decades (Figure 8).
Fine-line tattoos may include detailed images (Figure 5), including portraits. A further category is the amateur, jailhouse, prison, or joint tattoo (also referred to as black and gray), which was developed by prisoners making tattoos by hand using ink, ash, or other available pigments. These tattoos are characterized by being simplistic and monochromatic. It is not uncommon to attempt humor (Figures 6A and 6B).
Medicolegal Aspects of Tattoos

Tattoos can also be classified into nonpermanent and permanent. Nonpermanent tattoos include inked stamps (Figure 9), transfers, and henna tattoos. None of these are likely to have forensic significance. However, local skin reactions may occur and application of henna to the skin has the potential of causing life-threatening hemolysis in infants with glucose6-phosphate dehydrogenase deficiency.
Figure 5 A fine-line-style tattoo these tattoos may be intricate and highly detailed.
Figure 6 (A and B) Typical, monochromatic, amateur or jailhouse type of tattoos, with attempts at humor.
Figure 7 Fresh tattoo of traditional type. Note the vibrant colors.
Figure 9 Temporary, stamped ink tattoos of the type commonly acquired on admission to events.
Figure 8 This tattoo has become blurred due to its age.
Permanent tattoos may be unintentional or intentional. Unintentional tattoos include those related to work, such as due to coal mining or working with metals. Amalgam tattoos may be seen resulting from dental work and these may even be used in the subsequently edentulous subject for identification by radiographic comparison. Dust or dirt tattoos may be seen if an abrasion from a dirty surface is inadequately debrided; for example, if a motorcyclist sustains abrasions as a result of being thrown along a road. Gunpowder tattooing may be seen in close-range firearm injuries and can be utilized to assist with estimation of range and/or angle of fire. Permanent intentional tattoos may be of forensic relevance in a number of situations. Identification may be achieved through tattoos (Figure 10),
Figure 10 The former owner of this arm, recovered from water possibly after having been mauled by a shark, was identified by the tattoos.
particularly if they have unique features. Even in blackened, decomposed bodies, tattoos may be revealed by removing the epidermis, due to the persistence of the dye in the dermis (Figure 11). However, this may be hampered by the tendency of tattoos to smudge and fade with time in the elderly this can result in obscuration of details such as names or dates that might have been included in the tattoo. Occasionally tattoos may be used to alter appearances. They can hide scars or can be used in reconstruction operations (for example, to reproduce the areolar region of the breast following mastectomy). Appearances can be cosmetically modified using tattoos
around the lips or eyebrows. Tattoos may also be used to create permanent jewelry (Figures 12A and 12B). Tattoos may be indicative of culture (Figure 13) or lifestyle: mention has been made above of characteristic tattoos of racial groups and of prison-associated
tattoos. Members of the services such as the navy or military may bear tattoos. Gang members may wear a tattoo of allegiance and symbolism to indicate status or other aspects relevant to their particular group. Illicit drug users may have tattoos that identify them as belonging to a particular group or they can use tattoos to obscure injecting sites (Figure 14). In addition to the risk of disease due to lifestyle indicated by some forms of tattoos, tattoos themselves (particularly the amateur ones) carry a risk of bloodborne infections such as hepatitis.
Tattoo Removal
Permanent tattoos may be removed by processes including dermabrasion, cryosurgery, or resection. Laser ablation utilizes focused laser light to vaporize pigment granules in the dermis. All of these techniques usually leave scarring to some degree (Figure 15A). Unwanted tattoos may also be modified (Figure 15B).
Describing Tattoos
On external examination of the body at autopsy, tattoos should be recorded. Depending on the nature of the case, this may range from noting the presence of a tattoo on an anatomical site, such as the forearm, to a detailed description (for identification purposes). A detailed description should precisely note the anatomical location; the style or type (Celtic, traditional, amateur, fine-line) and the principal components (for example, skulls, ghosts, birds, figures) with
Figure 11 Because the pigment of the tattoo resides in the dermis, in a decomposing body the detail of a tattoo may be rendered more apparent by removing the epidermis.
Figure 12 (A and B) Examples of permanent, tattooed, jewelry as enhancers of appearance.
Figure 15 (A and B) Attempts to remove tattoos usually leave scarring. Names may be changed or simply tattooed over.
Figure 13 An example of a traditional tattoo denoting membership to Indian culture.
their physical relationship to each other; the observer should also record any written details such as names or dates. Finally, any tattoo of significance should be recorded photographically.
See Also
Yakuza
Further Reading
Miller J-C (1997) The Body Art Book. New York: Berkley Books. Sperry K (1991) Tattoos and tattooing. Part I: history and methodology. American Journal of Forensic Medicine and Pathology 12: 313319. Sperry K (1992) Tattoos and tattooing. Part II: gross pathology, histopathology, medical, complications, and applications. American Journal of Forensic Medicine and Pathology 13: 717. Swift B (2004) Body art and modification. In: Rutty GN (ed.) Essentials of Autopsy Practice, pp. 159186. London: Springer.
Figure 14 A particularly imaginative intravenous drug users tattoo an indicator of lifestyle, a possible clue as to the cause of death, and a warning of possible bloodborne infection.
TERRORISM/Medico-legal Aspects 269
TERRORISM
Contents Medico-legal Aspects Nuclear and Biological Suicide Bombing, Investigation
Medico-legal Aspects
A Aggrawal, Maulana Azad Medical College, New Delhi, India
Torture
Torture as a weapon of terrorism is not often seen now, although at one time organizations such as the Irish Republican Army (IRA) resorted to this very frequently. Small groups may still want to resort to this simple but effective technique to make a political statement. Common methods of torture include beating, whipping, burning and scalding, sexual torture, electrical torture, and certain specialized procedures such as falanga (beating of the soles of feet with canes or rods), knee-capping (a technique developed by the IRA to cripple rather than kill informers; the victim is shot through the knees, from posteriorly generally), submarining (repeated dipping of the victim in foul liquid such as sewage or urine mixed with feces), and telefono (repeated slapping of the sides of the head with open palms; this ruptures the tympanic membranes and damages the inner ear). It is vital for forensic physicians and forensic pathologists to be able to distinguish signs of torture.
Introduction
Very few words today have more meanings than the word terrorism. In a 1983 study Alex Schmid compiled all the definitions, and found there were a minimum of 109. It is believed that today more than 200 definitions of this word may exist (some representative definitions are given in Table 1). Notwithstanding the definition problem, most people think that they can recognize a terrorist act when they see one. The core meaning of the term is clear to most of us, even if its exact frontiers are not. If in the name of some political or ideological cause, a bomb goes off in an aircraft, a plane is hijacked, a parliament building is attacked, a suicide bomber blows himself up in a crowded area killing innocent citizens, or an airliner is rammed into a high-rise building, most people justifiably recognize it as terrorism. In the modern era, terrorist acts manifest in a number of ways such as torture, arson, robbery, kidnapping, hostage-taking, murder, bombings, aircraft sabotage, hijacking, and the use of weapons of mass destruction (WMD) such as chemical and biological agents. Target Blue ambush slayings of police officers may also be resorted to by some groups. Police officers may be selected at random, not because of who they are, but of what they represent. However the acts which are encountered most frequently, and those in which a forensic scientist/pathologist is involved in one way or the other are bombings, aircraft sabotage, and, to some extent, use of chemical and biological agents. The term antiterrorism describes defensive measures that reduce the vulnerability of individuals and property to a terrorist incident. Counterterrorism is a proactive step describing offensive measures taken to prevent, deter, and respond to terrorism.
Terrorist Bombings
Bombing is undoubtedly the most common method employed by terrorists. Typically the bomb is left indoors in public places or placed in a vehicle (blind date bombings). From 1969 till 1983, there were at least 220 incidents of terrorist bombings worldwide, which killed 463 persons and injured an additional 2894. Since then incidents of bombings and resulting deaths have increased exponentially. In the USA, there was an increase by 400% in the bombing attempts from 1984 (803 bombing incidents) till 1993 (3163 bombings). A number of devices have been used by terrorists. These include improvised explosive devices (IED), napalm bombs, Molotov cocktails, and a number of other such devices. Napalm bombs and Molotov cocktails are basically incendiary bombs, which primarily cause burns rather than explosive effects. Napalm generates a temperature of 1100 C (1800 F), and consists of a combination of oil and gasoline in a jelly form. Phosphorus and magnesium are sometimes added to the mixture, which can raise the effective temperature as high as 2150 C (3500 F), or higher.
270 TERRORISM/Medico-legal Aspects

Table 1 Some representative definitions of terrorism and terrorist acts 1. Terrorism is premeditated, politically motivated violence perpetrated against noncombatant targets by subnational groups or clandestine state agents, usually intended to influence an audience. (US State Department) 2. Terrorism is the unlawful use of force or violence against persons or property to intimidate or coerce a government, the civilian population, or any segment thereof, in furtherance of political or social objectives. (FBI) 3. An action of violence is labeled terrorist when its psychological effects are out of proportion to its purely physical result. (Raymond Aron) 4. It is not possible to give a precise definition of terrorism or to lay down what constitutes terrorism. But . . . it may be possible to describe it as use of violence when its most important result is not merely the physical and mental damage of the victim but the prolonged psychological effect it produces or has the potential of producing on the society as a whole . . . If the object of the activity is to disturb harmony of the society or to terrorize people and the society, with a view to disturb the even tempo, tranquility of the society, and a sense of fear and insecurity is created in the minds of a section of the society or society at large, then it will, undoubtedly be held to be a terrorist act . . .. (Supreme Court of India, in Mohd. Iqbal M. Sheikh v. State of Maharashtra (1998) 4 SCC 494) 5. Terrorism is the use or threatened use of force designed to bring about political change. (Brian Jenkins) 6. Terrorism constitutes the illegitimate use of force to achieve a political objective when innocent people are targeted. (Walter Laqueur) 7. A terrorist act is an act done by using weapons and explosive substances or other methods in a manner as to cause or likely to cause death or injuries to any person or persons or loss or damage to property or disruption of essential supplies and services or by any other means necessary with intent to threaten the unity and integrity of India or to strike terror in any section of the people. (Prevention of Terrorism Act 2002 [India] ) 8. Terrorism is the premeditated, deliberate, systematic murder, mayhem, and threatening of the innocent to create fear and intimidation in order to gain a political or tactical advantage, usually to influence an audience. (James M. Poland) 9. Terrorism is the unlawful use or threat of violence against persons or property to further political or social objectives. It is usually intended to intimidate or coerce a government, individuals or groups, or to modify their behavior or politics. (US Vice-President Gores Task Force, 1986) 10. Terrorist acts are acts where they are committed intentionally by individuals or groups against one or more countries or their institutions or population in order to threaten them and seriously undermine or even destroy their political, economic or social structures. (The European Commission, September 2001) 11. Terrorist acts are criminal acts intended or calculated to provoke a state of terror in the general public, a group of persons or particular persons for political purposes. These acts are in any circumstance unjustifiable, whatever the consideration of a political, philosophical, ideological, racial, ethnic, religious or other nature that may be invoked to justify them. (United Nations General Assembly, 1996 [GA Res. 51/210], commonly referred to as the GA 1996 definition of terrorism ) 12. The intentional use of violence real or threatened against one or more noncombatants and/or those services essential for or protective of their health, resulting in adverse health effects in those immediately affected and their community, ranging from a loss of well-being or security to injury, illness, or death. (A Proposed Universal Medical and Public Health Definition of Terrorism, proposed by 21 medical specialists from 16 different countries in Prehospital and Disaster Medicine 2003; 18(2): 4752.)
The Molotov cocktail has been a favorite of guerillas and terrorists. It consists of a bottle full of gasoline and a rag which serves as a wick. The wick is lit and the bottle is thrown at the target. Various chemicals and acids may be added to this cocktail to increase its destructive potential. Letter bombs are explosive devices sent through the mail in parcels. They consist of the detonating fuse, the explosive, the electronics for initiation and the energy source. They cause injuries sometimes fatal to the unsuspecting person who opens such parcels. For a forensic pathologist investigating terrorist bombings, it is important to realize that terrorist explosions may kill or maim in a number of ways. Terrorist bombs typically are small. They are typically delivered either in suitcases or parcels, weigh in the range between 1 and 15 kg (2 and 30 lbs), or in vehicles (car bombs), weigh up to 200 kg (500 lbs). What makes them deadly is not their size, but the fact that (1) they can be hidden effectively, often at places where a large number of people congregate and (2) they are often charged with penetrating devices such
as nuts, bolts, and nails which can fly about and cause injuries, much like missiles from a gun. Blast wave generation from the bomb can also cause damage, especially to air-containing organs such as lungs, ears, and intestines; since it is the gassolid interphase where most of the blast energy is dissipated. A blast may also throw a victim about, causing him to strike surrounding objects. Conversely surrounding objects may also fly around and cause injuries to the victim. A blast is essentially an expanding hot sphere of gas generating from the high explosive contained within the bomb. It can have an initial pressure of approximately 6.895 1010 pascals (10 million PSI, 6.805 105 atm). Human beings are endangered at 6.895 105 pascals (100 PSI, 6.805 atm) or above. The destructive capacity of the blast is due to this force (known as blast loading). This pressure (or the blast load) dissipates rapidly into the surrounding medium causing in quick succession the following three phases: (1) a positive pressure phase, (2) a negative pressure phase (lasting about five to six times the duration of the positive pressure phase),
and (3) the mass movement of wind (blast wind) (Figure 1). Most of the damage is due to the positive pressure component of the blast. The negative pressure component is always much weaker than the positive pressure component, and can never be greater than 15 psi, since this would produce a perfect vacuum. The positive pressure component however can theoretically rise to any value, depending on the amount of high explosive used. Blast front is the term used to denote the leading edge of the blast wave; blast overpressure denotes the maximum positive pressure achieved during the positive pressure phase; and blast strength denotes the ratio of blast overpressure to the ambient atmospheric pressure. Blast front propagates at supersonic speeds ranging from 3000 to 8000 m s1 (speed of sound in air is 340 m s1), but it loses its pressure and velocity exponentially with the distance from the source. The pressure generated by explosions is inversely related to the cubed distance from the focus of detonation. This is the reason that terrorist bombs, even though small, are lethal at very short ranges (Tables 2 and 3).
Table 3 Some representative pressures in pounds per square inch (psi)a
1 psi
1.55 psi 2.32 psi 3 psi 5 psi
6 psi 15 psi 15 psi 30 psi 60 psi 70 psi 80 psi 100 psi 110 psi
Breaks windows (1 psi is also the pressure below 2.3 feet of water) Normal diastolic blood pressure in man Normal systolic blood pressure in man Breaks walls Lowest pressure at which rupture of the human ear drum (most vulnerable organ to pressure) can occur Pressure produced by a 70 lb high explosive at a distance of 50 ft Pressure produced by a 70 lb high explosive at a distance of 30 ft Rupture of human ear drum occurs in 50% of the cases Pressure required in the tire of an average-sized car Pressure produced by a 70 lb high explosive at a distance of 18 ft Pulmonary damage seen in 50% of the victims Lethal in 50% of cases Endangers life of a human being in almost all cases Pressure produced by a 70 lb high explosive at a distance of 14 ft
Peak
Positive pressure phase Impulse Negative pressure phase Atmospheric pressure
0 ms 5 10 15 20 Time (in ms) Point of explosion Positive and negative pressure phases in an explosion 25 30 35
a Normal atmospheric pressure at sea level is 14.7 psi (it decreases by 1 psi for every 2343 feet as we go up). All the units given above are in PSIG and not in PSIA. It is important to appreciate the difference between PSIG or pounds per square inch Gauge and PSIA pounds per square inch Absolute. PSIA = PSIG + Normal atmospheric pressure. When we fill up our car tires at, say, 30 psi, the gauge used to measure the pressure ignores the normal atmospheric pressure. This is the PSIG, i.e. the pressure as measured by gauge. This is also the pressure, as we normally understand it, in our day-today life. If we were to measure absolute pressure in our car tire, we would have to add normal atmospheric pressure (14.7 psi) to it. Thus a tire at 30 psi (PSIG), would be at 44.7 PSIA. Saying that a pressure of 15 psi causes rupture of the human drum, means that the ear drum is exposed to 15 psi of pressure over and above the normal 14.7 psi, to which it is always exposed.
Pressure
Bomb Scene Management

The aim of a forensic scientist at the bomb scene is to gather and deduce as much information as possible. The police would be interested in raising several questions about the incident. Most frequently asked questions are: 1. What were the materials used to make the explosive device? 2. Where was the bomb placed? 3. What was the level of skill or expertise of the suspect? 4. What was the intended target of the bomb? 5. Who made the bomb and who placed it? 6. Was the explosion accidental or was there criminal intent?
Figure 1 Dissipation of blast pressure into the surrounding medium.
Table 2 Exponential fall of pressure from the distance of the source of detonation (30 kg (70 lb) charge)
Distance (m (feet)) Pressure (kg cm2 (psi))
4.20 (14) 5.4 (18) 9.0 (30) 15.0 (50)
7.48 (110) 4.08 (60) 1.02 (15) 0.40 (6)
7. How was the bomb detonated? 8. Who was the victim or intended victim? Many of these questions can be successfully answered if certain foolproof protocols are employed, and evidence is collected diligently. It is frequently necessary to know if a low explosive or a high explosive was used. This information can often lead the investigation agencies to look for particular terrorist groups. A low explosive such as gunpowder burns in a matter of milliseconds and generates a pressure of about 6000 atm. A high explosive such as nitroglycerine, on the other hand, burns in only microseconds and can generate pressures up to 275 000 atm. A low explosive functions by deflagration (very rapid burning), while a high explosive functions by detonation. The burning front in a low explosive moves relatively slowly typically much slower than the speed of sound; in a high explosive, the burning front moves with supersonic speeds typically from 900 to 7500 m s1 (3000 to 25000 ft s1). Low explosives typically need some sort of confinement to produce destructive effects as in a pipe bomb; high explosives do not need such kind of confinement. Destructive effects with high explosives are much worse. The difference between a low and a high explosive has been graphically described with this simile: It is the difference between being bumped into by a pedal cyclist or being knocked for six by an express train. The first response after a bombing incident should always be to call for emergency services. Their
services include extinguishing fires, rescuing the survivors, administering first-aid, and transporting casualties to the nearest hospital. Next the bomb scene manager takes control and determines the seat of explosion, which usually can be identified by the presence of a deep crater. Fragments will be found scattered all around the seat of explosion. The distance of the farthest fragment is determined from the center of the crater. To this is added, one-half of distance, and this gives the radius of the inner cordon (Figure 2). The area inside the inner cordon may only be visited by bomb scene manager, exhibits officer, and the members of the forensic team. An outer cordon is placed outside this. The area between the inner and outer cordon is used by police teams, members of emergency services, press, etc. Falling debris, especially pieces of glass, can often pose dangers to the team working within the inner cordon, so it is essential to wear protective gear including helmets.
Collection of Physical Evidence
Physical evidence to be collected from the site of explosion includes power sources such as batteries (ranging in size from Polaroid film batteries to car batteries), timers (chemical, mechanical, and electronic), detonators and igniters, switches, circuitry (such as wires and printed circuit boards, etc.), adhesive tapes (used in the construction of several bombs; these usually survive the explosion), explosive device containers, and other bomb-making equipment such as rolls of tape, rubber gloves, and booby traps.
Inner cordon Outer cordon Working area for police/ambulance workers S = Point of explosion a = Farthest distance at which debris/fragments were detected b = 1/2 a Inner cordon at = a + b Outer cordon at = some safe/ convenient distance C
Figure 2 Sketch of explosion site with inner and outer cordons marked.
A careful examination of all this evidence would often lead the investigators towards a particular terrorist group or groups. Additionally, matching of tool marks on one or more of these objects with the tools recovered from suspects possession can greatly strengthen the prosecutions case.
Collection of Explosive Residues
Detection of Bombers Signature
Particles of explosives recovered from the bomb scene may provide valuable clues. They can often provide clues regarding probable manufacturer and the brand of explosive. If a suspect is later found, the particles recovered from the crime scene may be compared with those found in his/her possession or on the body. Low-explosive residues are best collected by mechanical vacuuming. Collection of high-explosive residues is a more complex task. This is because they burn more completely, leaving only traces, and also because of the availability of a vast variety of different formulations and physical forms. Additionally since a high explosive is likely to involve a much wider crime scene, there is much greater dilution of residues than can be expected in the case of low-explosive blasts. Vapors at the crime scene may be sampled by passing the air through adsorbent materials such as Tenax. Alternatively a portable pump may be used in conjunction with charcoal. Explosive detectors developed for aviation safety are also very useful. One of the best known is the EGIS explosives detector, a field portable instrument which can detect many high-explosive residues such as those of TNT (trinitrotoluene), RDX (Research Department Explosive), PETN (pentaerythritol tetranitrate), NG (nitroglycerine), and EGDN (ethylene glycol dinitrate). An EGIS (Equipment Gesellschaft fu r Internat Systeme GmbH) explosives detector was used in the Oklahoma City bombing investigation. Basically this instrument uses high-speed gas chromatography, coupled with highly specific chemiluminescent detection, to identify explosive compounds. When a suspect is later apprehended, there could be traces of the explosive on his person and/or on the vehicle that was used to transport the bomb. Hand swabs and fingernail scrapings are taken in the same way as of that from a shooting suspect. Isopropanol is a suitable solvent. Many high explosives such as RDX are absorbed by the skin and may be detected up to 1 week after the incident. Clothing may also present traces of explosives. Suspects premises may also contain material which may match that recovered from the scene of the bombing.
Often a terrorist group can be identified by some definitive design feature or a unique choice of materials for making bombs. This is usually referred to as the bombers signature. The unique feature could be the design of the firing circuit, an improvised explosive, a combination of components, or a particular type of target. Sometimes the identifier can be quite unique. The Unabomber in the USA always included the initials FC on an internal component of his devices. The initials were deliberately placed so that they would survive the blast and fall into the hands of the investigators. Advanced psychological profiling techniques can now help in charting the personality of the bomber.
Dealing with Human Bodies
Human bodies lying around must be handled with great care. Life may still be present in people presenting an outward appearance of death. All such persons must be examined by medical personnel. Only when death is confirmed by medical personnel, should the work of transporting the bodies to the mortuary begin. Dead bodies lying at the scene may belong to the terrorists. Hands, feet and head may have been severed from the body due to the explosion. To preserve all possible evidence and to avoid contamination both hands, feet, and head of such bodies are bagged separately in nylon bags and sealed with tape. The bodies are then transported to the mortuary.
Autopsy
The postmortem examination in terrorist deaths can conveniently be divided into five important phases, each having a distinct and specific role. These are: (1) identification of bodies and preparation of a correct total body count, (2) radiological examination, (3) collection of surface evidence, (4) collection of internal samples, and (5) documentation of injuries. Identification of individual bodies may not only be necessary for insurance claim purposes, but also to identify possible suspects among them. A proper reconstruction of the face may aid in facial identification. Clothing and other personal possessions are also useful in several cases. In addition, standard identification protocols such as hair and eye color, scars, tattoos, dactylography, odontology, anthropology, osteology, and DNA-profiling techniques aid in the correct identification. A correct body count may be done by physical matching of body parts. Sometimes just a single unaccounted body part may indicate an additional body. Finding of tissues like testis,
prostate, and uterus will indicate the sex of the individuals. In badly mangled bodies the presence or absence of Barr bodies and Davidsons bodies in the cell nuclei can indicate true sex. Cases that cannot be resolved by any means may be resolved by means of DNA profiling. Radiological examination will enable the pathologist to correctly locate and retrieve various shreds of the original explosive device which might have been lodged in the body. This can help in identifying the bombing devices and often bombers signatures. A bullet may sometimes be found in the body, which may confound the uninitiated. But it could indicate that the victim was tortured and murdered before the explosion occurred. Collection of surface evidence includes collection of traces of powder, bomb fragments, and bomb chemicals from the bodies and body fragments using standard protocols. Materials from hands should be collected by standard wiping techniques. Finding stronger concentration of bomb chemicals on the hands than on rest of the body may indicate that the person had handled the bomb just before the explosion and might have been a perpetrator of the incident rather than an innocent victim. Many bomb chemicals tend to stick to clothes for long durations, and an examination of clothing can be very rewarding. Collection of internal samples includes collection of blood, urine, vitreous humor, bile, stomach and intestinal contents for toxicology, and hair and blood for DNA profiling. Findings of street drugs like cocaine and heroin in the blood may be significant. Finally the proper documentation of injuries is a vital task of the pathologist. Not only will it establish the cause of death, but also the manner of death and the position of the victim at the time of explosion. Two factors make the deduction of the position of explosion victims possible. Firstly, the explosive force declines exponentially with distance, and is very directional. As observed earlier, the explosive force declines as the cube of the distance. Since injuries are directly proportional to the explosive force, it effectively means that the injuries sustained are inversely proportional to the victims distance from the seat of explosion. Secondly, if the seat of explosion is on, for example, the right side of a victim, because of the unidirectionality of the explosive force, his right side would be badly mutilated. The position of the victim at the time of explosion can often indicate if he was indeed the perpetrator of the crime. For instance in one case of explosion that occurred in a car, the driver had the left part
of his body totally destroyed, and his colleague (co-passenger) the right part of his body. From these facts, it could be deduced that the bomb was lying between them at the front seat, and they were probably carrying it to some predestined location. This fact immediately pointed to the fact that they could be terrorists rather than innocent victims in whose vehicle the bomb had surreptitiously been placed. In another case, when a terrorist was bending over a bomb, it went off prematurely killing him instantaneously. In such cases, although chest, abdomen, and face showed severe injuries, the umbilicus was completely spared, because during bending forward, it gets trapped in folds of skin. Six types of injuries (listed below) are seen in explosion victims.
Primary Blast Injuries
These are the injuries that occur as a result of the direct pressure effects of the blast wave on the victim. These are more severe when the blast occurs in a confined space, primarily due to repeated reflection of the blast wave. Organs most likely to suffer damage due to this are those that contain air, for example, auditory apparatus, respiratory system, and gastrointestinal system. Blast waves tend to get reflected at the airfluid interphase, and since these organs contain such a boundary, they are more liable to be injured. Three mechanisms serving to augment blast injuries are spallation, implosion, and inertial effects. The tendency for a boundary between two different density media to be disrupted when a compression wave in the denser medium is reflected at the interphase is known as spallation. Implosion refers to a violent collapse inward (as of a highly evacuated glass vessel) and is usually applied to the inward collapse of a building that is being demolished in a controlled manner. In the context of primary blast injuries, implosion refers to the forceful compression of a bubble of gas by a shock wave passing through a liquid. This compression causes the bubble to implode, the pressure within the bubble rising up to the levels of shock pressure. When the shock wave passes, this pressure is suddenly released, and the bubble explodes outwards, severely damaging the local tissue. When two adjacent objects of different densities are acted upon by the same force, they may be accelerated differently, causing them to slide against each other. This inertial effect is the classic mechanism responsible for injuries such as retinal detachments seen in terrorist bombings. The organ most sensitive to blast effects is the ear. Classic injuries seen in terrorist bombings are rupture of the tympanic membrane and damage to the
Eustachian tube, the ossicular chain, and to the organ of Corti within the cochlea. While the ear is the most sensitive organ to blast effects, injuries to the lungs are the greatest cause of mortality. Lungs would often reveal the fatal lesion
in cases of deaths. There is some controversy as to whether the shock wave passes to the lungs directly through the chest wall, or through the air via oronasal orifices. Quite probably both mechanisms work together to produce injuries. Main injuries seen are
Table 4 Some significant major terrorist acts in history

Date/Year Event Deaths
1585 1925 1946 1969 1970s 1970s May 30, 1972 Sep. 5, 1972 Jun. 27, 1976; Jul. 4, 1976 1979 Aug. 1, 1980 Oct. 23, 1983 1983 Jun. 2223, 1985 1986 1987 1987 Dec. 21, 1988 1989 1989 Feb. 23, 1993 Mar. 12, 1993 Jul. 18, 1994 Mar. 20, 1995 Apr. 19, 1995 1997 1998 Sep. 11, 2001 May 14, 2002 Oct. 12, 2002
Antwerp, Belgiuma Bombing of Cathedral in Sofia, Bulgaria Nakam attack in Germany Cu Chi, Vietnam IRA bombings, UK PLO in Israel Tel Aviv airport shootings Terrorist attack in Olympic village in Munich, Germany Hijacking of an Air France jetliner from Tel Aviv to Entebbe Airport in Uganda Arson attack on a cinema in Abadan, Iran Bologna train station, Italy Bombing of the US Marine Barracks in Beirut, Lebanon In-flight bomb explosion in Gulf Air airliner, Bahrain Bombing of Air India passenger airliner over the Irish Sea Paris bombings Bombing of South Korean airliner near the ThailandBurma border Car bomb in bus station, Sri Lanka Bombing of Pan Am flight 103 over Lockerbie, Scotland Bombing of French UTA airliner over Niger In-flight bombing of Colombian Avianca aircraft, near Bogota Bomb detonated at the underground parking garage of World Trade Center, New York Bombings in Mumbai, India (10 explosions in less than 3 h) n Mutual Israelita Argentina), Buenos Aires AMIA (Asociacio Tokyo subway sarin gas attack by Aum Shinri Kyo cult Bombing of federal building in Oklahoma City, Oklahoma Car bomb in Kenya, attributed to Bin Laden Massacre in Algerias Relizane province, attributed to GIA Airliners flown into World Trade Center and Pentagon buildings Indiscriminate shooting at Kaluchak, India A massive explosion from a car bomb destroys a night club at the Kuta beach resort on the tourist island of Bali in Indonesia (most probably connected to the first anniversary of the beginning of the US air strikes in Afghanistan on Oct. 7) Chechnyan rebels seize a Moscow theatre, holding 750-plus hostages Indiscriminate shooting at Akshardham temple, Gujrat, India Car bomb explodes outside Marriott Hotel On this Black Monday, two bombs exploded in Mumbai, India. The first one at about 1 PM at the Gateway of India, and the second shortly thereafter at Zaveri Bazaar A female suicide bomber detonates herself inside a crowded train in Southern Russia (near the war-torn region of Chechnya). The morning train from Mineralnye Vody to Essentuki was crowded with students, workers and shoppers headed for a local market at 8 AM. The explosives were packed in a waist-belt A series of explosions at three Madrid railway stations. Ostensibly because Spain supported US during its Iraq war. Worst terrorist event in Spain On the morning of September 1 (Wednesday), a group of militants seize some 1200 people in the main school of the city of Beslan in Russias Caucasus Republic of North Ossetia. The hostages include students, parents and teachers. Russian forces storm the school on September 3 ending the siege
1000 160 100s (?) 15 100s 100s 27 17 10 477 84 241 112 329 20 117 113 278 171 107 6 235 89 12 168 213 412 About 5000 31 202
Oct. 26, 2002 Sep. 24, 2002 Aug. 5, 2003 Aug. 25, 2003 Dec. 5, 2003 (Friday)
118 28 13 52. Injured about 150 42 (36 died on first day)
Mar. 11, 2004 Sep. 13, 2004
200 Over 300 dead, half of them children. More than twice that number are injured
a The first recorded case of terrorist bombing. Seven tons of gunpowder were detonated to destroy a bridge on the River Schelt, reportedly killing 1000 soldiers. Sources: (1) Falkenrath RA, Newman RD and Thayer BA (2001). Americas Achilles Heel: Nuclear, Biological, and Chemical Terrorism and Covert Attack, p. 47. Boston: MIT Press. (2) Frykberg ER (2002) Medical management of disasters and mass casualties from terrorist bombings: how can we cope? Journal of Trauma 53: 201212.
widespread alveolar damage, tears in the visceral pleura, pulmonary hemorrhage, atelectasis, pneumothorax, hemothorax, pneumomediastinum, and traumatic lung cysts. Air emboli are common, which can be due to traumatic alveolarvenous fistulae. Subcutaneous emphysema and chest wall damage, including injuries to the ribs, are also seen. The blast wave causes rapid expansion of the hollow organs within the abdomen such as stomach and intestines. This can cause gastrointestinal hemorrhage, especially in the lower small intestines or the cecum where gas content is greater. Other abdominal injuries are intestinal perforation, especially at the ileocecal junction, retroperitoneal hemorrhage, and injuries to solid organs. Injuries to the cardiovascular system include myocardial contusion, myocardial laceration, coronary artery air embolism, and hemorrhage. Injuries to the central nervous system include concussion and various forms of intracerebral hemorrhage.
Secondary Blast Injuries
Explosive Injury
Typical injury seen in this category is the dust tattooing, which occurs due to small particles of dust entering the subcutaneous tissues.
Complete Disruption
If the victim is seated over or in very close proximity to the explosive device, his body would be completely disrupted. The individual body parts are thrown wide apart. These are the bodies that are the most difficult to identify.
Current Trends
Although terrorist bombings still remain the most common form of terrorism, new forms of terrorism have emerged in the twenty-first century. The beginnings of this century saw airplanes being used as missiles against tall buildings. Bioterrorism, nuclear terrorism, hijacking, and aircraft sabotage are other forms which forensic pathologists may have to face in the future. Finally, Table 4 lists some of the major terrorist acts recorded to date.
These are the injuries produced by flying objects produced by the explosion. These injuries resemble classic ballistic wounds, except that the entrance wound is very irregular. Small flying objects striking the body produce the classic triad of abrasions, bruises, and puncture lacerations. This triad is very characteristic of bombings.
Tertiary and Quaternary Blast Injuries
See Also
Ballistic Trauma, Overview and Statistics; Crimescene Investigation and Examination: Collection and Chain of Evidence; Major Incident Scene Management; Identification: Prints, Finger and Palm; Injury, Fatal and Nonfatal: Explosive Injury; Mass Disasters: Principles of Identification; Torture: Physical Findings
These are produced either when the victim is actually lifted up and thrown around by the blast wind, or when some heavy piece of masonry breaks and falls upon the victim (the latter have often been called quaternary blast injuries). These injuries resemble classic blunt force injuries.
Burns
Further Reading
Beveridge A (ed.) (1998) Forensic Investigation of Explosions. London: Taylor and Francis. Hertig CA (1988) The investigation of terrorist activity. In: Palmiotto MJ (ed.) Critical Issues in Criminal Investigation, pp. 235245. Cincinnati, CT: Anderson. Hogan DE, Burstein JL (2002) Disaster Medicine. Philadelphia, PA: Williams and Wilkins. Marshall TK (1976) Deaths from explosive devices. Medicine, Science and the Law 16: 235239. Mellor SG (1992) The relationship of blast loading to death and injury from explosion. World Journal of Surgery 16: 893898. Missliwetz J, Schneider B, Oppenheim H, Wieser I (1997) Injuries due to letter bombs. Journal of Forensic Sciences 42(6): 981985. van Krieken PJ (2002) Terrorism and the International Legal Order. The Hague: T.M.C. Asser Press.
The characteristic burns seen in explosions are flash burns. They are not due to flames, but rather due to extremely hot gases which strike the victim. Since the duration of exposure is infinitesimally small, these injuries are superficial in nature. Since the heat applied is the same, they are of uniform depth. If an object was in between the seat of explosion and the victim, it would cast its shadow, just as it would if there were a flash of lightning. Contours of the body also tend to cast their shadow over the burnt area. Areas protected by clothing are safe.
TERRORISM/Nuclear and Biological 277
Nuclear and Biological

A Aggrawal, Maulana Azad Medical College, New Delhi, India
contaminate a number of commodities, such as public drinking water and foodstuffs. It could also be placed at public places, agricultural land, apartment houses, production facilities, storehouses, and transport communications. Such a device is called a simple radiologic device (SRD).
Radiation Device
Introduction
Terrorist attacks on the US World Trade Center and subsequent anthrax threats have brought the universal awareness that terrorists would not refrain from using any device, however destructive, to terrorize. In fact the more destructive and terrorizing the device, the better is the purpose of terrorists served. Two innovative devices, which could be used in the near future by terrorists are nuclear bombs and microorganisms and their toxins.
Nuclear Terrorism
Nuclear terrorism is defined as the illegitimate use of radioactive material in any of its several forms to produce maximum disruption, panic, injury, and fear in the general population. Terrorists need not acquire an actual nuclear bomb to terrorize people. There are a number of different scenarios, with or without nuclear bombs, where terrorists can cause panic among general public.
Violation of Safe Operation of Nuclear Facilities
Brachytherapy sources, radiation oncology teletherapy devices, an industrial radiography source, an X-ray machine, or perhaps even a discarded medical irradiator could be misused for terrorist purposes. These devices could be hidden at public sites, causing radiation exposure for an unsuspecting public. Recently, 16 brachytherapy sources of 137Cs have been stolen from a hospital in North Carolina, and in Florida an industrial radiography source of 192Ir was stolen. None of these sources have been found to date. These devices may not cause much harm, but can create untold panic amongst the public, which is the main aim of terrorists.
Nuclear Material Theft and/or Nuclear Hoax
Theft of nuclear materials such as fissile 235Ur, or weapons-grade plutonium can in itself cause panic among people, without terrorists ever having to use them. After a nuclear threat, the terrorists can simply use nuclear hoaxes.
Radionuclide Dispersal Device (RDD) or a Dirty Bomb
This is perhaps the simplest terrorist scenario involving nuclear and radiation terrorism. A legitimate employee of a nuclear power plant, sympathetic to the terrorists cause, simply violates norms regarding the safe operation of nuclear facilities, resulting in release of radioactivity.
Radioactive Contamination
This is another simple terrorist scenario involving nuclear terrorism. Today radioactive elements are used for a number of legitimate purposes. These include nuclear power and engineering, metallurgy, geology, mining, meteorology, chemical and petroleum industries, medicine, and agriculture. Among others, 60 Co is used to irradiate food to kill pathogens and in cancer treatment, 137Ce in medical and scientific equipment, 241Am in smoke detectors and engineering gauges that measure moisture content in asphalt, tritium for emergency-exit signs that glow in the dark, 192 Ir in cameras that detect flaws in concrete and welding, and 63Ni for chemical analysis. Almost all countries have these radioactive elements, and these can potentially be acquired very easily. Once radioactive material is acquired, it could be used to
Radioactive material, such as 137Ce, 131I, 32P, and 67Ga, could be mixed with a conventional explosive. The resultant explosion would scatter radioactive material in the surrounding atmosphere, resulting in general panic. An attack on radioactive material in transit, such as crashing a bomb-laden truck, would have the same consequences.
Nuclear Plant Sabotage
There are 440 nuclear power reactors around the world today, and all of them are highly vulnerable to an attack similar to those launched on September 11, 2001. Most modern reactors are designed to withstand earthquakes, hurricanes, and impacts of a small plane. They have several concrete and steel barriers, yet crashing a large plane at high speed into a reactor could cause severe damage. This can trigger either a full-scale nuclear explosion or certainly a disaster like the one that occurred in Chernobyl. There is some evidence that United Airlines 93, traveling between Newark and San Francisco on September 11, 2001, but that crashed in rural Pennsylvania, may have been
278 TERRORISM/Nuclear and Biological
targeted at one of the three nuclear reactors in the south of the state, namely Three Mile Island, Peach Bottom, or Hope Creek, Salem.
Improvised Nuclear Device (IND)
of the radioactive material to be dispersed in the surrounding atmosphere. It would thus be a hybrid between a true RDD and a true nuclear weapon.
Tactical Nuclear Weapon
This is the so-called homemade nuclear bomb. It could perhaps be a suitcase-sized bomb, and one in which there would be real conversion of nuclear energy into blast, shock, and heat. The terrorists would need extensive technical capability to make this kind of device, but help from rogue nations could make their task easier. The yield would however be much less than that of the actual nuclear device, causing most
This is a true nuclear bomb having a yield ranging from 0.5 to 50 kT (Hiroshima and Nagasaki bombs had yields of 15 and 21 kT respectively; Tables 15 and Figure 1). Tactical nuclear weapons could be as small as a suitcase. It would be well nigh impossible for terrorists to construct such a bomb on their own, but stealing or illegal trading of an already made bomb from regular nuclear nations cannot be ruled
Table 1 Nuclear terrorism basic facts
Uranium, radioactive in all its isotopes, naturally consists of a mixture of uranium-238 (99.27%, 4 510 million-year half-life), uranium235 (0.72%, 713 million-year half-life), and uranium-234 (0.006%, 247 000-year half-life)
Fission occurs with slow neutrons in the relatively rare isotope uranium-235 (the only naturally occurring fissile material), which must
be separated from the plentiful isotope uranium-238 for its various uses. To make a nuclear weapon, uranium-235 must be concentrated to about 90% (from its natural state of 0.72%) After absorbing neutrons and undergoing negative beta decay, uranium-238 becomes the synthetic element plutonium, which is fissile with slow neutrons. Natural uranium can therefore be used in converter and breeder reactors, in which fission is sustained by the rare uranium-235 and plutonium is manufactured at the same time by the transmutation of uranium-238 The worlds first atomic bomb, the test bomb Trinity, tested by the USA at Alamogordo, in New Mexico on July 16, 1945, was of this type (also popularly known as a plutonium bomb). It did not kill anyone, because it was only a test bomb Fissile uranium-233 can be synthesized for use as a nuclear fuel from the nonfissile thorium isotope thorium-232, which is abundant in nature The explosive force, or yield, of a nuclear device is measured in the number of thousands of tons (kilotons) or millions of tons (megatons) of trinitrotoluene (TNT) it would take to generate an equivalently powerful blast. Fission bombs are usually measured in kilotons, while fusion bombs with yields of up to about 60 Mt have been tested Fission releases an enormous amount of energy relative to the material involved. When completely fissioned, 1 kg (2.2 lb) of uranium235 releases the energy equivalently produced by 17 kt of TNT. The test bomb Trinity had a yield of 21 kt The Hiroshima bomb was the first atomic bomb to be used in warfare. Less than 60 kg (130 lb) of uranium was used in its manufacture. It was dropped by the USA on Hiroshima, Japan, on August 6, 1945. The explosion instantly and completely devastated 10 km2 (4 square miles) of the heart of this city of 343 000 inhabitants. In addition to the injuries and fatalities, more than 67% of the citys structures were destroyed or damaged The Nagasaki bomb, made of plutonium, was dropped on August 9, 1945. Although it had a greater yield than the Hiroshima bomb, the terrain and smaller size of Nagasaki reduced the destruction of life and property; nevertheless, in addition to human losses, about 40% of the citys structures were destroyed or seriously damaged
Hiroshima bomb Nagasaki bomb
Name Weight Length Diameter Isotope used Yield Killed njured
Little Boy 4100 kg 3m 0.75 m Uranium-235 15 kt 66 000 69 000
Fat Man 4536 kg 3.5 m 1.5 m Plutonium-239 21 kt 39 000 25 000
The amount of material needed for an explosive is 510 kg of plutonium or uranium-233 or 1530 kg of highly enriched uranium, i.e.,
uranium containing 90% or more of the isotope uranium-235. Uranium enriched to as low as 20% could be used in nuclear weapons, but much more material would be required. Fissile material may be obtained by one of three routes. 1. Diversion of material from a civilian nuclear power program 2. Construction of facilities specifically designed to produce nuclear weapons material. Examples of such dedicated facilities are a small reactor to produce plutonium or an enrichment plant to yield highly enriched uranium 3. Purchase or theft of fissile material or even a complete weapon The Chernobyl accident occurred at 1.23 A.M. on April 26, 1986. Initially, the Chernobyl accident caused the deaths of 32 people. Dozens more developed serious radiation sickness. A terrorist nuclear plant meltdown scenario could have similar implications

Table 2 Nuclear terrorism some units
Unit Details
Rad
Gray (Gy) REM
Sievert (Sv)
Becquerel (Bq)
Curie (Ci)
Roentgen (R)(C kg1)
The rad is a unit used by radiologists to denote the radiation (such as X-rays) absorbed by a patient during diagnostic or therapeutic procedures. It is an acronym of radiation absorbed dose. A patient is said to have absorbed 1 rad of radiation when 1 g of his/her tissue absorbs 100 ergs of radiation energy The gray is another unit of absorbed radiation (named after the twentieth-century British radiobiologist Louis Harold Gray). It is equal to 100 rads Rem is an acronym for radiation equivalent in man. The biological effect of radiation in man depends not upon the radiation absorbed dose but on rem. This is because different types of radiations (such as X-rays, gamma-rays, low-energy beta particles, neutrons, and alpha particles) have different damaging potentials or quality factors For all radiations used in diagnostic nuclear medicine, the quality factors are roughly equal to one. Thus in clinical practice Rads and rems are equal and are used quite interchangeably, although they are different quantities. Table 3 enumerates the biological effects of radiation in terms of rads of X-rays, which in effect are equal to rems The rem has largely been superseded by the sievert (Sv) in the SI system of units. 1 rem is equivalent to 0.01 Sv (100 rem 1 Sv). 1 rem is also equal to 10 mSv. Table 4 gives some common day-to-day events and the corresponding exposure level in rems The becquerel is a unit of quantity of radioactive material, and not of the radiation emitted by that material. One becquerel is that quantity of radioactive material in which one disintegration (or other nuclear transformation) occurs per second. 1 Bq 2.703 1011 Ci. Larger units such as thousand-becquerels (kBq), million-becquerels (MBq) or even billion-becquerels (GBq) are often used The curie is also a unit of quantity of radioactive material. It is equal to that quantity of radioactive material in which 37 billion disintegrations occur every second. It is the radioactivity associated with the quantity of radon in equilibrium with 1 g of radium. 1 Ci 3.7 1010 Bq The roentgen is a unit of radiation intensity. 1 R is the intensity of radiation that would produce 2.58 104 coulombs of electric charge in 1 kg of dry air around it. It is also equal to the intensity that would create 2.08 109 ion pairs in a cubic centimeter of air, i.e., 1 R 2.08 109 ion pairs per cm3. 1 rem is approximately equal to 1 R of 200-kV X-radiation. For most medical purposes, 1 rad 1 rem 1 R
Table 3 The biological effects of radiation in terms of rads of X-rays

Rads (of X-rays) Effects
0.5 1 10 25 50 75 100 300 500 600
800 1000 1500 2000 3000 5000 10 000
Average background radiation Radiation absorbed by a patient during one computed tomography scan of head, or after 80 X-rays. Considered safe by most radiation biologists Possible increase in cancer and birth defects Hematopoietic depression tends to appear Increased cancer. Severe fetal damage Changes begin to occur in hair follicles Symptoms of radiation sickness start (nausea, vomiting, and diarrhea) Hair epilation occurs 50% of exposed persons would die within 60 days from marrow damage Erythema. Hematopoietic depression is maximized. Gastrointestinal tract threshold begins with a significant inflammatory response, culminating in desquamation of the gastrointestinal epithelial lining. This interferes with nutrition and may cause life-threatening bacterial invasion Prognosis is poor in patients who have acute whole-body exposures greater than this Dry desquamation of skin. Death within 7 days from gastrointestinal damage Entire gastrointestinal epithelium is desquamated Wet desquamation of skin Radionecrosis of deep tissue Death within 48 h from central nervous system injury Immediate incapacitation. Death within 24 h
out. J Deutch, the former director of the US Central Intelligence Authority, testified in 1996 that diversion of nuclear warheads or components had occurred in more than 100 instances. With the breakdown of
the former Soviet Union, a nuclear nation, much of the nuclear components and/or weapons may have fallen into unauthorized hands. A Russian general has stated publicly that 50100 nuclear weapons with 1 kT

Table 4 Common day-to-day events and the corresponding exposure level in rems
S. no. Exposure type Exposure level
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
11. 12. 13.
Viewing color television Sleeping next to someone Drinking water Transcontinental flight Dental x-ray Chest radiograph Background radiation Smoking CT head (nonspiral scanner) Currently accepted average annual dose allowed for radiation workers CT abdomen (nonspiral scanner) Bone scan Radiation treatment
1 mREM/yr 5 mREM/yr 5 mREM/yr 5 mREM/flight 10 mREM/film 12 mREM/film 250400 mREM/yr 280 mREM/year 1 REM 2 REM
radioactive fallout reduces by one-tenth after every 7 h and its multiples thereof. Thus, after 7 h, the radioactive fallout reduces by one-tenth; after 49 h (7 7) by another tenth; after 343 h (7 7 7) by another tenth; and so on. Sheltering for about 2 weeks would reduce the fallout to insignificant levels, and from this arises the concept of sheltering for at least 2 weeks following a nuclear detonation.
Types of Contamination
25 REM 5 REM 250300 REM
rating are unaccounted for in the former Soviet Union. The yield of a strategic nuclear weapon is typically greater than 1 MT (1000 kT).
Effects of Nuclear Weapons

After a nuclear blast, almost half of the total energy (50%) is released in the form of blast and shock, 35% in the form of heat, 5% in the form of an initial nuclear radiation, and 10% in the form of residual nuclear radiation. This percentage is constant and does not increase with weapon yield (unlike the blast and thermal effects). If a 1 kT nuclear weapon were to detonate, the blast and thermal effects would reach 360 m, and nuclear radiation would reach 800 m. Immediate radiation is in the form of alpha, beta, and gamma radiations and neutron radiation. Residual nuclear radiation can be subdivided into two types: induced radiation and fallout. Induced radiation, also known as neutron-induced gamma activity, is produced when certain materials are bombarded with neutrons. In biologic systems, the most important element to undergo this kind of change is the body sodium, which becomes 24 Na (half-life, 15 h). Fallout is the falling-off on earth of the various fission products that are produced during nuclear detonation. Radioactive residues that fall within the first 24 h comprise the early fallout. Residues falling after 24 h are classified under late or delayed fallout. Radioactive elements lingering in the atmosphere may cause an additional source of radiation in the form of cloud shine. Early and late fallouts are potential sources of radiation hazards.
Rule of Seven
Following a nuclear terrorism event, human bodies would suffer from three types of contamination: (1) irradiation; (2) external contamination; and (3) internal contamination. X-rays, gamma-rays, and neutrons can pass through human flesh; therefore, they will mainly cause the first type of contamination, irradiation. Beta-particles may penetrate up to about 1 cm of exposed skin. Thus they also cause irradiation. Alpha-particles (consisting of two protons and two neutrons) are massive. They only travel for a few centimeters in air and do not penetrate the epidermis of the skin. They are even stopped by ordinary paper (Figure 2). Ordinary clothing worn by people would be enough to stop alpha radiation. Alpha-particles can settle on clothes and skin, and cause external contamination. After a nuclear terrorist event, it is advisable to take a shower and to discard all clothing worn at the time of disaster. Alpha-particles can also contaminate open wounds, which may be common in any nuclear event, and hence become internalized, causing internal contamination. They can also be inhaled or ingested through contaminated foodstuffs, causing further internal contamination.
Acute Radiation Syndrome

In a nuclear event involving terrorism, how much radiation would be lethal to human beings? Almost everyone would perish within about 7 days if exposed to 10 Gy (1000 rads). Higher doses would kill much sooner. Whole-body exposure of 100 Gy or 10 000 rads would kill within 24 h, but local exposures of much greater amounts may be tolerated.
Case Study
Reduction of radioactive fallout can roughly be calculated by the rule of seven, which states that the
On August 21, 1945, H K Daghlian, Jr. (19211945), a scientist who was involved in the Manhattan project to manufacture the first ever atomic bomb, accidentally dropped a tungsten carbide brick (from his left hand) into the center of an assembly containing 239Pu, with the result that the assembly became supercritical for a fraction of a second. Although he realized his mistake and removed the brick immediately with

Table 5 Fifty major events in the history of bioterrorism and biowarfare
No. Date Event
1.
Mythological
2.
1500 BC and earlier
3. 4. 5.
400 BC Third century BC 184 BC
6. 7. 8. 9.
27 BC to fifth century AD
c. 1000
AD
1155 1171
10. 11.
1339 1346
12.
1422
13. 14. 15.
1495 Fifteenth century 1650
16.
1683
17. 18.
1710 175467
19.
1763
20.
1785
21.
1863 (July)
22.
1870
In Indian mythology, the king of demons, Ravana, entangled the heroes Lord Rama and his brother Lakshamana with snakes a phenomenon known in the vernacular as nagapash. Lord Rama and his brother were helped by a mythological bird Garuda, an enemy of the snakes, to get rid of them Ancient tribes hurled live beehives and hornets nests into their enemy camps. The sacred text of the Maya in Central America, the Popol Vuh, described an ingenious bee boobytrap used to repel besiegers Scythian archers used their arrows after dipping them in decomposing cadavers, feces, or blood mixed with manure During the Carthaginian wars (first Carthaginian war 264241 BC, second Carthaginian war 218201 BC), the Greco-Romans deliberately contaminated food and water sources with animal carcasses Hannibal, the unorthodox Carthaginian military general, ordered earthen pots filled with deadly snakes to be thrown on to the decks of Perganum ships during their naval battle against King Eumenes II of Perganum. Hannibal won the war During the days of the Roman Empire, the Roman military would put bodies of dead animals into their enemys drinking water Mahmud of Ahazna, during the siege of Sistan in Afghanistan, ordered his men to catapult sacks of serpents into the stronghold to terrorize the defenders of the fort The German king and Holy Roman Emperor Frederick I Barbarossa (11231190) used the bodies of dead soldiers to contaminate drinking wells during the battle of Tortona Emperor Manuel of the Italian city of Ragusa deliberately delayed discussions with an invading army of Venetians (under the command of the Doge of Venice), knowing fully well that they would eventually require water from previously contaminated wells. The Venetian fleet was forced to winter at Chios, where they eventually used the contaminated water. The fleet contracted a contagious disease and was forced to return to Venice The French cast dead horses and other carrion from their war engines into the castle of Thin on the Scheldt river during its storming The attacking Tartar forces catapulted their own plague-infected cadavers into besieged Caffa, a well-fortified, Genoese-controlled port on the Crimean coast (now Feodosia, Ukraine). The inhabitants of the city are reported to have died wildly At the ineffectual siege of Carolstein, Commander Corbut had the bodies of the killed besiegers and 200 cartloads of manure thrown into the town. A great number of defenders fell victim to the resulting fever During the Naples campaign, Spanish soldiers gave the French forces wine infected with blood from leprosy patients. They were unsuccessful in transmitting leprosy The Spanish conqueror Francisco Pizarro (14751541) presented indigenous peoples of South America with variola-contaminated clothing The Polish artillery general Siemenowics suggested constructing hollow spheres, which could be filled with slobber from rabid dogs (or other substances that could poison the atmosphere and cause epidemics) and thrown in enemy camps. His idea was never put into practice Anton van Leeuwenhoek (16321723), Dutch biologist and microscopist, saw and described bacteria. This was a watershed year in the history of biological warfare, as from now onwards, there would be a conscious shift away from using large animals like snakes (e.g., Hannibal in 184 BC) to microbes (e.g., anthrax spores in 2001) Russian troops battling Swedish forces hurled the bodies of dead plague victims on to their enemies During French and Indian wars, Sir Jeffery Amherst ordered smallpox-laden blankets to be given to indigenous Indians loyal to the French. The resulting epidemic led to the loss of Fort Carillon to the English Captain Simeon Ecuyer of the Royal Americans, fearing an attack from Native Americans, acquired variola virus-contaminated blankets and handkerchiefs and distributed them to the Native Americans in a false gesture of good will (June 24). He recorded in his journal that he hoped it would have the desired effect. Several outbreaks of smallpox occurred in tribes in the Ohio region Tunisian tribes that conquered the low areas of Tunisia became infected with plague. They tried to use this calamity to their advantage by throwing clothes from these plague victims over the fortifications wall in order to infect the Christians at La Calle During the American Civil War, the Confederate army under the command of General Joseph E. Johnston drove farm animals into ponds and shot them. General William Tecumseh Sherman of the Union army had to haul the stinking carcasses out of the water, and this delayed his armys advances During the siege of Paris in the Franco-Prussian war, a French physician proposed that smallpoxinfected clothes be abandoned when the French forces retreated so that the attacking Prussian forces would become infected. However, the proposal was never put into action Continued

t0025",13,"bib",5,0,5,0,505pt,505pt,0,0> t0025 Table 5 Continued
No. Date Event
23.
1892 (February)
24.
1915
25. 26.
19171918 1925
27.
1932
28.
1941
29. 30. 31.
1942 (July) 1945 1957
32.
1966
33. 34.
1969 1970
35.
19711972
36.
1972
37.
1978 (August)
38.
1978 (September)
39.
1979
Sir Arthur Conan Doyle published The Adventure of the Speckled Band in the Strand magazine, with nine illustrations by Sidney Paget. In this story, Dr. Grimesby Roylott terrorized his stepdaughter Helen Stoner by putting snakes in her room. This is perhaps the earliest fictional story dealing with bioterrorism A German-American doctor in the USA, with the support of the Imperial German government, produced a quantity of Bacillus anthracis and Pseudomonas mallei (glanders). It was used to infect 3000 horses, mules, and cattle being sent to the Allies in Europe About 200 mules died of anthrax and glanders, probably as a result of infection by German saboteurs in Argentina Protocol for the Prohibition of the Use in War of Asphyxiating, Poisonous or Other Gases, and of Bacteriological Methods of Warfare, was signed at Geneva on June 17. It is popularly known as the 1925 Geneva Protocol The Japanese Army created Unit 731, a biological weapons research center in Beiyinhe, Manchuria, under the command of Major Ishii Shiro. In late 1937, the unit transferred to a larger facility at Ping Fan near Harbin. It continued to operate there until it was burned in 1945. During this time approximately 1000 autopsies were performed in this unit on human guinea pigs, mostly prisoners and Chinese nationals, who had been killed with aerosolized anthrax The USA started a biological warfare research program at Camp Detrick, MD, in response to a perceived German biological warfare program threat (just as their nuclear program was in response to a perceived German bomb) Major Ishii led a biological weapons expedition to Nanking, China, where he distributed chocolates filled with anthrax spores to youngsters The Japanese stockpiled an estimated 400 kg of anthrax to be used in a specially designed fragmentation bomb The UK became one of the first nations voluntarily to halt research on offensive biological weapons. It had earlier manufactured 5 million anthrax-impregnated cattle cakes and a 225-kg (500-lb) anthrax bomb. By 1942, the UK had developed strategic amounts of anthrax. Their experiments on Gruinard Island made it uninhabitable for almost four decades because of high-level anthrax contamination A Japanese research bacteriologist contaminated food with microbes, causing several outbreaks of typhoid fever and dysentery in Japanese hospitals. Over 100 people were affected, of whom four died President Nixon put a stop to all offensive biological and toxin weapons research and production by an executive order In February, in Canada, a postdoctoral student in parasitology contaminated the food of four of his roommates with Ascaris suum, a pig parasite, causing them to become seriously ill. This relatively simple method could be used by terrorists Between May 1971 and May 1972, the USA destroyed all stockpiles of biological agents and munitions in the presence of monitors. Agents destroyed included botulinum toxin, staphylococcal enterotoxin B, Venezuelan equine encephalitis virus, and bacteria such as Bacillus anthracis, Francisella tularensis, Coxiella burnetti and Brucella suis Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on Their Destruction (popularly known as Biological Weapons Convention or BWC), was signed on April 10 and ratified by more than 140 nations to date Vladimir Kostov, a Bulgarian state radio and television correspondent, and a defector to Paris, was shot in the back with a small pellet of ricin, a Centers for Disease Control category B biologic agent, on August 26. He was admitted to hospital for 12 days with a fever, from which he recovered. On September 26, exactly 1 month later, the offending metal pellet was removed from his back Georgei Markov, a 49-year-old Bulgarian defector to the UK, was shot in the back of his right thigh on September 7, with a pellet of ricin. He died 4 days later on September 11. This is the first known case of successful assassination with ricin. Both Kostov and Markov had been close to Communist President Shivkov In April and May, an outbreak of pulmonary anthrax occurred in the Soviet city of Sverdlovsk, now Yekaterinberg. It was widely believed to be due to accidental release of anthrax spores from a Russian biological weapons laboratory. The tightly regulated Communist Russian regime however continued maintaining that it was an outbreak of intestinal anthrax, resulting from contaminated black-market meat. After the dissolution of erstwhile Soviet Union, US and Russian scientists carried out a detailed study in 19921993 in Sverdlovsk, and found that it was indeed an outbreak of pulmonary anthrax due to the release of spores from a biological weapons laboratory. At least 68 civilians downwind of the release had died, and 15 farm animals had to be slaughtered. An undisclosed number of military casualties also occurred

t0025",13,"bib",5,0,5,0,505pt,505pt,0,0> t0025 Table 5 Continued
No. Date Event
40.
19741981
41. 42.
1984 (spring) 1984
43. 44. 45. 46.
1990 (June) 1990 (December) 1991 1992
47.
1995
48.
1996 (October 29 to November 1)
49. 50.
1998 2001 (October to November)
Mycotoxins were used as biological warfare agents in Southeast Asia and Afghanistan. The toxins were delivered by aerial spraying, and fell in large droplets much like rain. The color of the spray gave rise to the popular terminology yellow rain. In Laos alone, 6500 deaths were attributed to yellow rain T-2 toxin (a mycotoxin) was recovered from Iranian soldiers attacked by Iraqi weapons Members of a religious commune intentionally contaminated salad bars with Salmonella typhimurium in the Dalles, OR, USA. The idea was to keep members of the public at home, so that they couldnt come out to vote for Wasco county commissioners on November 6, 1984 (the outcome of the elections could have been against the interest of the commune). A total of 751 persons were affected Nine people in Edinburgh, Scotland, were infected with Giardia lamblia, due to intentional contamination of water supply of their apartment building Iraqis filled 100 R400 bombs with botulinum toxin, 50 with anthrax and 16 with aflatoxin. In addition, 13 SCUD warheads were filled with botulinum toxin, 10 with anthrax, and 2 with aflatoxin In January, during the war with Kuwait, Iraq deployed R400 bombs and SCUD missiles loaded with biological agents to four locations. However they were never used during the war Executives of the Aum Shinrikyo (Supreme Truth) cult in Japan, sent members to former Zaire ostensibly to treat Ebola victims, but their actual aim was to obtain Ebola virus for weapons development Larry Wayne Harris (a resident of Lancaster, OH), a lab technician and a member of the American Society for Microbiology, ordered three vials of freeze-dried Yersinia pestis from the American Type Culture Collection (ATCC). He was found to be associated with extremist groups such as Aryan Nations and the Christian Identity Church. His intentions remain unclear to this day. Harris was convicted of wire fraud (for having lied to ATCC about being associated with a fictitious research laboratory), and received a 6-month suspended sentence An outbreak of shigellosis occurred in a medical center in Texas. Twelve laboratory workers experienced severe gastrointestinal illness after eating muffins and doughnuts anonymously left in their break room between the night and morning shifts of October 29. The eatables were contaminated with the medical centers own stock culture of Shigella dysenteriae type 2. The motive and method of contamination remain unknown A report in January revealed that Iraq had sent approximately a dozen biological warfare researchers to Libya. The aim was to equip Libya with biological weapons also After the September 11, 2001 attack on the World Trade Center and the Pentagon, anthrax spores were sent by mail to unsuspecting people. About 22 cases of anthrax were reported between October 4 and November 20, of which there were at least 5 deaths. The release caused such mass hysteria that at least 10 000 individuals were advised to undergo prophylaxis
4. REMs or Sieverts (SV) [Actual biological deterioration as measured by film badge]
1. Curies (ci) [Quantity of radioactive material]
2. Roentgen (R) [Radiation intensity producing ionization in surrounding air]
3. RADs or GRAY (GY) [Absorbed radiation measured in RADs]
Figure 1 Interrelationships between various radiation units.
Alpha radiation Beta radiation Gamma and X-rays
4 ++ 2 0 1 0 0 Paper Plastic Lead Concrete
lasting 23 weeks. The latent phase may be absent if the dose is high. During the latent phase, critical cell populations such as leukocytes and platelets begin to decrease.
Illness Phase
(A)
Overt symptoms such as nausea and vomiting return. Bleeding may be particularly troublesome.
Recovery or Death Phase
Alpha radiation Beta radiation Gamma and X-rays Neutron
4 ++ 2 0 1 0 0 1 N 0
Recovery occurs if the dose is less than 500 rad. The probability of recovery is less if the dose was higher. A dose higher than 1000 rad would cause death in most cases.
(B)
Figure 2 Penetrating distances of various radiations: (A) nonliving matter; (B) living matter.
Considerations of the Dead

In any nuclear scenario involving terrorism, the forensic pathologist would have to handle a number of bodies that are contaminated with radioactive nuclides. This calls for special considerations. Contaminated bodies may not be kept in a hospital morgue, because various pathology facilities could become contaminated. A temporary morgue must be set up. A mobile chilling unit, as used in the food industry, placed strategically on the hospital grounds, may be the ideal solution. It is important to note that the requirement is a chilling unit, not a freezing unit. With freezing, some forensic evidence can be lost.
Autopsy on Radioactive Bodies
his right hand, both his hands received severe amounts of radiation. It has been estimated that his left hand, that had held the fallen brick, possibly received 500015 000 rem and the right hand, used to push the brick away, was exposed to a considerably higher dose, in the range of 20 00040 000 rem. Daghlian suffered from acute radiation sickness and died on September 15, 1945, 26 days later. A similar accident occurred with another scientist, L Slotin (19101946), on May 21, 1946. He died 9 days later on May 30. In general whole-body exposures are considered sublethal at <2 Gy (<200 rad), lethal at 210 Gy (2001000 rad), and supralethal at >10 Gy (>1000 rad). After acute exposure to radiation, most individuals suffer from acute radiation syndrome (ARS). Rapidly dividing cells are most prone to damage by radiation. These include those within the hemopoeitic system, lining cells of the gastrointestinal tract, cells within the reproductive system, and fetal cells. Signs and symptoms of ARS occur in four distinct phases, the duration and onset of which depend on the exposure dose.
Prodromal Phase
Depending on the exposure, this can commence from a few minutes to a few hours after exposure. The symptoms include nausea, vomiting, and anorexia. At higher doses, additional symptoms such as fever, prostration, respiratory problems, erythema, conjunctivitis, and increased excitability are common.
Latent Phase
Opening up the dead body would necessarily release radionuclides that had been inhaled or ingested. Shielding of the pathologist is a concern; this could be achieved by wearing a radiology lead apron (0.5 mm lead or equivalent thickness). Long-handled instruments may be helpful in keeping the extremities away from the radioactive organs. Double gloves, hair and foot covers, splashguards, and fluid-resistant long-sleeved jump suits should be used to minimize radiation risk. A problem of special concern is a cut produced during autopsy. The wound should be debrided and rinsed thoroughly to remove as much radioactivity as possible. Placing plastic-backed paper on the floor around the autopsy table would facilitate decontamination. For similar reasons autopsy instruments must be wrapped in plastic.
Processing of Radioactive Tissues
With doses of 200300 rad, the symptoms will regress within 24 days, to be followed by a latent period
If tissues are preserved for histology, it must be kept in mind that they may be radioactive. Storage of such tissues may require leaded containers, which
may be available from the radiation safety officer. During processing of such tissues, usual precautions such as minimal handling time, double-gloving, wearing of protective apparel, and use of long-handled instruments would apply.
Embalming of Radioactive Bodies
would be, who did this act? In nuclear detonations, this may not be easy or possible, since it would cause widespread destruction of the scene. In other scenarios, such as placing of radioactive materials at public places , usual crime-scene and forensic protocols must be employed.
If the deceased has to be transported to a distant location (such as, for example, to a different country), the body would need to be embalmed, and this would pose special challenges to the embalmer. Fluids should be removed by means of a trocar and tubing in such a manner that the embalmer is not required to hold either item or be close to the body while the fluid is draining. Urine, pleural, and ascitic fluid may be radioactive and may be drained directly into the sewage system, but only after consultation with the radiation safety officer.
Decontamination of Instruments
Bioterrorism
Bioterrorism is defined as the illegal and illegitimate use of biological organisms (e.g., animals, plants, and microorganisms, including bacteria and viruses), dead or alive, in their natural state or after genetic modification, and/or their products (e.g., blood, toxins, a physiologically active protein or peptide), to produce fear, alarm, or dread in the general public with or without illness or death.
The Lure of Bioterrorism
After the autopsy, the instruments and clothing must be cleaned and decontaminated by repeated soaking in water with detergents. Sometimes an item may need to be kept aside for radioactivity to minimize by the usual decay process. Such items must be stored in a plastic bag with proper labels (including the date the item became contaminated and level of activity), and the bag stored in a remote location.
Disposal of Radioactive Bodies
Contaminated bodies must not be cremated, because nuclear material cannot be destroyed by fire. Cremating such bodies can actually disseminate radioactive material in the environment along with the fumes. In internally contaminated bodies (where radionuclides have entered the body through inhalation or ingestion), cremation may facilitate dispersal of radioactive nuclides in the environment. In addition, cremation would produce contaminated ash, which will again pose problems of disposal. Burial may be the ideal solution, but can cause problems if the religion of the deceased does not allow this. Counseling of a deceaseds relatives and of the relevant religious heads must be attempted.
Why would terrorists choose bioterrorism at all? Primarily, because it is cheap. Only about $10 000 worth of equipment and a 5 5 m room are needed. Furthermore, to produce mass casualties (killing greater than 50% of people in an area), terrorists would need to spend $2000 per km2 if they used conventional weapons, $800 if they used nuclear weapons, $600 if they used chemical weapons, and just $1 if they used biological weapons. Alternatively, using the same monetary resources, terrorists could inflict mass casualties in an area 2000 times larger if they chose to use biological weapons instead of conventional weapons such as bombs. Another lure of bioterrorism is that its onset is very insidious, and it can often be confused with a natural event. A chemical or a nuclear calamity would automatically imply an intentional attack by someone, most probably a terrorist group, but a sudden onset of, say, plague may not arouse any suspicion for quite some time. In addition, a bioterrorism event could be self-perpetuating because of contagiousness (Table 6).
Bioterrorism Agents
Forensic Considerations
Clues that could be suggestive of possible radiological or nuclear activity include the presence of unusual material that seems to emit heat with no sign of any external heat source and the presence of glowing or luminescent material or particles. Understandably the most important forensic question in such scenarios
It fairly soon became obvious to nations engaged in biowarfare research that, of the thousands of microbial agents found in nature, only 20 could survive long enough in the environment to be inhaled by their unsuspecting victims. These 20 agents were the most likely agents to be used in biowarfare programs. The Centers for Disease Control and Prevention (CDC) at Atlanta classifies the potential bioterrorism agents into three categories A, B, and C depending on several key factors (Table 7, Figure 3).
286 TERRORISM/Nuclear and Biological Category A Agents
Category A organisms are the most dangerous bioterrorism agents, as can be seen in Table 8. They can be deadly in extremely low doses (Figures 46).
Category B and Category C Agents
to disseminate. A listing of these agents is given in Table 7.
Forensic Considerations
It is very important to tell a bioterrorism event from a natural disease outbreak. Some indications that may arouse suspicion are: (1) the presence of an
These are less likely to be used by terrorists in view of their lower mortality rates. They are also less easy
Table 6 Why bioterrorism is an attractive option for terrorists 1. Cheaper, per casualty. Has been called the poor mans atomic bomb 2. More effective, delivery methods simpler 3. High mortality (in Ebola, as high as 90%) 4. Deployment silent, insidious onset, incubation periods make perpetrators difficult to identify 5. Contagious, exponential spread by asymptomatic and undiagnosed carriers, casualties may multiply rapidly if prompt action not taken 6. Humans no more immunized against some agents such as smallpox 7. Genetic manipulation of microorganisms can create novel forms, which could be virtually invincible 8. Mere mention of certain diseases such as smallpox, anthrax or plague cause terror in people
Figure 3 Rash on the face and body in smallpox. Courtesy of WHO.
Table 7 The critical bioterrorism agents according to CDC, Atlanta (http://www.bt.cdc.gov/agent/agentlistcategory.asp)

Category Description Agents
Category A
Category B
These are the high-priority agents and include organisms that pose a risk to national security because they: 1. can be easily disseminated or transmitted from person to person; 2. result in high mortality rates and have the potential for major public health impact; 3. might cause public panic and social disruption; and 4. require special action for public health preparedness The second-highest priority agents include agents that: 1. are moderately easy to disseminate; 2. result in moderate morbidity rates and low mortality rates; and 3. require specific enhancements of CDCs diagnostic capacity and enhanced disease surveillance
1. 2. 3. 4. 5. 6.
Variola major (smallpox) Bacillus anthracis (anthrax) Yersinia pestis (plague) Clostridium botulinum neurotoxins (botulism) Francisella tularensis (tularemia) Viral hemorrhagic fevers (filoviruses [e.g., Ebola, Marburg] and arenaviruses [e.g., Lassa, Machupo])
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 1. 2. 3. 4. 5. 6.
Coxiella burnetti (Q-fever) Brucella spp. (brucellosis) Burkholderia mallei (glanders) Burkholderia pseudomallei (Melioidosis) Chlamydia psittaci (Psittacosis) Rickettsia prowazekii (Typhus fever)
Category C
Emerging pathogens that could be engineered for mass dissemination in the future because of: 1. Availability; 2. Ease of production and dissemination; and 3. Potential for high morbidity and mortality and major public health impact
Alphaviruses: VEE, EEE, WEE (Venezuelan, Eastern, and Western encephalitis) Food safety threats (e.g., Salmonella species, Escherichia coli O157:H7, Shigella) Water safety threats (e.g., Vibrio cholerae, Cryptosporidium parvum ) Ricin toxin from Ricinus communis (castor beans) Epsilon toxin from Clostridium perfringens Staphylococcal enterotoxin B Nipah virus Hantaviruses Tick borne hemorrhagic fever viruses Tick borne encephalitis viruses Yellow fever virus Multidrug-resistant Mycobacterium tuberculosis

Table 8 Category A bioterrorism agents and their infectivity
Estimated infective dose (as in an aerosol)
S. no.
Microorganism Variola major
Illness caused
Incubation period
Major symptoms
Fatality rate
1.
Smallpox
10100 organisms
Classically described as between 717 days. Could be upto 19 days or possibly longer
2.
Bacillus anthracis
Anthrax
800050 000 spores
15 days
3.
Yersinia pestis
Plague
100500 organisms
23 days
4.
Clostridium botulinum
Botulism
0.001 microgram/ kg of body weight 1050 microorganisms
15 days
Illness begins with 23 days of high fever. Pox lesions, which are initially macular, but go on to become papular and then pustular. Scabs form in 89 days, and separate in 14 days, leaving a permanent hypopigmented scar Three main forms: 1. Cutaneous anthrax: Most common form, representing 95% of all cases. Skin shows the classic leathery, depressed, painless black eschar that falls off within 12 wk 2. Gastrointestinal anthrax: Nausea, vomiting, fever, severe abdominal pain, hematemesis, hematochezia, melena, and/or ascites 3. Inhalational anthrax: Dyspnea, chest pain, nonspecific influenza-like symptoms such as fever, chills, diaphoresis and headache Three main forms: 1. Bubonic plague accounting for over 75% of cases show tender lymph nodes (buboes) 2. Septicaemic plague shows hypotension and multiorgan dysfunction 3. Pneumonic plague shows predominantly respiratory symptoms such as cough, hemoptysis and chest pain Weakness, dry mouth, hypotension, gastrointestinal distress, paraesthesias Mainly six clinical forms: pulmonary, glandular, ulceroglandular, oculoglandular, oropharyngeal, and typhoidal. However, the most important clinical manifestation of intentionally released tularemia is the appearance of pneumonia Fever, rash, jaundice, shock
30%
8090%
Without antibiotic treatment, very high
5.
Francisella tularensis
Tularemia
210 days
Without antibiotic treatment, very high Variable
6.
Hemorrhagic fever viruses
Hemorrhagic fevers (viral)
110 organisms
421 days
Variable
Figure 4 Man infected by Bacillus anthracis. Courtesy of WHO, Eric Miller.
Figure 5 Microscope photograph of spores and vegetative cells of anthrax bacterium Bacillus anthracis. Courtesy of WHO, Eric Miller.
unusual number or cluster of illnesses; (2) abandoned spray devices; (3) atypical clinical presentation (e.g., a case of inhalational anthrax when cutaneous anthrax would be much more common); (4) confinement of an illness to a limited geographical area; (5) presence of dead fish or birds, which cannot be otherwise accounted for; (6) occurrence of a disease in an unusual season (e.g., Q fever usually occurs in the spring when sheep are born; a case of Q fever in winter should arouse suspicion); (7) incidents being concurrent with other terrorist activities (the occurrence of anthrax attacks immediately after the US World Trade Center attacks, for example);
Figure 6 The lesion of cutaneous anthrax: (A) hospital day 5; (B) hospital day 12; and (C) 2 months after discharge. Courtesy of Journal of American Medical Association and W. Bockowsky (2002) 287: 869874.
(8) illnesses with predominantly respiratory symptoms, fever, or gastrointestinal complaints; (9) unusual swarms of insects; and (10) unusual antibiotic resistance patterns.
Conclusion
The capacity to wage nuclear or biowarfare terrorism is available to nations and to others wishing to misuse them. The need for vigilance and an understanding of
TERRORISM/Suicide Bombing, Investigation 289
the theoretical issues behind them and the practical implication of such modes of attack has never been higher.
Suicide Bombing, Investigation

A Aggrawal, Maulana Azad Medical College, New Delhi, India M Tsokos, University of Hamburg, Hamburg, Germany
See Also
Terrorism: Medico-legal Aspects; Suicide Bombing, Investigation
Further Reading
Atlas RM (2002) Bioterrorism: from threat to reality. In: Ornston LN, Balows A, Gottesman S (eds.) Annual Reviews of Microbiology, vol. 56, pp. 167185. Palo, Alto, CA: Annual Reviews. Cameron G (2000) Nuclear terrorism reconsidered. Current History 99: 154157. Classic KL (2002) Autopsy of bodies containing radioactive materials. In: Ludwig J (ed.) Handbook of Autopsy Practice, pp. 123127. Totowa, NJ: Humana Press. Darling RG, Mothershead JL, Waeckerle JF, Eitzen EM (2002) Bioterrorism. Emergency Medicine Clinics of North America 20: 255535. Doyle RJ, Lee NC (1986) Microbes, warfare, religion, and human institutions. Canadian Journal of Microbiology 32: 193200. Falkenrath RA, Newman RD, Thayer BA (2001) Americas Achilles Heel Nuclear, Biological and Chemical Terrorism and Covert Attack. Cambridge, MA: MIT Press. Fong Jr., FH (2002) Nuclear detonations: evaluations and response. In: Hogan DE, Burstein JL (eds.) Disaster Medicine, pp. 317339. Lippincott/Williams & Wilkins. Greenfield RA, Bronze MS (eds.) (2002) Symposium: bioterrorism. American Journal of Medical Science 323: 289357. Helfand I, Forrow L, Tiwari J (2002) Nuclear terrorism. British Medical Journal 324: 356358. Lederberg J (ed.) (2000) Biological Weapons Limiting the Threat. Cambridge, MA: MIT Press. Leikin JB, McFee RB, Walter FG, Edsall K (2003) A primer for nuclear terrorism. Disease Monthly 49: 485516. Lesho E, Dorsey D, Bunner D (1998) Feces, dead horses, and fleas evolution of the hostile use of biological agents. Western Journal of Medicine 168: 512516. Mayor A (2003) Greek Fire, Poison Arrows and Scorpion Bombs Biological and Chemical Warfare in the Ancient World. New York, NY: Overlook Press, Peter Mayer. Robertson AG, Robertson LJ (1995) From asps to allegations: biological warfare in history. Military Medicine 160: 369372. Roy MJ (ed.) (2003) Physicians Guide to Terrorist Attack. Totowa, NJ: Humana Press.
Introduction
Injuries or deaths from explosions due to bombing have generally only been occasionally encountered in clinical and forensic pathological practice. However, with the recent rise in militant terrorism, there has been an increase in the incidence of terrorist bombings, and the forensic pathologist or medical examiner is likely to be confronted with such cases. Suicidal terrorism in one form or other has existed for years. It has been used by the Jewish sect of Zealots in Roman-occupied Judaea and by the Islamic Order of Assassins (hashashin) during the early Christian crusades. During World War II, the Japanese crashed explosive-laden warplanes on American ships, popularly known as kamikaze (divine wind). About 2000 of these suicide bombers rammed fully fueled fighter planes into more than 300 American ships in April 1945, in the Battle of Okinawa. About 5000 Americans were killed in those suicidal attacks. This has been the most costly naval battle in US history. More recently, suicidal bombing has been used increasingly to make a political statement e.g., on 21 May 1991, Rajiv Gandhi, former Prime Minister of India, and 16 others were killed by a female suicide bomber at Sriperumbudur, near Chennai. In general, deaths by bombings can be classified as (1) suicidal, (2) homicidal, (3) accidental, and (4) suicidal-homicidal (terrorist). In suicidal bombings, the main intention of the bomber is to kill himself or herself. The bomber takes care to choose an isolated spot, such as the interior of his/her own house, as he/she is not interested in injuring anyone else. Homicidal bombing is represented by cases where vehicles loaded with explosives are left at crowded places. Accidental explosions can occur in several situations such as bursting of gas tanks or when fire is kindled in areas where explosives are stored. Finally, suicidalhomicidal (terrorist) bombings are those where an individual either straps explosives on his/her body and detonates it in crowded places, or rams an explosive-laden vehicle into a crowd of people or into a building. An individual who straps explosives on his/her body may be referred to as a strapped
290 TERRORISM/Suicide Bombing, Investigation
human bomb (SHB). When he/she drives an explosive-laden vehicle into crowds, it is termed a vehicular human bomb (VHB). This article focuses on suicidal and suicidalhomicidal (terrorist) bombings. Among these, it is usually the latter situation, which merits more public attention. However, investigative procedures at the scene of explosion as well as autopsy findings are comparable. While in suicidal bombings, circumstantial findings reveal much information (e.g., death of a single person, isolated spot chosen, previous history of suicidal intention, or earlier suicide attempts), it is the suicidal-homicidal bombing that stretches the forensic pathologists and crime investigators skills to its maximum. In such cases, the forensic pathologist or medical examiner, as well as other investigative authorities involved must identify: the actual suicidal bomber among the casualties, the type and source of explosive devices and ignition systems used, the affiliation of the suicidal bomber to a particular terrorist group, and several other similar questions. Above all, the forensic pathologist and investigator teams may be required to reconstruct the sequence of events.
as 2,4,6-trinitrotoluene (TNT), black powder (potassium nitrate, sulfur, charcoal), liquid gasoline, or natural gas. The potential energy release of chemical explosives depends on the rate of decomposition, which in turn is determined by the chemical compounds used for the explosive; for example black powder has a lower rate of decomposition than TNT, which detonates at much higher speeds. Dispersed fragmentation is the mechanism primarily intended to kill persons in the vicinity of the explosion epicenter. Small metal objects, such as nails, screws, balls, or bearings, also form an integral part of the explosive device. With the blast wave (a radially propagating shock wave resulting from the explosion), these missiles scatter all over the surrounding environment and act like a spray of bullets. Many devices have a backup trigger system, such as an electronic timer, pager, or booby-trap type switch. If the attacker is killed, apprehended, or has to abort the attack by any other reason, a secondary trigger system then provides an alternative ignition.
Scene Investigation
In explosion-related fatalities, it is important to conduct inquiry by a team consisting of police investigators, bomb experts, and forensic pathologists. A terrorist attack should be initially suspected in each case of suicide involving explosives. Apart from death scene investigation, autopsy findings, and technical reconstruction of the explosive device, and the analysis of explosive residues using gas chromatographymass spectrometry, scanning electron microscopy, and stereomicroscopy, the history of the victim may give additional hints about the the mode of death suicide or homicide without a terrorist background. The determination whether the manner of death is suicide, homicide, or accident in such cases can present a difficult task to the investigative authorities, especially within the first ten hours following the incident. It is usually the intention of a terrorist bomber to cause as many casualties as possible, so a crowded place confined or open space is normally chosen for detonation of the explosive. Thus, the scene of suicide-homicide bombing is usually characterized by massive destruction (Figure 1). It must be kept in mind that when an initial attack has occurred, it may be followed by a (sometimes even more) powerful follow-on attack shortly thereafter, a tactic utilized in the terrorist bombing which killed over 200 in Bali, Indonesia in 2002. This second attack is timed to inflict the maximum number of casualties against the responding police, fire and emergency medical
Principles of the Design of Explosive Devices Used by Suicide-Homicide (Terrorist) Bombers

Explosives used by suicidal as well as suicidalhomicidal (terrorist) bombers are substances or devices capable of a sudden expansion of gas, which upon release of its potential energy creates a pressure wave. Based on the mechanism of energy release, explosives can be classified as chemical, mechanical, or nuclear. Chemical explosives, volatile or nonvolatile, decompose into gases upon detonation. In order to conduct a more effective investigation of a bombing incident, the forensic pathologist should at least be familiar with the basic design of bombs used by terrorists. Devices are generally concealed within an article of clothing worn close to the body such as a vest, belt, or jacket. Most bombing devices used by different terrorist organizations worldwide are mainly constructed based on similar principles, although there may be subtle differences. In general, such bombing devices consist of a simple push-button toggle switch for the ignition of the charge and the electric circuit is completed by using a simple battery. These ignition devices are relatively small in order to reduce the chances of discovery. The main explosive charge may consist of a military-grade plasticized explosive or homemade explosive mixtures. Most often used as the latter are chemical explosives such
Figure 1 Scene of suicidal-homicidal bombing with three victims lying on the floor in a totally destroyed courtroom. Massive destruction of walls, ceiling, and windows as well as debris scattered all over the floor. Bloodstains can be seen on the walls in the lower parts. Courtesy of Professor B. Madea, Institute of Legal Medicine, University of Bonn, Germany.
Figure 2 Posterior view of a bombing victim with deep lacerations and interspersed foreign body fragments on neck (A) and afa rik-University, Kos ice, Slovak Republic. occiput (B). Courtesy of Professor F. Longauer, Institute of Legal Medicine, Pavol-Jozef-S
service (EMS) responders, and gathering crowds. Thus, while EMS responders may arrive at the scene immediately to rescue the surviving injured persons, all other responding personnel and vehicles should stay clear of the immediate attack site. Gathering crowds and media personnel should be kept clear of the site. The crime scene investigators must try to locate the debris furthest from the object bombed. An inner cordon should then be placed at one-anda-half times this distance, and an outer cordon at some convenient distance outside of that. The area between the inner and outer cordon is used by police teams, members of emergency services, press, etc., while the area inside the inner cordon can only be
visited by the bomb scene manager, exhibits officers, and the members of the forensic pathologists team. As mentioned above, dispersed fragmentation is the primary killing mechanism in individual suicide bombing attacks. Fragmented components of the explosive device such as nails, or other smaller metal pieces, must therefore be looked for at the scene and on the outside as well as inside the bombing victims bodies. This will be occasionally helpful in identifying a particular terrorist group, or a particular explosives manufacturer or dealer. As with the location of burn injuries and splinter penetration (Figure 2), the location of damage to clothing is helpful in establishing the body posture
of a victim (or the attacker) at the time of the explosion. In addition, in suicidal bombings involving just one person (the suicidal), the pattern of bloodstains at the scene of explosion gives additional hints towards the reconstruction of events. It must be remembered that the scene of bombing may still contain undetonated explosives. Until the arrival of the bomb squad, no object should be touched as it may contain unexploded devices. Potential concealment areas for bombs include parked vehicles at the scene of bombing.
According to their etiology, injuries caused by explosions are traditionally classified into four categories: primary, secondary, tertiary, and quaternary blast injuries (Table 1). Primary blast injuries Injuries directly inflicted on the human body by the sudden increase in air pressure after an explosion are referred to as primary blast injuries and involve almost exclusively gas-containing internal organs such as the lungs, middle ear, and gastrointestinal tract, the organs most vulnerable to overpressure. Primary blast injuries on the external surface of the body are: scattered dermal abrasions and contusions, gross lacerations of the skin (Figure 3) that may be interspersed with foreign body material, mutilations or amputations of limbs, opening of body cavities (Figure 4), decapitation, near-total disruption of the body (Figure 5), or even complete body destruction. Primary blast injuries are estimated to contribute to 86% of fatal injuries in explosion victims. Secondary blast injuries Secondary blast injuries result from blast-energized bomb fragments and other displaced objects at the site of explosion such as glass, casing, and masonry causing splinter-induced penetrating trauma. Tertiary blast injuries Tertiary blast injuries occur when the body is accelerated from the blast wave initially and is then abruptly decelerated on rigid objects, thus resulting in a combination of blunt force and penetrating trauma. Quaternary blast injuries Quaternary blast injuries are defined as those derived due to the collapse of a
Autopsy Findings
Explosions in confined spaces are associated with more and a higher extent of severe injuries and a higher mortality rate compared with explosions that occur in open spaces, because the blast wave reflects back from the walls and the ceilings of buildings. It is usually impossible to draw any realistic conclusions from injuries sustained by the victims concerning the size of the explosive charge. Proof of air embolism is essential when the body surface is intact since air embolism is a major cause of death in blast victims. If the autopsy is not performed within a few hours after death, the differentiation between air and decomposition gases should be made with the pyrogallol test.
Gross Pathology
Appearance of external injuries based on the definition of blast injuries Instantly with the explosion, compression of air in front of the pressure wave that heats and accelerates air leads to a sudden increase in atmospheric pressue (overpressure) and temperature transmitted into the surrounding environment creating the blast wave.
Table 1 Classification of blast injuries caused by explosions according to etiology and types of injury
Category Etiology Type of injury
Primary blast injuries
(Direct) blast wave exposure
Secondary blast injuries Tertiary blast injuries
Quaternary blast injuries
Blast-energized bomb fragments and other debris (shrapnel) Abrupt deceleration of the body on rigid objects following acceleration due to (indirect) blast wave effect Collapse of a building or falling down of parts of a building where the explosion took place
Disruption of the body, traumatic amputation, gaping lacerations of the skin, rupture of gas-containing organs (e.g., ear, lungs, gastrointestinal tract), perforation of hollow organs Penetrating trauma Blunt force trauma, penetrating trauma
Miscellaneous; for the most part blunt force trauma
Figure 3 Gross laceration of the skin due to the suicidal explosion of an industrial explosive (Gelamindonarit) with superficial abrasions and bruising seen adjacent to the wounds margin.
Figure 5 Explosive-induced trauma of the upper posterior part of the trunk with decapitation and gaping lacerations of the superior parts of both thoracic cavities in a suicidal-homicidal bombing victim who was located in the immediate vicinity to the epicenter of the explosive device consisting of TNT.
Figure 4 Opening of the abdominal body cavity following the (probably accidental) explosion of a homemade pipe bomb containing black powder. Note peppering, bruising, and abrasions seen on and adjacent to the wounds margin.
Figure 6 Superficial flash burn injuries upon the skin of the anterior side of the lower parts of the trunk and more severe burns of the superior parts of the body deriving from local ignition of clothing following an accidental gas explosion.
building or parts of a building where the explosion took place. Burns Superficial flash burn injuries, together with singeing of head hair and eyebrows, derive from the enormous heat generated by the explosion (direct burns). More severe burns usually represent indirect burns that derive from local ignition of clothing. They can be differentiated from burns that result from a secondary fire at the scene of explosion by their restriction to areas of clothing of the victim (Figure 6). The clothes of the victims are possibly torn for the most part (Figure 7), depending mainly on the vicinity of the victim to the epicenter of explosion (the loss of clothing may also take place simply due to ignition).
The location of burn injuries and splinter penetration is helpful in determining the body posture of a victim (or the attacker) at the time of the explosion. Internal injuries Since, as explained above, external injuries inflicted on the human body by explosions are mediated by miscellaneous underlying mechanisms, victims usually suffer from a combination of primaryblast effects to gas-containing organs, blunt-force injuries, penetrating trauma, and burns. Internal injuries in explosion-related fatalities comprise perforation of hollow organs, such as the ear, gastrointestinal tract, and urinary bladder, in the absence of penetrating cranial or abdominal trauma. The gut may be torn off from the mesenterium.
Figure 7 Suicidal-homicidal bombing. The perpetrator is lying in a lateral position within glass, casing, and masonry displaced by the explosion. Clothing is torn off and lacerations and tissue loss of the limbs are seen. Courtesy of Professor B. Madea, Institute of Legal Medicine, University of Bonn, Germany.
Solid abdominal organs, such as the liver, kidneys, spleen, and pancreas, less frequently incur injury in the form of contusions or lacerations. In general, damage to the liver and spleen is only seen when the abdominal wall has been opened by the blast wave or secondary to penetrating trauma. In the lungs, unilateral or bilateral pneumothorax may be seen. Usually, the lungs show severe overdistension. Grossly visible lesions of the lungs are circumscribed or more confluent petechiae as well as contusion zones seen under the pleural surfaces or within the parenchyma on cut sections through the organ. These contusions may be focal, multifocal, or diffuse and are most often seen shining through the pleural surfaces adjacent to the diaphragm, medially next to the heart, and especially corresponding to protruding parts of the rib cage. Where fire fumes were inhaled, deposits of soot particles will be seen in the trachea and bronchi. Edema, mucosal bleeding, and patchy or vesicular detachment of the mucosa in the nose, mouth, pharynx, larynx, trachea, and bronchi are often indicative of an inhalation of hot gases. The nasopharynx, larynx, and trachea, comprising the upper respiratory tract, are usually involved in blast injury. Emphysematous bullae under the mucosa of the upper respiratory tract are another frequent finding in blast victims (Figure 8). Cardiac contusions, grossly manifesting as hemorrhages in the form of petechiae and hemorrhages are commonly located in the epicardium along the posterior surface of the heart next to the diaphragm and in the endocardium of the left
Figure 8 Emphysematous bullae under the mucosa of the pharynx and larynx and aspiration of soot upon the mucosa of the epiglottis and larynx in an explosion-related fatality.
ventricle. Myocardial ischemia may be caused by air emboli in survivors. The brain may undergo direct injury, such as cerebral contusion, or indirect injury such as cerebral infarction from air emboli in those victims who survive the incident.
Histopathology of Blast Lung Injury
Of the gas-containing organs, the lung is the most susceptible to primary blast effects and the extent
Figure 10 Interstitial perivascular hemorrhage showing a cufflike pattern around a larger pulmonary in human blast lung injury (25).
Recovery of Evidence from the Body
Figure 9 Blast lung injury. (A) Panoramic view of severe alveolar overdistension, enlargement of alveolar spaces, ruptures, and thinning of alveolar septae (25). (B) Close-up view of ruptures and thinning of alveolar septae (100).
of lung injury is the decisive parameter defining mortality in victims of explosions who survive in the first place. Alveolar ruptures, thinning of alveolar septae, and enlargement of alveolar spaces (Figure 9) as well as circumscribed subpleural, intraalveolar, and perivascular hemorrhages, the latter showing a cufflike pattern in the interstitial spaces around larger and smaller pulmonary vessels (Figure 10), are the main histopathologic findings in blast lung injury. Aspiration of soot is often seen in the bronchi. In addition, venous air embolism, bone marrow embolism, and pulmonary fat embolism are frequent findings. Leukostasis, an intense alveolar and interstitial edema, as well as interstitial inflammatory infiltrates can be observed in blast victims who survived the incident for a few hours.
Before undertaking the autopsy, it is essential to radiograph the whole body. This can reveal several radio-opaque and radiolucent bomb parts. Radioopaque parts usually recovered from within the body include various metallic missiles, portions of trigger mechanisms, such as screws, wires, gears, springs, and batteries. Wires may be among the most important evidences to recover, because they can often indicate the specific manufacturer. Removal of this evidence is most essential; this can sometimes be so intricately lodged in the tissue that it may even require tissue maceration. Radiolucent material may include fragments of the explosive wrapper, fragments of paraffin-coated paper (explosive cover), and other elements such as cloth, wood, cardboard, plastic, etc., used to conceal the bomb. It is essential to radiograph the survivors also, since some explosive device fragments may be lodged in their bodies. If they are operated on surgically, and some surgical specimen such as a badly mutilated limb is removed, it should also be radiographed for similar reasons. The examination of survivors should be undertaken at the earliest stage possible by individuals with forensic medical training. Finally, after all fragments have been removed, it is recommended to carry out radiography again in order to ensure that the fragments have been completely removed. Traces of explosives (burnt and unburnt) may be adhering to the body and should be recovered using a suitable solvent. Isopropranol is usually employed
to recover explosive residues, but methanol and ethanol can also be used. In some countries, certain special substances known as taggants are required by law to be added to all explosives. These taggants are small magnetic or fluorescent chips, which contain color-coded information. These taggants do not burn with the explosive, but are scattered at the scene. These can be recovered by a magnet (if they are magnetic), or by fluorescence. They can provide information regarding the manufacturer of the explosive, the year, month, and day of the manufacture, and also the batch number of the explosive.
Identification
Mass Disasters: Principles of Identification; Terrorism: Medico-legal Aspects; Nuclear and Biological; War Crimes: Pathological Investigation
Further Reading
Cooper GJ, Maynard RL, Cross NL, Hill JF (1983) Casualties from terrorist bombings. Journal of Trauma 23: 955967. Hiss J, Kahana T (1998) Suicide bombers in Israel. American Journal of Forensic Medicine and Pathology 19: 6366. Hiss J, Freund M, Motro U, Kahana T (2002) The medicolegal investigation of the El Aqsah Intifada. Israel Medical Association Journal 4: 549553. Kahana T, Freund M, Hiss J (1997) Suicidal terrorist bombings in Israel identification of human remains. Journal of Forensic Sciences 42: 260264. Laposata EA (1985) Collection of trace evidence from bombing victims at autopsy. Journal of Forensic Sciences 30: 789797. Mayorga MA (1997) The pathology of primary blast overpressure injury. Toxicology 121: 1728. Rajs J, Moberg B, Olsson JE (1987) Explosion-related deaths in Sweden: a forensic-pathologic and criminalistic study. Forensic Science International 34: 115. Shields LBE, Hunsaker DM, Hunsaker III JC, Humbert KA (2003) Nonterrorist suicidal deaths involving explosives. American Journal of Forensic Medicine and Pathology 24: 107113. Siciliano C, Costantinides F, Bernasconi P (2000) Suicide using a hand grenade. Journal of Forensic Sciences 45: 208210. Tsokos M, Paulsen F, Petri S, et al. (2003) Histologic, immunohistochemical, and ultrastructural findings in human blast lung injury. American Journal of Respiratory and Critical Care Medicine 168: 549555. Tsokos M, Tu rk EE, Madea B, et al. (2003) Pathologic features of suicidal deaths caused by explosives. American Journal of Forensic Medicine and Pathology 24: 5563.
In multiple deaths, identification of the deceased is an important task and even more important is to identify the person responsible for the attack. Usually, the body of the suicide bomber will be the worst damaged or perhaps completely disrupted. If isolated limbs are recovered, an unusually high concentration of explosive residues on hands would indicate that the person handled explosives. DNA sticking to clothes, belts, etc., may help reveal the identity of the suicide bomber. Rajiv Gandhi was assassinated by an LTTE (Liberation Tigers of Tamil Eelam) female bomber called Dhanu. In this case, the Special Investigation Team visited the scene of crime where they found parts of Dhanus dress, strips of the vest, and the belt-bomb she wore with pieces of flesh attached, two toggle switches, wires used in the bomb, and a half-burnt 9-V battery. DNA profiling of the pieces of flesh found at the spot was done, as also that found sticking to the belt. The flesh piece attached to the belt matched with the portion of the womans body found. That established convincingly the theory of the assassin being a human bomb.
See Also
Crime-scene Investigation and Examination: Collection and Chain of Evidence; Recovery of Human Remains;
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TORTURE
Contents Physical Findings Psychological Assessment
Physical Findings
D J Pounder, University of Dundee, Dundee, UK
Introduction
There is no simple definition of torture. The word is derived from the same root as distort, and originally it referred to the distortion of the human body on the rack or some other instrument. In modern law the three essential elements which constitute torture are: (1) the infliction of severe mental or physical pain or suffering; (2) the intentional or deliberate infliction of pain; and (3) the pursuit of a specific purpose, such as gaining information, punishment, or intimidation. The distinction between torture and other types of illtreatment is made on the basis of a difference in the intensity of the suffering inflicted. The severity or intensity of the suffering inflicted can be gauged by reference to its duration, physical and mental effects, the sex, age, and state of health of the victim, and the manner and method of its execution. Torture is further characterized by being a deliberate form of inhuman treatment. The purposive element of torture is recognized in the definition of torture in the 1987 United Nations Convention which states that:
the term torture means any act by which severe pain or suffering, whether physical or mental, is intentionally inflicted on a person for such purposes as obtaining from him or a third person information or a confession, punishing him for an act he or a third person has committed or is suspected of having committed, or intimidating or coercing him or a third person, or for any reason based on discrimination of any kind.
Ill-treatment that is not torture, in that it does not have sufficient intensity or purpose, will be classed as inhuman or degrading if it attains the required minimum level of severity. The assessment of the minimum level of severity is relative: it depends on all the circumstances of the case, such as the nature and context of the treatment or punishment, the duration of the treatment, its physical and mental effects, the manner and method of its execution, and in some cases, the sex, age, and state of health of the victim.
The notion of inhuman treatment covers at least treatment, which deliberately causes severe suffering, mental or physical, which in the particular situation is unjustifiable. Degrading treatment is that which arouses in its victims feelings of fear, anguish, and inferiority, capable of humiliating and debasing them. This has also been described as involving treatment which would lead to the breaking down of the physical or moral resistance of the victim, or driving the victim to act against his/her will or conscience. Relative factors such as the age and sex of the victim can have a greater impact in assessing whether treatment is degrading, in contrast to whether treatment is inhuman or torture, as the assessment of whether an individual has been subjected to degrading treatment is more subjective. It may well be sufficient that the victim is humiliated in his/her own eyes, even if not in the eyes of others. In this hierarchy of torture, inhuman treatment, and degrading treatment, it is axiomatic that all torture must be inhuman and degrading treatment, and all inhuman treatment must also be degrading. The starting point for assessing whether ill-treatment has taken place is a determination of whether or not physical force has been used at all against the detainee. Recourse to physical force, which has not been made strictly necessary by the detainees own conduct, is in principle an infringement of the prohibition of ill-treatment. The most obvious evidence of the use of physical force will be the presence of injuries or observable psychological trauma. If a detainee shows signs of injuries or ill-health, either upon release from detention or at any stage during the detention, then the burden will be on the detaining authorities to establish that the signs or symptoms are unrelated to the period or fact of detention. The burden of proof is firmly on the detaining authorities to provide a plausible account of how injuries occurred.
Torture Methods
The first global survey of torture, published by Amnesty International in 1973, showed that 72 out of 168 countries practiced torture systematically. A survey in 1997 reported torture and maltreatment in
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115 out of 215 countries. There are clear differences between regions and countries and even between police forces within countries in the frequency of the various methods of torture. Psychiatric abuse was almost unique to the Soviet Union; falanga (beatings on the sole of the feet) was frequent in Greece; shaking is practiced mostly in Israel; whipping is more frequent in the Middle East and Africa and almost unknown in Latin America; hanging by the feet or ankles is more universal than the parrots perch type of hanging which is more frequent in Brazil and Ethiopia. Soviet and Chinese techniques involved the use of solitary confinement, sleep deprivation, exposure to heat and cold, uncertainty, threats to family, starvation, offers of rewards, and the creation of a sense of hopelessness. The Israelis use prolonged sleep deprivation, blindfolding or hooding, forced prolonged maintenance of body positions that grow increasingly painful, confinement in closet-like spaces, exposure to temperature extremes, prolonged toilet and hygiene deprivation, degrading treatment, such as forcing detainees to eat and use the toilet at the same time, and verbal threats and insults. The techniques of hooding, sleep deprivation, and positional abuse, which the British employed in Northern Ireland, had also been used by them in Aden, Borneo/ Malaysia, British Cameroons, British Guiana, Brunei, Cyprus, Kenya, Malaya, Palestine, and the Persian Gulf. Torture methods have been classified into physical and psychological but this distinction is artificial, as is well seen with respect to sexual torture. The physical methods of torture challenge any possible classification because of their number and variety. The Human Rights Commissions of El Salvador and Chile listed 40 and 85 different types of torture, respectively. The most frequent methods of physical torture are beating, electrical torture, stretching, submersion in a liquid, suffocation, suspension, burning, and sexual assault. Sexual torture can be defined widely as including violence against the sexual organs, the introduction of foreign bodies into the vagina or rectum, rape and other forced sexual acts, and mental sexual assault such as forced nakedness, sexual humiliation, sexual threats, and the forced witnessing of sexual torture. Using this wide definition of sexual torture, its prevalence is very high in torture victims. Psychological methods of torture include induced exhaustion and debility through food, water, and sleep deprivation; isolation by blindfolding, hooding, and solitary confinement; threats of death and threats to the family; sensory deprivation through limitation of movement, continuous noise, and darkness or alternatively facing bright
lights; and witnessing the torture of other prisoners or family members.
Medical Examination
The physical manifestations of torture vary according to the method and its intensity, frequency, and duration, as well as the victims ability to protect him/ herself, and the physical health of the victim prior to torture. Many forms of torture produce no physical findings while some forms have very specific physical findings in the immediate aftermath or may be strongly associated with particular sequelae. Torturers may select methods of torture because they leave no physical evidence or may modify methods of torture to reduce the possibility of producing physical evidence. The role of the assessment of the physical evidence is to establish whether it is consistent or inconsistent with the history provided. Clearly in many instances an absence of physical findings will be the expected outcome of the examination of a torture survivor. Published epidemiological studies of torture may be useful in correlating regional practices of torture with individual allegations of abuse. A medical examination should be undertaken regardless of the length of time since the torture, but if it is alleged to have happened within the past 6 weeks, such an examination should be arranged urgently before acute signs fade. The history is a vital part of the examination because upon it rests the ability to match the account of the alleged abuse to the physical findings, and also to gain an idea of the psychological trauma that the victim has suffered. The history taken should include the prearrest psychosocial history, a summary overview of the detention and abuse, the circumstances of detention, conditions of detention, and methods of torture and ill-treatment. A torture survivor may have difficulty in recounting the specific details of the torture for several reasons, including fear, lack of trust in the questioner, the psychological impact of the trauma and impaired memory, protective coping mechanisms such as denial and avoidance, cultural factors, and factors during the torture itself such as blindfolding, drugging, and lapses of consciousness. The medical history should include any history of injuries sustained before the period of detention and any possible after effects. A description of acute injuries and symptoms resulting from the specific methods of abuse, and their evolution, and resolution or residual effects should be recorded. Chronic symptoms which the survivor believes were associated with the ill-treatment should also be noted.
The general examination should include the entire body surface to detect signs of generalized skin disease such as vitamin deficiency, pretorture lesions, and lesions inflicted by torture. The latter should be described by their location, shape, size, color, and surface characteristics. The documentation of scars should be carried out together with the subjects attribution of each separate one. Care should be taken to identify scars, which have been produced by tribal markings, traditional medicine, accident, or selfmutilation. Scars, while not in themselves specific, may be found in unusual locations, which conform to the description of the torture, thus corroborating the account. Otoscopy is necessary because trauma to the ears and rupture of the tympanic membrane are frequent consequences of heavy beatings. A common form of torture, known in Latin America as tele fono, is a hard slap of the palm of the hand to one or both ears, rapidly increasing pressure in the ear canal, and thus rupturing the eardrum. Prompt examination is necessary to detect these tympanic membrane ruptures less than 2 mm in diameter, which may heal within 10 days. The examination of the head and neck should include the oropharynx and gingiva. Referral for a dental examination may be appropriate in the light of the history of the torture methods. Complaints of musculoskeletal aches and pains are very common in torture survivors, and may be the result of repeated beatings, suspension, other positional torture, or the general physical environment of detention. Although nonspecific, they should be documented. The physical examination of the musculoskeletal system should include testing for mobility of joints, the spine, and the extremities. Pain with motion, contractures, strength, evidence of compartment syndrome, fractures with or without deformities, and dislocations should be noted. Radiography is the appropriate investigation for bony lesions but injuries to tendons, ligaments, and muscles are best evaluated with magnetic resonance imaging (MRI). In the acute stage, MRI can detect intramuscular hemorrhage, but since muscles usually heal completely without scarring later imaging studies can be expected to be negative. Denervated muscles and chronic compartment syndrome will be imaged as muscle fibrosis. A detailed neurological examination is necessary. Radiculopathies, other neuropathies, cranial nerve deficits, hyperalgesia, paresthesias, hyperesthesias, and changes in position and temperature sensation, motor function, gait, and coordination may all result from trauma associated with torture. Individuals who report having being suspended should be examined for evidence of brachial
plexopathy. A history of dizziness and vomiting should prompt a vestibular examination and a note of any nystagmus present.
Blunt-Force Injuries
The known methods of torture cover the entire spectrum of forms of physical trauma seen in general forensic practice and the principles applied to their documentation and interpretation are the same. Almost every torture session begins with a softening up of punching, kicking, and hitting with truncheons, rifle butts, or whatever weapons come to hand. Beatings and other forms of blunt-force trauma result in bruises, abrasions, and laceration whose overall pattern may be indicative of assault, but with generally nonspecific individual injuries. The dating of fresh injuries may establish that they occurred during the period of detention. However, beatings may be restricted to the first few days of detention so that injuries will have faded before the victim has to appear in court or is released from custody. Most blunt-force injuries heal within about 6 weeks, leaving no scars or nonspecific scars. Whips of barbed wire or thorn branches, or belts which have metal studs as well as heavy metal buckles, may leave a combination of linear scars and ragged scars where skin has been gouged out. Prolonged application of tight ligatures as a tourniquet (the garrotte of the Inquisition) may leave a circumferential linear zone of scarring around the arm or leg, typically at the wrist or ankle, an appearance that is diagnostic. More focal areas of hypo- or hyperpigmentation on the medial and lateral aspects of the wrists result from tight restraint. The tramline bruising characteristic of blows from a linear weapon with a circular crosssectional shape, such as a truncheon or a cane, may resolve to leave tramline hyperpigmented scarring. Lacerations heal as scars, and multiple depigmented, often hypertrophic, linear scars, with marginal hyperpigmentation are characteristic of whipping. The only differential diagnosis is plant dermatitis. In the north of India, in the Punjab, a torture known as ghotna involves rolling a wooden log up and down the thighs, while the log is weighted by one or two policemen standing on it. This causes exquisite pain and often unconsciousness and the victim is unable to walk for several weeks. The long-term effect is permanent pain on walking and abnormal tenderness on squeezing the quadriceps muscles. The ghotna may also be applied by placing it behind the knees and then forcibly flexing the legs over it. After this, there is permanent pain around the knee joints and tenderness in the popliteal fossae.
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Injury to the mouth and jaws may be coincidental to beatings or there may be specific use of dental torture. Facial trauma may result in temporomandibular joint syndrome with pain in the joint and limitation of lower-jaw movement. Dental torture may include breaking or extracting the teeth and the application of electric current to the teeth.
The whole length of the plantar aponeurosis may be tender on palpation. Pressure on the sole of the foot and dorsiflexion of the great toe may elicit pain. The more extreme complications described above are less often seen. In a victim of falanga, MRI is the preferred radiological examination to detect soft-tissue injury.
Suspension Falanga
Blunt-force trauma applied to the soles of the feet, or rarely to the palms of the hands or the hips, is known as falanga, or falaka, or basinado. A truncheon, rubber hose, baseball bat, or similar weapon is typically used. The resultant injuries are usually confined to the soft tissues with bruising, edema, and tissue disruption. The physical examination in the acute phase should be diagnostic. After the initial swelling and bruising have subsided there usually remains little external evidence. Sometimes, especially if a rough or jagged weapon has been used to beat the soles of the feet, there may be scarring. However, roughness, scarring, and pigmentation of the soles of the feet are often found normally in populations who habitually go barefoot or have lived in rough terrains. Fractures of the carpals, metacarpals, and phalanges can occur but are uncommon. Several complications and syndromes may occur, the most severe being closed-compartment syndrome, resulting in vascular obstruction and muscle necrosis, which may be complicated by gangrene of the distal foot or toes or fibrosis and contractures. However, permanent deformities of the feet are uncommon following falanga. Falanga may be complicated by crushed anterior foot pads and crushed heels. Disruption of these fibrofatty subcutaneous tissue pads results in loss of their cushioning effect and consequently pain on walking. The heel is no longer a firm smooth elastic pad but rather spreads under weight-bearing and on palpation feels thin with the underlying bone easily palpable. Rupture of the plantar aponeurosis results in loss of support for the arch of the foot with consequent difficulty in walking. Passive extension of the big toe may establish whether the aponeurosis has been torn. Normally the start of tension in the aponeurosis is palpable when the big toe is dorsiflexed to 20 and higher values suggest injury to the attachments of the aponeurosis. This clinical finding is rarely seen. The chronic effects of falanga are pain and difficulty on walking and survivors may be quite unable to run. In bed at night the added warmth causes burning pain deep in the calves and often as far up as the knees. The sole of the foot is tender on pressure over the metatarsal heads and squeezing the heel is abnormally painful. Suspension is a common form of torture that can produce extreme pain and leaves little, if any, visible evidence of injury. The strappado of the Inquisition now tends to be called Palestinian hanging, but the origin of this more modern terminology is obscure. For the strappado the victims hands were tied behind the back and then he was hoisted up by his wrists to a pulley on the ceiling. Weights could be attached to his legs for greater effect or he could be suddenly allowed to drop but be brought up with a sharp jerk that dislocated his arms at the shoulders. Other forms of suspension torture are the cross, with the arms tied to a horizontal bar; butchery suspension, by the wrists above the head; reverse butchery suspension, by the feet in a head-down position; and the parrots perch, with the knees flexed, the wrists tied to the ankles, and suspension by a bar passed behind the knees. The parrots perch may produce tears in the cruciate ligaments of the knees. Strappado is so painful that the victim usually loses consciousness within a few minutes and has to be revived before it is repeated. Beatings and electricshock torture are often carried out at the same time. The immediate result is total freezing of the shoulders and it may be weeks or months before the arms can be used again. Strappado and crucification can both produce brachial plexus damage because this is the shoulder region structure that is most sensitive to traction injury. In the acute period following suspension, the complications include weakness of the arms and/or the hands, pain and paresthesias, numbness, insensitivity to touch, to superficial pain, and to position, and tendon reflex loss. The intense deep-muscle pain may mask the muscle weakness. Raising the arms or lifting a weight may cause pain, numbness, or weakness, or may simply not be possible. Tears of the ligaments of the shoulder joints, dislocation of the scapulae, and muscle injury in the shoulder region may all occur. Damage to the long thoracic nerve or dislocation of the scapula may result in a winged scapula, with a prominent vertebral border of the scapula visible. Any brachial plexus injury manifests itself in motor, sensory, and reflex dysfunction. The most common finding on motor examination is asymmetrical muscle weakness more prominent distally, but
assessment may be difficult in the acute phase due to pain. With severe injuries muscle atrophy may be seen in the chronic phase. Complete loss of sensation or paresthesias along the sensory nerve pathways are common in the acute phase and, if still present after 3 weeks, then appropriate electrophysiological studies should be performed. A decrease in reflexes or a difference between the two extremities may be present. The neurological injury from brachial plexus traction in strappado results from posterior hyperextension of the arms and typically implicates the lower plexus and then the middle and upper plexus fibers. In crucification-type suspension with hyperabduction without hyperextension, it is the middle plexus fibers that are likely to be damaged first. Additionally the neurological injury is usually not the same in both arms as a result of the asymmetry of suspension. Damage to the lower plexus is reflected in weakness of the forearm and hand muscles with sensory deficiencies on the forearm and the ulnar nerve distribution on the medial aspect of the hand. Damage to the middle plexus is reflected in forearm, elbow, and finger extensor muscle weakness with weakness on pronation and radial flexion of the forearm. Sensory deficiency is of the forearm and the radial nerve distribution of the hand. Triceps reflexes may be lost. Damage to the upper plexus causes weakness of the shoulder muscles with deficiencies in abduction of the shoulder, axial rotation, and forearm pronationsupination. Sensory deficiency is in the deltoid region and may extend to the arms. The most constant long-term finding following strappado is tenderness and tension in the trapezius and scapular muscle groups, pain on raising the arms, often with limitation by pain, and especially extreme pain on internal rotation. Brachial plexus lesions, including winging of the scapulae and X-ray changes in the shoulder joints, are less common. In addition to the various forms of suspension there are many forms of positional torture, all of which restrain the victim in contorted, hyperextended, or other unnatural positions that cause severe pain and may produce injuries to ligaments, tendons, nerves, and blood vessels. Characteristically, these forms of torture leave few, if any, external marks or radiological findings despite the frequency of severe chronic disability that follows. Dependent upon the specific forced position adopted, complaints are characterized by pain in the respective region of the body and limitation of joint movement. In north India the police seat a victim on the floor, pulling the head back by the hair and with a knee in the back, while the legs are pulled apart up to 180 until the adductor muscles are torn off their origins, resulting in an audible tearing sound. This torture is given the name of cheera, which
means tearing in Punjabi. The immediate result is massive bruising in the groins. The later effects include permanent tenderness over the origin of the adductors and extreme pain on attempts at abduction of the hips with great difficulty in walking.
Burning and Electrical Torture

Burning is the method of torture that most frequently results in permanent skin changes, which can be of diagnostic value. Cigarette burns leave well-defined 510-mm circular or ovoid scars with a hyperpigmented thin indistinct margin enclosing a scar of hypopigmented tissue-paper appearance with a thickened center. Burning by the application of hot metal objects produces a branding effect, with the resultant burn reflecting the shape of the causative object. The shaped, sharply demarcated atrophic scar has a thin hyperpigmented marginal zone. Burning with a flame or a liquid, such as melted rubber from a tire, produces more irregular patterns. Any burning of dark-skinned persons may result in hypertrophic or keloid scars. Burning of the soles of the feet using lighted kerosene is a method of torture found in the Indian subcontinent. Electrical torture is carried out by attaching electrodes to the body and connecting them to a power source. The most common sites selected are the hands, feet, fingers, toes, ears, nipples, mouth, lips, and genitals. The power source may be a handcranked or gasoline generator, domestic electricity, a stun gun, a cattle prod, or any other electrical device. Since the electric current will follow the shortest route between the two electrodes the symptoms will reflect this, as all muscles along the route are tetanically contracted. Moderately high currents may lead to dislocation of the shoulder and produce lumbar and cervical radiculopathies. Electrical burn marks at the sites of application of the electrodes are usually redbrown circular lesions between 1 and 3 mm in diameter, which resolve to leave fine scars which may be hyperpigmented. Such lesions are not easily identifiable and need to be searched for carefully. When bare wires or needles have been used to apply electrical current, as in the Latin American technique of picana, there may be permanent pinpoint scars which can be identified if they are in clusters. Electrodes which have been clipped to the skin of the earlobe or scrotum may leave sharply defined scarring which is distinctive. To avoid leaving evidence of electrical burn marks, torturers may extend the electrical contact surface area through the use of water or gels. In the acute phase there may be myoglobinemia and myoglobinuria resulting from the tetanic contraction of muscles. The usefulness of skin biopsies in the
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diagnosis of the electrical burns is controversial because the histopathological changes, although specific, are not universally present and the procedure is intrusive.
negative physical examination does not rule out torture.
See Also
History of Torture; Injury, Fatal and Nonfatal: Blunt Injury; Burns and Scalds; Sexual Offenses, Adult: Injuries and Findings after Sexual Contact; Torture: Psychological Assessment
Asphyxia
Asphyxiation by a variety of methods is an increasingly common type of torture. It usually leaves no marks, produces a death experience with loss of consciousness, and recuperation is rapid. This method of torture was so widely used in Latin America that its Spanish name submarino became part of the human rights vocabulary. Wet submarino involves forcible immersion of the head into water, often contaminated with urine, feces, vomit, or other foul material. Dry submarino may be simply achieved by the use of a plastic bag placed over the head, a common practice of an antiterrorist section of the Spanish police. Other methods include forced closure of the mouth and nose, ligature pressure around the neck, or suspension by a ligature, i.e., hanging, and forced inhalation of dusts, cement, hot peppers, and other irritants.
Further Reading
Evans MD, Morgan R (1999) Preventing Torture: A Study of the European Committee for the Prevention of Torture and Inhuman or Degrading Treatment or Punishment. Oxford, UK: Clarendon Press. Mannix DP (2003) The History of Torture, Sutton History Classics. England: Sutton. Peel M, Iacopino V (eds.) (2002) The Medical Documentation of Torture. London: Greenwich Medical Media. Reidy A (2002) The Prohibition of Torture. A Guide to the Implementation of Article 3 of the European Convention on Human Rights. Human Rights Handbooks no. 6. Strasbourg, France: Council of Europe.
General Findings
Sexual torture including rape produces the range of physical findings found in rape victims in other settings. The extreme nature of the torture event is powerful enough on its own to produce mental and emotional consequences regardless of the individuals pretorture psychological status. There are clusters of symptoms and psychological reactions that have been observed and documented in torture survivors with some regularity. Since there is such a strong psychological element in the aftermath of torture, the borderline between physical and psychosomatic symptoms is certain to be blurred. There are almost universal symptoms, such as headache, and a form of backache which is characteristically most severe in the cervical and lower thoracic areas. Many attribute this to the actual blows received, but its physical cause is more likely to be the extreme movements induced by struggles to avoid the beating and prolonged forced imposition of extremes of posture. There is often muscle tension and altered posture of a psychological nature. Other common psychosomatic symptoms are palpitations and hyperventilation. Although acute torture-related injuries may be characteristic of the alleged ill-treatment, most injuries heal within about 6 weeks, leaving no scars or nonspecific scars. Many forms of torture leave no physical evidence. Consequently, a completely
Psychological Assessment
K Allden, Dartmouth Medical School, Hanover, NH, USA
Introduction
The psychological assessment of torture survivors and those who allege torture present physicians, clinicians, and social scientists with the challenge of evaluating individuals who have survived crises of life-threatening proportions. For many who have survived torture, the experience can cause profound effects at a deeply personal level that can persist and fluctuate for many years. Psychological consequences develop in the context of personal meaning and personality development; consequences will vary over time and are shaped by cultural, social, political, interpersonal, biological, and intrapsychic factors that are unique for each individual. In recent decades much has been learned about psychological, biological, and neuropsychiatric responses to extreme stress, including torture, and clusters of typical symptoms have emerged that are recognized across cultures. Recognizing these considerations, this article focuses on the psychological assessment of those who allege torture.
TORTURE/Psychological Assessment 303
In 1999, the United Nations (UN) High Commissioner for Human Rights endorsed the first comprehensive set of guidelines for the medicolegal investigation and documentation of torture. The document is the Principles and Manual on Effective Investigation and Documentation of Torture and Other Cruel, Inhuman or Degrading Treatment or Punishment, also known as the Istanbul protocol. The UN annexed the principles in April 2000 in resolution E/CN4/RES/2000/32. The Istanbul protocol is the result of 3 years of collaborative analysis by a committee of forensic physicians, medical specialists, psychologists, human rights specialists, and lawyers who represented 40 organizations and institutions from 15 countries. This important reference is now the internationally recognized standard on evaluating those who allege torture. The reader is urged to refer to these guidelines. The document contains a model protocol for legal investigations of torture with a description of procedures for determining an appropriate investigative body, interviewing alleged victims and witnesses, obtaining consent, safety concerns, use of interpreters, securing physical evidence, developing a commission of inquiry, choosing experts, performing the physical and psychological exam, interpretation of findings and recommended content, and format of final reports. In 1984, the UN Convention Against Torture defined torture as:
any act by which severe pain or suffering, whether physical or mental, is intentionally inflicted on a person for such purposes as obtaining from him or a third person information or a confession, punishing him for an act he or a third person has committed or is suspected of having committed, or intimidating or coercing him or a third person for any reason based on discrimination of any kind, when such pain or suffering is inflicted by or at the instigation of or with the consent or acquiescence of a public official or other person acting in an official capacity.
psychological wounds are the most personal, intimate, and enduring consequences of torture and can affect not only the victim but also his/her family and community, there are no objective signs, measurable parameters, lab tests, or X-rays that document psychological wounds. The second paradox is that, despite the fact that torture is an extraordinary life experience capable of causing a wide range of psychological suffering, extreme trauma such as torture does not always produce psychological problems. Therefore, if an individual does not have mental problems, it does not mean that he/she was not tortured. When there are no psychological findings, this does not refute or support whether torture actually occurred.
Psychological Torture
Recent terrorist events have led world leaders and the public to ponder the question of whether torture is ever justified. A utilitarian argument has been raised to address what to do about a ticking bomb, that perhaps torture may be justifiable under extreme circumstances to extract information from a suspected terrorist. Under this argument, a suspected terrorist is a threat, not by what he/she has done but what he/she could do. The subjective judgments that would be made under these circumstances, however, could lead to a slippery slope of increasing force being applied to a wider network of suspects. The discussion goes on to ask: once torture is permitted for some suspects, how is it stopped? Ultimately, this examination leads to the further discussion of what pressure can be utilized during interrogation without crossing the line into torture. Torture is not permitted under international humanitarian law. What constitutes physical torture is rarely disputed: it includes blunt trauma (beating, whipping, kicking, punching), positional torture, crush injuries, stabbing, burning, electric shock, and sexual assault. What constitutes psychological torture is under dispute by some, even though the UN definition of torture clearly states that torture includes mental suffering. The following is a very abbreviated list of methods that have been used as psychological torture: conditions of detention (small, overcrowded, or filthy cells), solitary confinement, forced nakedness, deprivation of normal sensory stimulation (light, sound, hooding, sense of time), deprivation of physiologic needs (food, water, toilet, bathing), sleep deprivation, social isolation, humiliation, threats of harm or death to family, threats of future torture, techniques to break down the individual such as forced betrayals, learned helplessness, contradictory or ambiguous messages, violation of cultural taboos,
This definition acknowledges that mental suffering is often the intention of the torturer. The goal of torture is not simply to physically incapacitate the victim, but, as several authors have described, the goal is to reduce the individual to a position of helplessness and distress and break his/her will. At the same time, torture sets horrific examples to those who come into contact with the victim, and can profoundly damage intimate relationships between spouses, parents, and children, and other family members, as well as relationships between the victims and their communities. In this way, torture can break or damage the will and coherence of entire communities. Evaluating the psychological consequences of torture presents two paradoxes. First, although
behavioral coercion (forced to harm others, destroy property, or betray someone), and being forced to witness atrocities. Medical, psychiatric, and psychological practitioners recognize that the distinction between physical and psychological impact of torture is blurred; consequences can and do overlap. Psychological torture has physical and psychological consequences. Physical torture has psychological and physical consequences. One needs only to consider the consequences of sleep deprivation to see how blurred the overlap is. The effects of sleep deprivation include cognitive impairment, disorientation, heightened sensitivity to pain, horizontal nystagmus, mild tremor, electroencephalographic changes, visual and tactile hallucinations, disturbances of perception, mood changes, paranoia, and even seizures. For further reading concerning the legal debate about what constitutes torture, the reader is referred to former UN Special Rapporteur on Torture Sir Nigel Rodleys book, The Treatment of Prisoners under International Law.
Social, Political, and Cultural Considerations
individuals beliefs about his/her experiences and meanings of the symptoms, as well as evaluating the presence or absence of symptoms of trauma-related mental disorders. Torture is powerful enough on its own to produce mental and emotional consequences, regardless of the individuals pretorture psychological status. Nevertheless, torture has variable effects on people because the social, cultural, and political contexts vary widely. Outcomes can be influenced by many interrelated factors that include, but are not limited to, the following: . circumstances, severity, and duration of the torture . cultural meaning of torture/trauma and cultural meaning of symptoms . age and developmental phase of the victim . genetic and biological vulnerabilities of the victim . perception and interpretation of torture by the victim . the social context before, during, and after the torture . community values and attitudes . political factors . prior history of trauma . preexisting personality. For example, compare the consequences for a young woman who is raped during torture and is from a culture that attaches a severe negative stigma of impurity to a woman who has been raped, with a military officer who is held as a prisoner of war and suffers longterm solitary confinement and multiple beatings. Both types of torture are severe, yet the impact on the individuals life is vastly different. The young woman might be socially ostracized and condemned by her family and community. The former military officer may have brain damage from beatings to the head with resultant long-term cognitive impairment.
There are three complimentary approaches for understanding the psychological impact of torture. The personal approach is the individuals story as told through testimony, oral history, literature, and art. The clinical approach utilizes a medical and psychological paradigm and relies on clinical history, physical exam, and mental status exam. The community approach involves epidemiological studies of traumatized groups and populations. In combination these approaches provide a broad and in-depth understanding of the impact of torture on human beings. Each approach requires consideration of the context of torture. Torture has unique cultural, social, and political meanings for each individual. These meanings will influence an individuals ability to describe and speak about his/her experiences. Similarly, these factors contribute to the impact that the torture inflicts psychologically and socially. Cross-cultural research reveals that phenomenological or descriptive methods are the best approaches when attempting to evaluate psychological or psychiatric reactions and disorders because what is considered disordered behavior or a disease in one culture may not be viewed as pathological in another. The World Health Organizations multicenter cross-cultural study of depression conducted in the 1980s provides a helpful guiding principle. That is, while some symptoms may be present across differing cultures, they may not be the symptoms that concern the individual the most. Therefore, the clinicians inquiry has to include the
Self-Report and the Controversy about Traumatic Memory

Self-reports of trauma and torture are often not believed or felt to be distortions or exaggerations for purposes of obtaining asylum, compensation, or other benefits and secondary gain. Self-reported physical and psychological symptoms are often construed as fabrications or exaggerations for the same reasons. This is reflected in the skepticism many refugees and asylum-seekers encounter when confronted by government officials and others in authority. Much recent neuropsychological research has focused on memory distortion, reconstructing the past, and psychological trauma. Some studies suggest that with
increased psychological symptoms there will be exaggeration of traumatic events. Other studies document a direct dose effect between exposure to trauma and level of psychological symptomatology. Contributing to this puzzle are descriptive clinical reports that reveal complaints of cognitive disturbances among diverse traumatized groups. Research about survivors of prisoner-of-war camps and Nazi concentration camps reveals neurocognitive deficits and suggests that physical insults, particularly starvation, vitamin deficiency, and beatings to the head, are major contributing factors. It is often underrecognized that many torture survivors have been subjected to physical injury to the brain from beatings to the head, suffocation, near drowning, and severe, prolonged nutritional deficiencies, and that these insults may lead to cognitive impairment in torture survivors. Complicating the picture even more is the finding that depression and posttraumatic stress disorder (PTSD) affect cognition. There are multiple hypotheses about why this may be true, ranging from alterations in neuroendocrine systems, to neurotoxic effects of severe stress on hippocampal neurons, to psychoanalytic mechanisms. Memory impairment as a result of these factors may affect the accuracy of the details a survivor is asked to provide about his/her torture. Despite these potential limitations, it is often of critical importance for a torture survivor to provide accurate details of his/her torture and trauma experiences because these details will be used in legal affidavits for political asylum, human rights investigations, and other legal and judicial purposes such as war-crime tribunals. The inability to produce detailed and precise recollections about dates, times, places, environmental descriptions, and descriptions of perpetrators can reflect negatively on the survivors credibility and lead to severely deleterious consequences such as deportation of the survivor back to an extremely dangerous home country, denial of family reunification, prolonged detention, or failure to produce evidence to convict war criminals. Because of these grave outcomes, the clinician must take care to put the survivors trauma history, clinical history, mental status exam, and physical exam together with knowledge of the political context of the country where the torture allegedly took place, cultural idioms and beliefs, social customs, and barriers to full disclosure of traumatic events. The clinician must attempt to obtain as complete a picture as possible of the individuals life experiences and the context in which they are experienced in order to vouch for the credibility of the story and the believability of the clinical symptomatology.
Risk Factors, and Natural History of Trauma and Torture-Related Disorders

Despite the variability due to personal, cultural, social, and political factors, certain psychological symptoms and clusters of symptoms have been observed among survivors of torture and other types of violence. Since 1980, the diagnosis of PTSD has been applied to an increasingly broad array of individuals suffering from the impact of widely varying types of violence. Although the utility of this diagnosis in nonwestern cultural groups has not been clearly established, evidence suggests that there are high rates of PTSD and depression symptoms among traumatized refugee populations from multiple different ethnic and cultural backgrounds. The core symptoms and signs of severe trauma and torture across cultures have become increasingly clear. Many are physiological reactions that can persist for years. The main psychiatric disorders associated with torture are PTSD and major depression. One does not have to be tortured to develop PTSD and/or major depression because these disorders appear in the general population. Similarly, everyone who has been tortured does not develop PTSD and major depression. The course of major depression and PTSD varies over time. There can be asymptomatic intervals, recurrent episodes, and episodes during which an individual is extremely symptomatic. Therefore, when conducting an evaluation of a torture survivor, one must consider the following questions: 1. What is the timeframe of onset of symptoms? Did symptoms occur immediately following the traumatic events or were they delayed for weeks, months, or even years? 2. Is there a history of recurring episodes of symptomatology? 3. How do problems and symptoms emerge over time? 4. Where is the survivor in the recovery process at the time of the assessment? In considering who may be at heightened risk for developing psychological problems, one must evaluate both general/overall risk factors as well as those risk factors specific to traumatized populations, including how trauma affects family and social relationships and other natural supports. The general risk factors for developing mental illness are based on age, sex, education, social class, divorced/ widowed status, history of mental illness, and family history of mental illness. Additional risk factors for torture survivors include war, political oppression, imprisonment, witnessing or experiencing atrocities,
loss of family and/or separation from family, and distortion of social relationships. If the torture survivor is also a refugee or asylum-seeker, he/she has the further risk factors of migration (loss of home, loved ones, and possessions), acculturation, poverty, prejudice, cultural beliefs and traditional roles, cultural and linguistic isolation, absence of adequate support systems, and unemployment or underemployment. The multiple layers of increasing risk present a clinical picture that has been described as one of cumulative synergistic adversity.
Conducting the Psychological Evaluation and Barriers to Full Disclosure

Psychological evaluations may take place in a variety of settings and contexts, resulting in important differences in the manner in which evaluations should be conducted and in the way symptoms are interpreted. The clinician should understand what the barriers preventing the alleged torture survivor from fully disclosing his/her story are. Barriers to obtaining the complete story include circumstances of the experience itself, such as blindfolding, drugging, and lapses of consciousness. In addition, due to threats during torture, the survivor may be afraid of placing self or others at risk. Whether or not certain sensitive questions can be asked safely will depend on the degree to which confidentiality and security can be assured. An evaluation by a clinician visiting a prison or detention center may be very brief and not allow for as detailed an evaluation as one performed in a clinic or private office that may take place over several sessions and last for several hours. Some symptoms and behaviors typically viewed as pathological may be viewed as adaptive or predictable, depending on the context. For example, diminished interest in activities, feelings of detachment, and estrangement would be understandable findings in a person in solitary confinement. Likewise, hypervigilance and avoidance behaviors may be necessary for those living under threat in repressive societies. The clinician should attempt to understand mental suffering in the context of the survivors circumstances, beliefs, and cultural norms rather than rush to diagnose and classify. Awareness of culture-specific syndromes and native languagebound idioms of distress is of paramount importance for conducting the interview and formulating the clinical impression and conclusion. When the interviewer has little or no knowledge about the victims language and culture, the assistance of an interpreter is essential. An interpreter from the victims country of origin will facilitate an understanding of the language, customs, religious traditions, and other
beliefs that will need to be considered during the evaluation. Clinicians should be aware of the potential emotional reactions that these evaluations may elicit in survivors; these reactions can present barriers to full disclosure. Fear, shame, rage, and guilt are typical reactions. A clinical interview may induce mistrust on the part of the torture survivor and possibly remind him/her of previous interrogations, thereby retraumatizing him/her. To reduce the effects of retraumatization, the clinician should communicate a sense of empathy and understanding. The victim may suspect the clinician of having voyeuristic and sadistic motivations or may have prejudices toward the clinician because he/she has not been tortured. The clinician is a person in a position of authority and for that reason may not be trusted with certain aspects of the trauma history. Alternatively, individuals still in custody may be too trusting in situations where the clinician cannot guarantee that there will be no reprisals for speaking about torture. Torture victims may fear that information that is revealed in the context of an evaluation cannot be safely kept from being accessed by persecuting governments. Fear and mistrust may be particularly strong in cases where physicians or other health workers were participants in the torture. In the context of evaluations conducted for legal purposes, the necessary attention to detail and the precise questioning about history are easily perceived as a sign of doubt on the part of the examiner. Under these pressures, survivors may feel overwhelmed with memories and affect or mobilize strong defenses such as withdrawal and affective flattening or numbing during evaluations. If the gender of the clinician and the torturer is the same, the interview situation may be perceived as resembling the torture more than if the genders were different. For example, a woman who was raped and tortured in prison by a male guard is likely to experience more distress, mistrust, and fear when facing a male clinician than she might experience with a female. However, it may be much more important to the survivor that the interviewer is a physician regardless of gender so as to ask specific medical questions following rape and sexual torture about possible pregnancy, ability to conceive later, and future of sexual relations between spouses. When listening to individuals speak of their torture clinicians should expect to have personal reactions and emotional responses themselves. Understanding these personal reactions is crucial because they can have an impact on ones ability to evaluate and address the physical and psychological consequences of torture. Reactions may include avoidance and defensive indifference in reaction to being exposed to
disturbing material; disillusionment, helplessness, and hopelessness that may lead to symptoms of depression or vicarious traumatization; grandiosity or feeling that one is the last hope for the survivors recovery and well-being; feelings of insecurity in ones professional skills in the face of extreme suffering; guilt over not sharing the torture survivors experience; or even anger when the clinician experiences doubt about the truth of the alleged torture history and the individual stands to benefit from an evaluation.
Diagnostic Considerations
It is prudent for clinicians to become familiar with the most commonly diagnosed disorders among trauma and torture survivors and to understand that it is not uncommon for more than one mental disorder to be present as there is considerable comorbidity among trauma-related mental disorders. The two most common classification systems are the International Classification of Disease (ICD-10), Classification of Mental and Behavioral Disorders, published by the World Health Organization, and the Diagnostic and Statistical Manual, 4th edition, of the American Psychiatric Association (DSM-IV). Clinicians, who are not full-time mental health professionals, such as internists and general practitioners who perform evaluations of torture survivors should be familiar with the common psychological responses to torture and be able to describe their clinical findings. They should be prepared to offer a psychiatric diagnosis if the case is not complicated. A psychiatrist or psychologist skilled in the differential diagnosis of mental disorders related to severe trauma will be needed for particularly emotional individuals, cases involving multiple symptoms or atypical symptom complexes, psychosis, or in cases presenting confusing clinical pictures. The diagnosis most commonly associated with torture is PTSD. Typical symptoms of PTSD include reexperiencing the trauma, avoidance, emotional numbing, and hyperarousal. Reexperiencing can take several forms: intrusive memories, flashbacks (the subjective sense that the traumatic event is happening all over again), recurrent nightmares, and distress at exposure to cues that symbolize or resemble the trauma. Avoidance and emotional numbing include avoidance of thoughts, conversations, activities, places, or people that arouse recollection of the trauma, feelings of detachment and estrangement from others, inability to recall an important aspect of the trauma, and a foreshortened sense of the future. Symptoms of hyperarousal include difficulty falling or staying asleep, irritability or outbursts of anger, difficulty concentrating, hypervigilance, and exaggerated startle response.
Depressive states are almost ubiquitous among survivors of torture. Depressive disorders may occur as a single episode or be recurrent. They can present with or without psychotic features. Symptoms of major depression include depressed mood, anhedonia (markedly diminished interest or pleasure in activities), appetite disturbance, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue and loss of energy, feelings of worthlessness and excessive guilt, difficulty concentrating, and thoughts of death, suicidal ideation, or suicide attempts. A survivor of severe trauma such as torture may experience dissociation or depersonalization. Dissociation is a disruption in the integration of consciousness, self-perception, memory, and actions. A person may be cut off or unaware of certain actions or may feel split in two and feel as if he/she is observing him/ herself from a distance. Depersonalization is feeling detached from oneself or ones body. Somatic symptoms, such as pain and headache and other physical complaints, with or without objective findings are common problems among torture victims. Pain may shift in location and vary in intensity. Somatic symptoms can be directly due to physical consequences of torture, or may be of psychological origin, or both. Also, various types of sexual dysfunction are not uncommon among survivors of torture, particularly, but not exclusively, among those who have suffered sexual torture or rape. Psychotic symptoms may be present, such as delusions, paranoia, hallucinations (auditory, visual, olfactory, or tactile), bizarre ideation, illusions, or perceptual distortions. Cultural and linguistic differences may be confused with psychotic symptoms. Before labeling something as psychotic, one must evaluate the symptoms within the individuals cultural context. Psychotic reactions may be brief or prolonged. It is not uncommon for torture victims to report occasionally hearing screams, his/her name being called, or seeing shadows, but not have florid signs or symptoms of psychosis. Individuals with a past history of mental illness such as bipolar disorder, recurrent major depression with psychotic features, schizophrenia, and schizoaffective disorder may experience an episode of that disorder. The ICD-10 includes the diagnosis enduring personality change. PTSD may precede this type of personality change. To make the ICD-10 diagnosis of enduring personality change, the following criteria must have been present for at least 2 years and must not have existed before the traumatic event or events. These criteria are: hostile or distrustful attitude toward the world, social withdrawal, feelings of emptiness or hopelessness, chronic feelings of being on edge as if constantly threatened, and estrangement.
Alcohol and drug abuse may develop secondarily in torture survivors as a way of blocking out traumatic memories, regulating affect, and managing anxiety. Other possible diagnoses include: generalized anxiety disorder, panic disorder, acute stress disorder, somatoform disorders, bipolar disorder, disorders due to a general medical condition (possibly in the form of brain impairment with resultant fluctuations or deficits in level of consciousness, orientation, attention, concentration, memory, and executive functioning), and phobias such as social phobia and agoraphobia.
5. What physical conditions contribute to the clinical picture? Pay special attention to head injury sustained during torture and/or detention. 6. Does the clinical picture suggest a false allegation of torture? When writing reports, clinicians should comment on the emotional state of the person during the interview, symptoms, history of detention and torture, and personal history prior to torture. Factors such as the onset of specific symptoms in relation to the trauma, the specificity of any particular psychological findings, as well as patterns of psychological functioning should be noted. Additional factors such as forced migration, resettlement, difficulties of acculturation, language problems, loss of home, family, and social status, as well as unemployment should be discussed. The relationship and consistency between events and symptoms should be evaluated and described. Physical conditions such as head trauma or brain injury may require further evaluation. It is possible that some people may falsely allege torture or exaggerate a relatively minor experience or symptoms for personal or political reasons. The clinician should keep in mind, however, that such fabrication requires a detailed knowledge about trauma-related symptoms that individuals rarely possess. Also, inconsistencies can occur for a number of valid reasons such as memory impairment due to brain injury, confusion, dissociation, cultural differences in perception of time, or fragmentation and repression of traumatic memories. Additional sessions should be scheduled to help clarify inconsistencies and, when possible, family or friends may be able to corroborate detail.
Psychological Testing and the Use of Checklists and Questionnaires

If an individual has trouble expressing in words his/ her experiences and symptoms; it may be useful to use a trauma event questionnaire or symptom checklist. These tools may facilitate disclosure of severely traumatic memories and reduce the anxiety often experienced in an unstructured interview. There are numerous questionnaires available; however, none is specific to torture victims. Much caution must be exercised in the interpretation of responses and scores because established norms do not exist for most nonmainstream western European and American populations. Similarly, there is little published information about the use of standard psychological and neuropsychological tests among torture survivors. Due to the fact that there is such wide cultural and linguistic diversity among this group, one should exercise extreme caution when requesting or employing psychological and psychometric tests of any kind, most of which have not been cross-culturally validated.
Formulating the Clinical Impression

Interpretation of the clinical findings is a complex task. The following questions from the Istanbul protocol will help guide the formulation of the clinical impression and diagnostic conclusions. 1. Are the psychological findings consistent with the alleged report of torture? 2. Are the psychological findings expected or typical reactions to extreme stress within the cultural and social context of the individual? 3. Given the fluctuating course of trauma-related mental disorders over time, what is the timeframe in relation to the torture events? Where in the course of recovery is the individual? 4. What are the coexisting stresses impinging on the individual (e.g., ongoing persecution, forced migration, exile, loss of family and social role)? What impact do these issues have on the victim?
See Also
History of Torture; Torture: Physical Findings; War Injuries
Further Reading
British Medical Association (2001) The Medical Professional and Human Rights: Handbook for a Changing Agenda. London: Zed Books. Danieli Y, Rodley N, Lars W (eds.) (1996) International Responses to Traumatic Stress. Amityville, NY: Baywood Publishing. Garrity E, Keane T, Tuma F (eds.) (2001) The Mental Health Consequences of Torture. New York: Kluwer Academic/Plenum. Jaranson J, Popkin M (eds.) (1998) Caring for Victims of Torture. Washington, DC: American Psychiatric Press. Marsella A, Bornemann T, Ekblad S, Orley J (eds.) (1998) Amidst Perial and Pain: The Mental Health and WellBeing of the Worlds Refugees. Washington, DC: American Psychological Association.
TOXICOLOGY/Overview 309 Peel M, Iacopino V (eds.) (2002) The Medical Documentation of Torture. London: Greenwich Medical Media. Physicians for Human Rights (2001) Examining Asylum Seekers: A Health Professionals Guide to Medical and Psychological Evaluation of Torture. Boston, MA: Physicians for Human Rights. Schacter D (ed.) (1997) Memory Distortion: How Minds, Brains, and Societies Reconstruct the Past. Cambridge, MA: Harvard University Press. United Nations (2001) Manual on the Effective Investigation and Documentation of Torture and Other Cruel, Inhuman or Degrading Treatment or Punishment. Istanbul Protocol. Professional training series no. 8. New York: United Nations Office of the High Commissioner for Human Rights. Wilson J, Keane T (eds.) (1997) Assessing Psychological Trauma and PTSD. New York: Guilford Press.
Torture, History of
See History of Torture
TOXICOLOGY
Contents Overview Methods of Analysis, Antemortem Methods of Analysis, Postmortem
Overview
O H Drummer, Victorian Institute of Forensic Medicine, Southbank, VIC, Australia
2005, Elsevier Ltd. All Rights Reserved. This article is adapted from Toxicology: Overview in Encyclopedia of Forensic Sciences, pp. 1364-1369, 2000, Elsevier Ltd.
analytical techniques need to be employed that are appropriately validated for use in case work. The conduct of suitable quality assurance is important to assure the analyst and clients of the quality of the result. These issues are discussed in this overview, while in other articles specific issues of techniques, specimens, and interpretation are further discussed.
Applications of Forensic Toxicology Introduction

Toxicology is the science of poisons, and, when applied to forensic and legal medicine, the terms forensic toxicology or analytical toxicology are often applied. A forensic toxicologist is concerned with the detection of drugs or poisons in samples and is capable of defending his/her result in a court of law. This distinction from an ordinary analytical toxicologist is important, since a conventional toxicologist is mainly concerned with the detection of substances, and may not understand the specific medicolegal requirements in forensic cases. The process of conducting toxicology is similar to other analytical disciplines, in that sufficiently suitable Forensic toxicology has a number of applications. Traditionally, it is used in death investigations. It provides physicians and pathologists with information of a possible drug taken in overdose, or authorities investigating a sudden death, or poisoning, of the possible substances(s) used. Ultimately toxicology testing results will assist the client in establishing the evidence of drug use, or refuting the use of relevant drugs. Toxicology testing is also important in victims of crime, or in persons apprehended for a crime. Drugs may have been given by the assailant to reduce consciousness of the victim, such as in rape cases. These drugs include the benzodiazepines (e.g., clorazepam,
310 TOXICOLOGY/Overview
flunitrazepam, diazepam), antihistaminics, and gamma-hydroxybutyrate (GHB). Toxicology also establishes if the victim used any drug which may have affected consciousness or behavior. Defendants arrested shortly after allegedly committing a violent crime may be under the influence of drugs. It is vital, therefore, that toxicology testing is conducted (on relevant specimens) to establish the extent of drug use, since allegations of drug use and its effect on intent or clinical state may be raised in legal proceedings. Driving under the influence of drugs is one of the main uses of toxicology testing. Forensic toxicology is also used in employment drug testing and in human performance testing. The former category relates to the detection of drugs of abuse in persons in a place of employment, prior to being hired by an employer, or even a person in detention, such as in a prison. Human performance testing relates to the detection of drugs that may have increased (usually) performance in athletic events or may mask the use of performance-enhancing drugs. This may even apply to animals such as horses. Specimens used in these cases are usually urine, although hair is increasingly used to provide a longer window of opportunity.
Specimen
Immunoassay
Chromatographic screen A
Alcohol screen
Chromatographic screen B
Tentative drugs confirmed by MS
Drug(s) quantified
Report issued
Figure 1 Schema showing identification, confirmation, and quantification processes in forensic toxicology. MS, mass spectrometry. Reproduced from Drummer OH. Toxicology: Overview. In: Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier. Table 1 Screening and confirmation techniques
Screening tests Confirmation tests
Initial Tests and Confirmation

The foremost goal in forensic toxicology is the need to provide a substantial proof of the presence of a substance(s). The use of conventional gas chromatography (GC), thin-layer chromatography (TLC), or high-performance liquid chromatography (HPLC) would not normally be sufficient to accept unequivocal proof of the presence of a chemical substance. Two or more independent tests are normally required, or the use of a more powerful analytical test, such as mass spectrometry (MS) is usually preferred. Because of the need to perform a rigorous analysis, the analytical schema is often broken up into two steps. The identification stage is termed the screening or initial test, while the second analytical test is the confirmation process. The confirmation process often also provides a quantitative measure of how much substance was present in the sample; otherwise a separate test is required to quantify the amount of substance present in the specimen. In all processes it is important that no analytical inconsistency appears, or a result may be invalidated (Figure 1). For example, in the identification of codeine in a blood specimen, an immunoassay positive to opiates is expected to be positive for codeine in the confirmation assay. The apparent detection of a drug in one analytical assay but not in another means that the drug was not confirmed, providing both assays are capable of detecting this drug. Table 1 provides a
Immunoassays Spectroscopy (UV, F, etc.) HPLC (UV, F, ECD, CD) GC (FID, NPD, TD) CE (UV, F) AAS, colorimetric tests
MS (LC, GC, CE) Second chromatographic test HPLC (DAD) AAS ICP-MS
MS, mass spectroscopy; LC, liquid chromatography; GC, gas chromatography; CE, capillary electrophoresis; UV, ultraviolet; F, fluorescence; HPLC, high-performance liquid chromatography; ECD, electrochemical; CD, conductivity detection; DAD, photodiode array detector; FID, flame ionization detector; NPD, nitrogen phosphorus detector; TD, thermionic detector; AAS, atomic absorption spectroscopy; ICP-MS, inductively coupled plasma mass spectrometry. Reproduced from Drummer OH. Toxicology: Overview. In: Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
listing of common techniques used in screening and confirmation assays. While MS is the preferred technique for confirmation of drugs and poisons, some substances display poor mass spectral definition. Compounds with base ions at mass/charge ratios of less than 100, or with common ions such as m/z 105 and with little or no ions in the higher mass range, are not recommended
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for confirmation by MS alone. Derivatization of a functional group to produce improved mass spectral properties can often be successful. Common derivatives include perfluoroacyl esters, trimethylsilyl ethers, etc. Alternatively, reliance on other chromatographic procedures can provide adequate confirmation. It is important when using any chromatographic procedure (such as HPLC, GC, or capillary electrophoresis (CE)), that the retention time of the substance being identified matches with that of an authentic standard. Some apparent analytical inconsistencies may provide important forensic information. For example, if a result for opiates is negative in urine, but positive in blood, it is possible that heroin was administered shortly before death, and therefore metabolites had not yet been excreted (heroin (diacetylmorphine) is rapidly metabolized to morphine through 6-acetylmorphine). This situation is often found in heroin users dying from an acute sudden death in which substantial urinary excretion has not yet occurred.
Common Drugs and Poisons

The most common drugs and poisons are clearly the initial targets of any forensic toxicological analysis, particularly if no specific information is available to direct the investigation. The most common substances can be categorized as fitting into four classes: (1) alcohol (ethanol); (2) illicit drugs; (3) licit (ethical) drugs; and (4) the nondrug poisons. An example of the distribution of drugs in various types of coroners cases is shown in Table 2. These data are likely to be similar throughout developed countries. Alcohol is the most frequent detection in many countries, and, when detected, can play an important role in any investigation because of its ability to depress the central nervous system (CNS). At best,
Table 2 Incidence of drugs in various types of death (%)a
Type of death Ethanol Opioidsb
alcohol will modify behavior, causing disinhibition and possible aggression; at worst it can cause death, either by itself, or in combination with another drug. Illicit drugs include the amphetamines, barbiturates, cocaine, heroin, and other opiates, cannabis, phencyclidine, designer fentanyls, GHB, and lysergic acid diethylamide (LSD). It should be borne in mind that some illicit drugs also have medical uses in some countries. Cocaine is used in some forms of facial and nasal surgery, amphetamine is used to treat narcolepsy and attention deficit hyperactivity disorder (ADHD), and cannabis is used (among other indications) to reduce nausea following chemotherapy. Ethical drugs include the whole range of prescription and over-the-counter drugs used in the treatment of minor to major ailments. Those of most interest include the antidepressants, major tranquilizers, narcotics and other forms of pain relievers, and anticonvulsants. Since these drugs are widely prescribed, this is by far the most common drug category encountered in toxicology. Each country will have its own list of registered drugs, hence laboratories will need to consider these as a matter of priority over other members of a particular class available elsewhere. For example, most countries only have a relatively small number of benzodiazepines registered for medical use, whereas over 35 are available throughout the world. From time to time laboratories will be required to consider drugs not legally available in their countries because of illicit supplies or through tourists visiting their country. The nondrug poisons include most commonly organophosphates and other pesticides, carbon monoxide, hydrogen cyanide and cyanide salts, and volatile substances (petrol, lower-molecular-weight hydrocarbons, and kerosene). Carbon monoxide and hydrogen cyanide are gases emitted by fires and are therefore frequent detections in fire victims. Other poisons include heavy metals (arsenic, mercury, thallium), plant-derived poisons (hyoscine from Belladonna
Benzodiazepines
Stimulantsc
Cannabis
Antipsychotics
Natural death Homicides Drivers of motor vehicles Nondrug-related suicides Licit drug deaths Illicit drug deaths All cases
15 38 27 33 40 35 27
13 11 6.2 10 41 96 20
9.4 11 4.3 21 59 61 20
1.4 4.0 4.3 2.9 3.2 7.1 3.1
2.3 16 16 13 8.0 38 12
2.6 0 <1 2.1 13 5.4 3.2
Data produced from the toxicology database of the Victorian Institute of Forensic Medicine. a Taken from 2000 cases. b Includes codeine and propoxyphene. c Includes legal stimulants, amphetamines, and cocaine. Reproduced from Drummer OH. Toxicology: Overview. In: Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
Table 3 Incidence of poisons in coroners cases in Australia
Poison Incidence
a
Organophosphates Butane and other hydrocarbons Other pesticides/herbicides Solvents (methanol, chloroform, etc.) Strychnine Potassium cyanide Plant-derived poisons Ethylene glycol Heavy metals Potassium Others
a
18 10 12 8 6 5 5 2 2 2 14
Taken from over 24 000 Victorian coroners cases from 1989 to 2000.
(antipsychotic drugs), and other CNS-depressant drugs would be included. The incorporation of a reasonably complete range of drugs in any testing protocol is important since many of these drugs are mood-altering, and can therefore affect behavior, as well as affecting the health status of an individual. Persons using benzodiazepines, for example, will be further adversely affected by cocaine and amphetamine use, and the use of other CNS-depressant drugs. The toxic concentrations of drugs are also influenced by the presence of other potentially toxic drugs. For example, the fatal dose for heroin is affected by the concomitant use of alcohol and other CNS-depressant drugs, since heroin effects are potentiated.
species, coniine from hemlock), strychnine, and toxins such as venoms. Performance-enhancing drugs such as the anabolic steroids may also be considered in some instances. This list is necessarily limited due to space. Practitioners should always consider the availability of drugs and poisons in certain occupational groups since this can give clues to the nature of a usual substance. In a review of 12 years of forensic cases from Victoria, Australia, the variety of unusual poisons is shown in Table 3. Obviously, the variety of drugs and poisons will vary from country to country.
Specimens
It is essential that the relevant specimens are taken whenever possible, since re-collection is rarely possible. The preferred specimens collected in forensic toxicology will of course depend on the nature of the case. In general, a blood specimen is a minimum requirement, although specimens such as urine can be useful for laboratories as a screening specimen, and to check for the use of drugs 2 days or more before sampling. Hair can provide an even longer memory of drug intake, lasting up to several months, depending on the length of hair. Drugs are usually incorporated into the growing root and appear as a band in the hair shaft when it externalizes from the skin. This process can therefore provide a history of when exposure to a drug or poison has occurred. Most drugs and poisons are incorporated into hair, although the extent will depend on the physiochemical properties of the substance. Basic drugs are often found in higher concentrations than acidic drugs, and invariably the parent drug is present rather than metabolites. For example, cocaine and the heroin metabolite 6-acetylmorphine are more likely to be found in hair of cocaine and heroin users than their corresponding metabolites found in blood and urine (benzoylecgonine and morphine, respectively). Drug will be absorbed into the hair from skin secretions adjacent to the hair follicles, and may even be incorporated from external contamination. Care and treatment of hair, such as washing and the use of dyes and bleaches will also affect the concentration of drug in hair. Consequently, any interpretation of drug content in hair needs to factor in these considerations. Courts and other legal processes usually require proof that the laboratory has taken all reasonable precautions against unwanted tampering or alteration of the evidence. This applies to specimens and
Scope of Testing Protocols

As the previous sections indicate, cases may involve a variety of ethical and illicit drugs, or unusual poisons. Worldwide experience also shows that forensic cases often involve more than one drug substance. Surveys of drug-related cases show that three or more drugs are present in more than 70% of cases. High rates of multiple drug use are also found in perpetrators and victims of violent crimes, suicides, and often also in accidents and road crashes. It is also well known by forensic toxicologists that the information provided to the laboratory concerning possible drug use may not accord with what is actually present. It is therefore strongly recommended that laboratories provide a systematic approach to their toxicology cases and include as wide a range of common ethical and illicit drugs as feasible. This approach is termed systematic toxicology analysis (STA). A laboratory using this approach would normally include a range of screening methods, often incorporating both chromatographic and immunological techniques. Drug classes such as alcohol, analgesics, opioid and nonopioid narcotics, amphetamines, antidepressants, benzodiazepines, barbiturates, cannabis, cocaine, major tranquilizers
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to physical exhibits used by the laboratory in its toxicology investigations (the term exhibit applies to both specimens and to physical items, such as tablets and syringes). Consequently, it is essential that the correct identifying details are recorded on the exhibit or specimen container, and an adequate record is kept of persons in possession of the exhibit(s). Alternatively, when couriers are used to transport exhibits, the exhibit must be adequately sealed to prevent unauthorized tampering and therefore show continuity of the exhibit. This is called the chain of evidence. Procedures are available to assist laboratories in establishing suitable chain of custody.
Quality Assurance and Validation

An essential part of any form of toxicological testing is validation and the conduct of quality assurance. It is important that the method used is appropriately validated, i.e., it has been shown to detect accurately and precisely the substance(s) detectable, there is little or no interference (from other drugs and from the matrix) with the specimens used, and a useful detection limit has been established. Moreover, it is essential that the method is rugged and will allow any suitably trained analyst to conduct the procedure and achieve the same results as another analyst. To achieve these aims, it will be necessary to trial the method in the laboratory over several assays with varying specimen quality before claiming a full validation has been conducted. It is strongly recommended to include internal quality controls with each batch of samples to enable an internal check of the reliability of each assay. These controls contain known drugs at known concentrations. Suitable acceptance criteria are required for these controls before results of unknown cases can be accepted and released to a client. Acceptance criteria vary depending on the analyte and application. For example, blood alcohol estimations often have acceptance criteria less than 5%, while postmortem blood procedures may be 1020%. (Normally the coefficient of variation of the mean is calculated as a standard deviation divided by the mean of the result.) An important feature of analytical assays in forensic toxicology is the use of internal standards. These are drugs of similar chemical and physical characteristics as the drug(s) being analyzed and, when added at the start of the extraction procedure, provide an ability to negate the effects of variable or low recoveries from the matrix. Hence, even when recoveries are low, the ratios of analyte and drug are essentially the same as for situations of higher recovery. An ideal recovery marker is when the internal standard is a deuterated analog of the analyte. When deuterated internal standards are used, it may not be necessary to match the calibration standards with the same matrix as the unknown samples, providing the laboratory has verified that no significant matrix effects occur. It is important, however, that absolute recoveries are reasonable, i.e., at least over 30%. This ensures less variability between samples and optimizes the detection limit. From time to time, it will be important to run unknown samples prepared by another laboratory, or a person not directly involved in laboratory work, to establish proficiency. These are known as proficiency programs or quality assurance programs. These trials are often conducted with many other
General Techniques
The ranges of techniques available to detect drugs in specimens are very similar through the range of applications. These range from commercial kit-based immunoassays (enzyme-multiplied immunoassay technique (EMIT), enzyme-linked immunosorbent assay (ELISA), fluorescence polarization immunoassay (FPIA), cloned enzyme donor immunoassay (CEDIA), radioimmunoassay (RIA)), traditional TLC, to instrumental separation techniques such as HPLC, GC, and CE. MS is the definitive technique used to establish proof of structure of an unknown substance, and can be linked to GC, HPLC, and CE. The use of appropriate extraction techniques is critical to all analytical methods. Three main types of extraction are used: liquidliquid, solid-phase, and direct injection. Traditionally, liquid techniques have been favored in which a blood or urine specimen is treated with a buffer of an appropriate pH followed by a solvent capable of partitioning the drug out of the matrix. Solvents used include chloroform, diethylether, ethylacetate, toluene, hexane, various alcohols and butyl chloride, and mixtures thereof. The solvent is then isolated from the mixture and either cleaned up by another extraction process or evaporated to dryness. Solid-phase techniques are becoming increasingly favored, since mixed phases offer the ability to extract substances of widely deferring polarity more readily than with liquid techniques. Often less solvent is used, or simple hydroalcoholic systems can be employed, rather than potentially volatile or inflammable solvents. Direct injection techniques into either GC or HPLC instruments bypass the extraction step, and can offer a very rapid analytical process. In GC, solid-phase microextraction (SPME) can be used, whilst HPLC tends to require use of precolumns which are backflushed with use of column-switching valves.
laboratories conducting similar work, and provide an independent assessment of the proficiency of the laboratory to detect (and quantify) specific drugs. The performance of the laboratory should be regularly assessed from these results, and any corrective action implemented, if appropriate. This process provides a measure of continuous improvement, an essential characteristic of any laboratory. There are a number of collaborative programs available throughout the world. The College of American Pathologists (CAP) organizes an excellent series of proficiency programs in forensic toxicology. The international (The International Association of Forensic Toxicologists (TIAFT)) and American (Society of Forensic Toxicologists) societies of forensic toxicology provide guidelines on the conduct of analytical assays and in quality assurance aspects of analyses.
unabsorbed drug (and excreted drug) and may be severely affected by postmortem processes. The variation in blood concentration at a specified time from a standard dose of drug is well known in clinical pharmacology, even in controlled situations. Therefore, it is not recommended to estimate dose, unless these factors are considered, and a range of doses is computed. Occasionally, it may be possible to compare blood (and tissue) concentrations to other cases in which doses were known, or by measuring the body burden in several tissues, including muscle and fat. Analysis of gastric and intestinal drug content will assist in this process, and also provide information on the route and time of ingestion.
Interpretation of Toxicological Results

Interpretation of any toxicological result is complex. Consideration must be given to the circumstances of the case, and in particular what significance may be drawn from the toxicology. For example, the finding of a drug in potentially toxic concentrations in a person killed by a gunshot wound to the head cannot reasonably lead to the conclusion that drugs caused the death. Alternatively, the absence of an obvious anatomical cause of death will lead investigators to consider the role of any drug use. Considerations must include the chronicity of drug use, the age of the person, the health of the person (presence of heart, liver, kidney disease), the use of multiple substances, and even genetic factors that may lead to a reduced metabolism.
Postmortem Artifacts in Analysis

The process of death imparts a number of special processes that affect the collection and analysis of specimens obtained at autopsy. These include postmortem redistribution, in which the concentration of a drug in blood has been affected by diffusion of drug from neighboring tissue sites and organs, such as the stomach contents. This is minimized, but not arrested, using peripheral blood from the femoral region. Even liver concentrations may be affected by diffusion from intestinal contents or from incomplete circulation and distribution within the liver. Some drugs are metabolized after death, i.e., nitrazepam, flunitrazepam, heroin, aspirin. Bacterial processes in decomposing bodies may even produce substances such as ethanol and cyanide.
Problems in Court Testimony

Forensic toxicologists and other analysts called to give evidence in court should consider that much of their technical evidence is beyond the ready comprehension of lay people in juries, legal counsel, and judges. Restricting their evidence to understandable language and simple concepts is highly recommended. A further problem relates to an assumption often made by legal counsel (and indeed other parties) that a toxicological investigation was exhaustive and all drugs and poisons were excluded in the testing processes. Most toxicology performed is restricted to a few analytical tests for a range of common drugs and poisons, unless the client (e.g., pathologist or police officer) has made a request to examine for (additional) specific chemicals. Analysts should make courts aware of the actual testing conducted and provide a list of substances incorporated in the investigation. Importantly, advice on any limitations applied to the interpretation of the analytical results should be provided,
Estimation of Dose
A common request from legal counsels and police is to estimate a dose from a blood or tissue concentration. This may relate to determining likely intent, or simply to rationalize the circumstances to specific amounts of drugs used. Dose can be estimated from knowledge of the volume of distribution (Vd) of drug (available from several sources, including the books edited by Baselt and Moffatt). The calculation multiplies the blood concentration by the volume of distribution corrected for the body weight of the person. Unfortunately, this calculation assumes one Vd for all persons, and importantly, assumes equilibrium has been established at the time of drug ingestion. This is rarely the case in toxicology cases, since recent drug ingestion is common. The calculation also fails to account for
TOXICOLOGY/Methods of Analysis, Antemortem 315
e.g., poor-quality specimens and postmortem artifacts. Above all, toxicologists must restrict their evidence to those areas in which they claim expertise. Stretching their expertise in the aim of assisting the court can lead to incorrect or misleading evidence, and damage the reputation of the expert and of toxicology.
See Also
Autopsy, Findings: Organic Toxins; Fire; Carbon Monoxide Poisoning: Clinical Findings, Sequelae In Survivors; Incidence and Findings at Postmortem; Immunoassays, Forensic Applications; Sexual Offenses, Adult: Drug-Facilitated Sexual Assault; Substance Misuse: Heroin; Urine Analysis; Toxicology: Methods of Analysis, Antemortem; Methods of Analysis, Postmortem
Further Reading
Barry L (1999) Principles of Forensic Toxicology. Washington, DC: American Association of Clinical Chemistry. Baselt RH (2000) Disposition of Toxic Drugs and Chemicals in Man, 5th edn. Foster City, CA: Year Book Medical. Drummer OH, Gerostamoulos J (2002) Review. Post-mortem drug analysis: analytical and toxicologic aspects. Therapeutic Drug Monitoring 24: 199220. Drummer OH, Odell M (2001) The Forensic Pharmacology of Drugs of Abuse. London: Arnold. Karch S (1998) Drug Abuse Handbook. Boca Raton, FL: CRC Press. Marcelline B (2003) Medical-Legal Aspects of Drugs. Tucson, AZ: Lawyers & Judges. Moffatt AC (ed.) (2003) Clarkes Isolation and Identification of Drugs, 3rd edn. London: Pharmaceutical Press.
or otherwise, of other evidence suggestive of drug use. Ultimately, drug screening assists the investigating authorities in providing forensic scientific information pertaining to relevant cases (Table 1). Toxicology testing is particularly important in victims of sexual assault, where drugs may have been given by the alleged assailant to reduce consciousness and memory of the victim. Drugs used in these cases are typically one of the benzodiazepines (clonazepam, flunitrazepam, alprazolam, etc.), gamma-hydroxybutyrate (GHB and its precursors such as 1,4-butanediol), or a number of other drugs. Perpetrators of violent crime may also have consumed alcohol, illicit drugs, or even be under prescribed medication. In practice, drug users committing crimes are likely to be under the influence of two or more drugs. Drivers involved in motor vehicle crashes or those causing traffic infringements are also frequently under the influence of two or more drugs. Toxicology testing on specimens taken soon after the investigated incident is more likely to assist in establishing any drug-induced behaviors of persons than when a specimen is obtained much later. For this reason it is more appropriate to test antemortem specimens from persons taken shortly after admission to hospital, rather than those taken later or at postmortem. This also reduces the interpretation problems associated with postmortem artifacts. Postmortem processes can change blood concentrations, complicating any interpretation of postmortem toxicology. These include redistribution, fermentation (for alcohol), and bioconversion. Since the great majority of cases (>70%) involve more than one drug, it is advisable to conduct a broad drug screening to include most of the common drugs of abuse, rather than target the analysis to one or a limited range of drugs suggested by the circumstances. This is termed systematic toxicological analysis.
Methods of Analysis, Antemortem

2005, Elsevier Ltd. All Rights Reserved. This article is adapted from Toxicology: Methods of Analysis Ante Mortem in Encyclopedia of Forensic Sciences, pp. 13971403, 2000, Elsevier Ltd.
Specimens
Specimens collected antemortem are most often whole blood or the plasma/serum portions, or urine. However, alternative specimens such as hair, sweat, and saliva have also been used to assess drug use and can be a valuable additional specimen (Table 2).
Blood and Plasma
Introduction
In the absence of some form of drug screening, drug use cannot be confirmed or eliminated as a reasonable possibility in relevant forensic cases. Toxicology testing also assists the courts in establishing the veracity,
Whole blood, or plasma/serum derived from blood, is the most useful specimen that can be collected since drugs present in this fluid can best be related to a physiological effect and can be used to assess the likelihood of recent drug use or exposure to chemicals. Blood contains predominantly red blood cells, white blood cells, and plasma. Plasma is obtained from
316 TOXICOLOGY/Methods of Analysis, Antemortem

Table 1 Reasons for drug testing in forensic cases Assisting death investigations to establish cause and mode of death Establishing drug use in alleged offenders of crimes Establishing drug use in victims of sexual and physical assaults Establishing drug use in drivers of motor vehicles and in pedestrians Establishing drug use in persons involved in workplace accidents Establishing workplace or environmental exposure of workers Assisting investigators with estimation of timing of drug use Adapted from Drummer OH. Toxicology: Methods of Analysis Ante Mortem. In: Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier. Table 2 Most common specimens collected antemortem or in clinical cases
Most common detection window a
alcohol detection; otherwise it should be kept at about 4 C for use within a few days or if required beyond a few days it should be frozen. Urine provides a valuable specimen to assess drug use over the previous day or two. Relatively large volumes (50 ml or more) can be collected, allowing sufficient specimen even for less sensitive techniques. However, drug presence in urine does not necessarily imply recent drug use, let alone assist in predicting possible drug effects. For this reason it is advisable to include blood testing if an assessment of possible drug effects is required.
Hair
Specimen
Examples of use
Blood and plasma (or serum) Urine
Hair Saliva
Detecting drug impairment, compliance, or drug testing in overdoses Workplace or correctional drug detection, sexual assault victims when delay to reporting has occurred Preemployment testing, detecting past exposure On-site drug testing for recent exposure (e.g., drivers)
Hours to day 13 days
Weeks to months Hours
Only approximate and will vary somewhat from drug to drug.
nonclotted blood by removal of the cells by centrifugation; serum is the liquid phase remaining after blood is allowed to clot. In this article blood, plasma, and serum are considered one specimen, unless otherwise differentiated. In forensic cases, and particularly postmortem cases, whole blood preserved with sodium fluoride (1%) is most often used, while in clinical cases plasma treated with some kind of anticoagulant, or serum, is most often used. Therapeutic drug-monitoring programs are frequently conducted in clinical toxicological laboratories in plasma and form the basis of therapeutic drug compliance and help to optimize drug doses. Typically, immunoassays are used in drug monitoring and screening, although high-performance liquid chromatography (HPLC), gas chromatography (GC), and mass spectrometry (MS) techniques are equally well suited.
Urine
This is a frequently collected specimen since concentrations of drugs and metabolites of drugs are usually much higher than for blood. Urine can be treated with sodium fluoride (1%) to prevent fermentation for
Hair has long been used to test for exposure to heavy metals such as arsenic, mercury, and lead and has also proven to be a useful specimen for the analysis of drugs. It is particularly useful to establish drug use many weeks to months prior to collection. Drug entry into hair is complicated and involves a number of processes. Incorporation by entrapment from the blood bathing the growing follicle is a major mechanism, although incorporation through direct contact of mature hair with sweat and/or sebaceous secretions is also a significant source of drug entry. Because of the ability of hair to absorb drug directly, contamination of hair by direct environmental exposure should also be reasonably excluded, if hair results are to be used. For example, nicotine is found in the hair of nonsmokers and cocaine is found in the hair of children of cocaine users. This is a major limitation of this specimen. In contrast to urine, the target analytes in hair are predominantly the parent drugs. Cocaine, D9-tetrahydrocannabinol (THC), heroin and its first metabolite 6-acetylmorphine, and benzodiazepines are found in higher concentrations than their corresponding metabolites. There are a number of factors that influence retention of drugs into hair. Hair color is well known to affect retention of drugs to hair. Hair color is a factor to consider when binding and retention of drugs are concerned. Pigmented hair has higher levels of cocaine than weakly pigmented hair. This is likely to be true for all basic drugs, which bind to melanin, the major pigment in hair. Acidic drugs tend to have lower concentrations than basic drugs. Bleaching and the excessive use of shampoo and conditioners can also reduce the concentration of drugs in hair. For this reason, and the various routes of drug intake into the hair, quantitative results in hair are rarely useful. Notwithstanding these issues, hair has become a particularly useful specimen to monitor drug use over months for persons seeking new employment,
in individuals under corrective services ordered to abstain from illicit drug use, and in custodial matters requiring proof of abstinence of drug use. Segmental analysis of 12-cm sections can also provide some picture of changing drug use over a longer period of time.
Sweat
Sweating is a physiological process providing a mechanism to reduce body temperature. Sweat is produced by eccrine glands located in the transdermal layer of most skin surfaces, and apocrine glands located in axillary and pubic regions. Approximately 40% of all sweat is produced by the trunk, 25% by the legs, and 35% by the head and upper extremities. Sweat is approximately 99% water, the remainder being sodium chloride. A rate of sweating of over 20 ml h1 can occur in stressed situations. Sweat glands are often associated with hair follicles and therefore it is sometimes difficult to differentiate the presence of drugs in hair and sweat. Sweat is normally collected using suitable absorbent devices such as sweat patches. Contact time may vary from a simple swipe over a portion of skin to days for a sweat patch to absorb accumulated sweat. The device used and collection time will affect the ability to detect excreted drugs. In some devices, local heating facilitates sweating, accelerating the detectability of drugs. Modern sweat patches have a low incidence of allergic reactions; however inadvertent or deliberate contamination can limit its usability. Drugs detected in sweat include alcohol (ethanol), amphetamines, cocaine, benzodiazepines, barbiturates, opioids, and phencyclidine.
Saliva
production of saliva. A number of such devices are available to facilitate the collection process. It is also essential that collection of saliva takes place at least 30 min after a meal, or consumption of a beverage or drug, and the oral cavity is free from food material and other objects before collection. The main disadvantage is that the saliva volumes are usually small, hence there will be limited ability to repeat analyses. Additionally, not all subjects will be able to provide saliva on demand. Certain drugs can dry the mouth and a number of physiological mechanisms can markedly reduce salivation. Interpretation of saliva drug concentrations is more difficult than blood since saliva concentrations are subject to more variables than blood, such as degree of protein binding and pKa of drug and pH of saliva. For some drugs saliva concentrations (e.g., benzodiazepines) are much lower than for blood, whereas for others (e.g., amphetamines) concentrations are higher. This specimen is being investigated as a possible on-site specimen to establish drug use at a workplace or roadside. Also, it does not require specialist medical or paramedical experience (e.g., for blood collection) or special collection facilities (e.g., urine collection).
Techniques
A range of techniques are available to detect drugs in specimens collected antemortem. These range from commercial kit-based immunoassays, traditional thin-layer chromatography (TLC), to sophisticated instrumental separation techniques such as HPLC, GC, and capillary electrophoresis (CE). MS is the definitive technique to establish proof of structure of an unknown substance, although a number of other detectors can be used to identify the presence of unknown substances in biological specimens.
Immunoassays
Saliva is primarily excreted by three glands: the parotid, submaxillary, and sublingual, and by other small glands such as labial, buccal, and palatal gland. Mixed saliva used for drug analysis consists of approximately 65% from the submandibular, 23% parotid, 4% sublingual; the remaining 8% is from the other three glands. The daily flow of saliva in an adult ranges from 500 to 1500 ml. Saliva flow is mediated by a number of physiological factors, particularly emotional factors, as well as age, gender, and food intake. Saliva is not an ultrafiltrate of blood, rather a complex fluid formed by different mechanisms against a concentration gradient, by pinocytosis, by ultrafiltration through pores in the membrane and by active transport. Passive diffusion is a dominant mechanism. Saliva is best collected by absorption on to an absorbent material or a device that stimulates
A number of different immunoassay methods are available for drugs of abuse. Numerous commercial kits now exist for this purpose. These include enzyme immunoassay (EIA) (e.g., enzyme-multiplied immunoassay technique (EMIT)) and enzyme-linked inmmunosorbent assays (ELISA), fluorescence polarization immunoassay (FPIA) (e.g., Abbott TDx and ADx), agglutination or kinetic interaction of microparticle immunoassays (e.g., Triage and Online), cloned enzyme donor immunoassay (CEDIA), and various radioimmunoassays (RIA). These kits also include devices for rapid on-site testing on blood, saliva, urine, and sweat without the need for biochemical analyzers.
These tests have the advantage of recognizing more than one member of a class of drugs, e.g., amphetamines, benzodiazepines, and opioids. However, not all members are detected with equal sensitivity. For this reason the sensitivity will not only be dependent on the cross-reactivities of the antibodies to the benzodiazepines, but also to the profile of metabolites present in the specimen, and the amount of the target drug ingested. Different batches of antibody will also influence the sensitivity and selectivity to benzodiazepines and their metabolites. The overall sensitivity in urine can also be increased by prior hydrolysis of urine to convert glucuronide and sulfate conjugates to substances that are detectable by the kit, although reducing recommended cutoff concentrations can accommodate most of the loss of sensitivity. This technique is particularly useful for cannabis, morphine, and the benzodiazepines that are metabolized to hydrolyzable conjugates. Urine-based kits, modified appropriately, can be used for all the specimens listed in Table 2. Precipitation of blood proteins by treatment with methanol, acetonitrile, dimethylformamide, or acetone, and direct analysis of the supernatant are frequently used techniques; however, the high-potency drugs will not always be detected. Prior extraction of blood with a solvent (e.g., butylchloride) provides improved detectability since a concentration step can be employed and most interference can be removed. With all these techniques, not all drugs are extracted. Individual validation must be conducted to ensure adequate detectability. For nonurine specimens it is recommended to use ELISA or DNA technology. In most cases this technique allows direct analysis without the need for specimen treatment. False-positive results with immunoassays occur, from structurally related drugs, from metabolites of other drugs which are recognized by the antibodies, or occasionally by artifacts such as adulterants affecting pH, detergents, and other surfactants. For this reason any positive result must be confirmed by an alternative technique, preferably chromatography with MS identification.
Thin-Layer Chromatography
less than an hour) and a number of samples can be run simultaneously with little cost. Drugs are identified by visualization under ultraviolet (UV) light (as a dark spot), or by spraying with one of a number of reagents which are directed to specific chemical moieties (as a colored spot), or to organic compounds generally. The retention factor (Rf) is calculated by dividing the distance moved from the origin over the distance moved by the solvent front. Characteristic colors of the spots, the presence of metabolite patterns, and the Rf values provide a good means of identifying drugs in biological specimens. Unfortunately, the technique is relatively insensitive and is usually limited to urine analysis, although analysis of gastric contents and liver extracts (in postmortem analysis) is also possible. Densitometry of TLC plates can provide some quantitation of the amount of drug present in an extract. Detection limits of 500 ng ml1 are possible from 5 ml of urine. The use of high-performance TLC (HPTLC) plates has been shown to provide higher sensitivity and can detect some drugs at levels of 100 ng ml1 from 1 ml of blood. Since specificity is not very high, it is advisable to confirm any positive result by an alternative technique, preferably MS identification.
Gas Chromatography
This is the oldest of the chromatographic techniques and is still used in some clinical and forensic laboratories as a screening technique. The movement of an organic-based solvent on a plate containing an absorbent material is based on the separation of drugs (and their metabolites). The stationary absorbent phase is typically silica, although other supports are used. Chromatography is usually rapid (taking
GC is based on the principle of partitioning a substance in a gaseous phase from a stationary liquid phase. The stationary phase is typically a polymeric liquid, which is either coated on to silica, or chemically coated on to the glass surface of the column itself. The nature of the functional groups and polarity of the polymer and the temperature of the column provide the means of varying the separation conditions. Typically, columns are flexible capillaries made of fused silica with internal diameters of 0.10.5 mm, and that are coated with heat-resistant polymers to promote flexibility. A large range of columns is available to provide analysts with a sufficient flexibility to optimize separation conditions. The type of columns range from low-polarity dimethylpolysiloxane, 14% cyanopropylphenyl, 5% diphenylmethylpolysiloxane, to the polar trifluoropropylpolysiloxane, and to 50% diphenyl methylpolysiloxane phases. The use of cyanopropylphenyl or 5% phenylmethylsilicone stationary phases can give better separation of a number of moderately polar compounds than a 100% methylsilicone phase. Due to the wide polarity differences of drugs, temperature programming is necessary for assays involving detection of a number of drugs.
A range of detectors is available for GC. Flame ionization detectors are workhorse detectors for any compounds containing carbon, whereas a number of detectors are available for specific functional groups. The nitrogen phosphorus detector (NPD) selectively detects compounds with either nitrogen or phosphorus, while the electron capture detector (ECD) relies on the ability of a compound to capture electrons when passing through an electric field. ECD detectors give the best detection limits ( 1 ng ml1) from 1.0 ml plasma, although NPD provided detection limits down to 5 ng ml1 for nitrogenous substances and better than 1 ng ml1 for phosphorus-containing substances (e.g., organophosphate pesticides) (Table 3). Poisonous and other gases can be detected using thermal conductivity detectors which do not rely on the presence of carbon or nitrogen. For drugs to be amenable to GC, they must be thermally stable to enable volatilization into an inert gas (e.g., helium and nitrogen). In many cases compounds can be derivatized to improve their thermal stability, or to alter their retention characteristics and thus enable a separation to occur (Table 4). Solid-phase microextraction is a relatively recent technique to enable rapid analysis of drugs without requiring extensive sample cleanup and concentration. Direct online injection using a dialysis technique involving a copolymer precolumn for absorption has also been reported on small sample volumes.
High-Performance Liquid Chromatography
Table 3 Examples of detection systems used in gas chromatography analysis of selected drugs
Drug class Detector
Alcohol and other volatiles Amphetamines Antidepressants Antipsychotics Benzodiazepines Cannabinoids (THC, carboxy-THC, etc.) Carbon monoxide, and other gases Cocaine and metabolites Heroin, morphine, and other opioids Organophosphate pesticides
FID NPD, EI MS, NCI (as derivative) NPD, EI MS NPD, EI MS NPD, ECD, NCI EI MS, NCI (as derivative) TCD NPD, EI MS (as derivative of BE) NPD, EI MS (as derivative of morphine) NPD, EI MS
FID, flame ionization detector; NPD, nitrogen phosphorus detector; EI MS, electron impact mass spectrometry; NCI, negative ion chemical ionization mass spectrometry; ECD, electron capture detector; THC, D9-tetrahydrocannabinol; TCD, thermal conductivity detector; BE, benzoylecgonine. Adapted from Drummer OH. Toxicology: Methods of Analysis Ante Mortem. In: Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier. Table 4 Examples of detection systems used in highperformance liquid chromatography analysis of selected drugs
Drug class Detector
Amphetamines, including ecstasy Analgesics (acetaminophen (paracetamol), salicylate) Anions (bromide, chloride, azide, etc.) Antidepressants Benzodiazepines Buprenorphine Cannabinoids (THC, carboxy-THC, etc.) Catecholamines (epinephrine (adrenaline), dopamine, etc.) Cocaine and metabolites Morphine/codeine Nonsteroidal antiinflammatory drugs
HPLC is a commonly used chromatographic system which involves the separation of compounds by partitioning between a pressurized moving liquid phase and a solid support containing very fine silica (410-mm diameter particles) or bonded silica. The bonded ligand acts as a pseudoliquid phase. Bonded groups include C2, C8, C18, CN-alkyl, and phenylalkyl chains. The physiochemical properties of the bonded phase and the moving phase determine the separation process. Moving phases are often hydroalcoholic solvent systems such as acetonitrile or methanol/unbuffered water to solvent/buffered phosphate solutions, the base modifier triethylamine, and ion-pairing reagents such as methane sulfonic acid, tetramethyl ammonium hydrogen sulfate, and tetrabutyl ammonium bromide. Gradient programming in which the composition of solvent is altered with time provides an ability to separate compounds of widely differing polarity. Normal-phase chromatography on a CN-, OH-bonded column or a silica column function in a similar way to TLC, except that resolution and sensitivity are far greater.
UV and F (of derivitized drug), MS UV and photodiode array Ion conductivity UV and photodiode array, MS UV and photodiode array, MS MS EC and photodiode array, MS ECD UV and photodiode array, MS EC, F and UV, MS UV, DAD
UV, ultraviolet; F, fluorescence; MS, mass spectrometry; THC, D9-tetrahydrocannabinol; EC, electrochemical; ECD, electron capture detector; DAD, diode array or multiwavelength detector.
Detection of the sample is most often by UV spectrophotometry at or near the maximum absorption wavelength. Alternatively, other physiochemical properties of the compound(s) can be exploited. These include infrared (IR), fluorescence (F), phosphorescence, electrochemical (EC) properties, and
conductivity (for ionically charged substances). Compounds with functional groups can be reacted with reagents to impart greater detectability with one or more detectors, or to allow resolution of stereoisomers (Table 4). Photodiode array or multiwavelength detection (to supplement UV detection) offers real advantages to analysts in identifying peaks and assisting in establishing peak purity. Photodiode array detection can be a very useful technique if MS instrumentation is not readily available, or if absolute proof of structure is not required. Detection limits around 1050 ng ml1 are expected for most compounds by HPLC, depending on the physiochemical properties of the drug, the volume of specimen extracted, and the method used. Lower detection limits are possible if larger amounts of sample are extracted and when a concentration step is employed. Solid-phase extraction (SPE) using small columns to absorb drug selectively from the matrix (e.g., Extrelut, Sep-Pak, Bond-Elut, etc.) provides an excellent alternative to conventional liquidliquid extraction techniques. Solid-phase techniques have been published for most analytes and tend to be quick, and often provide clean extracts. These SPE procedures can also be readily automated to improve throughput. Narrow-bore columns (12 mm internal diameter) require less specimen and can easily be interfaced with MS.
Capillary Electrophoresis
and electroosmosis caused by the osmotic migration of cations and water to the cathode because of ionization of the silylhydroxyl groups on the fused silica. The electroosmosis factor (EOF) can be altered by changing the pH of the buffer, ionic strength of buffer, modifiers added to buffer, and type of capillary internal wall coating. Electrokinetic micellar chromatography is capable of analyzing illicit drugs in urine and in plasma. It is also used in screening seized powders for the presence of illicit drugs. This is a powerful technique since it can separate a large range of compounds with high sensitivity and has the ability to separate compounds of widely differing polarity in one run. Multiwavelength UV detection can be used to provide an added degree of confirmation. The sensitivity is adequate for routine confirmatory analyses of presumptive positive urines for drugs of abuse. CE linked to mass spectrometers is an emerging versatile and sensitive analytical technique. The amount of sample or biological extract applied to CE is in the nanogram scale allowing for trace analysis with adequate sensitivity for most applications. It can operate in both qualitative and quantitative modes.
Mass Spectrometry
A powerful emerging technique showing widespread application in forensic science is that of CE. Capillary electrophoresis is actually a number of related techniques, including capillary zone electrophoresis (CZE), micellar electrokinetic capillary chromatography (MECC), capillary electrochromatography, capillary isotachophoresis, capillary gel electrophoresis, and capillary isoelectric focusing, and is complementary to HPLC with high separation power. Capillary electrophoresis consists in its most simple form of a separation capillary of 20100 mm internal diameter and up to 100 cm long, a high-voltage source, electrodes, an injection system, and a detector. The capillary is often fused silica coated with plastic polyimide to confer elasticity. The capillary ends are dipped in buffer and are held at a potential of up to 30 kV. The separation is based on migration of charged drug molecules against an electric field
MS is the definitive technique if unequivocal identification of unknown compounds is required for forensic purposes. MS is usually linked directly to a chromatographic separation process such as CE, HPLC, or GC, or even to another MS (MSMS). Mass spectrometers can be operated under full scan mode, i.e., from m/z 50 to m/z 550 or even higher depending on the molecular weight of the molecules and the size of fragment ions. For MSMS, fragmentation of one or more ions formed in the primary spectrum can also be produced under various reaction modes. Full scan MS provides optimum spectral information (abundance of ions at their respective m/z ratios). Mass spectrometers can also operate in a selected ion mode or equivalent. In this mode only a few ions are normally monitored. This is most commonly used to improve sensitivity for quantifications at lower concentrations or to confirm commonly observed drugs that have already been presumptively identified by other techniques. Compounds do not always show characteristic spectral detail (e.g., amphetamines). Consequently, it is recommended to prepare derivatives for such compounds, or for substances that show poor chromatographic properties (Table 5). One of the most

Table 5 Examples of derivatives used in gas chromatography mass spectrometry analysis of selected drugs
Drug class Derivatives
Amphetamines Barbiturates Benzodiazepines Cannabinoids (THC, carboxy-THC, etc.) Cocaine and metabolites Morphine
AA, HFBA, methyl chloroformate None, or iodomethane in TMAH t-butyl-DMS, TMS, PC/PI TFAA, TMS, PFPA/PFP, t-butyl-DMS t-butyl-DMS, PFPA/PFP, TMS PFPA/PFP, TMS
AA, acetic anhydride; HFBA, heptafluorobutyric anhydride; TMAH, tetramethylammonium hydroxide; t-butyl-DMS, t-butyl dimethylsilyl; TMS, trimethylsilyl; PC, propionyl chloride; PI, propyl iodide; THC, D9-tetrahydrocannabinol; TFAA, trifluoracetic anhydride; PFPA, pentafluoropropionic anhydride; PFP, pentafluoropropan-2-ol. Adapted from Drummer OH. Toxicology: Methods of Analysis Ante Mortem. In: Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
correct for this. For this reason, assays involving MS should use deuterated internal standards wherever possible. The combination of HPLC with MS (LC-MS) and tandem or ion-trap MS (LC-MS-MS) provides good examples of the separation power of HPLC with the sensitivity and specificity of MS. Detection limits range from 10 pg on-column, resulting in detection limits of better than 1 ng ml1 for many compounds using a thermospray or electrospray interface. This technique has become a desired technique in forensic chemical procedures because it can separate substances that are not normally amenable to GC, such as higher-molecular-weight substances or polar compounds that require derivatization. Examples of its use include anabolic and other steroids, diuretics, benzodiazepines, buprenorphine, and other opioids.
See Also
frequent derivatives described is the trimethylsilyl ether for amines, hydroxyl-, and carboxyl-containing substances. Alternatively, other silylethers such as t-butyl are used, and fluorinated acylanhydrides (e.g., pentafluoropropionic anhydride) are widely used for amines and hydroxy compounds, and a combination of a perfluorinated alcohol with a perfluorinated acylanhydride for carboxy-, hydroxy-, and amine-containing substances. Other derivatives are also known. Positive-ion chemical ionization produces a much higher-intensity molecular ion, and is often used to reduce fragmentation and to provide evidence of the molecular weight of the compound. In this mode reagent gases, such as methane, and ammonia are used to produce different ionmolecule collisions in the ion chamber (source). The use of negative-ion chemical ionization (NCI) affords a greatly enhanced detection limit for certain compounds compared to electron impact mass spectrometry (EI MS). In this NCI mode a single ion cluster is often observed and can provide for some drugs (e.g., benzodiazepines and derivatized THC) a detection limit of 0.1 ng ml1. The use of deuterated internal standards provides an ideal way of monitoring changes in chromatographic performance, and most importantly, essentially eliminating matrix effects caused by poor recoveries of drug. While recoveries of drug may vary from one matrix to another, and even from calibrators, the deuterated internal standard will
Alcohol: Breath Alcohol Analysis; Blood and Body Fluid Analysis; Acute and Chronic Use, Postmortem Findings; Autopsy, Findings: Drug Deaths; Organic Toxins; Carbon Monoxide Poisoning: Incidence and Findings at Postmortem; Toxicology: Methods of Analysis, Postmortem
Further Reading
Backer DR (ed.) (1995) Capillary Electrophoresis. New York: Wiley. De Zeeuw RA (1989) Modern chromatographic procedures in systematic toxicological analysis. Journal of Chromatography 488: 199213. Drummer OH (1999) Review: detection efficiency of screening techniques in forensic toxicology. Journal of Chromatography B 733: 2745. Karch SB (ed.) (1998) Drug Abuse Handbook. Boca Raton, FL: CRC Press. Kintz P (ed.) (1996) Drug Testing in Hair. Boca Raton, FL: CRC Press. Levine B (ed.) (1999) Principles of Forensic Toxicology. American Association of Clinical Chemistry. Moffat AC (ed.) (2003) Clarkes Isolation and Identification of Drugs, 3rd edn. London: Pharmaceutical Press. Polettini A (1999) Systematic toxicological analysis of drugs and poisons in biosamples by hyphenated chromatographic and spectroscopic techniques. Journal of Chromatography B 733: 4763. Snyder LR, Kirkland JJ, Glajch JL (1997) Practical HPLC Method Development, 2nd edn. New York: Wiley. United Nations (1998) Guidelines for Testing Drugs Under International Control in Hair, Sweat and Saliva. Vienna, Austria: United Nations.
322 TOXICOLOGY/Methods of Analysis, Postmortem
Methods of Analysis, Postmortem

2005, Elsevier Ltd. All Rights Reserved. This article is adapted from Toxicology: Methods of Analysis Post Mortem in Encyclopedia of Forensic Sciences, pp. 14041409, 2000, Elsevier Ltd.
Introduction
In postmortem cases, as with other forensic cases, toxicology assists the investigating authorities in the investigation of a case (Table 1). Ultimately toxicology testing results assist the coroner, medical examiner or the procurator fiscal (a legal officer in Scotland whose function is to investigate cases of sudden death, amongst other duties, whereas in other jurisdictions based on common law various combinations of coroner and/or medical examiner systems apply), or equivalent judicial officer in other legal systems in establishing the evidence of any drug use. In cases where toxicology fails to detect foreign substances, it allows the investigating pathologist to turn his attention to other relevant factors, since a pathological examination often does not show indicia suggestive of drug use. Drug use can only be confirmed by appropriate toxicology testing procedures. Toxicology testing is particularly important in victims of homicide in which drugs may have been given by the assailant to reduce consciousness of the victim and in cases in which drugs were used by the victim. In the latter scenario, modification of behavior and/or the state of mind by drug use may be important in criminal trials, not necessarily to mitigate the intent of the accused, but primarily to reconstruct, as far as possible, the events that led to the act. Such reconstruction may involve corroboration of witness accounts of drug-using behavior. Typical drugs used in these cases are alcohol, amphetamines, cocaine, or one of the benzodiazepines (alprazolam, diazepam, flunitrazepam, etc.). Victims
Table 1 Reasons for drug testing in postmortem cases Eliminating involvement of drugs in cases Establishing drug use in victims of homicide Establishing drug use in drivers of motor vehicles Establishing drug use in persons involved in workplace accidents Establishing drug use in other cases of sudden and unexpected death Assisting investigators with estimation of timing of drug use Reproduced from Drummer OH. Toxicology: Methods of Analysis Post Mortem. In: Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
or perpetrators of violent crime may also have consumed medication to treat a psychiatric problem or a host of other medical conditions. The presence of drugs may therefore allude to such treatment, or at least confirm that the person concerned has taken their medication. In some cases, these medications may even have contributed to behavioral problems. In practice, it has been observed that deceased persons have often consumed two or more drugs, and in many cases the investigating authority (pathologist, coroner, etc.) is not aware of all the drugs used. Since the great majority of cases (>70%) involve more than one drug, it is advisable to conduct a broad drug screening to include most of the common drugs, rather than target the analysis to one or a limited range of drugs suggested by the circumstances. This also allows experts to determine whether any adverse drug interactions have occurred.
Specimens
The preferred specimens collected at postmortem will depend on the type of case. Typically one or more blood specimens and urine are collected, although as Table 2 illustrates, a number of other specimens should be taken in certain case types. A useful forensic technical procedure in the autopsy suite is to take a full set of specimens, in all but the most obvious natural-cause investigations. This will avoid the embarrassment of insufficient or inappropriate specimens collected in a case and give the toxicologist the best chance to satisfactorily complete the analytical investigation. Against this may have to be balanced the legal and cultural sensitivities surrounding the collection and retention of tissue specimens at postmortem.
Table 2 Recommended postmortem
Type of case
minimum
specimens
collected
Recommended specimens collected
All cases
Homicides and suspicious cases Drug-related cases Volatile substance abuse cases Biochemical abnormalities (insulin, etc.) Heavy metal poisoning
Peripheral blood (2 10 ml), one tube preserved with fluoride to at least 1% w/v Urine (10 ml) Vitreous humor (25 ml) Plus liver, hair Plus gastric contents, liver, hair Plus lung fluid or tied-off lung, liver Plus serum
Plus liver, hair, kidney
Reproduced from Drummer OH. Toxicology: Methods of Analysis Post Mortem. In: Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
TOXICOLOGY/Methods of Analysis, Postmortem 323 Blood
Blood is the most useful specimen that can be collected since drugs present in this fluid can best be related to a physiological effect and can be used to assess the likelihood of recent drug use or exposure to chemicals. A number of problems are associated with the collection of this fluid in cadavers. Two 10-ml samples of blood are recommended, one to be used for blood alcohol analyses and the other for blood toxicology. The splitting of the two blood specimens reduces the possibility of contamination in the laboratory and enables the blood alcohol specimen to be retained separately to the other blood specimen. Forensic technicians or pathologists should be aware that the collection of peripheral blood reduces the possibility of postmortem artifacts frustrating interpretation of any positive results. The preferred collection site is the femoral vein (leg). However, failure to collect the specimen distal to a ligature or clamp applied to the femoral vein may allow blood to be drawn down from the inferior vena cava in the abdomen, where the concentration of drugs may be significantly higher. Similarly, the blood should be collected before the body is eviscerated, to avoid contamination. Autopsy procedures should therefore accommodate the need to obtain optimal blood specimens for toxicological purposes.
Urine
evidence of shaking, vitreous humor should only be taken after careful consideration and procedures such as retinal photography have been completed.
Liver
The liver is traditionally a favored tissue for toxicologists since drugs are often found in higher concentrations than blood and the liver can be readily homogenized. All cases of suspected drug use should have a portion of liver collected. A 100-g aliquot is sufficient for most analyses. The right lobe is preferred, since it is least subject to postmortem diffusion of drug from the bowel contents and the mesenteric circulation.
Gastric Contents
Urine is the second most important specimen collected. Since concentrations of drugs and metabolites of drugs are usually much higher than in blood, urine provides a valuable specimen to assess drug use over the previous day or two. Urine can be collected after opening of the abdomen, or by direct puncture of the bladder. An autopsy is therefore not necessary to collect this specimen. Blood and vitreous humor can also be taken by direct puncture of the relevant anatomical region. When blood is obtained by direct puncture, the site of collection should be specified on the specimen tube.
Vitreous Humor
Gastric contents are invaluable in cases of suspected poisoning. The aim of using this specimen is to establish the actual content of drug (or poison) remaining in this organ at death and gastric analysis may allow the route of drug administration to be determined. Drug residues can be isolated out by direct extraction with methanol, or another solvent, and analyzed by conventional chromatographic techniques. When little or no fluid is present in the stomach provision for the whole stomach allows the analyst to dissolve any drug adhered to the sides of the walls. Toxicologists should be aware that small quantities of drug will derive from the bile, especially during agonal processes, hence drug content in the stomach must not necessarily imply oral ingestion. Results should be reported in milligrams (total gastric content). If only an aliquot of gastric contents is supplied the results may need to be reported as a concentration. However, gastric contents are rarely homogeneous particularly after meals hence whole contents are preferred wherever possible. Occasionally, pathologists will need to examine the stomach. This should be done prior to collection of any contents.
Lungs
Vitreous humor is an ideal fluid to accompany positive blood-alcohol cases, since the alcohol content of vitreous is very similar to that of blood and can prove useful to exclude putrefactive formation of alcohol in blood, and visceral contamination. Vitreous humor is also a useful fluid for a range of drugs including digoxin and antidepressants, as well as a number of biochemical markers. Since vitreous humor can easily be collected, it is strongly recommended that this specimen should be included in a routine suddendeath investigation. In pediatric cases, where the eyes may need to be examined histologically for
Lung fluid (or tied-off lungs) is (are) recommended in cases of suspected volatile substance abuse. Since quantitative results are rarely interpretable, only detected or not detected results are usually sufficient (Table 3). In jurisdictions where tissue cannot be collected or retained freely, blood from the pulmonary vein or the left side of the heart can be used in this context.
Other Specimens
Occasionally other specimens can provide valuable information in a case. Hair can provide a history of drug use, or exposure to chemicals if chronic exposure is thought to have occurred. Hair can therefore

Table 3 Particular toxicological usefulness of various tissues
Tissue Substances detected
General Techniques
The range of techniques available to detect drugs in the specimens collected postmortem are essentially identical to those collected antemortem. These range from commercial kit-based immunoassays (ELISA, EMIT, FPIA, CEDIA, RIA, etc.), traditional thinlayer chromatography (TLC), to instrumental separation techniques such as high-performance liquid chromatography (HPLC), gas chromatography (GC), and capillary electrophoresis (CE). Mass spectrometry (MS) is the definitive technique to establish proof of structure of an unknown substance and can be linked to GC, HPLC, and CE. Even MS has its limitations, e.g., special techniques may be needed to characterize phenethylamines that do not have sufficiently unique spectra. The specimens analyzed in postmortem cases are most often blood and liver, rather than urine and serum that are used in antemortem analysis and the other specimens listed earlier. The use of blood and liver, and indeed all other postmortem specimens, require separate validation against those methods used in antemortem analysis. The methods used require modification to ensure a reliable extraction recovery, a low level of interference, and reproducible quantitative results. Special attention to these factors is required on partly or fully putrefied specimens to ensure no interference from endogenous substances. Cutoff values often used in workplace, sports, and drugs-of-abuse testing are no longer appropriate in postmortem cases involving alternative speciments to urine. Even postmortem urine should not normally be tested to cut-off limits used in drugs-of-abuse testing since the presence of a small concentration of drug may be of forensic significance. The range of immunoassays used in antemortem analysis can also be used in postmortem analysis provided suitable modification in the preparation of the specimen occurs. Urine-based kits can be used for urinalysis, but blood or tissue homogenates require special treatment to remove matrix effects. Urine is often unavailable in postmortem cases. Enzymelinked immunosorbent assay (ELISA) techniques have become the screening technique of choice for the direct analysis of blood (and other specimens such as hair digests) for drugs of abuse. False-positive results with immunoassays occur, either from structurally related drugs or from metabolites of other drugs that are recognized by the antibodies. While HPLC and GC techniques are more specific than immunoassays, any positive result should be confirmed by mass spectral identification, unless sufficient validation of another method has been conducted to ensure courts of the reliability of the result. Unconfirmed drug results, if reported, should
Blood/urine/liver/hair/ gastric contents Vitreous humor Bile Lungs
All drugs and poisons Alcohol, digoxin, creatinine, urea, glucose Morphine and other narcotics, benzodiazepines, colchicine Volatile substances (toluene and other solvents, butane and other aerosol gases, automobile and aviation fuels)
Reproduced from Drummer OH. Toxicology: Methods of Analysis Post Mortem. In: Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
provide evidence of drug use for much longer periods of time than urine. The relation between dose and hair concentration is usually poor, although some comparisons can be made as to the extent of drug use, e.g., regularity of heroin use. Bile can sometimes be a useful fluid for detecting morphine or heroin use since biliary concentrations are much higher than those in blood. A number of other drugs are also found in bile in relatively high (and therefore more easily detectable) concentrations including colchicine, other narcotics, benzodiazepines, and glucuronide metabolites. Bile may also occasionally be useful in late-stage paracetamol poisonings. Samples of brain tissue may be more relevant for some centrally active (the term central includes the brain and spinal cord) drugs such as morphine, and skin (with associated subcutaneous tissue) may show large deposits of drugs left behind after an injection. When taking skin for the purpose of determining a likely injection site it is important that a control site be also collected, for example, from the other arm. Results are normally expressed as milligrams per gram wet weight tissue. Other specimens may be useful in specific circumstances, e.g., cerebrospinal fluid in medical matters involving intrathecally administered drugs.
Specimens from a Putrified Body
In cases of extreme putrefaction, the recommended list of specimens will no longer be appropriate. Muscular tissue, hair, and bone can be useful specimens in this type of case, although the physical state of the body will determine what specimens are available for collection. Body fluids will be present in some putrefied bodies, however this is no longer blood, but rather liquified tissues; however, this fluid can be used to screen for the presence of drugs. Quantitative results are of little use in badly putrefied cases.
TOXICOLOGY/Methods of Analysis, Postmortem 325
be flagged as presumptive, or by words of similar meaning. Solid-phase extraction (SPE) using small columns to selectively absorb drug from the matrix (e.g., Extrelut, Sep-Pak, Bond-Elut, etc.) provides an excellent alternative to conventional liquidliquid extraction techniques. Solid-phase techniques have been published for most analytes, tend to be quick, often provide clean extracts, and can be readily automated. The use of deuterated internal standards provides an ideal way to monitor changes in chromatographic performance, and most importantly, essentially eliminating matrix effects caused by poor recoveries of drug. While recoveries of drug may vary from one matrix to another, and even from calibrators, the deuterated internal standard will correct for this. For this reason, assays involving MS should use deuterated internal standards wherever possible in postmortem analyses. The analyst should always be on the alert for unusual findings. For example, if a large acetone peak is seen in an alcohol analysis this might suggest
undiagnosed diabetes in life, or a peak not recognized as a drug in a library search on the MS may be evidence of an unusual or uncommon substance.
Recommended Techniques for Postmortem Analysis

As indicated before it is important that a drug screen encompasses the widest number of drugs and poisons without seriously compromising the ability of the laboratory to work on sufficient cases. Urinalysis (or blood or another fluid) using one of the commercial immunoassays, or even TLC, is recommended for the main classes of drugs. These usually include amphetamines, barbiturates, benzodiazepines, cannabinoids (cannabis metabolites), cocaine metabolite, and morphine-like opioids. In addition, a series of other (usually chromatographic) tests are strongly recommended. The schema shown in Figure 1 illustrates a typical analytical profile for routine case screening on blood.
Blood Alcohol analysis Volatile analysis Heavy-metal analysis Morphine analysis Other specific analyses
1. Adjust to pH 2 and extract 2. Precipitate proteins Acidic/neutral screen
1. Extract at pH 9--10 with butylchloride 2. Solid-phase extraction pH 9--10 Basic/neutral screen
Apply to HPLC or GC
Apply to GC-MS
Analgesics
Amphetamines
Antiinflammatories
Barbiturates
Antidiabetics
Benzodiazepines
Benzodiazepines
Antihistamines
Diuretics
Antidepressants
Xanthines
Cocaine
Herbicides
Narcotics
Anticonvulsants
Antipsychotics
Other acidic substances
Organophosphates Strychnine
Figure 1 Schematic showing extraction steps for blood analyses and substances classes likely to be detected. Reproduced from Drummer OH. Toxicology: Methods of Analysis Post Mortem. In: Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
Blood is analyzed for alcohol and is subject to screening techniques aimed at capturing a wide selection of common chemical substances. Only GC techniques are recommended for the analysis of alcohol (ethanol). An acidic screen includes the nonnarcotic analgesics (acetaminophen and aspirin), the nonsteroidal antiinflammatory drugs (celecoxib, naproxen, ketoprofen, ibuprofen, etc.), many of the diuretics (frusemide, hydrochlorothiazide, etc.), the anticonvulsants (carbamazepine, lamotrigine, phenobarbital, phenytoin and valproate), barbiturates and the more potent benzodiazepines, and the xanthines such as theophylline and caffeine. The use of a solvent extraction technique at acidic pH or simple precipitation of blood proteins with acetonitrile enables these substances to be detected by gradient HPLC with multiwavelength or photodiode array detection. A basic extraction procedure using butyl chloride (preferred solvent, but others are also suitable), or an SPE procedure using octadecyl-bonded cartridges or mixed-phase cartridges will provide a reasonably clean extract from postmortem blood (and other tissues) for analysis by capillary GC. The use of a MS detector is preferred (to allow simultaneous detection and confirmation), although a nitrogen phosphorous detector (NPD) will provide a higher sensitivity for many substances than full-scan MS. Electron capture detectors (ECD) are extremely useful for benzodiazepines. The use of dual detectors (NPD and MS, or NPD and ECD) provides an additional degree of specificity and detection over one detector alone. These two screening procedures will also enable a number of unusual poisons to be detected. Organophosphates and strychnine are readily detected by GCNPD, while HPLC of acid extracts enables detection of a number of herbicides and other agricultural chemicals. If circumstances suggest volatile substance abuse, exposure to heavy metals, lysergic acid diethylamide (LSD) and other nonamphetamine hallucinogens, or other noxious substances not covered earlier, specific additional tests need to be performed. It is advisable to perform a blood test for morphine if heroin or morphine use is suspected (or needs to be ruled out) and the urine test for opioid is negative. Heroin deaths have been missed if screening for morphine is restricted to urine since acute deaths in naive users may not show morphine in urine.
Redistribution
Foremost is the process of redistribution which affects all analyses in which concentrations of drugs in blood and tissues alter due to disruption of cellular membranes, causing alterations of drug concentrations within tissue elements and diffusion from one tissue to another. This process is particularly significant for drugs with high lipid solubility, since these drugs tend to show concentration differences in tissues and blood. Table 4 shows the extent of these changes for selected drugs when comparisons are made between blood collected from the heart and that collected from the femoral region. The femoral blood is least subject to redistribution after death; however, drugs with much higher concentrations in muscular tissue will still diffuse through the vessel walls and elevate the neighboring blood concentrations. If the femoral vessels are not tied off from the vena cava and aorta then the process of drawing blood can also extract blood from the abdominal cavity that has been contaminated from diffusion of gastric and intestinal contents. It is therefore advisable to reduce these processes by collecting blood specimens as soon as possible after death from the femoral region with blood vessels tied off to reduce contamination. In cases where death has occurred in hospital it is recommended to obtain specimens taken for clinical purposes immediately before death, or on admission to hospital, whichever is more appropriate. These processes are not limited to blood. Liver and lung tissues show differences in the concentration
Table 4 Likely extent of postmortem redistribution for selected drugs
Likely extent of postmortem redistributiona
Drug/drug class
Acetaminophen (paracetamol) Alcohol (ethanol) Amphetamines Antipsychotics Barbiturates Benzodiazepines Cocaine Digoxin Methadone Morphine, codeine Propoxyphene Salicylate Serotonin reuptake inhibitors Tetrahydrocannabinol (THC) Tricyclic antidepressants
Low Low Low to moderate Moderate to high Low to moderate Low to moderate Low Very high Moderate Low Very high Low Low to moderate Low to moderate High
Postmortem Artifacts in Analysis

The process of death imparts a number of special processes that affect the collection, analysis, and interpretation of specimens obtained at autopsy.
a Low, up to 20% elevation; moderate, 2150%; high, 50200%; very high, >200%. Reproduced from Drummer OH. Toxicology: Methods of Analysis Post Mortem. In: Encyclopedia of Forensic Sciences. Edited by Jay A Siegel, Pekka J Saukko and Geoffrey C Knupfer. Academic Press: London. 2000. With permission from Elsevier.
TOXICOLOGY/Methods of Analysis, Postmortem 327
of drugs depending on the nature of the drug and whether diffusion of drug has occurred from neighboring tissues or the blood supply. For example, the left lobe of the liver is more likely to exhibit elevated drug concentrations than the right lobe.
Metabolism and Bioconversion
A number of drugs can undergo chemical changes in a body after death. These chemical changes can be either metabolically mediated or caused by spontaneous degradative processes. For example, the metabolism of heroin to morphine occurs in life and in recently deceased persons by the action of blood and liver esterases. For this reason, heroin is rarely detected in cadaveric tissues. 6-Acetylmorphine is detected in urine for a few hours after last use. Morphine is the main target drug for most specimens. Aspirin is converted rapidly to salicylate by hydrolytic mechanisms. Most prodrugs activated by desterification or hydrolysis will be subject to similar processes. Nitro-containing drugs, such as the benzodiazepines, nitrazepam clonazepam, flunitrazepam, and others are also rapidly biotransformed after death to their respective amino metabolites by the action of certain types of bacteria (obligate anaerobes). Toxicologists must therefore target their analyses to these transformation products rather than the parent drug. Sulfur-containing drugs such as dothiepin, thiopental, thioridazine, etc., are also subject to bacterial attack during the postmortem interval leading to progressive losses due to putrefaction. Of course, the parallel process of tissue loss will also affect the tissue concentration during putrefaction. Chemical degradation occurs for a number of drugs and metabolites even when specimens are stored frozen at 20 C. Some benzodiazepines and benzodiazepine metabolites, antipsychotics such as thioridazine, and the beta stimulant fenoterol, show time-dependent losses. For many drugs, complete stability characteristics have not yet been evaluated. Alcohol will be lost by evaporation unless sealed tubes are stored at 80 C; however, alcohol (as ethanol) can also be produced by bacterial action on glucose and other sugars found in blood. The use of potassium fluoride as preservative (minimum 1% w/v) is required to prevent bacterial activity for up to one month after collection, when stored at 4 C.
HPLC, GCMS, etc.), on which specimens the analyses were conducted, and of course the result(s). The result(s) should be unambiguous using such terms as detected or not detected. The use of the term not present should be avoided, since it implies no possibility of the substance being present. A toxicologist can rarely be so definitive and can only indicate that a substance was not detected at a certain threshold concentration. For this reason, a detection limit alongside tests for specific substances should be provided for not detected results. For quantitative results, consistency in units is advised and should not be given with more significant digits than the accuracy will allow. For example, there is no point in reporting a result for blood morphine as 0.162 mg l1 when the accuracy and precision of the method is 20%. A result of 0.16 mg l1 would suffice. For drug screening results it is advisable to provide clients with an indication of the range of substances a method is capable of detecting, and some indication of the detection limit, i.e., at least therapeutic concentrations or only supratherapeutic concentrations. Positive immunoassay results should also be reported even if this presumptive detection has not been confirmed. This information can be useful since it may imply (to an expert later investigating the case) that the substance may have been present but at very low concentrations, or that there was another immunoreactive compound which was not excluded in the confirmation assay. To exclude these results could be construed by courts as a deliberate withholding of evidence. To enable proper interpretation of evidence all reports should indicate the site of blood sampling, and provide where relevant, some comment on the possibility of postmortem artifacts such as redistribution. By incorporating these comments, uninformed persons reading the report are less likely to unwittingly misinterpret the results.
See Also
Toxicology: Methods of Analysis, Antemortem
Further Reading
Chemical Toxicology Institute (2002) Baselts Disposition of Toxic Drugs and Chemicals in Man. Foster City: CTI. Drummer OH (1998) Adverse drug reactions. In: Selby H (ed.) The Inquest Handbook, pp. 122134. Leichhardt, NSW, Australia: The Federation Press. Drummer OH, Odell M (2001) The Forensic Pharmacology of Drugs of Abuse. London: Edward Arnold. Karch SB (ed.) (1998) Drug Abuse Handbook. Boca Raton, FL: CRC Press. Levine B (ed.) (1999) Principles of Forensic Toxicology. American Association of Clinical Chemistry.
Reports
Once an analysis is complete, a report must be issued to the client(s) that accurately details the analytical findings. These results should indicate the type of tests conducted, the analytical method used (i.e.,
328 TOXICOLOGY/Methods of Analysis, Postmortem Maurer HH (1992) Systematic toxicological analysis of drugs and their metabolites by gas chromatographymass spectrometry. Journal of Chromatography 118: 342. Moffatt AC (ed.) (2003) Clarkes Isolation and Identification of Drugs, 3rd edn. London: The Pharmaceutical Press. Polettini A (1999) Systematic toxicological analysis of drugs and poisons in biosamples by hyphenated chromatographic and spectroscopic techniques. Journal of Chromatography B 733: 4763. Pounder DJ (1993) The nightmare of post-mortem drug changes. Legal Medicine 163191. Pounder DJ, Jones GR (1990) Postmortem drug redistribution a toxicological nightmare. Forensic Science International 45: 253263.
Toxicology, Accreditation
See Accreditation: Toxicology
Toxicology, History of
See History of Toxicology
Toxicology, Internet and
See Internet: Toxicology
V
VENOM
J White, Womens and Childrens Hospital, Adelaide, SA, Australia
2005, J. White. Published by Elsevier Ltd. All Rights Reserved.
Definitions
Venom is a substance or mixture of substances produced by an animal, with the function of inducing deleterious toxic effects in another animal, for the purpose of prey acquisition, prey predigestion, or defense against a predator. Venom is usually a complex mixture of substances, in which proteins or peptides predominate.
Venomous Animals
Animals have evolved venom and venom delivery mechanisms on many separate occasions, in diverse environments and throughout the animal kingdom. A list of principal animal phyla that include venomous species is shown in Figure 1. From a perspective of risk to humans, several groups stand out as of major importance. These include venomous snakes, scorpions, spiders, insects, ticks, jellyfish, stinging fish, and selected molluscs. For all these animals it should be remembered that humans are neither a target prey nor predator species. Toxicity to humans from venom is, in some sense, an accident of nature. However, the predominance of humans in most environments and the ubiquitous nature of venomous animals ensure that humans are frequently at risk of envenoming.
displayed an ability to utilize modern transport infrastructure to extend their range and there is no reason to believe this process will not continue, and possibly accelerate over time. A specific example is the colonization of parts of Japan, with Osaka as the epicenter, by Australian redback spiders, a species that is already the leading cause of envenoming and requiring antivenom treatment. Highly toxic parthenogenetic scorpions have successfully colonized parts of urban Brazil and are well placed to be accidentally exported to other urban areas throughout the world. Venomous snakes are less easily exported successfully than arthropods, but with a rising number of illegal specimens in captivity and in transit between keepers, the possibility of release into the wild with successful colonization has moved from a theoretical risk to a real risk. Thus, while the risks of envenoming in most areas are almost wholly from native species, this cannot always be assumed to be the case. It is entirely possible for felonious envenoming to be perpetrated using species exotic to the area. Further, the growing trade in crude and refined venoms allows the use of these directly by individuals essentially everywhere.
Venom Delivery
Venom can be delivered by biting or stinging. Either mechanism may leave detectable marks, but may not always do so. Even for snakes, fang marks may not be visible, despite severe, even lethal envenoming. Thus, determining if envenoming has occurred rests not only on locating bite/sting marks, but evidence of local or systemic effects of envenoming, or detecting venom. The latter is only a routine diagnostic option in Australia and New Guinea for snakes specific to the region. In all other areas it remains essentially a restricted research tool. The principal types of venom delivery are listed in Table 1. It must be remembered that, for any venomous animal, there is usually variability in quantity and quality of venom delivered, often under some degree of voluntary control, as in snakes. This may result in the dry bite phenomenon, where, although
Overview of Epidemiology of Envenoming

Envenoming of humans has traditionally been associated with the rural tropics, especially for snakebite. It is now apparent that some of the more dangerous venomous animals, notably snakes, scorpions, and spiders, are adapting to more varied and urban environments, resulting in an increase in the areas where humans are at risk. Further, these animals have
330 VENOM
PHYLA Porifera Sponges Hydrozoa Hydroids Coelenterata Coelenterates Scyphozoa Jellyfish Anthozoa Sea anemones & corals Cephalopoda Squids, cuttlefish & octopuses Gastropoda Snails & slugs Crustacea Crustaceans Arachnida Scorpions, spiders & other arachnids Arthropoda Arthropods Diplopoda Millipedes Chilopoda Centipedes Insecta Insects Asteroidea Starfish Echinodermata Echinoderms Echinoidea Sea urchins Holothuroidea Sea cucumbers Chordata Chordates Vertebrata Vertebrates Chodrichthyes Cartilagenous fish Sharks & rays Osteichthyes Bony fish Amphibia Amphibians Reptilia Reptiles Aves Birds Mammalia Mammals SUBPHYLUM or CLASS CLASS
Mollusca Molluscs
clinical classification, as given in Table 2, is most useful. It should be remembered that venom is not immutable. Even in a single specimen, venom may vary in potency and relative concentration of components over time, either ontologically or seasonally. Major variations may occur within a single species, over a geographic range. Venom studies are either in vitro or in vivo, but the latter may not accurately indicate effects in humans, because each species may react quite distinctly to a given venom. For example, Australian funnel web spider venom, rapidly lethal in humans, is virtually harmless in most laboratory animals. Thus median lethal dose (LD50) determinations in mice may not give a useful guide to likely toxicity in humans. Similarly, toxic effects observed in other animals may be minor or absent in humans. The only reliable guide for human envenoming is data on human cases, regrettably distinguished by the paucity of such information for most venomous animals, even some species known to cause major envenoming frequently. Of the more important venom actions on humans, several stand out as major causes of morbidity and mortality. These are listed, with examples of animals likely to cause these effects, in Tables 36.
Clinical Effects
The major clinical effects follow from the clinical venom classification discussed above. It is important to understand these effects, as their presence can be of great diagnostic importance. For any given venomous species, a particular pattern of local and/or systemic effects will predominate. However, it is always possible that an individual specimen may have aberrant venom, resulting in atypical effects. In determining if envenoming is a sustainable diagnosis in an unexplained death, the pattern and onset of major clinical effects may be crucial.
Paralytic Neurotoxicity
Figure 1 Major phyla containing venomous animals. Julian White. Reproduced with permission.
a bite/sting occurs, insufficient venom is injected to cause medically significant effects. Rates of dry bites vary from species to species, from >90% to <10%. The nature of the bite/sting may be important in predicting the likelihood of a dry bite. Multiple bites/stings are usually associated with significant envenoming. The act of biting/stinging may be apparent to the human victim, but this is not always the case. Even for snakes, and certainly for other venomous animals, envenoming can be painless and go unnoticed by the victim, who may present later with unexplained symptoms that may not, initially, suggest envenoming.
Venom Activity
There are many ways of classifying venom activity and components. From a medical perspective, a
Paralytic neurotoxins are found in a variety of organisms (Table 3), but particularly in selected snakes, notably many elapids and some viperids. All are systemic toxins, exerting their effects throughout the body, not locally. They do not cause regional paralysis or hemiparesis. Paralytic neurotoxins generally affect the neuromuscular junction, either presynaptically (modified phospholipase A2 toxins), causing damage to the terminal axon and cessation of synaptic vesicle production and release, resulting in severe, prolonged, antivenom-insensitive paralysis, or postsynaptically, binding to the acetylcholine receptor, resulting in more rapid, but often reversible, paralysis, usually
VENOM 331
Table 1 Major types of venom delivery mechanisms
Type of animal Venom delivery mechanism
Immediate effects of venom delivery
Noticeability of wound
Snakes Scorpions Spiders Insects Ticks Venomous stinging fish Blue-ringed octopus Cone shells Jellyfish
Fangs biting Sting on tail (telson) Fangs biting Mostly stings Hypostome bite Venomous spines sting Beak biting Radula tooth harpooning Nematocysts stinging
Usually painful, but some major species can deliver painless lethal bites Usually immediate pain Vary from intense pain to painless Usually some degree of local discomfort Local irritation or painless Local pain
Fang marks are often visible, but may be very hard to see in some cases Sting site may not be prominent Except for large spiders, fang marks may not be apparent Sting may not be visible, but note the presence of sting and venom gland in honeybee stings Tick is usually in situ, but after removal, hypostome may be left in skin Spine puncture usually visible; spine tip may be left in the wound Bite marks generally hard to see Marks may be hard to see Usually a clear area of tentacle contact with local reaction, but area can be small and hard to find
Usually painless Painless to painful Mostly cause local pain, but a few potentially lethal species cause painless stings
Julian White. Reproduced with permission.
Table 2 Clinical classification of venom actions not an exhaustive list

Type of venom action Type of venom component Types of animal
General site of action
Clinical effects
Local toxins
Bite site and bitten limb
Necrotoxins, cytotoxins
Local effects; may include pain, swelling, blistering, bruising, necrosis
Paralytic toxins
Specific systemic (neuromuscular junction)
Myolytic toxins
Specific systemic (skeletal muscle) Specific systemic (interfere with hemostasis in a variety of ways, or may damage vessel walls and promote bleeding)
Neurotoxins (presynaptic, postsynaptic, dendrotoxins, fasciculins) Myotoxins
Progressive flaccid paralysis of skeletal muscle and diaphragm
Hematologic toxins
Nephrotoxic toxins Cardiotoxic toxins Neuroexcitatory toxins
Specific systemic (kidneys)
Procoagulants Fibrino(geno)lytics Anticoagulants Hemorrhagins Various other toxins affecting hemostasis Nephrotoxins
Destruction of skeletal muscle throughout body (or locally in bitten limb only for some crotalids) Varies, depending on type of toxin; may cause consumption coagulopathy, complete defibrination, active hemorrhage promoting, or even thrombosis and infarction or embolism (Martinique vipers only) Renal damage, failure, or necrosis
Snakes, spiders, insects, spiny fish, jellyfish Snakes, ticks, blueringed octopus, cone shells Snakes
Snakes,
Lonomia
caterpillars
Snakes,
Loxosceles
Specific systemic (heart)
Cardiotoxins
Cardiac arrhythmias, failure or arrest Widespread neuroexcitation, particularly of autonomic nervous system
Specific systemic (neural synapses throughout body, usually excluding central nervous system)
Neurotoxins (excitatory)
spiders Snakes, scorpions, jellyfish Scorpions, spiders, irukandji jellyfish
332 VENOM
Table 3 Major groups of venomous animals likely to cause flaccid neurotoxic paralysis
Type of animal Examples Type of neurotoxina Responsiveness to antivenomb
Elapid snakes
Viperid snakes
Kraits Coral snakes Mambas Cobras (some) King cobra Death adders Selected Australian snakes; tiger snakes, taipans, rough-scaled snake Sea snakes Mohave rattlesnake (some) Neotropical rattlesnakes Sri Lankan Russells viper Paralysis ticks Cone shells Blue-ringed octopus Box jellyfish
Pre- and postsynaptic Postsynaptic Dendrotoxins and fasciculins Postsynaptic Postsynaptic Postsynaptic Pre- and postsynaptic Postsynaptic Presynaptic Presynaptic Postsynaptic Presynaptic Presynaptic Presynaptic Presynaptic
Limited Reasonable Reasonable Reasonable Reasonable Reasonable Minimal Reasonable Limited Limited Reasonable (only for Pulchella tab) Limited None available None available Limited
Arthropods Molluscs Coelenterates

a b
Definite, predominant, or most likely major site of action in humans. Reasonable, reasonable likelihood of reversal; limited, only limited or incomplete reversal in most cases; minimal, minimal chance of reversal in most cases. Julian White. Reproduced with permission.
Table 4 Major groups of venomous animals likely to cause systemic myolysis

Type of animal
acetylcholine destruction, resulting in gross excess of neurotransmitter at the neuromuscular junction, causing both muscle weakness and twitching.
Myolysis
Examples
Elapid snakes
Viperid snakes
Sea snakes Selected Australian snakes: tiger snakes, roughscaled snake, taipans, mulga snakes, Colletts snake Some South American pit vipers (Crotalus spp., selected Bothrops spp.) Sri Lankan Russells viper
antivenom-sensitive. In both types, there will be a progressive onset of flaccid paralysis, usually first observed in the cranial nerves, with ptosis, ophthalmoplegia (Figure 2), dysphagia, drooling, loss of airway protection, then limb weakness, loss of deep tendon reflexes (DTRs), finally respiratory paralysis: the rate of progression from first signs to lethal respiratory failure varies from 1 h to >24 h. Those animals causing exclusively flaccid paralysis (kraits, a few cobras, coral snakes, selected other snakes, blueringed octopus, cone shells) may leave little local trace of a bite; the bite/sting may be painless and go unnoticed and the first sign may be progressive paralysis. Some patients may be bitten while asleep, dying of respiratory paralysis before others awake, or collapse in the water and drown. African mamba snakes have rather different neurotoxins that work synergistically (dendrotoxins and fasciculins), causing excessive acetylcholine release, coupled with decreased
A number of snake venoms cause systemic myolysis (Table 4). They target skeletal muscle, causing widespread disruption of muscle cells, but not the basement membrane, from which muscle regeneration can occur over a number of weeks. Muscle destruction may commence soon after envenoming and extend over several days, with delayed onset possible more than 24 h postbite. Clinically there will be muscle pain, tenderness, sometimes swelling, weakness, with red to black urine from myoglobin (Figure 3) and grossly elevated plasma levels of creatine phosphokinase (CK), which can greatly exceed 100 000 IU l1. Secondary hyperkalemia and renal failure can develop, and may prove lethal. Antivenom can modify the extent of myolysis. Biopsy of affected muscles will show characteristic muscle-cell damage.
Coagulopathy
Coagulopathy with promotion of bleeding is a common theme among venomous animals, especially snakes (Table 5). The mechanisms of coagulopathy in snake venoms are varied, with numerous points of attack (Table 7). Several distinct components in the venom may act synergistically. In particular, the combination of toxins that disrupt the coagulation pathways and hemorrhagins that disrupt small blood vessels, as seen in some viper venoms, is a potent
VENOM 333
Table 5 Major groups of venomous animals likely to cause primary coagulopathy
Type of animal Examples Type of venom action
Colubrid snakes Elapid snakes
Viperid snakes
Lonomia caterpillars
Boomslang, vine snake Yamakagashi, red-necked keelback Selected Australian snakes; tiger snakes, rough-scaled snakes, taipans, brown snakes, broad-headed snakes Selected Australian snakes; mulga snakes, Colletts snake, Papuan black snake Saw-scaled or carpet vipers Gaboon vipers and puff adders Russells vipers Malayan pit viper North American rattlesnakes North American copperheads South American pit vipers (selected Bothrops spp.) Asian green pit vipers (selected Trimeresurus spp.) EuroAsian vipers (selected Vipera spp.) Lonomia species from South America
Procoagulant Procoagulant Procoagulant
Anticoagulant
Procoagulant, disintegrins, hemorrhagins Procoagulant, antiplatelet, disintegrins, hemorrhagins Procoagulant, hemorrhagins Procoagulant, antiplatelet, hemorrhagins Procoagulant, fibrinolytic, antiplatelet, disintegrins, hemorrhagins Procoagulant, anticoagulant, fibrinolytic, disintegrins Procoagulant, anticoagulant, fibrinolytic, disintegrins, hemorrhagins Anticoagulant, fibrinolytic, antiplatelet, disintegrins, hemorrhagins Procoagulant, disintegrins, hemorrhagins Procoagulant
Table 6 Major groups of animals likely to cause local tissue damage

Type of animal Examples Type of venom action
Elapid snakes Atractaspid snakes Viperid snakes
Spiders Jellyfish
Selected Asian and African cobras (Naja spp.) A few species of side-fanged vipers (Atractaspis spp.) Saw-scaled vipers (Echis) Puff adders and relatives (Bitis spp.) European adders (Vipera and Macrovipera spp.) North American rattlesnakes (Crotalus spp.) South American lance-head vipers (Bothrops spp. and related genera) Asian green pit vipers, habu etc. (Trimeresurus spp.) Recluse spiders (Loxosceles spp.) Box jellyfish (Chironex fleckeri)
Local necrotoxin Local necrotoxin Local necrotoxin Local necrotoxin Local necrotoxin Local necrotoxin Local necrotoxin Local necrotoxin Local necrotoxin Local necrotoxin
cause of hemorrhage. Common clinical features include persistent oozing of blood from the bite site and venepuncture or cannulation sites (Figure 4), bleeding gums, and extensive hemorrhage or bruising into the skin of the bitten limb (Figure 5). In addition to the local damage caused by hemorrhage and the effects of blood loss, several organs are at special risk. Intracranial hemorrhage is usually lethal in this setting and can occur either spontaneously or following otherwise trivial head trauma, as may occur when a snakebite victim collapses (Figure 6). The kidneys may be damaged (Figure 7), resulting in acute renal failure or even bilateral renal cortical necrosis (particularly some South American lance head viper bites, Bothrops spp., and Australian taipans). Burmese Russells viper, Daboia russelli,
can cause anterior pituitary hemorrhage and infarction, resulting in Sheehans syndrome (Figure 8). Recent surgery can also result in specific hemorrhage, as the hyperfibrinolysis often associated with snakebite coagulopathy causes breakdown of healing wounds. While many snake venom coagulopathic toxins cause activation of clotting in vitro, in vivo, with one exception, it is hypocoagulability that predominates. Often there is partial or complete defibrination, resulting in fluid blood ante- and postmortem. However, in the early stages of envenoming for a few of these venoms, particularly Australian brown snakes, Pseudonaja spp., there may be a brief initial period where thrombosis occurs prior to fibrinolysis, resulting in occlusion of critical vessels. This is believed to be the explanation for
334 VENOM
Figure 2 Death adder envenoming, with mild ptosis and partial ophthalmoplegia. Julian White. Reproduced with permission.
Figure 4 Persistent bleeding from an intravenous site due to taipan envenoming coagulopathy. Julian White. Reproduced with permission.
Figure 3 Myoglobinuria due to myolysis following envenoming by a black tiger snake. Julian White. Reproduced with permission. Figure 5 Extensive bruising of the bitten limb due to green pit viper envenoming coagulopathy. Julian White. Reproduced with permission.
Table 7 Broad classification of types of action of snake coagulopathic and hemorrhagic toxins
Class of toxin Specific activity
Procoagulants
Anticoagulant
Fibrinolytic Vessel-wall interactive Platelet activity Plasma protein activators
Factor V-activating Factor X-activating Factor IX-activating Prothrombin-activating Fibrinogen-clotting Protein C-activating Factor IX/X-activating protein Thrombin inhibitor Phospholipase A2 Fibrin(ogen) degradation Plasminogen activation Hemorrhagins Platelet aggregation inducers Platelet aggregation inhibitors SERPIN inhibitors
One species of snake, the Martinique viper, Bothrops lanceolatus, has venom components that cause widespread thrombosis, resulting in deep-vein thrombosis and pulmonary emboli, with occasionally lethal effects. The South American hairy caterpillars of the genus Lonomia can inflict, through skin contact, coagulopathic envenoming causing severe, even lethal, coagulopathy and hemorrhage.
Local Necrosis
early cardiac collapse and death following bites by these snakes. As hyperfibrinolysis will quickly activate, such thrombi will have been consumed by autopsy.
A number of animals can cause moderate to severe local tissue injury at the envenoming site (Table 6). For snakes, such locally necrotic bites are usually painful from the start, with progressive development of local redness, swelling, blistering, and skin discoloration, often associated with local hemorrhagic tendency (Figure 9). Major swelling can develop rapidly, in minutes to a few hours, and can involve an entire limb in <24 h. Areas of necrotic skin may take longer
VENOM 335
Figure 6 Computed tomography head scan showing intracranial hemorrhage secondary to Brazilian lance head viper envenoming coagulopathy. David Warrell. Reproduced with permission.
Figure 8 Anterior pituitary infarction due to Burmese Russells viper envenoming. David Warrell. Reproduced with permission.
Figure 9 Local swelling, blistering, and bruising due to Malayan pit viper envenoming. David Warrell. Reproduced with permission.
Figure 7 Autopsy kidney showing acute damage due to Russells viper envenoming. David Warrell. Reproduced with permission.
to demarcate, but within days clear necrosis may be apparent and may involve extensive areas of skin and extend deeply into underlying tissues. There may be massive movements of fluid into affected areas, causing secondary shock, which can be lethal. Compartment syndrome can develop, though it is uncommon and overdiagnosed. Traditionally snakebite tissue necrosis has been associated with viper bites and not elapid bites. This view is incorrect. In Africa and Asia, many cobra species commonly cause moderate to severe tissue necrosis, especially
those species known to spit venom, although spat venom rarely causes major tissue injury, except to the eyes. These cobras are a major cause of bites, but other elapids do not cause significant local tissue injury. Selected Australian elapids may, on occasion, cause mild, rarely moderate local tissue injury, notably tiger snakes, Notechis spp., and black and mulga snakes, Pseudechis spp. Many vipers can cause local tissue necrosis, but some species cause only systemic effects, such as paralysis and myolysis, without significant local effects, notably South and Central American rattlesnakes, Crotalus spp. Some spiders (recluse spiders, Loxosceles spp.) and even a few scorpions (Hemiscorpius lepturus, Iran) can cause skin necrosis. Recluse spiders cause loxoscelism, either cutaneous (local tissue necrosis, which may be extensive, with a nonspecific and limited systemic illness) or viscerocutaneous (cutaneous form plus major and sometimes lethal systemic effects, including hemolysis, disseminated intravascular coagulation (DIC), renal failure, and
336 VENOM
shock). The bite is usually painless and goes unnoticed, often while the victim is asleep, with progressive development of local necrosis over 27 days, resulting in a very-slow-healing, often painful full-thickness skin necrosis (Figure 10). However, many other
causes for skin necrosis exist and it is now clear that loxoscelism is overdiagnosed, especially in North America. A similar overdiagnosis or inappropriate diagnosis occurs in Australia, in relation to the whitetailed spider, Lampona spp., which recent studies have shown to be unlikely to cause skin injury.
Venomous Snakes
Of the nearly 3000 species of snakes, most fall into four families containing venomous species. These are listed in Table 8. Most recent estimates published by the World Health Organization suggest that there are >2.5 million venomous snakebites globally each year, with >125 000 deaths. Of the survivors, many will be left with long-term injury, usually due to local tissue damage, but also occasionally due to systemic
Figure 10 Local necrotic lesion due to Brazilian recluse spider envenoming. David Warrell. Reproduced with permission.
Table 8 Families of venomous snakes

Approximate number of species
Family
Distribution
Fang structure and venom
Medical importance
Colubridae
2800
Global
Elapidae (cobra-type snakes, including sea snakes) Atractaspididae (side-fanged vipers)
297
Global
Most species lack fangs, but many may have toxic saliva. Some species have fangs, placed towards the rear of the mouth, with attached venom glands Small to moderate-sized fangs at the front of the mouth Fangs are forward-placed, designed to strike sideways at prey in burrows Moderate to large fangs in front of the mouth, rotate forward to strike, fold away at rest
Few species are able to inflict medically significant bites, but these can be lethal All species are venomous; many are hazardous, even lethal to humans All species are venomous, but only a few can inflict medically significant or lethal bites All species are venomous; many are hazardous, even lethal to humans
40
Africa and Middle East
Viperidae (vipers, pit vipers, rattlesnakes, adders)
380
Global except New Guinea and Australia
Table 9 Some major species of medically important colubrid snakes (note that a number of other colubrid snakes may cause envenoming)
Scientific name Dispholidus typus Thelatornis spp. Rhabdophis spp. Malpolon monspessulanus Elapomorphus bilineatus Tachymenis peruviana
a b
Common namea
Distributionb
Clinical effectsc
Boomslang Vine or bird snakes Yamakagashi, red-necked keelback Montpelier snake Argentine black-headed snake Culebra de cola corta
CF, SF SF JA, CK, SE NF, ME, EU SA SA
C, H, R C, H, R C, H, R, L P H, C C, H, L
Only a single common name is listed, but a variety of common names may exist. Distribution is only approximate and to continental or subcontinental level; actual distribution may be far more restricted within regions listed: CF, Central and western Africa; SF, southern Africa; JA, Japan; CK, China and Korea; SE, Southeast Asia; NF, North Africa; ME, Middle East; EU, Europe; SA, South America. c Only principal or common major clinical effects are listed: C, coagulopathy; H, hemorrhagic; R, renal damage; L, significant local tissue reaction (swelling/blisters/hemorrhage/bruising); P, paralysis. Julian White. Reproduced with permission.
VENOM 337
effects. The majority of cases still occur in tropical regions, especially Asia, Africa, and South America. Many of the effects of snakebite have already been discussed. Some medically important members of each major venomous snake family are listed in Tables 911.
Diagnosis of Snakebite
Diagnosis may be obvious from the history, but may be obscure, whether because the victim was found collapsed or dead, or was unable to give a history, or was unaware of being bitten. Classic signs suggestive
of snakebite, such as progressive flaccid paralysis, though readily detectable if looked for, may be missed if snakebite is not considered. Snakebite should therefore be considered in the differential diagnosis of a variety of presentations, including unexplained collapse, convulsions, coagulopathy, thrombosis (in Martinique), renal failure, myolysis, flaccid paralysis, and local tissue injury. Bite marks should be looked for, but may be obscure. Classically there will be two distinct fang punctures (Figure 11), but often a different pattern will be seen, such as a single
Table 10 Some major species of medically important elapid snakes

Scientific name Notechis spp.; Tropidechis carinatus Hoplocephalus spp. Austrelaps spp. Pseudonaja spp. Pseudechis spp. Pseudechis spp. Oxyuranus spp. Micropechis ikaheka Acanthophis spp. Calliophis spp. Maticora spp. Naja kaouthia Naja siamensis and related species Naja philippinensis Ophiophagus hannah Bungarus spp. Naja atra Naja naja Walterinnesia aegyptia Naja haje Boulengeria spp. Naja melanoleuca Dendroaspis spp. Naja mossambica Naja nigricolis Naja nivea Hemachatus haemachatus Aspidelaps spp. Elapsoidea spp. Pseudohaje spp. Paranaja multifasciata Micruroides euryxanthus Micrurus spp. Enhydrina schistosa Aipysurus spp., Astrotia stokesii, Hydrophis spp., Laticauda spp., Hydrelaps spp., Lapemis spp., Pelamis platurus
a b
Common namea
Distributionb
Clinical effectsc
Tiger snakes, rough-scaled snake Broad-headed snakes Copperheads Brown snakes Mulga, Papuan black and Colletts snakes Red-bellied black Taipans New Guinea small-eyed snake Death adders Asian coral snakes Asian coral snakes Monocled cobra Thai spitting cobra Philippines cobra King cobra Kraits Chinese cobra Indian cobra Desert black snake Egyptian cobra Water cobras Forest cobra Mambas Mozambique spitting cobra Black-necked spitting cobra Cape cobra Rinkhals spitting cobra African coral snakes African garter snakes Tree cobras Burrowing cobra American coral snake American coral snakes Beaked sea snake Other species of sea snakes
AU AU AU AU AU AU AU AU AU, SE SE SE SE SE SE SE SE, IN, CK SE, CK IN ME, NF NF, ME CF CF, SF CF, SF SF CF, SF, NF SF SF SF SF SF, CF SF, CF NA, CA SA, CA Indo-Pacific Oceans Indo-Pacific Oceans Only Pelamis is pelagic
P, M, C, R C P, M C, R, (P) M, R, Ca M P, C, M, R P, Ca, M P P P L, N, P L, N, (P) P P, L P P P, L P P P P P L, N L, N P L, N, P P L L L P P M, P M, P
Only a single common name is listed, but a variety of common names may exist. Distribution is approximate only and to continental or subcontinental level; actual distribution may be far more restricted within regions listed: AU, Australia and New Guinea; SE, Southeast Asia; IN, Indian subcontinent, including Sri Lanka; CK, China and Korea; ME, Middle East; NF, North Africa; CF, Central and western Africa; SF, southern Africa; NA, North America; CA, Central America; SA, South America. c Only principal or common major clinical effects are listed: P, paralysis; M, myolysis; C, coagulopathy; R, renal damage; Ca, anticoagulant; L, significant local tissue reaction (swelling/blisters/hemorrhage/bruising); N, necrotoxic or likely to cause significant injury to the bitten area. Julian White. Reproduced with permission.
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Table 11 Some major species of medically important viperid snakes
Scientific name Common namea Distributionb Clinical effectsc
Viperinae
Daboia russelli Echis spp. Pseudocerastes spp. Vipera spp. Includes those Vipera now assigned to Macrovipera Vipera ammodytes Cerastes spp. Causus spp. Atheris spp. Bitis arietans Bitis gabonica Bitis nasicornis Bitis spp.
Russells viper Carpet or saw-scaled vipers Horned vipers Vipers Long-nosed viper Horned vipers Night adders Bush vipers Puff adder Gaboon viper Rhinoceros viper Other African vipers Green tree pit vipers Asian pit vipers, including mamushis Malayan pit viper Hundred-pace viper Hump-nosed vipers Terciopelo Lancehead Jararaca Jararacusu Brazilian lancehead Fer de lance Lancehead vipers Jumping pit vipers Palm pit vipers Montane pit vipers Montane pit vipers Horned pit viper Bushmaster Neotropical rattlesnake or cascabel Other Central and South American rattlesnakes North American rattlesnakes Mojave rattlesnake Pygmy rattlesnakes and massasauga Copperhead, cottonmouth, cantil
SE, IN IN, ME, AS, NF, CF ME, AS ME, AS, EU, NF EU, AS NF NF, CF, SF NF, CF, SF CF, SF CF, SF NF, CF, SF SE, CK, JA, IN SE, CK, JA, AS SE CK IN SA SA SA
C, H, R, M, P, N, L C, H, R, N, L P L, H, C, V, R, P L, P L, C L, P L, N, C, H, V, R L, N, C, H, V, R L L, C, H L, C, H, N L, N, H, C, R L, N, H, C L L, N, C, H L, N, C, H L, N, C, H, R, M
Crotalinae
Trimeresurus spp. Includes Ovophis, Tropidolaemus Gloydius spp. Calloselasma rhodostoma Deinagkistrodon acutus Hypnale spp. Bothrops asper Bothrops atrox Bothrops jararaca Bothrops jararacusu Bothrops moojeni Bothrops lanceolatus Bothrops spp. Includes ex Bothriopsis spp. Atropoides spp. Bothriechis spp. Cerriphidion spp. Porthidium spp. Ophryacus spp. Lachesis muta Crotalus durissus Crotalus spp. Crotalus spp. Crotalus scutulatus Sistrurus spp. Agkistrodon spp.
a b
CA SA, CA CA CA CA CA CA CA, SA CA, SA CA, SA NA NA NA CA, NA
L, N, C, H L, N, C, H L, N L, N L, N L, N L, N L, N, C P, M, R, C, H, (L) P, L, R L, N, H, C, (R) P, L, (N), (C), (H) L, N, (H) L, N, C, H, R
Only a single common name is listed, but a variety of common names may exist. Distribution is approximate only and to continental or subcontinental level; actual distribution may be far more restricted within regions listed: SE, Southeast Asia; IN, Indian subcontinent, including Sri Lanka; ME, Middle East; AS, Asia; NF, North Africa; CF, Central and western Africa; EU, Europe; SF, southern Africa; CK, China and Korea; JA, Japan; SA, South America; CA, Central America; NA, North America. c Only principal or common major clinical effects are listed: C, coagulopathy; H, hemorrhagic; R, renal damage; M, myolysis; P, paralysis; N, necrotoxic or likely to cause significant injury to the bitten area; L, significant local tissue reaction (swelling/blisters/ hemorrhage/bruising); V, cardiovascular. Julian White. Reproduced with permission.
fang puncture, or scratches where fangs have dragged through the skin (Figure 12), or multiple teeth marks from fangs and other teeth (Figures 13 and 14). Occasionally a fang may be left in the skin. The distance between clear fang marks may indicate the approximate size of the snake, but this may be confusing if there are other teeth marks or multiple
bites. The latter indicate a high likelihood of major envenoming. Laboratory tests may be crucial in determining a diagnosis of snakebite and its extent antemortem. In particular, extensive coagulation studies may reveal the presence and type of coagulopathy, which may point toward snakebite and even the type of snake.
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Figure 11 Distinct twin fang punctures. Julian White. Reproduced with permission. Figure 14 Multiple bite marks from a single taipan bite, with impressions from fangs, postmaxillary, and pterygopalatine teeth. Julian White. Reproduced with permission.
Figure 12 Scratches from fangs dragged through skin. Julian White. Reproduced with permission.
Figure 13 Double bite with multiple teeth marks, also local erythema and bruising, following two bites from a tiger snake. Julian White. Reproduced with permission.
Figure 15 Diagnostic algorithm for local effects following Australian snakebite. Julian White. Reproduced with permission.
For example, in Australia, if the coagulopathy is a defibrination type, with low fibrinogen and elevated degradation products, it suggests a bite by a brown snake, tiger snake, taipan, rough-scaled snake, or broad-headed snake. The pattern of other effects, particularly paralysis and myolysis, can further narrow the likely culprit (Figures 15 and 16). If the coagulopathy is of the pure anticoagulant type, with normal fibrinogen levels, it indicates a mulga or Colletts snake bite. Similar diagnostic algorithms
are being developed for other regions and will be made available on the Clinical Toxinology Resources website (www.toxinology.com). CK should be measured, as an indicator of myolysis. Renal function should be assessed, together with electrolytes, especially potassium level. Venom detection is currently only available in Australia and New Guinea to determine the type of snake (CSL snake venom detection kit; sandwich enzyme-linked immunosorbent assay) (Figure 17). It
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Is there a coagulopathy?
YES
NO
Defibrination Coagulopathy low fibrinogen raised FDP/XDP
Anticoagulation normal fibrinogen normal FDP/XDP
Is there paralysis?
YES
Is there paralysis 6 myolysis? Is there major paralysis? Is there major myolysis?
NO
Is there major myolysis?
YES
NO
NO
YES
NO
YES
NO
Consider tiger snake rough scaled snake taipan
Consider death adder copperhead
Consider brown snake broad headed snake Stephen's banded snake
Consider red bellied black snake yellow faced whip snake
Consider mulga snake Collett's snake spotted black snake small eyed snake
Figure 16 Diagnostic algorithm for systemic effects following Australian snakebite. Julian White. Reproduced with permission.
Figure 17 Australian snake venom detection kit showing positive. Julian White. Reproduced with permission.
can detect down to nanograms per milliliter (ng ml1) of venom, the best sample being a swab from the bite site. Urine can also be tested, but can give false positives or occasionally false negatives if venom levels are too high. Blood is not reliable, though it can also be tested. Postmortem diagnosis of snakebite will rely on the same elements as clinical diagnosis, if they are available, but the history may be absent and if the patient has been found dead, with no certain cause, many vital diagnostic clinical clues will be missing. While exposure to snakes would seem an appropriate question, it must be remembered that snakes
do enter houses, even in westernized countries like Australia and the USA and snakebite can occur while the victim is asleep in bed. Indeed, the latter is common for krait bites in Sri Lanka. If venom detection is available, either commercially (i.e., in Australia) or experimentally, then choice of a sample site will include the bite site if it can be found urine, and vitreous humor. The postmortem should be thorough enough to detect renal damage, extensive hemorrhage into tissues, intracranial hemorrhage, and systemic myolysis. Histopathology of skeletal muscle, kidneys, lungs, and brain is important. In muscle, look for both muscle-cell damage and damage to the neuromuscular junction. If snakebite is just one of several possible diagnoses, ensure tissue samples are collected and stored, should later attempts to detect venom become appropriate. Generally postmortem coagulation studies are not helpful. Some cases of snakebite will have been clearly diagnosed during life, but despite, or possibly because of, treatment, the patient has died, requiring postmortem assessment of cause of death. In considering this situation, some understanding of snakebite treatment is required. The mainstay of treatment is the use of appropriate antivenom, an antivenom that will neutralize important components of the target venom. This may be a specific monovalent antivenom for that snake species, or a polyvalent antivenom, which includes that species in the immunizing mix, or an antivenom against another related species, where cross-protection is believed to exist. It is clear from this that one potential error in treatment is to use the wrong antivenom, which is likely if the type of snake has been misidentified. Second, sufficient antivenom must be given by the right route. Only intravenous is appropriate and often multiple vials are required, both as a starting dose and as followup dosing. A common mistake is to use too little antivenom or fail to give follow-up doses. Some antivenoms, notably the North American CroFab, for rattlesnake envenoming, is F(ab) rather than whole immunoglobulin G (IgG) or F(ab)2, with the result that it is rapidly cleared, requiring regular repeat dosing over many hours. Recurrent coagulopathy is a well-recognized phenomenon with this antivenom. All antivenoms are produced from animal immunoglobin, most commonly equine IgG, and therefore carry the risk of acute and delayed adverse reactions, especially anaphylaxis and serum sickness. The former has a real potential for lethality and is generally not true IgE-mediated anaphylaxis, so can occur even on first exposure to antivenom. It is most common with crude IgG antivenoms, such as some of those from Asia and the old North American Wyeth product, but can occur with any antivenom. A recent
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shift to nonequine antivenom, such as the sheepbased CroFAb, has resulted in a lower rate of such adverse effects. Apart from problems with antivenom, snakebite patients may die due to untreated respiratory paralysis and failure, or secondary effects of such paralysis, such as airway obstruction or aspiration pneumonia. Myolysis can prove lethal, especially if there is secondary renal failure and hyperkalemia. Coagulopathy, untreated or while reversing, poses the risk of catastrophic hemorrhage, especially intracranial. Renal failure can prove lethal, primarily or through secondary complications, as can its treatment, by peritoneal or hemodialysis. Severe local-tissue injury can result in local infection becoming septicemia or in massive fluid shifts with shock, especially in children. Longer term, there may be other sequelae, such as Sheehans syndrome, or secondary carcinoma in a chronic wound following necrotic snakebite (Figure 18).
Scorpion Sting
There are around 1250 species of scorpions globally, only a minority of which can effectively sting humans, but this small group (Table 12) causes a large number of cases and significant mortality. In Mexico alone, it
is reliably estimated there are more than 250 000 significant scorpion stings each year. The advent of antivenom has reduced the previous high pediatric mortality to relatively small numbers. Most medically important scorpion stings have a similar pattern of effects. The venom contains neuroexcitatory toxins of great potency, mostly potassium and sodium channel toxins that cause neurotransmitter release that, for some species, can induce a catecholamine storm-like effect. The sting is nearly always intensely painful, may cause early collapse, and systemic envenoming is swift, sometimes within minutes of the sting. There can be massive stimulation of the autonomic system, cardiovascular decompensation, or pulmonary edema or failure. Other effects are generally secondary and less common. Some Central American species can induce pancreatitis (Tityus trinitatis, Trinidad). Treatment is controversial, with proponents and opponents of intravenous antivenom, which, in any case, is only available in some major at-risk areas. Postmortem findings will relate to the nature of envenoming in the individual case, as noted above.
Spider Bite
There are many thousands of spider species, most of which are too small, too rarely encountered, or have too weak a venom to harm humans. A few types of spider do cause envenoming of humans, with morbidity, but rarely mortality, except for the Australian funnel web spiders. These medically important spiders (Table 13) have a common theme of neuroexcitatory venoms, except for the recluse spiders, mentioned earlier under necrotoxic venoms. Of the neuroexcitatory spiders, the Australian funnel web spiders, comprising around 40 species in two genera, Atrax and Hadronyche, distributed throughout coastal eastern Australia (from Cape York to Hobart) and parts of South Australia, are the most dangerous, and are clearly able to kill adult humans, though deaths are now very rare since the advent of a
Figure 18 Squamous cell carcinoma developed in a chronic wound following Malayan pit viper envenoming. David Warrell. Reproduced with permission.
Table 12 Medically important scorpions not an exhaustive list

Genus Centruroides Tityus Leiurus Androctonus Buthus Hemiscorpion Parabuthus Mesobuthus Region Clinical effect
Central America into southern USA Central and South America North Africa and Middle East North Africa and Middle East North Africa and Middle East Iran Southern Africa Indian subcontinent
Neuroexcitatory, autonomic storm Neuroexcitatory, autonomic storm Neuroexcitatory, autonomic storm Neuroexcitatory, autonomic storm Neuroexcitatory, autonomic storm Local necrosis Neuroexcitatory, autonomic storm Neuroexcitatory, autonomic storm
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Table 13 Medically important spiders not an exhaustive list
Genus Distribution Clinical effect
Australian funnel web spiders; Atrax and Hadronyche Widow spiders; Latrodectus Banana spiders; Phoneutria Recluse spiders; Loxosceles
Eastern Australia Global South America Global except Australia (but introduced there)
Catecholamine storm, significant lethal potential Neuroexcitatory, low lethal potential Neuroexcitatory, low lethal potential Local dermonecrosis; less common systemic effects
specific antivenom. Envenoming rates are low, possibly below 10%, but when envenoming does occur, it is rapidly systemic, with deaths recorded in <60 min. The bite is painful, the large fangs leaving clear puncture marks. Systemic envenoming is heralded by onset of perioral tingling, then nausea, abdominal pain, tachycardia, hypertension, profuse sweating, salivation, piloerection, then pulmonary edema, hypoxia, coma, and death, or later death due to intractable hypotension and cardiac arrest. Status epilepticus has been recorded. The early symptoms of envenoming can be confused with other poisonings, notably organophosphate poisoning, but the lack of response to atropine and the dramatic response to antivenom are highly suggestive of funnel web envenoming. There are no specific laboratory abnormalities, nor is venom detection available. Autopsy should concentrate on features expected from the clinical effects of envenoming. Widow spiders, genus Latrodectus (latrodectism), including the Australian redback spider, are globally distributed. Their bites cause significant morbidity, but a low likelihood of mortality, with the rare fatality generally due to secondary problems, not primary venom toxicity. Envenoming is characterized by progressive local, regional, then generalized pain, with associated local or generalized sweating, hypertension, nausea, and malaise, though many other symptoms can occur. Without antivenom, which is the only effective treatment, the course of envenoming will show ultimate resolution, after a period of days or longer. There are very rare reports of severe envenoming with pulmonary edema. Clearly this should be considered in any autopsy on a fatal case. There are no diagnostic laboratory abnormalities. Banana spiders, genus Phoneutria, from South America, cause similar effects to widow spiders, except priapism in boys is common. Antivenom is available in Brazil and is considered effective. While morbidity is significant, mortality is rare.
neurotoxin that causes progressive flaccid paralysis, which is worse in children, and often presenting first as ataxic gait. Most patients develop a local allergic reaction rather than paralysis. Paralysis usually requires the tick to attach for a period, with progressive paralysis developing over days rather than hours. A tick will be present, but may be difficult to locate, burrowed into the skin, especially in the scalp, behind and in the ears and in body folds. More than one tick may be present. Once the tick is removed, the paralytic effects subside, except for Australian ticks, where paralysis may progress for up to 48 h postremoval. Death is usually due to respiratory paralysis. There are documented cases where, at autopsy, the still-living tick was found on the deceased. There are no specific laboratory tests for tick envenoming, though the victim may have circulating antibodies to tick saliva.
Insects
A number of insects produce toxins, but the most important medically are the Hymenoptera, including bees, wasps, and ants, many of which have stings and venom glands. While the venom can be toxic, usually vast numbers of stings are required to cause clinically detectable toxicity, most commonly manifest as hemolysis. Far more common is acute severe allergy to the venom, typified by anaphylaxis to honeybee sting. As this is not a direct venom toxicity effect, it will not be further discussed here.
Venomous Stinging Fish

Several families of bony fish have developed venom glands enveloping sharp spines, which may be dorsal (stonefish), ventral, lateral, behind the head, or on the tail. For most species nothing is known about their venom. For all species the venom is defensive: potential predators, including humans stepping on or picking up these fish, immediately suffer severe pain as the spines drive through the skin, compressing the venom gland and injecting venom beneath the surface. While the venom causes intense pain, it does not cause local necrosis or systemic effects, at least in humans. The only exception is a handful of older case reports of
Ticks
There are a few ticks in Australia, North America, and Southern Africa whose saliva contains a paralytic
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stonefish envenoming causing pulmonary edema and death. Little detail is available about these exceptional cases. The venom appears heat-sensitive, and immersion in hot water effectively abolishes the pain. Antivenom is only available for stonefish stings and its role is analgesic rather than life-saving. Numerous cartilaginous fish, specifically some rays, have evolved a venomous spine on their tail. This venom induces severe local pain, but not systemic effects, although some fresh-water rays from South America cause significant local necrosis. The major effect of stingray injuries is mechanical trauma, with cases of massive laceration, transection of nerves, tendons, and major vessels, with exsanguination, all having been reported. There are even cases of direct thoracic puncture damaging the heart, with fatal outcome.
Blue-Ringed Octopus
These small octopuses from Australian and Pacific coastal waters have tetrodotoxin, a potent, rapidacting paralytic neurotoxin in their saliva. Bites, which may be painless, can result in rapid development of flaccid paralysis, respiratory failure, and death in <60 min. There are no specific laboratory abnormalities. There is no antivenom, so treatment is supportive. As paralysis can occur quickly, before the victim has left the water, drowning may occur. Bites only happen if the octopus is molested, generally when it is removed from the water and placed in contact with the skin.
where tentacular contact is greater than half of one limb, millions of nematocysts will discharge, many directly into skin capillaries, causing instant envenoming and cardiotoxic collapse and death within 5 min. Tentacles will often remain adherent on victims and it is possible to identify the species of jellyfish from skin scrapings of nematocysts, a key feature of autopsies in fatal cases. Those with slightly less severe envenoming may develop respiratory failure. The remainder of less severe cases develop local effects only, which can include necrosis of skin along tentacle contact areas. The other major jellyfish is the irukandji group, comprising a number of species, some very small, whose venom induces a delayed autonomic storm effect, with back and muscle pain, sweating, pulmonary edema, and severe hypertension, that is potentially, though rarely, lethal. There are no specific tests, apart from skin scrapings from tentacular or bell contact, to identify the species. As the area of contact may be very small and the sting not felt, finding an area to scrape may prove difficult.
Summary
There are a vast number of venomous animals, spanning the globe, causing a diverse array of clinical effects, often specific for each animal, a knowledge of which may assist in postmortem diagnosis. Because of the specialized nature of toxinology, pathologists involved in autopsies on definite or suspected cases of envenoming are advised to seek the involvement of a clinical toxinologist early, to ensure all necessary investigations are performed. In only a few selected situations will venom detection be available to assist the process. Detailed information on venomous animals will progressively become available on the Clinical Toxinology Resources website (www.toxinology.com). Most fatal cases of envenoming or poisoning by toxins will be accidental, but the possibility of suicide or homicide should not be overlooked. A clever felon using a toxin for homicide might easily hide his/her activity from all but the most vigilant forensic pathologist. It is not appropriate to list here the ways in which toxins could be used for homicide, but envenoming or toxin poisoning should be considered in unexplained cases of collapse, convulsions, coagulopathy, myolysis, paralysis, renal failure, and even cardiac arrest, as there are certain toxins that can directly cause such cardiac effects. To be effective, venoms need to be injected, as ingestion will generally result in their breakdown to inactive forms, but felonious, even homicidal injection of snake venom is known. Indeed, in India it is reported to be used to
Cone Shells
These predatory tropical molluscs have a venomtipped harpoon structure (radula teeth) that is fired into prey, causing almost instantaneous systemic and lethal envenoming. Stings occur when the snail is molested. The sting may be painful or painless and systemic envenoming can occur rapidly, with respiratory paralysis, similar to the blue-ringed octopus, though cone snail venoms are quite different in structure. There is no antivenom and no diagnostic tests.
Jellyfish
All jellyfish are venomous, possessing up to millions of individual stinging cells or nematocysts. A few species can cause major, even lethal, envenoming. Principal among these are the cubomedusid box jellyfish, especially the Australian Chironex fleckeri, which, until recently, killed at least two people every year. Stings are intensely painful and, in severe cases,
344 VETERINARY ASPECTS OF FORENSIC MEDICINE, WILD ANIMALS
kill cattle, by introducing venom-impregnated cloth into the rectum. Use of an injection to introduce venom would likely be noticed by the victim and should leave some mark. As death is rarely very rapid, there would usually be time for the victim to make known that he/she had been attacked, but this might not always be the case. Introduction of a venomous animal, especially a snake or scorpion, into sleeping quarters, might also result in effective homicide, which, if within the normal distribution of the animal, might go unproven or undetected. Though not discussed elsewhere in this article, it should be noted that a number of toxins, particularly from marine animals, can prove lethal if ingested, so could be introduced via a meal. Indeed, some poisonous fish (fugu fish, which contain tetrodotoxin) are routinely eaten in some countries, a mild degree of poisoning being a desired effect. Plant toxins are also used for suicide in some countries. Another bizarre possibility is the use of snakebite to hide some other form of homicidal poisoning, some device being used to mimic fang marks and introduce poison into the victim (e.g., the use, in India, of Abrus precatorius poison, injected by paired sui (sharp spikes), mimicking snakebite, used to hide felonious killing of cattle or even humans). Careful examination of the wound and pattern of effects may reveal the true cause in such cases.
See Also
Animal Attacks and Injuries: Fatal and Nonfatal; Predation; Autopsy, Findings: Organic Toxins
Further Reading
Covacevich J, Davie P, Pearn J (1987) Toxic Plants and Animals; A Guide for Australia. Brisbane: Queensland Museum. Harvey A (1991) Snake Toxins. London: Pergamon Press. Mebs D (2002) Venomous and Poisonous Animals. Boca Raton, FL: CRC Press. Meier J, White J (eds.) (1995) Handbook of Clinical Toxicology of Animal Venoms and Poisons. Boca Raton, FL: CRC Press. Shier W, Mebs D (1990) Handbook of Toxinology. New York: Marcel Dekker Inc. Sutherland S, Tibballs J (2001) Australian Animal Toxins. Melbourne: Oxford University Press. Weatherall D, Ledingham J, Warrell D (eds.) (1996) The Oxford Textbook of Medicine, 3rd edn., pp. 11241160. Oxford, UK: Oxford University Press. White J, Pounder D (1984) Fatal snakebite in Australia. American Journal of Forensic Medicine and Pathology 5: 137143. Williamson J, Fenner P, Burnett J, Rifkin J (eds.) (1996) Venomous and Poisonous Marine Animals; A Medical and Biological Handbook. Sydney: University of NSW Press.
VETERINARY ASPECTS OF FORENSIC MEDICINE, WILD ANIMALS

K Goddard, National Fish and Wildlife Services, Ashland, OR, USA
Published by Elsevier Ltd.
Introduction
Prior to 1975, the application of forensic science protocols to animal- and wildlife-related evidence was mostly limited to tentative family, genus, and species identifications of blood stains and loose hairs found at human crime scenes. These identifications were usually based upon immunodiffusion tests using relatively nonspecific antisera, and microscopic comparisons utilizing small collections of knowns. The results were frequently more useful in eliminating a suspect (i.e., the blood on the suspects shirt is not of human origin) than in trying to link suspect, victim, and crime scene.
During this time period, applications of forensic protocols to wildlife law enforcement were generally limited to the identification of blood, meat, and hair from locally hunted species, utilizing the same immunodiffusion and microscopic comparison techniques. The few laboratories that performed this work were uniformly understaffed (one or two scientists), underfunded, and lacking in comprehensive comparison collections. On July 1, 1975, 80 nations formally agreed to work together to enforce each others endangeredspecies laws through the establishment of the Convention on International Trade in Endangered Species Fauna and Flora (CITES) (www.cites.org). This international agreement, although voluntary in scope, encouraged the enforcement of import and export laws related to lists of endangered, threatened, and protected species. In doing so, the agreement also
VETERINARY ASPECTS OF FORENSIC MEDICINE, WILD ANIMALS 345
raised an underlying forensic issue: that illegal trafficking of regulated species would be in the form of parts and products, and that species-specific identifications would be needed to enforce the CITES regulations in courts of law. Thus the need for wildlife forensics on an international scale was born. In 1986, in response to this need, the US established the National Fish and Wildlife Forensics Laboratory in Ashland, OR (www.lab.fws.gov) (Figure 1). The mission of the laboratory is to develop reliable wildlife forensic procedures, and to provide forensic support to wildlife law enforcement officers at state, federal, and international levels. In 1993, at a meeting of the Environmental Crimes Group of Interpol in Lyons, France, the role of the laboratory in assisting CITES and Interpol was documented in the form of signed letters of agreement. The laboratory works with scientists and law enforcement officers from the CITES and Interpol organizations to develop continually and refine reliable methods of identifying wildlife parts and products. They also work to link suspect, victim, and crime scene in suspected criminal cases. While the science of wildlife forensics is still very much in its infancy, numerous protocols have been established for the identification and comparison of wildlife-related evidence. These protocols are typically divided into the following analytical categories: 1. 2. 3. 4. 5. pathology molecular biology (genetics) morphology criminalistics analytical chemistry.
wounds caused by bullets, arrows, spears, and traps. A comprehensive toxicological workup of blood, urine, tissue, and stomach/crop contents to eliminate or confirm a poison or a contaminant as a cause of death; and a professional evaluation of the underlying health of the animal prior to death may also be carried out. In the process of conducting these examinations, the veterinary pathologist will also search for signs of disease vectors that may indicate a natural cause of death. Issues that often complicate a cause-of-death determination in an animal (but should not impact the results of a careful and professional necropsy examination), include: 1. The possibility that the animal may have been struck by additional (nonlethal or crippling) bullets, pellets, or other projectiles days, months, or years prior to the questioned incident. 2. The possibility that an illicit bow-hunter has shot the animal with a firearm first (because of the difficulty in getting close to an alert animal), and then stuck an arrow into the bullet wound. 3. The possibility that the animal was killed or fatally weakened by a modern pesticide or poison designed (as the result of environmental protection laws) to decompose rapidly after a few hours of exposure to air or sunlight. 4. The likelihood that scavengers will have destroyed a considerable amount of useful blood, tissue, or bone evidence if the carcass was not found and collected in a timely manner (Figure 2). In conducting necropsies involving bullet wounds, it is often extremely important that the veterinary pathologist determine the trajectory of the bullet into or through the body. This information may resolve the question of whether the accused hunter was properly defending him/herself against a charging animal, or illegally hunting a protected species (Figure 3). The information may also be used by
Pathology
Veterinary pathologists are responsible for determining cause of death of an animal carcass submitted as evidence. This is accomplished through necropsy (autopsy) protocols involving a search for lethal
Figure 1 The National Fish & Wildlife Forensics Laboratory in Ashland, OR, USA.
Figure 2 Cause of death can be difficult to determine if the only evidence is the skeleton of the victim in this case a wolf.
hybridization techniques. However, new PCR methods for detecting single-locus short tandem repeat (STR) markers have been developed and applied in human forensic casework, demonstrating the technical feasibility of similar applications to animal species. Pending the arrival of new technologies, wildlife research and forensic laboratories focus a considerable amount of effort on the development of STR markers for determining the individual origins of wildlife evidence tissues.
Morphology
Figure 3 The bullet trajectories related to wounds on a bear can help prove a hunters claim of self-defense.
investigators, during the interview process, in determining the veracity of suspects and witnesses.
Molecular Biology (Genetics)

Molecular biology involves the study of genetic information encoded in the DNA molecule, and the expression of that coding into proteins and related biological structures. Given the incredible diversity of biological structures present in the known plant and animal kingdoms, molecular biology offers the wildlife forensic scientist an extremely powerful tool to: 1. determine family, genus, and species 2. determine gender 3. individualize blood and tissue samples.
Family/Genus/Species Identification
The forensic process of determining the species origin of an unknown tissue normally begins with a series of screening (immunological) tests designed to narrow the possibilities down to the species comprising a single family (e.g., bears family Ursidae, or deer family Cervidae). Once the family source of the specimen is determined, the examiners can go forward with either protein or DNA/polymerase chain reaction (PCR) analysis (along with the necessary and comprehensive databases) to determine the actual genus and species involved.
Gender Identification
A number of nuclear DNA-based gender-determining tests are available for blood and tissue samples from mammalian species. The tests generally use PCR amplification to detect specific sequences of the ZFY and/or SRY genes, both of which are located on the mammalian Y chromosome.
Individualization of Blood and Tissue
Morphology is the study of structure and shape. In wildlife forensic science, morphological examinations of submitted evidence items are normally conducted by eye, and with the use of simple, compound, or scanning electron microscopes. These are often the simplest examinations performed in a wildlife crime lab; but at the same time, they address some of the most complex and difficult identification problems. As an example, the vast majority of mothers and fathers in this world are perfectly capable of identifying their sons or daughters from 10 000 similar young men or women. But could these people create a written protocol that would enable another individual (i.e., a forensic scientist) to make that same positive identification with the same degree of certainty? The answer is almost certainly no. The reasons why such a protocol would be difficult to write lie in the heart of the morphological problem: the lack of standard definitions for individuals, and the fact that no two individuals (even genetic twins) are exactly alike. Two animals (e.g., two whitetail deer that are genetic twins) may start out looking very much alike, but the normal wear and tear that a young whitetail deer experiences literally from the moment of birth creates individual characteristics (a healed cut, a chipped hoof, or broken antler) that quickly separate those twins into distinct individuals. So the immediate problem for a wildlife forensic scientist is to come up with class characteristics that distinguish and identify family, genus, and species of animals that are separate and distinct from population and individual characteristics. This is not a problem with whole animals, but is very much a problem in the case of wildlife parts and products wherein the commonly occurring species-defining characteristics of the animal source may not be present. These identification characteristics typically fall within one of the following morphological categories: 1. hair and fur 2. leather and hides 3. bones and skulls (Figure 4)
Early work on individualizing animal blood and tissue samples involved multilocus DNA probe
VETERINARY ASPECTS OF FORENSIC MEDICINE, WILD ANIMALS 347
4. the tendency of the suspect to take the victim from the scene 5. the tendency of the suspect to reuse the same firearm frequently. Unlike human crime situations in which the victim is most commonly killed with a pistol at short (contact to 25 m) distances, the typical animal kill involves a high-powered (and large-caliber) rifle or a shotgun at relatively long distances (50300 m). Given the nature of the typical hunting area (brush, trees, and ground cover), it is often difficult for an illicit hunter to retrieve expended casings; however, the long shooting distances and the fact that the shot could have come from any 360 vector point makes it extremely difficult for a crime-scene investigator to locate the shooting point, much less the expended casings. However, all of these advantages (to the illicit hunter) tend to be negated by two simple facts: 1. The whole point of the illicit hunting is for the suspect to take the victim (as a trophy or meat) back home. Thus, the bullet is likely to either be in the carcass of the animal, or in the gut pile left at the scene (which can be matched to the trophy head or meat with DNA techniques). 2. The typical illicit hunter spends a lot of money on a rifle or shotgun, and is rarely willing to discard this weapon after a single illicit kill. Thus, it is very likely that a succession of illegal kills can be linked to a single poacher by matching the spent bullets or casings to the rifle or shotgun.
Other Weapons
Figure 4 Morphologists Drs Peppes Trail, Bonnie Yates, and Cookie Sims examine bone evidence.
4. 5. 6. 7.
teeth, claws, and beaks hooves, horns, and antlers feathers and down other miscellaneous parts.
Criminalistics
Wildlife forensic scientists frequently process evidence from an illegal hunt much in the same way that a police forensic scientist works evidence from a homicide scene. In fact, the events associated with a typical illegal hunt often involve the following categories of criminalistics (or police forensic science) evidence: 1. 2. 3. 4. 5. 6. trace evidence firearms other weapons impression marks latent fingerprints questioned documents.
Other hunting weapons typically associated with an illicit animal kill include: 1. 2. 3. 4. 5. 6. long bows and arrows crossbows and bolts spears spring traps poison discharge devices (Figure 5) nets.
Trace Evidence
Trace evidence in an animal case can involve a wide range of materials. A classic example is a case in which a mountain lion was held captive for a period of time and then killed in an illegal canned hunt. As it turned out, the mountain lion tried to chew his way loose from the synthetic fiber ropes (two types were used by the suspects to secure the lion), and a forensic scientist was able to link the fibers from the lions stomach back to chewed ropes found at the crime scene.
Firearms
Impression Marks
The typical circumstances in which an animal is killed with a firearm vary greatly from those of a homicide case. The most significant differences include: 1. the distance from suspect to victim 2. the choice of firearm 3. the ability of the suspect to clean up the scene
The fact that most illicit hunting situations occur in remote areas or off road situations makes it extremely likely that the suspect will leave tire tracks and boot impressions in soil, mud, or snow. And the fact that these tires and boots are typically used in offroad situations makes it all the more likely that the tire or boot treads will possess individualistic wear marks.
Latent Fingerprints
Latent fingerprints are the classical means of linking suspect, victim, and crime scene through physical
a necropsy. As such, a forensic scientist assigned to the chemistry section of a wildlife crime laboratory spends a great deal of time examining blood, urine, tissue, and stomach/crop contents in a search for pesticides and poisons. Analytical chemistry procedures (that utilize chemical biomarkers) are also used to identify the species source of animal products such as bear bile and deer musk; and standard toxicological methods are routinely employed to identify chemical baits and poisons used to trap and kill wildlife.
See Also
Figure 5 A sheep carcass illegally laced with Aldicarb to kill eagles.
Crime-scene Investigation and Examination: Collection and Chain of Evidence
Further Reading
Aasen E, Medrano JF (1990) Amplification of the ZFY and ZFX genes for sex determination in humans, cattle, sheep and goats. Biotechnology 8: 12791281. Adamczyk M, Gebler JC (1997) Electrospray mass spectrometry of a and b chains of selected hemoglobins and their TNBA and TNB conjugates. Bioconjugate Chemistry 8: 400406. Andrasko J, Rosen B (1994) Sensitive identification of hemoglobin in bloodstains from different species by high performance liquid chromatography with combined UV and fluoresense detection. Journal of Forensic Science 39: 10181025. Ashton GC (1958) Beta-globulin polymorphism in cattle, sheep and goats. Science 182: 945. Clarke FD (1914) Forensic value of the precipitin test in the enforcement of game laws in California. University of California Publications in Pathology 2: 131. Dilworth TG, McKenzie JA (1970) Attempts to identify meat of game animals by starch-gel electrophoresis. Journal of Wildlife Management 34: 917. Espinoza EO, Kirms MA, Filipek MS (1996) Identification and quantitation of source from hemoglobin of blood and blood mixtures by high performance liquid chromatography. Journal of Forensic Science 41: 804811. Espinoza EO, Cech Lindley N, Gordon KM, Ekhoff JA, Kirms MA (1999) Electrospray ionization mass spectrometric analysis of blood for differentiation of species. Analytical Biochemistry 268: 252261. Fain SR, LeMay JP (1995) Gender identification of humans and mammalian wildlife species from PCR amplified sexlinked genes. Proceedings of the 47th American Academy of Forensic Sciences 1: 34. Fenstermacher R, Pomeroy BS (1938) Identification of suspected beaver blood stains. Cornell Veterinarian 28: 257. Gay FP (1908) A contribution to the forensic value of the musculo-precipitin test. Journal of Medical Research 19: 219. Grabar P, Burtin P (1964) Immuno-electrophoretic Analysis. New York: Elsevier.
evidence. The following types of latent-bearing evidence are frequently submitted to a crime lab in wildlife cases: 1. 2. 3. 4. 5. 6. firearms expended casings (shotgun and rifle) knives no trespassing and no hunting signs game tags import/export (CITES) permits.
Questioned Documents
Questioned documents are frequently encountered in wildlife investigations involving the import and/or export of wildlife parts and products. The question most frequently asked by the investigator is whether or not the seized documents (typically import/export permits) are valid. This can be an extremely difficult question to answer when the authorizing seals vary between countries, the names of individuals authorized to approve import/export documents change on a frequent basis, and the shipments must be cleared (the documents examined and approved) at the local port of entry. Questioned documents typically associated with a wildlife case include: 1. forged or altered hunting licenses 2. forged or altered game tags 3. forged or altered import/export permits.
Analytical Chemistry
Chemical analysis techniques are most often used in a wildlife crime lab to provide toxicological information for a veterinary pathologist conducting
VICTIM SUPPORT 349 Irwin DM, Kocher TD, Wilson AC (1991) Evolution of the cytochrome b gene of mammals. Journal of Molecular Evolution 32: 128144. Karpas AB, Wyers WL, Segre D (1970) Serologic identification of species of origin of sausage meats. Journal of Food Science 36: 150. Lawrence B (1951) Post-cranial skeletal characteristics of deer, pronghorn and sheep-goat, with notes on bos and bison. Papers of the Peabody Museum of Archeology and Ethnology 35(3), part II Harvard. Myers M (1900) Experiments upon the new specific test for blood. Preliminary note. British Medical Journal 1: 1141. Ouchterlony O (1948) Antigenantibody reaction in gels. Acta Pathologica Microbiologica Scandinavica 25: 186. Sibley CS, Hendrickson HT (1970) A comparative electrophoretic study of avian plasma proteins. Condor 72: 43. Taylor AJ, Linforth R, Weir O, Hutton T, Green B (1993) Potential of electrospray mass spectrometry for meat pigment identification. Meat Science 33: 7583. VanTets P, McT I (1966) Cowan. Some sources of variation in the blood sera of deer (Odocoileus) as revealed by starch gel electrophoresis. Canadian Journal of Zoology 44: 631. Wolfe HR (1933) Factors which may modify precipitin tests in their applications to zoology and medicine. Physiol. Zool. 6: 55. Wolfe HR (1939) Serologic relationships among bovidae and cervidae. Zoologica 24: 309.
VICTIM SUPPORT
M DArcy and L Olle, Royal Womens Hospital, Carlton, VIC, Australia
1. Recommend protective measures for victims and witnesses in accordance with the Article 22 of the Statute, and 2. Provide counseling and support for them, in particular in cases of rape and sexual assault. This article discusses the role of professional support workers in relation to victims of personal offenses. For this purpose the term professional support worker encompasses anyone who may come into contact with someone who has been a victim of an offense against the person. It can include forensic medical officers, forensic physicians, police, prosecutors, psychologists, counselors, allied health professionals, or services whose primary role is to support victims of crime or specialist support services. Most developed countries now have agencies whose role is to provide support, counseling, information, and advocacy for victims of crime. In addition, there are specialist agencies, which provide support to victims of particular types of crime such as family and friends of homicide victims, child victims or victims of domestic violence or sexual assault. Generally these services are government-funded or through charitable trusts or corporate sponsors; in most cases the services will be provided free of charge. It is important that all professionals involved in responding to victims of crime have a broad understanding of the services available in their area and can refer people to those most appropriate to address their needs. There are a number of websites that can assist in finding the appropriate service; in the UK, for instance, www.home.office.gov.uk provides links to victim support services, and in the USA
Introduction
Responses from clinical, legal, and support professionals can impact significantly in the recovery process for victims of interpersonal crime. Appropriate helping responses can further allay trauma and help set the victim on a path to recovery. Inappropriate responses can do a great deal of further damage and even exacerbate trauma. The need for support for victims of crime has been increasingly recognized around the world, with most western countries now having some form of formalized support for victims. The International Criminal Tribunal Former Yugoslavia (ICTY) has recognized the need for support for victims and witnesses by establishing a victims and witnesses section. Article 22 in the Statute of the International Tribunal addresses the protection of victims and witnesses, and states:
ICTY shall provide in its rules of procedure and evidence for the protection of victims and witnesses. Such protection measures shall include, but shall not be limited to, the conduct of in camera proceedings and the protection of the victims identity.
Under the rules of Evidence and Procedure, Rule 34 was established. This specifically stated that: There shall be setup under the authority of the Registrar a Victims and Witnesses section consisting of qualified staff to:
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www.ncjrs.org has a directory of services which can be searched by location and type of offense. The role of professional support workers may involve contact with medical and legal processes and may also entail ongoing or long-term support. A professional support worker may also instigate and coordinate various specialist medical and legal supports throughout crisis service provision and the legal process, in which case it is not necessary to be an expert on medical treatment or the legal process itself. Some professionals in community settings may have only intermittent contact with victims of crime in medical or legal and forensic contexts, while others may be involved in roles that do not include direct provision of support services for example, a forensic psychologist undertaking a court-ordered assessment. It is important to be clear about role limitations and to remember that making judgments about crime is the role of the legal system; the role of the support professional is only to support. Even where the role of a professional may appear to conflict with a victim support role, such as a specialist engaged by a defendant, or a law enforcement officer charged with the task of collecting a witness statement, the principle of do no harm is an ethical responsibility. No additional harm or retraumatization should befall victims and witnesses, and professionals involved in forensic contexts should strive to ensure that contact with medical, legal, and forensic processes is strengthening and healing for victims. This article sets out the primary principles of supporting a victim of interpersonal crime, taking as its foundation the principles used in supporting victim/ survivors of sexual assault. Feminist services have led the way in focusing attention on victims needs and rights in ways that have value and applicability to all victims of crime, because of their emphasis on principles such as empowerment and advocacy, and on justice rather than revenge. These principles can be applied across a wide range of support needs in widely varied situations and stages of traumatic experience. Viewing the experience of crime from the perspective of the victim/survivor underpins this approach to providing appropriate and effective professional and paraprofessional responses. The term victim/survivor exemplifies language that is applicable in a setting that facilitates empowerment and the regaining of agency. Victim acknowledges the trauma of criminal harm, and survivor acknowledges the agency, personal integrity, and dignity of the person seeking support. A critical part of the recovery process for victim/survivors is regaining control and agency, as discussed below. Individual responses to crime can be complex and can vary widely according to the individual victim/
survivors background, previous life experience, and current life situation. Consequently support needs will vary from person to person. Posttraumatic stress responses are relatively common following the experience of interpersonal crime. The nature and incidence of posttraumatic stress disorder (PTSD) in crime victims will also be explored in this article, with a view to diminishing harm and providing grounds for recovery. Some simple and fundamental skills and attention to detail can help to minimize trauma and the ongoing impact of crime, and to prepare the ground for a process of healing for individual victim/survivors. Throughout this article some apparently simple but important steps available to those working to support victims of crime will be explored. The fundamental steps to supporting crime victims are: . introductions . explaining role and any limitations to that role . allowing time for talking about the impact of the crime, and for questions . providing information about normal or predictable responses . avoiding assumptions based on the victims response . being aware of impersonal language. It is important to recognize that no one person can provide for all the needs of a victim of crime. There are agencies and services that provide specialist care in a range of fields, extending the range of choice victim/ survivors have in their own endeavors to recover. This article focuses on issues to do with reporting a crime and ways to make it less traumatic. It must also be acknowledged that sometimes not reporting a crime to police or seeing it not being prosecuted will leave the victim/survivor with a sense of injustice and lack of closure that could prolong the sense of trauma. Providing comprehensive information and support can assist the victim/survivor to make the decision about whether or not to report. It is important that victim/survivors make the decision themselves, as they will be the ones who have to make the police statement and give evidence in court and deal with the outcomes. Utilizing the steps outlined below will go some way towards ensuring that victim/survivors feel more comfortable about reporting the crime to police, assisting in the investigation process, and providing evidence in court, thus holding offenders accountable for their crimes.
Dealing with the Immediate Crisis

One of the shared characteristics of being a victim of a crime, particularly a crime of violence, is that
VICTIM SUPPORT 351
the victim loses control. An important element of the crisis response is to ensure that the victim regains a sense of control as soon as possible. When a crime is reported to the police, particularly a serious crime such as armed robbery or sexual assault, there are a number of players that become involved, most with the aim of investigating the crime and apprehending the offender. Often the needs of the victim are lost in the investigation process. There is a real danger that the loss of control, which was a feature of the crime, will continue. The loss of control during the process of reporting can be significantly increased if the decision to report is taken away from the victim. Examples of this include friends or family of homicide victims, cases where witnesses to a crime involve the police, or where the victim suffers a serious injury and police are involved by medical personnel. There will also be cases where victims may be unable to make a report a patient in a psychiatric hospital, for instance, or a young child. In these cases it is the responsibility of those who are aware that a crime may have been committed to take appropriate steps to ensure the case is investigated and the possibility of continuing victimization is minimized. In cases where victims are able to make the decision for themselves about reporting, it is important that they are informed about the procedure and prepared for what may happen after they report. Information about requirements for evidence-gathering, including forensic medical examinations, helps the victim to make an informed choice about reporting. However, once the report to police has been made, there are some very simple steps which any professional or practitioner involved in the process of immediate response to a report of a crime can take that will assist the victim to feel some form of control over the process and help on the path to healing. Helping victims feel comfortable, recognizing the trauma they have suffered, and treating them with dignity and respect will also assist with the investigation process by encouraging victims to cooperate with the investigating officers and provide as much information as possible.
Explaining Ones Role and any Limitations to That Role
The time immediately following the report of a crime can be completely bewildering for victims. They will meet a number of personnel, including police, forensic physicians, and support people. Personnel involved can help to reduce the confusion by clearly explaining their role, what they can do, and the limitations of their role. Provision of a card or written material will help victims to reflect on this information when they are past the immediate crisis.
Allowing Time for Talking About the Impact of the Crime, and for Questions
Allowing time for telling the story of what happened and for questions about the process of reporting a crime can give victim/survivors some sense of understanding and choice about their options. Victim/ survivors of violent crimes have identified the usefulness of being allowed to tell their story in their own words and to seek clarification about processes and procedures. In some circumstances, it may be preferable to limit unnecessary retelling of a traumatic incident. However, allowing some time during the interaction for victims to talk about feelings and air their concerns can be a first step on the path to healing.
Providing Information About Normal or Predictable Responses
Whatever role the professional plays, helping victims understand that their response is a normal response to trauma will assist them in the healing process. The range of responses reported by victim/survivors of sexual assault include low self-esteem, anger, depression, guilt, sense of vulnerability, confusion, sadness, and grief, to name a few. Victims may think that they should be able to cope or that they will never regain a sense of normalcy. Comments like it is not unusual to feel like this, and what you are experiencing is a fairly common response to trauma help victims understand that they are not alone and that there is a possibility of recovery from the experience.
Avoiding Assumptions Based on the Victims Response
The Fundamental Steps to Supporting Crime Victims

Introduction
By introducing themselves to a victim/survivor of crime and explaining their role, support professionals can increase victim/survivors sense of personal visibility and integrity, in direct contrast to feelings they have experienced in the course of the crime or crimes committed against them.
While there are common responses to being a victim of crime, it should be remembered that every victims response is unique and will be affected by their personality, gender, culture, background, the degree of support from family and friends, and a range of other factors. Thus, it is important not to assume that someone with a veneer of control and calmness is
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unaffected or that someone who is almost incoherent is incapable of making decisions.

Being Aware of Impersonal Language
As noted earlier, the sense of regaining control, of seeing themselves as whole beings entitled to dignity and respect, will help set the groundwork for healing. Support professionals should be aware that the language used could assist or hinder the process. The use of impersonal language is endemic to legal process and sometimes medical care, where a victim/survivor of criminal activity is progressively reduced to a subject or a case, a statistic, a witness, and an outcome in terms of closed cases or clear-up rates. Professionals can address this in their own communication with victim/survivors of crime. The use of terms like case and subject can be alienating, and may exacerbate a sense of dissociation that follows criminal victimization, where the person has been treated as an object and deprived of personhood. Be aware that asking seemingly innocent questions may carry a message to victims that somehow the crime was their fault. Questions like: were you drinking prior to the assault? or are you a virgin? may be necessary to contextualize forensic evidence, but it is important to explain why they are being asked.
increased amongst certain groups - for example women who have experienced violence as children, especially sexual abuse, and among women who have experienced violence, including sexual violence, in adult life. Research also indicates that initial negative dealings with formal support agencies and personnel can impact on the posttrauma responses of victims of violent crime. Campbell and coworkers and Filipas and Ullman found that, while a positive reaction to reports of violent crime had a negligible impact on victims recovery, negative social reactions (e.g., blaming) hindered recovery. Further to these findings, Andrews and coworkers noted that negative responses and satisfaction with support provided had a significant association with PTSD symptoms. The importance for long-term health outcomes of victims of violent crime points to the high level of vigilance required in early stages of supporting victims. A small negative intervention can significantly impede ongoing recovery processes.
The Legal Process

Surveys of victims of crime show that dealing with the legal process is akin to reexperiencing the sense of disempowerment brought about by the crime itself. Interpersonal crime commonly provokes a traumatization of victims, resulting in the violation of their sense of order in the world, as described by Herman. The legal process is often understood as a part of the order of the world, and when that process also appears to be working against the interests of victims of crime, their sense of collapsing order can escalate. Sometimes this decision to report or to initiate an investigation will be out of the control of the victim/ survivor. Where possible, victim/survivors should be provided with sufficient information to allow them to make the decision about whether or not they want the crime investigated and their choices should be respected. It may seem desirable to the onlooker that crimes of violence, particularly premeditated and vicious ones, should be reported. However, where there are no other witnesses, the burden for establishing the case will fall on the victim/witness and he/she should always have the option not to proceed. Providing comprehensive and relevant information about rights, the legal process, and support services can restore a sense of control over decisionmaking, and allow an understanding of the choices that are available within the constraints of the legal system. It is helpful to recognize that the legal process is only a part of a victims life. Consider, for example, a woman who is reporting being raped by a friend. She
Ongoing Trauma or Trauma Reignited in Cyclical or Life Events Beyond the Initial Crime Event
The initial trauma of crime victimization can recur periodically or throughout the life of a victim/survivor. Early appropriate and effective support can provide an important grounding to assist victim/survivors cope with the recurrence. It is common for victim/survivors to report triggers that evoke feelings like fear, anxiety, or grief associated with strong memories of the crime itself. Such triggers can be cyclical, significant one-off events, important life events, or subtle reminders of the original crime, and even repeat crimes. Individuals may not be aware that the distress associated with the trigger event is related to the crime(s) committed against them. Posttraumatic stress responses can become embedded in a victim/survivors normalized responses and manifest as depression, PTSD, dissociation, personal relationship difficulties, suicide ideation or completion, anxiety, panic disorder, and substance use disorder.
Posttraumatic Stress Response

PTSD is recognized as a significant health outcome for many victims of violent crime. Rates of traumatic stress disorder, PTSD, and depression are greatly
VICTIM SUPPORT 353
has three young children: two attend school and one is in day-care while she works. The demands of the legal process may require her to undergo a forensic examination, make a lengthy statement to police, assist police with their enquiries, give evidence and undergo cross-examination in one or more court hearings, make an application, and attend a hearing for compensation. Throughout all this she must maintain a regular routine for her children and keep her employment and social networks intact. This can become onerous while she is also dealing with the trauma of sexual assault and the legal process. Good communication to identify her needs and planning of support services can ease her burden considerably. Examples of support might include: . ensuring that appropriate care for her children is available during times when she is required to attend investigation and trial . providing documentation for her employer explaining that she is unfit for work for a period of time, without disclosing the nature of her injury . helping her explore ways of talking about the crime to mutual friends so that contact with the perpetrator can be avoided . advocating with the investigating officers to ensure she is kept informed about the progress of the investigations . providing her with information about supports that are available during the court process and assisting her to access them . assisting her to prepare for giving evidence by showing her the courtroom prior to trial and explaining who will be present and what their roles are . helping her prepare to answer questions clearly and honestly and preparing her for strategies that may be used by defense counsel to confuse her and therefore reduce her credibility. Supporting a victim/survivor through the legal process requires a careful explanation of what is involved and what can be expected from the legal system. Common understandings of the legal system include an expectation that fairness and justice will result from contact with the system. This expectation is often shattered in the process of dealing with police and judicial officers where a victim of crime is relevant to the law as no more than a site of evidence or state witness. Just and fair outcomes can appear to be absent from consideration in the machinations of legal process. In the aftermath of the dehumanizing effect of the crime itself, this experience can compound a victim/survivors sense of disorientation. Responses of victim/witnesses can vary from expressive to controlled. A man who has been in a
senior management position may fear showing any sense of vulnerability if he is a victim of a crime such as armed robbery in the workplace and may present a fac ade of being in control. It would be wrong to assume that he will have access to the information needed to deal with a legal process or that he does not need support. Not exploring the full range of options for information and support could translate to the victim/survivor as a judgment about undeserving status. Conversely, with information, victims are empowered to exercise choice and make informed decisions about what action to take, thus reclaiming a sense of order. In the instance of charges proceeding to trial, a victim/survivor will require specific information about the trial process. Legal proceedings will sometimes be modified in recognition of the impact of particular crimes. In the case of sexual assault trials in Australia, courts have the capacity to order the use of screens or closed-circuit television so that the witness is protected from view of the alleged perpetrator. This is not an automatic right for victims, and only by knowing about the provision can they request its use. Such provisions can considerably lessen the impact of court experiences. Support professionals who are unaccustomed to provide support in such instances should refer to or seek the advice of agencies that have been established for the purpose. Some in-house court support personnel are dedicated to this task, while others provide information and contact with paralegal services that can give specific information. Consideration should be given to issues such as disability, indigenous heritage, and cultural heritage different from the prevailing institutional culture, especially where language is a factor, or there has been a prior negative experience with the legal system. Each of these factors, or a combination, will serve to decrease a victim/survivors sense of control over the proceedings at hand. Specialist support is critical in this event. Agencies providing specialist support, cultural liaison, or interpreters should be contacted for appropriate advice and additional support.
Summary
The support of victim/survivors of crime needs to be approached from a perspective that includes the principles outlined in the introduction, and with respect for their specific wishes and needs. Legal processes commonly appear to occur either without or specifically against the consent or best interests of victim/ survivors. Effective support entails responding to victim/survivors in a nonjudgmental fashion, explaining the normal responses to trauma induced by crime, and listening to and validating their experience. Effective
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support helps to restore control through providing information, advocacy, and coordination of victim support services and maximizes the possibility of cooperation with the investigative process. Providing effective support empowers victim/survivors to make decisions in their best interests, thereby maximizing their chances of regaining a sense of control.
See Also
Domestic Violence; Preparation of Witnesses: Scotland; United States of America; Sexual Offenses, Adult: Management Postassault; Male Sexual Assault; Drug-Facilitated Sexual Assault; War Crimes: Tribunals
Further Reading
Andrews B, Brewin CR, Rose S (2003) Gender, social support, and PTSD in victims of violent crime. Journal of Traumatic Stress 16: 421427. Astbury J (2001) Mental health effects of SVAW: outcomes and research questions. Parallel Session on Moving Sexual Violence Research forward, The 10/90 gap in Health Research: Assessing the Progress. Forum 5, Geneva 9-12 October. http://www.globalforumhealth.org/ non_compliant_pages/forum5/sessionsheet/108.html (12 May, 2004). Burgess A, Holmstrom L (1974) Rape trauma syndrome. American Journal of Psychiatry 131: 981986. Campbell R, Ahrens CE, Sefl T, Wasco SM, Barnes HE (2001) Social reactions to rape victims: healing and hurtful effects on psychological and physical health outcomes. Violence and Victims 16: 287302. Cook B, David F, Grant A (1999) Victims Needs, Victims Rights: Policies and Programs for Victims of Crime in Australia. Australian Institute of Criminology Research and Public Policy series no 19. Canberra, Australia: Australian Institute of Criminology.
DArcy M (1999) Speaking the Unspeakable. Melbourne, Australia: CASA House. Derhammer F, Lucente V, Reed III JF, Young MJ (2000) Using a SANE interdisciplinary approach to care of sexual assault victims. Joint Commission Journal on Quality Improvement 26: 488496. Dutton DG, Painter S (1993) The battered woman syndrome: effects of severity and intermittency of abuse. American Journal of Orthopsychiatry 63: 614622. Filipas HH, Ullman SE (2001) Social reactions to sexual assault victims from various support sources. Violence and Victims 16: 673692. Herman J (1992) Trauma and Recovery: From Domestic Abuse to Political Terror. London: Pandora. Hoff L (1989) People in Crisis: Understanding and Helping. Menlo Park, CA: Addison-Wesley. Scott D, Walker L, Gilmore K (1995) Breaking the Silence: A Guide to Supporting Adult Survivors of Sexual Assault, 2nd edn. Melbourne, Australia: CASA House. Taylor CS (2001) The Legal Construction of Victim/Survivors in ParentChild Intrafamilial Sexual Abuse Trials in the Victorian County Court of Australia in 1995. Unpublished thesis. School of Behavioural and Social Sciences and Humanities, University of Ballarat. Victorian Law Reform Commission, Inquiry Into Sexual Offenses. Interim Report 2003. World Health Organization (1997) Violence Against Women: Health Consequences. http://www.who.int/gender/violence/ prioreng/en/ World Health Organization (1997) Violence Against Women: Definition and Scope of the Problem. http:// www.who.int/gender/violence/prioreng/en/ World Health Organization (1997) Mapping a Global Pandemic: Review of Current Literature on Rape, Sexual Assault and Sexual Harassment of Women Consultation on Sexual Violence Against Women. http://www.who.int/ gender/violence/prioreng/en/
W
WAR CRIMES
Contents Site Investigation Pathological Investigation Tribunals
Site Investigation
W D Haglund, Physicians for Human Rights, Washington, DC, USA
take place under the auspices of the International Criminal Tribunal for the former Yugoslavia (ICTY).
War Crimes Law and Site Investigations

Law historically referred to as crimes of war law is derived from various agreements, treaties, or laws that regulate treatment of combatants in the conduct of war between states. The plight of civilians and protection of combatants in internal conflicts (as distinct from wars between states) was addressed in the four Geneva Conventions of 1949 and their Additional Protocols of 1977; together these comprise what is known as international humanitarian law. Contemporary investigations of war crimes overlap with the crimes of genocide and crimes against humanity and now include investigations of conflict, for example in trials of ICTY and ICTR (International Criminal Tribunal for Rwanda). There are multiple goals of international forensic investigations. First is to collect physical evidence relating to cause and the circumstances surrounding the crime and the identity of the victims. Second is to hold accountable those who are responsible. Of course, a major goal of investigations involving human remains should always be their identification and return to survivors. A further hope is that exposure of findings to world opinion and the knowledge that those responsible will be held accountable will serve as a deterrent to repetition of similar acts in the future. Exhumation of a particular mass grave may or may not address all of these objectives. Some mass grave exhumations are performed for purely humanitarian reasons with no goal of prosecutions in mind.
Crime Scene Investigation

The objectives of investigating war crime sites are the same as applied in any other crime scene: to recognize, collect, preserve, interpret, and reconstruct all relevant physical evidence of the scene and its context. Sites potentially yield many types of information ranging from identification of suspects, linkage of perpetrators and victims, and support or contradiction of witness statements. Often scene investigations provide vital investigative leads. At the conclusion of site investigation and subsequent analyses, one should be able to defend interpretations based on documentation of the process and evidence collected. Forensic accounts of past war crimes site investigations are relatively meager, often sequestered in the reports of experts. Todays landscape of conflicts around the globe has spurred the development of systematic approaches to site investigations, which produce valid data presentable as evidence in courts of law. This article summarizes the goals of war crimes site investigations, discusses the preliminary site assessment, and lays out issues involved in putting a team into the field to carry out investigations. Historical examples of significant past investigative efforts are presented. The article concludes with a case example, that of the site investigation of the Cerska mass grave, the first major exhumation to
356 WAR CRIMES/Site Investigation
Investigation of domestic murders may involve sites of encounter, abduction, or transportation of victims, as well as locations of captivity, killing, and disposition. Most often, in the context of war crimes investigations, the majority of sites are either severely contaminated or are no longer available. Site investigations have included alleged locations targeted by combatants, places of detention and torture, or sites of massacres. However, the most common experience has been that by the time a forensic response can be mounted, sites that can potentially yield the maximum physical evidence are limited to graves. Even then, grave-sites have often been tampered with or completely destroyed. This may be at the hands of those accountable in an effort to hide their crimes, by well-meaning families desperate to learn the fate of their missing, or by authorities hoping to garner attention that atrocities have taken place. Prior to commitment of experts to the field, basic questions need to be addressed and a series of prerequisites satisfied. Investigations must take place under established international, national, or local laws.
Table 1 Stages in the investigation of a mass grave site

Stage Activities
Permission and identification of site
Legal authority and access Identification of potential site(s)

Assessment
Determine whether human remains are present Determine the security and logistical needs Determine the professional needs of an exhumation Work with investigators to determine if exhumation is likely to meet judicial needs
Planning
Funding Purchase or otherwise acquire equipment and supplies Security Personnel Logistics, including transport and equipment, meals, and accommodation Prioritization of sites for investigation Handling of media
Site investigation
The Need to Investigate War Crimes Sites

Rationalizations for investigation of war crimes sites are several-fold. Often there is a tendency for such crimes to be ignored or mischaracterized by governments in order to cover up their own abuses. There may be a lack of will stemming from perpetrators holding or having influence over political power. Some nations may lack expertise and/or resources to carry out forensic investigations. In certain situations, even if there is a will and national experts are available, it may be unsafe for them to conduct investigations. Distrust of national governments may also motivate advocacy of more impartial investigations. Such distrust may come from citizens who have suffered under their governments actions and/or the international community, which has concerns that objective investigations and fair trials take place. International war crimes investigations can be distinguished from those in the domestic arena on several levels. In the domestic context, authority to investigate, rapid response, site access, security, and infrastructure support for criminal investigation are taken for granted. This is in sharp contrast to investigations of international crimes in the conflict or postconflict arena. Global observers often watch as the potential crimes unfold. Before international experts can begin, there must be an invitation by national governments or, when international investigations are proposed, the national government involved must concur. There may be special
Site preparation Survey for unexploded ordinance and removal Establishment of security perimeter and control point Site planning (site office, eating, washing and toilet facilities, staging area for vehicles and heavy equipment, placement of removed overburden) Collection of surface evidence prior to excavation Exhumation Trenching to determine perimeters and depth Removal of overburden Exposure and delineation of remains and evidence Documentation: mapping of remains and other evidence in situ, video and still photography of location and removal process Removal Clean-up and departure
circumstances in place, such as with ICTY and ICTR. Experts must be assured of security and that an impartial mechanism of accountability is in place. Investigators need assurance of adequate expert, technical, and administrative support, plus objective legal advice to insure that the investigations will produce admissible evidence for later criminal proceedings. Once these issues have been addressed, a strategic plan based on site assessment is in order. Only then should the actual site investigation take place. Table 1 gives an overview of a typical international forensic project involving a mass grave.
Assessments
The purpose of the assessment is to determine an investigations feasibility and necessary requirements to carry out the work. The first step is to establish that an investigation would have legal authority and permission for access.
WAR CRIMES/Site Investigation 357
Assessments set the stage for planning and involve funding, staffing requirements, and security needs. Among subjects that have at times become major impediments, when not properly considered, are issues of security, the potential impact of weather, and sensitivity to local cultural or religious customs and beliefs. Table 1 enumerates major issues to be considered in assessments. The assessment phase should remain a phase of documentation and evaluation alone and should not include collection of evidence from the scene unless absolutely necessary. Documentation via photography and mapping is of critical importance both for the assessment and for individuals who may work on the site in the future. Site visits allow evaluation of the complexity, size, and stability or vulnerability of a site. Logistical factors to be considered include getting equipment and people into and out of the area, estimation of the time required to complete the sites investigation, and whether extraordinary specialists, equipment, or logistics are needed. Site investigation is a multidisciplinary effort. For small sites a few experts may need to perform multiple tasks. For larger sites, such as exhumation and examination of victims of a medium to large-sized mass grave, much of the basic infrastructure that is taken for granted in industrialized countries, such as examination facilities, storage for remains, water, and electrical utilities, needs to be put into place. Generally, sites are too numerous for all of them to receive detailed forensic attention due to limitations of time, security, and funding. Assessment of multiple sites allows judicious prioritization of specific sites to be investigated. Security of forensic experts and the site is a primary concern. The lack of guarantees of international security renders the investigation of certain graves impossible. For example, without the North Atlantic Treaty Organization (NATO) security in the Balkans, mass grave exhumations for ICTY could not have taken place. An absolute necessity, prior to working at a site, is a survey for unexploded ordnance and its subsequent removal. Site security ideally should be continuous from the time the site is discovered to completion of the investigation. Unfortunately, from the time of discovery to the site investigation, periodic monitoring is usually the most that can be achieved. Once the forensic work has commenced, 24-h site security is essential. Cultural and religious issues can become highly volatile when undertaking forensic exhumations. Sensitivity to local customs is a crucial contribution to the well-being and peace of mind of survivors and other members of the community. Major religious
issues tend to revolve around the prohibitions on disturbing buried remains, the need for presence of religious authority(s), the handling and packaging of remains, and rituals and/or prayers to be performed at various stages of the forensic investigation. Failure to adhere to customs and traditions can cause unrest and dissent among the population and even result in the closing of the local operation. For example, in May 2001, an attempt was made to investigate the 1941 execution and burial site of an alleged 1600 Polish Jews on the outskirts of the hamlet of Jadwabne, Poland. The exhumation was an effort on the part of the Polish government to set the record straight on whether the killers were occupying Nazis or fellow Polish neighbors of the victims. The objections of Orthodox Jews to the disturbance of Jewish graves, however, were successful in closing down the exhumation efforts (Figure 1). Planning the fielding of an expert team involves funding, organization, securing staff and resources, and finalizing logistical preparations. The planning phase is the time for experts and officials to come to final understanding regarding issues such as division of labor, independence of the investigation, decision as to who will be allowed onto the site, and media policy. It should be kept in mind that site investigations do not occur in a vacuum. It would be irresponsible to undertake the exhumation of a mass grave without considering the wider context of a complete investigation that incorporates the linkages between and among site investigation, laboratory examinations, eventual identification of victims, and humanitarian concerns of families and communities. These are usually assumed extensions of domestic coroner/ medical examiner investigations, but are too often ignored in international work. While establishing relations with families and communities may be a difficult part of operating internationally, the incorporation of a team of psychosocial workers into the planning and operational phases can often bridge the gap between the scientific experts and the families of the missing.
Historical Investigations
Accounts of forensic investigations of war crimes sites date to World War II. The majority of these sites have been mass graves. The Nazis 1943 investigation into the massacre of over 11 000 Polish prisoners in the Katyn Forest near Smolensk, in present-day Russia has been commented on by many authors. The victims were primarily Polish officers who had been held as prisoners of war by the Soviets and executed in 1941. The graves were first brought to the attention
Figure 1 Exhumation of the 1941 execution and burial site of an alleged 1600 Polish Jews on the outskirts of Jadwabne, Poland was discontinued due to religious objections.
of the public by the Germans in April 1943. Earlier, in February of that year, German troops advancing through the Katyn Forest had discovered suspicious earth mounds planted over with young pine trees. Preliminary excavations confirmed the existence of mass graves. A concern of the Nazi government was that they would be blamed for the deaths, which however, had occurred at a time when the region was under Russian occupation. In May 1943, strategizing to counter future allegations that they had carried out the massacres, the Germans established an international medical mission composed of professors of forensic medicine from nine German-occupied European nations, Italy, and neutral Switzerland. The commission was to report manner, cause, time of death, and probable culpability in the deaths. The report, edited and issued by German authorities in April 1943 relates that 4143 bodies were exhumed and 2914 were identified on the basis of personal artifacts and documents recovered from the bodies. A majority of the victims had been shot in the head. Five percent were found with their hands tied behind their backs. The report commented that absence of insects, as well as the presence of documents, correspondence, diaries, and newspapers in the grave, indicate that the deaths had occurred in MarchMay 1940. The Soviets reoccupied Smolensk in September 1943. They vigorously denied charges that they were responsible for the Katyn atrocities and began their own investigations that in turn laid blame on the Nazi German government for the executions. At the insistence of the Soviets and over the reluctance of the French, British, and American prosecutors,
allegations of the massacre were included in Count Three of the Indictment at the Nuremberg War Crimes Trial. Although the falsity of these indictments was strongly suspected by many, they were allowed to stand though they were not mentioned in the verdict. It has now become clear that the Soviets were responsible for these mass executions and recent accounts have since been published. Two forensic pathologists should be recognized for their participation in World War II war crimes investigations: Arthur Mant and Charles Larson. Mants primary assignment with the British Army Medical Corps was to identify missing allied air force personnel in Europe. In doing so, Mant contributed to seminal observations on the variables affecting decomposition of remains in mass graves. Lesser known are the investigations of Charles Larson, an American forensic pathologist, who was detailed to the American War Crimes Investigation Team Number 6823. One of Larsons first assignments was to inspect a train near Seeshaupt consisting of nearly 60 boxcars that had been the target both of strafing by allied bombing and of Germans firing on the train on May 5, 1945. The train had been transporting an estimated 1500 prisoners. Known causalties consisted of 65 dead and 163 hospitalized wounded. Larson also conducted postmortem examinations on victims from the Dachau concentration camp. Both Larson and Mant investigated medical experimentation carried out by the Nazis. Over the decades since World War II, other gravesites have been exhumed. In Asia, graves outside Nanking, China were opened for the Nanking War Crimes Trials, but currently it appears that no
detailed reports on this investigation are available. Mass graves were investigated in Saipan and in the Ukraine as well. The latter investigation was carried out by an Australian forensic team in June 1990 with the cooperation of Russian authorities and experts as part of an investigation by the Australian government into the case of Nazi officer Ivan Polyukhovich, who was indicted for his involvement in a massacre of Jewish citizens outside the town of Serniki in the fall of 1942. Due to time and resource constraints, limited examinations were carried out at the graveside with the goal of estimating age and sex and determining cause of death. Only the topmost remains of the grave were examined. Based on 553 selected skulls, 407 were found to be female while 98 were male. (Skull according to Bevan is inclusive of both the cranium and mandible, but here cranium only is intended.) Sex for 48 individuals could not be determined (skeletal determination of sex is problematic in pre-adolescent individuals for whom secondary sex characteristics are not developed; also, skeletal material was found to be decomposed and damaged). Of these individuals 410 had died of gunshot wounds to the head. Cause of death was not established in 133 cases. After World War II there followed four decades with little or no forensic attention to sites that would qualify as war crimes investigations. Then in 1984 came a request from Argentinas newly elected President Alphons n directed to the American Association for the Advancement of Sciences (AAAS) Committee on Scientific Freedom and Responsibility for an investigation of the disappeared in Argentinas dirty war. The lesson from Argentina was the recognition that physical evidence resulting from forensic investigations provides resilient documentation countering historical revisionists who often claim that such abuses never occurred, were not as extreme as stated, or were only a measured response to a national emergency. Forensic investigations enabled expert testimony to be presented in court and provided immeasurable comfort and solace to many family members of victims. The Argentine experience launched a new period of forensic investigation into a diversity of conflicts ranging from undeclared wars between nations, fullscale civil wars, low-intensity conflicts between national political groups, and dirty wars of repression. A series of investigations has followed throughout Latin America including Guatemala, Honduras, El Salvador, Chile, and Peru. Assessments or major investigations of sites have also taken place in Iraqi Kurdistan, Afghanistan, the Congo, East Timor, and Sierra Leone. Less-publicized investigations have occurred in Somaliland, Sri Lanka, Indonesia, and Bangladesh.
Over the past 15 years, the United Nations (UN) has been aided by experts provided by organizations such as the Boston-based Physicians for Human Rights (PHR) and the Forensic Anthropology Teams of Argentina (EAAF) and Guatemala (EAFG) (their old title was EAFG; today, however, they are FAFG). Representatives of these groups have been major players in providing experts to exhume individual and mass graves worldwide. They have developed strategies for assisting and educating families and communities with regard to issues concerning forensic work. More recently governments have supported ad hoc teams that have responded to investigations, for example, in Kosovo and East Timor. The advent of ICTR and ICTY and subsequent forensic investigations initiated in 1996 stand as a watershed event for international war crimes investigations. The first major grave to be exhumed under the auspices of ICTY forensic investigators was a grave known as Cerska, located alongside a road through the mountainous Cerska Valley in what is now the Republika Srpska region of Bosnia and Herzegovina.
The Cerska Mass Grave

In July 1995, the UN-declared safe area of Srebrenica fell. In the immediate aftermath of the fall approximately 7000 men and boys went missing, having last been seen in the hands of Bosnian Serb forces or attempting to reach territory controlled by the Bosnian army. On November 16, 1996, ICTY indictment IT-95-18-I was issued for genocide and crimes against humanity and violations of the laws and customs of war that occurred following the take-over of Srebrenica. The initial suspicion that the missing men and boys of Srebrenica were executed and buried in mass graves has subsequently been confirmed through ICTY exhumations conducted over 7 years, as well as by investigations conducted by the Bosnian commission on missing persons. The following is a brief account of the Cerska grave-site investigation, the first major forensic investigation that took place under the auspices of ICTY, in July 1996. The Cerska grave extended 32.5 m along one side of a relatively remote gravel road leading to the Cerska Valley (Figure 2). The limits of the site included the grave, the embankment on the opposite side of the road, and the road surface. The embankment containing the grave was a sloped incline. Soil to cover the remains had been taken from the opposite side of the road and the wall of a hillside cut which was originally made during the construction of the road. Cartridge casings were strewn over the road and the roadside opposite the grave.
Figure 2 The Cerska grave-site prior to investigation, 1 year after the killings. Victims were shot at the site and their bodies covered over on the inclined embankment.
Discovery of the grave was assisted by witness testimony. An initial assessment of the site was conducted in late May 1996. Three small test excavations revealed the presence of decomposed human remains. The remains were left undisturbed and the excavations refilled. Initial mapping and collection of many spent cartridge casings were conducted at the time of the assessment. Round-the-clock security of the site was not available but the site did receive periodic monitoring from the International Implementation Force (IFOR) troops between its discovery and beginning of the actual final investigation on July 7, 1996. At the time of the actual investigation, a generous security perimeter was established, large enough to allow for staging and working on the site. A holding area was designated for visitors and media. US IFOR troops provided 24-h security. Basic equipment and supplies were staged and later a refrigerated container for body storage and evidence was obtained. The exhumation was performed by a 12-member multidisciplinary team consisting of archeologists, anthropologists, a photographer, a crime scene officer, logistician, and a backhoe driver. Workers arrived daily in a military convoy from a local military base where they were lodged. IFOR soldiers maintained overnight security and tripwire flares were strategically placed at the site perimeters. Prior to their arrival a group of Bradley tanks was dispatched well beyond the upper and lower limits of the site. During working hours soldiers were stationed at the highway turnoff of the Cerska Road and at the immediate security perimeter of the grave-site.
Prior to experts working at the scene, a check for the presence of unexploded ordnance and mines was undertaken by two dogs and their handlers provided by Norwegian Peoples Aid (NPA). Once the site had been determined safe, initial overall photography and mapping of the site took place. Surface evidence consisting of cartridges on the surface and sides of the road was documented and collected. While this was taking place the vegetation over the grave was cut and removed. Defining the grave boundaries and reopening the test assessment excavations to determine the depth and condition of the remains initiated the excavation. The overburden was then removed in incremental levels by a backhoe that was closely monitored. Once the level of remains was reached, hand tools were used to expose and delineate the remains (Figure 3). Bodies had become partially skeletonized during the 1 year since death. This was the result of several factors. The depth of burial was shallow, beginning at 50 cm. This shallowness, loose compaction of the overburden, and efficient drainage of the inclined site combined to form an environment that hastened decomposition and skeletonization of the victims. The grave area was expansive enough to allow for several excavation teams of two individuals each to work simultaneously. Each of the remains was delineated so that the full extent of the individual could be determined. The area was then cleaned in preparation for photography. Assignment of a case number was made prior to removal of each individual. Overall photos were taken in order to demonstrate the relative location
Figure 3 A group of remains prior to removal.
of the remains and close-up photos to record significant details, such as bindings and observable fractures. A brief description of the remains was dictated and the outline of the body mapped. Remains were then wrapped in a plastic body-bag liner and placed into a correspondingly numbered zippered body bag for refrigerated storage and transport to the examination facility. Upon completion of the exhumation, the incline upon which the victims rested was examined and passed over with a metal detector. In addition to still photos of each of the remains and video taping of the exhumation process, final site documentation included a topographic and feature map of the site including the location of the human remains and other evidence. The exhumation at Cerska was concluded on July 18, 1996, and 150 individuals were exhumed. Remains were transported to the Kalecija examination facility under the coordination of UN police observers and cooperative security provided by IFOR and local Republika Srbska and Bosnian police. Evidence from the Cerska site supported the scenario of victims having been lined up on the side of the road overlooking the inclined embankment. They were shot from behind with automatic weapons. The bodies then fell, coming to rest upon the embankment surface. Cartridge case distribution showed the position of the killers on the far side of the road behind them. A digging machine was used to take fill from the hillside cut behind the killers in order to cover the dead. Autopsy examinations were carried out at a temporary morgue in a war-damaged clothing factory
in Bosnia Herzegovina. All 150 victims were male some adolescent and some elderly. The majority were between the late teens and mid-forties in age. One-third had their wrists wired behind their backs (Figure 4). The cause of death for 149 victims was gunshot wounds (Figure 5). The majority died of multiple gunshot wounds. Cause of death for one individual could not be determined. Documents found on nine victims provided leads to personal identification. This evidence was presented in the trial of General Radislov Krstic .
Expectations and Issues for the Future

The trend in recent international war crimes investigations is that they are requested to occur in the near aftermath of conflicts or in environments of uneasy peace. Immediate responses are sought. This entails high security concerns. For large responses, detailed preparation and, significant funding are critical. Current estimates are that 4050 conflict areas exist in the world today. The number may be higher. If the past is any indication, most will never be investigated. Heightened awareness of war crimes has increased the expectations of forensic investigations and forensic experts, at least for the highest-profile conflicts. Experience has shown that to simply recover and examine remains to determine circumstances and cause of death is no longer a sufficient outcome. There is an expectation that the humanitarian needs of communities and survivors will be considered and,
Figure 4 One-third of the 150 victims of the Cerska grave had their wrists wired behind their backs.
See Also
Anthropology: Archeology, Excavation and Retrieval of Remains; War Crimes: Pathological Investigation; Tribunals
Further Reading
Abarinov V (1993) The Murders of Katyn. New York: Hippocrene Books. Bevan D (1994) A Case to Answer: The Story of Australias First European War Crimes Prosecution. Kent Town, South Australia: Wakefield Printing. Fitzgibbon C (1971) Katyn. New York: Charles Scribners Sons. Gutman R, Rief D (1999) Crimes of War. New York: WW Norton. Haglund WD (2001) Recent mass graves: an introduction. In: Haglund WD, Sorg, MH (eds.) Advances Forensic Taphonomy, pp. 243262. New York: CPR Press. International Criminal Tribunal for the Former Yugoslavia (2000) ICTY Case No. IT-98-33 Defendant Krstic , May 29, 2000. Keough ME, Kahn S, Andrejevic A (2000) Disclosing the truth: informed participation in the antemortem database project for survivors of Srebrenica. Health and Human Rights 5(1): 6987. Nayare A (1998) War Crimes: Brutality, Genocide, Terror, and the Struggle for Justice. New York: Random House. Neuffer E (2001) The Key to My Neighbors House: Seeking Justice in Bosnia and Rwanda. New York: Picador. Physicians for Human Rights (1996) War Crimes in the Balkans: Medicine under Siege in the Former Yugoslavia 19911995. Boston, MA: PHR.
Figure 5 The cause of death for 149 of the Cerska victims was gunshot wounds. The arrow shows an exit wound.
thus, that the victims will be identified and returned to their families. An evolving concept is that there must be a balance between the tension between justice and humanitarian needs.
WAR CRIMES/Pathological Investigation 363 Stover E, Peress G (1998) The Graves: Srebrenica and Vukovar. Zurich, Switzerland: Scalo. Stover E, Ryan, M (2001) Breaking bread with the dead. Historical Archeology 35(1): 725. Stover E, Haglund W, Samuels M (2003) Exhumation of mass graves in Iraq: considerations for forensic investigations, humanitarian needs, and the demands of justice. Journal of the American Medical Association 290: 663666. Taylor T (1992) The Anatomy of the Nuremberg Trials: A Personal Memoir. New York: Alfred A. Knopf. Zawondy JA (1962) Death in the Forest: The Story of the Katyn Forest Massacre. South Bend: University of Notre Dame Press.
Pathological Investigation
J Clark, University of Glasgow, Glasgow, UK
Introduction
The concept of war crimes has been around now for over a century, but the use of scientific expertise to investigate them is a much more recent development. That principle having been established, however, pathologists, anthropologists, and those from other disciplines are increasingly being involved in the investigation of alleged atrocities throughout the world some recent, some from decades past. Much expertise has been built up from the wars in the former Yugoslavia but there have been ongoing investigations in other parts of the world for many years and, undoubtedly, conflicts in the Middle East, and possibly again in Africa, will be a focus of attention for the future. War crimes has a strict legal definition but, in terms of the scientific involvement, the same general principles apply to all deaths related to repression and conflict, whatever the subsequent charge.
and examined by a German-inspired European medical commission in 1943 to refute future allegations that they (the Germans) were responsible; 50 years later the Soviets eventually admitted to the crime. The examination of the bodies revealed that all had been shot in the back of the head, some had bayonet wounds, and a proportion had their hands tied behind their backs. In the years following the war, Mant, working for the British War Crimes Group, examined a total of 150 bodies, some of them concentration camp victims but mostly members of the armed forces, primarily aircrew allegedly shot after crash landing. One incident involved eight soldiers who had been forced to dig their own grave before being shot. Examination of each of the bodies revealed a wound in the back of the head. The exhumations were carried out both to gather criminal evidence and to identify the victims. In the 1990s further World War II graves were examined in Poland, the Pacific, and the Ukraine. In the last of these, an Australian commission examined three graves and uncovered the bodies of 778 adults and children. Despite the remains having been there for almost 50 years, it was still possible to establish that the vast majority had been killed by a single gunshot injury to the head, vital evidence that corroborated eyewitness accounts.
Latin America
Development
World War II
The first main record of bodies of war victims being medically examined dates from World War II, when evidence was presented to the Nuremberg trials in 1945 by the Soviet War Crimes Commission, which had examined corpses from concentration camps. Also presented was evidence of the massacre, in 1941, of 4153 Polish soldiers at Katyn forest near Smolensk in Russia. The bodies had been exhumed
The next main focus of work was in Latin America, with the establishment of forensic teams to investigate the extensive human rights violations in that part of the world during the 1970s and 1980s. In 1984, with a return to democracy, the Argentine Forensic Anthropology Team Equipo Argentino Anthropolog a Forense (EAAF) was established to examine sites alleged to contain the bodies of many of an estimated 10 000 disappeared individuals. A similar team was subsequently established in Guatemala Fundacio n de Anthropolog a Forense de Guatemala (FAFG) to investigate crimes from 36 years of civil war. Members of both teams have since contributed to missions in many other countries throughout the world, and in recent years members of EAAF have given testimony of their scientific findings to courts in both Argentina and in Europe, as countries such as France, Germany, and Italy pursue prosecutions related to nationals killed during the military dictatorship of 19761983. Forensic teams are now also established in Colombia, Venezuela, and, more recently, in Peru where Equipo Peruano de Anthropolog a Forense (EPAF), an independent and self-funded group, is beginning to undertake exhumations of the bodies of
364 WAR CRIMES/Pathological Investigation
some of the alleged 7000 individuals who disappeared in the 1980s and 1990s. As with the other Latin American teams, however, the main expertise is anthropological rather than pathological, with little direct involvement of medically trained individuals (Figure 1).
Rwanda
sex of the victims (more than half were infants or people under the age of 18) and evidence of trauma and cause of death (the majority had machete-type wounds and/or blunt-force trauma).
Former Yugoslavia
On another continent, the war in Rwanda in 1994, in which interracial violence claimed the lives of more than half a million people, led to the United Nations (UN) passing a resolution in November of that year to establish an International Criminal Tribunal. A further resolution in February 1995 decided that the Tribunal should sit in Arusha. At the end of 1995 Physicians for Human Rights (PHR) was asked to examine mass graves in the country and, with a team of archeologists, anthropologists, pathologists, and technicians drawn from a number of countries, they exhumed graves in Kigali and at Kibuye. (PHR was established in the USA in 1986 and exists to use medical and scientific methods to investigate and expose violations of human rights worldwide. The International Forensics Program was founded in 1995 and formally brought together a team of pathologists and anthropologists. They were the first to be involved in the wars in the Balkans, carrying out work there before the International Tribunal established its own forensic team.) Kibuye was the site of a massacre of hundreds of people who had taken refuge in a church, and the team uncovered the remains of over 450 bodies there. Using an on-site temporary mortuary it was possible to established the age and
More than any other conflict, the wars in the Balkans have demonstrated the value of scientific assistance in the investigation of war crimes. From them, much expertise has been acquired and well-tested procedures established, which can form the basis of any similar work in the future. The wars accompanied the political break-up of Yugoslavia and the rise of Serb nationalism. Beginning with a brief confrontation in Slovenia in 1991, the conflict progressed to a prolonged and bitter struggle in Croatia which began later that year and continued on and off for the next 4 years. In 1992 the focus moved to Bosnia, with Bosnian Serbs occupying large parts of the country and displacing, imprisoning, and killing much of the Muslim population. Concentration camps were established in the north of the country, the capital Sarajevo was besieged for 3 years, and 7000 men were massacred at Srebrenica in 1995. Monitored peace was achieved later that year but in 1998 aggression and killing resurfaced in the Serbian province of Kosovo, continuing until the intervention of North Atlantic Treaty Organization (NATO) forces in 1999. In the 9 years of conflict throughout Yugoslavia it is estimated that 4 million people, a quarter of the population, were displaced from their homes and more than 150 000 were killed (some sources give a figure of 250 000).
Figure 1 Major sites of war crimes examinations since 1945.
WAR CRIMES/Pathological Investigation 365
Bosnia and Croatia The first bodies examined medically were in Croatia where, through a wellcoordinated system of regional forensic and medical centers, all recovered remains, whether civilian, police, or military, were examined, primarily for identification purposes but also for documentation of injuries and cause of death. By 1993 almost 6500 of an estimated 14 000 missing persons had been identified, principally by fingerprints but also by dental records and primary observational data. In reporting these findings at the time, the Croatian investigators highlighted the need for a single international organization to oversee this work, stressing the impartiality that such a body would have and the information which could be obtained in pursuing criminal convictions. A well-developed identification program continues today. In 1992 a UN Commission of Experts invited PHR to investigate an alleged mass grave near Vukovar, in the east of Croatia. The presence of the site was confirmed but it was not until 1996 that it could be fully explored. The uncovering of 200 bodies, the artifacts associated with them, and the nature of the injuries found, provided strong corroborative evidence for the allegations that the grave contained civilian victims taken from Vukovar hospital in 1991 to an execution site at Ovcara. Unlike Rwanda, the examination of the bodies was carried out, not at the gravesite, but at an established mortuary some distance away: this procedure formed the basis for all such future work in the Balkans. In Bosnia, the first reports of concentration camps and the killing of inmates appeared in 1992 while in 1995, after the fall of Srebrenica, the world was alerted to the existence of mass graves and reports of mass killings. By this time the UN Security Council had established the International Criminal Tribunal for the former Yugoslavia (ICTY), which was given a mandate in 1993 to investigate and prosecute alleged violations of international humanitarian law in that country. With the end of hostilities in November 1995, ICTY set about planning a program of exhumations. The first major exercise was in the summer and fall of 1996 when PHR assisted the Prosecutors Office to exhume four gravesites around Srebrenica. A total of 480 bodies were uncovered, the vast majority with gunshot injuries, many with their hands tied and, in one grave, many with blindfolds. There was also clear evidence of two of the graves having been robbed, that is, partly emptied and the bodies reburied elsewhere, presumably in an attempt to hide the primary graves. ICTY subsequently established its own fulltime forensic unit to provide assistance to the teams of
investigators working on cases in both Bosnia and Croatia. The unit was augmented each working season by professionals and others drawn from many countries throughout the world archeologists and anthropologists at the gravesite exhuming the bodies, and pathologists and anthropologists examining the remains in the mortuary, both groups assisted by the scenes of crime, technical, secretarial, and logistical back-up necessary for such an exercise. The main exhumation program lasted from 1997 until 2001, with a variety of sites explored, not only from Srebrenica, but also from other killings in the Drina Valley, prison camps, and specific incidents in both Bosnia and Croatia, the latter including Serb victims. Most sites were typically large graves but bodies were also recovered from potholes, wells, and wooded slopes. Of the dug graves, some were primary, some were disturbed graves, and some were secondary, that is, reburials from the primary graves. The mortuary process, the difficulties inherent in such work, and the typical findings in such cases will be discussed in more detail in later sections. From the first sites explored in 1996 until the end of 2001 some 40005000 bodies were examined but there are many graves still to be exhumed and probably many still to be discovered. While the major forensic program of ICTY is now largely complete, exhumations continue on behalf of the Bosnian Commission for Missing Persons. Working closely with the International Commission on Missing Persons (ICMP), new graves are being opened up by teams composed mainly of local staff, the focus now being on identification rather than evidence for criminal prosecutions. As recently as August 2003, one of the largest graves found in Bosnia so far was uncovered in the Zvornik region, and is estimated to contain up to 700 bodies. Monitors from ICTY will still often be present at new exhumations and criminal evidence can still be recovered. There is close liaison between the different organizations involved. Identification is no longer the unrewarding exercise it once was and new DNA laboratories established in Bosnia and funded by ICMP are achieving considerable success with many of the thousands of bodies stored in Tuzla from the work of the past 8 years. In July 2003, on the eighth anniversary of the massacre, 282 identified victims were buried at a special gravesite near Srebrenica, alongside 600 others placed there 4 months earlier. Kosovo Since 1999, there have been parallel operations in Kosovo. They started while hostilities were still ongoing when a Finnish forensic team accompanied pathologists from Belarus and Yugoslavia in
investigating an alleged massacre of 40 local Albanians in the village of Racak in January 1999. While there is continuing controversy over the findings the manner (as opposed to the cause) of death was given as undetermined, although the incident was subsequently described by one of the Finnish team as a crime against humanity the event received international attention and was probably the trigger for NATOs intervention 2 months later. When the fighting ended in June, various ad hoc forensic teams arrived from a number of countries and began exhuming graves. They used makeshift mortuaries or other local facilities, carried out postmortem examinations to varying standards, and used differing protocols. By the following year, ICTY had established a team similar to that in Bosnia and had set up proper mortuary facilities and a proper database. Many of the bodies being examined came from individual graves and their identity was known, having been buried by relatives. This differed from the large mass graves of Bosnia, as did the fact that there was a higher proportion of women and children. As in Bosnia, work continues in Kosovo under the direction of the Office on (sic) Missing Persons and Forensics (OMPF), examining and reexamining bodies to determine identity, primarily through DNA testing but also through recognition of clothing and personal artifacts. Encouragingly, many local staff are being involved in the process, including pathologists, and the intention is for them to take over fully in due course, but of approximately 4600 bodies exhumed since 1999, many remain formally unidentified. Serbia In Serbia itself, several mass graves have been unearthed in the past few years. These graves are alleged to contain the bodies of Albanian victims from Kosovo, transported to Serbia in freezer trucks and buried at various sites. The bodies have been examined by forensic pathologists from Serbia, with international observers usually present. By February 2003, 807 bodies had been exhumed from a police training center at Batanica near Belgrade and a further 139 from sites in the east and west of the country. A number have already been identified and returned to relatives in Kosovo.
East Timor
to flee the country. A UN peace-keeping mission subsequently enabled a forensic team to travel from Australia to examine bodies there, an exercise that is still ongoing. In 2002, Indonesia inaugurated a Human Rights Court to try those alleged to have been involved in the atrocities.
Other Conflicts
The listing of the investigations above unfortunately does not reflect the much wider occurrence of war crimes throughout the world, past and present, and merely describes those in which there has been significant scientific inquiry. Nor do they take into account individual smaller missions there may have been in other areas, e.g., Turkey, the Middle East, West Africa, Sri Lanka, Southeast Asia, and elsewhere. Accurate figures are difficult to achieve but a reasonable estimate for the number of people killed in wars worldwide between 1997 and 2002 is just over 3 million, of whom 75% will have been civilians. While no major forensic investigations have therefore been carried out on the vast majority of victims of war, that does not in any way diminish the importance of what has been done and what has been learnt. In Iraq, many grave sites have been identified from a variety of wars and alleged atrocities since the 1980s, and plans have already been drawn up by potential investigators as to how any forensic examination of these sites should be carried out if, and when, this becomes feasible.
Scope of the Pathology Investigation

The purpose of the examination of victims of alleged war crimes is threefold: 1. to record injuries, establish cause of death, and note any other relevant findings 2. to record physical information that may assist with identification 3. to recover evidential material for possible future prosecution. For pathologists, this is no different to what would be done for any suspicious death in their own jurisdiction. The emphasis may be different, but the pathological principles and standards are the same. The pathologist does not, of course, work alone but will be part of a team with a variety of expertise. With the work in the former Yugoslavia, for instance, three or four pathologists would normally be involved at any one time, and there would be equal numbers of anthropologists, a dentist, radiographer, photographer, several scenes of crime officers to examine
In 1999, East Timors vote for independence from Indonesia was both preceded, and followed, by large-scale oppression by paramilitaries. Around 1000 people died and about 200 000 were forced
Figure 2 The advantages of a fixed, albeit temporary, mortuary greatly outweigh the benefits of performing autopsies at the grave site (Visoko, Bosnia).
clothing and receive samples, technicians, and secretarial staff. In any exercise therefore, anything up to 20 people might be working in the mortuary at the same time, thereby necessitating the use of facilities with plenty of space (Figure 2). Special mention should be made of the role of the anthropologist and of his/her relationship with the pathologist. Bodies will be partly or wholly skeletonized, bodies in a mass grave may be intermingled, and bodies will have fragmented bones. The anthropologist has an invaluable role in articulating skeletons, identifying commingled remains, and reconstructing fragmented bone. This is quite apart from their role in helping to assess age, sex, and stature. The pathologist will assist in reconstructing and identifying injuries but will have the unique role of interpreting what these injuries mean and their likely effect. Only he/she has a full appreciation of the internal tissues of the body, the structures likely to have been injured, and whether or not the injury would have proved fatal. As with any death, the pathologist is ultimately responsible for the interpretation of the findings and for the production of the final autopsy report, albeit greatly assisted by the other members of the team. As indicated at the start of this section the autopsy is being carried out both to obtain evidence for a criminal conviction and to try to establish the identity of the body. In the context of war crimes the prime focus must be the former, and while every effort must be made to document identifying features and take appropriate samples, the process of eventually putting a name to a person and returning the body to
relatives is normally dealt with by other organizations, that is, local and international commissions for missing persons. Identification is a lengthy process and, while the mortuary team must always be mindful of its role and responsibility in helping to pursue this, the logistics of the exercise are such that it is properly dealt with by other agencies who have both the time and the resources. The International Committee of the Red Cross (ICRC) is a major player in this respect and has done a great deal of work in maintaining lists of missing persons and in enabling identification and return of bodies to relatives. In February 2003, they launched an initiative called The Missing in which they stressed the ethical responsibilities of forensic specialists in giving priority to the needs of families affected by persons who are missing. While the basic pathological principles may be the same, the nature of autopsy work in the war crimes situation does necessarily differ from normal routine practice. It differs in the volume of cases being dealt with, in the less than perfect state of most of the bodies, and in the often limited mortuary facilities available. These are factors beyond anyones control and are the realities that must be faced. They will place important limitations on the pathology evidence being gathered, something that must be clearly spelt out in any evidence submitted to the courts.
Limitations of the Pathology Evidence
The main areas of difficulty in the pathology findings are described below. Recognition of injuries as having occurred in life as opposed to after death Given that bodies from mass graves and other sites have often been there for months or years, the search for injuries is necessarily based on the examination of decomposed tissues or skeletal remains. In normal pathology practice, deciding on whether an injury has occurred in life is determined by looking at things such as bruising, swelling, and bleeding. In decomposed bodies this becomes very difficult and in skeletonized remains it is impossible. A fracture occurring any time in the days before death, before the healing process has begun, can look like one produced in the weeks or so afterwards. Theoretically, therefore, in decomposed remains, it is virtually impossible to be certain that any of the injuries found have necessarily occurred in life, even the obvious gunshot ones. With mass graves it is possible to counter this argument with the common-sense approach that all these people must have died in some way and that if it was not from the injuries found, then it must have been
from some other cause, no longer obvious and presumably common to all, and that they must then have been shot or otherwise injured after death, often multiple times. Undoubtedly injuries do occur after death, whether from initial collection and disposal of the bodies, from compaction and decay within the grave or well, or from the exhumation process itself, and it is obviously important to recognize this possibility. Certain patterns of injury are relatively characteristic of postmortem damage, for example, lines of fractured ribs down each side of the chest, crushing fractures of the pelvis, and separation of limbs, but it is often far from easy to decide, certainly with nongunshot trauma. To a large extent, the final interpretation must be based on consideration of the likelihood of there being a postmortem explanation for a particular injury and to err on that side rather than on the other. Proving an injury as being due to gunshot or shrapnel as opposed to other causes By the nature of modern war crimes, most people die of gunshot or blast injuries (Rwanda being an exception), and so the commonest trauma found will be of those types. Typical bullet damage to bone, either low- or highvelocity, is distinctive and can be backed up by demonstrating bullet fragments on fluoroscopy or X-ray, but sometimes the damage is not that clearcut and may be very difficult to distinguish from blunt-force trauma, whether antemortem or postmortem. Minimal diagnostic criteria have to be set: when taken together with the difficulty of trying to decide whether the damage was from one or multiple bullets, and having no idea about those bullets that might have struck the body without damaging the skeleton, overall there is probably a tendency to underestimate the number of shots fired. In addition, the presence of bullets or shrapnel in the remains does not always prove the case as, in the context of a mass killing and bodies falling on top of each other, some of these may well have struck the body after death. With commingled remains in a mass grave, bullets might also fall from body to body with the steady decay over the years and during the exhumation process. Accepting the injuries found as being the cause of death As already discussed, in decomposed and skeletonized bodies the only remaining evidence of trauma is usually in the skeleton. Unfortunately, it is not damage to bone that kills people but the associated damage to internal organs and tissues. From a strictly pathological point of view therefore, it is seldom possible to prove a precise cause of death, only to
imply it. This is not an unreasonable implication, however, as common sense dictates that a bullet passing through the skull will also pass through the brain, and a bullet striking the ribs or spine will almost certainly also damage the heart, lungs, or major vessels. Difficulties arise where the only findings are injuries to the arms or legs. Such injuries would not normally be expected to prove immediately fatal and, although one could argue that they would certainly be disabling and without medical aid would eventually cause death through fluid loss and lack of general support, this cannot necessarily be proved and something else may have supervened. The cause of death may well therefore have to be left as unascertained. The precise wording of cause of death will vary from pathologist to pathologist. Some will just give what is the main fatal injury while others may be more inclusive and list all the injuries present. This has to be borne in mind when interpreting overall findings from a site or conflict, as does the differing approach to description and interpretation according to each pathologists accustomed practice in his/her own country.
Contribution of the Pathology Evidence

The evidence obtained from the postmortem examination of victims of alleged war crimes is important. Self-evidently it confirms that people have died, and it will alert investigators to the nature of such deaths. It can confirm specific allegations but, equally importantly, refute them, whether these come from local witnesses or from the aggressors. The postmortem examination is not just about injuries and there is additional evidence to be gained from clothing, artifacts, and the state of the body. A list of the sort of information normally looked for is given in Table 1. In the context of the overall incident and of the gravesite as a whole, the pathological investigations should be trying to ascertain the following points (Figure 3): . number of individuals present, their demographic features, and whether civilian or military . estimation of how long they might have been in the grave . evidence of restraint, beating, or torture prior to death . nature of the injuries whether gunshot, blast, sharp instrument, blunt-force, or a combination . if gunshot, how many shots, evidence of targeting, direction of fire, type of weapon . common patterns within the group as a whole.

Table 1 Findings to look for in the postmortem examination Clothing Personal possessions Preservation Military or civilian Bullet holes, burning, other defects Identifying documents, evidence of lifestyle, medication Weapons, ammunition Survival of soft tissue, estimation of time since death Parts missing, commingling Sex, age, stature Disabilities, old fractures, surgical procedures, disease Material used, how applied, common patterns Number, parts injured, direction of fire, distance of fire Type of weapon, ammunition recovered Nature and localization of damage, burning Shrapnel recovered Evidence in soft tissue or bone, type of weapon Soft-tissue injuries, internal bleeding, fractures, defense injuries Healing fractures, bandaged injuries Soft tissues, bones, fracture ends Postmortem/antemortem Postmortem disruption of body, attempts to conceal or destroy
Negative Autopsy
Identifying features Blindfolds, ligatures, etc. Gunshot injuries
Blast injuries Sharp instrument Blunt-force trauma Burning Dismemberment
A common defense is that the victims were military and that they were killed in the normal course of a conflict. The postmortem examination of the bodies can do much to refute this in terms of defining the population of those in the grave, their clothing, age, and disabilities, and the nature of their injuries. In the trial of Radislav Krstic, Deputy Commander of the Serbian forces at the time of the Srebrenica massacre, the defense assertion that the 340 bodies in the gravesite at Kozluk were combat casualties could be countered by the pathology evidence that 41% of the victims had their hands tied behind their back, 13% had blindfolds, and 5% had significant disabilities. Further, all the injuries were bullet injuries (i.e., there were no injuries from shells), 77% had shots to the back with only 23% to the front, and in 10% the only injury was a single gunshot wound at the back of the head. At the trial in 2001 Krstic was found guilty of genocide and sentenced to 46 years imprisonment, the only person convicted of genocide so far by the Tribunal. (In April 2004, appeal judges overruled this verdict, changing it to one of aiding and abetting genocide, and reducing the sentence to 35 years. In so doing, however, they nonetheless ruled that the massacre at Srebrenica was genocide.)
The postmortem examination will provide information in many cases but in a substantial number there will be very little to find. This could be because of antemortem trauma being obscured or destroyed by decomposition or postmortem damage not all bullets will strike bone and a fatal shot through the abdomen would be completely missed in skeletonized remains, as would most stab wounds, cut-throat injuries, and internal bleeding from blunt-force trauma to the head, chest, or abdomen. Other potential causes of death would be equally difficult to prove, such as drowning, asphyxia, and smoke inhalation. Likewise a person may have died of natural disease or, in certain circumstances, dehydration or sunstroke, all impossible to demonstrate. In all of these cases, the pathologist has no option but to give the cause of death as unascertained. In one grave from the north of Bosnia alleged to contain the bodies of 73 men from a nearby prison camp, a cause of death could only be established in 18 cases and for the other 55 it was given as unascertained. Most of the latter did have injuries fractures of ribs, scapulae, arms, and skull, in keeping with allegations of prolonged beatings but it was not possible to say that these necessarily caused death. Suggestions of internal bleeding, ruptured organs, knife wounds, heat stroke, pneumonia, and other infections could only remain speculative, however tempting it was to attribute them.
Future Contribution
Undoubtedly much scientific expertise has been gained in the past 20 years in examining the bodies of victims of alleged war crimes, and undoubtedly this will continue in newer conflicts. It is impossible to separate the work of anthropologist and pathologist in this respect as their roles are now so closely intermingled. For the anthropologist, new data on population aging have been accumulated and new techniques for estimating them developed; for those involved in DNA work much expertise has been acquired in processing samples from decomposed remains; and for the pathologist, much experience has been gained by individuals on the nature of gunshot and blast injuries, in the variability of the decomposition process, and in the important contribution of other disciplines. The value of multidisciplinary investigative teams has been clearly established and the need for maintaining the highest professional standards emphasized. These are being translated into the emergence of permanent organizations to provide assistance
Figure 3 Potential findings at postmortem examination: (A) blindfold around head; (B) bullet hole in surviving skin; (C) personal possessions from clothing; (D) old fracture to assist in identification; (E) healing fracture from blunt force trauma (beating); (F) gunshot defects in scapula and rib; and (G) high-velocity ammunition recovered.
worldwide in future missions. PHR in the USA is long established, while in the UK the Center for International Forensic Assistance (CIFA) and International Forensic Center of Excellence (INFORCE) for the investigation of genocide are newer beings.
Further Reading
Black S, Vanezis P (2003) The forensic investigation of mass graves and war crimes. In: Payne-James J, Busuttil A, Smock W (eds.) Forensic Medicine, Clinical and Pathological Aspects, pp. 6778. London: Greenwich Medical Media. Blewitt G (1997) The role of forensic investigations in genocide prosecutions before an international criminal tribunal. Medicine, Science and the Law 37: 284288. EAAF (2002) Annual Report 2002. Buenos Aires: Argentine Forensic Anthropology Team.
See Also
Anthropology: Archeology, Excavation and Retrieval of Remains; Bone Pathology and Antemortem Trauma; War Crimes: Site Investigation; Tribunals; War Injuries
WAR CRIMES/Tribunals 371 Ferllini R (2003) The development of human rights investigations since 1945. Science and Justice 43: 219224. Haglund WD, Sorg MH (2001) Advances in Forensic Taphonomy. Boca Raton, FL: CRC Press. Mant AK (1987) Knowledge acquired from post-war exhumations. In: Boddington A, Garland AN, Janaway RC (eds.) Death, Decay and Reconstruction, Approaches to Archaeology and Forensic Science, pp. 6578. Manchester, UK: Manchester University Press. Parvanic K (1999) The Killing Days. London: Blake. Rainio J, Lalu K, Pentiiila A (2001) Independent forensic autopsies in an armed conflict: investigation of victims from Racak, Kosovo. Forensic Science International 116: 171185. Raszeja S, Chroscielewski E (1994) Medico-legal reconstruction of the Katyn forest massacre. Forensic Science International 68: 16. Robertson G (1999) Crimes Against Humanity. London: Penguin Books. Smith D (2003) The Atlas of War and Peace, 4th edn. London: Earthscan. Sprogoe-Jakobsen S, Eriksson A, Hougen HP, et al. (2001) Mobile autopsy teams in the investigation of war crimes in Kosovo 1999. Journal of Forensic Sciences 46: 13921396. Strinovic D, Skavic J, Kostovic I, et al. (1994) Identification of war victims in Croatia. Medicine, Science and the Law 34: 207212.
Tribunals
J D Wilets, Nova Southeastern University, Fort Lauderdale, FL, USA
Historical Overview of the International War Crime Tribunals and International Criminal Law
Trials of defeated military leaders for violations of the Geneva Convention, or for other violations of the norms of combat, have existed for well over a century. However, the modern era of truly international warcrime tribunals, where the world community is the judge, and international law is the applicable law, began with the allied victory in the Second World War.
The Nuremberg Tribunal
In 1945, the victorious Allies in the Second World War established the International Military Tribunal, commonly known as the Nuremberg Tribunal, to try Nazi war criminals. The tribunal was established pursuant to the Nuremberg charter, dated August 8, 1945 and signed by the USA, the provisional government of the French Republic, the UK, and the
Union of Soviet Socialist Republics. In addition, the following members of the United Nations (UN) expressed their adherence to the agreement, creating the tribunal: Australia, Belgium, Czechoslovakia, Denmark, Ethiopia, Greece, Haiti, Honduras, India, Luxembourg, the Netherlands, New Zealand, Norway, Panama, Paraguay, Poland, Uruguay, Venezuela, and Yugoslavia. The Nuremberg Tribunal created a new era in international criminal law for several reasons. First, the Allies created principles of individual liability for war crimes that were codified and accepted by the international community as binding norms of international law. Second, the Nuremberg Tribunal established the revolutionary principle of individual responsibility for the crime of attacking international peace. Violations of international peace had already been established as a violation of international law under the KellogBriand pact, but individual criminal liability for its violation had not been contemplated until the Nuremberg Tribunal. Third, the Nuremberg Tribunal marked the first time that countries with very different legal systems created a joint system of criminal procedure, a step that is vastly more complicated than the system of civil procedure created under the previous Permanent International Court of Justice of the defunct League of Nations. Three crimes were prosecutable under the Nuremberg charter: (1) crimes against peace; (2) war crimes; and (3) crimes against humanity. Crimes against peace included planning, preparation, initiating, or waging a war of aggression, or a war in violation of international treaties, agreements or assurances, or participation in a common plan or conspiracy for the accomplishment of any of the foregoing. War crimes included violations of the laws or customs of war, including, but not limited to, murder, ill treatment, or deportation to slave labor or for any other purpose of civilian population or in the occupied territory, murder or ill treatment of prisoners of war or persons on the seas, killing of hostages, plunder of public or private property, wanton destruction of cities, towns, or villages, or devastation not justified by military necessity. Crimes against humanity included murder, extermination, enslavement, deportation, and other inhumane acts committed against any civilian population, before or during the war, or persecutions on political, racial, or religious grounds in execution of or in connection with any crime within the jurisdiction of the tribunal, whether or not in violation of the domestic law of the country where perpetrated. It is notable that the charter further extended the ambit of liability by providing that leaders,
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organizers, instigators, and accomplices participating in the formulation or execution of a common plan or conspiracy to commit any of the foregoing crimes were responsible for all acts performed by any persons in execution of such a plan.
The International Military Tribunal for the Far East (the Tokyo Tribunal)
In 1946, the Allies established the International Military Tribunal for the Far East, commonly known as the Tokyo Tribunal, to prosecute Japanese war criminals. The Tokyo Tribunal was established pursuant to the charter of the International Military Tribunal for the Far East (the IMTFE charter). The judges of the tribunal were appointed by the Supreme Commander for the Allied Powers from names submitted by the Signatories to the Instrument of Surrender, as well as India, and the Commonwealth of the Philippines. Although the Tokyo Tribunal was the most visible forum for the trial of Japanese war criminals, it was far from the only such tribunal. Approximately 5000 Japanese were tried by Asian countries victimized by Japan, approximately 900 were executed, and more than 2000 were sentenced to life in prison. Nevertheless, because American forces controlled Japan, the most prominent Japanese war leaders came under MacArthurs jurisdiction. The crimes defined in the IMTFE charter were essentially the same as those covered under the Nuremberg charter. Those crimes included crimes against peace, conventional war crimes, and crimes against humanity. The definitions of those crimes also largely tracked the definitions found in the Nuremberg charter. The Tokyo Tribunal trials began on May 3, 1946, and lasted two and a half years. All of the defendants were found guilty: seven were sentenced to death, sixteen to life terms, two to lesser terms, two died during the trials, and one was found insane. On December 23, 1948, General Tojo and six others were hanged at Sugamo prison. General MacArthur, wary of antagonizing the Japanese people, barred photography of any kind and brought in four members of the Allied Council to act as official witnesses. It should be noted that the Nuremberg and Tokyo Tribunal proceedings were not without legal controversy. Various legal commentators have referred to the proceedings as victors justice and the retroactive application of law. Other legal commentators have responded that customary international law and common law have always involved the retroactive application of law to some extent. Those courts arguably retroactively apply new law every time they analogize existing legal principles to the specific facts
before them. Under this reasoning, to the extent that the German and Japanese leaders understood that their actions violated basic moral principles (and arguably natural law), and the principles contained in the Geneva Convention, the Kellog Briand pact, and general principles of law, the punishment of their actions was not entirely retroactive. Other commentators have noted that law is always created by the victors. The ultimate test of that law, at least in the international context, is whether the principles and norms advanced by that law achieve international acceptance. To the extent that the principles contained in the Nuremberg and IMTFE charters have been codified in international law and accepted as customary international law, and even jus cogens, the principles advanced by the Nuremberg and IMTFE charters would appear to have met that test.
Codification of the Nuremberg and IMTFE Charters and Further Development of International Criminal Law
The international community began codifying the concepts contained in the Nuremberg and IMTFE charters shortly after the creation of those tribunals. In 1947, the UN adopted the UN Convention on the Prevention and Punishment of the Crime of Genocide. Article VI of the Convention provided that persons charged with the crime of genocide shall be tried by a competent tribunal of the State in the territory of which the act was committed or by such international penal tribunal as may have jurisdiction. The General Assembly also invited the International Law Commission (ILC) to begin studying the feasibility of creating an international organ for trying persons charged with genocide. The ILC continued working throughout the 1950s, but eventually ceased its work due to strong differences among the ILCs members. In 1989, the General Assembly requested the ILC to resume its work on an international criminal court (the ICC) and requested the ILC to include drug trafficking as a crime under ICC jurisdiction. The ILC submitted a draft ICC statute to the UN General Assembly in 1994, after which the General Assembly established an ad hoc Committee on the Establishment of an International Criminal Court. The UN Conference of Plenipotentiaries in Rome adopted the Statute of the International Criminal Court (the Rome statute) on July 17, 1998. A total of 160 states, 33 intergovernmental organizations, and 235 nongovernmental organizations participated in the conference: 120 countries voted in favor, seven voted against, and 21 countries abstained. The ICC was established as an organization independent of the UN and with its own budget.
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On April 11, 2002, the ICC formally came into existence after the sixtieth country ratified the Rome statute. Mr. Luis Moreno-Ocampo from Argentina was elected by the States Parties to the ICC as the first Chief Prosecutor. Concurrently with the development of the ICC, the horrendous atrocities in Yugoslavia and Central and West Africa prompted the UN to create ad hoc criminal tribunals for the prosecution of those responsible for the violations of international criminal law. In 1993, the UN Security Council created the ad hoc International Criminal Tribunal for the Former Yugoslavia (the ICTY), to address crimes committed by leaders of that ethnic-based conflict. The next year, the UN Security Council created the International Criminal Tribunal for Rwanda (ICTR) to prosecute individuals responsible for violations of international humanitarian law in the territory of Rwanda, and Rwandan citizens responsible for violations in the territory of neighboring states. In January 2002, the UN and the government of Sierra Leone reached an agreement to establish a special court (a kind of hybrid nationalinternational court) to try alleged perpetrators of international crimes committed in Sierra Leones civil war after November 30, 1996.
(g) rape; (h) persecutions on political, racial, and religious grounds; and (i) other inhumane acts. Under article 1 of the ICTY statute, the ICTY has jurisdiction to try individuals for these crimes committed on the territory of the former Yugoslavia since 1991. The ICTY only has jurisdiction over individuals. Under article 9 of the ICTY statute, the ICTY and national courts have concurrent jurisdiction, but under article 9(2), the ICTY will exercise primacy over national courts in the event that the country where the defendant is located is unwilling or unable to try the individual effectively. In that case, the ICTY reserves the right to claim primacy over national courts in the interest of international justice, and is, in practice, the principal circumstance in which the court will exercise jurisdiction at all.
Structure
International War Crime Tribunal for the Former Yugoslavia

The ICTY was formally known as the International Criminal Tribunal for the Prosecution of Persons Responsible for Serious Violations of International Humanitarian Law Committed in the Territory of the Former Yugoslavia since 1991. The ICTY is located in The Hague, Netherlands, and was established on May 25, 1993 by Security Council Resolution 827. The ICTY is governed by the statute of the International Criminal Tribunal for the Former Yugoslavia (ICTY statute). Of particular interest to those involved in forensic practice are the Rules of Procedure and Evidence for the ICTY (as amended). Both these documents may be accessed at http:// www.un.org/icty/legaldoc/index.htm.
Jurisdiction
The Chambers of the ICTY consist of sixteen permanent judges and a maximum at any one time of nine ad litem judges (trial-specific judges). The sixteen permanent judges are elected by the UN General Assembly for four-year terms and can be reelected. The ad litem judges are also elected by the UN General Assembly for four-year terms, but their terms are not renewable. The judges are divided between three trial chambers and one appeals chamber. Each trial chamber consists of three permanent judges and a maximum, at any one time, of six ad litem judges. A trial chamber may be divided into mixed sections of three judges (one permanent and two ad litem, or two permanent and one ad litem). Each trial chamber can be comprised of up to three sections. The appeals chamber consists of seven permanent judges: five from the permanent judges of the ICTY, and two from the eleven permanent judges of the ICTR. These seven judges also constitute the appeals chamber of the ICTR. Each appeal is heard and decided by five judges. The judges represent the main legal systems in the world and bring to the ICTR a diverse body of legal expertise. The permanent judges not only conduct the trial proceedings, they also perform regulatory functions such as drafting legal instruments regulating the functioning of the ICTY.
Office of the Prosecutor (OTP)
The ICTY has jurisdiction to prosecute and try four types of offences: (1) grave breaches of the 1949 Geneva Conventions; (2) violations of the laws or customs of war; (3) genocide; and (4) crimes against humanity. Under article 5 of the ICTY statute, crimes against humanity are broadly defined and include: (a) murder; (b) extermination; (c) enslavement; (d) deportation; (e) imprisonment; (f) torture;
The OTP operates independently of the Security Council or of any state, international organization, or any other organs of the ICTY. Its members are experienced police officers, crime experts, analysts, lawyers, and trial attorneys. The OTP conducts investigations (collecting evidence, identifying witnesses, exhuming mass graves), prepares indictments, and conducts prosecutions before the ICTY.
374 WAR CRIMES/Tribunals The Registry
The Registry provides support services for the ICTY. These include translation and interpreting court proceedings and organizing hearings, legal filings, and archives. The Registry also operates the legal aid program for indigent defendants, provides assistance and protection to witnesses, and manages the Detention Unit. The Registrar is in charge of all communications with the ICTY and, along with the President, carries out diplomatic functions.
Proceedings
Investigations are initiated by the Prosecutor at his/ her own discretion and an ICTY judge will confirm the indictment before it becomes effective. The trial commences when the accused is physically present before the ICTY. As would be expected from an international court, the trial procedure incorporates legal elements of both civil law and common law.
Custody and Sentencing
The accused are held in the ICTY detention unit, which is managed by the Registry and is located in The Hague. The maximum sentence that can be imposed on an accused is life imprisonment. The sentences are served in one of the state parties that have agreed to accept persons convicted by the ICTY.
Forensic Investigations
Forensic investigators from Physicians for Human Rights went to the former Yugoslavia in 1993 to investigate atrocities in Vucovar and in Pakracka Poljana. Forensic experts used, among the most current technological equipment, electronic mapping procedures to map precisely the entire crime site area, including artifacts, human remains, and other objects. Still photography and video cameras were employed to record all activity at the grave-site, including all forensic activities. After growth and topsoil were removed, small utensil tools were used to expose the remains.
between 1 January and 31 December 1994 (ICTR). On February 11, 1995, the Security Council decided, pursuant to resolution 977, that the ICTR would be located in Arusha, Tanzania. The ICTR has jurisdiction to try individuals responsible for genocide and other serious violations of international humanitarian law committed in the territory of Rwanda between January 1, 1994 and December 31, 1994. It also has jurisdiction to try Rwandan citizens responsible for genocide and other serious violations of international law committed in the territory of neighboring states. The ICTR is governed by the Statute of the International Criminal Tribunal for Rwanda (the ICTR statute), annexed to Security Council Resolution 955 and can be accessed at http://www.ictr.org/ENGLISH/ basicdocs/statute.html. Of particular interest to those involved in forensic practice is the Rules of Procedure and Evidence for the ICTR (as amended). The rules, which the judges adopted in accordance with article 14 of the statute, establish the necessary framework for the functioning of the judicial system and largely track the rules of the ICTY. The rules can be accessed at http:// www.ictr.org/ENGLISH/rules/index.htm. Like the ICTY, the Tribunals structure is established by article 10 of the ICTR statute, and consists of three organs. The first organ is the chambers and the appeals chamber, the composition of which is provided for in article 11 of the ICTR statute. The appeals chamber is shared with that of the ICTY. The second organ is the Office of the Prosecutor, established pursuant to article 15 of the ICTR statute. The Prosecutor is in charge of investigations and prosecutions. The third organ is the Registry, established pursuant to article 16 of the ICTR statute. The Registry is responsible for providing administrative support to the chambers and the prosecutor.
The International Criminal Court and the Rome Statute

The ICC was established by the international community inter alia to remedy the deficiencies of the ad hoc tribunals, to assume jurisdiction when national courts are unable or unwilling to act, and to deter future war criminals. The ICC is governed by the Rome Statute of the International Court (the statute) and entered into force on July 1, 2002. The statute can be accessed at http://www.un.org/law/icc/statute/romefra.htm. Anyone who commits any of the crimes under the statute after that date is liable for prosecution by the ICC. One hundred and thirty-nine countries had
International Criminal Tribunal for Rwanda

On November 8, 1994, the Security Council, acting pursuant to Chapter VII of the UN charter, passed a resolution to create the International Criminal Tribunal for the Prosecution of Persons Responsible for Genocide and Other Serious Violations of International Humanitarian Law Committed in the Territory of Rwanda and Rwandan Citizens Responsible for Genocide and Other Such Violations Committed in the Territory of Neighbouring States
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signed the statute as of November 2003 and 92 states had ratified the statute (state parties). The ICCs governing body is the Assembly of States Parties to the Rome Statute of the International Criminal Court (Assembly of States Parties). In September 2002, the first session of the Assembly of States Parties adopted a number of instruments, including two of particular relevance to those practicing forensic medicine or law: the Rules of Procedure and Evidence and Elements of Crimes.
Structure and Administration of the Court

Part four of the statute addresses the composition and administration of the ICC. Article 34 of the statute provides for the following ICC organs: (1) the presidency, consisting of the President and the first and second Vice-Presidents; (2) the appeals court; (3) the trials court and the pretrial chamber; (4) the prosecutors office; and (5) the registry. Article 38 of the statute provides for the ICC to be comprised of 18 judges. The judges and prosecutor are elected by the Assembly of States Parties and the court registrar is elected by the judges. The working languages of the court are English and French. The official languages are Arabic, Chinese, English, French, Russian, and Spanish.
The Judges
The ICCs Competence (Subject Matter Jurisdiction)

The statute provides for subject matter jurisdiction (also referred to in some circumstances as competence) over the crimes of genocide, crimes against humanity, and war crimes. The court only has jurisdiction over crimes committed after the statute came into effect (July 1, 2002). The ICC may accept cases submitted by the Security Council, a state party, or by the ex-officio Prosecutor, acting on the basis of information received in particular from victims, nongovernmental organizations, or other sources the Prosecutor considers appropriate. When cases are submitted to the court (other than by the Security Council), the court may only exercise its competence when the state on whose territory the crimes took place, or the state of which the person accused of the crime is a citizen, has either (1) ratified the statute, or (2) accepted the Courts competence by means of a declaration filed with the Court Registrar. Under article 1 of the statute, the Court complements national jurisdiction, which means in practice that it may only exercise its jurisdiction if the states concerned are unable or unwilling to prosecute the perpetrators of justiciable crimes. Under article 21, the court has no jurisdiction over states or of legal entities (associations, companies) other than individuals (natural persons). Under article 26, the court has jurisdiction over individuals who were over 18 at the time of their crimes. Under article 27, there is no immunity for a defendants position as head of state, head of government, or any other official state position. Under article 28, the statute lastly provides for the responsibility of military chiefs and civilian superiors in respect of crimes committed by their subordinates when, knowing about these crimes, they did not take the necessary measures to prevent them from being carried out or to quell them. Finally, under article 29, there is no statute of limitations over these crimes falling within the competence of the court.
Under article 36, the 18 ICC judges are elected by the Assembly of the States Parties for staggered terms of nine years and are not eligible for reelection. They must be persons of high moral character, impartiality, and integrity who possess the qualifications required in the respective states for appointment to the highest judicial offices. The Assembly of States Parties is to take into account representation of the principal legal systems of the world, equitable geographical representation, and a fair representation of female and male judges. All the judges must be nationals of state parties.
The Presidency
Under article 38 of the statute, the presidency is composed of the President and first and second Vice-Presidents, all of whom are elected by an absolute majority of judges for a three-year renewable term. The presidency is responsible for the proper administration of the ICC, with the exception of the Office of the Prosecutor. However, the presidency will coordinate and seek the concurrence of the Prosecutor on all matters of mutual concern.
Chambers
Under article 39 of the statute, the judiciary of the ICC is composed of three divisions or chambers: (1) the Appeals Division; (2) the Trial Division; and (3) the Pretrial Division.
The Office of the Prosecutor
Under article 42 of the statute, the Office of the Prosecutor is an independent organ of the ICC and is responsible for receiving referrals of situations and information on crimes within the jurisdiction of the Court. The Prosecutor commences an investigation upon referral by a state party, the Security Council
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(acting under Chapter VII of the UN charter) in which there is a reasonable basis to believe that crimes have been, or are being, committed. The Prosecutor may also receive information on such crimes provided by other sources and may begin investigations after a preliminary examination of the material received and authorization by the Pretrial Chamber.
The Registry
Under article 43, the Registry is responsible for the nonjudicial aspects of the administration and servicing of the Court. It is headed by the Registrar, who is the principal administrative officer of the Court and exercises his/her functions under the authority of the President of the Court. The Registrar is elected by the judges in plenary session, taking into account any recommendation by the Assembly of the States Parties.
The Rules of Procedure and Evidence
The Rules of Procedure and Evidence for the ICC (the rules) are subordinate to the Rome statute and do not affect the procedural rules for any national court in national proceedings. The rules are particularly important for any person or organization dealing with assembling forensic or other evidence for prosecutions. Rules 16 through 19 of the rules address the creation and operation of the Victims and Witnesses Unit, of particular interest for anyone engaging in forensic or other evidence-gathering with respect to prosecutions under the ICC. Rules 6378 and 8184 provide rules regarding evidence. Rules 111 and 115116 address the collection of evidence and rule 138 addresses the custody of evidence. Rules 6572, 7476, and 8688 address the rules regarding witnesses (overlapping in some cases with the rules regarding evidence).
See Also
Mass Murder; Torture: Physical Findings; War Crimes: Site Investigation; Pathological Investigation
Further Reading
Abour L (1999) The prosecution of international crimes. Washington University Journal of Law and Policy. Abrahams F, Stover E (2002) A Village Destroyed, May 19, 1999: War Crimes in Kosovo. University of California Press. Anne MH (1999) There will be no justice until women are part of that justice: rape in Bosnia, the ICTY and gender sensitive prosecution. Wisconsin Womens Law Journal 155.
Cherif Bassiouni M (1994) The United Nations commission of experts established pursuant to security council resolution 780. American Journal of International Law 784. Chiedu Moghalu K (2002) Image and reality of war crimes justice: external perceptions of the international criminal tribunal for Rwanda. Fletcher Forum of World Affairs 21. Concannon B Jr (2000) Beyond complementarity: the international criminal court and national prosecutions, a view from Haiti. Columbia Human Rights Law Review 201. Gellately R, Kiernan B (eds.) (2003) The Specter of Genocide: Mass Murder in Historical Perspective. Cambridge University Press. Jeffrey LS (2003) Sitting in the dock of the day: applying lessons learned from the prosecution of war criminals and other bad actors in post-conflict Iraq and beyond. Military Law Review 96. Keegan MJ (1997) Symposium: prosecuting international crimes: an inside view of the preparation of cases for the icty. Transnational Law and Contemporary Problems 119. Kelly MJ (2002) Can sovereigns be brought to justice? The crime of genocides evolution and the meaning of the Milosevic trial. St. Johns Law Review 257. Kelly DA (2003) Reflections on some of the most significant achievements of the ICTY. New England Law Review 903. Kirk McDonald G (2001) Reflections on the contributions of the international criminal tribunal for the former Yugoslavia. Hastings International and Comparative Law Review 155. Laber J, Nizich I (1994) The war crimes tribunal for the former Yugoslavia: problems and prospects. Fletcher Forum of World Affairs 7. Marshall M, Inglis S (2003) The disempowerment of human rights-based justice in the United Nations mission in Kosovo. Harvard Human Rights Journal 16. Michael PS (1997) Panel Ii: adjudicating violence: problems confronting international law and policy on war crimes and crimes against humanity the prosecutor V. Dusko Tadic: an appraisal of the first international war crimes trial since Nuremberg. Albany Law Review 861. Michael PS (2000) The tools for enforcing international criminal justice in the new millennium: lessons from the Yugoslavia tribunal. DePaul Law Review 925. Morris V, Scharf MP (1997) The International Criminal Tribunal for Rwanda. Transnational Publishers. Patricia MW (2003) General Radislav Krstic: a war crimes case study. Georgetown Journal of Legal Ethics 445. Peress G, Stover E (1998) The Graves: Forensic Efforts at Srebrenica and Vukovar. Zurich: Scalo. Robertson G (2002) Crimes Against Humanity: the Struggle for Global Justice. Penguin Books. Van Lierop RF (1999) Report on the international criminal tribunal for Rwanda. Hofstra Law & Policy Symposium 203. William AS (2001) An Introduction to the International Criminal Court. Cambridge University Press.
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WAR INJURIES
J Clark, University of Glasgow, Glasgow, UK
Introduction
The injuries seen in the victims of war crimes are part of the broader picture of injuries occurring in wars generally. Knowledge of the latter can, however, be of great help in interpreting the former, particularly in countering arguments about armed conflicts. With the notable recent exceptions of Afghanistan and Iraq, most conflicts nowadays are within states rather than between states, and most injuries will be from the use of high-velocity bullets and from explosive devices. International conflicts will bring into play the use of heavy artillery, in addition to naval and airborne delivery systems, reflected usually in increasing numbers of casualties and damage of increasing severity.
These proportions of dead and wounded can be contrasted with ratios of 0 or less than 1 seen in nonconflict incidents, e.g., the Katyn (western Russia) massacre of 1940 (4143 dead, 0 wounded), the Japanese Embassy siege in Peru in 1997 (14 dead, 0 wounded), and various civilian random mass shootings throughout the world. Such figures tend to point to the use of firearms against people who are in a situation where they cannot escape and are generally defenseless, an observation important for those investigating alleged war crimes. Thus, in Bosnia, there were no reports of large numbers of wounded being taken to hospitals around Srebrenica, and very few of the victims from the mass graves had any healing or bandaged injuries, as might have been expected if they were combat casualties.
Explosions or Bullets
Injury Statistics
The Ratio of Wounded to Killed
The mortality of a particular injury depends not only on the nature of that injury and the weapon used, but also on the context in which it occurs and whether the person has access to medical treatment. In modern warfare the number of wounded normally substantially exceeds the number of those killed. In a review of various conflicts worldwide from 1945 to 1992, the ratio of wounded to killed was reported as ranging from 1.9 to 13, with Vietnam being 4.0. In the Korean War of 195053, there were 19 585 American dead and 92 363 wounded (4.7); and in the Falklands War of 1982, 255 British dead and 777 wounded (3.0), with 639 deaths on the Argentine side. Accurate statistics for the Gulf War of 19901991 are hard to come by ranging from initial estimates of 100 000 Iraqi dead and 300 000 wounded, to revised estimates of fewer than 10 000 dead and up to 24 000 wounded, although US casualties are well documented, with 148 dead and 467 wounded, including those from friendly fire. The figures for both sides therefore still give a ratio of around 3 to 1 for wounded to dead. Unverified figures from more recent conflicts in the Middle East, Sri Lanka, India/ Pakistan, and Africa show similarly positive ratios, while statistics from the Iraq War in 2003 record 397 American deaths and 1967 wounded as of November that year.
The other main observation from modern conflicts is that more people are generally killed from explosive devices than from bullets. While accurate statistics are difficult to obtain for most conflicts because of their very nature, and while comparisons between conflicts are equally difficult because of different methods of recording, some figures are available (Table 1). These figures clearly indicate that the main mortality and morbidity in armed conflicts come from explosive devices (specifically fragmentation), in striking contrast to the experience in victims of war crimes where bullet injuries very much predominate. Explosive injuries are still found in the latter but the incidence is relatively low and usually related to specific events.
Nature of Weapons Deployed

Weapons are primarily designed to incapacitate and suppress an opponent, and modern developments seek to achieve this by minimizing the risk to the user. The weaponry of modern warfare ranges from the individual firearms carried by soldiers (small arms),
Table 1 Major conflict statistics (194592)

Conflict Explosives Bullets
For fatalities:
For wounded: For all casualties:
World War II (194549) Korea (195053) Croatia (199192) Falklands (1982) Gulf (199091) Vietnam (1970) Lebanon (1982)
56% 63% 44% 56% 81% 45% 36%
32% 33% 33% 32% 19% 30% 20%
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through a variety of land-based explosive devices (grenades, shells, mines), to the larger explosives delivered by aircraft or ships (bombs and rockets). Weapons of mass destruction, whether nuclear, biological, or chemical, are beyond the scope of this article.
Small Arms
Table 2 Explosive munitions in modern warfare Primary fragmentation devices Grenades Metal or plastic casing filled with explosive, the casing fragmenting naturally or in a preformed way, and sometimes with additional shrapnel inside Usually thrown by hand but greater distances can be achieved with a grenade launcher Concussion grenades are different, in causing blast effect without fragmentation Mortars Metal shell casing containing explosive, fired indirectly up into the air and capable of traveling thousands of meters Artillery Firing shells of varying size; includes tanks Rockets Self-propelled devices which can travel considerable distances and usually guided after being fired from trucks, helicopters, aircraft; also used for incendiary purposes Fragmentation plus blast Landmines Static ground-based devices designed to destroy or damage equipment or personnel and detonated by actions of the target, e.g., pressure, heat, or by controlled means Can be either antitank (to incapacitate the vehicle as opposed to killing the crew) or antipersonnel (to incapacitate or kill individuals) Bombs Dropped from aircraft and designed for a variety of purposes: Blast: detonation of high explosives producing very high pressures and very high temperatures, the former compressing the surrounding air and causing the blast effect; intended to destroy buildings and machinery Fragmentation: break-up of the bomb on detonation, the fragments traveling at up to 3000 m s1 (10 000 ft s1); directed against troops, vehicles, and aircraft Cratering: allowing penetration before detonation Incendiary: producing intense heat and igniting combustible materials Bombs can be general-purpose (50% explosive by weight), fragmentation, penetrating (shaped charge) or cluster Missiles Land-, ship-, submarine-, or air-launched, with various guidance systems and traveling long distances (e.g., 965 km (600 miles) for Tomahawk cruise missile); primarily destroying buildings and other structures
The personal weapon used by most soldiers and paramilitaries is the assault rifle, although machine guns and submachine guns may also feature. Assault rifles These are automatic weapons firing intermediate rifle ammunition, either as single shots or as automatic bursts; they have a detachable magazine of 20 rounds or more. Most popular is the Russian-made AK-47 (Kalashnikov), firing 7.62 39 mm caliber ammunition at 600 rounds per minute over a range of 300 m, although the newer model (AK-74) fires 5.45-mm bullets; they are used by former Warsaw Pact armies and other armies of Eastern Europe and Asia. The American Armalite M16 (5.56 45 mm), the British SA 80, the German HKG36, and the Israeli IM Galil are some of the other more commonly used weapons worldwide. Machine guns Machine guns are automatic rifles intended for very high firing rates, requiring a secure mount for their operation (e.g., armoured personnel carriers, tanks, etc.), and some of the heavier variety are used as antiaircraft weapons. They fire highercaliber ammunition (from 7.62 to 12.7 mm diameter), which is fed from belts, and they have a greater range. Submachine guns/machine pistols Submachine guns are fully automatic rifled weapons firing pistol ammunition; their muzzle velocity (300 m s1) and effective range (up to 50 m) is less than for assault rifles. In addition to their military use, they are used by many police forces throughout the world, by far the most popular being the Israeli UZI and the German Heckler and Koch MP-5, both of them firing 9-mm bullets.
Explosive Devices
Explosive devices cause injury and death from the heat, blast, and fragments they produce, and may generate additional trauma from the buildings and other structures that they destroy. They range from a grenade thrown by hand to a missile fired from another continent, but all have the same basic construction of explosives packed inside a hollow container. There is a huge and ever-increasing array of modern war munitions, some intended primarily to destroy buildings and other structures (antimaterial, with a high blast component) and some directed mainly
against people (antipersonnel, with a high fragmentation component). A basic guide is given in Table 2. The list does not include the additional terrorist arsenal of car and truck bombs, nor the suicide bomber, each of which will produce a varied combination of blast and fragmentation effects which can be as devastating as any of the conventional devices.
Injuries
The injuries seen in victims of war will obviously reflect the weapons and munitions being used and
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the particulars of the situation. As previously stated, in modern conflicts more people die of fragmentation injuries than from bullets or blast.
Injuries from Bullets
Bullet injuries will invariably be of the type caused by centerfire bullets traveling at velocities of around 900 m s1, i.e., at high velocity. Damage will be caused not simply by the physical passage of the bullet through the tissues but by additional temporary cavitation around the track, with structural disruption radiating out into the surrounding tissues. The severity of internal damage and cavitation is determined by the amount of kinetic energy lost by the bullet as it passes through the body; this, in turn, depends on factors such as the weight and velocity of the bullet, its stability in the body (i.e., extent of yawing), the nature of the tissues through which it travels, the degree of retardation, and the length of the track. Those losing the greatest amount of energy (high-energy transfer) cause most damage while those losing the least (low-energy transfer) cause damage largely restricted to the track. Wounds from assault rifles and the like are often referred to as high-velocity injuries but such terminology is not entirely appropriate as similar damage can sometimes be caused by low-velocity weapons such as handguns. For this reason, use of the terms high- and low-energy transfer is preferred. Cavitation does not occur on immediate entry into the body and requires a certain depth of penetration for it to develop, varying from one type of bullet to another. It will not necessarily be visible to the naked eye and the internal damage may appear no more
striking than that caused by a simple handgun, even where the bullet is passing through a thin bone such as a rib. Bullets passing through dense tissue will be retarded much more than those traveling only through loose tissue such as lung or muscle, with a corresponding greater loss of energy and greater physical damage. Thus, where a bullet strikes solid bone, the latter will shatter, secondary bone fragments will penetrate the surrounding tissues, and the bullet will often fragment. Most striking are bullet injuries to the head, where formation of a temporary cavity inside the rigid skull causes gross fragmentation, with multiple radiating fractures around the entrance hole and a large disruptive exit opposite, including wide tearing of the skin (Figure 1). Military bullets are fully jacketed, i.e., they comprise a lead or steel core covered by a copper jacket. This is to reduce the chances of a bullet disrupting inside the body and causing unnecessary wound severity. Such requirements are enshrined in the Hague Declaration of 1899; there are also regulations about the overall shape of the bullet. On the other hand, the bullets used by most police forces in their machine pistols are only partly jacketed (hollow point, soft point), the intention here being to limit penetration by causing the bullet to break up and not to exit. Inside the body, bullets can be deflected and so may exit in a different direction. Also, not all bullets will exit although military ammunition is intended to pass through the body and exit without breaking up certain bullets, notably the M16 5.56-mm round, do fragment readily and may remain inside or produce multiple exits. The penetration and track of a bullet may be further altered if it passes through something
Figure 1 Bullet injury to skull (high energy transfer): (A) entrance hole (arrowed) with radiating fractures and (B) large exit defect on opposite side.
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or someone else beforehand (intermediate target), possibly including another part of the persons own body such as an arm or a leg. Those with gunshot injuries may have a single wound or may have multiple, perhaps 20 or more, if subjected to the full discharge of an automatic weapon. Depending on what part of the body is struck bullet injuries are survivable, but clearly, high-energy transfer injuries to the head carry a very high mortality, as do those striking vital organs in the chest or abdomen. In a war situation, the clinical management of injured persons differs considerably from civilian practice where fully equipped facilities and specialized teams are readily available and injured numbers are low. Similarly for the pathologist examining the bodies of war victims, facilities will probably be less than ideal and numbers of bodies large. Further difficulties will arise if there is a significant delay between death and autopsy, particularly in hot countries without refrigeration. Multiple and crisscrossing wound tracks, uncertainty over entrance and exit wounds, and additional damage from fragments, blast, and heat may all add to the problem. The cause of death may be self-evident but information regarding direction of fire, survivability, and the nature of the weapon used may all be important information for any future inquiry.
Injuries from Explosive Munitions
Figure 2 Deep lacerating wounds from fragments.
Explosive devices vary greatly in power and purpose but will all cause injury by a combination of fragmentation, blast, and heat. At one end of the scale, grenades will generally only cause fragmentation injuries while, at the other, bombs will kill primarily from blast effect and heat. Fragmentation injuries When a grenade, shell, or bomb detonates, the casing will break up into multiple fragments, either in a natural way or into preformed pieces of uniform size and weight (e.g., a serrated wire coil inserted into the casing). Some grenades and shells will also contain items inside, such as ball bearings or arrow-like flechettes; the latter are capable of penetrating very deeply. Fragments of any nature are commonly referred to as shrapnel but, strictly speaking, Lieutenant Henry Shrapnel gave his name to a shell he designed in the late eighteenth century to carry musket balls thousands of meters before dispersing them. Fragments disperse initially at considerable velocity but this declines rapidly with range, as does their penetrating capacity. They are designed to incapacitate rather than necessarily to kill and are the
most common injury seen in modern warfare. Military munitions are designed to produce fragments in a predictable way over a well-defined range, but terrorist bombs are much more unpredictable. The effects will obviously vary according to the size of the device and how close the person is when it explodes. They will range from multiple surface abrasions and lacerations to deeply penetrating tracks and gross tissue disruption, perhaps including amputation of limbs (Figure 2). For those close to the point of detonation mortality will be high, due to penetration of vital organs and severing of limbs, but many other victims will survive and reach medical services. As wounds tend to be multiple and irregular, contamination and infection will be common in the latter situation. For the pathologist, fragmentation (shrapnel) injuries can sometimes closely resemble those caused by bullets, particularly in decomposed and skeletonized remains, but the irregularity of the damage to tissue and bone, and the retrieval of characteristically shaped metal will usually point to the true nature. Unlike blast effect, fragmentation injuries are entirely directional, i.e., they are found on the surface of the body facing the explosion and most severe on the part closest to it. Blast injuries Blast is the other main feature of explosive munitions, sometimes accompanying fragmentation, sometimes dominating the picture.
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It describes the high-pressure shock wave produced by explosives when they detonate and undergo exothermic chemical decomposition. A rapidly expanding sphere of gas spreads out in all directions, reaching its peak almost instantaneously and passing through and around objects in its path. It is followed by a wave of negative pressure and will be accompanied by a blast wind, fire, and dispersed fragments, the fire being limited to the immediate vicinity of the blast but the fragments spreading out over a wide area, much further than the shock wave itself. As the wave travels, it will be reflected off the ground and off any buildings or other solid objects in its way, being reinforced as it does so (triple points and Mach systems), such that anyone in front of a building may suffer greater injury than if he/she were out in the open. Around every explosion there will be a lethal zone within which no one will survive. Those at the very center will suffer complete disruption of the body (due to the blast wind), while those around will remain largely intact but with loss of various parts and perhaps disruption of body cavities; they will also show flash burns from the intense heat and flame generated. Beyond this, there will be varying degrees of internal blast damage plus almost certain fragmentation injuries that, close to the lethal zone, are very likely to prove fatal, particularly with military munitions. Further away from the center of the blast, there will be variable survival depending on the nature of the injuries. Body armour will protect effectively against fragments but will do nothing for blast waves. Primary blast injury occurs when the blast wave hits the body and the resulting forces cause displacement and distortion of the body tissues. Stress waves and shear waves are produced, the former causing
their maximum damage at the interface between areas of differing density. Classically this occurs in the hollow organs where air and solid tissues abut, notably in the lungs, bowel, and the ears. In the lungs there is pulmonary contusion, with hemorrhage into alveoli, plus possible disruption of bronchi and pneumothorax. Severe blast injury to the lungs will be fatal; lesser degrees are survivable, although other injuries may supervene. In the bowel, damage will range from rupture to mucosal hemorrhage, while in the ear, the tympanic membrane may be disrupted. Although the solid organs will be unaffected by these forces, accompanying shear waves may cause them to be torn from their attachments. The victim of any military or terrorist explosive device will often show a mixture of injuries, not always easy to categorize specifically, bearing in mind the variety of mechanisms potentially involved in their causation (Figure 3). Injuries are often classified as: 1. primary blast injuries the injuries directly caused by the blast wave, i.e., damage to the lungs 2. secondary injuries caused by the accompanying fragments, often the most lethal damage for those not immediately at the center of the explosion 3. tertiary injuries from the blast wind, producing variable degrees of disruption and amputation, and additional injuries from being thrown against solid surfaces 4. quaternary injuries burns from materials ignited, crush injuries from masonry. In those closest to the blast it may be difficult to work out what caused what, with the potential for the additional injuries to obscure the first two categories, particularly burning. There is also likely to be heavy
Figure 3 Victim close to center of bomb blast, showing partial disruption of body and multiple fragment injuries.
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Figure 4 Antitank landmine injury with amputation of right leg and fragment injuries on left leg.
contamination of the body by debris and dust, plus extensive tearing of the clothing, some of which may be shed completely. Looking at one specific exploding device: landmines do not usually kill, they are primarily designed to incapacitate. They can be antitank (high-explosive content and detonated only by heavy pressure) or antipersonnel (low amount of explosive but requiring relatively little pressure to detonate). For most mines, detonation occurs when the mine is run over by a vehicle, stood upon, or handled. It will produce combined blast and fragmentation effects, with injuries confined to the part of the body closest to the explosion. Traumatic amputation is very common (in one survey of antipersonnel mine injuries the figures were 93% for lower limb and 80% for upper limb); lowerlimb amputations are most commonly of the foot or lower leg. The surrounding tissues will be heavily lacerated and contaminated by various fragments, both from the mine and from the surroundings, including footwear. Occasionally, fatalities will occur. Figure 4 shows the victim of an antitank landmine explosion who suffered traumatic amputation at the top of the leg.
picture. While, to most observers, the cause of death may appear self-evident and the need for forensic investigation unnecessary and socially intrusive, information about things such as who and where the victims were, the nature of their injuries, the devices causing them, and the potential for survival may be of considerable importance in both a clinical and legal settings.
See Also
Ballistic Trauma, Overview and Statistics; Torture: Physical Findings
Further Reading
Coupland RM, Meddings DR (1999) Mortality associated with use of weapons in armed conflicts, wartime atrocities and civilian mass shootings: literature review. British Medical Journal 339: 407410. Di Maio V (1999) Gunshot Wounds. Boca Raton, FL: CRC Press. Hiss J, Kahana T (2000) Modern war wounds. In: Mason JK, Purdue BN (eds.) The Pathology of Trauma, pp. 89102. London: Arnold. Kuzman M, Tomic B, Stevanovic R, et al. (1993) Fatalities in the war in Croatia, 1991 and 1992: underlying and external cause of death. Journal of the American Medical Association 270: 626628. Ryan JM, Rich NM, Dale RF, Morgans BT, Cooper GJ (eds.) (1997) Ballistic Trauma: Clinical Relevance in Peace and War. London: Arnold. Smith D (2003) The Atlas of War and Peace. London: Earthscan Publications.
Conclusions
Weapons of war and the injuries they cause do not feature greatly in the work of most forensic practitioners. For those in certain parts of the world they do, and for those involved in the investigation of war crimes it is important to appreciate the wider
Y
YAKUZA
S Tsunenari and S Mimasaka, Kumamoto University, Kumamoto, Japan
Introduction
Criminal behavior can be classified into several types using sociological criteria such as the criminal career of the offender, group support for criminal behavior, correspondence between criminal and legitimate behaviors, and societys reaction. The crime types are: (1) violent personal crime, (2) occasional property crime, (3) occupational crime, (4) political crime, (5) public order crime, (6) conventional crime, (7) organized crime, and (8) professional crime. Among these, organized crime includes prostitution, gambling, and peddling narcotics and firearms. In every country there are groups of people who cannot adjust to normal society and disturb public peace and order. The offenders pursue crime as a way of life, and the Mafia in the USA and Italy, and the Shetou, the Snake Head, in the Peoples Republic of China are well-known organized crime groups. In Japan the Yakuza represent an organized crime group. They maintain family-like groups with fictitious kinship ties, following the traditions of the Japanese family system in the feudal era, and make a living through organized crime. They live partly as ordinary citizens and partly in the criminal underworld. The Yakuza can be sociologically defined as a psychopathological group that lives by a social code different from that of the rest of society. A study of the personalities of Yakuza suggested that they have deviant personalities in the following ways: (1) a quest for power, which is expressed in the primitive form of simple physical violence; (2) a need to prove their masculinity in this regard tattooing is a symbol of manhood by being a sign of the ability to bear extreme physical pain; (3) aggressiveness and belief in a law of the jungle; (4) a fatalistic way of thinking and a tendency to live only for the moment; (5) social parasitism; (6) self-glorification; and (7)
inability to moderate behaviour. Deviant personalities such as those described above are closely connected with primitive customs in the Yakuza society, e.g., tattooing and cutting off the little finger(s) as evidence of apology or loyalty to the leader of the group. Implantation of penile spheres can also be considered in this category. It is believed that this unusual sexual device helps to maintain relationships with several women or to keep their parasitic hold over one woman through sexual gratification. International criminal offenses such as the smuggling of contraband drugs and other items and fraud associated with international trade are often reported. It is possible that members of the Yakuza may be involved in these international criminal activities. Forensic practitioners and police worldwide should be aware of the identifying characteristics of the Yakuza and other organized crime groups.
The Sociology and Criminology of the Yakuza

The term Yakuza is derived from a combination of three numbers: 8 (ya), 9 (ku), and 3 (san or za). This can be traced back to professional gamblers slang in the variation of the Hanafuda game named San-Mai or three cards. Hanafuda is a version of a card game introduced to Japan by Dutch sailors at the end of the sixteenth century. The name Hanafuda is derived from the fact that each of the cards is decorated with a flower design. A pine tree, cherry blossoms, paulownia, or rainfall each symbolic of scenes of natural beauty in certain months of the year is drawn primarily in red, blue, and black after the style of a woodblock print. There are 48 cards divided into four sets of 12 cards, representing one of the months of the year and worth anything from one to 20 points. Professional gamblers or Bakuchi-Uchi first appeared in Japan in the Muromachi period (1336 1568) and they formed a modest Yakuza group in the middle of the Edo period (1700s) with the development of gambling dens. Their society was based on
384 YAKUZA
a feudal hierarchy together with fictitious parental relationships. The rules of giri and nijyo which can be translated as justice and charity, duty and humanity, or duty and love, were strictly enforced between a boss called oyabun (parent), and his followers, called kobun (child). Poor peasants who were exploited in the rural communities then sometimes trusted the Yakuza organization. Group affiliations are very important in Japanese society in terms of personal fashionable alignments or habatsu, family interrelationships, school provenance or academic clique, and personal patronage and recommendation. A sense of hierarchy is fundamental and all-pervasive in Japanese society, giving it shape and character. Japan is divided into numerous groups, each organized into multiple layers of status. Many modern groups achieve a hierarchical pattern through a strong sense of age distribution and a concept of love and duty. The basic concept of the Yakuzas world, therefore, is similar to that of some Japanese groups. They also follow the concept of the premodern Japanese family, known as the ie in Japanese; this includes subordinate-branch families under the authority of the main family and often other members who were distant kin or not related at all. It also gave the father or family council absolute authority over individual members. Popular literature, drama, and films of Japan have taken their themes from the Yakuzas world and have idealized the harsh realities of their life and deviant personalities. Todays Yakuza still follows a family-like form with fictitious parental relationships and makes money by gambling, prostitution, and distribution of weapons, narcotics, and pornography. Some of the groups prosper because of the in demand, but illegal, services they provide for the public. The total numbers of the Yakuza are about 85 300 as of the start of the twenty-first century. Most (91.7%) are members of 24 large-scale criminal syndicates over large geographic areas of Japan. The largest Yakuza group is the Yamaguchi-Gumi, or Yamaguchi gang (consisting of about 17 900 Yakuza), based in Kobe city with subfamilies in almost all prefectures throughout Japan. The Japanese police have a special division to obtain information about the Yakuza and to try to control them. According to the police, the Yakuza are divided into two types: (1) Boryoku-Dan or organized racketeers and (2) Boryoku-Joshu-Sha or habitual violent criminals, who are often ex-members or reserve members of the Boryoku-Dan. In the Kumamoto prefecture with a population of 1 850 000, there are 49 Boryoku-Dan groups with 741 members. All have direct or indirect associations with the main Yakuza groups. There are 28 bosses, 244 staff members, 359 ordinary members, and 110 semimembers.
A single group can have 580 members, but 15 is the average. There are 355 members of the BoryokuJoshu-Sha known to the police. About half of the Yakuza are between 3039 years of age. A strict ranking exists in their society, which is determined by the period of service, experience, political ability, and physical strength. Members above 40 years of age are mostly either bosses or staff members. As the police attack the Yakuzas illegal fundraising activities such as black-market businesses and open gambling dens, the Yakuza move into an increasing number of legitimate businesses such as public entertainment, money lending, and construction work. However, they remain antisocial and criminal, and this is clearly shown in their criminal records. The average number of terms of imprisonment and police arrest were 3.4 and 2.3 for Boryoku-Dan and 5.9 and 3.3 for Boryoku-Joshu-Sha, respectively. Only 15% and 18% of the Boryoku-Dan members had no records of imprisonment and police arrest, respectively. In the Boryoku-Joshu-Sha, only 2% had no record of imprisonment and 12% no record of police arrest. Their crimes are usually those against the person in illegal acts such as murder, manslaughter, aggravated assault, and intimidation, or against public order such as gambling, prostitution, disturbing the peace, and the use of narcotics. Crimes against property, such as robbery, larceny, and fraud are also often committed. Police statistics for 2001 showed that stimulant drug control law violation topped the list of arrests with 7298 (23.6% of the total), followed by bodily injury (4838: 15.6%), blackmailing (3070: 9.9%), and robbery (2757: 8.9%). Many victims do not report the crimes to the police, because they know that those crimes were carried out by an organized group and victims fear revenge. Yakuza members carry unlawful weapons, especially knives, daggers, and revolvers, to protect themselves from rival Yakuza members. Unlawful possession of weapons is a crime usually only committed by the Yakuza, it is rare in the general public. Boryoku-Dan have stepped up their international activities in recent years. They have expanded into foreign countries with the aim of procuring firearms and stimulant drugs and securing funds through realestate investment. In addition, Boryoku-Dan have acted as brokers in the illegal entry of foreigners into Japan; provided females as show dancers or prostitutes and males as construction workers; and taken part of their wages in the form of kickbacks. In 1993 it was revealed that Boryoku-Dan, with close ties to Chinese organized criminals, the Shetou, the Snake Head, played a role in the illegal entry of a group of Chinese into Japan in order to secure a new source of funds. In addition, companies involved with
YAKUZA 385
Boryoku-Dan were charged with violation of foreign exchange and foreign trade control law. The police have been conducting two types of crackdown operation (direct and indirect control) against the Yakuza. Direct control is designed to divide and destroy the organization of the Yakuza by an all-out attack on the members, their weapons, and their source of funds. Indirect control attempts to isolate them from legitimate society.
The Physical Characteristics of the Yakuza

An average Japanese person will find it easy to recognize Yakuza from their way of speech, behavior, clothes, and personal ornaments. The ability to notice these differences can only be acquired by living in Japan for some time and by getting to know the Japanese, who are a relatively homogeneous race and have a unique cultural background. A foreigner, therefore, will find it difficult to recognize Yakuza. This section describes the physical characteristics useful for forensic identification of the Yakuza (Figure 1).
Tattooing
The art of Japanese tattoo has both unique beauty and deep social implications. Flourishing in the late
eighteenth and early nineteenth centuries, it shared much with other popular Japanese arts of that time, particularly with the Ukiyo-E woodblock print. The prints of artists such as Hokusai and Kuniyoshi played a large part in the development of tattoo, both by depicting tattooed heroes and then by providing models for tattoo designs. This tattoo tradition has continued so far. Today the clients of Japanese tattoo masters are primarily laborers, craftsmen, and the Yakuza. Though now fully legal, tattooing has strong criminal associations, and remains part of the underworld. The traditional tattooing technique is not that of rubbing colors into skin wounds but direct penetration of colors into the skin by needles. Two or more needles are always used together, even for delicate or fine work, because the capillarity established by two needles facilitates absorption of pigment. Ordinary needles are fixed to the tips of hard slender sticks and tied into a bundle. The skin to be tattooed is spread taut between the thumb and little finger of the left hand, so that it will not yield under the needle. Using various grips on a bunch of needles, the tattoo artist uses the sticks as a lever, with the left thumb acting as fulcrum. Originally, only a few colors were used sumi black (an indigo or deep-blue color under the skin), red, and occasionally brown. Now a variety of new chemical inks is used, offering wider color
Figure 1 The physical characteristics of the Yakuza: tattooing, digital amputation, and penile spheres. The deceased here is a 59year-old Yakuza member who died from a myocardial infarction.
386 YAKUZA
possibilities. The process of tattooing is divided into two major parts, drawing the outline and then filling in and shading. It takes over a year and costs about US$9000 to complete a large tattoo. Just how painful is the entire process only the client knows, and he does not usually say, as having a tattoo is in part a demonstration of masculinity and thus the individual would not admit to pain. Nonetheless, one can imagine the pain of tattooing by comparison with a routine flu shot. Tattooing is most frequently performed on the upper arms, shoulders, and chest, followed by back, groins, thighs, and genitalia. The principal idea is that the Japanese tattoo should be covered when it is not on display. Traditional tattoos never appear on body parts uncovered with clothes. The designs are limited to various flora and fauna, religious motifs, and the representation of various heroes and folk figures all of which have symbolic qualities. In all countries, tattooing stresses strength and bravery, but only in Japan are attributes such as loyalty, devotion, service, and obligation included (Figure 2). The Yakuza man wears his tattoos to show that he has been initiated to the group, and as an identifying emblem to show lifelong involvement with the Nakama, or those who are on the inside. It is also a symbol of manhood, signifying the ability to bear extreme physical pain and by extension any difficulty, and increases sexual attraction in the eyes of some. In a survey, it was found that half of Yakuza are tattooed. Although tattoos are usually covered by clothing, some Yakuza wear tiny spot tattoos at the corner of the eye, beside the mouth or on the dorsum of fingers. They also shave the outer ends of the eyebrows and then tattoo this area, and tattoo a ring or
the emblem of the group on the ring finger or the outside of the forearm. These tiny tattoos, which are not in the traditional style, are usually done by the Yakuza himself or by a friend to show that he is wearing tattoos to frighten others. Junior members of the Yakuza often have only tiny tattoos.
Digital Amputation
Yubizume or digital amputation is another physical characteristic of the Yakuza and is observed in about one-third. This is just one of the brutal customs in the Yakuza world. It is done either to apologize or to show loyalty to the boss. The amputated fingertip is dedicated to the boss as a concrete visible symbol of his power. It was found that 194 of 741 (or 26%) members of Boryoku-Dan and 95 of 355 (or 27%) members of Boryoku-Josho-Sha have had their fingers cut off. Digital amputation is usually done at the middle phalanx of the left little finger. In cases of multidigit amputations, a particular order of operation sites is found: the left and right fifth middle phalanges followed by the left and right fourth ones. Voluntary digital amputation cannot be distinguished from an accidental one, because the Yakuza member, who has cut off his fingers by himself, seeks medical care. Digital amputation was formerly a shameful ceremony for the Yakuza, but it is now often performed by young members of Yakuza to indicate manliness and heroism. It has almost become a fashion among the Yakuza.
Penile Spheres
Figure 2 Typical Japanese tattoos on the body of a Yakuza member.
Some of the Yakuza have an unusual sexual device under the penile skin, penile spheres (Table 1). These spheres are usually made of plastic such as toothbrush handles, combs, and buttons. They are ground by hand into globular or rod shapes. Sometimes silicone for plastic surgery is used. As many as 31 spheres have been found in one penile shaft, and their total weight varies from 0.1 to 9.2 g. The insertion of the spheres is usually performed by the Yakuza himself while in prison. Pinching up the skin of the penile shaft, a small tunnel is made under the skin with a sharpened chopstick, and then the spheres are pushed into this tunnel. It takes only a few seconds (Figures 3 and 4). In a survey at a local prison it was found that 28 of 130 prisoners (21.5%) had penile spheres. It was impossible to be sure how many were Yakuza, but judging from their stated occupations and prison records, most were gangsters. The precise number of Yakuza who have this unusual sexual device is unknown, because the police have not included it in
YAKUZA 387
Table 1 Penile spheres observed in forensic autopsies in Kumamoto, Japan
No Year Age Materials Numbers Weight (g)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 Ranges
1968 1969 1969 1972 1972 1973 1976 1977 1981 1981 1981 1982 1982 1982 1984 1985 1985 1985 1986 1987 1988 1988 1989 1989 1989 1990 1990 1990 1992 1997 1997 1998 1999 2001 2001 2002 2004
22 40 32 38 25 29 36 37 40 30 40 41 37 39 32 34 36 28 25 60 39 54 40 39 34 34 49 43 58 38 52 30 39 51 47 31 54 22 $ 60
Plastics Plastics Plastics Plastics Plastics Plastics Plastics Plastics Plastics Plastics Plastics Plastics Plastics Plastics Plastics Plastics Plastics Plastics Plastics Silicones Plastics Plastics Plastics Plastics Plastics Plastics Plastics Silicones Plastics Plastics Silicones Silicones Plastics Plastics Plastics Plastics Plastics
1 1 3 1 11 2 6 6 9 4 6 1 1 1 6 31 2 2 1 3 13 1 13 28 16 4 7 6 3 3 4 8 12 3 2 3 1 1 $ 31
0.3 0.5 1.2 0.4 1.3 0.5 3.1 1.7 6.6 1.6 1.5 0.2 0.2 0.1 1.8 3.8 0.9 0.7 0.2 0.6 2.9 0.8 4.2 9.2 2.1 0.7 2.2 3.1 0.9 0.4 1.7 1.8 1.6 0.9 0.2 0.4 0.3 0.1 $ 9.2
their Yakuza identification booklet, nor recorded it in their files. Penile spheres may be thought of as one type of sexual behavior, an unusual form of sadomasochism. In forensic practice the presence of penile spheres may be useful as an unusual means of criminal and personal identification.
The New Generations of the Yakuza

The image of the punch-permed Yakuza, with his missing little finger and Yamaguchi-Gumi pin on his lapel, is a stereotype that is quickly becoming as outdated as the geisha and samurai. The 1990s were a time of enormous change for the denizens of Japans underworld, and the Yakuza have changed more since
the 1990s than they did in the entire postwar period. The biggest change is that the Yakuza groups are becoming less obtrusive. They are doing their best to blend in with the local population and the Yakuza member today probably looks more like an office worker than a character in Yakuza movies. They are finding new sources of income, gangs are restructuring, and they are operating in a legal and economic environment that is radically different from in the 1990s. The anti-Boryoku-Dan law passed in 1991 has had a huge effect on gang structures and membership. The law made it illegal to belong to an organization which had a certain percentage of people with criminal records, or that engaged in designated activities that were not technically crimes and so had been difficult to prosecute in the past. Activities like demanding hush money, coercing businesses into using subcontractors affiliated with Yakuza, and even forcing members to get tattoos or cut off their fingers are now prohibited. Gang membership is decreasing steadily, and recruitment is becoming more and more difficult. Many members have officially left gangs, but still maintain ties with their former gangs and continue to engage in illegal activities. There are many different kinds of groups affiliated with the Yakuza, from Tekiya (street vendors) to Sokaiya (corporate racketeers) to Bosozoku (biker gangs) and almost all of their members have at least some connection with the mainstream gangs. To combat the anti-Boryoku-Dan law, many gangs have set up frontcompanies that appear to be completely legitimate. Business-suit Yakuza now make up approximately one-third of total gang membership in Japan. There are many social changes occurring in the Japanese underworld too. The big black foreign cars that were once a symbol of the Yakuza are becoming a thing of the past, and have been replaced with Japanese Toyota or Nissan cars. Tattoos are less common and the practice of digital amputation and/or penile spheres is also gradually becoming a thing of the past. Loyalty to the gang is decreasing, and a surprising number of criminals are taking advantage of anti-Boryoku-Dan association programs which help them to leave their gangs and reenter society. Ritualistic sake drinking is becoming less common as an entrance ceremony, and money is becoming more important than the traditional family ties that once held the syndicates together. This change is reflected in a shift in public opinion. Newspapers and police now refer to them as Boryoku-Dan (violent gangs) and many shopkeepers are taking advantage of seminars and public programs that help them to fight back against organized crime. However, if the
388 YAKUZA
Figure 3 Penile sphere in situ. A plastic ball of 0.3 g has been inserted under the penile skin (arrow).
Figure 4 Collections of penile spheres. (A) No. 22, a plastic ball, 0.8 g; (B) no. 24, a pearl (arrow) and 27 plastic balls, 9.2 g; (C) no. 27, seven plastic balls, 2.2 g; (D) no. 32, eight silicone balls, 1.8 g.
Yakuza of today are not as colorful of those of the past, and if their future is not as certain as it once was, it does not mean that they are any less significant a force in Japanese society.
See Also
Court Systems: Law, Japan; Death Investigation Systems: Japan; Deliberate Self-Harm, Patterns; Tattoos, Medico-legal Significance
YAKUZA 389
Further Reading
Khol K (1982) Hanafuda. In: The Japan Culture Institute. Discover Japan Words, Customs and Concepts, vol. 1, pp. 132133. Tokyo: Kodansha. Miyawaki R (1979) Crackdown operations against organized racketeer groups (Yakuza) in Japan. International Criminology and Police Reviews 329: 167169. Reischauer EO (1978) The Japanese, pp. 122133. Tokyo: Charles E. Tuttle.
Richie D, Buruma I (1980) The Japanese Tattoo. New York: Weatherhill. Tsunenari S, Idaka T, Kanda M, Koga Y (1981) Self-mutilation plastic spherules in penile skin in Yakuza, Japans racketeers. American Journal of Forensic Medicine and Pathology 2: 203207.
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Encyclopedia of Forensic e Bookand Legal Medicine

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Encyclopedia of Forensic e Bookand Legal Medicine

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ROAD TRAFFIC ACCIDENTS, AIRBAG-RELATED INJURIES AND DEATHS 1

ROAD TRAFFIC ACCIDENTS, AIRBAG-RELATED INJURIES AND DEATHS

The History of Airbag Research and Development

2 ROAD TRAFFIC ACCIDENTS, AIRBAG-RELATED INJURIES AND DEATHS

Airbag Tethers and Covers

Phases of Airbag Deployment

ROAD TRAFFIC ACCIDENTS, AIRBAG-RELATED INJURIES AND DEATHS 3

Figure 8 Chemosis and hyphema from a passenger-side airbag.

4 ROAD TRAFFIC ACCIDENTS, AIRBAG-RELATED INJURIES AND DEATHS

Figure 9 Periorbital contusions and abrasions from a passenger-side airbag.

ROAD TRAFFIC ACCIDENTS, AIRBAG-RELATED INJURIES AND DEATHS 5

6 ROAD TRAFFIC ACCIDENTS, AIRBAG-RELATED INJURIES AND DEATHS

ROAD TRAFFIC ACCIDENTS, AIRBAG-RELATED INJURIES AND DEATHS 7

Figure 22 Partial thumb amputation from a passenger airbag.

8 ROAD TRAFFIC ACCIDENTS, AIRBAG-RELATED INJURIES AND DEATHS

ROAD TRAFFIC ACCIDENTS, AIRBAG-RELATED INJURIES AND DEATHS 9

Lower Extremity Injuries

Figure 32 Blood on the airbag can be matched to an occupant, driver, or passenger.

10 ROAD TRAFFIC ACCIDENTS, AIRBAG-RELATED INJURIES AND DEATHS

Determination of Occupant Role

ROAD TRAFFIC ACCIDENTS, AIRBAG-RELATED INJURIES AND DEATHS 11

12 ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/Sobriety Tests and Drug Recognition

ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE

Sobriety Tests and Drug Recognition

Introduction and Background

ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/Sobriety Tests and Drug Recognition 13

14 ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/Sobriety Tests and Drug Recognition

ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/Sobriety Tests and Drug Recognition 15

16 ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/Sobriety Tests and Drug Recognition

Table 2 Continued ONE LEG STAND

Repeat procedure with each foot FINGER AND NOSE TEST

already been arrested

ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/Sobriety Tests and Drug Recognition 17

Drug Recognition Training

18 ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/Sobriety Tests and Drug Recognition

Central Nervous System Stimulants

ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/Sobriety Tests and Drug Recognition 19

Amphetamine Methamphetamine Ecstasy Cocaine Cocaine Cocaine

Injected By mouth Smoked Injected Snorted

48 h 46 h 510 min 4590 min 3090 min

. grinding teeth (bruxism) . impaired perception of time.

20 ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/Sobriety Tests and Drug Recognition

ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/General 21

Determination of Driver Fitness

22 ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/General

Cardiovascular Medical Conditions That May Impair the Driver

ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/General 23 Congestive Heart Failure

24 ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/General

Neurological Conditions That May Impair the Driver

ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/General 25

26 ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/General

until they have undergone medical assessment and appropriate treatment.

Traumatic Brain Injury That May Impair the Driver

Metabolic Conditions That May Impair the Driver

ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/General 27

Respiratory Conditions That May Impair the Driver

Sensory Conditions That May Impair the Driver

Renal Condition That May Impair the Driver

Sleeping Disorders That May Impair the Driver

28 ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/General

Deficits of the Extremities That May Impair the Driver

Medications and Their Effects on Drivers Fitness

ROAD TRAFFIC, DETERMINATION OF FITNESS TO DRIVE/General 29