Volume 2, Issue 3

i
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Volume 2, Issue 3 July - September, 2014
ii

Editorial Board
Senior Editor-in-Chief
Prof. Nazeer Khan
Executive Editors
Syed Salman Ahmed,
Sajid Ali
Editor-in-Chief
Asfandyar Sheikh
Managing Editor
Syed Arsalan Ali
Assistant Editor-in-Chief
Haris Sheikh

Assistant Managing Editor
Shanawer Khan

Prof. Asaad Javaid,
Dr. Ye Yang,
Dr. Abdul Hafeez Baloch,
Dr. Mansoor Husain,
Dr. Manit Arora
Dr. Muzaffar H Qazilbash,
Dr. Tasneem Z Naqvi,
Dr. Asim A Shah,
Prof. Shahid Wahab,
Senior Editors
Dr. Samina Abidi,
Dr. Rashid Mazhar,
Dr. Mosaddiq Iqbal,
Prof. Javed Akram,
Prof. Abdul Bari Khan,
Prof. Ashraf Ganatra,
Dr. Raza Ur Rehman,
Dr. Waris Qidwai,
Dr. Muhammad Ishaq Ghori,
Dr. Akber Agha,
Dr. Adnan Mustafa Zubairi,
Dr. Saqib Ansari,
Dr. Mohsina Ibrahim,
Dr. Qamaruddin Nizami,
Dr. Samra Bashir,
Dr. Nabeel Manzar,
Muhammad Ashar Malik
Section Editors
Ali Sajjad,
Hafiz Muhammad Aslam,
Syed Askari Hasan,
Muhammad Uzair Rauf,
Syed Mumtaz Ali Naqvi

Statistics Editors
Mehwish Hussain,
Syed Ali Adnan
Editors
Shaikh Hamiz Ul Fawwad,
Gulrayz Ahmed,
Uzair Ahmed Siddiqui,
Dr. Hussain Muhammad
Abdullah,
Asfandyar Khan Niazi,
Muhammad Danish Saleem,
Iqra Ansari

Production Editors
Noorulain Chishti,
Muhammad Hamid
Chaudhary,
Adnan Salim,
Bushra Mufti,
Parisa Aijaz,
Marium Farooqi
Assistant Editors
Raza Mahmood Hussain,
Maheen Anwer,
Anum Saleem,
Hira Hussain Khan,
Imran Jawaid,
Hina Azhar Usmani,
Hira Burhan,
Kiran Yaqub,
Quratulain Ghori,
Bushra Iqbal,
Maria Rahim

v

Table of Contents
FrontPage i
Editorial Board ii
Call for Papers iii
Health Poster iv
Table of Contents v

Original Articles

Dislodged feeding tubes: Should bedside x-rays be abandoned for advanced
imaging?
Rachel G Eisenstadt, Rachel L Sensenig, Daniel N Holena, Carrie Sims, Benjamin Braslow,
Jose L Pascual
184

The epidemiology of fractures around the elbow joint
Stuart A Aitken, Margaret M McQueen, Charles M Court-Brown
189

Clinical and echocardiographic study of patients in heart failure with a
normal/near normal ejection fraction
Asif Hasan, Muhammad Uwais Ashraf, Nazih Ahmad C L, Anjum Parvez
195

Comparison of transcerebellar diameter in growth restricted and normal
singleton fetuses for the assessment of gestational age: A case control
study
Sumera Aziz Ali, Azrah Bano Khuwaja
200

Adherence to guidelines of healthy diet is low in patients with diabetes
clinical inertia
Masoumeh Akhlaghi, Fatemeh Hemmati
205

Genital hygiene behaviors and associated factors in women living in rural
areas of Turkey
Derya Adbelli, Nur zlem Kln, Yaam Kemal Akpak, Dilek Kl
210

A comparative study of open tracheostomy and percutaneous
tracheostomy in ICU setting
Bipin Kishore Prasad, Devjani Ghosh Shrestha
215

Effect of pesticides on color vision and anterior ocular structure of farmers
Sharanjeet Kaur, Azizan Izzah Azreena, Khang Nie Leong, Sumithira Narayanasamy
219

vi

Antibiotic susceptibility pattern of Serratia marcescens isolates from wound
infections in a tertiary health institution in Calabar, Nigeria
Ofonime Mark Ogba, Baki Idasa Mandor, Helena Martin Omang
223

The applicability of proprioceptive and endurance measurement protocols
to treat patients with chronic non-specific neck pain
J Arami, A Rezasoltani, J Eghlidi, Z Ebrahimabadi, J Ylinen
227

Role of ultrasound in determining small bowel intestinal obstruction:
Findings at a public sector hospital of Pakistan
Zahid Ali Memon, Huzaifa Dawood, Muhammad Danish Saleem, Shaikh Hamizul Fawwad,
Naheed Sultan
231

Phytochemical screening and high performance thin layer chromatography
finger printing analysis of green hull of Juglans regia (walnut)
Pardeep Sharma, Duraisamy Gomathi, Ganesan Ravikumar, Manokaran Kalaiselvi,
Uma Chandrasekaran
235

Collaborative care for schizophrenic patients in primary care: A double
blind, randomized clinical trial of efficacy and safety
Saad Salman, Jawaria Idrees, Muhammad Anees, Mashaal Arifullah, Mansoor Al Waeel,
Muhammad Ismail, Mehreen Hassan, Zahid Nazar
240

Short Reports

Audit of orthopedic trauma theatre usage: Observation from a secondary
regional referral hospital in Oman
Dinesh Dhar
245

Hybrid NOTES cholecystectomy - A safe and economic innovation
Momin Malik, Sherif Saleh, Irfan Ahmed
248

Review

Microinflammation as a candidate for diabetic nephropathy
Amal Abd El Hafez
251

Unmet need for contraception and unintended pregnancies among women
of reproductive age group: A situation analysis
Sumera Aziz Ali, Savera Aziz Ali
259

The burden of malaria with historical perspective in Nigerian concept and
world view
Olugbenga Adekunle Olowe, Rita A Olowe, O A Awa
266

vii

Hepatocellular carcinoma: Could stem cell therapy ever be a viable
solution?
Ahmer Irfan, Irfan Ahmed
273

Case Reports

Successful conservative management in placenta previa percreta involving
urinary bladder
Latika Sahu, Gouri Gandhi, Nalini Bala, Priyanka Thakur
277

Multimodality imaging features of Poland syndrome associated with
cervical rib and elongated transverse process of cervical vertebrae
Muammer Akyol, Onur Gokdemir, Tulin Ozturk
282

Surgical approach in giant retrosternal goiter
Bipin Kishore Prasad, Rajnish Talwar, Manoj Kumar
286

Kidney transplantation from a donor with nutcracker syndrome
Cem Tugmen, Eyup Kebapci, Ismail Sert, Mehmet Tanrisev, Hlya Colak, Yeliz Pekcevik,
Sait Murat Dogan, Mustafa Olmez, Cezmi Karaca
288

Giant unilocular hydatid cyst of spleen
Shahbaz Habib Faridi, Bushra Siddiqui, Mohammad Aslam
291

Merkel cell carcinoma of the head and neck: A case presentation in the light
of literature
Feryal Karaca, Ferhat Ozden, Fatma Sert
293

Dental management of severe early childhood caries
Gurusamy Kayalvizhi, T D Vishwas, R Mahantesh, Balaji Subramaniyan
296

A case of Stevens-Johnson syndrome
S V S G Nirmala, R Dadeepya, V Lalitha, N Sivakumar, C Sandeep
299

Concomitant occurrence of fibrous dysplasia and epilepsy: Report of an
unusual case
Amita Aditya, Manjushri Waingade
301

Opinions and Debates

What if the patient says No! in the ambulance: An ethical perspective for
assessment of capacity in the prehospital emergency setting
Hasan Erbay
304

viii

Scope of nutritional assessment in community and clinical settings
Saurabh RamBihariLal Shrivastava, Prateek Saurabh Shrivastava, Jegadeesh Ramasamy
307

Essays

Spatial information processing by the human visual system
Azadeh A Rikani, Zia Choudhry, Adnan Maqsood Choudhry, Nasir Rizvi, Huma Ikram
309

Phage therapy: The new old antibacterial therapy
Omar Anwar Elkadi
311

Oral health and pregnancy
Nida Zahid, Anna Ali
313

Integrated teaching in medical curriculum in India
Mohammed Abdul Hannan Hazari
314

Letters to Editor

Renal transplant recipient undergoing cardiac surgery: Immunosuppressive
management
Junsheng Mu, Xianshuai Li, Jianqun Zhang, Ping Bo
315

Munchausen syndrome presenting with recurrent abdominal pain and
coagulation disorder
Hakan Demirci, Fatih Ermis, Zulfikar Polat, Murat Kantarcioglu, Ahmet Uygun, Sait Bagci
317

Traumatic asphyxial deaths
G N Pramod Kumar, B Manjunatha, Smitha Rani, B M Balaraj, Y P Raghavendra Babu
319

A fatal situation: Diabetes insipidus and superimposed acute polyuric
kidney injury
Sena Memnune Ulu, Mehmet Polat, Abdullah Altug, Seref Yuksel
321

Appendices

Instructions to Authors ix
Sponsorship Information xiii

184 http://www.mednifico.com/index.php/elmedj/article/view/203

Open Access Original Article
2014 Eisenstadt et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Eisenstadt RG, Sensenig RL, Holena DN, Sims C, Braslow B, Pascual JL: Dislodged feeding tubes: Should bedside x-rays be abandoned for advanced imaging? El Mednifico Journal 2014, 2(3):
184-188.
Dislodged feeding tubes: Should bedside x-rays be abandoned for advanced imaging?
Rachel G Eisenstadt
1
, Rachel L Sensenig
1
, Daniel N Holena
1
, Carrie Sims
1
, Benjamin Braslow
1
, Jose L Pascual
1

Background
The placement of feeding access is a common procedure performed
by both general and acute care surgeons. Enteral access is the pre-
ferred method to nutritional delivery nutrition whenever possible
and has been shown to decrease mucosal atrophy and preserve the
gut immune barrier [1, 2]. Regardless of the technique and site cho-
sen for enteral access, a number of complications may occur [3-5].
Most commonly, these include procedural injuries to adjacent vis-
cera and vessels, surgical site infections, tube site leakage, tube oc-
clusion/malfunction, and tube dislodgement [6, 7]. Dislodgement of
enteral feeding tubes in hospitalized patients is an underestimated
occurrence [8, 9]. In most series, dislodgement rates for tube gas-
trostomies and jejunostomies range from 15-40% with 10% of cases
requiring surgical intervention [8-10].
While several studies have investigated the safety and effectiveness
of different surgical tube insertion techniques, few have evaluated
dislodged tubes and their acute management [11]. Inadvertent pull-
ing on the feeding tube or its accidental removal, particularly in the
first weeks after placement, may occur in combative or confused pa-
tients or during routine patient turning or transfer. In cases where
the tube has not been completely removed, imaging is often used
to determine if it has become malpositioned prior to resumption of
use [12]. In cases where the tube has been inadvertently pulled out,
it is common to attempt replacement through the cutaneo-enteric
tract, followed by an imaging study to confirm correct replacement
and absence of tube site or track leakage [13]. Imaging may also be
obtained to rule out enteric leak if there is concern regarding tract
maturity [14]. Central to management of dislodged feeding tubes is
the rapid determination if immediate surgery is warranted to prevent
ongoing peritoneal contamination, septic shock, and death [15].

1
Division of Traumatology, Surgical Critical Care & Emergency Surgery, Department
of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia,
Pennsylvania, United States
Objective
In this study, we reviewed the imaging studies used in cases where
suspected tube dislodgement led to operative exploration. We eval-
uated how effective common imaging modalities (bedside contrast
abdominal radiograph, CT scan, contrast fluoroscopy) were in cor-
rectly identifying tube malposition, the time each modality required
to ultimately result in patient transfer to the operating room, and the
degree of intra-operative contamination encountered.
Methods
After IRB approval was obtained from the tertiary care hospital, the
billing records of the Emergency Surgery, Gastrointestinal Surgery
and the Surgical Access Services were queried for all abdominal op-
erations performed at the tertiary care hospital between 2005 and
2012. All Current Procedural Terminology (CPT) codes relevant to
non-oral/nasal surgical feeding tubes (43653, 43760, 43830, 43840,
43870, 44015, 44300, 44373, 44602, 44620, 44625, 44626, 49450-
49452) were used to abstract selected cases. The subjects medical
record was consulted to determine inclusion in the study if the sur-
geon identified a pre-existingly placed, feeding tube found dis-
lodged in the operating room. The types of feeding access investi-
gated included open gastrostomy, percutaneous endoscopically
placed gastrostomy (PEG), jejunostomy, percutaneous endoscopi-
cally placed jejunostomy (PEJ), and gastrostomy combined with je-
junostomy (G-J tube). These cases were selected for analysis irre-
spective of who (surgeon, interventional radiologist, gastroenterolo-
gist), where (ICU bedside, operating room, GI suite, IR suite), when
or how (percutaneous, fluoroscopic, open) the index tube placement
was placed. Demographic and clinical parameters were extracted
from the medical record and included age, sex, body mass index
(BMI), length of hospital stay and mortality.
Correspondence: Jose L Pascual
Email: jose.pascual@uphs.upenn.edu

Abstract
Background: Feeding tube dislodgement is common and timely detection is important to prevent peritoneal contamination. It is unknown
which imaging modality is preferable when tube dislodgement is suspected. We hypothesized that a bedside abdominal radiograph with
contrast via the feeding tube (TS) would be inferior to non-bedside imaging.
Methods: Current Procedural Terminology (CPT) codes involving repair/replacement of feeding tubes were queried at a tertiary care
hospital from 2005-12. Demographics, laboratory results and operative records were queried to obtain case details. Radiological studies
(TS, computed tomography [CT], fluoroscopy [FL]) obtained prior to laparotomy and time to surgery was evaluated.
Results: Of 1451 emergency surgical operative cases during the study period, 37 were identified to be operations for dislodged tubes
where 18 had tube removals only, two repairs, and 17 tube removals and replacements at an alternate site. Ten patients had no imaging
prior to laparotomy. The remainder underwent TS (6), CT (18) and FL (3) as first line imaging. First line imaging with TS was associated
with less subsequent operative contamination and a greater ability to maintain feeding access (p<0.05). Imaging correctly identified need
for surgery in 71%, 90% and 66% for TS, CT and FL respectively.
Conclusion: When feeding tube dislodgement is suspected, a bedside contrast tube study may not cause undue delays to the operating
room or lead to worsened peritoneal contamination. CT as a first line test is not more expeditious and may be associated with worsened
outcomes. Bedside tube studies are useful and often sufficient to lead directly to laparotomy. (El Med J 2:3; 2014)
Keywords: Dislodgement, Feeding Tube Complication, Gastrostomy, Imaging, Jejunostomy, Percutaneous Endoscopic Gastrostomy
Eisenstadt RG, Sensenig RL, Holena DN 185
http://www.mednifico.com/index.php/elmedj/article/view/203
Imaging prior to surgery for a dislodged feeding tube
General Electrics Centricity
TM
PACS database at the tertiary care hos-
pital (GE Healthcare Pty Ltd Piscataway, NJ) was searched for any
abdominal imaging techniques used in identified subjects prior to
the index surgery. Subjects were classified depending on which ra-
diological study, if any, was obtained first after suspicion of a dis-
lodged or leaking feeding tube was identified. This included a bed-
side abdominal radiograph with contrast injected via the tube (TS),
an abdominal/pelvis computed tomography with or without IV/PO
contrast (CT) or a formal GI radiology suite fluoroscopic study with
contrast injected through the tube (FL). Patients that did not un-
dergo any imaging study prior to transfer to the operating room
were also recorded. In imaged patients, any additional abdominal
imaging subsequently performed was also noted. For each imaging
study identified, the official radiologist report was used to ascertain
degree of certainty in identifying a dislodged or malpositioned tube.
Patient data
In an attempt to characterize the degree of physiologic derangement
prior to surgery, blood work results were compiled from each patient
in the 24 hours preceding operative intervention to correct tube dis-
lodgement. This included: renal function (maximal creatinine), sepsis
(maximal white blood cell count, [WBC]) and acidosis (maximal lac-
tate, minimal serum bicarbonate [HCO3]). To determine progression
or resolution of sepsis the same parameters were extracted from
medical records for the 48 hours following the index surgery.
Anesthesia, surgery and clinical records were examined to determine
operative details and severity of intraoperative sepsis and septic
shock. Through the review of the operative note, intra-operative ab-
dominal contamination was scored as severe (large/significant visi-
ble contamination evident upon opening, gross spillage), mild (some
contamination, not obvious on opening) or minimal (no contamina-
tion seen anywhere, clean abdominal cavity, no fluid seen). Tech-
nical details were reviewed to determine whether feeding access was
maintained and cases were classified as tube removals (R), tube site
repaired/revised with index tube left in situ (r) and tube removed,
site repaired/excised and a new tube placed at a different site (RR).
Time delay to reach the operating room from obtaining initial imag-
ing was determined as well as operative duration and need for intra-
operative vaso pressors (1 or more continuous infusions or more
than two boluses during the case) were recorded.
Statistical analyses
All data is presented as mean standard deviation. The Fisher's Exact
Test and Kruskal-Wallis Test were used to compare categorical and
nominal variables between groups, respectively. Two tailed statistical
significance was set at p < 0.05. SPSS version 19.0 (IBM Corporation,
Armonk, NY) was used for all data analyses.
Results
Demographics and operative cases queried
1451 coded operative procedures performed between 2005 and
2012 by the surgical services were reviewed as they had been iden-
tified with Current Procedural Terminology (CPT) codes relevant to
non-oral/nasal feeding tubes. Gender was equally distributed with
51.4% being males and mean age was 58 (19-91) years. Thirty-seven
operative cases were identified where the surgeon reported finding
a dislodged feeding tube (surgical PEG [n=20], IR PEG [n=4], open G-
tube [n=8], IR J-tube [n=1], open J tube [n=4]). Dislodgements oc-
curred < 2 weeks after placement (n =20), between 2-12 weeks after
placement (n=15), or >12 weeks after placement (n=1) (Table 1).
Length of time from original tube placement to repair of dislodge-
ment was significantly shorter in patients where first imaging choice
was TS (p=0.02). One patient transferred from another hospital had
no record of the original date of feeding tube placement. Surgical
procedures consisted in 18 tube removals (R), two tube sites repaired
with the tube left in situ (r) and 17 tubes removed and replaced in a
different site (RR).
Radiological imaging
Ten of the 37 patients identified did not undergo any imaging prior
to surgery and were taken directly for laparotomy (Table 2). Of the
remaining 27 cases, six first underwent a TS, 18 a CT scan and three
a fluoroscopic study in the GI suite. Of the imaged patients, four un-
derwent an additional imaging study to clarify the need for emer-
gent surgery. Three patients who had a TS subsequently underwent
a CT and one patient with an initial CT (without tube contrast) un-
derwent a TS. There were no significant differences in which initial
radiological test was selected in relationship to age, gender, or BMI
(Table 2).
Table 2: Demographics and major outcomes

No Studies
(n=10)
1
st
imaging: TS
(n=6)
1
st
imaging:
CT/FL (n=21)
Age 58.9 17.0 44.8 29.1 61.5 13.5
% Male 50.0 50.0 52.4
BMI 29.74 5.8 25.3 6.1 32.6 14.0
LOS (d) 69.9 60.7* 36.5 18.4 50.3 28.7
% Mortality 20.0 0.0 42.9
*No studies vs. TS: p=0.04
Table 1: Time from original tube placement and operation for correction of dislodgement

No Studies
(n=10)
1st imaging TS
(n=6)
1st imaging CT/FL
(n=20)*
P-value
(TS vs. CT/FL)
Elapsed time from tube placement to surgical correction (days) 34.8 75.3 8.3 2.7 22.4 18.9 (n=18) 0.02
Tube displaced <2 weeks after placement (%) 70.0 100.0 35.0 0.01
Tube displaced 2-12 weeks after placement (%) 20.0 0.0 65.0 0.01
Tube displaced >12 weeks after placement (%) 10.0 0.0 0.0 1.00
*In one patient who underwent a CT scan prior to surgery, the date of original tube placement could not be determined from the medical record

186 Ideal imaging for dislodged feeding tubes
Vol 2, No 3
Table 3: Radiological diagnosis and accuracy of findings
1
st
imaging: TS (n=6) 1
st
imaging: CT/FL (n=21) P (TS vs. CT/FL)
Required only 1 study (%) 50.0 95.2 0.02
If only 1 study, likelihood to identify dislodgement (%) 83.3 90.9 0.54
Elapsed time (from 1
st
study to OR) (hours) 6.7 5.4 10.7 9.1 0.48

Patients undergoing no studies prior to laparotomy had a signifi-
cantly greater hospital length of stay than those who underwent an
initial bedside tube study (TS). Imaging correctly identified the need
for laparotomy in 90% (19/21) of the CT group, 71% of cases of the
TS group (5/7) and in 67% of cases using fluoroscopy in the radiology
suite (2/3). Half of patients that obtained a TS as the first line study
required a second study (CT in all cases), whereas only one of the
cases where CT was used initially, a confirmatory TS was subse-
quently required (p=0.02) (Table 3).
Clinical parameters
Patients preoperative WBC count, renal function and acid base sta-
tus did not differ regardless of which imaging was chosen first (Table
4). The lowest mean WBC count was in the TS group and the highest
creatinine, in the CT group but these levels did not differ significantly
from values in the other groups. Laboratory bloodwork sample sizes
were small particularly in patients undergoing no radiographic stud-
ies prior to surgery.
Postoperative renal failure, sepsis and acid-base status
Postoperative laboratory studies were similar across groups for the
48 hours that followed surgery (Table 5). Change from preoperative
levels for all parameters in each patient group (worsening or improv-
ing) was also not found to be significantly different, (data not
shown).
Time to reach the operating room
The time interval from first imaging study to start of operation was
also evaluated for each 1st line imaging modality. When (TS) was
used 1st, mean time to the operating room was 6.7 5.4 hours,
regardless of whether a second imaging test was used. When TS was
the only imaging modality used the average time was 6.0 7.3 hours
but when non-bedside studies were used (CT/FL) alone the average
time to surgery was 10.9 9.3 hours, but differences in these time
intervals to the operating room were not statistically significant. Of
note, if the first imaging was a TS, obtaining a subsequent CT scan
did not add a significant delay to surgery (p = 0.96).
Intraoperative Status
Three operative surrogate markers of degree of peritoneal contami-
nation were evaluated: Length of operation, peritoneal leakage de-
scribed and ability to maintain feeding access. The average duration
of surgery was 184 47 minutes when no radiological studies were
performed, 190 80 minutes with an initial bedside (TS) and 182
74 minutes with an initial CT or FL study (Table 6). As compared with
non-bedside imaging, obtaining a bedside TS study prior to surgery
was associated with a significantly lower chance of having severe
abdominal contamination (0.0% vs.57.1%, p=0.02) as described in
operative notes by the surgeon. Hospital length of stay did not differ
among imaged groups. However, patients undergoing a bedside TS
as the first line study retained their feeding access more often than
those who underwent other imaging studies prior to surgery
(p=0.03). Of note, patients going directly to surgery without imaging
also had feeding access maintained more often than those undergo-
ing non-bedside imaging (p=0.03). The no studies group required
intra-operative vasopressor support more often than the (TS) group,
though these differences were not statistically significant.
Discussion
Enteral feeding access is often required in chronically ill patients and
subsequent complications are common and potentially serious [8, 9,
15]. One retrospective study evaluating 96 feeding jejunostomies
placed surgically found 11 cases where complications occurred fol-
lowing tube dislodgment [9]. Additionally, in a retrospective review
evaluating the natural history of more than 500 PEG tubes placed in
a three year period, the rate of lifetime accidental tube dislodgement
was 12.8% with more than half of these occurring after patients were

Table 4: Blood work obtained in the day (within 24 hours) prior to surgery
Lab Value (mean SD) No Studies 1
st
imaging: TS 1
st
imaging: CT/FL
Max WBC (x 10
3
/L) 14.5 6.0 11.6 3.5 15.6 10.1
Max creatinine (mg/dl) 1.15 1.0 1.23 1.6 1.75 1.1
Max lactic acid (mg/dl) 5.5 3.4 5.8 3.5 3.8 3.5
Min HCO3
-
(mmol/L) 22.1 5.0 22.0 6.3 24 7.0

Table 5: Blood work obtained in the 48 hours following surgery
Lab Value (mean SD) No Studies 1
st
imaging: TS 1
st
imaging: CT/FL
Max WBC (x 10
3
/L) 14.6 5.9 14.2 4.3 16.6 7.4
Max creatinine (mg/dl) 1.19 0.9 1.76 2.7 2.24 2.1
Max lactic acid (mg/dl) 4.8 3.3 1.9 0.2 4.1 4.8
Min HCO3
-
(mmol/L) 22.0 4.9 23.2 2.0 20.7 5.7

Eisenstadt RG, Sensenig RL, Holena DN 187
Table 6: Intraoperative status
No Studies (n=10) 1st imaging TS (n=6) 1st imaging CT/FL (n=21) P (TS vs. CT/FL)
Severe OR contamination (%) 20.0 0.0 57.1 0.02
Mild OR contamination (%) 20.0 33.3 23.8 0.63
Minimal OR contamination (%) 60.0
#
66.7 19.1 0.04
Feeding access maintained [r/RR] (%) 80.0
#
83.3 28.6 0.03
Feeding Access removed [R] (%) 20.0 16.7 71.4 0.03
Length of surgery (min) 184.1 46.7 189.5 79.6 182 74.1 0.84
Intraoperative use of pressors (%) 60.0 50.0 81.0 0.29
#
NO vs. CT: p<0.05
discharged from the hospital [8]. Though only a third of these dis-
lodgements occurred within a week of placement, the vast majority
required a radiographic confirmation of tube positioning and surgi-
cal intervention, resulting in an average charge of $1200 per dis-
lodgement.
Dislodgement can lead to significant abdominal sepsis and death.
The surviving sepsis campaign has established the importance of
rapid source control in sepsis and therefore, early diagnosis of dis-
lodgement may be critical to patient survival [16, 17]. Most cases of
peritonitis require laparotomy for gastrotomy/enterotomy closure
and peritoneal cavity irrigation [18]. Tube dislodgement may also
lead to abdominal wall necrotizing infection [19]. While we could not
find any previously published comparison of different radiographic
techniques used in evaluating tube dislodgements, considerable re-
search has been done to determine what imaging modality is most
helpful in the diagnosis of abdominal sepsis [20, 21].
We hypothesized that a TS would prove inferior to CT in the rapid
diagnosis of tube dislodgement. Contrary to our suspicion, only half
of patients who initially underwent a TS required a confirmatory CT.
On the other hand, virtually none of those who underwent a CT re-
quired further imaging.
Ten of 37 patients went directly to the operating room without im-
aging. This may have occurred because they were too ill to wait for
imaging or because they already displayed signs of peritonitis. Their
significantly longer LOS would argue they were a cohort of more se-
verely ill patients. Yet, we were unable to demonstrate that this co-
hort demonstrated worse laboratory work pre or post-operatively. In
fact, this group demonstrated less peritoneal contamination intra-
operatively and was more likely to maintain feeding access at the
index operation. It is difficult to interpret the overall severity of illness
in this group but the diminished intraoperative contamination was
perhaps due to a more expeditious transferred to the operating
room resulting in a better outcome at the index surgery.
Obtaining a TS as the first imaging study also was associated with
finding less abdominal contamination and a greater likelihood of
maintaining feeding access, regardless of whether or not an addi-
tional imaging study was required. This was the case even though
time delay between initial feeding tube placement and surgical cor-
rection of dislodgement was the shortest; in all cases where TS was
obtained as a first line study the index tube had been placed in the
preceding two weeks. These would be considered tubes where the
cutaneous tract may have been immature and risk of contamination
the greatest. Mean transfer time to surgery in the TS group was 30%
lower than when using CT as first imaging but this was not statisti-
cally significant. Mean hospital length of stay in patients obtaining
TS first was the lowest of all groups and significantly shorter than
that of patients transferred directly to the operating room without
imaging.
CT scanning as the first line of imaging in patients who required lap-
arotomy was 90% accurate for demonstrating tube dislodgement or
malposition. Furthermore, only in one instance was an additional im-
aging study required. However, delay to surgery tended to be longer
and intraoperative findings demonstrated more advanced contami-
nation with a lower likelihood of maintaining feeding access in this
group. The association between less intraoperative abdominal con-
tamination and likelihood of maintaining tube presence was likewise
demonstrated in both no studies and TS groups. Imaging first with
a TS may thus be more expeditious and result in less ongoing con-
tamination than with a CT scan, but is less accurate.
To our knowledge no other study has examined patterns of imaging
techniques when feeding tube dislodgement is suspected and may
require immediate surgery. Nonetheless this small study has a num-
ber of limitations. First, the sample size was small and this despite
combining the 7-year experience of three surgical services in a ter-
tiary care academic center. Second, our data does not capture how
the degree of physiologic derangement seen in these patients im-
pacts initial imaging choices. Despite our finding of similar septic and
renal laboratory work preoperatively in all groups, knowing systemic
markers of illness such as vital signs or the Acute Physiology and
Chronic Health Evaluation (APACHE) scores would have been prefer-
able. However, only a few of these patients were in an ICU setting
preoperatively and our institution does not record APACHE scores in
non-ICU patients. Also, controlling for comorbidities would have
been helpful. Third, different CT scan protocols exist and could po-
tentially have affected the diagnosis of a dislodged tube. Our study
had too few patients to allow subgroup analyses in patients where
the CT scan involved oral or IV contrast or a combination of both.
Lastly, our study did not evaluate the utility of imaging to diagnose
and intervene in tube dislodgements that did not go to the operat-
ing room. Patients who had a tube dislodged, replaced and con-
firmed with imaging were not evaluated.
Conclusion
In conclusion, we have shown in a small retrospective study that
there are few drawbacks to first obtaining a bedside tube study in
patients who are suspected of having a dislodged feeding tube and
188 Ideal imaging for dislodged feeding tubes
Vol 2, No 3
do not otherwise require immediate transfer to the operating room.
Whether this may result in a faster transfer to the operating room
and result in less progression of abdominal contamination and a
greater chance to maintain feeding access will need further study.
We have shown that an initial TS will require a confirmatory radio-
logic study far more often than a CT scan. However, a bedside TS is
a quick and easy study to perform and in half of cases, provides suf-
ficient information to proceed to immediate surgical intervention. If
it is inconclusive a CT scan should be obtained. A prospective study
with greater sample size will be necessary to determine the validity
of this practice.
Competing interests: The authors declare that no competing interests exist.
Received: 10 June 2014 Accepted: 22 July 2014
Published Online: 22 July 2014
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2014 Aitken et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Aitken SA, McQueen MM, Court-Brown CM: The epidemiology of fractures around the elbow joint. El Mednifico Journal 2014, 2(3): 189-194.
The epidemiology of fractures around the elbow joint
Stuart A Aitken
1
, Margaret M McQueen
1
, Charles M Court-Brown
1

Introduction
The epidemiological characteristics of distal humerus, proximal ulna
and proximal radius fractures have been described by a number of
authors, analyzing distinct populations over differing time periods
[1-10]. With changing population demographics, it has been pro-
posed that the incidence of certain elbow fracture subgroups will
change considerably in the future, particularly in older adult groups
[2]. In addition, the relationship between socioeconomic deprivation
and adult fracture incidence has been identified [11].
The aim of this study was to capture and define the incidence and
causes of all elbow fractures in our adult population over a one-year
period. The secondary aim was to identify any potential relationship
between the epidemiology of elbow fractures and socioeconomic
deprivation.
Materials and Methods
Regional ethics committee approval was not required for this retro-
spective analysis of prospectively collected trauma data. Our institu-
tion receives all adult trauma (patients 15 years and older) for the
regional population. Data on all patients presenting with acute frac-
tures were prospectively recorded by one author (SAA, SORT-IT
trauma fellow) for a 12-month period, beginning 1
st
July 2007. Pa-
tients residing outwith the region were excluded from analysis. Pa-
tients aged less than 15 years were treated at a separate pediatric
institution, and were unavailable for analysis. During the study pe-
riod the population at risk numbered 545,081 (47.5% men) [12].
Demographic (age, gender, socioeconomic status) and trauma data
(injury mode, fracture classification, associated skeletal injuries) were
recorded prospectively for each patient. A database search identified
all patients who had sustained acute fractures of the distal humerus,

1
The Orthopedic Trauma Unit, Royal Infirmary of Edinburgh, Edinburgh, Scotland,
UK.
Correspondence: Stuart Aitken
Email: stuart.aitken@nhs.net
proximal radius or proximal ulna. For the purposes of analysis, any
combination of ipsilateral elbow fractures was defined as a com-
bined fracture.
Radiographic classification
Standard radiographs of the elbow consisted of antero-posterior and
lateral views. The distal humerus was defined according to the crite-
ria set out by Muller (... that part of the bone that lies within a
square, whose base is the distance between the medial and lateral
epicondyles, on an antero-posterior radiograph), and fractures of
this region were classified according to the AO comprehensive long
bone classification system [13, 14]. Olecranon fractures and coronoid
fractures were described using the Mayo and Regan and Morrey clas-
sification systems, shown in Figures 1 and 2, respectively [4, 5]. Frac-
tures of the radial head and neck were classified by the system orig-
inally presented by Mason, but later modified by Johnston, then Mor-
rey [8, 15, 16].
Socioeconomic deprivation
Deprivation data for the population at risk were obtained from Scot-
tish Government sources [17]. The Scottish Index of Multiple Depri-
vation (SIMD) uses income, employment, health, education, skills
and training, housing, geographic access to services, and crime data
to calculate a deprivation index. The SIMD identifies small area con-
centrations of deprivation based on postal code groupings, known
as datazones. Datazones are ranked nationally from the most de-
prived to the least deprived areas, and are subsequently allocated to
one of five groups (or quintiles). Quintile 1 represents the most de-
prived regions and quintile 5 the least deprived. The population at
risk within each quintile was derived from Scottish government data,
allowing the calculation of fracture incidence in relation to the SIMD.

Abstract
Background: The epidemiology of fractures of the distal humerus, proximal ulna and proximal radius has been individually studied. We
sought to determine the epidemiological characteristics of all adult elbow fractures in our region, and look specifically for a relationship
between their incidence and socioeconomic deprivation.
Methods: We analyzed a prospectively collected trauma database from an institution serving a population of 545,000 adults. The
demographic, injury and deprivation details for all patients suffering acute fractures of the distal humerus, proximal radius or proximal
ulna were analyzed. Fractures were classified according to the AO, Mayo, Regan and Morrey, and modified Mason systems. Deprivation
status was determined by using the Index of Multiple Deprivation.
Results: We identified 405 elbow fractures in 382 patients, with an incidence of 7.4/10,000/yr. The incidence was higher in women,
particularly in the elderly. In men the distribution was bimodal. Distal humerus, proximal ulna and proximal radius fractures displayed
distinct epidemiological characteristics. A correlation was identified between increasing proximal forearm fracture incidence with
increasing levels of deprivation.
Conclusion: This report documents the current age-related incidence of these injuries and adds to the growing body of evidence that
socioeconomic status influences the rate and patterns of skeletal injury in adults. Future work should examine whether the epidemiological
characteristics of these injuries continue to change as our population demographics evolve over time. (El Med J 2:3; 2014)
Keywords: Epidemiology, Deprivation, Distal Humerus, Radial Neck, Radial Head, Coronoid, Olecranon, Fracture, Edinburgh, Scotland
190 The epidemiology of fractures around the elbow joint
Vol 2, No 3

Figure 1: The Mayo classification of olecranon fractures [4]. Type
3 fractures are associated with ulno-humeral joint instability.

Figure 2: The Regan and Morrey classification of fractures of the
coronoid process [5]. Type I an avulsion of the tip of the coro-
noid process. Type II a single or comminuted fragment involv-
ing 50% of the process, or less. Type III a single or comminuted
fragment involving more than 50% of the process.
Statistical analysis
The 95% confidence interval (CI) around the fracture incidence
(n/10,000/yr) was estimated using the cumulative Poisson distribu-
tion. Age was found to be asymmetrically distributed, according to
the Kolmogorov-Smirnov test, and was therefore presented in terms
of the median and interquartile range (IQr). Median values between
groups were compared using the Mann-Whitney U (MWU) test for
dichotomous variables (gender, fracture subtype), the Kruskal-Wallis
(KW) test for variables with three or more groups (injury mode, frac-
ture type). Categorical variables were compared using the Chi square
test. The Jonckheere-Terpstra (JT) test was used to compare values
across ordinal categories (Mason fracture types, SIMD quintiles). A
two-tailed p-value of <0.05 was considered statistically significant,
and p <0.1 a statistical trend. Spearmans correlation coefficient (rho)
for ordinal data was calculated to reflect the extent of a linear rela-
tionship between deprivation quintile and fracture incidence. The
strength of correlation was described as strong (r=0.5-1.0), moderate
(r=0.30-0.49) or weak (r0.29) according to the guidelines of Cohen
[18].
Results
A total of 405 elbow fractures was sustained by 382 patients (55%
women), accounting for 10% of upper limb fractures and 6% of all
adult fractures identified. Elbow fracture incidence was 7.4/10,000/yr
(CI 6.7-8.2), and was higher in women (7.8/10,000/yr, CI 6.8-8.8) than
in men (7.1/10,000/yr, CI 6.1-8.1). The resultant fracture distribution
curve shows a bimodal incidence in men and unimodal incidence in
older women (Figure 3).

Figure 3: The distribution curve for fractures around the elbow
joint in Edinburgh adults.
There were 46 isolated fractures of the distal humerus, and three fur-
ther combined fractures sustained with ipsilateral proximal radius
fractures. There were 66 isolated fractures of the proximal ulna, and
13 combined fractures. Radial head and neck fractures numbered
263, with seven patients suffering bilateral injuries, and one patient
sustaining a recurrent radial head fracture several months after his
index injury. An additional 15 cases were combined fractures. The
frequency of open fractures was low (n=5 patients, 1.3%). The distri-
bution of fractures around the elbow, and the gender-related inci-
dences, are shown in Table 1.
Distal humerus
Two-thirds of isolated distal humerus fractures occurred in adults
aged 55 years or older (n=30), with a simple fall from standing ac-
counted for 90% of cases, and 83% occurring in women. Fractures
affecting patients aged less than 55 years (n=16) occurred more of-
ten in men (69%) and 44% were caused by a simple fall. The remain-
der resulted from sporting activity, RTAs or direct blows. Table 2
shows the distribution of extra-articular (type A), partial articular
(type B) and complete articular (type C) fractures, according to the
AO classification [14].
The 13-A2 subtype, denoting a simple extra-articular metaphyseal
fracture, occurred predominantly in older women. The 13-A1
apophyseal avulsion fractures more frequently involved the medial
epicondyle (83%), and affected younger male patients. Five partial
articular fractures occurred in the sagittal plane (subtypes B1 and
B2), with a further five identified as coronal plane shear fractures
(subtype B3). Type C fractures represented the smallest group, and
all occurred as a result of a low energy fall from standing.

0
10
20
30
n/
10,000/
yr
Age group (yrs)
Fractures around the elbow
joint
Male
Aitken SA, McQueen MM, Court-Brown CM 191
Table 1: The overall incidence and distribution of fractures around the elbow joint in the adult Edinburgh population.
Distal humerus Proximal ulna Proximal radius Combined fractures p-value
Fractures (n, %) 46 (11.4) 66 (16.3) 263 (64.9) 30 (7.4) -
Gender ratio (M:F, %) 35:65 47:53 47:53 33:67 p=0.087*
Incidence (n/10,000/yr) Male 0.6 (0.3-1.0) 1.2 (0.8-1.7) 4.9 (4.1-5.8) 0.2 (0.1-0.5)
-
Female 1.0 (0.7-1.5) 1.2 (0.8-1.7) 4.8 (4.0-5.7) 0.3 (0.2-0.6)
Median age (yrs, IQr) 71.5 (36-83) 59 (36-75.5) 43 (28-56) 58 (30-85) p<0.001
Men 28 (16-63) 53 (29-70) 37 (23-47) 42 (27-67.5) p=0.207
Women 78.5 (62-85) 72 (42-78) 51.5 (33-63) 69.5 (49-86) p<0.001
Mode of injury (n, %) Simple fall 34 (73.9) 43 (65.2) 145 (55.1) 21 (70.0)
p=0.017*
Sports-related 4 (8.7) 6 (9.1) 45 (17.1) 0 (0.0)
Direct blow 1 (2.2) 4 (6.1) 6 (2.3) 2 (6.7)
Other 3 (6.5) 1 (1.5) 10 (3.8) 1 (3.3)
RTA 4 (8.7) 4 (6.1) 32 (12.2) 0 (0.0)
Fall down stairs 0 (0.0) 5 (7.6) 11 (4.2) 4 (13.3)
Fall from a height 0 (0.0) 3 (4.5) 14 (5.3) 2 (6.7)
Open injuries (n, %) 0 (0.0) 3 (4.5) 0 (0.0) 4 (13.3) p<0.001*
*Chi square test; KW test; RTA= road traffic accident.

Table 2: The distribution of distal humerus fractures by AO group. The frequency of elbow dislocation at the time of presentation
is also shown.
Fracture groups Number (%) Mean age (yrs, range) M (n) F (n) % with elbow dislocation % from RTA / Height
A1 12 40.4 (15-90) 7 5 25.0 25.0
A2 18 78.7 (38-93) 4 14 0 0
A3 2 71.0 (57-85) 0 2 0 0
All type A 32 (69.6) 63.8 (15-93) 11 21 9.4 9.4
B1 3 36.0 (16-60) 3 0 0 0
B2 2 85.0 (82-88) 0 2 0 0
B3 5 48.4 (16-81) 1 4 0 20.0
All type B 10 (21.7) 52.0 (16-88) 4 6 0 10.0
C1 2 50.5 (22-79) 1 1 0 0
C2 2 55.0 (37-73) 0 2 0 0
C3 0 - - - - -
All type C 4 (8.7) 52.8 (22-79) 1 3 0 0
Total 46 (100) 60.3 (15-93) 16 30 6.5 8.7
RTA= road traffic accident; Height= fall from a height.

Proximal ulna
Isolated proximal ulna fractures were distributed evenly between
men and women, and Table 3 shows there distribution. The median
age of men was 50 yrs (IQr, 29-69); ten years older than for other
elbow fractures. The median age of affected women was 72 years
(IQr, 45-78). Despite its subcutaneous nature, only three open proxi-
mal ulna fractures (4.5%) were identified.
Proximal radius
Two thirds of adult elbow fractures involved the proximal radius.
Male incidence peaked in those aged 35 to 39 years with female in-
cidence greatest in those aged 65 to 69 years. The frequency of high
energy trauma (RTAs, falls from height, sports-related injury) was
greater in men than in women (p<0.001, Chi square test). Isolated
radial head fractures outnumbered those of the radial neck by ap-
proximately two to one, although the frequency of patients with as-
sociated fractures was similar for both subtypes.
Combined elbow fractures and associated injuries
Thirty combined elbow fractures were sustained by 15 patients as a
result of 15 accidents. The proximal radius was involved in each case
(14 radial head and one radial neck fracture). The associated injuries
involved the olecranon (n=4), coronoid process (n=4), olecranon
plus coronoid (n=2), distal humerus (n=3) and fracture of the ulnar
shaft just distal to the coronoid (n=2). Seven patients sustaining
combined elbow fractures had suffered an elbow dislocation. There
were nine elbow dislocations seen in the isolated proximal radial
fracture group (the Mason type 4 injuries). In total, the frequency of
elbow dislocation with all proximal radius fractures in this series was
5.8%.
Vol 2, No 3
Table 3: The distribution of fractures of the proximal ulna. NB. One fracture was not classified due to unavailable radiographs.
Subtype (n) (%) M (n) F (n) Mean age (yrs, range) % RTA / Height % open fractures
Mayo 1A 8 12.3 3 5 47.3 (15-80) 12.5 0
1B 3 4.6 2 1 47.7 (21-75) 0 0
2A 29 44.6 15 14 58.6 (16-97) 3.4 3.4
2B 15 23.1 5 10 60.6 (31-90) 20.0 0
3A 0 - - - - - -
3B 1 1.5 1 0 25 100 100
All olecranon 56 86.1 26 30 56.3 (15-97) 9.1 3.6
Type I 5 7.7 3 2 44.0 (18-68) 20.0 0
Type II 0 - - - - - -
Type III 2 3.1 2 0 46.5 (29-64) 0 0
All coronoid 7 10.8 5 2 44.7 (18-68) 14.3 0
Extra-articular 2 3.1 0 2 77.0 (74-80) 0 0
All 65 100 31 34 55.7 (15-97) 10.8 3.1
RTA= road traffic accident; Height= fall from a height.

Table 4. The distribution of proximal radius fractures according to the modified Mason classification system.
Mason 1 Mason 2 Mason 3 Mason 4 p-value
Fractures (n, %) 209 (74.9) 42 (15.1) 11 (3.9) 17 (6.1) -
Gender ratio (M:F, %) 48:52 50:50 64:36 53:47 p=0.76*
Median age
(yrs, IQr)
43 (27-56) 46 (35-57) 42 (37-65) 55 (31-68) rho=0.12, p=0.04
p=0.043
JT

% associated
fractures
14.4 14.3 36.4 47.1 p=0.002*
*Chi square test; rho= Spearmans correlation coefficient, with associated p-value; JTJonckheere-Terpstra test.

Table 5: The association between the distribution and incidence of elbow fractures and socioeconomic deprivation. Incidence is
presented as n/100,000/yr.
IMD Population Distal humerus #s Prox ulna #s Prox radius #s
quintile n (%) n (%) Incidence n (%) Incidence n (%) Incidence
1 57,247 (11) 10 (21) 17.5 14 (22) 24.5 31 (12) 54.2
2 89,280 (17) 5 (10) 5.6 12 (19) 13.4 53 (20) 59.4
3 89,910 (17) 11 (23) 12.2 10 (16) 11.1 47 (18) 52.3
4 99,476 (18) 9 (19) 9.1 8 (12) 8.0 41 (15) 41.2
5 201,518 (37) 13 (27) 6.5 20 (31) 9.9 93 (35) 46.1
The expected pro-
portion
*p=0.1 rho= -0.4
p= 0.51
*p=0.07 rho= -0.9
p= 0.04
*p=0.59 rho= -0.8
p= 0.1
*Chi square test; rho= Spearmans correlation coefficient, with associated p-value.

Thirty two of 263 (12.2%) isolated proximal radius fractures, and four
of 30 (13.3%) combined elbow fractures, were associated with frac-
tures outwith the elbow region. Proximal radius fractures were ana-
lyzed according to Masons classification, where increasing fracture
complexity was associated with increasing frequency of associated
fractures, and a progressively older patient group (Table 4).
Socioeconomic deprivation
The distribution of elbow fractures did not vary across quintiles of
deprivation (p=0.2, Chi square test). However, analysis of proximal
ulna fractures revealed an inverse linear relationship (rho= -0.9) be-
tween incidence and deprivation category; their incidence increased
with increasing levels of deprivation. A stronger correlation seen in
men (rho= -0.7) than in women (rho= -0.6), (Table 5). There was a
statistical trend towards a similar correlation between proximal ra-
dius fracture incidence and deprivation. Patient age varied signifi-
cantly across the quintiles; the most deprived patients suffered el-
bow fractures at a younger age than the least deprived (p=0.02, JT
test).
Discussion
Approximately 5% to 7% of fractures in adults occur around the el-
bow joint, and we have documented the epidemiological character-
istics of distal humerus, proximal ulna and proximal radius fractures
in our adult population [6, 19].
Aitken SA, McQueen MM, Court-Brown CM 193
Distal humerus fractures represent challenging orthopedic injuries,
especially as they occur in predominantly older adult groups. The
literature has documented the increase in their incidence, although
recent Finnish work suggests this trend may be stabilizing [1, 2]. Rob-
inson et al studied distal humerus fractures in Edinburgh adults be-
tween 1988 and 1997, reporting an incidence of 0.5/10,000/yr dis-
tributed equally between men (mean age 37 yrs) and women (mean
age 60 yrs) [3]. Fifteen years later, we have reported an increased
proportion (65%) of older women (aged 78 yrs) and an increased
overall incidence (0.8/10,000/yr, CI 0.5-1.1). These differences should
be interpreted with caution, however, due to small patient numbers
and the limited data capture period of our study. The distribution of
AO fracture type reported by Robinson (type A 39%; type B 24%;
type C 37%) differs from that reported here (70% / 21% / 9%), but it
must be noted that Robinson used standard radiographs supple-
mented by intra-operative findings to determine the fracture types
[3]. We accept that subtle intra-articular split fractures can be difficult
to identify on plain radiographs and may have been misdiagnosed
as type A injuries.
The AO classification of proximal forearm fractures combines injuries
of the proximal ulna with those of the proximal radius, and is not
particularly useful. We have used the Mayo system, as proposed by
Morrey, for fractures of the olecranon process [4]. It is useful in that
it distinguishes factors that have a direct influence on treatment,
namely fracture displacement and comminution. Twenty percent of
these injuries were undisplaced (Mayo type 1), and approximately
half of these involved comminution of the trochlear notch (type 1B).
Displaced fractures (type 2) were more common, accounting for 80%
of olecranon fractures. Despite displaced fractures occurring in an
older patient group, we found no higher frequency of comminution.
Fractures of the coronoid process are rare injuries, reported to occur
in 2% to 10% of patients who suffer a dislocation of the elbow. They
may also present as isolated injuries following a subtle subluxation
event [5]. Current opinion would suggest that a varus posteromedial
force produces a fracture of the tip of the coronoid (Regan and Mor-
rey type I), whereas a posteriorly directed force can produce any-
thing from a tip fracture to a larger single fragment (type II and III)
[6].
Fractures of the proximal radius were originally reported as occurring
almost exclusively in young men, but subsequent epidemiological
work has shown this is no longer the case [7-10, 20]. van Riet et al
reported on 333 radial head fractures in adults from 1997 to 2002,
with a mean age of 45 years [10]. Kaas and colleagues retrospectively
reviewed a series of patients (60% women) between 2006 and 2008,
where women represented an older cohort (mean age 53 yrs) when
compared with men (mean 41 yrs) [7]. We found a similar gender-
related pattern in our population, although it must be noted we in-
cluded fractures of the radial neck.
Our reported frequencies of Mason type 1 (75%), type 2 (15%), type
3 (4%) and type 4 (6%) fractures are consistent with the literature.
We have identified a weak correlation between increasing proximal
radius fracture severity and increasing patient age, a relationship that
other authors have suspected might exist [7]. Admittedly, when ra-
dial neck fractures are excluded from the same statistical analyses,
the result becomes a trend only (p<0.1 for Spearmans correlation
and Jonckheere-Terpstra tests). The frequency of associated bony in-
jury at the time of proximal radius fracture ranges from 10% to 23%
[7, 10, 20]. We, and others, have shown that associated injury is more
commonly encountered with increasingly severe fractures [7].
A number of studies have described the influence of socioeconomic
deprivation on fracture epidemiology [21-23]. We have identified a
strong correlation with increasing deprivation and proximal ulna
fracture incidence, and a similar trend was seen in relation to the
proximal radius. In keeping with other authors reports on hand in-
juries, the relationship seems more pronounced in male patients [21,
23]. This suggests that the causative factors are less related to prob-
lems with skeletal health and bone mineral density, and are more
likely related to patterns of behavior that confer a greater risk of skel-
etal injury.
Conclusions
We have defined the epidemiology of all elbow fractures identified
in our adult population, and explored the association between frac-
ture incidence and deprivation. This report documents the current
age-related incidence of these injuries and adds to the growing body
of evidence that socioeconomic status influences the rate and pat-
terns of skeletal injury in adults. Future work should examine
whether the epidemiological characteristics of these injuries con-
tinue to change as our population demographics evolve over time.
Source of funding: No external funding source was used for this study.
Disclaimer: No benefits of any form have been received or will be received from a
commercial party related directly or indirectly to the production of this article.
Ethics committee approval was not required and this study was defined as audit
according to regional guidelines.
Acknowledgment: We would like to thank the Scottish Orthopaedic Research Trust
into Trauma (SORT-IT) for their assistance in performing this study.
Received: 16 May 2014 Accepted: 6 August 2014
Published Online: 6 August 2014
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2014 Hasan et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Hasan A, Ashraf MU, L NAC, Parvez A: Clinical and echocardiographic study of patients in heart failure with a normal/near normal ejection fraction. El Mednifico Journal 2014, 2(3): 195-199
Clinical and echocardiographic study of patients in heart failure with a normal/near normal ejection
fraction
Asif Hasan
1
, Muhammad Uwais Ashraf
1
, Nazih Ahmad C L
1
, Anjum Parvez
1

Introduction
Heart failure affects more than twenty million people worldwide. The
overall prevalence of heart failure is thought to be increasing. One
of the reasons behind an increase in the prevalence of heart failure
is the advent of newer therapies for cardiac disorders which allow
patients to survive longer. Although heart failure was previously
thought to arise primarily in the setting of a depressed left ventricu-
lar ejection fraction, epidemiological studies have shown that ap-
proximately one-half of the patients who develop heart failure have
a normal or near normal ejection fraction i.e. HFNEF [1].
Previous studies have defined the prevalence of HFNEF in various
heart failure populations and have documented a population of 50
to 55% [2-4]. Also, the prevalence of HFNEF among patients with
heart failure varies dramatically with age and gender [5]. The precise
underlying pathophysiology of HFNEF is still debatable. Recent work
has demonstrated that abnormalities exist in LV systolic properties,
ventricular-arterial coupling, LV diastolic function, ventricular-ven-
tricular interaction, pericardial constraint and pulmonary hyperten-
sion.
The diagnosis of HFNEF is difficult as compared to those with re-
duced ejection fraction, and so is the treatment. HFNEF is a complex

1
Department of Medicine, J N Medical College, Aligarh, India
Correspondence: Muhammad Uwais Ashraf
Email: uwaisashraf@gmail.com
syndrome. It is caused by diastolic ventricular dysfunction demon-
strated by complementary methods. It affects primarily the elderly
individuals with co-morbidities such as hypertension, diabetes, obe-
sity, renal dysfunction, atrial fibrillation etc. Clinical scenario is wors-
ening grade of dyspnea, pedal edema and episodes of pulmonary
edema.
The echocardiogram is a very useful method of diagnosing structural
alterations, abnormal filling, impaired relaxation and restrictive filling
associated with diastolic dysfunction. The pulsed Doppler allows the
analysis of transmitral diastolic flow, which allows determination of
primary function indices and stratification of dysfunction severity [6].
The analysis of flow in the pulmonary veins through the pulsed Dop-
pler allows the indirect assessment of the atrial pressure, which, in
the absence of mitral valvulopathy, corresponds to the LV diastolic
pressure. The normal LA pressure allows a constant flow from the
pulmonary veins, except during the atrial contraction, when there is
small reverse flow.
Since many patients of HFNEF present with breathlessness and no
signs of fluid overload, symptoms are considered sufficient clinical
evidence to suggest the presence of congestive heart failure, even
in the absence of signs. Non-invasive diagnostic evidence of diastolic

Abstract
Background: Heart failure affects more than twenty million people worldwide. Epidemiological studies have shown that approximately
one-half of the patients who develop heart failure have a normal or near normal ejection fraction. The diagnosis of heart failure with a
normal ejection fraction (HFNEF) is difficult as compared to those with reduced ejection fraction, and so is the treatment. It is caused
by diastolic ventricular dysfunction demonstrated by complementary methods. It affects primarily the elderly individuals with co-
morbidities such as hypertension, diabetes, obesity, renal dysfunction, atrial fibrillation etc. The aim of this research was to study the
clinical and echocardiographic profile of patients in heart failure with a normal/near normal ejection fraction.
Methods: This was a prospective, open-labeled, observational study conducted on 70 subjects. All patients with suspected heart failure,
fulfilling the Framingham criteria were included in the study. Patients with a reduced ejection fraction (<40%) were excluded from the
study. A detailed history, thorough medical examination and Doppler echocardiography were carried out on all the patients. LVDD
grade 1-4 was determined by detailed echocardiographic study (pulsed wave and tissue Doppler studies).
Results: The mean age of patients was 64.84 11.59 years. Maximum number of patients was observed in the 61-70 year age group.
The majority of patients were females i.e. 38 out of 70 (54.3%). 36 patients were hypertensive (51.4%), 38 had a history of coronary
artery disease (54.3%) and 21 patients had a history of diabetes mellitus (30%). 40% patients had a serum creatinine level of >1.2 mg%.
Mean creatinine was 1.35 0.65 mg%. 63% patients in the study group were anemic with a mean hemoglobin level of 11.3 2.27 g%.
57% of the cases had HbA1c 5.7% of which, 28% had HbA1c in the pre-diabetic range. 16 patients (22.85%) had a history of atrial
fibrillation. 22.8% patients had left ventricular diastolic dysfunction (LVDD) grade 1, 54.3% patients had LVDD grade 2, 20% has LVDD
grade 3 and 2.85% had LVDD grad 4. 16 cases had a prolonged deceleration time (DT), with a mean DT of 225 ms. In cases of mild
diastolic dysfunction due to impaired relaxation, IVRT was prolonged. Mean IVRT values in the LVDD grade 1 was 119 ms. The
echocardiographic indices of restrictive cardiomyopathy showed an E/A ratio of >2.4 (mean 2.76) and E/e >15 (mean 17.51). IVRT was
markedly reduced in patients with restrictive cardiomyopathy (mean IVRT was 51.09 ms).
Conclusion: In the current study, we have seen that heart failure with normal or near normal ejection fraction is more common in
females and in the elderly. Hypertension, diabetes mellitus, renal dysfunction, thyroid disorders and atrial fibrillation are associated
commonly with HFNEF. Abnormal relaxation, pseudonormal filling pattern and restrictive filling are the mechanisms responsible for
diastolic dysfunction. (El Med J 2:3; 2014)
Keywords: Heart Failure, Ejection Fraction, Echocardiography
196 Heart failure with normal/near normal ejection fraction
Vol 2, No 3
LV dysfunction is preferably derived from myocardial tissue Doppler
(TD). If myocardial TD yields values suggestive but non-diagnostic
for LV dysfunction (15>E/E>8), TD needs to be implemented with
other non-invasive investigations to provide diagnostic evidence of
diastolic LV dysfunction. These non-invasive investigations can con-
sist of: (i) a blood flow Doppler of mitral valve flow velocity (E/A ratio
and DT combined), or of pulmonary vein flow velocity (Ard-Ad in-
dex); (ii) an echocardiographic measure of LV mass index or of left
atrial volume index; (iii) an electrocardiogram with evidence of atrial
fibrillation; and (iv) a determination of plasma BNP or NT-proBNP.
If plasma NT-proBNP is >220 pg/ml or BNP is >200 pg/ml, diagnostic
evidence of diastolic LV dysfunction also requires additional non-in-
vasive investigations, which can consist of: (i) TD (E/E ratio); (ii) a
blood flow Doppler (E/A ratio and DT combined; Ard-Ad index); (iii)
echo measures of LV mass index or left atrial volume index; and (iv)
electrocardiographic evidence of atrial fibrillation.
The proposed use of different echocardiographic techniques, which
includes measures derived from mitral valve flow velocity (E/A, DT),
pulmonary vein flow velocity (Ard-Ad index) and TD (E) allows for a
comprehensive non-invasive assessment of LV relaxation, LV dias-
tolic stiffness and LV filling pressures.
The current study was undertaken to study the clinical and echocar-
diographic profile of patients with HFNEF, because there is paucity
of data on the same at present, especially in North India.
This was a prospective, open-labeled, observational study conducted
on 70 subjects. The subjects were either admitted in medical wards
or were attending Medicine OPDs/Cardiology OPDs of the J N Medi-
cal College, AMU, Aligarh. All patients with suspected heart failure,
fulfilling the Framingham criteria were included in the study. Patients
with a reduced ejection fraction (<40%) were excluded from the
study.
A detailed history and thorough medical examination were carried
out on all the patients. Doppler echocardiography was done and pa-
tients were thoroughly investigated for diastolic dysfunction. LVDD
grade 1-4 was determined by detailed echocardiographic study
(pulsed wave and tissue Doppler studies).
Statistical analysis
All statistical data were analyzed using SPSS version 20. Chi square
test was used for comparison of categorical variables, while contin-
uous variables were compared using the student t test for independ-
ent groups. ANOVA with Scheffes post hoc analysis was used for
comparison of means between 3 or more groups. All p-values were
two-tailed and p-values <0.05 were considered statistically signifi-
cant. All confidence levels were calculated at 95% level.
Results
Of the 70 patients included in the study, the maximum age was 95
years and minimum was 25 years with a mean age of 64.84 11.59
years. Maximum number of patients was observed in the 61-70 year
age group. The majority of patients were females i.e. 38 out of 70
(54.3%). 36 patients were hypertensive (51.4%), 38 had a history of
CAD (54.3%) and 21 patients had a history of diabetes mellitus (30%).
36 (51.4%) patients had BMI in the normal range, whereas, 18
(25.7%) were classified as overweight and 16 (22.8%) as obese. 16
patients (22.85%) had a history of atrial fibrillation. 23 patients
(32.85%) had deranged RFT. 5 (7.14%) patients had thyrotoxicosis
whereas 2 (2.86%) had hypothyroidism thyroid disorders. 40% pa-
tients had a serum creatinine level of >1.2 mg%. Mean creatinine was
1.35 0.65 mg%. 63% patients in the study group were anemic with
a mean hemoglobin level of 11.3 2.27 g%. 57.1% (40) of the cases
had HbA1c 5.7% of which, 19 (27.1%) had HbA1c in the pre-diabetic
range.
90% of the patients had a history of dyspnea on exertion. Table 1
shows the distribution of clinical features in the study group.
Table 1: Clinical features in the study group
Feature Percentage
Dyspnea on exertion 90%
Orthopnea 45%
Paroxysmal nocturnal dyspnea 33%
Raised JVP 36%
S3 28%
S4 28%
Rales 88%
Hepatomegaly 16%
Pedal edema 34%

A standard 12- lead EKG was done in all patients, which showed the
following results (Table 2).
Table 2: ECG results in the study group
Feature Number of patients Percentage
LVH 31 44%
LAE 24 34%
Atrial fibrillation 16 22.8%
QS complexes 12 17%

In the current study, it was observed that 22.8% patients had LVDD
grade 1, 54.3% patients had LVDD grade 2, 20% has LVDD grade 3
and 2.85% had LVDD grade 4. 10 patients (out of 14) with LVDD
grade 3 had restrictive cardiomyopathy, while 4 had hypertrophic
cardiomyopathy. Out of the two patients with LVDD grade 4, 1 had
restrictive cardiomyopathy, and 1 had hypertrophic cardiomyopathy
(Tables 3 and 4).
It was observed in our study that 16 cases had a prolonged deceler-
ation time (DT), with a mean DT of 225 ms. Table 5 shows DT values
in different LVDD groups. Our study also observed that, in cases of
mild diastolic dysfunction due to impaired relaxation, IVRT was pro-
longed. Mean IVRT values in the LVDD grade 1 was 119 ms. As the
severity of diastolic dysfunction increased, a reduction in IVRT was
noted. Mean IVRT values of different groups are given in Table 6.
Tables 7 and 8 show e and E/e values and other indices in different
LVDD grades.
Hasan A, Ashraf MU, L NAC et al. 197
Table 3: E (Early diastolic) and A (Late diastolic) filling velocities in LVDD groups
Mean (E), cm/s S.D Mean (A), cm/s S.D Min E, cm/s Max E, cm/s Min A, cm/s Max A, cm/s
LVDD1 (n=16) 60.1 4.30 73.63 6.29 50 66 64 84
LVDD2 (n= 38) 69.19 6.87 58.1 8.24 60 89 46 80
LVDD3 (n=14) 82.1 3.35 30.28 2.05 78 87 28 34
LVDD4 (n=2) 82 2.83 29 1.41 80 84 28 30

Table 4: Mean E/A ratio in the LVDD groups
Mean (E/A) S.D Min (E/A) Max (E/A)
LVDD1 (n=16) 0.82 0.08 0.68 0.94
LVDD2 (n= 38) 1.19 0.10 0.85 1.46
LVDD3 (n=14) 2.73 0.26 2.41 3.11
LVDD4 (n=2) 2.82 0.04 2.80 2.85

Table 5: DT values in different LVDD groups
Mean DT, ms S.D Min DT, ms Max DT, ms
LVDD1 (n=16) 225 15.43 200 250
LVDD2 (n= 38) 176 13.26 150 200
LVDD3 (n=14) 100 13.84 80 120
LVDD4 (n=2) 60 0 60 60

Table 6: IVRT values in different LVDD groups
Mean IVRT, ms S.D Min IVRT, ms Max IVRT, ms
LVDD1 (n=16) 119 13.88 100 140
LVDD2 (n= 38) 89.32 11.19 60 110
LVDD3 (n=14) 51.29 5.19 45 60
LVDD4 (n=2) 50 0 50 50

Table 7: e and E/evalues in different LVDD grades
Mean e S.D. Mean E/e S.D. Min e Max e Min E/e Max E/e
LVDD1 (n=16) 7.46 0.53 8.08 0.77 6.5 8 6.25 9
LVDD2 (n= 38) 5.93 0.66 11.76 0.66 5 7 9.14 14.4
LVDD3 (n=14) 4.71 0.35 17.52 1.64 4 5.2 15.6 21.5
LVDD4 (n=2) 4.25 0.70 19.3 0.99 4.2 4.3 18.6 20

Table 8: Mean values of echocardiographic indices in diastolic dysfunction
INDICES LVDD 1 LVDD 2 LVDD 3 LVDD 4
E, cm/s 60.06 69.1 82.1 82
A, cm/s 74.56 58.1 30.2 29
E/A 0.81 1.19 2.72 2.83
E, cm/s 7.44 5.93 4.71 4.25
E/e 8.1 11.76 17.52 19.3
DT, ms 225 176 100 60
IVRT, ms 118 81.32 51.29 50
Pulmonary S/D S>D D>S D>S D>S

198 Heart failure with normal/near normal ejection fraction
Vol 2, No 3
Table 9: Echocardiographic indices of patients with restrictive cardiomyopathy and LVDD in our study
E, cm/s A cm/s E/A DT, ms IVRT, ms E, cm/s E/e
Mean 81.91 30.18 2.73 95.45 51.09 4.7 17.51
SD 3.05 2.08 0.22 22.07 4.34 0.34 1.42
Max 87 34 3.10 120 60 5.2 20
Min 78 28 2.41 60 40 4.2 15.6
The echocardiographic indices of restrictive cardiomyopathy showed
an E/A ratio of >2.4 (mean 2.76) and E/e >15 (mean 17.51). IVRT was
markedly reduced in patients with restrictive cardiomyopathy (mean
IVRT was 51.09 ms). Table 9 shows echocardiographic indices of pa-
tients with restrictive cardiomyopathy and LVDD in our study.
Discussion
Heart failure with normal ejection fraction (HFNEF) is increasingly be-
ing recognized as a major health problem worldwide. It is now
known that more than 50% of patients presenting with heart failure
have a normal or preserved ejection fraction. In the current study,
we have made an attempt to study the clinical features, co-morbid
conditions and echocardiographic features of such patients.
In the current study, it was observed that maximum age was 95 years
and minimum age was 25 years. Maximum number of patients was
in the age group of 61-70 years (37.14%), with a mean age of 64.89
11.59 years. There was a predominant involvement of the female
sex (54.3%). Ageing is associated with numerous changes and adap-
tations in the cardiovascular system. Vascular and ventricular wall
thickness increase, whereas arterial compliance, endothelial function
and ventricular contractility decline. The correlation between age
and grading of LV diastolic dysfunction was found to be statistically
significant (p value <0.001). This observation is in concert with vari-
ous previous studies [7-9]. Previous studies have also shown higher
female preponderance [10-12].
Hypertension constitutes a common cause of diastolic dysfunction
and diastolic dysfunction may be present early in the development
of hypertensive disease. 51.4% patients in the current study had hy-
pertension. Philbin et al showed in their study on 312 patients that
49% were hypertensive [13]. Similar results were seen in many other
studies conducted worldwide [12, 14, 15].
Diabetes mellitus is a well-known risk factor for atherosclerosis and
coronary artery disease, but its role in the development of heart fail-
ure is less established. The prevalence of diabetes in HFNEF is re-
ported to be around 30-40% [11]. LV diastolic dysfunction has been
shown previously to be the first manifestation of diabetic heart dis-
ease in both type 1 and type 2 diabetes [16]. In the current study, 21
out of the total 70 patients were diabetic, which is about 30% and
this data is in concordance with a study conducted by Owan et al
[11]. Also, 27% of the patients had an HbA1c in the pre-diabetic
range. Insulin resistance with impaired myocardial glucose uptake
and increased turnover of FFAs in diabetic patients leads to myocar-
dial lipotoxicity, uncoupling of mitochondrial oxidative phosphory-
lation contributing to diastolic dysfunction [17].
Obesity and dyslipidemia are proven risk factors for hypertension
and heart failure. Mean BMI in the present study was 25.4 kg/m
2
.
Similar results have been observed by Gustafson et al [18]. Atrial fi-
brillation (AF) is one of the factors responsible for acute decompen-
sation in patients of HFNEF. In the current study, 23% of the patients
with HFNEF had AF. This data was shown to be around 29% and 23%
in two previous studies [10, 18].
The present study has also shown a significant correlation between
anemia and HFNEF. Adaptation to an anemic state involves augmen-
tation of the heart rate and cardiac index and increased plasma vol-
ume. This overall increase in sympathetic and inotropic activity
places additional stress on the myocardium, leading to remodeling
of the myocytes. Mean Hb in the current study was 11.3 2.27 g%.
Previous studies have also shown similar results [11].
One of the earliest abnormalities in diastolic function is myocardial
relaxation. The velocity of mitral annular movement during early di-
astole, designated as e, correlates well with invasive measurements
of the time constant of myocardial relaxation time [19]. In individuals
with diastolic dysfunction, relaxation or e is reduced and remains so
in all stages of diastolic dysfunction, and a normal e velocity is unu-
sual in diastolic dysfunction [6, 20]. The present study also observed
that none of the patients had a septal e of more than 8. Mean e of
cases with impaired relaxation was 7.46. Similar observations were
recorded by Brun P et al [20].
Mitral annular velocities (e) can be used to draw inferences about
LV relaxation and along with mitral peak E velocity (E/e ratio) can be
used to predict LV filling pressures. Using the septal E/e ratio, a ratio
<8 is usually associated with normal LV filling pressures, whereas a
ratio 15 is associated with increased LV filling pressures [21]. In the
present study, a mean E/e ratio of 17.52 was observed in grade 3
LVDD, and in grade 4 LVDD it was 19.3.
Normally, the early diastolic mitral velocity (E) is higher than the late
velocity (A), so that E/A is >1. An early abnormality of diastolic filling
is abnormal myocardial relaxation. In the current study, mean A value
of 74.56 cm/s was noted against a mean E value of 60.06 cm/s. Thus
22.8% of the cases had impaired relaxation or LVDD grade 1. A de-
crease in preload, by having the patient sit or perform valsalva ma-
neuver, unmasks the underlying impaired relaxation, decreasing the
E/A ratio more than 0.5. 38 patients had E/A between 1 and 1.5.
Valsalva was performed only in 10 patients due to lack of coopera-
tion. But all 10 patients showed a change in E/A 0.5
Restrictive filling with severe diastolic dysfunction is characterized
by increased E velocity, decreased A velocity (markedly less than E)
and an E/A ratio higher than 2, and shortened DT (<160 ms) and IVRT
(<70 ms). We observed that 16 patients had E/A >2. This is sugges-
tive of restrictive filling physiology which was present in 22.8% of
the patients.
Hasan A, Ashraf MU, L NAC et al. 199
With further decrease in LV compliance and increase in LA pressure,
diastolic filling becomes restrictive. There is reduced chamber com-
pliance in association with severely elevated LAP. The present study
observed a mean DT of 100 ms in grade 3 and 60 ms in grade 4
LVDD. These values are similar to those reported by Diwan A et al in
2005 [22].
Conclusion
In the current study, we have seen that heart failure with nor-
mal/near normal ejection fraction is more common in females and in
the elderly. There is significant correlation between ageing and dias-
tolic dysfunction. Hypertension, diabetes mellitus, renal dysfunction,
thyroid disorders and atrial fibrillation are associated commonly with
HFNEF. Abnormal relaxation, pseudonormal filling pattern and re-
strictive filling are the mechanisms responsible for diastolic dysfunc-
tion. Change in E/A ratio with valsava is important in diagnosing di-
astolic dysfunction in cases with pseudonormal filling pattern. Tissue
Doppler imaging with recording of mitral annular velocity (e) and
E/eratio are helpful in diagnosing diastolic dysfunction.
Received: 28 April 2014 Accepted: 2 August 2014
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2014 Ali et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits
unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Ali SA, Khuwaja AB: Comparison of transcerebellar diameter in growth restricted and normal singleton fetuses for the assessment of gestational age: A case control study. El Mednifico Journal
2014, 2(3): 200-204.
Comparison of transcerebellar diameter in growth restricted and normal singleton fetuses for the
assessment of gestational age: A case control study
Sumera Aziz Ali
1
, Azrah Bano Khuwaja
2

Introduction
Estimation of gestational age is important in clinical practice to en-
sure the appropriate management of labor and to differentiate be-
tween normal and growth restricted fetuses [1]. Prediction of gesta-
tional age based on sonographic parameters is the cornerstone in
modern obstetrics [2]. Many parameters like head circumference
(HC), biparietal diameter (BPD), abdominal circumference (AC), fe-
mur length (FL), and transcerebellar diameter (TCD) can be used for
establishing gestational age [3].
The cerebellum is well protected in the fetal head and among all
organs of the body, it is the last organ to be affected by reduced
blood flow [1]. Moreover, transcerebellar diameter is less affected in
growth restricted fetuses, suggesting a cerebellar growth protection
mechanism as compared to other encephalic areas [4]. Transcerebel-
lar diameter is the distance between lateral aspects of the cerebel-
lum and incorporates the width of cerebellar vermis [5]. It is a relia-
ble parameter for estimating gestational age, not only in singletons
but also in twins [6]. Positive relationship has been found between
TCD and gestational age with specificity and sensitivity of more than
90% [7]. Furthermore, TCD is not influenced by alterations in the
growth of the fetus such as macrosomia or restricted intrauterine
growth [1].
Intrauterine growth restriction (IUGR) is one of the common causes
of perinatal mortality after prematurity and is defined as estimated
fetal weight below the 10
th
percentile for gestational age with a path-
ologic restriction of fetal growth [7]. Every year 30 million fetal
growth restricted births occur globally and 75% of these restricted
births take place in South Central Asia, 20% occur in Africa, and ap-
proximately 5% in Latin America [8]. Several developing countries

1
Department of Community Health Sciences, Aga Khan University, Pakistan.
2
Abbasi Shaheed Hospital, Karachi, Pakistan.
Correspondence: Sumera Aziz Ali
Email: sumera.ali@aku.edu
have surpassed the recommended IUGR cut-off levels [8]. The inci-
dence of IUGR in Pakistan is 25%, more than the WHO criteria for
starting a public health action [9]. According to community based
study in Karachi Pakistan, the incidence of fetal growth restriction
was found to be 24.4% among 738 singleton births [10].
Fetal growth restriction causes a spectrum of perinatal complications
and the impact of fetal growth restriction continue into adult life [7].
In adulthood, these babies appear to be at increased risk of high
cholesterol, increased cortisol level, cardiovascular diseases, diabe-
tes, renal damage, cerebral palsy and epilepsy [7]. Recognition of
IUGR is an important component in the management of various com-
plications, which begins with the assessment of gestational age and
multiple biometric parameters including transcerebellar diameter
can be used to predict the gestational age [3]. Whether transcere-
bellar diameter can be used similarly for assessing gestational age in
normal and growth restricted fetuses needs to be determined in Pa-
kistani population. However, many studies have been conducted on
this topic internationally, but the data from Pakistan especially fo-
cusing on this issue is negligible [1, 3].
Objective
The objective of the study was to measure and compare transcere-
bellar diameter between growth restricted and normal fetuses
among pregnant women presenting to the tertiary care Hospital of
Karachi.
A case control study was conducted on pregnant women attending
the outpatient department at obstetrics and gynecology unit of Ab-
basi Shaheed Hospital Karachi Pakistan from April 1, 2010 to October

Abstract
Background: Intrauterine growth restriction (IUGR) is an important cause of perinatal mortality. Early diagnosis of IUGR babies is an
essential component in the management of various complications. Recognition of IUGR begins with the assessment of gestational age.
Multiple biometric parameters including transcerebellar diameter can be used to predict the gestational age. Whether transcerebellar
diameter can be used similarly for assessing gestational age in normal and growth restricted fetuses needs to be determined in Pakistani
population. Thus, this study was designed to measure and compare the transcerebellar diameter between normal and growth restricted
fetuses among pregnant women presenting to a tertiary care hospital of Karachi.
Methods: This was a case control study. Singleton fetuses with intrauterine growth retardation were identified as cases and all the
singleton fetuses with normal growth were identified as controls. Logistic regression was used to analyze the data.
Results: Mean transcerebellar diameter of normal fetuses group was 34.023.56 mm, while mean transcerebellar diameter of growth
restricted fetuses group was 35.293.37 mm. Moreover, no significant difference was found in transcerebellar diameter between normal
and IUGR fetuses while adjusting for maternal age and parity (OR: 0.92, 95% CI: 0.813-1.041).
Conclusion: Transcerebellar diameter was found to be same between normal and growth restricted fetuses. Therefore this parameter can
be used as one of the important tools in assessing the gestational age in normal and growth restricted fetuses and can be helpful for
obstetricians in appropriate management of various complications during pregnancy. (El Med J 2:3; 2014)
Keywords: Gestational Age, Growth Restricted Fetuses, Transcerebellar Diameter, Ultrasound
Ali SA, Khuwaja AB 201
1, 2010. Cases with intrauterine growth retardation were defined as
fetal weight below the 10
th
percentile for gestational age and con-
trols with normal growth were defined as fetal weight above the
10th percentile for gestational age [7]. In order to be able to detect
a mean difference of 0.4mm, with variance of 0.51 and with power
of 80%, using 95% confidence interval and a ratio of 1:1 between
cases and controls, at least 102 alive fetuses (51 normal fetuses and
51 growth restricted fetuses) were required to conduct this study.
All pregnant women with alive singleton fetuses having gestational
age of 28-40 weeks assessed by last menstrual period (LMP) and con-
firmed by early scan were included in the study. The range of 28-40
weeks was chosen because fetal growth restriction typically starts
before term [11]. All pregnant women whose gestational age was
not confirmed by early scan or fetuses with central nervous system
anomalies like hydrocephalus, anencephaly and any other abnormal-
ity of the brain development, women with multiple pregnancies,
gestational diabetes mellitus and women who did not give informed
consent were excluded from the study.
All the eligible pregnant women were invited to participate in this
study and the demographic data was collected from women. Those
women who gave the informed consent were given appointment for
obstetrical ultrasound, which was done by an expert radiologist. Par-
ticipants were explained about the procedure in a private room and
it was performed in supine position with extended hips and knees.
Before doing the ultrasound, a gel was applied and ultrasound probe
was adjusted by holding it with right hand. All the required meas-
urements were performed by the one radiologist and were calcu-
lated in millimeters. Detailed methods regarding placement of cali-
per, criteria of imaging and averaging of at least two measurements
were followed for each participant. The measurements were ob-
tained with commercially available ultrasound, equipped with a 3.5
MHz transducer. After adjusting the ultrasound probe, calipers were
placed at the outer margins of the cerebellum and the distance be-
tween outer lateral borders of cerebellum was taken on ultrasound
machine by incorporating the width of cerebellar vermis (Figures 1
and 2). A single radiologist performed all the measurements to de-
crease the inter-observer variability, while the average value of two
measurements was taken to overcome the intra-observer variability.

Figure 1: Landmarks for transcerebellar diameter.

Figure 2: Measurement of TCD (Measurements were obtained
by placing the calipers of the ultrasound machine at the outer-
to-outer margins of the cerebellum).
All biometric measurements like BPD, HC, AC, and FL were taken with
special emphasis on transverse cerebellar diameter. The sonologist
was blinded of early dating scan notes and gestational age of the
woman before taking the transcerebellar diameter. The measure-
ments were plotted on a preexisting standardized chart for gesta-
tional age. Information about variables including maternal age, par-
ity, gestational age, ultrasound findings (IUGR normal or growth) and
transcerebellar diameter were documented. This study was con-
ducted after taking the approval from research evaluation unit of
college of physician and surgeon, Karachi Pakistan.
Statistical analysis was carried out by using the statistical software
SPSS version-19.0. Normality of continuous data was assessed by us-
ing histograms and Kolmogorov test. For the categorical variables,
frequencies with percentages were generated for both cases and
controls. Chi-square or Fisher exact test was applied when appropri-
ate. For continuous variables such as maternal age, gestational age
and transcerebellar diameter, mean with standard deviation (SD)
was computed for both cases and controls. Independent t test or
Mann Whitney U test was applied when appropriate.
The association between transcerebellar diameter and fetus status
was assessed by logistic regression. A p-value of <0.05 was consid-
ered as significant for univariate analysis [12]. This was followed by
multicollinearity assessment between independent variables. Pear-
son chi square test was used to assess collinearity between continu-
ous variables and cutoff of 0.8 was considered as an inter-correla-
tion between these variables. ETA was used to assess the collinearity
between categorical and continuous variables and cut off of 0.5
was considered as an inter-correlation between these variables [13].
Multivariate analysis was done by purposeful selection method. The
significance of each independent variable in the multivariate analysis
was assessed by its p-value and likelihood ratio test. Statistical sig-
nificance was defined as p-value of <0.05. All biologically plausible
interactions were evaluated and p-value of <0.1 was considered to
be significant for any interaction. Hosmer-Lemeshow test was ap-
plied to test the fit of the final model [12].
Results
There were around 102 singleton fetuses who met the inclusion cri-
teria for this study. Mean maternal age of women of normal fetus
202 Transcerebellar diameter for assessment of gestational age
Vol 2, No 3
group was 29.404.98 years and of IUGR group was 27.244.57 (Ta-
ble 1). The difference of age between two groups was significantly
different with the p-value of 0.02. The most common maternal age
group was 25-29 years as shown in Figure 3.
Age groups (years)
35-39 30-34 25-29 18-24
N
u
m
b
e
r

o
f

w
o
m
e
n
25
20
15
10
5
0
Growth
Normal
IUGR
10
12
19
10
3
14
22
12
Figure 3: Comparison of maternal age between normal and
growth restricted fetus groups.
Mean gestational age of pregnant women with normal fetuses was
33.512.9 weeks as compared to the mean gestational age of preg-
nant women with growth restricted fetuses i.e. 34.743.01 weeks
(Table 1). The difference of gestational age between two groups was
significantly different with the p-value of 0.04. The most common
gestational age group was 33-36 weeks (Figure 4).

Figure 4: Comparison of gestational age between normal and
growth restricted fetus groups.
Mean transcerebellar diameter of normal fetus group was 34.023.56
mm while the mean transcerebellar diameter of growth restricted
fetus group was 35.293.37 mm (Table 1). The transcerebellar diam-
eter between two groups was not significantly different with the p-
value of 0.07.
Initially for the variable of parity three categories were made (Table
2) but due to insufficient cell count (<5) in third category it was
merged with second category and parity was generated as a binary
variable (parity_code) (Table 1).
Of the 51 pregnant women with IUGR singleton fetuses included in
the study, 70.5% had less than or equal to 1 child with respect to
parity and 29.4% had more than or equal to 2 children. Of the 51,
pregnant women with normal fetuses 51% had less than or equal to
1 child and 49% had more than or equal to 2 children (Table 1).
Univariate analysis through logistic regression (Table 3) revealed that
with one millimeter increase in transcerebellar diameter the odds of
growth retardation among fetuses decreased by 2. However, 95% CIs
were overlapping therefore results were not statistically significant.
This indicated that transcerebellar diameter is not significantly dif-
ferent in IUGR and normal growth singleton fetuses (p=0.075).
According to the above mentioned criteria, no multicollinearity was
found between any of the continuous or categorical variables and
univariate analysis was followed by multivariate analysis. In model 1
(Table 3), adjustment was done for maternal age and by keeping this
variable in the model the OR slightly increased from 0.898 to 0.912
and 95% CIs were overlapping, thus the results were insignificant (p
=0.139). Model 2 (Table 3) was adjusted for maternal age and par-
ity_code and OR slightly increased from 0.898 to 0.920 and 95% CIs
were overlapping therefore the results were insignificant (p=0.189).
Thus the findings showed that there is no significant difference in
transcerebellar diameter between normal and IUGR singleton fetuses
while adjusting for maternal age and parity (Table 3). After assess-
ment of confounding, these variables (maternal age and parity) were
further assessed for interaction. Interaction was not found either be-
tween transcerebellar diameter and maternal age (p=0.19), or be-
tween transcerebellar diameter and parity_code (p=0.45).
Discussion
Accurate assessment of gestational age is highly significant for the
management of pregnancies, especially for fetuses with growth dis-
turbances (IUGR and large fetuses) [14]. Findings from this study
have shown an inverse association between transcerebellar diameter
and growth retarded fetuses but the results were not statistically sig-
nificant. This indicates that transcerebellar diameter is not signifi-
cantly different in intrauterine growth restricted (IUGR) singleton fe-
tuses and normal growth singleton fetuses (P=0.075). After adjusting
for potential confounders like maternal age and parity, no significant
difference in transcerebellar diameter was found between normal
and intrauterine growth restricted (IUGR) fetuses.
Table 1: Base line characteristics by intrauterine growth retarded and normal growth singleton fetuses
Characteristics Cases (IUGR fetuses) n=51 Controls (Normal Growth fetuses) n=51 p-value
Maternal age (years) 27.244.57
29.404.98
0.02*
Gestational age (weeks) 34.743.01
33.512.9
0.04*
Trans cerebellar diameter (millimeters) 35.293.37
34.023.56
0.07
Parity 1 36 (70.5%) 26(51%) 0.039*
2 15(29.4%) 25(49%)
Mean SD (All such values), Individual numbers with percentages n (%); * P- values < 0.05 (by applying independent t-test and Chi square)

Ali SA, Khuwaja AB 203

Table 3: Difference in transcerebellar diameter between two groups; crude, adjusted Odds ratios and 95% CI
Modeling N OR 95% CIs P- Value
Crude 102 0.898 (0.798,1.011) 0.075
Model 1* 102 0.912 (0.080,1.030) 0.139
Model 2* 102 0.920 (0.813,1.041) 0.189
*Model 1 was adjusted for maternal age; *Model 2 was adjusted for parity_code and maternal age.
These study findings can be explained by the fact that cerebellar
growth is not affected among fetuses with growth restriction, there-
fore can be helpful in defining the gestational age among both nor-
mal and growth restricted fetuses. Thus, the hypothesis of human
cerebellar growth is relatively resistant to chronic hypoxemia as a
result of the brain sparing phenomenon is supported by our study
findings [1]. This proposes a special mechanism in the conservation
of cerebellar growth and cerebellum is also not liable to change in
form and size because of dense surrounding petrous ridges and oc-
cipital bone as compared to other structures of brain [15]. These re-
sults are coherent with the findings from the studies of primate mod-
els which reveal that, blood flow to the cerebellum, brain stem and
midbrain is higher as compared to cerebrum [16]. Moreover, these
results are encouraging and consistent with other studies around the
world [17]. These studies have described the use of TCD as an im-
portant method to assess the gestational age and identifying the
IUGR fetuses on right time to manage various pregnancy related
complications [18].
On the other hand; few studies have shown contradictory findings
and have established that TCD measurement cannot be used as an
important method to assess the gestational age [19, 20]. One of the
studies found that measurement of TCD can be used to assess the
gestational age in asymmetrically growth restricted fetuses but not
in symmetrically growth restricted fetuses [20].
These contradictions may be because of different definitions of IUGR,
used in different studies. For example definition of fetal birth weight
below the 10
th
centile was used in this study which contrasts with
the other study whose definition was based on a fetal birth weight
under the 5
th
centile [19]. Moreover, the contradiction in findings
might be due to differences in in sample size. Thus, several general
limitations to the current body of evidence should be highlighted.
First of all, the sample size of this study was small and secondly this
study was conducted only in one tertiary hospital of Karachi there-
fore one need to be cautious, while generalizing the results to the
whole population of Pakistan. Moreover, this study could not assess
the difference in TCD at different trimesters of pregnancy. In re-
sponse to these limitations, several suggestions for future research
can be made. Community based studies with larger sample size are
required in future to support our study findings. In addition further
studies are required to focus on all trimesters so that the difference
in TCD can be seen at all levels of pregnancy in both normal and
IUGR fetuses.
Despite these limitations, our results demonstrate that TCD can be
used as an important sonographic biometric parameter in singleton
intrauterine growth restricted and normal growth fetuses for predic-
tion of gestational age. Hence, it is recommended that transverse
cerebellar diameter can be used as an important parameter to assess
the gestational age for timely management of various complications
during pregnancy.
Conclusion
This study showed the clinical importance of TCD measurements for
the assessment of gestational age in normal and growth restricted
singleton fetuses. Transcerebellar diameter was found to be same
between normal and growth restricted singleton fetuses.
Recommendations
Thus, it can be recommended that TCD measurements may be help-
ful in predicting gestational age in similar manner in both normal
and growth restricted singleton fetuses. Therefore this parameter
can be used as one of the important tools in assessing the gesta-
tional age in normal and growth restricted singleton fetuses and can
be helpful for obstetricians in appropriate management of various
complications during pregnancy. Further community based studies
Table 2: Parity status in normal and intra uterine growth retarded singleton fetus groups
Parity status in normal and growth restricted fetus groups
Status of fetus
Total IUGR fetuses Normal Growth fetuses
Parity 1 (Primipara) n 36 26 62
% 70.5% 51%
2-4 (Multipara) n 14 25 39
% 27.0% 49.0%
5 (Grand Multipara) n 1 0 1
% 2.0% 0%
Total n 51 51 102
% 100.0% 100.0% 100.0%
204 Transcerebellar diameter for assessment of gestational age
Vol 2, No 3
should be done to derive the population based comparisons be-
tween the two groups.
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2014 Akhlaghi et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Akhlaghi M, Hemmati F: Adherence to guidelines of healthy diet is low in patients with diabetes clinical inertia. El Mednifico Journal 2014, 2(3): 205-209.
Adherence to guidelines of healthy diet is low in patients with diabetes clinical inertia
Masoumeh Akhlaghi
1
, Fatemeh Hemmati
1

Background
Diabetes is one of the most prevalent metabolic disorders affecting
382 million people worldwide and 8.7% of Iranian population aged
between 15 and 64 years [1, 2]. Despite conspicuous advances in the
management of diabetes, the rate of diabetic complications is still
remarkably high [3-5]. Although some of these complications may
be attenuated by intensive glycemic control from early stages of di-
abetes, macrovascular complications including cardiovascular events
may progress in patients with normal levels of glycosylated hemo-
globin [6]. This suggests that for integral prevention of diabetic com-
plications, other therapeutic strategies such as prevention of
dyslipidemia are necessary [7].
Regulatory effects of insulin are not exclusive to glucose; insulin has
regulatory effects on the metabolism of plasma lipoproteins and ad-
ipose tissue as well [8, 9]. As a result, abnormal levels of plasma lipids
appear in plasma in conditions of insulin deficiency or insulin re-
sistance. Diabetes-induced dyslipidemia include increased levels of
triglycerides and small dense low-density lipoprotein and decreased
levels of high-density lipoprotein, providing the condition for the ap-
pearance of metabolic syndrome and cardiovascular diseases [10,
11]. Therefore, proper management of diabetes requires synchro-
nous control of glucose and lipid levels in blood.
Diet and lifestyle therapy is the first line of control of diabetes and
prevention of its complications [12]. Diets rich in fruit, vegetables,
whole-grains, and legumes and low in refined carbohydrates are
generally recommended for the control of diabetes and mitigating
progression of diabetes-related vascular changes [12-14]. In the pre-
sent study, we investigated consumption of dietary items and asso-
ciations between diet and glycemic and lipid profile in patients with

1
School of Nutrition and Food Sciences, Shiraz University of Medical Sciences,
Shiraz, Iran
Correspondence: Masoumeh Akhlaghi
Email: akhlaghi_m@sums.ac.ir
diabetes clinical inertia. By definition, clinical inertia is the failure of
health care providers to initiate or intensify therapy when indicated
[15]. Whereas most faults in determining causative factors of clinical
inertia are believed to be the failure of health care professionals,
question remains as to what extent patients with clinical inertia of
diabetes adhere to guidelines of healthy diet and that if the patients
adherence to these guidelines is associated with better glycemic
control in such patients. Results of this study demonstrate some of
existing problems in the dietary pattern of patients with diabetes
and delineate targets for appropriate interventions.
Patients and Methods
Patients
This was a cross-sectional observational study performed on 200 pa-
tients with diabetes, mainly type 2 diabetes. The study subjects were
recruited from attendees of the Diabetes Care Unit of Shahid
Motahari Polyclinic in Shiraz, Iran. Attendees of this clinic are gener-
ally referred from other diabetes clinics in Shiraz when there is a fail-
ure in the management of their diabetes, a condition known as clin-
ical inertia. Participants were selected through convenient sampling
from those attendees of the Diabetes Care Clinic who had blood glu-
cose and lipids examined during the last 3 months prior to the study.
The consent of the patients was also a prerequisite of participating
in the study. The protocol of the study was approved by the Ethics
Committee of Shiraz University of Medical Sciences. All information
was kept confidential and used for study purposes only.
Data Collection
Information was gathered by a trained dietitian through interview. A

Abstract
Background: Diabetes is one of the most prevalent metabolic disorders affecting 382 million people worldwide and 8.7% of Iranian
population aged between 15 and 64 years. We investigated adherence to healthy diet guidelines in patients with diabetes clinical inertia.
Methods: This cross-sectional observational study was performed on 200 patients with diabetes (mostly type 2 diabetes) involved in poor
glycemic control. The patients were recruited from a Diabetes Care Clinic in Iran. Biographic and medical information was obtained by
interview. A semi-quantitative food frequency questionnaire was used to estimate consumption of food items. Data on plasma glucose
and lipids was obtained from patients dossiers in the clinic. Individuals were excluded if their laboratory tests had been carried out earlier
than 3 months prior to the study.
Results: Mean hemoglobin A1c (HbA1c) was 8.3 1.9%, 62.7% of the patients had HbA1c 7.5%, and 88.5% had at least one form of
dyslipidemia. Consumption of dairy, fruit, and vegetables was lower than dietary recommendations for healthy individuals in 55%, 54.5%,
and 83%, respectively, but 72% consumed high-fiber breads. Among the investigated dietary factors only consumption of high-fiber
breads was significantly associated with lower HbA1c (P=0.03). Consumption of none of dietary items was associated with low- and high-
density lipoproteins, but there were significant associations between triglycerides and consumption of vegetables (P=0.004), fish (P=0.02),
soy (P=0.02), vegetable oils (P=0.047), and high-fiber breads (P=0.04).
Conclusion: The patients adhered poorly to the guidelines of healthy diet. However, even if following these guidelines is not effective in
the control of hyperglycemia in patients with diabetes clinical inertia, it may help to attenuate hypertriglyceridemia. (El Med J 2:3; 2014)
Keywords: Diabetes, Diet, Glycemic Control, Triglycerides
206 Adherence to guidelines of healthy diet
Vol 2, No 3
questionnaire was used to collect information on demographic char-
acteristics, medical history, and medications. Consumption of dietary
items that are known to have an impact on blood glucose and lipids,
including dairy products, fruit and vegetables, oils, soy, and fish was
questioned using a semi-quantitative food frequency questionnaire.
The questionnaire was a concise form of the 168-item questionnaire
which has been tested for validity and reliability on Iranian popula-
tion [16]. Participants were asked to report the frequency and the
amount of consumed foods during the previous year on a daily,
weekly, or monthly basis. The amounts of consumption of food items
were compared with Dietary Guidelines of U.S. Department of Agri-
culture and U.S. Department of Health and Human Services [17].
Height and weight was measured to calculate body mass index
(BMI). Weight was recorded with minimal clothing to the nearest 0.1
kg using a weighing scale (Seca, Germany) and height was measured
without shoes to the nearest 0.1 cm with a non-stretchable tape. BMI
was calculated by dividing weight in kilogram by height squared in
meters. Classification of BMI according to World Health Organization
is as follows: underweight: <18.5 kg/m
2
, normal: 18.5-24.9 kg/m
2
,
overweight: 25-29.9 kg/m
2
, obese: 30 kg/m
2
[18].
Information on plasma glucose and lipid tests was obtained from
patients dossiers in the Diabetes Care Clinic. The biochemical tests
were performed in the accredited medical laboratory of Shahid
Motahari Polyclinic. Patients whose blood tests were older than 3
months were excluded. Glucose data were fasting blood glucose, 2-
hr postprandial blood glucose, and hemoglobin A1c (HbA1c). The cut-
off points used to demonstrate high levels of glucose were 126
mg/dl for fasting blood glucose, 180 mg/dl for 2-h postprandial
blood glucose, and 7.5% for HbA1c (optimal blood glucose with low
risk of hypoglycemia) as suggested by the American Diabetes Asso-
ciation [19]. Lipid data included triglycerides, total cholesterol, and
low-density lipoprotein cholesterol (LDL-C), and high-density lipo-
protein cholesterol (HDL-C). The cut-off points of undesirable levels
of plasma lipids were 150 mg/dl for triglycerides, 200 mg/dl for TC,
100 mg/dl for LDL-C, and 40 mg/dl for HDL-C [20].
Statistical Analysis
Data was analyzed by SPSS, version 16. Data was presented as fre-
quency and percentage or as means SD. Associations between se-
rum glucose and lipoprotein levels and dietary consumption of food
groups was examined with Chi-square test. Statistical significance
was set at P<0.05.
Results
Participant characteristics are presented in Table 1. Patients were
mostly females (80%) and older than 50 years (75.5%). The mean
duration of diabetes was 9.9 7.9 years, being 8 months the mini-
mum and 45 years the maximum duration. Fifty seven percent of the
patients had the diabetes duration of less than 10 years. Most of the
participants (69.5%) were either overweight (BMI 25-29.9 kg/m
2
) or
obese (BMI 30 kg/m
2
) and only 28.5% had normal BMI (BMI 18.5-
24.9 kg/m
2
).
The majority of the patients were not in good glycemic control. Fast-
ing blood glucose was 126 mg/dl in 72.5% and 2-h postprandial
glucose was 180 mg/dl in 68.7%. Mean HbA1c was 8.3 1.9 percent
and 62.7% of the patients had HbA1c of 7.5% (Table 2). Ninety eight
percent of the patients were on anti-diabetic medications. Most of
the patients (80.7%) were on oral hypoglycemic pills, i.e. glyben-
clamide and/or metformin, and 17.2% were on either insulin alone
or insulin and at least one of the hypoglycemic pills.

More than half of the patients (63.5%) did not take lipid-lowering
medications and 54.5%, 32%, 57%, and 63% had abnormal levels of
triglycerides, total cholesterol, LDL-C, and HDL-C, respectively (Table
2). Of the total, 88.5% of the patients had at least one form of
dyslipidemia.
Investigating consumption of food groups and individual food items
showed that many patients did not consume vegetables, fruit, and
dairy as recommended in the guidelines of healthy eating (Table 3).
But, they mostly (72%) used breads with relatively high amounts of
fiber. Also, the majority of them avoided saturated fats such as butter
and ghee.
Consumption of breads with high fiber content was associated with
HbA1c < 7.5% (Table 4). Other dietary items were not associated with
HbA1c. Similarly, none of food groups or items was associated with
either LDL-C or HDL-C. In contrast, consumption of several foods in-
cluding vegetables, high-fiber breads, fish, soy, and vegetable oils
was associated with triglycerides <150 mg/dl.
Discussion
Participants of the present study were diabetes patients with clinical
inertia and poorly controlled diabetes. They had generally low ad-
herence to dietary guidelines recommended by U.S. Department of
Agriculture and U.S. Department of Health and Human Services [17].
Many patients did not consume sufficient amounts of fruit and veg-
etables, dairy products, and fish, with vegetables being the least con-
sumed food items. No association was observed between consump-
tion of most food items and HbA1c. In contrast, there were significant
Table 1: Demographic characteristics, duration of diabetes,
and BMI of the participants
Categories Frequency (percentage)
Age <50 y 42 (21%)
50-59 y 70 (35%)
60-69 y 69 (34.5%)
70 y 19 (9.5%)
Sex

Male 40 (20%)
Female 160 (80%)
Diabetes duration <5 y 58 (29%)
5-9 y 56 (28%)
10 y 86 (43%)
BMI (kg/m
2
) <18.5 4 (2%)
18.5-24.9 57 (28.5%)
25-29.9 91 (45.5%)
30 48 (24%)
Akhlaghi M, Hemmati F 207
Table 2: Glycemic and lipid profile of the participants
Glycemic profile Lipid profile
FBG (mg/dl) <126 55 (27.5%) TG (mg/dl) <150 91 (45.5%)
126 144 (72.5%) 150 109 (54.5%)
2hPP (mg/dl) <180 46 (31.3%) TC (mg/dl) <200 136 (68%)
180 101 (68.7%) 200 64 (32%)
HbA1c (%) <7.5 44 (37.3%) LDL-C (mg/dl) <100 86 (43%)
7.5 74 (62.7%) 100 114 (57%)
Hypoglycemic agents
`
No 4 (2%) HDL-C (mg/dl) 40 74 (37%)
Tablet 159 (80.7%) >40 126 (63%)
Insulin 12 (6.1%) Lipid lowering medications No 127 (63.5%)
Both 22 (11.2%) Yes 73 (36.5%)
Abbreviations: FBG, fasting blood glucose; 2hPP, 2-h postprandial glucose; HbA1c, hemoglobin A1c; TG, triglycerides; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C,
high-density lipoprotein cholesterol.

Table 3: Consumption of major food groups or special food items in the participants
Food groups/items Categories Frequency (percentage) Food Items Frequency (percentage)
Dairy
<2 servings/day 110 (55%)
Fruit
<2 servings/day 109 (54.5%)
2 servings/day 90 (45%) 2 servings/day 91 (45.5%)
Meat & chicken
<60 g/day 189 (94.5%)
Vegetables
60 g/day 11 (5.5%) 3 servings/day 34 (17%)
Fish
No consumption 38 (19%)
Bread
Low fiber 56 (28%)
Consumption 162 (81%) High fiber 144 (72%)
Oil
Vegetable oils 163 (81.5%)
Soy
Vegetable oils, butter & ghee 37 (18.5%) Consumption 128 (64%)

inverse associations between serum triglycerides (but not LDL-C and
HDL-C) and a variety of foods including vegetables, soy, and fish.
These results suggest that even where meeting dietary guidelines
does not improve glycemic control it may lower serum triglycerides.
Although fiber-containing foods, such as fruit, vegetables, high-fiber
breads, and soy are well known to ameliorate hyperglycemia, with
the exception of high-fiber breads, we did not observe considerable
association between consumption of these dietary items and HbA1c
[21]. A previous study on a group of patients with uncontrolled type
1 diabetes has also found no association between dietary compo-
nents and glycemic control [22]. This could have been partly because
of the existence of uncontrolled diabetes in participants of both
studies. In such poor glycemic conditions, improvement in glycemic
control may not be achievable through dietary rectifications alone;
instead complementary strategies, such as lifestyle changes, weight
reduction, increased physical activity, and also frequent follow-ups
may be required for better management of diabetes [23-25]. In this
regard, we found that patients whose physical activity was 1 hour or
more per week had significantly lower levels of HbA1c than those
with less than 1 hour per week (data not shown). Although this level
of physical activity is low, studies have shown that even mild physical
activity can be effective in improving glycemic control [26].
Triglyceride-rich lipoproteins have been recognized as independent
risk factors of cardiovascular diseases [27]. High serum triglycerides
are usually associated with abundant consumption of cereals, chiefly
bread and rice, which are staple foods in Iran [28, 29]. Adding sources
of fiber to the diet may attenuate this carbohydrate-induced hyper-
triglyceridemia/hyperglycemia [30]. In the current study, 54.5% of
the patients had high serum triglycerides which were associated
with lower rates of consuming fiber-containing foods, i.e. vegetables,
soy, and high fiber breads. Fruits are also sources of fiber; however,
no association was observed between fruit intake and serum triglyc-
erides. Recent notions have preponderated advantages of vegeta-
bles over fruits in the incidence of type 2 diabetes [31]. This suggests
208 Adherence to guidelines of healthy diet
Vol 2, No 3
Table 4: Associations between consumption of food groups/items and plasma levels of HbA1c, triglycerides, LDL-C, and HDL-C
Food items Categories HbA1c (7.5%) P value
TG
(150 mg/dl)
P value
LDL-C
(100 mg/dl)
p-value
HDL-C
(40 mg/dl)
P value
Dairy
0.85
57 (52%)
0.4
64 (58%)
0.71
36 (33%)
0.17
2 servings/day 35 (64%) 52 (58%) 50 (56%) 38 (42%)
Vegetables
0.49
98 (59%)
0.004
94 (57%)
0.81
107 (65%)
0.35
3 servings/day 13 (57%) 11 (32%) 20 (59%) 19 (56%)
Fruit
0.39
61 (56%)
0.65
60 (55%)
0.54
72 (66%)
0.33
2 servings/day 36 (59%) 48 (53%) 54 (59%) 54 (59%)
Bread
Low fiber 23 (79%)
0.033
37 (66%)
0.040
33 (59%)
0.73
25 (45%)
0.16
High fiber 51 (57%) 72 (50%) 81 (56%) 49 (34%)
Fish
0.090
27 (71%)
0.023
26 (68%)
0.11
12 (32%)
0.44
Consumption 54 (59%) 82 (51%) 88 (54%) 62 (38%)
Oil
Vegetable oils 63 (64%)
0.64
84 (51%)
0.047
91 (56%)
0.36
57 (35%)
0.16
Vegetable oils, butter & ghee 11 (58%) 25 (69%) 23 (64%) 17 (47%)
Soy
0.42
47 (65%)
0.022
45 (63%)
0.24
28 (39%)
0.68
Consumption 45 (60%) 62 (48%) 69 (54%) 46 (36%)

that different sources of fiber may exert different biological effects.
Also, ingredients other than fiber may be responsible for vegetables
beneficial effects over fruits.
Consumption of fish was associated with lower rate of hypertriglyc-
eridemia. Previous studies have also demonstrated triglyceride-low-
ering effect of fish and its omega-3 fatty acids, eicosapentaenoic acid
(EPA) and docosahexaenoic acid (DHA) [32, 33]. Mechanisms by
which EPA and DHA reduce serum triglycerides include increased
fatty acid degradation, enhanced clearance of plasma triglycerides,
and decreased hepatic synthesis of very low density lipoprotein
(VLDL) [34].
Lack of association between food items and LDL-C and HDL-C is un-
clear. Previous studies have shown a lowering effect of very high-
fiber diets on serum LDL-C [35]. Therefore, in the current study con-
sumption of soy, high-fiber breads, vegetables, or fruit may not have
been high enough to lower LDL-C. Similar to LDL-C, consumption of
the investigated foods were not associated with HDL-C. However,
except fish which has demonstrated to increase HDL-C, other inves-
tigated food items are less likely to influence HDL-C [36]. Nonethe-
less, we did not find an association between consumption of fish and
HDL-C, probably because fish was not consumed in fairly good
amounts by participants of our study. Only 1% of the patients were
consuming 2-3 servings of fish per day, while to obtain its beneficial
effects on HDL-C one should consume 4 g/day of EPA and DHA,
which are equal to approximately 350 g of fish.
A limitation of our study was that we did not use food recall or record
methods and therefore could not calculate total daily energy intake
and contributions of carbohydrates and fats to total energy intake to
see if some abnormalities in blood glucose and lipid levels are due
to consuming inappropriate amounts of carbohydrates and fats.
Also, for more effective interventions, participants awareness of the
guidelines of the healthy diet for diabetes should be determined.
Future studies may be directed towards finding causes of the poor
adherence of people with diabetes clinical inertia to the recommen-
dations of the healthy diet.
Conclusion
Adherence to the guidelines of the healthy diet was low among dia-
betes patients involved in diabetes clinical inertia, especially for a
number of food items including vegetables, fruit, and dairy. How-
ever, as most dietary items were not associated with HbA1c, one may
deduce that meeting the healthy diet guidelines may not be associ-
ated with the betterment of glycemic control in such conditions of
refractory hyperglycemia. Contrariwise, significant associations be-
tween serum triglycerides and consumption of vegetables, fish, soy,
vegetable oils, and high-fiber breads suggest that following dietary
guidelines may be associated with improved triglyceridemia. Apart
from dietary advice, strategies such as increased physical activity
may be required for better control of hyperglycemia in people with
diabetes clinical inertia. The results of this study emphasize the need
of effective educational programs for people with diabetes on the
guidelines of healthy diet and also operative follow-up sessions to
ensure patients adherence to recommendations.
Acknowledgment: We are thankful to the participants and staff of Shiraz Shahid
Motahari Polyclinic.
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2014 Adbelli et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Adbelli D, Kln N, Akpak YK, Kl D: Genital hygiene behaviors and associated factors in women living in rural areas of Turkey. El Mednifico Journal 2014, 2(3): 210-214.
Genital hygiene behaviors and associated factors in women living in rural areas of Turkey
Derya Adbelli
1
, Nur zlem Kln
1
, Yaam Kemal Akpak
2
, Dilek Kl
1

Background
The problems related to reproductive health comprise an important
part of the womens health problems, and genital infections of the
female upset the physical, communal and social balances [1]. The
underlying causes of reproductive health problems in women are in-
sufficiency of health services, absence of social security, the inferior
social status and insufficient education of women, extreme fecun-
dity, marriage at very early ages and associated gynecologic prob-
lems, false beliefs and incorrect applications related to genital health,
and genital infections [2].
The sexual and reproductive lives of many women are limited by lack
of knowledge, high-risk sexual behaviors, inappropriate or unquali-
fied reproductive health services, discriminatory social behaviors,
and negative behaviors toward women. The predisposing factors for
genital infections include multiple and unsafe abortions, bad hy-
gienic conditions, lack of knowledge on genital hygiene, womens
false beliefs and incorrect applications related to genital hygiene,
feeling shame of sex organ disorders and so being ashamed of visit-
ing the doctor, lack of social security, insufficient income, contracep-
tive methods used, use of antibiotics for a long time [3, 4]. Particu-
larly in traditional societies, the religious beliefs and cultural struc-
ture of the society hinder women from getting health care and may
lead them to traditional applications which is seen also in reproduc-
tive health [5, 6].
Studies have shown that diseases with vaginal discharge are quite
prevalent in rural areas because women have lack of knowledge on
diseases of the reproductive system and overlook symptoms. In the
study by Yldrm, as many as 35.4% of women were found to have
vaginal infections [4].

1
Faculty of Health Sciences, Department of Public Health Nursing, Turkey
2
Ankara Mevki Military Hospital, Dkap, Obstetrics and Gynecology Clinic, Turkey
Correspondence: Derya Adbelli
Email: aricanderya@gmail.com
Objective
In the light of these findings, this study was made with the purpose
of determining the genital hygiene behaviors and associated factors
of women living in rural areas.
Type of study
This is a descriptive study.
Place and time of Study
The study was conducted in Sarkam, Turkey, on dates between
December 1, 2012, and March 15, 2013.
Study population and sampling
The population of the study was 2043 women aged between 20 and
49 and registered at the Sarkam Erenler and Inn Centers of Fam-
ily Health. The sampling of the study included 197 voluntary women
from this population. The insufficient answers by the rural women
comprise an important limitation of this study because women per-
ceived the questions on genital hygiene applications as interference
in their private lives.
Data collection instruments
For data collection, a questionnaire form in accordance with relevant
literature prepared by the authors was used along with a valid and
reliable tool, Genital Hygiene Behavior Inventory (GHBI). The data
was collected with face-to-face interview with women referring to
the family health centers and volunteering to be included in the
study.

Abstract
Background: In traditional societies, religious beliefs and cultural structure direct women more towards conventional behaviors and
applications. This descriptive study was carried out with the purpose of determining the genital hygiene behaviors and associated factors
in women living in rural areas.
Methods: The sample of the study included 197 voluntary single and married women with age range from 20 to 49, registered at the
Sarkam Erenler and Inn Centers of Family Health in Turkey. The data was collected with a questionnaire form prepared according to
the relevant literature and genital hygiene behavior inventory. The results were evaluated with one way analysis of variance, and Kruskal
Wallis and Mann Whitney-U tests.
Results: Most of the women used a vaginal douche (66%) and underwent no gynecologic control annually (57.9%). There were statistically
significant differences in genital hygiene behaviors between women with regards to womens education, marital status, profession/work,
presence or absence of social security, income and husbands work and education (p<0.05). 50.3% changed underwear every day, 36.5%
and 56.9% washed hands before and after changing menstrual pads, respectively, and 41.6% and 66.5% washed hands before and after
using the toilet.
Conclusion: Most of the women living in the rural used vaginal douche and had inferior standards of behavior related to genital hygiene.
Nurses, as trainers and consultants, may help women particularly in rural areas for attaining good standards of reproductive health. (El
Med J 2:3; 2014)
Keywords: Genital Hygiene, Rural Area, Turkey, Women
Adbelli D, Kln N, Akpak YK et al. 211
Questionnaire form
The questionnaire form included socio-demographic questions such
as womens age, education, profession, marital status, social security,
and monthly income of the home as well as gynecologic and obstet-
rical questions such as total number of pregnancies, number of live
children, abortions and still births, frequency of sexual intercourse,
utilization of family planning methods, gynecologic control at least
once a year, bathing in menstrual period, material used in menstrual
period, and use of vaginal douche.
Genital hygiene behavior inventory
The inventory, in the format of a four-level Likert item, was devel-
oped by Ege and Erylmaz in 2005 to determine the genital behaviors
of women aged between 15 and 49 [3]. The inventory is single-di-
mensional and includes 24 positive and 3 negative items. Each item
includes the alternative answers never, sometimes, frequently,
and always. For items with positive statements, the answer never
received 1 point, and the other answers 2, 3, and 4 points,
respectively. For items with negative statements the grading was
done in the reverse way. In the inventory, the lowest and highest
total points are 27 and 108 points, respectively. The high total points
showed good behavior related to genital hygiene. The Cronbachs
alpha value of the inventory was found as 0.86 by Ege and Erylmaz
whereas as 0.87 by us in this study.
Data analysis
The analysis of data was done with SPSS (Statistical Package for So-
cial Science) 20.0 package program. The data was evaluated by using
one way analysis of variance (ANOVA) and Kruskal Wallis and Mann
Whitney U tests. All women were initially informed about the study,
and informed consent was taken from all participants along with ver-
bal and written consents for participation in the study.
Results
The socio-demographic characteristics of women living in rural areas
are shown in Table 1. The demographic characteristics of the women
were as follows: most (45.7%, n=197) in the age group between 30
and 39, 54.3% with high school or university education, 93.4% mar-
ried, 60.9% housewives, % 91.4% with social security, and 39.1% with
monthly family income of 1000 TL or less (n=197).
More than half of the women (52.8%) changed disposable or cloth
menstrual pads in every 3-4 hours in the menstrual period, 25.9% did
not bathe during the menstrual period, 66% used vaginal douches
after sexual intercourse, 21.8% used soap or an antiseptic beside wa-
ter in vaginal douching, and more than half (57.9%) were formerly
informed on genital infections and genital cleaning with patient ed-
ucation and counselling by the nurses. When the genital hygiene be-
haviors of women were compared according to their socio-demo-
graphic characteristics (Table 2); there was no significant difference
between the age groups (F=1.933 p=0.148). This findings implies
that genital hygiene behaviors were similar in all age groups.
There were statistically significant differences in genital hygiene be-
haviors between women with regards to womens education
(F=60.497 p=.000), marital status (KW=6.368 p=.041), profes-
sion/work (t=6.417 p=.000), presence or absence of social security
(U=926.500 p=.018), income (KW=56.658 p=.000), and husbands
work (KW=9.824 p=.007) and education (KW=57.139 p=.000).
Table 1: Distribution of women as to their socio-demo-
graphic characteristics
Characteristics N %
Age 20-29 55 27.9
30-39 90 45.7
40 and over 52 26.4
Education Can read and write 40 20.3
Primary school 50 25.4
Senior high school and over 107 54.3
Marital
status
Married 184 93.4
Single 9 4.6
Widow/Divorced 3 1.5
Profession Not working 75 38.1
Housewife 120 60.9
Work of
husband
Not working 12 6.1
Working 166 84.3
Retired 9 4.6
Education of
husband
Can read and write 7 3.6
Primary school 70 35.5
Senior high school and over 110 55.8
Social
Security
Yes 180 91.4
No 16 8.1
Monthly
income
1000 TL or less 77 39.1
Between 1001 and 2000 TL 46 23.4
2001 TL or more 74 37.6

When the genital hygiene behaviors of women were compared ac-
cording to their obstetrical characteristics (Table 3), there were sig-
nificant differences between (p<0.05) the total number of pregnan-
cies (KW=32342 p=.000), total number of live children (KW=37.272
p=.000), stillbirths (U=484.000 p=.015), frequency of sexual inter-
course (KW=7.914 p=.048) and use of a family planning method
(t=2.513 p=.013). A significant difference also existed (p<0.05) with
smoking (KW=27.615 p=.000) and at least one annual gynecologic
control (t=1.969 p=.050).
There were significant differences in genital hygiene behavior be-
tween women (p<0.05) with regard to changing disposable or cloth
menstrual pads during menstrual period (KW=23.742 p=.000), type
of bathing in the menstrual period (KW=70.562 p=.000), and being
priorly informed on genital infections and genital cleaning (t=7.556
p=.000). Additionally, 50.3% changed underwear every day, 36.5%
and 56.9% washed hands before and after changing menstrual pads,
respectively and 41.6% and 66.5% washed hands before and after
toilet, respectively.
In our study, the Cronbachs alpha value of GHBI was found as 0.87,
and all the item-total point correlations of the inventory were found
significant. The findings indicate the appropriate consistency of the
structure of the inventory.
212 Genital hygiene behaviors of women living in rural areas
Vol 2, No 3
Table 2: Comparison of the genital hygiene behaviors of women according to socio-demographic variables
Characteristics X SD Test P
Age Between 20 and 29 73.44 12.742 F=1.933 .148
Between 30 and 39 76.46 12.525
40 and over 72.13 15.506
Education Can read and write 62.68 11.319
Primary school 67.86 8.836 F=60.497 .000
Senior high school and over 81.97 11.115
Marital status Married 75.12 13.098
Single 70.56 9.207 KW=6.368 .041
Widow/Divorced 46.33 20.648
Profession/Work Working 81.64 12.464 t=6.417 .000
Housewife 70.07 12.187
Work of husband Not working 76.67 11.492 KW=9.824 .007
Working 75.61 12.891
Retired 55.00 16.941
Education of husband Can read and write 52.00 17.991 KW=57.139 .000
Primary school 67.46 8.862
Senior high school and over 80.73 12.194
Social security Yes 75.08 13.612 U=926.500 .018
No 68.44 10.702
Monthly income 1000 TL or under 66.40 11.168 F=56.658 .000
Between 1001 and 2000 TL 71.52 12.103
2001 TL and more 84.70 9.407

Discussion
Problems related to reproductive health comprise an important part
of the womens health problems, and in traditional communities the
religious beliefs and cultural structure hindering women to get
health service divert women more towards conventional behaviors
and applications [7]. In this study, it was found 28.4% of the women
changed 1 or 2 disposable or cloth menstrual pads daily and 25.9%
did not bath during menstrual period. The study by Yamur reported
that 46.5% changed 1 or 2 pads daily and 38% did not bathe during
menstrual period [8]. The study by nsal et al reported that 42% of
the women never bathed when menstruating [9]. In a study on the
genital hygiene behaviors of female prisoners, 27.3% did not bathe
during menstrual period [10].
Another study reported that 21.3% of the women changed pads with
10-hour or longer intervals and that 63.9% used soap and water in
vaginal douching [1]. Thus, the findings of this study are in accord-
ance with the relevant findings in the literature. The accumulation of
menstrual blood in pads present a humid, warm and bloody medium
which enhances bacterial growth, increasing the risk of infection.
When limitations in money and transportation necessitate the use of
cloth menstrual pads, the cloth menstrual pads should be frequently
changed, washed by boiling, and ironed. Such pads should be made
of cotton and kept in a clean place until the time of use [2]. One of
the important findings in this study was that 57.9% of the women
did have no gynecologic control at least once annually. Urogenital
infections which can be prevalent are sometimes may be perceived
as not diseases by women of low socio-economic level, particularly
by those living in rural areas. Although some women know that
these infections are diseases, they refrain from gynecologic exami-
nation or perceive genital diseases as stigmatizing and consequently
resort to self-treatment instead of seeking medical care [11, 12].
Our study showed that 66% of the women used a vaginal douche
after sexual intercourse and 21.8% used soap and antiseptics with
water for vaginal douching. The rates of women using vaginal
douche were reported as 43% by Yamur, 72.1% by Karatay and
zvar, 87% by Kotu and Beyda, and 20-40% in the United States
by Anderson and et al [1, 2, 8, 13]. It was also reported that 63.9%
of the women used soap and water in vaginal douching [2]. Other
studies showed that more than half of the women used vaginal
douche [14-16]. The relevant findings of our study are in accordance
with the literature. Vagina douche is associated with cultural or reli-
gious values [5, 17]. Sometimes menstruation is described as get-
ting dirty by women. Married women describe themselves as dirty
after sexual intercourse because of seminal fluid in the vagina [18].
Other reasons for using vaginal douche are to get rid of vaginal dis-
charge, irritation or odor, to prevent or treat vaginal infections, and
to contracept pregnancy [6, 19]. Vaginal douche leads to chronic col-
onization of bacteria and enhances their migration into upper geni-
tal tract. A meta-analysis has shown that vaginal douche increases
the risk of pelvic inflammatory disease by 73% [20]. In women using
vaginal douche, the changes in vaginal flora caused by bacterial vagi-
nosis also increase the risk of HIV infection. The traditional habit of
Adbelli D, Kln N, Akpak YK et al. 213
Table 3: Comparison of the genital hygiene behaviors of women according to obstetrical and gynecologic variables
Characteristics X SD Test P
Number of total pregnancies No pregnancy 74.18 14.905 KW=32.342 .000
1, 2 or 3 pregnancies 78.04 12.450
4 or more pregnancies 63.90 11.548
Number of live children No children 74.05 14.361 KW=37.272 .000
1, 2 or 3 children 77.85 12.013
4 or more children 60.63 11.379
Spontaneous abortion Yes 73.96 14.872 t=.396 .693
No 74.88 13.296
Self-induced abortion Yes 68.37 16.412 U=1218.500 .085
No 75.37 13.179
Still birth Yes 64.40 10.783 U=484.000 .015
No 75.24 13.594
Frequency of sexual intercourse Once a month 69.44 16.488
Once a week 75.00 13.004 KW=7.914 .048
2-3 times a week 76.27 13.109
Every day 60.33 13.837
Use of family planning Yes 76.58 12.799 t=2.513 .013
No 71.31 14.878
Smoking Never smoked 71.82 12.707
Smoked but quitted 86.23 10.023 KW=27.615 .000
Less than a package daily 76.54 13.585
More than a package daily 61.50 20.506
Gynecologic control visits Yes 76.67 12.339 t=1.969 .050
No 72.87 14.114
vaginal douching after sexual intercourse is probably the highest risk
factor for vaginal infections. Vaginal douche is widely used as a tool
of female hygiene.
In our study, when the genital hygiene behaviors of women were
compared according age, there was no significant difference be-
tween the age groups (p>0.05). However, there were statistically sig-
nificant differences in education, marital status, profession/work,
presence or absence of social security, and income (p<0.05). Ege and
Erylmaz reported no significant relationship between genital hy-
giene behavior and age and monthly income of women [3]. The find-
ing related to age is in accordance with our study, but the finding
related to income is not. In our study we noted that genital hygiene
behavior was better in women with good monthly income. Increase
in monthly income may bring better conditions of life and health
care, leading to a better application of appropriate hygienic
measures.
Yamur reported that women with high educational level, good in-
come and job bathed more frequently [8]. Ege and Erylmaz reported
that senior-high school graduates had higher averages of GHDI
points [3]. These findings might indicate that parallel to the increase
in educational level, knowledge on genital hygiene and awareness
of genital infections increase in women. Additionally, Yamur
showed that applications for genital hygiene were better in working
women [8]. Also Ege and Erylmaz found a significant relationship
between profession/work and genital hygiene applications [3]. This
finding leads us to think that the interactive relations in a social en-
vironment and relatively better economic conditions of a working
woman positively affect her genital hygiene behavior.
In our study, we found that the husbands profession/work and edu-
cation significantly affected the womens genital hygiene behaviors.
Likewise, Ege and Erylmaz reported that the higher was the hus-
bands education level, the better was the wifes genital hygiene be-
havior [3]. Our study showed that only half of the women changed
their underwear everday, almost half of the women washed hands
before changing menstrual pads and before toilet, and more than
half of the women washed hands after changing pads and after toi-
let. The rate of women changing underwear every day was reported
as 40% by et al and as 81.8% by Arslan zkan and Kulaka [9, 10].
The findings of the studies in the literature on the relationship be-
tween hand hygiene and genital hygiene are in accordance with our
results. Arslan zkan and Kulaka reported that 60% of the women
washed hands before toilet, 69% before sexual intercourse, and
69.1% before changing pad [10]. In daily life, hands have the most
contact with the environment and consequently are the dirtiest or-
gans. We think that increased hand-washing after contact with
214 Genital hygiene behaviors of women living in rural areas
Vol 2, No 3
genitals shows that women accept the genital region as dirty and do
not wash hands if hands are not apparently dirty.
Conclusions and recommendations
In conclusion, most of the women use vaginal douche and have in-
adequate behavior related to genital hygiene. Life in the rural are
limits attaining protective health measures and relevant training.
Training individuals on and making them responsible for appropriate
genital hygiene behavior are the duty of nurses who are in closest
contact with the individuals/patients in the community. Nurses, as
trainers and consultants, may help women particularly in rural areas
for attaining good standards of reproductive health.
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2014 Prasad et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Prasad BK, Shrestha DG: A comparative study of open tracheostomy and percutaneous tracheostomy in ICU setting. El Mednifico Journal 2014, 2(3): 215-218.
A comparative study of open tracheostomy and percutaneous tracheostomy in ICU setting
Bipin Kishore Prasad
1
, Devjani Ghosh Shrestha
2

Background
The earliest known depiction of a tracheotomy is found on two Egyp-
tian tablets dating back to circa 3600 BC [1]. Antonio Musa Bras-
savola (14901554) of Ferrara successfully treated a patient suffering
from peritonsillar abscess by tracheotomy. Brassavola published his
account in 1546. This operation has been identified as the first rec-
orded successful tracheostomy, despite the many ancient references
to this operation [2]. However in 1909, Philadelphia laryngologist,
Chevalier Jackson (18651958) described a standard operative tech-
nique for tracheotomy that has remained little changed over more
than a hundred years [3]. Alternative procedures like percutaneous
tracheostomy have evolved recently due to advance in technology
and interest in minimally invasive procedures.
The origin of percutaneous tracheostomy is not certain, although the
Italian surgeon Sanctorius was probably the first to describe the
technique in the 16
th
century. Sheldon et al used the term percuta-
neous tracheotomy in 1955 and described the method using cutting
trocar as an alternative to the surgical route [4]. Toye and Weinstein
introduced the technique using the Seldinger guidewire technique
based on a single tapered dilator with a recessed cutting blade [5].
However the cutting trocar and blade caused lot of complications
hence it has since been refined with various modifications.
The percutaneous dilatational tracheostomy (PDT) introduced by
Ciaglia et al in 1985, which involves progressive dilatation with se-
quentially larger blunt-tipped dilators, is the most frequently used
and evaluated in the literature [6]. In 1990, Griggs et al further im-
proved the technique by using the guidewire dilating forceps
(GWDF), a modified Howard-Kelly forceps with blunt edges [7]. In

1
Department of ENT, Military Hospital, Kirkee, Pune, Maharashtra, India.
2
Department of ENT, NRS Medical College, Kolkata, West Bengal, India.
Correspondence: Bipin Kishore Prasad
Email: bipin1405@gmail.com
2000, Byhahn et al introduced the Ciaglia Blue Rhino (CBR), a modi-
fied version of the Ciaglia technique where dilation of the stoma was
done in a single step by means of a hydrophilically coated curved
dilator, the Blue Rhino [8]. This markedly reduced the complications.
In 2002, the latest variation of PCT was introduced by Frova and
called PercuTwist technique which involves controlled rotating dila-
tion using a single screw dilator [9]. CBR method is currently the
most commonly used PDT procedure worldwide.
This is a pilot study conducted in a tertiary care medical referral cen-
ter of Indian Army, and reports the comparison of open surgical
standard tracheostomy with percutaneous tracheostomy.
Objectives
The objectives of the study were:
(i) To compare the techniques of open standard tracheostomy with
percutaneous guidewire dilating forceps (GWDF) method and
PercuTwist tracheotomy method;
(ii) To compare the complications of the open standard tracheost-
omy with percutaneous tracheostomy.
This study was conducted by Department of ENT and head and neck
surgery in a tertiary care Indian Army hospital.
Inclusion criteria: patients who were in ICU, intubated and on pro-
longed ventilation needing elective tracheostomy were included in
the study. Type of tracheostomy was decided on the basis of se-
quence of need for tracheostomy in ICU. Thus, the first patient need-
ing tracheostomy underwent open standard tracheostomy (OST)

Abstract
Background: The standard tracheostomy involves open standard dissection technique, established more than a hundred years ago.
Alternative procedures like percutaneous tracheostomy (PCT) have evolved recently due to advance in technology and interest in
minimally invasive procedures. A systematic randomized comparative cohort study was done with the aim to compare standard open
tracheostomy with percutaneous tracheostomy techniques, namely serial guide wire dilating forceps (GWDF) and PercuTwist.
Methods: This study was carried out in the Department of ENT and head and neck surgery in a tertiary referral medical center of Indian
Army. The patients were followed up for one year post-decannulation or till their death due to medical morbidities. 45 adult patients in
ICU, intubated and on prolonged mechanical ventilation, needing elective tracheostomy were included in the study. Pediatric cases,
patients with distorted neck anatomy and those requiring emergency tracheostomy were excluded. 15 patients underwent standard open
surgical tracheostomy. Amongst the other 30 cases, 15 percutaneous tracheostomy were done by guide wire dilating forceps technique
and remaining 15 by PercuTwist.
Results: Although the indications were limited and another surgeon was required to keep a watch through bronchoscope, it was observed
that PCT was easier and quicker than open standard tracheostomy. It involved small incision and no dissection, less tissue trauma and
better cosmetic result. Comparatively, the complication rate was also less.
Conclusion: It can be concluded that training of surgeons and proper case selection makes percutaneous tracheostomy as good and safe
as open technique. (El Med J 2:3; 2014)
Keywords: Tracheostomy, Percutaneous, Guidewire Dilating Forceps, PercuTwist, Bronchoscope
216 Open tracheostomy and percutaneous tracheostomy in ICU
Vol 2, No 3
whereas the second was chosen for GWDF and the third for PercuT-
wist. The fourth patient was again chosen for OST and so on and so
forth.
Exclusion criteria: Pediatric patients, patients with distorted neck
anatomy and unidentifiable anatomic landmarks, patients with co-
agulopathy and patients requiring emergency airway access were
excluded from the study.
Technique of percutaneous tracheostomy: The GWDF set consists
of a Seldinger type 14 gauge Teflon cannula and needle, a J-guide
wire, sharply tapered & angled dilator with a soft hydrophilically
coated tip and the dilating forceps. In PercuTwist set, instead of di-
lator and dilating forceps, a step dilator with self-tapping screw is
used. In addition to the set, one also needs local anesthetic with
adrenaline, lubricating jelly, fiber optic bronchoscope, catheter
mount to accept the scope and standby trolley for open surgical tra-
cheostomy.
The patient is positioned with neck extended to bring the trachea as
much anterior as possible. Parts prepared and draped. Important
landmarks identified and marked, namely- laryngeal notch, cricoid,
suprasternal notch and the incision site ie gap between 2
nd
and 3
rd

tracheal ring. Bronchoscope is introduced through endotracheal
tube which is withdrawn up to subglottis. Local anesthetic with
adrenaline is infiltrated subcutaneously. Horizontal 1 cm incision is
made with a scalpel. Introducer needle with cannula with a syringe
is inserted between 2
nd
and 3
rd
tracheal rings and advanced at 45
degree to the skin, till air is aspirated from trachea. Trick is to be
always in midline. Syringe with needle is withdrawn. J-tip guide wire
is introduced through the cannula into the trachea. Its position is
confirmed by visualizing through the bronchoscope. It is this guide
wire that forms the backbone over which dilators are inserted.
In GWDF technique, a small dilator is introduced for initial dilatation
over the guide wire. Then a specially designed grooved (Howard
Kelly) forceps is threaded on the guide wire through a hole in the tip
of the closed forceps, and inserted into the trachea. Spreading the
forceps dilates the trachea to the desired point at which the chosen
tracheostomy tube can be inserted. In PercuTwist, a single step screw
type dilator is used. This is threaded into the tracheal stoma using a
lifting motion, thus widening the initial access to the trachea by care-
fully rotating the dilator clockwise into the soft tissue. The end of the
thread of the dilator cuts through the anterior tracheal wall and is
endoscopically seen in the trachea. Dilation process is continued by
gentle elevation of the anterior tracheal wall with the dilator while
screwing it further intra-tracheally. Dilator is removed by carefully
rotating it in a counter-clockwise direction out of the trachea, with
the guide wire remaining in the trachea. Once the desired tracheal
dilation has been achieved, suitable size cuffed tracheostomy tube
is inserted into the trachea with the help of an introducer which is
threaded over the guide wire. Finally the guide wire, the introducer
and the endotracheal tube are removed and ventilator is connected
to the tracheostomy tube. It is secured with tapes.
Results
Subjects in this study were 45 adult patients on long-term mechani-
cal ventilation in ICU. There were 32 male and 13 female patients.
Only 9 patients were below 50 years where as 36 were above 50
years of age. 15 patients underwent standard open surgical trache-
ostomy and 30 underwent percutaneous tracheostomy (PCT). Out of
these 30, 15 PCTs were done by GWDF technique and 15 by PercuT-
wist (Table 1). Majority of the patients were of head injury (21 pa-
tients) and cerebrovascular accidents (12 patients) (Table 2).
Table 1: Tracheostomy techniques in patient groups
Technique N Gender Age of patients (years)

M F 15-25 26-49 50-64 65-85
OST* 15 10 5 1 1 8 5
GWDF* 15 11 4 1 2 7 5
PT* 15 11 4 1 3 8 3
Total 45 32 13 3 6 23 13
*OST: Open standard technique; GWDF: Guidewire dilating forceps; PT: PercuTwist technique.

Table 2: Diagnosis of patients undergoing tracheostomy
Diagnosis OST* GWDF* PT* Total
Head injury 7 7 7 21
Cerebrovascular accident 3 4 5 12
Intracranial SOL
#
1 1 - 2
Multisystem failure 2 2 1 5
Underlying malignancy - 1 1 2
Diabetes with ESRD
#
- - 1 1
GuillainBarr syndrome 1 - - 1
Chronic subdural hematoma 1 - 1
Total 15 15 15 45
#
SOL: Space occupying lesion; ESRD: End-stage renal disease.

The decision to perform tracheostomy was taken within 6 to 15 days
of endotracheal intubations depending on the requirements of the
intensive care specialists. The mean duration of percutaneous tra-
cheostomy in our patients by both methods i.e. from skin incision to
successful insertion of tracheostomy tube was 8 minutes with a
range of 6 to 14 minutes. The duration varied between 10 to 30
minutes in open surgical technique. Two of our patients (13.3%) who
underwent percutaneous tracheostomy with PercuTwist technique
had chip fracture of tracheal cartilage ring. There was no other com-
plication in any patient undergoing percutaneous tracheostomy.
Per-operative bleeding was the main complication in patients
(33.3%) undergoing standard open tracheostomy, which in all cases,
could be easily controlled by cautery (Table 3).
Table 3: Intra-operative complications
Complication OST* GWDF* PT*
Bleeding 5(33.3%) - -
False passage - - -
Oxygen desaturation - - -
Hypotension - - -
Fracture of tracheal ring - - 2(13.3%)
Damage to posterior tracheal wall - - -
Prasad BK, Shrestha DG 217
All cases of percutaneous tracheostomy had uneventful post-opera-
tive period, although the short length of the tracheostomy tubes in-
situ was a cause of unnecessary concern to the anesthesiologists.
During post-operative period of patients who had undergone open
standard tracheostomy, two had minor bleeding, which was man-
aged conservatively with stomal packs. Subcutaneous emphysema
was noticed in one patients. One patient had excessive purulent ex-
udate at stoma (Table 4).
Table 4: Post-operative complications
Complication OST* GWDF* PT*
Bleeding 2 (13.3%) - -
Surgical emphysema 1 (6.67%) - -
Wound infection 1 (6.67%) - -
Tube displacement - - -
Tube blockage - - -
Pneumothorax - - -
Tracheo-esophageal fistula - - -

Successful decannulation was achieved in 14 patients (31.1%). Con-
version to permanent tracheostomy was not necessary in any pa-
tient. Wound approximation by surgery was required in one patient
(2.2%) after decannulation. 24 patients (53.3%) died as a conse-
quence of the primary disease. Six patients (13.3%) were lost to fol-
low up (Table 5).
Table 5: Outcome of patients
Outcome OST* GWDF* PT* Total
Successful decannulation 5 5 4 14(31.1%)
Permanent tracheostomy - - - -
Surgical closure of stoma 1 - - 1(2.2%)
Died due to primary disease 9 6 9 24(53.3%)
Lost to follow up 2 1 3 6(13.3%)

Discussion
Percutaneous tracheostomy is an established procedure for airway
management in critically ill patients who require long-term respira-
tory support and has already replaced the surgical route in several
intensive care units. Though the incidence of complications with per-
cutaneous tracheostomy varies with the different techniques used, it
is fewer compared to open surgical technique [10]. Some authors
have also suggested use of fiber optic bronchoscope to reduce th
procedural complications. This has been mainly due to the fact that
bronchoscopy can help to verify the safe placement of needle and
guide wire and to avoid trauma to posterior tracheal wall during di-
latation [11].
We performed percutaneous tracheostomy using GWDF and PercuT-
wist technique with the aid of bronchoscope. The placement of nee-
dle in the trachea was confirmed by free aspiration of air as well as
bubbling of air through the drop of fluid placed over the hub of the
needle. In addition the free movement of guide wire at each stage
of the procedure was taken as prerequisite for proceeding further.
With bronchoscopic assistance, the tip of the ETT as well as the nee-
dle puncture site in the midline of the trachea and dilation of the
tracheal stoma can be visualized.
By strictly adhering to these simple precautions, we were able to
achieve successful and accurate placement of tracheostomy tube in
all our patients without any major complications. In our study, there
was no desaturation, accidental extubation, endotracheal tube or
cuff puncture. The only significant complication encountered was
fracture of tracheal ring during PercuTwist dilatation in 2 of our pa-
tients which has been reported with PercuTwist by Emmanuel Scher-
rer and with Ciaglia Blue Rhino technique by Christian Byhahn [8,
12].
The duration of the percutaneous tracheostomy is much shorter than
conventional technique and in our patients (Mean: 8 min, range: 6
to 14 min) it was comparable to some other studies with duration of
4.3 to 13.6 min 13. None of the 15 patients, available for follow up
till one year, had any late complications like left-sided vocal cord pa-
ralysis, abnormal granulation tissue, hoarseness of voice and voice
change, as was revealed by an ENT examination performed one
month after decannulation.
Conclusion
This study concludes that percutaneous tracheostomy is now a well-
established technique used in the critical care setting. In general it is
an elective procedure, and not suitable for the emergency airway.
Both the techniques, percutaneous GWDF method and PercuTwist
tracheotomy are easy, safe, quick and have low rate of complications.
Although the technique may be performed without visualization, as-
sistance of fiber optic bronchoscope helps to maintain excellent
safety record.
Recommendation
Percutaneous tracheostomy is a good alternative to standard open
tracheostomy in intubated patients. It should be encouraged be-
cause of its procedural ease, quick and safe technique and low com-
plication rate. It is however mandatory to keep a standby trolley
ready for open tracheostomy.
Received: 1 February 2014 Accepted: 1 August 2014
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2014 Kaur et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits
Cite this article as: Kaur S, Azreena AI, Leong KN, Narayanasamy S: Effect of pesticides on color vision and anterior ocular structure of farmers. El Mednifico Journal 2014, 2(3): 219-222.
Effect of pesticides on color vision and anterior ocular structure of farmers
Sharanjeet Kaur
1
, Azizan Izzah Azreena
1
, Khang Nie Leong
1
, Sumithira Narayanasamy
1

Introduction
Pesticides are a broad range of substances which are most com-
monly used to control insects, weeds, fungi and other plant diseases.
There is continual evidence that pesticide exposure is associated
with impaired health. The exposure is associated with a range of
symptoms as well as deficits in neurobehavioral performance, abnor-
malities in nerve function and changes in ocular structures.
In Malaysia, it has been reported that 98% of the farmers apply the
use of pesticides in their farms and 54% of the farmers have been
reported with pesticide poisoning due to the exposure [1]. The main
source of income for the district of Cameron Highlands is through
hydroelectric generator and agriculture. The agricultural land in
Cameron Highlands consists of vegetation farming, tea farms, flower
farms and fruit farms [2]. Therefore, there is a wide range for the use
of pesticides in this district. Most pesticides used are insecticides.
Prominent insecticide families include organochlorines, organophos-
phates and carbamates.
Studies have shown that exposure to pesticides may result in
changes of the ocular structures such as symblepharon, edema and
hyperemia in conjunctiva, edema, scarring, ulceration, perforation
and vascularization in cornea, and cataract [3-5]. Pesticides have also
been known to cause several types of color vision defects. Toluene,
which is one of the chemical compounds in pesticides, has been
known to affect both visual acuity and color discrimination [6]. Color
vision loss in the blue-yellow range has also been reported due to
exposure to toluene [7]. Perchloroethylene, another compound in
pesticide, also affects color vision. It has been known that workers
exposed to perchloroethyelene performed significantly worse than
those that are not exposed [8]. Solvent mixtures, such as those that
consist of toluene, xylene, acetone, and methyl butyl ketone have
also been known to cause color vision defects in workers exposed to

1
Optometry & Vision Sciences Program, Center for Healthcare Sciences, Faculty of
Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda, Kuala Lumpur,
Malaysia.
it, exhibiting blue-yellow loss through the FM100Hue Test [9]. Work-
ers who had been exposed to a mixture of solvents, chlorofluorocar-
bons or pesticides had been reported to have defect in color vision,
which includes blue-yellow loss and complex loss (blue-yellow and
red green) [9].
Objectives
This study was conducted to determine the incidence of color vision
defects and anterior ocular structure abnormalities among farmers
using pesticides in Cameron Highlands, Malaysia. The second objec-
tive was to determine the correlation between exposure duration
with anterior ocular structure abnormalities and color vision defects
among these farmers.
This study was carried out in the farms in Cameron Highland, Pa-
hang, Malaysia. It was a cross-sectional study with convenient sam-
pling. Sample size was calculated using the Cochrane Formulae [10].
A representative sample for proportions among a large population
of farmers was calculated; thus 74 farmers were recruited.
Written consent was obtained before examination. Approval from
the Research & Ethical Committee of Universiti Kebangsaan Malaysia
was obtained. The study was conducted according to the tenets of
Declaration of Helsinki.
An official letter of invitation was sent to the Cameron Highlands
Farmers Association to invite all members to participate in the study.
The farmers who came were given a consent form, information sheet
about the research and questionnaire to fill up. The questionnaire
aided in recruiting eligible farmers by using inclusion and exclusion
criteria. Inclusion criteria included farmers age range of 20 to 60
Correspondence: Sharanjeet Kaur
Email: sharanjeet.kaur32@yahoo.com
Abstract
Background: Studies have shown that exposure to pesticides can affect ocular structure and color vision. The objectives of this study were
to determine the incidence and effect of exposure on anterior ocular structure and color vision among farmers using pesticides in Cameron
Highlands, Malaysia.
Methods: Farmers in Cameron Highlands using pesticides that volunteered and fulfilled the inclusion criteria were recruited. A
comprehensive optometric examination was conducted. Color vision was assessed using Ishihara plates, D-15 test and FM100Hue test
under daylight illumination.
Results: Seventy-four farmers of mean age 32.24 1.23 years old were recruited. The only anterior ocular changes observed was bulbar
conjunctival hyperemia with an incidence of 25.7%. The mean working hours was 8.83 3.58 and the mean working years was 7.69 8.35.
Only 23% of farmers wore goggles to protect their eyes. The incidence of farmers with color vision defects was 5% using Ishihara Plates,
29% using D15 test and 49% using FM100Hue test. Majority of the color defects were of non-polar type. The mean total error score of the
color vision defectives was 170.67 for the right eye and 163.81 for the left eye. There was a significant correlation between the duration of
working hours (r=0.46, p=0.000) with the total error score.
Conclusion: Exposure to pesticides can cause hyperemia and color vision defects in farmers and the severity correlates highly with
exposure duration for color vision defects. (El Med J 2:3; 2014)
Keywords: Anterior Ocular Structures, Color Vision, Farmers, Pesticides
220 Effect of pesticides on color vision and anterior ocular structure
Vol 2, No 3
years old and working in the field/farm for more than 3 years. Exclu-
sion criteria include taking any kind of medications, such as pheny-
toin, ethambutol, chloroquine, digitalis and others for more than six
months, any history of trauma or surgery on any part of the head or
the eye. Only nonsmokers and nonalcoholic farmers were recruited.
The questionnaire also included information such as age, years of
employment, working hours in the field, the use of protective eye-
wear when handling pesticides, and history of head injury.
Eligible farmers underwent several tests. An optometric examination
was conducted which included vision assessment for distance and
near, subjective non-cycloplegic refraction, binocular vision assess-
ment and ophthalmoscopy. If all was found to be within the eligible
criteria, slit lamp biomicroscopy (Handheld Slit Lamp Kowa (SL- HR
150 561646) was carried out to assess anterior ocular structures and
their eyes were photographed using a DSLR camera, Nikon D90 with
the Nikon DX AF-S NIKKOR 18-105mm lens.
After the photography, the farmers were given 30 minutes to recover
from the after images created by the bright light of the slit lamp.
Color vision was then assessed using Ishihara plates, D-15 test and
FM100Hue test. The color vision tests were performed using the cor-
rect illumination as recommended by the test manuals under day-
light illumination (using the Philips Fluotone Lifemax TL-D 36W/54
lighting). All tests were conducted monocularly.
Results
The normality of the data was determined by using the Shapiro-Wilk
test. According to the test, certain collected data was normally dis-
tributed. Therefore all data analysis was analyzed by using non par-
ametric tests. All data were analyzed using the SPSS Program, Ver-
sion 16.
Anterior ocular structures
The mean age of the farmers recruited was 32.24 1.23 year old. The
only changes observed was bulbar conjunctival hyperemia. The ob-
served changes were found to be similar for right eye and left eye,
and as such, data of the right eye only is presented here. Incidence
of bulbar conjunctival hyperemia was found to be 25.7%. Means and
standard deviation of duration of exposure to pesticides with
changes in anterior ocular structure was analyzed in terms of work-
ing years and working hours by using Independent t-test. There was
no statistically significant correlation between changes in ocular
structure and working hours of the farmers. There was no statistically
significant difference found for means of working years (t=0.019,
p=0.985) and working hours (t=1.014, p=0.314) among farmers with
hyperemia and without hyperemia. (Table 1) In addition, Chi Square
test showed that there was no association between the use of pro-
tective eyewear with bulbar conjunctival hyperemia [
2
(1,N=74)
=2.238, p=0.135]. Although the results showed that there was no di-
rect correlation between the uses of protective eyewear with
changes in the anterior ocular structures, the prevalence of hypere-
mia was higher among farmers who did not use protective eyewear
that was 29.8%, if compared with farmers who used protective eye-
wear that was 11.8 % (Table 2 and 3).
Color vision status
The color vision status tested in the right eye and left eye was similar.
As such, only data for the right eye is presented.
Table 2: Number of farmers using protective eye wear and
having bulbar conjunctival hyperemia.
Bulbar conjunctival hyperemia
Total No Yes
Eye wear Yes 15 (88.2%) 2 (11.8%) 17
No 40 (70.2%) 17 (29.8%) 57
Total 55 19 74

Table 3: Chi Square test of use of protective eyewear with
hyperemia at level of precision, = 0.05
2
dk P
2.238 1 0.135

Figure 1 shows the number and percentage of farmers that passed
and failed the Ishihara Plates Tests for both eyes. Figure 2 and Figure
3 show the types of color defects found in the farmers with the D15
test and FM100Hue test respectively.
Five percent of farmers failed the Ishihara plates test indicating a
possible congenital color vision defect. D15 test revealed that 29%
of farmers failed the test with 23% showing a non-polar type of color
defect. FM100Hue test showed that 49% of farmers had color vision
defects with 27% showing a non-polar type of color defect.
There was a statistically significant correlation between total error
score and working hours (Spearman rho=0.371, p=0.001) of the
farmers. In addition, Chi Square test showed that there was an asso-
ciation between the use of protective eyewear with not having a
color vision defect [
2
(1,N=74)=4.078, p=0.0435]. It can be seen from
Figure 4 and Table 4 that the prevalence of having a color vision
defect is higher when no protective eye wear is used by the farmers.

Table 1: Means and standard deviation in terms of working years and working hours with hyperemia and Independent t-test at
level of precision = 0.05.
Bulbar conjunctival hyperemia N Means Standard deviation Std. Error Mean t value
Working years No 55 7.15 7.913 1.067 t = 0.019
Yes 19 7.11 8.530 1.957 p = 0.985
Working hours No 55 9.78 2.780 0.375 t = 1.014
Yes 19 8.95 3.880 0.890 p = 0.314
Kaur S, Azreena AI, Leong KN et al. 221

Figure 1: Number and percentage of farmers that failed and
passed the Ishihara Plates Test.

Figure 2: Performance of farmers with the D-15 Test.

Figure 3: Performance of farmers with FM100Hue Test.

Figure 4: Number and percentage of farmers wearing goggles.
Table 4: Number of farmers wearing protective eye wear
and having color vision defects.
Color defects
Total No Yes
Eye wear Yes 8 (18.8%) 12 (16.2%) 20
No 8 (18.8%) 46 (62.2%) 54
Total 16 58 74
Discussion
This study showed that the anterior ocular structure changes devel-
oped in farmers exposed to pesticides was bulbar conjunctival hy-
peremia only. This was also shown by a study by Mckeag et al [11].
There was however, no association between having bulbar conjunc-
tical hyperemia with duration of working hours or wearing protec-
tive eye wear. Although the results showed that there was no direct
correlation between the uses of protective eyewear with changes in
the anterior ocular structures, the incidence of hyperemia was higher
among farmers who did not use protective eyewear which was 17
out of 57 agricultural workers (29.8%) when compared to 2 of 17
agricultural workers who used protective eyewear (11.8%). Jaga &
Dharmani reported that long-term exposure to pesticides may ini-
tially not manifest any toxic effects in the exposed population [12].
There may be pathological effects at the cellular level in the eye,
which may take years to progress into a clinical ocular condition but
the exact duration of clinical significant ocular conditions to be de-
veloped cannot be determined. Thus, lack of eye protection and
poor protective practices are believed to contribute to the major
causes of toxic exposures of eyes instead of duration of exposure.
In the study by Center of Disease Control (CDC) on Hydrogen Cyan-
amide (plant growth regulator) exposure, 14 of 21 agricultural work-
ers (67%) who did not use complete or no personal protective equip-
ment especially protective eye goggles were found to have in-
creased eye symptoms [13]. Although the prevalence of increased
eye symptoms for CDC study was higher, but due to the small sam-
ple size of the present study, a relationship of eye signs and symp-
toms (bulbar conjunctival hyperemia) with protective eyewear could
not be established. Nevertheless, farmers are recommended to wear
protective goggles when they are exposed to the pesticides to re-
duce chances of increased eye symptoms such as hyperemia.
The present study also found that 29% and 49% of farmers exposed
to pesticides had a color vision defect when tested with the D15 test
and FM100Hue Test respectively. Those who developed color vision
defects had been working for duration of 10.71 1.97 hours per day
compared to 5.25 2.32 hours per day for those who had no color
vision defects. There was a statistically significant correlation be-
tween total error score and working hours (spearman rho=0.371,
p=0.001) of the agricultural workers. In addition, Chi Square test
showed that there was an association between the use of protective
eyewear with not having a color vision defect (
2
(1,N=74)=4.078,
p=0.0435).
Many studies have shown that color vision was very sensitive to oc-
cupational chemicals (toluene, styrene, mixture of organic solvents)
and the effects were dose-dependent [14-20]. In a number of studies,
0
10
20
30
40
50
60
70
N=70 (95%)
N=4 (5%)
Pass
Fail
0
10
20
30
40
50
60
N=52 (70%)
N=1 (1.4%)
N=4 (5.4%)
N=17 (23%)
Normal
Protan
Deutan
Non-polar
0
10
20
30
40
N=38 (51%)
N=1 (1.4%)
N=15 (20%)
N=20 (27%)
Normal
Deutan
0
10
20
30
40
50
60
N=20 (27%)
N=54 (73%)
Yes No
222 Effect of pesticides on color vision and anterior ocular structure
Vol 2, No 3
the observed color vision impairment was dose-related. The quanti-
tative indices of color vision loss were found to increase with expo-
sure level [21, 22]. Other studies have shown that low level expo-
sures of organic solvents which are below the occupational exposure
limit can affect color vision [23, 24].
The issue of a possible long term cumulative effect from exposure to
styrene was studied by Castillo et al [25]. They showed that color
vision improved for workers whose styrene exposure decreased
(over 8 years), though impairment of other visual functions (e.g. con-
trast sensitivity) indicated cumulative exposure and chronic damage
to the neuro-optic pathway. The possible cumulative effects of sol-
vent mixtures were addressed by a few studies. Gonzales et al
showed that exposed workers with a higher cumulative exposure
had a more complex loss, i.e. anarchic type of defect [26]. They also
found a correlation of color vision loss with the total duration of ex-
posure to solvents. Semple et al also found similar trends in their
study and demonstrated that reduced color discrimination was sig-
nificantly associated with annual exposure as well as to cumulative
exposure [27]. This was also observed in the present study. However,
there are some previous studies that have shown that there is no
correlation between working hours and total error score of the
FM100Hue test [26, 28, 29]. Therefore, the pathogenesis of the effect
of solvents on color vision is still unclear.
Conclusion
Exposure to pesticides can cause bulbar conjunctival hyperemia and
color vision defects in farmers exposed to pesticides. The color vision
defect correlates highly with exposure duration and use of protective
eye wear.
Recommendations
Farmers who use pesticides should wear protective eye wear to pro-
tect their eyes from harmful effects. This study shows that long term
exposure to pesticides can affect color vision.
Received: 23 January 2014 Accepted: 7 August 2014
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2014 Ogba et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Ogba OM, Mandor BI, Omang H: Antibiotic susceptibility pattern of Serratia marcescens isolates from wound infections in a tertiary health institution in Calabar, Nigeria. El Mednifico Journal
2014, 2(3): 223-226.
Antibiotic susceptibility pattern of Serratia marcescens isolates from wound infections in a tertiary
health institution in Calabar, Nigeria
Ofonime Mark Ogba
1
, Baki Idasa Mandor
2
, Helena Martin Omang
2

Background
Serratia marcescens are opportunistic gram-negative, motile, faculta-
tive anaerobic bacilli. They are classified in the tribe Klebsielleae and
the large family Enterobacteriaceae. They are widespread in the envi-
ronment, but are not a common component of the human fecal
flora. Over the last 40 years, Serratia marcescens has become an im-
portant cause of nosocomial infections [1, 2].
Serratia marcescens grows at 37C, but it can grow in temperatures
that range from 540C. They grow in pH levels that range from 5 to
9. The organism is well known for the red pigmentation it produces
called prodigiosin. However, many pathogenic strains are not pig-
ment producers. The pigmented bacterium is found in various eco-
logical niches, including soil, water, air, plants and animals [3, 4]. The
potential of S. marcescens to utilize a wide range of nutrients is ex-
pressed clearly by its ability to survive and grow under extreme con-
ditions, like in disinfectants, antiseptics and double-distilled water [5-
8].
S. marcescens infections have increased over the last few years. It
now causes 11% of burn-related surgical wound infections [2]. Yu et
al reported 5% prevalence rates among surgical wound patients [9].
This emergence is mainly attributed to the acquisition of multiple
antibiotic resistances and to the ability of the bacteria to adhere and
persist on unanimated surfaces [10, 11]. The organism has also been
implicated in pneumonia, lung abscess, empyema, meningitis, uri-
nary tract infections, endocarditis, septic arthritis, osteomyelitis, per-
itonitis, sinusitis and septicemia [4, 12]. Patients at risk are those with
debilitating disorders, those treated with broad-spectrum antibiotics
and those in intensive care who are subjected to instrumentation
such as tracheostomy tubes or indwelling catheters {4]. S. marcescens

1
Department of Medical Laboratory Science, University of Calabar, Calabar, Nigeria
2
Department of Medical Microbiology/Parasitology, University of Calabar Teaching
Hospital, Calabar, Nigeria
infections are known to be transmitted through hand-to-hand con-
tact by medical personnel. Solutions used for medical purposes,
catheterizations, and needle punctures can be contaminated and in-
fect patients [13].
Most members of the genus Serratia, including S. marcescens are usu-
ally resistant to ampicillin, amoxicillin, amoxiclav, ampicillin-sulbac-
tam, narrow spectrum cephalosporins, cephamycins, cefuroxime, ni-
trofurantoin, and colistin [14, 15]. S. marcescens also harbors a chro-
mosomal ampC gene that can extend resistance to several more-lac-
tam antibiotics. In addition, some strains carry chromosomally en-
coded carbapenemases, and plasmid-mediated-enzymes can be ac-
quired to further extend resistance to -lactams. Sensitivities to
other antimicrobials, such as the quinolones, trimethoprim-sulfa-
methoxazole and aminoglycosides, are more variable [15-17].
Infections caused by S. marcescens may be difficult to treat because
of resistance to a variety of antibiotics, including ampicillin, first and
second generation cephalosporins. Aminoglycosides have good ac-
tivity against S. marcescens, but resistant strains have also been re-
ported recently [2]. Clinically, infections are mostly nosocomial, as-
sociated with long hospital stay, numerous and prolonged antibiotic
courses.
Keeping the above in mind, the following study was designed to de-
termine the prevalence of Serratia marcescens wound infections and
their susceptibility profile in our institution.
Materials and methods
The prospective study was carried out between April 2012 to June
2013 in the University of Calabar Teaching Hospital (UCTH), Calabar.
Correspondence: Ofonime Mark Ogba
Email: ofonimemark@yahoo.com
Abstract
Background: Serratia marcescens, a ubiquitous rod-shaped gram-negative bacterium is an opportunistic pathogen causing a plethora of
nosocomial infections in humans including wound infections. They are identified in their ecological niches by their red pigment,
prodigiosin. Information concerning these organisms in association with wound infections are sparse in our locality. This study was
designed to determine the prevalence of Serratia marcescens in wound infections and their antimicrobial susceptibility profile.
Methods: Wound swabs and pus were collected from the patients after receiving informed consent from them. Samples were inoculated
on appropriate media and cultures were incubated at 37C aerobically. Cultures were examined macroscopically and bacterial isolates
were gram stained and microscopically examined. Pathogens were identified by their red pigment and other biochemical tests. The Kirby-
Bauer disk diffusion method was used for antibiotic susceptibility testing.
Results: Out of the 251 wound samples collected during the study period, 25 (9.9%) were Serratia marcescens. Males [18 (72.0%)] were
more susceptible than females [7 (28.0%)], but there was no influence of gender on the rates of infection (p=0.3). The susceptibility profile
of the isolates to antibiotics tested ranged between 4% and 76%. The most sensitive antibiotic was levofloxacin [19 (76%)] followed by
gentamicin [17 (68%)]. All the isolates were absolutely resistant to ampicillin.
Conclusion: Fluoroquinolones have shown a good activity against Serratia marcescens and should be considered as a first line antibiotic
against these infections in our locality. To stay ahead in the fight against these infections, effective infection control should be practiced,
antibiotic usage should be optimized and empirical treatment reduced. (El Med J 2:3; 2014)
Keywords: Antibiotic Susceptibility Testing, Serratia marcescens, Wound Infections
224 Antibiotic susceptibility pattern of Serratia marcescens isolates
Vol 2, No 3
Two hundred and fifty one subjects were enrolled after obtaining
their informed consent. Ethical approval was obtained from the eth-
ical research committee of the University of Calabar Teaching Hospi-
tal. Wound swabs and pus were collected from the 251 patients with
complaints of discharge, pain, swelling, foul smelling, delayed and
non-healing, by medical officers and nurses in the out-patient clinics
and wards, and by Medical Laboratory Scientists in the laboratory
using commercially available sterile cotton swabs. Only one swab per
patient was collected. The samples were transported to the microbi-
ology laboratory within one hour of collection to prevent drying of
the swabs.
Swabs were immediately inoculated on chocolate agar, blood agar
and cystine lactose electrolyte-deficient agar (CLED) and incubated
at 37C aerobically for 24 to 48 hours. Anaerobic cultures were not
done because of lack of materials and equipment. Identification of
bacterial isolates was based on gross morphological characteristics,
gram staining and biochemical tests. Antibiotic susceptibility testing
was determined by the Kirby-Bauer disc diffusion method on Muller
Hinton agar, and interpreted according to the recommendations of
the Clinical Laboratory Standards Institute [14]. The class of antibiot-
ics used in the study were: penicillins, sulphonamides, macrolides,
cephalosporins, quinolones and aminoglycosides. The antibiotics
tested were ampicillin 10 g, co-trimoxazole 25 g, ceftazidime 30
g, ceftriaxone 30 g, amoxiclav 30 g, gentamicin 10 g, roce-
phine 30 g, ofloxacin 5 g, ciprofloxacin 5 g and levofloxacin 5
g.
Data was analyzed using Epi Info 2000 (CDC, Atlanta, Georgia, USA)
statistical software. Descriptive statistics were carried out. Frequen-
cies (prevalence, etc.) were calculated for categorical variables. Dif-
ferences in antibiotic resistance between wound types and between
sexes and age groups were analyzed using 2 test. A difference of p
0.05 was considered significant.
Results
A total of 251 samples comprising wound swabs and pus were ana-
lyzed at the Microbiology/Parasitology Department of the University
of Calabar Teaching Hospital. There were 147 (58.6%) males and 104
(41.4%) females with a male to female ratio of 0.6 : 0.4. The mean
age was 36.98 15.49.
Table 1 shows the age and gender distribution of the patients with
S. marcescens infection among subjects. Males [18 (72.0%)] had a
higher infection rate than females [7 (28.0%)]. The peak isolation rate
[8 (32.0%)] occurred among age 21-30 years while the lowest rate [1
(4.0%)] occurred among age 71-80 years. There was no infection
among age 0-10 years. There was no significant influence of age and
gender on S. marcescens infection. Table 2 shows the distribution of
S. marcescens infections according to wound types. Post-operative
wound samples accounted for most [18 (72.0%)] of the S. marcescens
infections followed by non-operative wounds [6 (24.0%)]. The least
was from burns [1(4.0%)]. There was no association between the
wound types and S. marcescens infection (
2
= 7.7, p=0.25). Table 3
shows the different specimens from which S. marcescens was iso-
lated. Out of the 251 wound samples collected, 186(74.1%) were
wound swabs with 16 (8.6%) S. marcescens isolates, while 65 (25.9%)
were pus with 9 (13.8%) isolates.
Table 1: Age and gender distribution of subjects with
S. marcescens infection
Age (years) No. (%) positive (n=251)
Females Males Total
0-10 0(0.0) 0(0.0) 0(0.0)
11-20 1(33.3) 2(66.7) 3(12.0)
21-30 3(37.5) 5(62.5) 8(32.0)
31-40 2(50.0) 2(50.0) 4(16.0)
41-50 1(25.0) 3(75.0) 4(16.0)
51-60 0(0.0) 3(100) 3(12.0)
61-70 0(0.0) 2(100) 2(8.0)
71-80 0(0.0) 1(100) 1(4.0)
Total 7(28.0) 18(72.0) 25(9.9)

Table 2: Distribution of S. marcescens infection according to
wound types
Types of wound No. (%) of subjects No. (%) positive
Non-operative 105(41.8) 6(24.0)
Post-operative 145(57.8) 18(72.0)
Burns 1(0.4) 1(4.0)
Total 251 25

Table 3: Distribution of S. marcescens isolates in wound sam-
ples*
Type of specimen No. (%) of specimen
collected
No. (%)
positive
Wound swab 186(74.1%) 16(8.6%)
Pus 65(25.9%) 9(13.8%)
Total 251 25(9.9%)
*X
2
=1.89, df=2, p=0.38

Out of the 25 (9.9%) Serratia marcescens isolates from patients, 13
(52.0%) were pure growth while 12 (48.0%) were mixed with other
bacterial agents (Figure 1).

Figure 1: Types of Serratia marcescens isolates from patients
PURE
ISOLATES
52%
MIXED
ISOLATES
48%
S. MARCESCENS ISOLATES
Ogba OM, Mandor BI, Omang H 225
Table 4 shows the antibiotic sensitivity and resistance pattern of S.
marcescens to various antibiotics. All isolates were tested. The sus-
ceptibility profile of the isolates to antibiotics tested ranged from 4%
to 76%. The most sensitive antibiotic was levofloxacin [19 (76%)] fol-
lowed by gentamicin [17 (68%)]. Ceftriaxone [14 (56%)] also showed
some level of sensitivity. All the isolates were absolutely resistant [25
(100%)] to ampicillin. They exhibited a very high resistance to Amox-
iclav (92%) and amoxicillin (96%).
Table 4: In vitro antibiotic susceptibility and resistance pattern of
S. marcescens from wound specimens
Type of antibiotic No. sensitive % sensitive % resistant
Ciprofloxacin 11 44% 56%
Ofloxacin 8 32% 68%
Levofloxacin 19 76% 24%
Fortum 11 44% 56%
Zinaceff 3 12% 88%
Rocephin 8 32% 68%
Ceftriaxone 14 56% 44%
Cefuroxime 3 12% 88%
Co-trimoxazole 5 20% 80%
Gentamicin 17 68% 32%
Ampicillin 0 0% 100%
Augmentin 2 8% 92%
Amoxicillin 1 4% 96%
*No. of isolates tested = 25

Discussion
In this study, an infection rate of 9.9% was recorded. This is lower
than the 13% and 11% reported by Passaro et al and Polsuszny et al,
among cardiovascular surgery patients in California, USA, and surgi-
cal wound patients in Chicago USA, respectively [2, 3]. It was how-
ever, higher than the 5% prevalence reported by Yu et al among
surgical wound patients with bacteremia in Taichung, Taiwan [9].
The lower rates in our study compared to Passaro and his colleagues
report may be due to the fact that they were investigating an out-
break among cardiovascular surgery patients which was traced to an
out-of-hospital source. Though we did not investigate the source of
the infection in our study, it could have been an in-hospital outbreak
as most of the Serratia marcescens infected patients were post-oper-
ative patients. The infections may have been transmitted through
hand-to-hand contact by medical personnel.
Most of the infections occurred amongst age group 21-30 years. This
may be attributed to the fact that this is the most active and produc-
tive age, and as such, prone to wounds and infections. Males were
more infected than females in the study, but there was no statisti-
cally significant influence of gender on subjects infected (p= 0.8), as
both males and females were active and productive.
Serratia species are often fairly sensitive to quinolones [16]. In this
study S. marcescens susceptibility to quinolones were: 76%, 44% and
32% respectively for levofloxacin, ciprofloxacin and ofloxacin. This is
different from the 100% susceptibility to levofloxacin reported by
Mahen [17]. Sheng et al, however, found that there was a decreasing
trend in fluoroquinolone sensitivity among S. marcescens isolates
which could be due to mutation, acquisition of resistance plasmids
or chromosomal determinants [18].
The aminoglycoside gentamicin was the second most effective anti-
biotic with 68% susceptibility to the isolates. This is higher than the
57.3% sensitivity reported in Japan, Korea and Formosa by Shimizu
et al [19]. The increase in sensitivity may be due to the fact that gen-
tamicin which is an injectable aminoglycoside is not highly abused,
or due to the reduction in usage because of its nephrotoxic effect.
In this study S. marcescens displayed absolute resistance to ampicillin
and a very high resistance to Amoxiclav 92% and amoxicillin 96%.
Serratia species are intrinsically resistant to several -lactam antibi-
otics, including ampicillin, amoxicillin, amoxiclav, cefuroxime, and
narrow-spectrum cephalosporins [17].
Conclusion
Serratia marcescens is one of the bacterial agents causing wound in-
fections in our Institution. Fluoroquinolones have shown a good ac-
tivity against S. marcescens and should be considered as a first line
antibiotic for these infections in our locality.
Recommendation
To stay ahead in the fight against these infections, effective infection
control should be practiced, including hand washing by medical per-
sonnel, disinfection of environmental hand contact surfaces and
multiuse equipment to reduce transmission of infection. Antibiotic
usage should be optimized and empirical treatment reduced. The
choice of appropriate antimicrobial agents is necessary for the treat-
ment of S. marcescens infections to combat multidrug resistance.
Authors Contributions: OO conceived the study, BM and HO contributed to the
design of the study; OO and HO performed laboratory studies. OO analyzed the
data, drafted the manuscript and all authors read and approved the final version.
OO is guarantor of the paper.
Acknowledgements: We thank Professor l Abia-Bassey for making time to read this
work and for her constructive suggestions. We are grateful to Mrs Gloria Adie,
Assistant Director/Coordinator, Department of Microbiology/Parasitology, UCTH,
Calabar.
Received: 31 May 2014 Accepted: 23 July 2014
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2014 Arami et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Arami J, Rezasoltani A, Eghlidi J, Ebrahimabadi Z, Ylinen J: The applicability of proprioceptive and endurance measurement protocols to treat patients with chron-ic non-specific neck pain. El
Mednifico Journal 2014, 2(3): 227-230.
The applicability of proprioceptive and endurance measurement protocols to treat patients with chronic
non-specific neck pain
J Arami
1
, A Rezasoltani
2
, J Eghlidi
2
, Z Ebrahimabadi
2
, J Ylinen
3

Introduction
Neck pain constitutes a common disorder in modern societies, par-
ticularly in the industrialized world, imposing large healthcare and
therapeutic costs on individuals and societies, as one of the major
causes of occupational disabilities [1-5]. Numerous complications
and episodes of recurrence have been observed with neck pain while
few statistically evidence-based exercise protocols have been de-
signed. Repeated movements and long wrong or incorrect postures
may modify characteristics of tissue and motion patterns, resulting
in pain or motor dysfunction [6].
The normal function of neuromuscular system is essential to provide
normal motion, force tolerance and protection of organs against in-
jury [7, 8]. Any factor affecting this coordination will lead to the dys-
function and consequently poor control of joint position and abnor-
mal uncontrolled motions [9-14]. The pathophysiologic mechanism
of neck pain remains unknown in the majority of cases; nevertheless,
it is believed to be a multifactorial condition [15]. Any disorder in
articular and muscular biomechanics will induce pain and compro-
mise proprioception sense, resulting in inappropriate adaptation re-
sponses from the CNS [16-20]. Proprioceptive information plays a
pivotal role in maintenance of motion, posture and joint position and
any factor that disrupts this information may be considered a major
element of incorrect motion patterns and syndromes of chronic re-
current pain.
Nowadays, exercise therapy is accepted as an efficient option for
neck pain; however, treating neck pain remains a major challenge.

1
Department of Physiotherapy, Amir-al-Momenin Hospital, Ahvaz, Iran.
2
Faculty of Rehabilitation Sciences, Shahid Beheshti University of Medical Sciences,
Tehran, Iran.
3
Central Hospital of Central Finland, Keskusaaralantie, Jyvaskyla, Finland.
Researchers have stated that it is necessary to determine the func-
tional disorders and practical goals prior to rehabilitation. Thus, it is
obvious that application of different types of exercise will be guided
by the therapists knowledge of their efficacy.
The present study is crucial in determining the short-term effects of
proprioceptive exercise in patients with chronic non-specific neck
pain. The aim of the present study is to compare the effects of two
exercise protocols, endurance of neck flexors and proprioceptive ex-
ercise, in patients with chronic non-specific neck pain.
Methods
Forty seven patients, (16 men and 31 women, aged 18-40 years) with
chronic non-specific neck pain participated in this study. The pa-
tients were randomly assigned to two groups. Twenty three patients
took part in endurance, 24 patients in proprioceptive training pro-
gram. Our inclusion criteria were patients with history of neck pain
that continued at least for three months and neck pain not due to
inflammation, malignancy congenital abnormality, prolapse of cervi-
cal intervertebral disc, trauma or radiculopathy [21, 22].
Demographic data was obtained through a general questionnaire.
Pain intensity and level of disability were obtained through the visual
analog scale (VAS), Neck Pain Scale (NPS) and standardized Persian
version of Neck Pain and Disability Scale (NPDS) [23].
Afterwards, joint repositioning test and neck flexor muscles endur-
ance test were performed according to the methods of Roren et al.,
2009 and Full et al., 2009. All evaluations were performed four times-
Correspondence: J Eghlidi
Email: a_rezasoltani@sbmu.ac.ir
Abstract
Background: Neck pain constitutes a common disorder in modern societies. Numerous complications and episodes of recurrence have
been observed with neck pain while few statistically evidence-based exercise protocols have been designed. The objective of this study
was to detect and compare the applicability of two proprioceptive and endurance measurement protocols to treat patients with chronic
non-specific neck pain.
Methods: This was a single blinded, randomized clinical trial conducted at Mostapha Khomeini Hospital, Behbahan, Iran. Forty seven
patients (16 males and 31 females) with chronic non-specific neck pain participated in this study. Subjects were randomized into two
groups: endurance training and proprioceptive training. Each training was performed for ten subsequent days. A pressure biofeedback
was used to measure the endurance of neck muscles and a laser resource device to measure the cervicocranial joint position error prior
to therapy, on fifth, tenth sessions after the 1
st
day of treatment and 45 days after the last treatment day.
Results: Significant differences were found between before and after therapy in terms of endurance index, joint position error, and pain
measurements (p<0.05, p<0.01 and p<0.05) in both groups. After therapy, endurance index was significantly more pronounced in the
endurance group, whereas the improvement in joint position error index was more pronounced in the proprioceptive group.
Conclusion: The use of endurance and proprioceptive based measurement programs as was used in this study can be recommended to
improve endurance, reduce proprioceptive error and pain in patients with chronic non-specific neck pain. Endurance exercise was a more
efficient method for improving endurance and proprioceptive training was better in resolving joint position error and pain. Both protocols
appeared to be applicable to treat patients with chronic non-specific neck pain. (El Med J 2:3; 2014)
Keywords: Non-specific Chronic Neck Pain, Proprioceptive, Endurance Training
228 Applicability of proprioceptive and endurance measurement
Vol 2, No 3
prior to therapy, after fifth session, after tenth session and 45 days
after the last treatment session. All methods used in this study were
discussed and approved by the Ethics Committee at Shahid Beheshti
University of Medical Sciences. After the participants were given a
complete description of the study, written informed consent was ob-
tained from all participants.
All methods of the evaluation of neck joint repositioning error and
the way of computing of the angle have been explained previously
[18]. The procedure was repeated three times and the mean value
was recorded as the repositioning. All tests were performed by a sec-
ond physiotherapist who was blinded to the either group and each
exercise was repeated 10 times in each session. After all evaluation,
each patient was assigned a random code and categorized in to en-
durance and proprioceptive groups.
Therapeutic protocols
A hot pack was applied to the cervical region for 15 minutes prior to
each exercise. Each training group received 10 days of treatments in
the presence of an experienced physiotherapist.
Proprioceptive Training
The patient sat comfortably on a chair with a backrest. A biking hel-
met equipped with a laser beam on its top was worn on the patients
head. The laser beam was adjusted at a distance of 90 cm from a
circle target with a diameter of 40 cm and concentric circles 2 cm
apart. A vertical and a horizontal axis, adjusted with a plummet, di-
vided the target into 4 quadrants. The center of the circle was con-
sidered as the reference point, the patient memorized the initial sta-
tus (reference point), performed a maximal extension and rotation
to one direction (randomly chosen and on the horizontal plane),
kept this position for 2 seconds and then returned to the initial status
without changing the speed. The exercise was repeated for 10 times
[18].
Endurance Training
The exercise consisted of craniocervical flexions by nodding in su-
pine position in each series of 10 repetitions [12]. The gauge of the
sphygmomanometer was adjusted in such a way as to allow both
the therapist and the patient to see it. The patient lay down in supine
position with knees bent and both foot plants on the ground. A 3
cm mat in thickness was placed under patients head to preserve the
neutral position of head and neck. The endurance level was meas-
ured in the manner explained before and recorded for each session
[21]. The exercise was started at the level with which he/she felt com-
fortable. Some patients could only raise the pressure by 2 mmHg and
perform the 10-second movement only 4 times without fatigue;
thus, training and exercise started at this level.
Statistical Analysis
Routine statistical methods were used for calculating mean, standard
deviation, and range of variables. ICC was used to assess the repeat-
ability of both methods of measurements. All variables were com-
pared using repeated measurement of ANOVA. The mean percent-
age difference was calculated to compare two groups by means of
the level of changes between before and after training using the fol-
lowing equation:
X = [(x1-x2) / (x1+x2) / 2] x 100
T-test was computed to compare the mean percentage of difference
between two groups. All statistical calculations were performed us-
ing SPSS software version 16.
Results
Table 1 provides an overview of the demographics. The inter-tester
reliability of both endurance and proprioceptive measurements
were high (ICC >96). Prior to therapy, the endurance of deep flexor
muscles were significantly different between the endurance group
and the proprioceptive group, with the endurance group having a
smaller endurance index compared to the proprioceptive group (p
< 0.05). On fifth and tenth sessions of therapy, the mean percentage
of improvement of the endurance index was significantly different
between two groups, with the endurance group indicating better
improvement compared to the proprioceptive group (p < 0.01) (Fig-
ure 1). On tenth session of therapy, the endurance index was higher
for the endurance group compared to the proprioceptive group, alt-
hough the difference was not statistically significant.

Figure 1: Mean percentage differences for dependent variables
(Endurance, VAS, JPE, NPDS and NDI) between before and after
endurance & proprioception therapy programs.
Table 1: Descriptive analysis for basic data of patients in study (n=47)
Cranio-cervical flexion exercise intervention (n=23) Proprioception exercise intervention (n=24)
Gender Male: 8 Female:15 Male: 8 Female: 16
Range Mean Standard Deviation Range Mean Standard Deviation
Age (year) 20-40 34 5.73 20-40 29.5 6.34
Height (cm) 153-178 163 7.63 150-185 166 10.23
Weight (Kg) 55-84 66 8 45-85 65.54 10.68
BMI (Kg/cm
2
) 20.04-29.96 24.78 2.93 20-29.70 23.68 2.66
Arami J, Rezasoltani A, Eghlidi J et al. 229
Two groups were not significantly different in terms of cervical joint
positioning error index before therapy, while evaluations conducted
on the fifth and tenth sessions of therapy indicated a significant dif-
ference (p < 0.05). Comparing the mean percentage of difference in
cervical joint positioning error before and after therapy indicated
that it had improved further in the proprioceptive group compared
to the endurance group (p < 0.01).
Furthermore, after the first five days of exercise, the indices of neck
flexor muscle endurance, neck repositioning error, NDI, NPDS, and
pain improved significantly in the proprioceptive group (p < 0.05),
while the endurance index improved significantly for the endurance
group (p < 0.01).
Prior to therapy, the NPDS index was not significantly different be-
tween two groups. Moreover, the mean percentage difference in the
NPDS index before and after therapy was not significantly different
between two groups. The difference between NDI index before ther-
apy and after ten sessions of exercise was not significantly different
between two groups. In addition, the mean percentage of difference
in NDI before and after therapy was not significantly different be-
tween two groups.
The pain index was significantly different between two groups prior
to therapy (p < 0.05), with patients in the proprioceptive group feel-
ing more pain. After 10 sessions of training, the level of pain was
reduced up to 81% in proprioceptive group and 61% in endurance
group.
Moreover, the indices of endurance, positioning error, NDI and NPDS,
and pain were significantly improved in both groups after 45 days (p
< 0.01).
Discussion
In the present study, we used craniocervical flexion for exercise for
the endurance group and joint positioning correction for the propri-
oceptive group to treat patients with chronic non-specific neck pain.
As mentioned earlier in the result section, the first evaluation per-
formed after therapy (the fifth session of therapy) indicated that the
endurance index improved significantly in the endurance group,
whereas in the proprioceptive group, the cervical joint positioning
error and pain improved significantly. Furthermore, the efficacy of
proprioceptive exercise was higher in the first 5 days of therapy com-
pared to endurance exercises. These short-term effects of exercise
program appears that proprioceptive exercises act more rapidly
compared to endurance exercises, as the latter require longer time
for learning.
Khalkhali et al. (2004, 2008) reported proprioceptive correction exer-
cises and stabilizing exercises to improve joint positioning error in
the lumbar region after 10 sessions of therapy [22, 24]. Many possi-
ble mechanisms account for the improved proprioception after ex-
ercise: Ashton Miller et al. (2003) account for the improvement of
joint positioning error through the fact that proprioceptive exercises
probably improve cerebral attention to proprioceptive signals, first
consciously and then automatically after completion of exercises
[25]. They stated that another possible mechanism for the improved
proprioception after exercise may involve the activation of neural
pathways in the sensory area observed in plasticity [24].
Another theory regarding the improvement of proprioception fol-
lowing craniocervical flexion exercise involves the repeated reposi-
tioning of a certain state; i.e. similar to the proprioceptive exercises
which deal with joint repositioning, flexion exercises repeatedly re-
position the joints to achieve a target state [26].
Reduced neck pain and disability has been reported using deep cer-
vical muscle flexion exercise over 6-week endurance protocol to treat
patients with chronic neck pain, Considering the disruption in sen-
sory-motor system resulting from pain and the diminished muscular
activity through inhibitory reflex [27], it is possible that reduced pain
and increased endurance will enhance the function of the sensory-
motor system [28]. Moreover, given the role of proprioceptive recep-
tors of cervical musculature in shaping the motor signals of the brain
to maintain head and neck in a proper position, amelioration of head
and neck proprioception will lead to better posture and positioning
of head and neck. On the other hand, it appears that the close phys-
iologic relationship between pain and proprioceptive indices may
explain the significant improvement of pain and positioning error in
the proprioceptive exercise group. In this regard, improvement of
proprioception and its major impact on head and neck kinesthesia is
the probable mechanism responsible for pain relief following propri-
oceptive exercise [28].
The authors suggested that short-term positive effects of acupunc-
ture may improve cervical JPE (joint position error) and pain via
changing muscle spindle activity. The proper functioning of propri-
oception system plays an important role in producing a sufficient
neck muscles contraction to keep head and neck in an upright posi-
tion [29].
Rezasoltani et al. compared the effect of a neuromuscular facilitation
exercise and traditional neck exercise therapy to treat patients with
chronic non-specific neck pain after 10 sessions of training. Authors
showed a significant reduction in pain (up to 78% and 31%) in neu-
romuscular facilitation exercise and traditional exercise groups. As a
result, the strength of neck extensor and flexor muscles were im-
proved up to 24.6% and 21.5% in neuromuscular facilitation exercise
group and 13.8% and 11% in traditional neck exercise therapy group
respectively. It was revealed that short-term neuromuscular facilita-
tion exercise could be useful to decrease pain and increase muscle
strength in patients with chronic non-specific neck pain. Short-term
proprioceptive exercise training may improve muscle activity and
JPE [30].
Pain also has been reported to be suppressed after endurance (dy-
namic) exercises training in patients with neck pain [31]. Falla et al.
(2006) reported that endurance exercises training may directly acti-
vate the deep cervical flexor muscles. Cervical muscles are rich in
muscular spindles, thus repeated contractions caused by cervicocra-
nial flexion will enhance the function of muscular spindles and facil-
itate cervical proprioception consequently [26]. Improved endurance
following an endurance exercise may be attributed to the increased
capacity of using motor units by the deep flexors as well as enhanced
coordination between deep and superficial muscles [28].
230 Applicability of proprioceptive and endurance measurement
Vol 2, No 3
In the present study, the NDI and NPDS indices before and after ther-
apy (tenth session) were not significantly different between the two
groups. In both groups, endurance exercise and proprioceptive cor-
rection resulted in improved disability. Disruption of endurance of
postural muscles of the spine and reduced proprioception leading to
poor understanding of head and neck position are the causes of dis-
ability when performing activities such as reading, working with
computers and driving [26]. In addition, our findings indicate that
both protocols of endurance and proprioceptive exercise yield sig-
nificant improvements in all indices 45 days after the first therapy.
This indicates the durability of therapy outcome in the long term,
thus accentuating the importance of both therapy protocols in long-
term rehabilitation programs.
In this randomized clinical control trial, we used two methods of
deep cervical endurance test and head and neck positioning error
test to evaluate and treat patients with chronic non-specific neck
pain. Both tests were indicated to be useful therapeutic tools in their
own scope of evaluation after the intervention. That is, the endur-
ance exercise and the proprioceptive exercise were most efficient in
improving endurance and proprioception, respectively. The present
study warrants further studies about the effect of these exercise form
to in the long-term.
Conclusion
Proprioceptive exercise therapy is a short-term method to decrease
pain and improve JPE. Therefore, using this exercise program to re-
habilitate patients with chronic neck pain is recommended.
Acknowledgments: We would like to thank the patients participated in this study
and Physical Therapy Department of Shahid Beheshti University of Medical Sciences
for their kind cooperation.
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4. Vonk F, Verhagen A.P, W Twisk J, Koke J.A, Marlies W.C.T L, and Koes B. W.
Effectiveness of a behaviour graded activity program versus conventional
exercise for chronic neck pain patients . Eur J pain 2008; 6: 1010-16.
5. Webb R, Brammah T, Lunt M, Allison T and Symmons D. Prevalence and
predictors of intense, chronic and disabling neck and back pain in the UK
general population. Spine 2003; 28: 1195-202.
6. Sahrmann SA. Posture and muscle imbalance: faulty lumbar pelvic alignment
and associated musculoskeletal pain syndromes. Orthopedic Division Review:
Nov/Dec 1992; 13-20.
7. Janda V. Introduction to functional pathology of motor system: Proceedings
of the VII common wealth and international Conference on sports.
Physiotherapy in Sport 1982;3:39.
8. Lewit K. Functional pathology of motor system: Proceedings of the Fourth
Congress FIMM. Rehabilitation 1975 (suppl 10-11).
9. Bergmark A. Stability of the lumbar spine. A study in mechanical engineering.
Acta Orthop Scan 1989;230(60), 20-24.
10. Comerford MJ and Mottram SL. Movement and stability dysfunction:
contemporary developments. Man Ther 2001; 6(1): 15-26.
11. Hodges PW and Richardson CA. Inefficient muscular stabilization of the lumbar
spine associated with low back pain: a motor control evaluation of transverses
abdominis. Spine 1996; 21(22), 2640-50.
12. Jull G, Barrett C., Magee R and Ho P.Further clinical clarification of the muscle
dysfunction in cervical headache. Cephalalgia 1999; 19(3):179-85.
13. OSullivan PB, Twomey L and Allison G. Evaluation of specific stabilizing
exercises in the treatment of chronic low back pain with rsdiological diagnosis
of spondylosis or spondylolisthesis. Spine 1997; 22(24): 2959-67.
14. Falla D, O'leary S, Fagan A. and Jull G. Recruitment of the deep cervical flexor
muscles during a postural correction exercise performed in sitting. Man Ther
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15. Hush J.M, Michaleff Z, Maher C and Refshauge KM. Individual, physical and
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16. Jull G, Kristjansson E, Dall'Alba P. Impairment in the cervical flexors: a
comparison of whiplash and insidious onset neck pain patients. Man Ther
2004;9(2): 89-94.
17. Falla DL, Jull GA and Hodges PW. Patients with neck pain demonstrate reduced
electromyographic activity of the deep cervical flexor muscles during
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2014 Memon et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Memon ZA, Dawood H, Saleem MD, Fawwad SH, Sultan N: Role of ultrasound in determining small bowel intestinal obstruction: Findings at a public sector hospital of Pakistan. El Mednifico
Journal 2014, 2(3): 231-234.
Role of ultrasound in determining small bowel intestinal obstruction: Findings at a public sector
hospital of Pakistan
Zahid Ali Memon
1
, Huzaifa Dawood
2
, Muhammad Danish Saleem
2
, Shaikh Hamizul Fawwad
2
, Naheed Sultan
1

Introduction
Acute abdominal pain is the most common cause of admission in
surgical departments in the United States [1]. Despite recent ad-
vances in technology and investigative science, acute abdomen pa-
tients present a diagnostic and therapeutic challenge to emergency
clinicians [2]. Common surgical causes of acute abdominal pain in-
clude appendicitis, intestinal obstruction and biliary disease and
show variation with age [3, 4].
Intestinal obstruction (IO) accounts for nearly 20% of surgical admis-
sions for acute abdominal conditions [5, 6]. Mechanical intestinal ob-
struction is a frequently encountered surgical emergency in our
setup. Keeping in view the wide array of etiological causes, prompt
diagnosis of intestinal obstruction as the etiological cause behind
acute abdominal pain is often difficult and deferred.
Baloch et al. reports a significant percentage of the population being
diagnosed each year with the numbers being significantly higher in
the public sector hospitals than the private due to their higher pa-
tient output [7]. Common causes responsible for mechanical ob-
struction of the small bowel in our setting are intestinal adhesions,
hernias, intestinal tumors and intestinal tuberculosis. Large bowel
obstruction is relatively uncommon with colorectal cancer, volvulus,
impacted feces and strictures being the commonly encountered
causes [7].
Careful medical history, physical examination adjuvant with relevant
laboratory and radiological investigations is necessary [8]. The key
radiological procedures used for this purpose are abdominal x-ray,

1
Surgical Unit 1, Civil Hospital Karachi, Dow University of Health Sciences, Pakistan.
2
Dow Medical College, Dow University of Health Sciences, Pakistan.
Correspondence: Muhammad Danish Saleem
Email: mdanishsaleem@gmail.com
ultrasound and CT scan. With the ever increasing patient load on
public sector university hospitals expensive tests such as CT scans
become a hassle not only for the poor non-affording patients but
also to the limited resources of the hospitals.Numerous studies both
locally and abroad have shown the efficacy of CT scans over the tra-
ditional abdominal x-rays and ultrasounds. Recently a study by Shakil
et al. proved by a retrospective analysis at Aga Khan University Hos-
pital that CT scan is a superior modality as far as diagnosing IO but
was not as effective in determining the etiology [9].
X-rays and ultrasound are still more conventional and common
methods of routinely diagnosing mechanical intestinal obstruction.
Besides being cheaper and easier to perform they pose a lesser radi-
ation threat to the patient. Ultrasounds and x-rays which are portable
now can provide an immediate bedside diagnosis facilitating the sur-
gery process as well [10].
Civil hospital Karachi is a 1700 bed public sector tertiary care hospi-
tal. Each year hundreds of patients are diagnosed with IO. Most of
these patients are admitted to the surgical wards with a diagnosis of
IO based on history, examination and diagnostic radiology usually
selected by the attending surgeon. X-ray and ultrasound are the
usual modalities chosen due to their being cost effective, faster and
having a reasonable diagnostic accuracy.
Hence, we formulated this retrospective analysis to evaluate the role
of ultrasound as a cheaper yet effective alternative in diagnosing me-
chanical intestinal obstruction of the small bowel in the setting of a
public sector hospital of Karachi.

Abstract
Background: Intestinal obstruction accounts for nearly 20% of surgical admissions for acute abdominal conditions. Keeping in view the
wide array of etiological causes, prompt diagnosis of intestinal obstruction as the etiological cause behind acute abdominal pain is often
difficult and deferred. In the present study, we evaluated the role of ultrasound in diagnosing intestinal obstruction of the small bowel in
the setting of a public sector hospital of Karachi.
Methods: This was a retrospective analysis of 150 patients who presented with small bowel obstruction at Civil Hospital, Karachi (June
2011 to June 2012). Those that underwent a pre-laparotomy abdominal ultrasound were included while mixed bowel obstruction or
incomplete files were excluded. Ultrasound was used to identify the presence of obstruction, cause of obstruction, site of obstruction and
presence of mass. All radiological findings were matched with surgical notes of laparotomy.
Results: Abdominal ultrasound failed to detect mechanical obstruction in only 18.7% (n=28) cases (sensitivity 81.33%). However,
ultrasound was not very effective in distinguishing the segment of bowel involved in obstruction in almost half the cases (56%). Ileo-
jejunal loops were the most common site of obstruction as identified by ultrasound and later discovered upon laparotomy. The most
common etiology reported was tuberculosis (30.7%), adhesions (24.7%), hernia (17.3%) and mass. Ultrasound detected mass as etiological
cause in 14 out of 30 cases.
Conclusion: Ultrasound is a cheap, safe and efficient mode of diagnosing mechanical intestinal obstruction involving small bowel in
public sector hospitals. (El Med J 2:3; 2014)
Keywords: Ultrasound, Intestinal Obstruction, Small Bowel, Pakistan
232 Role of ultrasound in determining small bowel intestinal obstruction
Vol 2, No 3
Subjects and Methods
This was a retrospective analytical study of all patients who pre-
sented with mechanical intestinal obstruction of the small bowel in
the surgical wards of Civil Hospital Karachi from the period June 2011
to June 2012.
A total of 150 patients were enrolled in the study. Both males and
females, between the ages of 12 and 80 years were included by pur-
posive sampling. Only those cases were included that underwent an
abdominal ultrasound before their exploratory laparotomy. Patients
referred from both emergency and OPD were included. Patients who
had mixed bowel obstruction or those whose files had incomplete
information were not included.
Intestinal obstruction was defined by the presence of distended
bowel loops (>2.5 cm in small bowel and >6.0 cm in large bowel),
proximal to a point of obstruction, transitioning into a collapsed seg-
ment of the small bowel distal to the point of obstruction.
Intestinal obstruction was diagnosed on the basis of clinical exami-
nation adjuvant with ultrasound. Abdominal ultrasound was used to
identify the presence of significant visible obstruction, cause of ob-
struction, site of obstruction, presence of mass and type of mass. To
minimize the artifact of hindsight we used the original radiology re-
port and did not have the images rechecked with the radiology de-
partment. All the radiological findings were confirmed and matched
with the surgical notes of the exploratory laparotomy. For each pa-
tient, the surgical notes of the subsequent exploratory laparotomy
were thoroughly reviewed to see if the surgical findings corrobo-
rated with those of the radiological in terms of presence, level and
etiology of mechanical bowel obstruction. The surgical diagnosis was
deemed to be the definitive diagnosis i.e. the gold standard, against
which the findings of the techniques were compared.
Abdominal ultrasound was performed with patients in supine posi-
tion, using hand-held probe after application of water based gel over
abdominal area to be examined. All ultrasounds were performed by
trained and experienced technicians, and findings were reported by
consultant radiologists.
Data was collected on standard questionnaires, entered and ana-
lyzed on SPSS v18.0 to calculate simple frequencies and percentages.
Patient demographics (age and gender) and the presentation and
etiology of the bowel obstruction were summarized by calculating
the means for continuous variables and proportions for categorical
ones.
The study was approved by the Institutional Review Board of Dow
University of Health Sciences and ethical considerations were found
to be satisfactory.
Results
Out of 150 patients included, 76% (n=114) patients were males and
only 24% (n=36) were females with male to female ratio of over 3.
Mean age of the patients was 35.45 16 years.
Most patients (86%, n=129) had an acute onset of symptoms and a
total of 90.7% (n=136) were admitted via Emergency Department.
Most of these patients presented with complaints of abdominal pain
(98%), nausea/vomiting (73%) and bowel distension (66%).
Abdominal ultrasound failed to detect mechanical obstruction in
18.7% (n=28) cases. However, they were surgically explored in emer-
gency, based on their physical examination and presentation and
signs and features suggestive of peritonitis and were found to have
mechanical intestinal obstruction upon laparotomy. Hence sensitiv-
ity was 81.33%. Refer to Table 1.
Table 1: Frequency of intestinal obstruction detected upon
ultrasound
N %
Intestinal obstruction
detected upon ultrasound
Yes 122 81.3%
No 28 18.7%
Total 150 100%

Ultrasound was not effective in distinguishing the segment of bowel
involved in obstruction and in most cases (56%, n=84), the site of
obstruction was indistinguishable. In 38 cases, ultrasound identified
involvement of Ileo-jejunal loops in obstruction. However, actual
numbers of cases with Ileo-jejunal loops as site of obstruction were
137 as seen per laparotomy. Ileo-jejunal loops were the most com-
mon site of obstruction as identified by ultrasound and discovered
upon laparotomy.
The most common etiology reported upon laparotomy amongst
these cases was tuberculosis (30.7%, n=46), adhesions (24.7%, n=37)
and hernia (17.3%, n=26) while mass obstructing the bowel lumen
was also a common finding (14.7%, n=22). Figure 1 shows the etio-
logic distribution of mechanical intestinal obstruction of small bowel
as per laparotomy.

Figure 1: Etiology of intestinal obstruction as found on
laparotomy
Ultrasound detected mass as etiological cause in 14 cases. The cases
were under reported as upon laparotomy, 22 cases with mass as the
cause of obstruction was observed. Type of mass was not identified
24.7
17.3
2.8
7.3
30.7
14.7
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1.6
0
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10
15
20
25
30
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Etiology of Intestinal obstruction as found
on Laparotomy
Ultrasound
Memon ZA, Dawood H, Saleem MD et al. 233
by the ultrasound except as being tumor, foreign body or non-tu-
mor/non-foreign body. Most common ultrasonography feature re-
ported was the presence of dilated bowel loops with free fluid be-
tween the loops.
Discussion
Being cheaper and easily available, abdominal ultrasound is pre-
ferred over CT scan in evaluating acute abdomen in our setup, espe-
cially when patients present in Emergency Department. CT scans in
our setup are advised only in cases of suspected malignancy as in-
dicative by history and physical examination. We conducted this
study to evaluate the role and effectiveness of abdominal U/S in di-
agnosing patients with mechanical obstruction of the small bowel.
Although CT scan is reported to have very high sensitivity and spec-
ificity in detecting bowel obstruction. Its use as an initial investiga-
tion in assessment of all cases of acute abdomen, especially in sus-
pected bowel obstruction, is controversial. Not only, CT scan is costly,
but also it often fails to detect low grade bowel obstruction. In a
study by Meglinte et al, the overall accuracy of CT scan in cases with
low grade bowel obstruction was considerably low .i.e. 66% [11]. In
comparison, our study reported a substantial sensitivity of 81.3% of
ultrasound in diagnosing small bowel obstruction. This has also been
validated by other studies like that of Schmutz who reported 81.3%
accuracy for ultrasound [15]. When the bowel is taken as whole, the
accuracy of CT scan is non-comparable to ultrasound as reported by
Shakeel with sensitivity as high as 93% but when small bowel is se-
lectively evaluated for obstruction, ultrasound is more suitable than
CT scan in terms of accuracy and cost [9]. However according to
Stroker J et al. CT scan is the most accurate imaging technique in
diagnosing bowel obstruction and is the modality of choice when
abdominal ultrasound fails to diagnose the cause of acute abdomen
[12].
The role of ultrasound in detecting bowel obstruction is a matter of
debate. When cost and radiation exposure are primary concern, ul-
trasound becomes the primary imaging technique [12]. In our set-
ting, cost of the imaging modality is an important consideration and
thus, abdominal ultrasound is preferred over CT scan. The cost of one
abdominal ultrasound amounts to only PKR 400-500 (US$ 4-5) in
comparison to CT scan with a cost of around PKR 7000-10000 (US$
75-100). The 24 hours availability of ultrasound is also something
that has brought it into the frontline as a diagnostic modality espe-
cially in emergency rooms of hospitals like CHK where CT scan is not
available 24 hours. The disadvantage of CT scan in emergency situa-
tions is that patient has to be moved from the resuscitation room
and it takes longer time to obtain the image [20]. On the other hand,
with the advent of portable ultrasound devices, patients doesnt
need to be unnecessarily moved and they can be evaluated bedside
thus decreasing the patients discomfort. As small bowel obstruction
is more common than large bowel obstruction and it usually pre-
sents as an emergency, ultrasound becomes the modality of choice
in our setup because of its 24 hours availability [14]. Ultrasound is
also a far better option in patients who are contraindicated for CT
with contrast as reported by studies.
Our study reported that abdominal ultrasound is not very effective
in detecting the site of obstruction and failed to distinguish it in 44%
of the cases. The finding is consistent with previous literature that
reports the upper hand of CT scan in distinguishing the site of bowel
obstruction over other imaging modalities [13]. However, in cases
where ultrasound was effective, Ileo-jejunal loops were most com-
monly involved. The greater percentage of Ileo-jejunal obstructions
can be explained by high prevalence of TB and adhesions as the
cause of obstruction [18, 19].
In patients who had mass as an etiology, abdominal ultrasound failed
to detect it in only 6 cases, an outcome comparable to CT scan. The
low efficacy of ultrasound in diagnosing the presence and type of
mass can be ignored as mass usually presents in the large bowel in
our setup in relation to tumors.
Schmutz GR et al showed the importance of ultrasound in small
bowel obstruction in a study on 123 patients with small bowel ob-
struction, wherein the accuracy was 91.7 % when the 'gassy' patients
were excluded and 81.3 % overall [15]. Most common sonographic
feature suggesting mechanical intestinal obstruction reported in our
study was dilated bowel loops with free fluid between bowel loops.
The amount of free fluid may help in the assessment of the severity
of bowel obstruction and thus, govern the management of the pa-
tients. Grassi et al. pointed out the relevance of free fluid between
intestinal loops detected by sonography in the clinical assessment of
small bowel obstruction. The presence of large amount of fluid be-
tween dilated small bowel loops suggest worsening mechanical
small bowel obstruction, which required immediate surgery [16].
Moreover, abdominal ultrasound is particularly valuable in differen-
tiating between mechanical and functional bowel obstruction [10,
17].
In summary, abdominal ultrasound is considerably affective tool in
diagnosing mechanical intestinal obstruction, especially when cost
of the procedure is of primary concern in a setup like ours. The re-
sults for accuracy were comparable with CT scan when the small ob-
struction is concerned. As it usually presents with an acute onset on
the emergencies, ultrasound can easily be used as the first diagnostic
procedure especially if emergency laparotomy has to be performed.
Our study findings may have its limitations given its retrospective
nature; however our findings are comparable to international studies
on the same topic. As the purpose of the study was to justify the role
of ultrasound as a cheaper, safer and faster diagnostic tool for small
bowel obstruction only, its deficiency in large bowel needs to be ig-
nored. To be used for maximum benefit there also need to be expe-
rienced and trained sonologists who can identify the obstructions
and surgeons who proceed to conduct the laparotomy based on
clinical and physical findings adjuvant with the ultrasound.
Conclusion
Ultrasound is a cheap, safe and efficient mode of diagnosing me-
chanical intestinal obstruction involving small bowelin public sector
hospitals, with particular efficacy in case of obstructions resulting
from tuberculosis, adhesions, and hernia- the most common causes
in our setup.
234 Role of ultrasound in determining small bowel intestinal obstruction
Vol 2, No 3
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2014 Sharma et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Sharma P, Gomathi D, Ravikumar G, Kalaiselvi M, Uma C: Phytochemical screening and high performance thin layer chromatography finger printing analysis of green hull of Juglans regia
(walnut). El Mednifico Journal 2014, 2(3): 235-239.
Phytochemical screening and high performance thin layer chromatography finger printing analysis of
green hull of Juglans regia (walnut)
Pardeep Sharma
1
, Duraisamy Gomathi
1
, Ganesan Ravikumar
1
, Manokaran Kalaiselvi
2
, Chandrasekar Uma
3

Introduction
Plants have been an important source of medicine for thousands of
years. Even today, the World Health Organization estimates that up
to 80 percent of people still rely mainly on traditional remedies such
as herbs for their medicines. The use of traditional medicines holds
great promise as an easily available source as effective medicinal
agents to cure a wide range of ailments particularly in tropical devel-
oping countries like India. Its civilization is very ancient and the coun-
try as a whole has long been known for its rich resources of medical
plants [1-3]. In this context, the people consume several plants or
plant derived formulations to cure helminthic infections and treat-
ment of wounds [4, 5].
Walnut (Juglans regia) belongs to the family juglandaceae. This tree
grows only in Kashmir in India. The green hull of walnut is full of
phytochemicals which are used in traditional medicines for many
years. Green hull extract has various pharmacological effects, astrin-
gent and keratolytic, antidiarrheal, antifungal and anthelminthic and
tonic [6]. The green leaves and green shell of Juglans regia have been
widely used as an herbal remedy for the treatment of various endo-
crine diseases such as diabetes. Juglone is quinine produced in the
leaves and green hull of walnut fruit. It possesses antiviral, antimi-
crobial and antifungal properties. The mechanism of action respon-
sible for these effects of juglone may involve the inhibition of the
peptidyl-prolyl isomerase inhibition of transcription. This inhibition
is described in terms of allelopathic effects of plants.
High performance thin layer chromatographic (HPTLC) is an invalu-
able quality assessment tool for the evaluation of botanical materials.
It allows for the analysis of a broad number of compounds both ef-
ficiently and cost effectively. Additionally, numerous samples can be
run in a single analysis thereby dramatically reducing analytical time.

1
Department of Biochemistry, Karpagam University, Coimbatore, India
2
Department of Biotechnology, Kongunadu Arts and Science College, Coimbatore,
India
3
Hawasaa University, Ethiopia
With HPTLC, the same analysis can be viewed using different wave-
lengths of light thereby providing a more complete profile of the
plant than is typically observed with more specific types of analysis.
It is used for identification and quality control of medicinal plants [7].
The present study was aimed at the screening of phytochemicals and
finger printing analysis of various extracts (ethyl acetate, ethanol and
water) of green hull of Juglans regia by using HPTLC method.
Collection of plant material
The green hull of Juglans regia was procured from Kashmir. This tree
grows only in Kashmir in India.
Preparation of plant extract
The green hull of Juglans regia air dried at 25
o
C for 10 days in the
absence of sunlight and powdered well using a mixer and stored in
an air tight container. The powdered medicinal plant material was
taken and subjected to successive solvent extraction. About 50g of
powdered plant material was mixed with 250ml of various solvents
(petroleum ether, chloroform, ethyl acetate, ethanol and distilled wa-
ter). The extraction was carried out for 16 hours with the following
solvents in the increasing order of polarity. The plant extracts were
prepared by using soxhlet apparatus collected and stored in a vial
for further studies.
Phytochemical screening
Phytochemical screening was carried out to assess the qualitative
chemical composition of crude extracts using commonly employed
precipitation and coloration to identify the major natural chemical
groups such as steroids, reducing sugars, alkaloids, phenolic com-
pounds, saponins, tannins, flavonoids, amino acids, fixed oils, fats
Correspondence: Chandrasekar Uma
Email: umachandrasekaran29@gmail.com
Abstract
Background: Medicinal plants are the richest bio-resource of drugs of traditional systems of medicine, modern medicines, nutraceuticals,
food supplements, folk medicines, pharmaceutical intermediates and chemical entities for synthetic drugs. Therefore, researchers today are
emphasizing on evaluation and characterization of various plants and plant constituents against a number of diseases. The aim of the study
was to investigate the secondary metabolites and high performance thin layer chromatographic (HPTLC) finger printing of different extracts
of Juglone regia.
Methods: The secondary metabolites were analyzed for various extracts by using standard techniques and HPTLC method has also been
established to study the presence of various flavonoids and phenolic compounds for different extracts of Juglone regia.
Results: A preliminary phytochemical study confirmed the presence of active chemical constituents in the plant extract and the result
showed a positive report for the presence of flavonoids, alkaloids and cardiac glycosides.
Conclusion: These substances are known components of medicinal plants and may explain the use of the preparations of the herbs under
study for managing a number of common ailments including dysentery, diabetes, hypertension and some microbial infections. (El Med J
2:3; 2014)
Keywords: Juglans regia, Secondary Metabolites, HPTLC Finger Printing, Ethanolic Extract
236 HPTLC analysis of green hull of Juglans regia
Vol 2, No 3
and cardiac glycosides. General reactions in these analysis revealed
the presence or absence of these compounds in the crude extracts
tested [8, 9].
The quantitative assays for flavonoid and phenolic compounds were
studied by using Ordan et al and Sadasivam and Manickam, and the
yield of plant material in different solvent were also calculated [10,
11].
HPTLC finger printing analysis of plant material
Of the given plant extracts 100mg was dissolved in 1ml of appropri-
ate solvents and centrifuged at 3000rpm for 5min. These solutions
were used as test solution for HPTLC analysis. 2l of standard solu-
tion and 2l of the above test solution was loaded as 5mm band
length in the 5 x 10 Silica gel 60F254 TLC plate using Hamilton syringe
and CAMAG LINOMAT 5 instrument. The samples loaded plate was
kept in TLC twin trough developing chamber (after saturated with
solvent vapor) with respective mobile phase (flavonoid and phenols)
and the plate was developed in the respective mobile phase up to
90mm. The developed plate was dried by hot air to evaporate sol-
vents from the plate. The plate was kept in photo-documentation
chamber (CAMAG REPROSTAR 3) and images were captured at White
light, UV 254nm and UV 366nm. The developed plate was sprayed
with respective spray reagent (flavonoids and phenols) and dried at
100C in hot air oven. The plate was photo-documented at day light
and UV 366nm mode using photo-documentation (CAMAG REPROS-
TAR 3) chamber. After derivatization, the plate was fixed in scanner
stage (CAMAG TLC SCANNER 3) and scanning was done at 366nm.
Results
To identify the phytochemical components in Juglans regia the phy-
tochemical screening test was conducted after the successive sol-
vent extraction had been completed (Table 1). The ethanolic and
aqueous extracts of green hull of Juglans regia showed the presence
of alkaloid, tannin, phenolic compounds, flavonoid, terpenoids and
cardiac glycosides. The rest of the phytochemical components were
absent.
Table 1: Phytochemical analysis of Juglena regia
Phytochemical
constituents
Solvents
PE* CL* EA* ET* WA*
Alkaloids - - - + +
Steroids - - + + -
Flavonoids - - - + +
Tannins / phenols - - - + +
Amino acids and proteins - - - - +
Carbohydrates - - - + +
Cardiac glycosides - + + + +
Saponins + + - - +
Terpenoids - - - + +
Oils and fats - - - - -
*PE: Petroleum Ether; CL: Chloroform; EA: Ethyl Acetate; ET: Ethanol; WA: Water;
+: present; -: absent
Percentage yield
The percentage yield of the extracts of solvents from green hull of
Jugelena regia is tabulated in Table 2. The ethanolic extract of green
hull of Jugelena regia had the highest yield (7.12%). Next was water
(2.88%) whereas petroleum ether (1.88%) had the lowest yield.
Table 2: Percentage yield
Solvent % Yield
Petroleum Ether 1.88
Chloroform 1.99
Ethyl acetate 2.6
Ethanol 7.12
Water 5.12
Biochemical characterization
Estimation of total phenols and flavonoid were shown in Table 3. The
total phenol and flavonoid content of the ethanolic extract of hull
Juglans regia were studied. Total phenol content was found to be
46.88mg/g and total flavonoid content of ethanolic extract of green
hull was found to be 12.88mg/g of tannic acid equivalent. The car-
bohydrates were found to be 42.65mg/g of quercetin equivalent.
Table 3: Biochemical characterization of green hull of
Juglena regia (mean SD)
Particulars Ethanolic extract of Juglena regia
Carbohydrates (mg/g) 42.65 0.341
Total Phenols (mg/g) 46.88 0.362
Total flavonoids (mg/g) 12.88 0.452
HPTLC profile of ethanolic extract of Juglans regia was recorded in
Tables 4 and 5 for flavonoids and phenols of different extracts like
ethyl acetate, ethanol and water respectively. Yellow colored fluores-
cent zone at UV 366nm for flavonoid and blue colored zones for phe-
nols in the chromatogram. The extracts were run along with the
standard flavonoid and phenolic compounds. Table 4 showed the
presence of flavonoids in ethanolic and water extract except ethyl
acetate extract and Table 5 showed the presence of phenolic com-
pound in all three extracts especially quercetin.
Analysis Details for Flavonoids
Mobile Phase
Ethyl acetate-butanone-formic acid-water (5:3:1:1).
Spray reagent
1% ethanolic aluminium chloride reagent.
Detection
Yellow colored fluorescent zone at UV 366nm mode present in the
given standard and sample tracks (except ethyl acetate extract) ob-
served in the chromatogram after derivatization, which confirmed
the presence of flavonoid in the given standard and in the samples
(except ethyl acetate extract) (Figures 1 and 2).
Analysis Details for Phenols
Mobile Phase
Toluene-acetone-formic acid (4.5:4.5:1).
Sharma P, Gomathi D, Ravikumar G et al 237
Table 4: Peak table with Rf values, height and area of flavonoids and unknown compounds
Track Peak Rf Height Area Assigned substance
RUT 1 0.41 320.7 10970.1 Rutin standard
Sample A 1 0.66 13.4 478.4 Flavonoid 1
2 0.76 10.3 71.5 Unknown
3 0.96 147.9 5344.4 Unknown
Sample B 1 0.66 12.4 435.0 Flavonoid 1
2 0.71 31.4 853.0 Unknown
3 0.75 11.1 165.7 Unknown
4 0.95 92.7 3098.6 Unknown
Sample C 1 0.95 290.8 11760.9 Unknown

Table 5: Peak table with Rf values, height and area of phenolic & unknown compounds in ethanolic, water & ethyl acetate extract
Track Peak Rf Height Area Assigned substance
QUE 1 0.67 529.8 8615.5 Quercetin standard
Sample A 1 0.10 37.3 1663.8 Unknown
2 0.23 26.1 933.5 Unknown
3 0.35 16.9 468.9 Phenolic 1
4 0.51 16.7 571.2 Unknown
5 0.67 255.5 8506.7 Phenolic 2 (Quercetin)
6 0.72 98.7 3509.9 Unknown
7 0.88 13.8 217.7 Unknown
8 0.97 78.8 2052.2 Unknown
Sample B 1 0.20 13.6 240.0 Unknown
2 0.24 25.2 871.6 Unknown
3 0.27 35.7 683.8 Unknown
5 0.72 109.2 4767.4 Unknown
6 0.84 28.0 817.7 Unknown
7 0.97 70.6 1776.8 Unknown
Sample C 1 0.09 21.2 591.5 Unknown
2 0.30 16.7 384.8 Unknown
3 0.49 20.8 483.6 Unknown
4 0.51 25.9 557.9 Unknown
6 0.81 20.7 937.4 Unknown
7 0.92 27.0 591.9 Unknown
8 0.97 46.5 1071.8 Unknown

Figure 1: Chromatograms of extract in HPTLC analysis- Before derivatization
under day light, Under UV 254nm, Under UV 366nm. After derivatization
under day light. A-Ethanolic extract, B-Water extract, C-Ethyl acetate extract,
Standard: RUT

Figure 2: Densitogram, baseline and 3D analysis for flavonoid profile for
various extracts
238 HPTLC analysis of green hull of Juglans regia
Vol 2, No 3
Spray reagent
20% Sodium carbonate solution sprayed and brief dried followed by
Folin Cio-calteu reagent.
Detection
Blue colored zone at day light mode present in the given standard
and sample tracks observed in the chromatogram after derivatiza-
tion, which confirmed the presence of phenolic compounds in the
given standard and in all three samples (Figures 3 and 4).

Figure 3: Chromatograms of various extracts for phenolic profile in HPTLC
analysis- Before derivatization under day light, Under UV 254nm, Under UV
366nm. After derivatization under day light. A-Ethanolic extract, B-Water ex-
tract, C-Ethyl acetate extract, Standard: RUT

Figure 4: Densitogram, baseline and 3D analysis for phenolic profile for
various extracts
Discussion
Plants can be used in food industry for their organoleptic and nutri-
tional qualities, as source of antioxidants to preserve food quality
and also for medicinal purposes, since medicinal plants are still a ma-
jor source of healthcare and disease prevention for a great part of
the world population. Knowledge of the phytochemical constituents
of plants is desirable, not only for the discovery of therapeutic
agents, but also because such information may be of value in dis-
closing new sources of such economic materials as tannins, oils,
gums, flavonoids, saponins, essential oils precursors for the synthesis
of complex chemical substances [12].
Phytochemical screening helps to reveal the chemical nature of the
constituents of the plant extract and the one that predominates over
the others. It may also be used to search for bioactive agents that
could be used in the synthesis of very useful drugs [13, 14]. The phy-
tochemical screening of Juglans regia hull extract showed the pres-
ence of alkaloid, saponin, tannin and phenolic compounds, flavonoid
and carbohydrates.
Medicinal plants are popular remedies for diseases used by a vast
majority of the worlds population [15]. HPTLC finger printing analy-
sis also revealed the presence of phenolic compound (Quercetin) in
all the three extracts. Phenol is one of the major active principles
whose antioxidant activity has been documented earlier. The possi-
ble mechanism may be that antioxidant potentiality of phenols can
scavenge free radicals and protect the cell membrane from destruc-
tion [16, 17]. Chemically polyphenolic compounds are tannins which
accomplish anthelmintic activity. It is possible that tannins present
in the extracts of J. regia L., just like synthetic phenolic anthelmintic,
interfered with energy generation in helminthic parasites by uncou-
pling oxidative phosphorylation [18].
Conclusion
The plant selected for the study could be an answer to the people
seeking for better therapeutic agents from natural sources which is
believed to be more efficient with little or no side effects when com-
pared to the commonly used synthetic chemotherapeutic agents.
The present study verified the traditional use of Juglans regia for hu-
man ailments and partly explained its use in herbal medicine as rich
source of phytochemicals with the presence of tannins, phenols, sap-
onins, steroids, flavonoids and terpenoids. Thus, Juglans regia can be
utilized as a pharmacotherapeutic agent in future.
Acknowledgment
We the authors thankful to the Registrar, Vice-chancellor and Chan-
cellor of Karpagam University.
Received: 2 January 2014 Accepted: 13 July 2014
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2014 Salman et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Salman S, Idrees J, Anees M, Arifullah M, Waeel MA, Ismail M, Hassan M, Nazar Z: Collaborative care for schizophrenic patients in primary care: A double blind, randomized clinical trial of
efficacy and safety. El Mednifico Journal 2014, 2(3): 240-244.
Collaborative care for schizophrenic patients in primary care: A double blind, randomized clinical trial of
efficacy and safety
Saad Salman
1
, Jawaria Idrees
2
, Muhammad Anees
3
, Mashaal Arifullah
4
, Mansoor Al Waeel
1
, Muhammad Ismail
1
, Mehreen Hassan
5
, Zahid Nazar
5

Introduction
Services rendered by clinical pharmacists in the care of inpatients
generally results in improved care, with no evidence of harm. Inter-
viewing patients, reconciling medications, providing patient dis-
charge counseling and follow-up and interacting with health care
team on rounds results in improved health outcomes [1]. Schizo-
phrenia is one of the most severe psychiatric illnesses, with a preva-
lence of approximately 1% in the population worldwide [2]. Clinical
pharmacists cooperate with the patient and other professionals in
designing, implementing and monitoring a therapeutic plan and
pharmacotherapy recommendations that will produce specific ther-
apeutic outcomes for the patient. They are involved in several im-
portant roles towards the patient with schizophrenia in the provision
of antipsychotic therapy [3].
Efforts to improve the outcomes of patients with mental illness often
involve integrating the skills of a variety of health care professionals
into collaborative care models. Clinical pharmacists have contributed
to these care models in capacities ranging from educators to con-
sultants to providers for over 30 years. Pharmaceutical care is the
responsible endowment of drug therapy for the purpose of achiev-
ing definite outcomes: reducing medication overuse, medication
costs and drug-related adverse events, results in a decreased rate of
re-hospitalization, a decrease in total neuroleptic dosage, shorter

1
Department of Pharmacy, University of Peshawar, Pakistan
2
Department of Zoology, Islamia College University Peshawar, Pakistan.
3
Khyber Medical College, Peshawar, Pakistan.
4
Jinnah College for Women, Pakistan.
length of hospital stay, fewer medication-related side-effects, and
improved quality of life and compliance [2-4]. Psychiatric pharmacy
services focus mainly on cost benefits and overuse of psychotropic
medication, improvement of clinical response and drug-induced ex-
trapyramidal symptoms [5, 6].
Adherence to therapies is a potentially dynamic phenomenon with
lower utilization of acute care services and greater engagement in
outpatient mental-health treatment. Poor adherence declines opti-
mum clinical benefits and therefore reduces the overall effectiveness
of health systems and results in more psychiatric re-hospitalizations
[7, 8]. Hence, medication management of chronic schizophrenic out-
patients with expanding the roles of a clinical pharmacist may prove
to be significant [3].
Pharmacists observe drug non-adherence, unexplained discrepan-
cies between patients' preadmission medication regimens and dis-
charge medication orders of patients and unexplained discrepancies
between discharge medication and post-discharge regimens of pa-
tients. A practical pharmacy-based intervention has been shown to
improve antipsychotic adherence among patients with schizophre-
nia, schizoaffective, or bipolar disorder (SMI) [9, 10]. Patricia et al de-
termined the effects of a psychiatric pharmacist on clinical outcomes
of acute care psychiatric inpatients. The results showed that the pro-
vision of intensive clinical services by a psychiatric pharmacist on an
5
Lady Reading Hospital, Post Graduate Medical Institute, Peshawar, Pakistan.
Correspondence: Saad Salman
Email: saadirph@gmail.com
Abstract
Background: Schizophrenia is one of the most severe psychiatric illnesses, with a prevalence of approximately 1% in the population.
Pharmacists cooperate with the patient and other professionals in designing, implementing and monitoring a therapeutic plan and
pharmacotherapy recommendations that will produce specific therapeutic outcomes for such patients. The objective of this study was
to assess the role of clinical pharmacists involvement in Psychiatry ward for the treatment of schizophrenic patients.
Methods: A double blind randomized control study was carried out in Psychiatry ward for a period of one year and three months at
Lady Reading hospital, Khyber Pakhtunkhwa, Peshawar, Pakistan. Clinical response was determined in schizophrenic patients i.e. first
episode psychosis, with objective rating scales, length of stay, adverse events, and patient compliance with the first clinic visit scheduled
after discharge, and patient satisfaction on likert scale. Different scales were used to check the severity of positive, negative and general
symptoms of the disorder, adherence to the medication and quality of life. Diary cards were given to the patients attendant so that
they may remind their patient of their medication.
Results: A total of 96 patients were enrolled in which 46 in control 50 in intervention groups. 3 patients in intervention group and 2
patients in control were under-diagnosed. We compared the outcomes of subjects treated in this collaborative care model, 46 in
intervention group with 46 controlled group subjects receiving usual hospital care. After 6 months, the intervention group showed a
significantly higher drug adherence rate than that of the control group. Morisky medication adherence scale (MMAS) and medication
adherence report scale (MARS) showed p-value 0.006 and 0.001, respectively. The positive and negative syndrome scale (PANSS) showed
p-value of 0.01 with change scores of -4.8 for intervention group. The SF-12 for quality of life (QOL) questionnaire showed p-value 0.002
in physical component summary (PCS), 0.001 in both mental component summary (MCS) and general health respectively. Patient
satisfaction on likert scale showed a mean of 4.45 (SD=0.52) in the intervention group.
Conclusion: Medication adherence and the quality of life of the schizophrenic patients were improved. Patients with co-morbidity were
identified. Patient education and counseling regarding indication and medication adherence was helpful. Clinical improvement was
noted in both groups, but the difference in intervened group was significant. (El Med J 2:3; 2014)
Keywords: Medication Adherence, Collaborative Care, Patient Satisfaction, Randomized Controlled Trial, Schizophrenia
Salman S, Idrees J, Anees M et al. 241
acute care psychiatric unit had significantly greater positive effects
on patient outcomes than when these services were not provided
[4].
Many study analyses have been performed. Most of them are retro-
spective and have not used objective rating scales to measure ther-
apeutic outcomes. Patient satisfactions with pharmaceutical services,
adherence to the therapeutic plan, and quality of life have not been
emphasized with improvements in rating-scale scores for clinical re-
sponse. The purpose of this study was to examine the effects of col-
laborative care model on drug adherence rates, quality of life, patient
outcomes and patient satisfaction through a randomized controlled
trial.
This double blind randomized controlled trial was conducted at Psy-
chiatry ward of Lady Reading Hospital, Post Graduate Medical Insti-
tute Peshawar. Potential study subjects were referred to the protocol
by their primary care provider immediately after starting antipsy-
chotic therapy for the expressed purpose of treating schizophrenic
symptoms. Physicians were instructed to exclude patients meeting
the following criteria: evidence that subjects had received an antide-
pressant-antipsychotic, alone or in combination during the preced-
ing 6 months; co-morbid mania or bipolar disorder; psychotic symp-
toms; eminent suicidality; and substance use disorder or depend-
ence. There were no significant differences between the two groups
with respect to age, gender, duration of illness, number of hospitali-
zations, and number of months since the last hospitalization.
Out of 152 patients, 96 consented for the study and were kept in two
groups by simple random sampling after examining their PANNS
(positive and negative syndrome scale) score [9]. All study proce-
dures were explained to the study participants and their attendants
and informed consent was obtained before induction. They were al-
lotted to different groups, resulting in 46 in usual care (controlled)
and 50 in collaborative care (intervention) (Figure 1). The control and
intervention group patients socio-demographic information, other
data associated to medication adherence and quality of life (QOL)
was collected by utilizing Morisky medication adherence scale
(MMAS-4) and SF-12 questionnaires at the baseline, respectively.
Both the groups were provided with dairy cards as a medication ad-
herence remainder and inquired to come for follow up every one
month. The intervention group patients were counseled on educa-
tion regarding: disease, pharmaceuticals and their administration.
Both groups were asked to give the persevering approval infor-
mation about pharmacist supplied counseling and services through
a patient approval questionnaire. Throughout the follow-up the
dairy cards of both group patients were collected. The obtained data
was noted and subjected for statistical analysis.
Subjects assigned to the interventional care treatment arm received
brief counseling on the prescribed drug, therapeutic end points, and
side effects in a manner consistent with patient education regarding
safe and effective use of drugs. An intake interview was conducted
by the care managers immediately after randomization. The care
managers assessed the severity of psychopathology, identifying po-
tential stressors and other predisposing factors. Past medication his-
tory, psychiatric, surgical, medical, drug therapy histories were also
recorded, and these were weighed against pre-defined inclusion/ex-
clusion criteria.

Figure 1: Patient recruitment and progress through the trial.
Patient education was another important component of the inter-
view. The positive, negative and general symptoms, etiology, and
prognosis of schizophrenia were discussed, and a detailed explana-
tion of the role of antipsychotics was presented, including its thera-
peutic benefits and adverse effects. Family members were actively
engaged in the educational component of the collaborative model.
After the initial intake interview, patients in the intervention group
were scheduled for frequent follow-up after every two weeks that
included both telephone calls and clinic appointments. During these
calls and follow ups, pharmacists followed a standardized set of
questions that assessed drug adherence, therapeutic effects and out-
comes, adverse effects, and other social, psychological and medical
factors. As clinical response became apparent, the pharmacists iden-
tified activities that the patients neglected during their illness and
provided encouragement to resume these pursuits.
Brief clinic visits were scheduled for weeks 2, 6, 12 and 24 for regular
psychiatric follow-ups. Pharmacists evaluated clinical progress dur-
ing this face-to-face encounter. At week 12, patients returned for
their final visit, during which time the necessity of maintenance
treatment was determined. Patients were advised to contact the
pharmacist if they were considering the discontinuation of therapy
at any time during the therapy.
The supervision and involvement of a designated psychiatric mentor
was one of the most fundamental aspects of this treatment model.
Clinical pharmacists met with the psychiatrist approximately daily for
242 Collaborative care for schizophrenic patients in primary care
Vol 2, No 3
half an hour, 2 hours each week at least, summarizing the presenta-
tion of new patients with the psychologist assistance, as well as
providing updates on the clinical progress of other subjects, and dis-
cussing it with the head clinical psychologists in the ward as well.
Patient satisfaction was evaluated at month 3 (along with clinical and
functional outcomes) through a 14-item survey mailed to both study
groups. The first 10 items asked patients to assess their satisfaction
with various aspects of treatment on a 5-point scale, with responses
ranging from very satisfied to very dissatisfy. The study protocol was
approved by the ethical committee of Lady Reading Hospital.
Results
Demographic variables and other baseline values were compared
between both the groups. For these values and other outcome
measures, a t-test was performed for continuous data and a
2
anal-
ysis was conducted for categorical or dichotomous data. Potential
differences were reported in terms of statistical significance (p
value), as well as odds ratio (OR) when applicable. Statistically signif-
icant differences were defined as a p value less than 0.05. SPSS 17.0
was used to analyze the data.
Drug adherence standards and quality of life were contrasted be-
tween study groups in an intent-to-treat fashion. Clinical and pur-
poseful outcomes were contrasted as community means got at base-
line and 3 months, as well as the change in community means oc-
curring between the two time points. For all items on the patient
satisfaction survey comprising of a 5-point scale, facts and figures
were contrasted by utilizing a t test or a 2 analysis of disintegrated
data (i.e., persuaded vs dispersuaded or neither).
Most patients were feminine (56.1% in the intervention group, 54.8%
among controls), and no statistically important differences were doc-
umented between group in age, health comorbidity, functional im-
pairments, despondency severity, education or social status, drug
class and dose of antipsychotics (Table 1). At baseline the diagnosed
schizophrenia patients were 32 (69.5%) vs 36 (78.2%) and schizoaf-
fective disorder 14 (30.4%) vs 10 (21.7%) in control and intervention
groups, respectively.
Table 2 shows the MMAS scores [mean (SD)] at baseline and first
follow-up. In the control group it was 4.13(1.20), 3.17(0.49) and in
intervention group 4.11(1.23) and 4.67(0.55), respectively. For base-
line, p=0.244 and for follow-up p=0.006. This shows that there was a
good improvement in medication adherence behavior in interven-
tion group. MARS scores [mean (SD)] at baseline and first follow-up
in control group was 22.88(3.31), 21.26(1.45) and in intervention
group 24.03(2.20), 26.67(0.22) respectively. For baseline, p=0.282,
and for follow-up, p<0.001.
Table 3 shows that there was a fair improvement/positive influence
on the pharmacist supplied education about medication adherence
performance. This positively leveraged their QOL. The mental com-
ponent summary and physical component summary at baseline in
control and intervention group were 41.26(SD=8.61), 43.21(SD=8.26)
with p=0.758 and 34.44(SD=4.11), 36.38(SD=4.71) with p=0.314 and
at first follow-up was 46.33(SD=8.14), 68.31(SD=9.11) with a signifi-
cant p-value of 0.001 and 35.20(SD=4.86), 46.71(SD=5.71) with a sig-
nificant p value of 0.002 respectively. The body pains component of
QOL at baseline, in control group and intervention group was
47.88(SD=26.90), 46.79(SD=14.71) with a p-value 0.729. At follow up,
the score of control group and intervention group were
46.70(SD=28.31), 64.52(SD=13.32) with value of as 0.003 respec-
tively. General Health at baseline in control group and intervention
group was 38.75(SD=29.86), 34.33(SD=22.39) with a p-value 0.678.
At follow up, the score of control group and intervention group were
33.75(SD=26.39), 54.79(SD=25.47) with value of as p=0.001 respec-
tively. Mental Health at baseline, in control group and intervention
group was 65.63(SD=16.99), 61.98(SD=15.41) with a p-value 0.340.
At follow up, the score of control group and intervention group were
65.19(SD=16.18), 78.33(SD=10.79) with p-value of 0.001 respectively.
This is apparently displayed that the medication adherence was ob-
scurely advanced the QOL in intervention group when compared to
the control group patients.
Table 2: Scores of MMAS
#
and MARS
#

Items Usual care
group
Collaborative
care group
P value
MMAS Baseline 4.13 (1.20) 4.11 (1.23) 0.244
At 6 months 3.17 (0.49) 4.67 (0.55) 0.006*
MARS Baseline 22.88 (3.31) 24.03 (2.20) 0.282
At 6 months 21.26 (1.45) 26.67 (0.22) <0.001*
#
MMAS: Morisky Medication Adherence Scale Scores; MARS: Medication adherence report scale.
*Significant at P<0.05.

Table 4 shows that there was a 43% decline in PANSS scores for the
intervention group and a 17% decline in groups for control topics
(p=0.01). Table 5 displays the patients approval about the pharma-
cist supplied clinical services with a total score of 57.27 (SD=8.01).
Significant tendencies were noted in the percentage of patients ac-
complishing remission and those exhibiting a therapeutic response
in the intervention group.
Table 1: Baseline characteristics of the participants.
Demographics Usual care
group
(n = 39)
Collaborative
care group
(n = 41)
Age, mean (SD) 37.3 (10.2) 36.9 (10.1)
Gender, % male/female 43.9/56.1 45.2/54.8
Married % 66.3 57.9
Diagnosis n (%) Schizophrenia 32 (69.5) 36 (78.2)
Schizoaffective
disorder
14 (30.4) 10 (21.7)
Hospitalizations
n (%)
0 4 (8.6) 5 (10.8)
110 6 (13.04) 4 (8.69)
Educational level
(%)
High 22.7 23.2
Average 33.0 31.8
Low 44.3 45.0
Social status (%) Employed 40.3 41.2
Unemployed 46.1 55.7
House wife 13.6 3.1

Salman S, Idrees J, Anees M et al. 243
Table 3: Quality of life scores [mean (SD)] of the patients.
Items Usual care
group
Collaborative
care group
P value
Mental
component
summary
B
#
41.26(8.61) 43.21(8.26) 0.758
F
#
46.33(8.14) 68.31(9.11) 0.001*
Physical
Functioning
B
#
38.11(35.91) 38.42(25.17) 0.771
F
#
40.16(35.72) 38.99(28.47) 0.557
Vitality B
#
57.29(23.86) 57.29(22.70) 1.000
F
#
55.21(22.09) 56.25(21.17) 0.868
Physical role B
#
51.17(25.07) 52.52(19.21) 0.776
F
#
51.04(25.25) 51.04(19.31) 1.000
Body Pains B
#
47.88(26.90) 46.79(14.71) 0.729
F
#
46.70(28.31) 64.52(13.32) 0.003*
Physical
component
summary
B
#
34.44(4.11) 36.38(4.71) 0.314
F
#
35.20(4.86) 46.71(5.71) 0.002*
General
Health
B
#
38.75(29.86) 34.33(22.39) 0.678
F
#
33.75(26.39) 54.79(25.47) 0.001*
Social
Functioning
B
#
53.17(21.70) 51.04(15.52) 0.570
F
#
57.29(18.77) 69.79(18.03) 0.766
Emotional
role
B
#
57.00(23.16) 58.08(20.32) 1.000
F
#
50.52(21.66) 52.40(21.80) 0.861
Mental
Health
B
#
65.63(16.99) 61.98(15.41) 0.340
F
#
65.19(16.18) 78.33(10.79) 0.001*
*B: Baseline; F: At 6 months. *Significant at P<0.05.

Table 4: Baseline PANSS scores (mean and SD) and follow up
PANSS scores (mean and SD) after treatment for patients who
completed the trial
PANSS
#
Usual care
group
Collaborative
care group
P value
Positive B
#
19.5 (5.50) 18.7 (5.31) 0.3
F
#

-3.8 (6.87) -4.1 (7.05)
Negative B
#

21.3 (5.20)
18.2 (4.18) 0.23
F
#
0.0 (9.64) -2.3 (7.63)
General B
#
41.2 (8.42) 40.3 (8.11) 0.22
F
#
-3.7 (10.13) -5.2 (15.88)
Total B
#
82.0 77.2 0.01*
F
#
-7.5 -11.6
*PANSS: Positive And Negative Syndrome Scale; B: Baseline; F: At 6 months.
*Significant at P<0.05.

Discussion
We conducted a randomized test of 92 patients being discharged
dwelling from the general service at a public sector hospital. Patients
in the intervention assembly received pharmacist counseling at dis-
charge and a follow-up phone call 3 to 5 days subsequent. Interven-
tions concentrated on clarifying medication regimens, reviewing
suggestions, directions, screening for obstacles to adherence and
supplying patient therapy and/or doctor response when appropri-
ate.
Table 5: Patient satisfaction with pharmacy services*
Items Mean SD
Explanation of Schizophrenia 4.38 0.51
I learned about managing my mental illness 4.25 0.63
I understand more about how medication
affects me
4.33 0.56
Explanation on the purpose of the medicine 4.12 0.38
I had a chance to ask questions 4.42 0.41
learned about my treatment 4.08 0.61
Advice on how best to take medicine 4.51 0.72
My counselor was helpful 4.67 0.48
I am satisfied with this counseling study 4.67 0.48
Explanation on possible side effects 4.44 0.62
Would recommend this type of counseling
to a friend
4.42 0.54
Medication and Diary card counseling 4.48 0.57
People in the study treated me with respect 4.50 0.45
Total mean score 57.27 8.01
*Items rated on Likert scale by patients on a 1 as strongly disagree to 5 as strongly agree.
A methodical review assessing the influence of pharmacists in men-
tal well-being from 19722013, reported that out of 65 studies, out-
comes of the 26 investigations were affirmative, illustrating improve-
ments in conclusions, prescribing practices, persevering satisfaction,
and asset use. Nineteen of the investigations examined the function
of pharmacists in providing remedy recommendations and patient
learning, five boasted pharmacists with prescriptive authority, and
the remaining two described the influence pharmacists in consign-
ing education to the psychiatric employees [2]. The results propose
that there is a need to encourage community pharmacists' participa-
tion in extending education and to improve liaison with other com-
munity wellbeing professionals such as community psychiatric doc-
tors [5].
Pharmacists discerned the following drug-related problems in the
intervention group: unexplained discrepancies between patients'
pre-admission medication regimens and release medication orders
in 49% of patients, unexplained discrepancies between release med-
ication registers were observed and post release regimens in 29% of
patients. Medication non-adherence was seen in 23%. Comparing
test outcomes 30 days after release, preventable issues were noticed
in 11% of patients in the control group and 1% of patients in the
intervention group (p=0.01).
Cohen put ahead the idea that pharmacists helping patients with
schizophrenia consolidate the medications they take by investigat-
ing if the total number of doses or tablets can be decreased. They
can assist in informing patients on how to contend with harmful
pharmaceutical consequences and by following up to glimpse if pa-
tients are acting on physicians directions. He furthermore indicated
that pharmacists can take advantage of their usual communicate
with patients in the provision of antipsychotic pharmaceuticals, and
244 Collaborative care for schizophrenic patients in primary care
Vol 2, No 3
thus, are ideal prime care constituents of the schizophrenia health
care group. Both Cohen and Donoghue were of the view that com-
munity pharmacists need to become more proactive in proposing
advice and data to patients with schizophrenia, since the majority of
pharmacists are asked for advice only rarely. In general, most publi-
cations stated that the role of the pharmacists as an advisor for pa-
tients with schizophrenia needs to be expanded, in which optimal
motivation will probably be the best guarantee for achievement [9,
11].
Pharmacists today propose to collaborate with psychiatrists to
evolve remedy algorithms and clues based guidelines for pharma-
ceutical classes and infection states as well as to compose mono-
graphs recounting the use of specific agencies [3, 12, 13]. Cohen
stated that any drug that can significantly decrease hospitalization
rate will decrease general costs of treatment [11]. Furthermore, Co-
hen also claimed that pharmacists are adept to supervising the ad-
herence to therapeutic guidelines and that they may use prescrip-
tion notes in alignment to supply data for improving value of treat-
ment. By doing this, the incident of adverse consequences may be
traced by noticing non-compliance and irrational drug use, which
are often prescribed by physicians.
Donoghue reported that general practitioners may benefit if phar-
macists are active in boosting patients to self-medicate minor ail-
ments rather than take up surgery time with an avoidable appoint-
ment [13]. By doing so, general practitioners consulting hours can
be utilized for severe psychiatric patients. In conclusion, pharmaceu-
tical care achievement is reliant on the perception of the new func-
tion of the pharmacist among the complete mental healthcare
group. Pharmacists can take up straightforward assesses to boost
their visibility, by construction connections with prime and second-
ary mental health care groups. Furthermore, extending education
between and with all values of mental wellbeing care may facilitate
collaboration and data exchange.
Maslen et al described about the need to improve the liaison of the
community pharmacist with community psychiatric doctors [14]. The
last mentioned group furthermore supplied medication-related rec-
ommendations and data to patients with schizophrenia. Their study
disclosed that it is also of growing importance to lift the perception
of community psychiatric doctors about the function of the commu-
nity pharmacist, since there are actually numerous unmet desires in
both disciplines.
Conclusion
The present study displays that the clinical pharmacist involvement
in schizophrenia has affirmative influence in creating awareness
about the disease, and its usage and in advancing the QOL. This
study concluded that continuous counseling should be undertaken
for schizophrenia to focus and re-focus the significance of medica-
tion adherence and quality of Life, reduce progression of disease and
ultimately minimize hospitalization, thereby minimizing the cost and
advancing better quality of life.
Acknowledgment: The following individuals are acknowledged for their support,
encouragement and guidance. Dr. Sareer Badshah, Dr. Gohar Ali, Dr. Ziadh, Dr.
Shahab, Dr. Imad, Dr. Benish, Dr. Naila Riaz Awan and Maam Sehrish. Psychologists
(interns): Ayesha, Mehreen, Faiza and Sumreen for their help. We thank Dr.
Muhammad Idrees and Sir Farooq Ali for the private funding of this research.
References
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Open Access Short Report
2014 Dhar; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits
.Cite this article as: Dhar D: Audit of orthopedic trauma theatre usage: Observation from a secondary regional referral hospital in Oman. El Mednifico Journal 2014, 2(3): 245-247.
Audit of orthopedic trauma theatre usage: Observation from a secondary regional referral hospital in
Oman
Dinesh Dhar
1

Introduction
Trauma is the leading cause of admission to our hospital and its un-
predictability along with mismatch in demand and supply requires
more use of resources and system streamlining. The operation thea-
tre is described as the engine room of the hospital [1]. To run this
engine efficiently and to maximize utilization requires coordinated
activity between all personnel involved. It also represents large pro-
portion of the hospital budget, and its maximum utilization is there-
fore important to ensure optimum cost benefit [2]. The cost of the
healthcare is increasing every year and the situation for orthopedic
trauma surgeon is complicated by increasing trauma in this part of
world which in turn increases the demand on orthopedic operation
theatre.
There is no audit from Gulf region on the orthopedic operation the-
atre usage. The present study was undertaken to assess theatre uti-
lization in our hospital and identify areas where improvement could
be done which in turn can be applied to other surgical specialties in
our hospital and beyond.
Findings
Methods
This prospective audit was carried out in 303 bedded regional refer-
ral Nizwa hospital in the Department of Orthopedics. The hospital
has a fully dedicated orthopedic operation theatre working 5 days a
week (Saturday to Wednesday), with one anesthetist and three op-
eration theatre personnel separately assigned to it. The operation

1
Department of Orthopedics, Nizwa Regional Referral Hospital, Oman
Correspondence: Dinesh Dhar
Email: dinesh612012@live.com
electively is operational from 0730 hrs to 1400 hrs with no scheduled
break amounting to 390 min/day. The same is used for emergency
trauma surgery between 1400 hrs to 0700 hrs the following day. The
operation theatre complex is located on the same floor as the surgi-
cal wards and consists of four operation theatres along with one
common patient recovery room. There are 2-3 porters for the whole
operation theatre complex responsible for moving the patients to
and fro from the ward to operation theatre.
A total of 853 cases were electively operated upon during 12 months
period from 1
st
January 2011 to 31
st
December 2011 in orthopedic
operation theatre which was run for 261 days electively during that
period. Cases performed on public holidays or during weekend
(Thursday/Friday) and after 1400 hrs were excluded and classified as
emergency procedures. The data was recorded from the time the
patient entered the operation theatre (Enter OT) to the time he left
(Exit OT). The data was recorded for surgery, anesthesia, changeover,
total operating time respectively and calculations made for other
variables as shown below:
1. Allocated theatre time (ATT): Time from scheduled start to finish
of theatre session.
2. Surgical time (ST): Time from start of incision to closure of inci-
sion (End surgery-start surgery).
3. Anesthesia time (AT): (Exit OT-Enter OT)-ST.
4. Changeover time (CT): Time when one patient exits the OT and
next patient enters.
5. Late start time (LST): Time lost at start of OT list due to delays.

Abstract
Background: Trauma is the leading cause of admission to our hospital and its unpredictability along with mismatch in demand and
supply requires more use of resources and system streamlining. The operation theatre is described as the engine room of the hospital.
There is no audit from Gulf region on the orthopedic operation theatre usage. The present study was undertaken to assess theatre
utilization in our hospital and identify areas where improvement could be done which in turn can be applied to other surgical specialties
in our hospital and beyond.
Findings: This prospective audit was carried out in 303 bedded regional referral Nizwa hospital in the Department of Orthopedics. A total
of 853 cases were electively operated upon during 12 months period from 1
st
January 2011 to 31
st
December 2011 in orthopedic operation
theatre which was run for 261 days electively during that period. Cases performed on public holidays or during weekend and after 1400
hrs were excluded and classified as emergency procedures. The data was recorded from the time the patient entered the operation
theatre (Enter OT) to the time he left (Exit OT). The data was recorded for surgery, anesthesia, changeover, total operating time
respectively and calculations made for other variables. 632 cases (74%) started later than scheduled time with average of 22.8 min late
start time. Delay in starting the list was due to late arrival of surgeons (22.2%) or anesthetist (28%) in 50.2% cases. Delay due to late or
incomplete preparation of the patient or transportation of patient accounted for 44.4% cases. Other causes of delay such as physician or
anesthesia review prior to surgery accounted for 5.4% of the delay.
Conclusion: Operation theatre, being an area of maximum and complex activity in any hospital, needs multipronged strategy to improve
its utilization continuously with regular theatre committee meetings to discuss and anticipate problems and chalk out new ideas and
strategies. (El Med J 2:3; 2014)
Keywords: Orthopedic, Trauma, Operation, Theatre, Audit
246 Audit of orthopedic trauma theatre usage
Vol 2, No 3
6. No useful activity (NUA): Difference between the scheduled fin-
ish time and actual time the last patient exits the operating the-
atre. 1-(AT+ST+CT+LST)/ATTx100%.
7. Operation time (OT): ATT- CT.
8. End utilization (EU): (AT+ST/OT)x100%.
9. Operation theatre utilization (OUT): (AT+ST+CT/ATT)x100%.
Results
The orthopedic operation theatre in our hospital was functioning for
261 days during year 2011 and a total of 853 cases were operated
upon during this time (Table 1). 632 cases (74%) started later than
scheduled time with average of 22.8 min late start time. Delay in
starting the list was due to late arrival of surgeons (22.2%) or anes-
thetist (28%) in 50.2% cases. Delay due to late or incomplete prepa-
ration of the patient or transportation of patient accounted for 44.4%
cases. Other causes of delay such as physician or anesthesia review
prior to surgery accounted for 5.4% of the delay.
Table 1: Operations done during period from 1
st
January to
31
st
December 2011
Month No. of
working days
Total
N Operations
Mean of
operations
January 23 64 2.7
February 19 65 3.4
March 23 65 2.8
April 22 93 4.2
May 23 65 2.8
June 22 67 3.0
July 23 57 2.4
August 22 74 3.3
September 20 66 3.3
October 23 89 3.8
November 18 67 3.7
December 23 81 3.5
Total 261 853 3.24
The total operating time (OT) was 1403.02 hrs accounting for 81% of
the total allocated theatre time (ATT) with a mean of 5:15 hrs. The
total surgical and anesthesia time was 1076.35 hrs (63%) and 256.28
hrs (15%), respectively. Changeover time was 70.39 hrs (4%) with
average of 22.6 min and no useful activity (NUA) amounted to total
of 310.32 hrs (18%) (Table 2). Based on above calculations, it
amounted to end utilization (EU) of 94% and operation theatre utili-
zation (OUT) of 81.8% respectively. The period between end of one
surgery to start of next surgery averaged 51 min. 11.9% (102/853)
cases finished before 14:00 hrs accounting for 151:44 hrs (8% of the
ATT). This loss can be avoided if standby cases are kept fasting ten-
tatively to be done instead of cancelled cases. Total of 36 cases
(4.2%) were cancelled for various reasons as enumerated in Table 3.
Discussion
Efficient utilization of the operation theatre complex in any hospital
is important for many reasons. First, for clearing the waiting lists, sec-
ond, for financial considerations and last if not least, it serves as the
index of surgeons efficiency. Theatre time as per NHS release is said
to cost 400 sterling pounds/hr excluding consumables [3]. The audit
will help to understand the scheduling of elective operation list,
shortcomings and measures to make it more cost efficient.

Table 2: Time distribution in Operation Theatre
Year 2011, Jan-Dec Total
Allocated theatre time (hrs) 1713.34
Total operating time (hrs) 1403.02 (81%)
Surgical time (hrs) 1076.35 (63%)
Anesthesia time (hrs) 256.28 (15%)
Changeover time (hrs) 70.39 (4%)
Time wasted (hrs) 310.34 (18%)

Table 3: Reasons for cancellation
Reason N %
Lack of time 23 63.9
Lack of fitness 08 22.2
Emergency surgery 04 11.1
Consent Delay 01 2.8
Total 36 100

Late starting of lists (LST): This problem is acknowledged worldwide
.In the present study 74% cases started late with average of 22.8 min.
after scheduled time which is unacceptable. The main reason for LST
was anesthetics related problem and non-standardization of start
time. Vinukondaiah et al and Ricketts et al have reported 40% and
94% delay in starting surgery respectively [4, 5]. The average delay
in starting time of 22.8 min in our series was unacceptable as induc-
tion of anesthesia should start at the scheduled start time and hence
LST should be zero. Other authors have also reported average delay
of 26.5, 18 and 18.8 minutes respectively [5-7]. This problem needs
multidisciplinary approach with involvement of ward/theatre in-
charge, senior surgeon and anesthetist preferably of consultant
grade to ensure that the OT list starts on time [7]. It has been ob-
served that anesthetists are not happy anesthetizing a patient unless
the surgeon is around [5]. Presence of consultant anesthetist and
surgeon at the start of operation list and during it will surely decrease
the delay in starting the list. Preoperative discussion with the ward
and OT staff about the scheduling of cases and preoperative prepa-
ration will go a long way in preventing delay in smooth starting and
subsequent delay between cases thereby increasing the utilization
of operation time.
Operating Timing: The total OT in our series was 81% of the total
ATT which is comparable to other studies 91.5%, 60%, 48% and 82%
[4, 5, 7, 8]. The mean total OT in our setup was around 05 hrs 15 min
per day which is short. This can be attributed to shortage of anes-
thetist, only one available OT and many public holidays and week-
ends which in turn decrease the availability of operating room.
Changeover time: The general observation is that longer the dura-
tion of surgery the longer is the associated changeover time [2]. The
changeover time ranges from 3.6 min in pediatric surgery to 23.4
min for cardiothoracic surgery with average time of 14.1 min [2]. For
trauma surgery which is usually longer the approximate standard-
ized changeover time is set around 15 min. Our changeover time of
Dhar D 247
22.6 min is more than the acceptable standard. Changeover time can
be quicker by the presence of consultant surgeon [5]. Architectural
changes in operation theatre complex in form of having OT with in-
built induction and early recovery room so that the anesthetist can
induce in induction room and early recovery from anesthesia takes
place in recovery room from where the patient after some time can
be transferred by nursing staff to main recovery area without need
of anesthetist to accompany the patient and he can proceed with
preparation of next patient in the neighboring anesthetic room [9].
By such architectural changes it has been found that non-operative
time (anesthetic and changeover time) was reduced by 29 min.
Other commentators have suggested to improve this problem by
having surgeon run two operation theatres simultaneously [7].
End Utilization: Audit Commission UK has set 77% as standard target
for end utilization time [10]. In our study, it was 94% compared to
other studies by Ricketts (60%), Durani (75%) and Delaney (78.8%)
[5-7]. The only problem is that surgical and anesthetic times are over-
estimated in arriving at end utilization time as we are adding the
time taken preparation of patient as positioning, draping, dressings,
plaster application and transfer of patients onto bed in our calcula-
tions. Therefore, further refinements in auditing are required to con-
sider these variables in order to arrive at accurate end utilization time
[7].
Operation theatre utilization: In our study the operating theatre uti-
lization was 81.8% which is less than set standard of 85-90% [8].
Taken however with standard changeover time of 15 min, which
shows that extra average 7.6 min changeover time in our series
needs to be deducted from each changeover time which would
leave us with final theatre utilization of around 70.2% which is much
below the standard.
Day of week: There was no significant statistical difference between
the number of operations performed during the days of week, Sat-
urday to Wednesday. There was however late start of list on Wednes-
day by around 20 min due to morning departmental CME on that
day.
Grade of surgeon and anesthetist: In our series, 82% of the opera-
tions were done with senior surgeon of the rank of senior specialist
scrubbed in. There was no difference in timing of surgery performed
by specialist and junior specialist. Complicated procedures took
more time but if carried out by senior surgeon timing was reduced
due to their faster operating speed. Turnover time was shortest for
senior surgeons and senior anesthetist. Specialist and junior special-
ist administered anesthesia in 73% cases. Delay in starting the list
was found to be more with junior anesthetists.
Conclusion
Operation theatre, being an area of maximum and complex activity
in any hospital, needs multipronged strategy to improve its utiliza-
tion continuously with regular theatre committee meetings to dis-
cuss and anticipate problems, chalk out new ideas and strategies,
the foremost among them being to start OT list in time, minimize
changeover time to acceptable 15 minutes, aligning demand and
supply and maximizing theatre utilization within the existing re-
sources.
Competing interests: The author declares that no competing interests exist.
Received: 16 January 2014 Accepted: 3 April 2014
Published Online: 3 April 2014
References
1. Sebastain V, Brey Z, Numanoglu A: Improving operating theatre efficiency in
South Africa.SAMJ 2011, 101(7): 444-447.
2. Jan F, Tabish S, Qazi S: Time utilization of operating rooms at a large teaching
hospital. J Acad Hosp Adm 2003,15: 1-6.
3. NHS Institute: The productive theatre-improving quality and efficiency in
operating theatre [http://www.institute.nhs.uk/quality_and_value/
productivity_series/the_productive_operating_theatre.html].
4. Vinukondaiah K, Ananthankrishnan N, Ravishankar M: Audit of operation
theatre utilization in general surgery. Natl Med J India 2000, 13: 118-121.
5. Ricketts D, Hartley J, Patterson M, Harries W, Hitchin D: An orthopaedic theatre
timings survey. Ann R Coll Surg Engl 1994, 76: 200-204.
6. Durain P, Seagrave M, Neumann L: The usage of theatre time in elective
orthopaedic surgery. Ann R Coll Surg Engl 2005, 87: 170-172.
7. Delaney C, Davis N, Tamblyn P: Audit of utilization of time in an orthopaedic
trauma theatre. ANZ J Surg. 2010, 80: 217-222.
8. Tyler D, Pasquariello C, Chen C-H: Determining optimum operating theatre
utilization. Anaesth Analg 2003, 96: 1114-1121.
9. Sandberg W, Daily B, Egan M et al: Deliberate perioperative systems design
improves operating room throughput. J Anesth 2005, 103: 406-418.
10. Audit commission operating theatre. A bulletin for health bodies. London:
Audit commission, 2002 (May).


Open Access Short Report
2014 Malik et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Sheikh: Hybrid NOTES cholecystectomy - A safe and economic innovation. El Mednifico Journal 2014, 2(3): 248-250.
Hybrid NOTES cholecystectomy - A safe and economic innovation
Momin Malik
1
, Sherif Saleh
1
, Irfan Ahmed
1

Background
Minimally invasive techniques have revolutionized surgery, reducing
post-operative morbidity and hospital stay by reducing abdominal
wall trauma. There is also a significant cosmetic advantage with
these newer techniques. Minimally invasive surgery has opened the
floodgates of innovation as surgeons open up to possibilities of new
instrumentation and techniques different from those practiced for
centuries.
To further improve cosmetic results and improve clinical outcomes
concept of NOTES (natural orifice transluminal endoscopic surgery)
was introduced. Due to technical difficulties and cost of newer in-
struments this concept is still in the experimental stages. Recent in-
troduction of single incision laparoscopic surgery has generated sig-
nificant interest among surgeons. We have a large experience of sin-
gle incision laparoscopic surgical techniques at the local level. After
establishing safety profile at the in our institution we now present
another modification of single incision laparoscopic cholecystec-
tomy by using natural orifice with conventional instruments.
Methods
The techniques were discussed with the patients in detail explaining
the nature of operation and mentioning lack of safety profile. A full
informed consent was obtained from the patients. Operation theatre
staff was informed of the procedure. SS (Consultant Gynecologist)
helped with the insertion and removal of the vaginal port. Opera-
tions were carried by IA (Consultant Surgeon) and MM (Senior Clini-
cal Fellow). The operations were recorded without identifying the
patients after taking consent. These procedures were performed on
patients diagnosed with gallstone disease and scheduled to undergo
elective interval single-incision laparoscopic cholecystectomy.
Standard laparoscopic ports, straight laparoscopic instruments and
5mm 30 scopes were used. A standard day case general anesthesia

1
Aberdeen Royal Infirmary, United Kingdom
Correspondence: Momin Malik
Email: momin.malik@nhs.net
regimen was used and one dose of prophylactic antibiotics was ad-
ministered.
The patient was placed in Lloyd-Davies position. A low profile 5mm
umbilical port with a gas channel was inserted using open Hassan
technique. A 5mm, 30 straight scope was inserted to get a general
view of the abdominal cavity (Figure 1). The gynecologist (SS) intro-
duced a long 5mm laparoscopic port through the posterior fornix of
vagina, using a uterine sound to position the uterus in anteverted
position and maintaining internal visualization on screen through
the umbilical camera. After safe insertion, the scope was then trans-
ferred to the vaginal port.

Abstract
Background: Minimally invasive techniques have revolutionized surgery, making great impact in terms of reduced postoperative morbidity
and shorter hospital stay by reducing abdominal wall trauma. Recent introduction of single incision laparoscopic surgery has introduced
another debate. After establishing safety profile at the local level, we now present another modification of single incision cholecystectomy.
Findings: These procedures were performed on two female patients diagnosed with gallstone disease and scheduled to undergo elective
single incision laparoscopic surgery (SILS). Standard laparoscopic ports, straight laparoscopic instruments and 5mm 30 scopes were used.
The scope was inserted per vaginum using a long 5mm laparoscopic port. The operation was performed using two instruments introduced
through the umbilicus using two standard 5mm laparoscopic ports. The 5mm umbilical fascial defects did not require formal closure. No
intra-operative or postoperative complication was reported. Operation was made technically easy because this modification provided
greater flexibility of movement for operating instruments by decreasing crowding at the umbilical port without compromising on
postoperative recovery or cosmetics.
Conclusion: The use of laparoscope through vagina is a viable and safe modification of single incision laparoscopic surgery. (El Med J 2:3;
2014)
Keywords: Cholecystectomy, Laparoscopic, Single Incision, SILS, NOTES

Figure 1: Setup for hybrid NOTES cholecystectomy.
Malik M, Saleh S, Ahmed I 249
Another low profile 5mm umbilical port was introduced through the
same umbilical skin incision but separate stab incision for introduc-
tion of two operating instruments. Assistant was positioned between
the patients legs sitting on a stool and the surgeon stood on the
patients left side. Scrub nurse was positioned on patients right side.
Good visualization of the abdominal cavity was obtained via the high
definition 5mm 30 camera inserted through vaginal port.
A 2/0 multibraided silk suture on a straight, cutting needle was in-
serted percutaneously in the epigastrium (site of 12mm port in
standard 4 port lap-cholecystectomy). This suture was then passed
twice through the Hartmanns pouch and passed out through the
skin in right flank. The needle was cut and the two ends of the suture
were secured outside with artery forceps. Traction on one or the
other end of the suture was now used to flip the gallbladder neck
(flag maneuver) to give the critical anterior and posterior views of
Calots triangle without the need for an additional port.
Standard dissection was carried out in the Calots triangle adhering
to the standard safety protocol. Cystic duct and artery were visual-
ized and clipped using a disposable 5mm clip applier. The gallblad-
der was dissected off the liver bed using diathermy hook. As 5mm
incisions were not suitable for removal of the gallbladder through
umbilicus vaginal extraction of the gall bladder was carried out after
shifting the camera to one of the 5mm umbilical ports. This avoided
the need for a bigger incision at the umbilicus.

The 5mm umbilical fascial defects did not require formal closure and
so decrease probability of post-operative port site incisional hernia.
The vaginal port defect also measured 5mm and did not require for-
mal closure. The patients had an uneventful recovery from surgery.
One patient complained of minor spotting per vagina, which settled
on the first post-operative day.
Discussion
We found that using a laparoscopic camera per vaginum offered a
suitable and safe view of the gallbladder area. However, since a cam-
era introduced through the posterior fornix angulates upwards over
the bowel, it is noted that the use of a 30 scope is essential and a 0
scope would not be able to provide a suitable view. We feel that a
45 camera might provide better visualization but it was not availa-
ble at the time of surgery. It was also felt that use of a longer camera
(or a camera with good zoom function) would afford better view
because of the increased port operative area distance.
We found the cholecystectomy to be easier technically with only two
instruments sharing the umbilical port (instead of 3 in standard SILS
technique). There was less sword-fighting between the instruments,
and no interference of the camera in assistants hand with the oper-
ating surgeons hand. The Hartmanns pouch stitch is easy and safe
to place and we use it as a standard technique in our SILS cases.
Once in position, it provides a good critical view of Calots triangle
similar to standard laparoscopic cholecystectomy, which is im-
portant for safe dissection and assists in the learning curve for sur-
geons new to single port techniques.
The gallbladder was easily removed via vaginal port site since vaginal
wall is more easily stretchable than abdominal wall layers. The 5mm
port site in the vagina was too small to require formal suturing. The
overall operative time was comparable with standard single port lap-
aroscopic cholecystectomy. The patients had an uneventful recovery
from surgery. One patient complained of spotting per vagina, which
settled on the first post-operative day.
Since the first reports of transluminal interventional procedures in
porcine models in 2000 and humans in 2003, there have been many
advancements and variations in technique [1]. However, since its
conception, concerns about NOTES remain almost unchanged and
include reservations about safety of iatrogenic injury, danger of hem-
orrhage and how to control it, introduction of infection and long-
term effects eg adhesion formation, dyspareunia, etc [2]. The vaginal
route offers many advantages because it is easier to disinfect, there
is less risk of hemorrhage due to the alignment of blood vessels, the
camera assistant can sit comfortably and keep out of the way of op-
erating surgeon and the wall repairs itself without leaving scars or
herniae [3].
Single incision laparoscopic surgery (SILS) focuses at minimizing the
number of scars of ports on the abdominal wall, while adhering to
the standard laparoscopic principles. The umbilicus is the favored
port site, both for cholecystectomy and appendicectomy by this
technique. A number of single ports with channels for multiple in-
struments have been introduced in the market. Using standard lap-
aroscopic ports through individual rectus sheath, fasciotomies under
a common skin incision eliminates the need for a special port while
giving the same cosmetic result [4]. There may, however, be issues
like gas leak from around the ports, difficult closure of fascial inci-
sions and increased risk of umbilical incisional hernia post opera-
tively when using three ports with this technique.
Hybrid procedures combine a transluminal endoscope with a lapa-
roscope for direct visualization, or with the use of retractors, graspers
and clip applicators through additional standard laparoscopic ports
[5]. Our hybrid technique aims to utilize the advantages of each in-
dividual method, while minimizing the disadvantages. The vagina is
associated with lowest NOTES complications eg leaks or infection.
Restricting the vaginal port size to 5mm excludes the necessity for
formal closure. The use of two standard laparoscopic ports through

Figure 2: Hartmann's pouch stitch.
250 Hybrid NOTES cholecystectomy
Vol 2, No 3
a single umbilical skin incision is understandably easier than using
three ports. It gives all the cosmetic advantages of single port sur-
gery without the added expense of a specialized port. This also al-
lows wider range of movement of two instruments since they move
on independent fulcrums. When coupled with the Hartmanns pouch
stitch, the safety and ease for purposes of training matches that of
standard laparoscopic surgery.
Post-operatively, the two separate 5mm cuts in the rectus sheath are
too small to merit formal closure. It is hoped that this technique
would reduce incidence of umbilical incisional hernia formation as
this remains one of the reservation of SILS technique. However, more
evidence will need to be collected to confirm this hypothesis. Cos-
metically, this technique leaves an invisible umbilical scar similar to
those for single ports.
Conclusion
The use of laparoscope through vagina is a viable and safe modifica-
tion of single incision laparoscopic surgery.
Received: 16 March 2014 Accepted: 28 July 2014
References
1. ASGE Technology Committee. Natural orifice translumenal endoscopic
surgery. J Gastrointest Surg. 2008;68(4):617-20.
2. Arulampalam T, Paterson-Brown S, Morris AJ, Parker MC. Natural orifice
transluminal endoscopic surgery consensus statement. London, United
Kingdom;2009 May. 11p.
3. Stark M, Benhidjeb T. Natural orifice surgery: transdouglas surgery a new
concept. JSLS. 2008;12:295-8.
4. Ching Li L, Ming-Te H, Soul-Chin C, Po-Li W, Chih-Hsiung W, Weu W. Initial
experience of single laparoscopic cholecystectomy (with video). Surg Laparosc
Endosc Percutan Tech. 2010 Aug;20(4):243-6.
5. Tsin DA, Colombero LT, Lambeck J, Manolas P. Minilaparoscopy assisted
natural orifice surgery. JSLS. 2007;11:24-9.


Open Access Review
2014 Hafez et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Hafez AAE: Microinflammation as a candidate for diabetic nephropathy. El Mednifico Journal 2014, 2(3): 251-258.
Microinflammation as a candidate for diabetic nephropathy
Amal Abd El Hafez
1

Introduction
Diabetes mellitus (DM) and its complications have become a public
health problem [1]. Diabetic nephropathy (DN) is a major cause of
mortality in patients with type 1 and type 2 diabetes throughout the
world [2]. Between 20% and 40% of diabetic patients ultimately de-
velop nephropathy [3]. In human glomeruli, glomerular hypertrophy,
expansion of diffuse mesangial matrices, exudative lesions, segmen-
tal nodular sclerosis (thickening of the glomerular basement mem-
brane) and/or podocyte loss with compensatory expansion of the
remaining podocyte foot processes are the main pathological fea-
tures of diabetic nephropathy which direct to the ultimate develop-
ment of glomerulosclerosis, tubulointerstitial fibrosis, impairment of
renal function and progression to end-stage renal disease (ESRD) [3,
4].
Microinflammation as a candidate for DN
Traditionally, multiple mechanisms were accredited to contribute to
the development and outcomes of DN, such as an interaction be-
tween metabolic and hemodynamic factors, oxidative stress, hormo-
nal factors, adipokines and genetic susceptibility which sets a con-
tinuous perpetuation for kidney injury [5-7]. However, new perspec-
tives in activated innate immunity and inflammation appear to be
important factors in the pathogenesis of DM and its associated com-
plications. Hence, recent studies disclosed that these conventional
mechanisms are only partially responsible for the development
and/or progression of DN, and that low-grade or subclinical inflam-
mation, termed microinflammation, plays a vital role in the patho-
genesis of this diabetic complication [2, 8-10]. The relationships be-
tween microinflammation and the pre-existing traditional factors
during the development and progression of DN involve complex
pathways with hyperglycemia laying at upstream and microinflam-
mation and subsequent evolution of DN representing downstream
of these pathways addressed here in brief (Figure 1).
Metabolic factors
Chronic hyperglycemia has long been implicated as a major contrib-
utor to several diabetic complications through three major mecha-

1
Pathology Department, Faculty of Medicine, Mansoura University, Egypt
Correspondence: Amal Abd El Hafez
Email: amalabdelhafez@gmail.com
nisms: non-enzymatic glycosylation that generates advanced glyco-
sylation end (AGE) products, activation of protein kinase C (PKC), and
acceleration of the aldose reductase (polyol) pathway. Oxidative
stress seems to be a theme common to all three mechanisms [11].
Mesangial cell expansion, increased mesangial cell matrix production
and mesangial cell apoptosis seem to be mediated in part by an in-
crease in the mesangial cell glucose concentration, since similar ef-
fects can be induced in a normal glucose environment by overex-
pression of glucose transporters, such as GLUT1 and GLUT4, thereby
increasing glucose entry into the cells [12, 13]. Besides, hyperglyce-
mia induces mesangial fibrosis that requires activation of interleukin
(IL)-8. As a contributor in renal inflammation, high glucose promotes
mesangial production of macrophage chemoattractant protein-1
(MCP-1 also known as CCL2, CC chemokine ligand 2), IL-6, and tumor
necrosis factor (TNF)-, which, together with adhesion molecules,
favor leukocyte recruitment and adhesion to endothelial cells [14,
15].
Furthermore, AGE products and AGE-modified proteins may bind to
leukocytes, stimulating the synthesis and release of proinflammatory
cytokines in DN [16]. Hyperglycemia might also upregulate vascular
endothelial growth factor (VEGF) expression in podocytes, which
could markedly increase vascular permeability [17, 18].
The mechanism by which hyperglycemia leads to PKC activation in-
volves de novo formation of diacylglycerol, oxidative stress and in-
duction of the activity of mitogen-activated protein kinases (MAPK)
in response to extracellular stimuli [19]. The subsequent events for
this intracellular signaling in glomerular endothelial cells include en-
dothelial dysfunction, inflammation and microvascular thrombosis
[14, 15].
Additionally, hyperlipidemia represents another independent meta-
bolic risk factor for the progression of DN. Its molecular mechanism
involves toll-like receptor 4 (TLR4) interaction with its potent ligand
S100 calcium binding protein A8 (calgranulin A; S100A8), in macro-
phages infiltrating the glomeruli of DN patients. Also, activation of

Abstract
Diabetic nephropathy (DN) is a major cause of mortality in patients with type 1 and 2 diabetes throughout the world. This review draws
attention to the important role of microinflammation and the complex pathways implicated in the development and progression of DN.
These pathways include the collaboration of metabolic, hemodynamic and hormonal factors with oxidative stress in patients with genetic
susceptibility to create an inflammatory milieu. The key role of inflammatory cells in the kidney, particularly infiltrating macrophages and T-
lymphocytes is highlighted. The major inflammatory cytokines and chemokines, receptors, adhesion molecules as well as transcription factors
and transduction pathways involved in the pathogenesis of DN are also discussed. Understanding of these inflammatory pathways guides
important therapeutic appliances and improves the discovery of new therapeutic targets that can be translated into clinical treatments for
DN. (El Med J 2:3; 2014)
Keywords: Diabetic Nephropathy, Microinflammation, Pathways, Cytokines, Macrophage, Lymphocyte, Therapeutic
252 Microinflammation as a candidate for diabetic nephropathy
Vol 2, No 3

Figure 1: Schematic illustration of various elements that contribute to the micoinflammation in diabetic nephropathy. An interaction
of several factors creates an inflammatory milieu with a continuous perpetuation of injury progressing to end stage renal damage.
S100A8/TLR4 signaling was elucidated in an animal model of dia-
betic glomerular injury accompanied with hyperlipidemia, which
may provide a novel therapeutic target in progressive diabetic
nephropathy [20].
Hemodynamic factors
It is highly probable that hemodynamic factors in DN may trigger the
inflammatory responses and cytokine production [21]. Hemody-
namic factors imply the activation of various vasoactive hormone
systems, such as the reninangiotensinaldosterone and endothelin
systems. In response, the secretion of profibrotic cytokines, such as
transforming growth factor 1 (TGF-1) is increased and additional
hemodynamic alterations ensue, such as increased systemic and in-
traglomerular pressure. The increased intraglomerular pressure en-
tails decreased resistance in the afferent and, to a lesser extent, in
the efferent arterioles of the glomeruli predisposing to glomerular
hyperperfusion. Many other factors have been reported to be in-
volved in this defective autoregulation, including prostanoids, nitric
oxide and VEGF. These early hemodynamic changes facilitate albu-
min leakage from the glomerular capillaries and overproduction of
mesangial cell matrix, as well as thickening of the glomerular base-
ment membrane and podocyte injury [5, 17].
Oxidative stress
Accumulating evidence suggests that oxidative stress plays a central
part in the pathogenesis of DN [22]. For the source of oxidative
stress, vascular NADPH oxidase, uncoupled endothelial nitric oxide
synthetase (eNOS) and mitochondria were the major candidates
[23]. High glucose induces intracellular reactive oxygen species
(ROS) directly via glucose metabolism and auto-oxidation and indi-
rectly through the formation of AGEs and their receptor binding [24].
ROS mediate many negative biological effects in DM, including pe-
roxidation of cell membrane lipids, oxidation of proteins, renal vaso-
constriction and damage to DNA. The metabolism of glucose
through harmful alternate pathways, such as via PKC activation and
AGE formation, in the setting of hyperglycemia also seems partly de-
pendent on ROS [6]. In addition, ROS upregulates TGF-1, PAI-
1(plasminogen activator inhibitor-1) and extracellular matrix pro-
teins (ECM) by glomerular mesangial cells, thus leading to mesangial
expansion. Also, ROS activate other signaling molecules, such as PKC
and MAPKs, and transcription factors, such as nuclear factor (NF)-B,
AP-1 (activator protein-1), and Sp-1 (specificity protein-1), leading to
transcription of genes encoding cytokines, growth factors and ECM
proteins [24].
Hormonal factors and adipokines
Formerly, increased plasma pro-renin activity was noted as a risk fac-
tor for the development of DN. Pro-renin binds to a specific tissue
receptor that promotes activation of MAPK [7]. Also, activated renin-
angiotensin-aldosterone system has been proven to be a crucial de-
terminant of leukocyte activation and cytokine expression in gener-
ating proinflammatory and proliferative effects [25].
Hafez AAE 253
Currently, various adipocyte-secreted factors and hormones termed
adipokines including adiponectin, leptin, resistin, visfatin, chemerin
and vaspin have been identified and they may link the metabolic
abnormalities and microinflammation in Type 2 DM. An increase in
leptin and resistin or a reduction in adiponectin activity would be
potential participants in diabetes pathology [1].
The most well-known member of this family is leptin which exert
several pro-inflammatory effects. It also impairs endothelial cell func-
tions, stimulates the proliferation of glomerular endothelial cells, in-
creases TGF-1 synthesis and collagen type IV production and up-
regulates surface TGF- type II receptors through signal transduc-
tion pathways involving PI3K (phosphoinositide 3-kinase) [17]. In hu-
man settings, several reports demonstrated that serum leptin levels
correlated with proteinuria in Type 2 DM [26]. However, others re-
ported no association of serum leptin levels and the presence of DN
[27]. Leptin also stimulates hypertrophy, but not proliferation of cul-
tured rat mesangial cells, and infusion of leptin for 3 weeks into nor-
mal rats promotes the development of glomerulosclerosis and pro-
teinuria [17].
On the contrary, adiponectin has shown differential roles in the var-
ious stages of diabetic nephropathy. At early stages of DN, adiponec-
tin suppresses the activation of NF-B, TNF-induced monocyte ad-
hesion to aortic endothelial cells and the expression of intercellular
adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule
(VCAM-1) and selectins in animal models. In addition, ADIPORs (adi-
ponectin receptors) coupled with intracellular signaling pathways in-
volving AMPK and cAMP/PKA (cAMP-dependent protein kinase)
have been implicated in the function of endothelial cells and inflam-
matory cells. Moreover, adiponectin is implicated in the biology of
podocytes and adiponectin-knockout mice exhibit increased albumi-
nuria and fusion of podocyte foot processes, and therapeutic infu-
sion of adiponectin increases the activity of MAPK, reduces oxidative
stress and reverse the albuminuria in these mice. Nonetheless, in
overt DN with macroalbuminuria or renal insufficiency, serum adi-
ponectin level was found to be increased and positively correlated
with the degree of insulin resistance in type 2 DM [28].
Genetic susceptibility
Familial clustering of diabetic nephropathy was also reported in both
type 1 and 2 DM, strongly suggesting the association of genetic fac-
tors with DN. Several candidate genes, such as those for the renin
angiotensin system, genes for glucose and lipid metabolism, genes
for the PCK system and inflammatory cytokine genes (IL-1, IL-6, IL-
18, TNF- and MCP-1) might be candidate genes for conferring sus-
ceptibility to DN [8, 29]. In addition there is an evidence for the as-
sociation of angiotensin-converting enzyme (ACE) gene I/D polymor-
phism and the methylenetetrahydrofolate reductase (MTHFR) gene
C677T polymorphism with development of DN in Type 2 DM [30].
Macrophage/lymphocyte sharing and interaction
The recruitment of leukocytes is a key event in DN. Increased infiltra-
tion of immune cells including monocytes/macrophages, T cells, B
cells and mast cells into the kidney, as well as augmented expres-
sions of inflammatory cytokines, chemokines, adhesion molecules,
receptors and transcription factors which modulate the local inflam-
matory response in the kidneys, have been reported in patients with
DN [1, 31-35].
It is generally accepted that chronic hyperglycemia results in endo-
thelial dysfunction and microvascular thrombosis in the glomerular
vessels and leads to mesangial expansion and glomerulosclerosis.
Concurrently, hyperglycemia hastens renal inflammatory mono-
cyte/macrophage infiltration and adhesion provoked by the vascular
pathological environment and by increasing proinflammatory cyto-
kine secretion from renal cells [14, 15].
Accumulation and activation of monocytes/macrophages has been
demonstrated in renal biopsies in both experimental diabetes and
patients with diabetic nephropathy being aggravated with the dura-
tion of diabetes and the severity of renal injury [36-38]. Disturbance
in proinflammatory CD14(+), CD16(+) monocytes was noted in type
2 DM and DN uremic patients. Such immunological dysfunction may
be related to the activation of TLR4/NF-B and STAT5 (signal trans-
ducer and activator of transcription) signaling pathways [2].
The interaction of monocytes/macrophages with mesangial cells
drives monocytes/macrophages to migrate from the circulation to
the kidney in the early stages of DN. Increased renal expression of
MCP-1 is considered to be important in the initiation of this process.
In addition to MCP-1, IL-6, TNF- and a variety of other chemokines
produced by mesangial cells promote leukocyte recruitment and ad-
hesion to endothelial cells [15]. This adhesion is mediated through
mesangial activation of ICAM-1, VCAM-1, E-selectin, P-selectin and
integrin-1, with the resulting attachment of inflammatory cells to
vascular endothelial cells and their infiltration into both the glomer-
uli and the interstitium [38]. Consequently, the infiltrating mono-
cytes/macrophages may induce or accelerate the mesangial cell pro-
liferation, glomerulosclerosis and injury in diabetic kidneys [14, 15].
As an organ-specific autoimmune disease both activation of the T-
cell-mediated immune system leading to insulitis and humoral B cell
response producing immunoglobulins against beta cell autoanti-
gens participate in the pathogenesis of type 1 DM [39]. Developing
a more aggressive T-cell phenotype and changing the balance be-
tween CD4
+
Th1 (T-helper) cells and Th2 cells to confer a more pro-
inflammatory milieu (Th1 dominant) may be associated with the pro-
gression towards overt diabetes. Furthermore, evidence demonstrat-
ing the association of the CD4
+
Th17 and Tregs subsets with patho-
genesis of Type 1 DM is rapidly accumulating [40, 41]. By contrast,
adipose tissue inflammation is now recognized as a crucial process
leading to the metabolic syndrome, insulin resistance and Type 2
DM. Akin to macrophage, T cell infiltration of adipose tissue has been
described in Type 2 DM, and the interaction between T lymphocytes
with macrophages can regulate the inflammatory cascade in this dis-
ease [42-44]. Moreover, CD8
+
T cells play essential roles in the initia-
tion and maintenance of adipose tissue inflammation and systemic
insulin resistance [45].
As T cells express LFA-1 (lymphocyte function associated antigen-1;
the receptor for ICAM-1), and as ICAM-1 expression is found on renal
endothelial, epithelial, and mesangial cells, it is likely that this inter-
action plays a significant role in T cell migration into the diabetic
Vol 2, No 3
kidney [46]. Within the kidney, activated T cells can cause injury di-
rectly through cytotoxic effects and indirectly by recruiting and acti-
vating macrophages. Proinflammatory cytokines secreted by T
(CD4
+
, CD8
+
) cells could activate neighboring macrophages directly
or indirectly by stimulating mesangial cell production of colony stim-
ulating factor-1 (CSF) and MCP-1. Once macrophages have activated,
they can release nitric oxide, ROS, IL-1, TNF-, complement factors,
and metalloproteinases (MMPs), all of which promote renal injury
[47]. Besides, T cells express the receptor for AGEs and the activation
of CD4
+
and CD8
+
T cells by AGE can initiate interferon (IFN)- secre-
tion by T cells, which could induce further inflammation and oxida-
tive stress within the diabetic kidney [48]. Although, CD8
+
cells may
perform a cytolytic function in the diabetic kidney, the function of
CD8
+
T cells, however, becomes more significant at later stages of
the disease when tissue loss is evident [49, 50].
The infiltration of Th1 cells in the glomeruli in patients with type 1
DM was closely related with elevated levels of ICAM1, P-selectin and
IFN [46]. However, in type 2 DM, little is known about the mecha-
nism of Th1 activation, although increased serum levels of IFN and
IL-2R (IL-2 receptor) have been reported in this disease [35]. Mean-
while, Th2 cells producing IL-4 and IL-10, can contribute to suppress
Th1 cell activation as IL-10 exerts anti-inflammatory and immuno-
suppressive effects. Th17 is a distinct subset of helper T-cells which
is critically involved in the pathogenesis of autoimmune diseases
such as rheumatoid arthritis. Therefore, some studies have sug-
gested that Th17 cells promote inflammation through elevated IFN
and IL-17A in human Type 1 and 2 DM [51, 52].
Intrinsic renal cells
The intrinsic renal cells (endothelial, mesangial, podocyes, glomeru-
lar, and tubular epithelial cells) are able to synthesize many proin-
flammatory cytokines [53]. At high glucose levels, podocytes are
considered the major sources of IL-1 and IL-1, and they may also
produce MCP-1 [54]. Elements of the diabetic milieu such as high
glucose and advanced glycation end products (AGEs) act as potent
stimulators of renal cells to elaborate chemokines. In addition, pro-
inflammatory cytokines produced by leukocytes such as IL-1, TNF-
and INF- can induce the intrinsic renal cells to produce a spectrum
of chemokines. These chemokines include: IL-8 (CXCL8), MCP-1, INF-
inducible protein (CXCL10), macrophage inflammatory protein-1
(MIP-1/CCL3), and RANTES (CCL5). The elaborated chemokines
then further direct the migration of additional leukocytes into the
kidney and set up an inflammatory cycle [48].
Cytokines and chemokines
A described earlier, activated macrophages, lymphocyes as well as
the intrinsic renal cells elaborate a host of proinflammatory, profi-
brotic, chemotactic and antiangiogenic factors which contribute to
the progression of renal injury either directly or indirectly [32]. In the
context of hyperglycemia, NF-B is activated through PKC and ROS
to rapidly stimulate the expression of several cytokines [55]. Further-
more, AGE products and AGE-modified proteins can bind to the re-
ceptor for AGE on macrophages and T cells, stimulating synthesis
and release of proinflammatory cytokines in DM [16]. The increase in
the systemic and/or renal tissue expressions of these cytokines was
reported to correlate with the severity of DN or with urinary albumin
excretion [8].
Inflammatory cytokines including, but not limited to, TGF-, TNF-,
IL-1, IL-6, IL10, IL12, IL-18, PAI-1, MMPs, platelet-derived growth fac-
tor (PDGF), angiotensin II and endothelin are critically involved in
pathogenesis of DN [32, 49]. For example, increased secretion of
TGF- by peripheral blood mononuclear cells has been reported in
patients with DN and seems to be responsible for fibrogenic and
proliferative effects on renal fibroblasts [56, 57]. It is also a crucial
pleiotropic cytokine associated with the development of Tregs and
Th17 cells [58].
Monocytes and macrophages are the primary source of TNF-, alt-
hough intrinsic renal cells are also able to synthesize this cytokine.
Moreover, it has been shown that increased urinary TNF- excretion,
as well as increased TNF- levels in renal interstitial fluid, precede
the significant increase in albuminuria [59]. TNF- significantly con-
tributes to sodium retention and renal hypertrophy, characteristic al-
terations during the early stages of DN, whereas exposure of tubular
epithelial cells to TNF- significantly increases the synthesis and se-
cretion of lymphocyte and neutrophil chemoattractant factors, as
well as the cell-surface expression of ICAM-1 [59]. Finally, TNF-, in-
dependent from hemodynamic factors or effects of recruited inflam-
matory cells, promotes the local generation of ROS, with alterations
in the barrier function of the glomerular capillary wall resulting in
enhanced albumin permeability [1]. Similarly, it has been demon-
strated that IL-1 increases vascular endothelial permeability, and it is
involved in the proliferation of mesangial cells and matrix synthesis,
as well as in the development of intraglomerular hemodynamic ab-
normalities related to prostaglandin synthesis [60].
It is likely that IL-6 affects ECM dynamics at the mesangial cell and
podocyte levels, contributing to both mesangial expansion and glo-
merular basement membrane thickening. Renal IL-6 expression has
been related to mesangial proliferation, tubular atrophy and the in-
tensity of interstitial infiltrates in animal models of renal disease [61].
In addition, elevated IL-10 levels were observed in the sera of the
patients with diabetic nephropathy, and a positive correlation of IL-
10 and albuminuria was found [16, 32].
High-glucose concentrations and AGE may induce macrophage pro-
duction of IL-12, which can stimulate CD4
+
cell production of IFN-
and augments natural killer cell activity [62, 63]. Likewise, IFN- se-
cretion by T cells can initiate and further accelerates inflammation
by the activation of macrophages and vascular cells and exacerba-
tion of oxidative stress within renal tissues [16. 32]. Besides, IL-18
levels increase in diabetic patients with the development of urinary
albumin excretion [64]. So, elevated urinary excretion levels of IL-18
reported in patients with diabetic nephropathy seems to be closely
related to the progression of diabetic nephropathy [63].
Chemotactic cytokines are also major factors that induce the recruit-
ment of inflammatory cells into the kidney, subsequently amplifying
the immune-mediated damage [65]. Studies suggest that renal MCP-
1 is involved in the direction of macrophage migration into the dia-
betic kidney through interaction with its chemokine receptor (CCR)-
2 on macrophages [66]. MCP-1 is upregulated in patients with DN
Hafez AAE 255
and its expression levels correlate with the number of infiltrating in-
terstitial macrophages [67]. In addition, up-regulation of kidney
MCP-1 has been shown as a feature of human diabetic renal injury
associated urinary albumin excretion, tubulointerstitial injury and
disease progression; meanwhile proteinuria itself may contribute to
the upregulation of MCP-1 in DN [66].
Moreover, constitutive chemotactic RANTES expression directs sub-
set-specific homing of CD4
+
T cells in the kidney [68]. CXCL12 (CXC
chemokine ligand 12) is produced by podocytes, contributing to po-
docyte loss [69]. CX3CL1 (CX3C chemokine ligand 1; also known as
fractalkine) exists in two forms as a membrane-anchored or as a shed
95-kDa glycoprotein. The soluble CX3CL1 has potent chemoattract-
ant activity for T-cells and monocytes and induces adhesion between
activated endothelial cells, which express its receptor CX3CR1 (CX3C
chemokine receptor 1) [63].
Adhesion molecules
In patients with DN, soluble forms of VCAM1 and ICAM, P and E-se-
lectin are elevated during the progression from microalbuminuria to
overt nephropathy [70, 71]. Increased expression of ICAM-1, which
serves as a ligand for LFA-1 on monocytes and lymphocytes, was de-
tected in animal models of in type 1 and 2 DM [72]. It has been
shown that patients with both type 1 and 2 DM complicated with
DN have elevated concentrations of ICAM-1 compared with subjects
without renal injury, suggesting that this molecule can be of patho-
genic importance for the development of renal damage [70]. ICAM-
1 expression found on renal endothelial, epithelial, and mesangial
cells, plays a significant role in facilitating leukocyte adhesion, trans-
migration and activation within the kidney [72, 73]. Previous studies
demonstrated that mice deficient in ICAM-1 have defects in macro-
phages and leukocytes homing into renal tissues, resulting in sub-
stantial reduction of renal injury [74].
In addition, cross-sectional clinical studies have shown an elevation
of circulating VCAM-1, P and E-selectin levels in patients with DN,
which may result from underlying systemic endothelial dysfunction,
increased production in damaged renal tubular or glomerular epi-
thelial cells and/or decreased renal clearance of this molecule, de-
pending on the stage of nephropathy [75]. More importantly, clinical
prospective investigations in individuals with type 2DM have shown
that patients with increased albuminuria and high plasma concen-
trations of soluble VCAM-1 had an increased risk of death [74].
Receptors
In addition to the formerly addressed chemokine receptors, in-
creased expression of TLR4 but not of TLR2 was noticed in the renal
tubules of human kidneys with DN. In addition, TLR9 is expressed on
infiltrating antigen-presenting cells during immune injury. TLR-me-
diated immune activation may occur during any type of renal injury
by exposure to an increasing number of exogenous or endogenous
molecules [76]. Interaction of the TIR (Toll/IL-1 receptor) domain of
TLR4 and the adapter protein MyD88 (myeloid differentiation factor
88) triggers a downstream signaling cascade, leading to activation
of the NF-B pathway, which then activates the transcription of
many pro-inflammatory genes that encode inflammatory molecules,
including cytokines, chemokines and other effectors of the innate
immune response [77]. The intensity of tubular TLR4 expression cor-
relates directly with interstitial macrophage infiltration and hemo-
globin A1c level and inversely with estimated glomerular filtration
rate. The renal tubules also upregulate the endogenous TLR4 ligand
high-mobility group box 1 in DN. In vitro, high glucose induces TLR4
expression via PKC activation, resulting in upregulation of IL-6 and
chemokine ligands. Taken together, these data suggest that a TLR4-
mediated pathway may promote tubulointerstitial inflammation in
DN [78].
c-fms is the receptor for CSF-1, a major cytokine promoting macro-
phage accumulation, activation, and survival. Administration of a
neutralizing anti-c-fms monoclonal antibody to diabetic mice with
established albuminuria suppressed inflammation in the diabetic
kidney, as evidenced by the reduction in macrophage accumulation,
activation and proliferation [48].
Transcription factors and transduction pathways
Several transcription factors such as USF (upstream stimulatory fac-
tor) 1 and 2, AP1 (activator protein 1), NF-B, CREB (cAMP-response-
element-binding protein), NFAT (nuclear factor of activated T-cells)
and Sp1 (stimulating protein 1) are activated in hyperglycaemic en-
vironments. These transcription factors regulate the genes related to
inflammation and ECM turnover [79]. Among the transcription fac-
tors, NF-B is the most important in the pathogenesis of diabetic
nephropathy. NF-B is activated by a wide variety of stimuli such as
cytokines, oxygen radicals, inhaled particles, ultraviolet irradiation
and bacterial or viral products. In diabetic kidney disease, proteinuria
itself is the important activator for NF-B [80]. NF-B binds to the
promoter regions of several genes that play a pivotal role in the path-
ogenesis of diabetic nephropathy, such as those encoding TGF-1,
MCP-1 and ICAM1 [81]. NF-B is also integrated in various biological
pathways that are functionally involved in the pathogenesis of dia-
betic nephropathy, such as PKC [82], renin-angiotesin system [83],
AGE accumulation [84] and oxidative stress [85].
Furthermore, the JAK2 (Janus kinase 2), SAPK-2 (stress-activated pro-
tein kinase-2) and STAT-1, -3 and -5 pathways are enhanced by vari-
ous stimuli within the diabetic milieu, such as high glucose concen-
tration, AGEs and angiotensin II, and various chemokines, growth
factors. It is worthy to note that, ECM proteins are STAT-dependent
genes and are closely related to mesangial cell proliferation [86].
Other factors
Immune complexes formed in response to abnormal proteins gener-
ated in DM such as oxidized low-density lipoproteins (LDL) have
been shown in vitro to stimulate production of MCP-1 and CSF-1,
and promote glomerular fibrosis by stimulating collagen production
by mesangial cells. Oxidized LDL immune complexes are also capa-
ble of activating the classical pathway of complement and inducing
proinflammatory cytokine production by human macrophages, in-
cluding IL-1, IL-6, and TNF-. These responses occur through the li-
gation of Fc receptors on mesangial cells and macrophages and
may involve the activation of the p38 MAPK, JNK (c-Jun N-terminal
kinase) and PKC pathways [87].
Vol 2, No 3
Therapeutic appliances
Accordingly, a variety of therapeutic strategies involving modulation
of the inflammatory response are currently being investigated in di-
abetic kidney disease [10,88]. Some authors have shown that block-
ade of the reninangiotensin system in patients with type 2DM and
DN is associated with a reduction in urinary MCP-1 levels as well as
an improvement in renal function [89]. Combination therapy with
eicosapentaenoic acid (EPA), i.e. anti-microinflammation effect, an-
giotensin converting inhibitors (ACE-I) and angiotensin II type 1 re-
ceptor blockers (ARB), and 1,25-dihydroxyvitamin D3, i.e. anti-hyper-
tensive and anti-reactive oxygen species effects, have shown efficacy
in the treatment of diabetic nephropathy in experimental animal
models [4]. Injection with the anti-microinflammatory EPA improved
type 2 diabetic nephropathy in experimental animal models by de-
creasing hypertriglyceridemia and albuminuria and improving glu-
cose tolerance [4]. Glomerular mesangial matrix expansion and seg-
mental sclerosis, as well as interstitial fibrosis were markedly de-
creased by EPA treatment. Diabetes induced up-regulation of MCP-
1 and TGF- expressions were inhibited by EPA, together with a re-
duction of glomerular macrophage infiltration and oxidative stress.
It appears that EPA might be an effective therapeutic agent for DN
[90].
Neutralizing MCP-1 activity could be an important therapeutic goal
in the treatment of DN. From this perspective, a recent experimental
study has shown that blockade of the MCP-1/CCR2 pathway amelio-
rated glomerulosclerosis [91]. Also, the inhibition of JAK/STAT path-
ways by AG-490, a specific JAK2 inhibitor ameliorated the progres-
sion of diabetic neuropathy by improving inflammatory responses
by suppressing CCL2 and TGF- [92]. Thus, understanding of these
inflammatory pathways guides important therapeutic appliances
and improves the discovery of new therapeutic targets that can be
translated into clinical treatments for DN.
Abbreviations: AGE, advanced glycation end-product; ACE, angiotensin-
converting enzyme; ADIPORs, adiponectin receptors; AP1, activator protein 1;
cAMP/PKA, cAMP-dependent protein kinase; CCL2, CC chemokine ligand 2 also
known as MCP-1 (monocyte chemoattractant protein-1); CCL5, RANTES; CCR
chemokine receptor 2; CD, cluster differentiation; CREB, cAMP-response-element-
binding protein; CSF, colony stimulating factor; CXCL, CXC chemokine ligand;
CX3CL1, CX3C chemokine ligand 1; CX3CR1, CX3C chemokine receptor 1; DN,
Diabetic nephropathy; DM, diabetus mellitus; ECM, extracellular matrix; eNOS,
endothelial nitric oxide synthetase; ESRD, end-stage renal disease; GLUT, glucose
transporter; ICAM1, intercellular adhesion molecule 1; IFN , interferon ; IL,
interleukin; ILR, interleukin receptor; JNK, c-Jun N-terminal kinase; JAK2, Janus
kinase 2; LDL, low-density lipoproteins; LFA-1, lymphocyte function associated
antigen-1; MAPK, mitogen activated protein kinase; MCP-1, macrophage
chemoattractant protein-1; MIP-1/CCL3, macrophage inflammatory protein-1;
MMP, matrix metalloproteinase; MTHFR, methylenetetrahydrofolate reductase;
MyD88, myeloid differentiation factor 88; NFAT, nuclear factor of activated T-cells;
NF-B, nuclear factor B; PAI-1, plasminogen activator inhibitor-1; PDGF, platelet
derived growth factor; PI3K, phosphoinositide 3- kinase; PKC, protein kinase C;
RAGE, receptor for AGE; ROS, reactive oxygen species; S100A8, S100 calcium
binding protein A8; SAPK-2, stress-activated protein kinase-2; Sp1, stimulating
protein 1; Sp-1,specificity protein-1; STAT, signal transducer and activator of
transcription; TGF, transforming growth factor; Th, T helper; TIR, Toll/IL-1 receptor;
TLR, Toll-like receptor; TNF, tumor necrosis factor; VCAM1, vascular cell adhesion
molecule 1; VEGF, vascular endothelial growth factor.
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Open Access Review
2014 Ali et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits
Cite this article as: Ali SA, Ali SA: Unmet need for contraception and unintended pregnancies among women of reproductive age group: A situation analysis. El Mednifico Journal 2014, 2(3): 259-265.
Unmet need for contraception and unintended pregnancies among women of reproductive age group:
A situation analysis
Sumera Aziz Ali
1
, Savera Aziz Ali
2

Introduction
According to World Health Organization (WHO) and Population Ref-
erence Bureau statistics, the current population of the world is little
over 7 billion and it continues to grow by 75 to 78 million people
annually [1-3]. Developing countries account for 97% of this growth
due to combination of high birth rates and increase proportion of
young population [1]. It is estimated that population of most devel-
oped countries will decrease by 2050 but simultaneously there will
be an increase in the population of developing countries [4]. Coun-
tries in Asia and Africa will contribute 90% of the increase in popula-
tion [4]. The reason that developing countries will contribute more
towards worlds population is because of their high birth rate, which
in turn is due to low contraceptive use [4].
Worldwide, use of modern method of contraception has increased
slightly from 54% to 57% [5]; however contraceptive usage rates
vary widely across the world. In developed countries, more than 80%
of women in reproductive age group (15-49 years) use contracep-
tives, while contraceptive use is much lower in African (21%) and
Asian (67%) countries [4]. The relatively high usage rates in Asia are
driven to a large extent by near abundant usage in China (85%), Iran
(79%), Sri Lanka (68%), Japan (54%), India (54%), Bhutan (66%) and
Indonesia (61%). While Pakistan (35%), Afghanistan (23%), Maldives
(35%) and Nepal (48%) still lag behind [6, 7]. Low contraceptive prev-
alence rates are directly related to a high number of unintended
pregnancies [8].

1
Department of Community Health Sciences, Aga Khan University, Pakistan.
2
School of Nursing and Midwifery, Aga Khan University, Pakistan.
Correspondence: Sumera Aziz Ali
Email: sumera.ali@aku.edu
Global Prevalence of unintended pregnancy
Unintended pregnancy is a global problem. Around 210 million
women become pregnant annually worldwide [4, 9]. Out of them
every year, 75 to 80 million women experience unintended pregnan-
cies, of which approximately 42 to 46 million pregnancies are termi-
nated [4, 9, 10]. It is anticipated that unmet need for contraceptives,
growing number of women of reproductive age (15 to 49 years) and
a desire in the reduction of family size will increase the number of
unintended pregnancies globally to 92 million by 2015 [11, 12]. Fig-
ure 1 gives classification of pregnancies [13].

Figure 1: Classification of pregnancies
Currently both developed and developing countries are facing the
problem of unintended pregnancies. Although worldwide, from
1995 to 2008 the rate of unintended pregnancy has declined by 20%,
from 69 to 55 per 1000 women. This decline in the rate of unin-
tended pregnancy was greater in the developed world, where it fell
by 29 percent (from 59 to 42 per 1000 women); while it declined by

Abstract
Each year approximately 210 million pregnancies occur worldwide and more than one-third (75 to 80 million) of these are unintended,
more than half of these (46 million) unintended pregnancies undergo unsafe abortions. In Pakistan 16% of the births are reported to be
unwanted and if the unwanted fertility is eliminated, total fertility in Pakistan would be 3.1 births per woman. Total demand for family
planning in Pakistan is 55%, while the contraceptive prevalence rate is 35% and unmet need for family planning is 20%. Reasons for
unmet need and unintended pregnancy include lack of permission, fear of side effects, poor quality and limited access to family planning
services. Moreover, non-use of contraceptive methods and method failure are important reasons for unintended pregnancy. Women of
reproductive age experience multiple adverse outcomes due to unintended pregnancy. These women neither care for themselves nor
for their family and due to such careless behavior the likelihood of maternal and neonatal morbidity and mortality increases. Research
on intervention programs for unintended pregnancy needs to be done in future. It is important to focus on how intervention programs
should be designed, delivered and examined. Intervention strategies should aim to reduce unintended pregnancy by focusing on all the
identified factors so that infant and maternal mortality and morbidity as well as the need for abortion is decreased and the overall well-
being of the family is maintained and enhanced. Thus, improved community efforts are required to educate women about family planning
as well about the proper use of family planning methods. Improved counseling and proper follow up is required especially of those
women who adopt any method. Since improper treatment, incomplete follow up and limited choice of method might lead the women
to discontinue the methods, therefore role of quality of care of existing services in improving womens ability to achieve their desired
reproductive goals should be given an attention. In addition to improving the quality of existing family planning services, the focus
should be on the follow up of women for assessing the adherence to method and addressing their problems related to any method. (El
Med J 2:3; 2014)
Keywords: Family Planning, Unintended Pregnancy, Unmet Need
260 Unintended pregnancies among women
Vol 2, No 3
20 percent, from 71 to 57 per 1000 women in the developing coun-
tries [14, 15]. The highest rates of unintended pregnancies were in
Africa (86/1000 women) and the lowest were in Europe (38/1000
women).
Despite such decline in rates of unintended pregnancies, its propor-
tion is still high. About 4 out of 10 pregnancies (40%) were unin-
tended worldwide in 2008, with a high proportion in South America
and Southern Africa, where 6 out of 10 pregnancies were unintended
[14, 15]. It was even more in developing regions like Latin America
and the Caribbean region (58%), South Africa (59%) and South
America (64%) [14, 15].
Prevalence of unintended pregnancy in Asia
Unplanned pregnancy is one of the leading causes of maternal mor-
tality and morbidity in South Asia [4]. It is estimated that every year
about one-third pregnancies are declared unintended in South and
South-East Asia. In 2008, the proportion of unintended pregnancies
in Bangladesh was 30%, while it was 21% in India and 35% in both
Iran and Nepal and it was about 46% in Yamagata (Japan) [4, 16, 17].
Like other countries, unintended pregnancies are of particular con-
cern in Pakistan too. According to Pakistan Demographic and Health
Survey (PDHS) 2012-2013, the proportion of unintended pregnan-
cies in Pakistan is 16%, of which 9% pregnancies are mistimed and
7% are unwanted. Currently total fertility rate of Pakistan is 3.8 births
per woman and if the unwanted fertility is eliminated, total fertility
in Pakistan would be 3.1 births per woman [7].
Reasons for unintended pregnancies
Based on literature search, various reasons for unintended pregnan-
cies have been identified. They are broadly divided into two main
categories:
1. Non-use of contraceptive methods: Non-use of contraceptive
methods is one of the important reasons for unintended preg-
nancy, which is mainly due to high unmet need for contracep-
tives [18]. According to the standard DHS (Demographic health
survey) definition: The unmet need group consists of all those
fecund women who are married and thus presumed to be sex-
ually active, who either do not want any more children and who
wish to postpone the birth of their next child for at least two
more years but are not using any method of contraception [7,
19, 20].
2. Contraceptive method failure: Contraceptive method failure in-
corporates both users and technological faults [21, 22]. Findings
from one study conducted in United States found that 52% of
the unintended pregnancies was attributed to unmet need for
family planning, while 43% of the unintended pregnancies were
due to inconsistent and incorrect use and 5% were due to
method failure [23]. Similarly findings from a study conducted in
Egypt showed that 33.6% of mistimed and 8.8% of unwanted
pregnancies were attributed to unmet need for spacing births,
while 14.9% of mistimed and 39.7% of unwanted pregnancies
were attributed to unmet need for limiting the births [24].
Global and regional estimates of unmet need
According to WHO, currently 222 million couples want to stop or
delay childbearing worldwide, but are not using any method of con-
traception and it is estimated that maternal deaths can be reduced
to one third by satisfying the unmet need for family planning [5].
However from 1990s to the mid 2000 unmet need has been declined
among married women in all major regions. In Asia it has declined
from 18% to 13%, in Latin America decline is from 16% to 10%, while
in SubSaharan Africa it has declined from 24% to 22% [15]. Despite
such decline, about 61 million married women are living with unmet
need for contraception in Asia which is about 58% of the total mar-
ried women for the developing countries. While in Sub-Saharan Af-
rica, 24 million married women have unmet need for contraception
which is 22% of the total married women for the developing coun-
tries. Approximately 11 million married women in Latin America, 8
million married women in North Africa and Middle East and 1.1 mil-
lion married women in Central Asian Republics are facing the prob-
lem of unmet need for contraception [19].
Overall in 2008, about 140 million women in developing world had
an unmet need for contraception and in addition to this, 75 million
women were using traditional methods which are not very effective
in preventing pregnancy [15]. Meeting the required need for contra-
ception is very important as it can avert womens social, physical and
psychological issues [25, 26]. According to one report it has been
estimated that around 52 to 54 million unintended pregnancies can
be prevented every year by addressing the unmet need for family
planning services in developing countries and this in turn would pro-
tect about 1.5 million womens lives [27].
Unmet need for contraception in Pakistan
Situation regarding the unmet need for family planning is not differ-
ent in Pakistan. In Pakistan unmet need for family planning services
has slightly decreased from 28% in (1991) to 20% in (2012) over the
period of more than 20 years, with 9% having an unmet need for
spacing and 11% having an unmet need for limiting [7, 28]. Women
of rural areas have greater unmet need (21.6%) as compared to the
women of urban areas (17%) [7]. There is also substantial variation
of unmet need across four provinces of Pakistan. It is lowest for Pun-
jab province (17%) and highest for Baluchistan (31.2%) and NWFP
(now KPK) (25.5%) while it is 20.8% for Sindh province [7].
In Pakistan, about 55% of the women have total demand (both un-
met and met need) for using contraceptive methods and only 35%
of demand for family planning is being satisfied [7]. This high unmet
need has an important impact on contraceptive prevalence rate and
this high unmet need is reflected through current contraceptive
prevalence rate of Pakistan (35%) and only one third of the women
are using contraceptive methods including both traditional and
modern methods [7, 29, 30]. Moreover, the use of traditional meth-
ods increases the risk of unintended pregnancies due to high failure
rates of such methods [31].
Predictors or determinants of high unmet need and
unintended pregnancies
There are different factors, which can predict or determine the un-
met need and unintended pregnancy and studies have reported dif-
ferent predictors of unintended pregnancies. These factors can be
divided into demographic, socioeconomic, fertility related factors
Ali SA, Ali SA 261
and access related factors as shown in fish bone diagram (Figure 2)
[32].

Figure 2: Fish bone diagram/Ishikawa diagram, showing the de-
terminants of unintended pregnancy.
Demographic factors include age of the husband and wife, spousal
age difference. Socioeconomic factors include mothers and fathers
education, occupation of husband and wife, income of husband and
wife [32]. Sociocultural factors include religion, residential region of
couple and autonomy of woman. Fertility related factors include the
marital status of woman, age at time of marriage, gravidity, parity,
number of alive children, number of previous alive sons, previous
unintended pregnancy, and outcome of last pregnancy [33]. Access
related factors include the awareness about family planning person-
nel or center, access to media, geographic distance from the family
planning outlets. Finally factors related to family planning methods
include knowledge about family planning methods, use of family
planning methods and barriers to using contraceptive methods [33].
Although these factors can predict the unintended pregnancy but
different studies have found strong and significant association be-
tween the following predictors and unintended pregnancy.
Socio-demographic, socio-economic and sociocultural
factors
Maternal age
On the basis of literature review it has been identified that at the
extremes of ages (younger and older) women usually experience un-
intended pregnancies. Advancing maternal age as well as young ma-
ternal age are risk factors for unintended pregnancies [13, 34-37].
At a younger age, women usually want to give space between two
pregnancies but due to unmet need for contraceptives they usually
end up with mistimed pregnancies. On the other hand, advancing
age has also positive association with unintended pregnancy, which
means higher the age of women, the higher the probability of having
current pregnancy as unintended. The effect of age on unintended
pregnancy can be explained by the fact that as the women gets
older, her fertility choices are usually completed but due to unmet
need for contraceptives, these women experience unintended preg-
nancies [7, 12]. Studies conducted among married pregnant of re-
productive age group in Ecuador New York, Iran , Nigeria, Vietnam,
China, Bangladesh showed that as the age of the woman increases,
the likelihood of unintended pregnancy also increases [6, 17].
Socioeconomic status
The burden of unintended pregnancies is concentrated in socially
disadvantaged women [38]. If the woman belongs to the lower so-
cioeconomic status she is more likely to have unintended pregnancy,
as compared to the woman who belongs to the higher socioeco-
nomic status [7, 11, 35, 37].
Womans and her husbands educational status
It has been found that highly educated women have usually more
knowledge about the use and benefits of contraceptives, which
helps the woman in planning the pregnancy very cautiously. How-
ever, there is conflicting data regarding the association of level of
education with unintended pregnancy. Some of these studies sug-
gest that as the womans educational status increases, the chances
of unintended pregnancies decreases, while the other shows either
no significant association or significant positive association with un-
intended pregnancy [11, 13, 17, 35, 39-41].
Working status of the woman
Pakistan demographic and health survey has identified that the
women has the same pattern of contraceptive use at the two ex-
tremes of working status (currently working and never worked). On
the other hand, those women who worked only after marriage have
reported more use of contraceptives. Use of contraceptives is indi-
rectly related to the intention of pregnancy [7].
Place of residence
Those women living in urban areas have more opportunity to use
the family planning methods compared to those who are living in
rural areas. Due to insufficient utilization of family planning methods
women in rural areas have more unintended pregnancies compared
to the women living in urban areas [11].
Decision-making power/Autonomy of the woman
Based on the literature review it has been found that autonomy of
the woman has also been associated with unintended pregnancy. In
a male-dominant society, women are often given less opportunity to
take decision for themselves and they have to depend on the male
partners/relatives for their survival and other life matters [37, 42].
Besides this, social norms limit womens freedom to make important
decisions [37]. In some regions of South Asia, women have substan-
tially lower social status and autonomy than men [43, 44]. It has been
found that lower status and autonomy seems to be associated with
lower fertility control and such women who cannot take decision for
themselves independently are more likely to face the problem of un-
intended pregnancies compared to those who have some degree of
autonomy [11, 37, 41, 45].
Fertility related factors
Age at the time of marriage
One of the important predictors of unintended pregnancy is age at
the time of marriage and it has been found that age at the time of
marriage is inversely related to unintended pregnancy. Studies from
Nepal and Japan have reported significant inverse association be-
tween age at first marriage and unintended pregnancy [11, 17]. This
means that smaller the age at time of marriage, the likelihood of un-
intended pregnancy increases. One of the reasons could be that early
marriage leads to earlier initiation of sexual intercourse, which ex-
poses women to an extended period when they are at risk of getting
Vol 2, No 3
pregnant and is thus related to a higher likelihood of experiencing
unintended pregnancy [7]. On the basis of previous study findings it
has been identified that if the woman marries at a younger age, she
has significantly higher rate of unintended pregnancy compared to
the woman who marries later in life [11, 17, 36, 39, 40].
Total number of pregnancies (gravidity)
Increase gravidity is associated with unintended pregnancy [11, 17].
Gravidity is defined as the total number of pregnancies, including
the current one if any, regardless of outcome.
Total number of alive children
Like gravidity, this variable has the similar association with unin-
tended pregnancy. A woman is more likely to experience unintended
pregnancy if she has more alive children compared to women who
have less number of alive children [7, 11, 46].
Total number of alive sons
If the woman has no alive son prior to the current pregnancy she will
less likely to have unintended pregnancy compare to the woman
who have more sons prior to the current pregnancy [7, 36, 41].
Factors related to family planning methods
Knowledge and use of family planning methods
Since the knowledge of contraceptive methods is an essential factor
for making the decision to use the contraceptive methods,
knowledge about family planning methods is one of the important
factors in explaining unintended pregnancy [7, 40]. It has also been
found in various studies that those women who have higher
knowledge of family planning methods are less likely to face the
problem of unintended pregnancies compared to those who do not
have knowledge of any method [11]. Another important factor for
unintended pregnancy is the use of contraceptive methods, which is
positively associated with unintended pregnancy. Studies from Vi-
etnam, Bangladesh and Ecuador found the strong positive associa-
tion between users of modern family planning and unintended preg-
nancy [13, 40, 47]. This can be explained by the fact that users of
methods might have high expectations about limiting or spacing
their pregnancies thus, more likely to view their pregnancy as unin-
tended.
Access related factors
Lack of access to FP services is considered as an important factor
contributing to unmet need and unintended pregnancies [5, 7, 8].
Access is defined as the extent to which an appropriate package of
contraceptive methods can be obtained by individuals in a given lo-
cation [48]. Access has been measured in different ways, including
distance or travel time to family planning outlets, knowledge of a
source of contraceptives, the number of family planning personnel
serving a population and door to door visits by health workers [49].
Unintended pregnancy and its negative consequences can be pre-
vented by access to contraceptive services. The availability of reliable
contraception for all, regardless of age or ability to pay, is an essential
first step [50]. This can be achieved by investing in programs aimed
at providing contraceptive services at the door step of women [51].
Physical access or distance from homes to family planning
centers
Studies have revealed that general health care utilization for any kind
of service is affected by distance from those services and is defined
as a decay effect of the distance on the health care service utilization.
The latter explains that distance from the services is inversely pro-
portional to health care utilization i.e. as the distance increases from
the health care facilities, utilization of services is reduced [52-54].This
relationship is further aggravated with lack of transportation partic-
ularly in developing countries[55]. The access to a vehicle for visiting
any facility is more important particularly in rural areas where dis-
tances are relatively longer, roads are of poor quality, and public
transportation is rarely accessible [56]. This access in family planning
services can be viewed as multi-dimensional paradigm which con-
sists of various important elements. These important elements of ac-
cess comprise of economic accessibility, administrative accessibility,
cognitive accessibility, psychological accessibility and geographic ac-
cessibility [48]. Geographic accessibility is generally defined as the
extent to which family planning service delivery and supply points
are located so that a larger proportion of the target population can
reach them with an acceptable level of effort [48].
Slight work has been done so far regarding the geographic access to
family planning services. Findings from 10 countries (Colombia, Do-
minican Republic, Ecuador, Egypt, Guate- mala, Thailand, Togo, Tu-
nisia, Uganda, and Zimbabwe) revealed that distance from the family
planning services is inversely proportional to contraceptive preva-
lence rate [57]. The findings showed that when the distance from
the services is 0-4km the contraceptive prevalence rate (CPR) is 36%
on average, while at 5-14km CPR is 33% and at 15+ km CPR is 31%
[57]. Another study conducted in Nepal showed that the respond-
ents who were living near centers providing family planning services
(<30 min travel distance) experienced significantly much lower un-
intended pregnancies (38%) as compared to those who resided far
away (>1 hour travel distance) from the family planning services
(54%) [11]. Similarly, findings from one study conducted in Bangla-
desh showed that rural women living 5 miles away from a clinic were
less likely to use contraceptives than those living 3-4 miles away [58].
Door step family planning services by health workers
Based on the literature review it has been found that door to door
facilities provided by LHWs at home has also been associated with
unintended pregnancy [11]. The effect of door to door visits on
contraceptive use and unintended pregnancies is mixed. For
example, in Philippines, the frequency of a midwife's visits to a
supply point had a significant and positive impact on clinical
measures of contraceptive prevalence [59]. Actual frequency of
mobile team visits had a strong effect on IUD use in Indonesia [60].
In Egypt, the number of medical family planning workers had little
effect on use, but the actual number of family planning extension
workers serving a village made current contraceptive use more likely
among women over age 25 [61]. On the other hand, according to
Easterlin and his colleagues, neither family planning nor medical
personnel in Egypt had a significant relationship with contraceptive
use and unintended pregnancy [49].
Ali SA, Ali SA 263
Outcomes of unintended pregnancy
Unintended pregnancies have been considered as an important pub-
lic health issue both in developed as well as in developing countries.
Such pregnancies pose a significant burden not only on the woman
herself but also on the whole family and it has substantial long term
social and economic consequences for the whole society [13].
An unintended pregnancy can lead to various health outcomes re-
lated to maternal behavior during antenatal period and after deliv-
ery, outcomes of birth and well-being of infant and child [62]. These
outcomes are categorized as antenatal outcomes, delivery outcomes
and postpartum outcomes as shown in Figure 3.

Figure 2: Outcomes of unintended pregnancy.
Antenatal Outcomes
It has been observed that women who experience unintended preg-
nancies are less likely to pursue appropriate antenatal care [40], are
less like to consume recommended amount of folic acid and are
more likely to smoke during antenatal period. According to one
study in Ecuador, it was found that women with unwanted pregnan-
cies were 25% less likely to initiate care in the first trimester, 32% less
likely to seek prenatal care and 29% less likely to receive adequate
number of antenatal visits than the women with planned pregnan-
cies [63]. Regarding the wellbeing of the woman, study findings from
Indonesia showed that women who had reported ever experiencing
an unintended pregnancy were nearly three times more likely to be
in the low well-being than in the high well-being cluster (OR = 2.8;
95 percent CI: 1.55.1) [64].
Delivery Outcomes
With respect to delivery outcomes, women with unintended preg-
nancy are more likely to smoke after delivery, are more likely to ex-
perience unsafe abortions and deliver low birth weight babies [40,
65, 66]. Moreover, findings from a systematic review show that there
are increasing odds of LBW [OR:1.36,95% CI:1.25,1.48] and preterm
birth (PTB) [OR:1.31,95% CI:1.09,1.58] among unintended pregnan-
cies ending in live birth [67]. Longitudinal study findings from United
States showed that women who reported their pregnancy as un-
wanted, were more than two times more likely to deliver infants who
died within the first 28 days of life than were women reporting ac-
cepted pregnancies [RR = 2.4; CI: 1.54.0] [68].
Postpartum Outcomes
With respect to maternal postpartum behaviors, it has been reported
that women with unwanted pregnancies, are less likely to breast
feed their children and are more likely to report postpartum depres-
sion [69, 70]. Findings from one study conducted in United States
showed that women with unwanted pregnancies were more likely
not to initiate breast feeding [OR:1.76,95% CI:1.26,2.44], more likely
not to continue breastfeeding [OR:1.69,95% CI:1.12,2.55] and were
more likely not to breast feed [OR:2.50,95% CI:1.34,4.87] than the
intended ones [71]. As far as child rearing is concerned, study from
Japan found that unintended pregnancy was associated with a
higher risk of negative child-rearing outcomes, including lower
mother-to-child attachment, increased negative feelings of mothers
and a lower level of participation of fathers in child rearing [72].
With respect to the preventive and curative care, findings from study
conducted in India shows that unwanted births were 1.38 (95% CI:
1.011.87) times as likely as wanted births to receive inadequate
childhood vaccinations and similarly births that were identified as
mistimed/unwanted had 83% higher risk of neonatal mortality as
compared to wanted births [73]. Findings from eleven countries and
one large Indian state showed that unwanted children are between
10% and 50% more likely to become ill than are wanted children
[74]. Study conducted in Bangladesh indicated that unwanted in-
fants may be significantly more likely to die in the neonatal or post
neonatal periods than wanted infants (OR exceed 2.0) [75]. With re-
spect to the nutritional status of the child, study findings from Bolivia
showed that children of 1235 months age from mistimed pregnan-
cies (adjusted prevalence risk ratio (PRadj: 1.33, 95% CI: 1.031.72)
and unwanted pregnancies (PRadj: 1.28, 95% CI: 1.041.56) were at
about 30% greater risk for stunting than children from intended
pregnancies [76].
Conclusion
It seems that multiple factors play role in predicting the unintended
pregnancy and multiple unfavorable outcomes occur due to it. Thus,
improved community efforts are required to educate women about
family planning as well as about the proper use of family planning
methods. Improved counseling and proper follow up is required es-
pecially of those women who adopt any method. Since improper
treatment, incomplete follow up and limited choice of method might
lead the women to discontinue the methods, therefore role of qual-
ity of care of existing services in improving womens ability to
achieve their desired reproductive goals should be given an atten-
tion. In addition to improving the quality of existing family planning
services, the focus should be on the follow up of women for as-
sessing the adherence to method and addressing their problems re-
lated to any method. Research on intervention programs for unin-
tended pregnancy needs to be done in future. It is important to focus
on how intervention programs should be designed, delivered and
examined. Intervention strategies should aim to reduce unintended
pregnancy by focusing on all the identified factors so that infant and
maternal mortality and morbidity as well as the need for abortion is
decreased and the overall well-being of the family is maintained and
enhanced.

Vol 2, No 3
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Open Access Review
2014 Olowe et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Olowe OA, Olowe RA, Awa OA: The burden of malaria with historical perspective in Nigerian concept and world view. El Mednifico Journal 2014, 2(3): 266-272.
The burden of malaria with historical perspective in Nigerian concept and world view
Olugbenga Adekunle Olowe
1
, Rita A Olowe
2
, O A Awa
1

Introduction and historical perspectives
Malaria is a life threatening protozoan disease caused by malaria par-
asites belonging to the genus Plasmodium. Malaria parasites most
commonly infecting humans belong to four species: P. falciparum, P.
vivax, P. malariae and P. ovale. While these four species do not ordi-
narily infect animals, there is evidence that chimpanzees may act as
a reservoir host for P. malariae in Africa, providing a possible source
of human infection [1].
Malaria is an old disease, whose name is derived from the Italian
(mal-aria) or bad air and it has also been known as Roman fever,
ague, marsh fever, periodic fever, paludisme [2]. There were numer-
ous, sometimes bizarre theories on how malaria was transmitted un-
til 1898 when Dr. Ronald Ross discovered that the female Anopheles
mosquito was actually responsible for transmitting malaria parasite.
This discovery revolutionized malaria control, which had hitherto of-
ten been haphazard or based purely on treating the patient by killing
the malaria parasites [1, 3, 4].
There are lots of controversy with regards to the origin of malaria.
However, malaria probably originated in Africa and accompanied hu-
man migration to the Mediterranean shores, India and South East
Asia. In the past it used to be common in the marshy areas around
Rome. As malaria is a disease mostly of tropical and subtropical areas,
it is particularly prevalent in sub-Saharan Africa, but also common
throughout other tropical regions of China, India, Southeast Asia,
South and Central America [1, 4].
In Nigeria, before independence, the colonialists established Govern-
ment Reservation Areas (GRA) in an attempt to build their homes far
away from the natives as it was found that the travelling/flying dis-
tance of these mosquitoes from the breeding grounds was a limiting
factor in spreading the parasites. Nigerias quest for effective control

1
Department of Medical Microbiology & Parasitology, College of Health Sciences,
Ladoke Akintola University of Technology, Osogbo, Osun State, Nigeria.
2
Research Laboratory Unit, Department of Medical Microbiology & Parasitology,
Ladoke Akintola University of Technology Teaching Hospital, Osogbo, Osun State,
Nigeria.
of malaria began well before the WHO global malaria eradication pe-
riod between 1955 and 1968 [5]. From 1955, however, a more fo-
cused egalitarian attempt at evolving strategic plans and interven-
tions resulted in pre-eradication pilot studies such as the Kankiya
District Project and the establishment of a division in Ministry of
Health to deal with the mosquito and malaria problem.
The National Malaria Control Committee (NMCC) was set up in 1975,
with the set mandate to reduce the malaria burden by 25%. It pro-
duced a five year plan of action that terminated in 1980; however, it
recorded only modest achievements. It took another 8 years before
progress was made when a major health system reform was carried
out in 1988, with the adoption of a Health Policy for the country.
Within this policy, malaria was to be eradicated using the concept of
primary health care. The Ministry of Health subsequently prepared
guidelines for malaria control in 1989 and Government finally came
out with a National Malaria Control Plan of Action in 1996.
Past and present malaria control programmers as well as the most
recent Malaria Control Program Plan achieved limited success in
eradicating the scourge [6]. In spite of this, the malaria situation has
steadily worsened and currently it is estimated that malaria accounts
for 65 percent of all diseases reported in Nigerian health facilities and
that 42% of pregnant women are diagnosed with malaria which af-
fects the birth weight of infants [7]. Moreover, it is estimated that at
least 1 million people die of malaria each year, mostly children under
5 years of age and more than 80% of the deaths worldwide occur in
sub-Saharan African [8, 9].
Life cycle of malaria parasite
Malaria parasites exhibit a complex life cycle involving alternating
cycles of asexual division (schizogony) occurring in man, an interme-
diate host, and sexual development (sporogony) occurring in female
Anopheles mosquito which serves as the definitive host [1, 4, 10].
Correspondence: Olugbenga Adekunle Olowe
Email: olowekunle@yahoo.com
Abstract
Malaria is an infection of humans and other animals caused by eukaryotic organisms of the genus, Plasmodium. The protozoan first infects
the liver, subsequently acts as a parasite within the system in the red blood cells, causing symptoms that typically include fever and
headache, in severe cases progressing to coma and/or death. The disease is widespread in tropical and subtropical regions in a broad band
around the equator, including much of sub-Sahara Africa, Asia and the United States of America with its attendant burden on drug and
drug resistance. Four species of Plasmodium most commonly infect and can be transmitted by humans. Severe disease is largely caused by
P. falciparum while the disease caused by P. vivax, P. ovale and P. malariae is generally a milder form that is rarely fatal. Malaria is prevalent
in tropical regions because the significant amounts of rainfall, consistently high temperatures and high humidity, along with stagnant waters
in which mosquito larvae readily mature, provide with the environment needed for continuous breeding. Disease transmission can be
reduced by preventing mosquito bites, distribution and use of mosquito nets and insect repellents, or with mosquito-control measures such
as spraying insecticides, prevention of bushy environment and draining stagnant water. The World Health Organization continues to work
hard to reduce the burden of malaria in Nigeria and Africa as a whole. (El Med J 2:3; 2014)
Keywords: Malaria, Plasmodium, Public Health, Control
Olowe OA, Olowe RA, Awa OA 267
Human cycle
The sporozoites are the infective form of the parasite. They are pre-
sent in the salivary glands of female Anopheles mosquito and are in-
jected directly into the blood stream when it bites a man.
i. Primary exoerythrocytic schizogony: After injection, all the
sporozoites leave the blood stream and enter into liver paren-
chyma cells where they undergo development into primary ex-
oerythrocytic schizont. Thereafter, the liver cells ruptures and re-
lease merozoites into the blood stream [1].
ii. Erythrocytic schizogony: The liberated merozoites enter the
blood stream and invade red blood cells where they multiply at
the expense of the red cells. They pass through the stages of
trophozoites, schizonts and merozoites, then the red cell rupture
to release the individual merozoites which then infect fresh red
blood cells. This parasitic multiplication at this phase is respon-
sible for clinical attack of malaria [1]. This erythrocytic schizog-
ony maybe continued for a considerable period, but in the
course of time the infection tends to die out [1, 4].
iii. Gametogony: After the malaria parasites have undergone eryth-
rocytic schizogony for certain period, some merozoites develop
within red cells into male and female gametocytes known as mi-
crogametocytes and macrogametocytes, respectively. The devel-
opment occurs in the red blood cells of the capillaries of internal
organs like spleen and bone marrow. Only mature gametocytes
are found in the peripheral blood without causing any febrile
condition in human host, they are produced for the propagation
and continuance of the species [1, 4].
iv. Secondary exoerythrocytic schizongony: Occurs only in cases
of P. vivax and P. ovale. some injected sporozoites on entering
into hepatocytes enter into a resting (dormant) stage, called
hypnozoites, before undergoing asexual multiplication while
others undergo multiplication without delay. After a period of
weeks, months or years these hypnozoites are reactivated to be-
come secondary exoerythrocytic schizonts and they release mer-
ozoites which infect red blood cells producing relapse of malaria
[1, 4]. The relapse is the situation in which the erythrocytic infec-
tion is eliminated and a relapse occurs later because of a new
invasion of the red blood cells from the liver merozoites. Hypno-
zoites are not formed in case of P. falciparum and P. malariae,
therefore relapse does not occur in disease caused by these spe-
cies. On the other hand, recrudescence occurs when red blood
cell infection is not eliminated by the immune system or by ther-
apy and the number in the red blood cells begins to increase
again with subsequent clinical symptoms [1, 4].
Mosquito cycle
Sexual cycle starts in the human host itself by the formation of ga-
metocytes that are present in the peripheral blood. Both sexual and
asexual forms of the parasite are ingested by the female Anopheles
mosquito during its blood meal on infected patient, but only the
mature sexual forms are capable of further development. In the
stomach of the mosquito, microgametes are formed from microga-
metocyte by the process of exflagellation. It develops into a macro-
gamete, its nucleus shifts to the surface where a projection is formed.
Fertilization occurs when a microgamete penetrates this projection
forming the zygote. The zygote matures into ookinete which pene-
trates the epithelial lining of mosquitos stomach and lies between
the external border of the epithelial cell and peritrophic membrane
[1, 4]. Here it develops into oocyst inside which, the sporozoite de-
velops. The oocyst when fully mature, ruptures and releases sporo-
zoites in the body cavity of the mosquito. They accumulate in the
salivary ducts and at this stage, the mosquito is capable of transmit-
ting infection to man [1].
Malaria transmission pattern
Malaria transmission and severity of the disease vary greatly from
region to region, village to village and even from person to person
[11]. Mortality rate from malaria is higher in children between the
ages of 6 months and 5 years [9, 12]. Children below the ages of 6
months are protected due to passive immunity acquired from the
mother and the fact that fetal hemoglobin does not support parasite
growth [9]. The protection ceases after 6 months and the child is
vulnerable till the age of 5 years. Afterwards, immunity is developed
as a result of repeated attacks of malaria [13].
Up to 70% of individuals living in endemic areas carry the parasite
without manifesting the symptom (asymptomatic malaria). Up to
20% of school age children have been shown to carry sub-micro-
scopic levels of the malaria parasites (sub-patient parasitemia) that
can only be detected by polymerase chain reaction [14].
The factors that contribute to the spread and transmission of malaria
depend on the interaction between the human host, Anopheles vec-
tor, malaria parasite and environmental conditions [15]. The preva-
lence is higher in rainy season than in dry season due to the breeding
habitat of mosquitoes such as water, ponds, potholes and uncovered
ditches [4]. Other factors contributing to the persistence of malaria
in the country include resistance of P. falciparum to drugs such as
chloroquine and of Anopheles mosquitoes to insecticides, impover-
ished economy, increased urbanization and development of epidem-
ics following natural disasters and social unrest [4]. Furthermore, if
red cells of donors who recently visited or who have lived in a coun-
try where malaria is present are used, malaria parasites, which resist
storage at 4
o
C, may therefore be transmitted to the recipient of in-
fected red cells [16].
Pathology and clinical manifestation of malaria
Rapid multiplication of the parasites result in destruction of the red
cells. This causes a short bout of shivering, fever, sweating and the
loss of healthy red cells which can lead to anemia. When the next
batch of parasites are released, symptoms reappear [17]. In addition,
it starts with a cold stage (rigor) in which the patient shivers and feel
cold, even though his temperature is rising. A hot stage follows in
which the temperature rises to its maximum, headache is severe and
there are back and joint pains, vomiting and diarrhea. The final stage
is when the patient perspires, the temperature falls, the headache
and other pains are relieved and the patient feels exhausted. Sple-
nomegaly occurs in all forms of malaria with repeated attacks caus-
ing a greatly enlarged spleen, jaundice, coma and fatigue [18, 19].
Hemolytic anemia and acute renal impairment are also features of
malaria [20].
268 The burden of malaria and drugs effect
Vol 2, No 3
Malaria caused by P. falciparum which is referred to as falciparum
malaria, formerly known as subtertian or malignant tertian malaria is
the most widespread and pathogenic of the human species with un-
treated infections causing severe disease and death, particularly in
young children, pregnant women and non-immune adults [21].
The pathogenicity of P. falciparum is mainly due to the cytoadher-
ence of P. falciparum parasitized red cells, causing the cells to adhere
to one another and to the walls of capillaries in the brain, muscle,
kidneys and elsewhere. Sequestration of parasitized cells in the mi-
crocirculation causes congestion, hypoxia, blockage and rupturing of
small blood vessels [22]. High levels of parasitemia result in activa-
tion of cytokines and destruction of red cells [23].
The burden of malaria and Africa initiatives
More than one million children die annually from malaria in Africa
[24]. A child dies every 30 second from malaria in Africa; 70% of
deaths occur in children less than 5 years of age, and even in the first
6 months of life [4, 9]. In Nigeria, there is an estimated 25% to 30%
mortality in children under five, an estimated 300,000 deaths each
year due to malaria [25].
In April 2004, Nigerias Health minister reported that it spent over $1
billion annually in treating malaria and that malaria was the cause of
one out of three deaths in children and one out of ten deaths of
pregnant women [26]. Chloroquine resistance was cited as a grow-
ing problem, owing in part to counterfeit drugs [27, 28]. Also, a di-
rector at the World Health Organization, disclosed that residents of
Lagos State in Nigeria spend about N1 trillion annually on malaria
treatment.
Growing political commitment by African leaders for action on ma-
laria was given a boost by the founding of the Roll Back Malaria
(RBM) global partnership in 1998. Less than two years later African
heads of state and their representatives met in Abuja, Nigeria to
translate RBM's goal of halving the malaria burden by 2010 into tan-
gible political action.
The Abuja Declaration endorsed RBM's goal and established a series
of interim targets for the number of people having access to treat-
ment, protective measures or, in the case of pregnant women, re-
ceiving intermittent preventive treatment to ensure that progress
would be made towards the goal and malaria-endemic countries and
other RBM partners held responsible. Considerable progress has
been made since Abuja. Almost 20 African countries have reduced
or eliminated taxes and tariffs on insecticide-treated nets (ITNs) to
make them more affordable. More than half the malaria-endemic Af-
rican countries, representing almost half the population at risk have
established Country Strategic Plans (CSPs) to achieve the RBM goal
and the targets set in Abuja. CSPs are all based on the four technical
elements of Roll Back Malaria and the evidence-based interventions
associated with them prompt access to effective treatment promo-
tion of ITNs and improved vector control, prevention and manage-
ment of malaria in pregnancy and improving the prevention of, and
response to, malaria epidemics and malaria in complex emergencies
[1, 4].
Countries are now working through local partnerships to develop
the capacity to fully implement their CSPs using ongoing health sec-
tor reforms and linkages to other initiatives, such as IMCI (Integrated
Management of Childhood Illness) and MPS (Making Pregnancy
Safer), to improve access to key interventions. CSPs have been suc-
cessful in attracting new resources for malaria control. However, only
20% of necessary funds are available locally. African countries, work-
ing with their partners and donors, must identify and mobilize re-
sources for the remainder. Countries are looking to a variety of
sources to ensure sustainable financing of their efforts to Roll Back
Malaria. This includes traditional sources of funding, from the na-
tional treasury and donor community as well as the exploration of
new opportunities through debt relief schemes and the Global Fund
to Fight AIDS, TB and Malaria [29].
Malaria burden and the economy
Malaria limits international trade and development. The parts of the
world that are continuously at high risk of malaria are predominantly
the poorest [30]. Malaria is the major cause of absenteeism from
work and school in Africa and reduced productivity, reduction in la-
bor supply, illness and death [31].
Laboratory diagnosis of malaria
Microscopy and staining
A number of Romanowsky stains like Fields, Giemsa, Wrights and
Leishman are suitable for staining the smears. Thick films are ideally
stained by the rapid Fields technique or Giemsa stain for screening
of parasites. The sensitivity of a thick blood film is 5-10 parasites/l.
The blood films stained by Giemsas or Leishman stain are useful for
specification of parasites and for the stippling of infected red cells
and have a sensitivity 200parasites/l [32].
The exacting needs of the blood smear examination, detection of
low levels of parasitemia, sequestered parasites of P. falciparum and
past infections in aspiring blood donors, ascertaining viability of the
detected parasites, difficulties in maintaining the required technical
skills are some of the deficiencies with the blood smear examination
[33].
Alternative microscopic methods have been tried, including faster
methods of preparation, dark field microscopy and stains like ben-
zothiocarboxypurine, acridine orange and Rhodamine-123 [34]. Ac-
ridine orange has been tried as a direct staining technique with con-
centration methods such as thick blood film or the centrifugal quan-
titative buffy coat system and with excitation filter in the Kawamoto
technique [35]. The inability to easily differentiate the Plasmodium
species, requirements of expensive equipment, supplies and special
training as well as the high cost limit the use of these methods [36].
Fixed and preserved blood smears of patients for malaria are used
for comparative analysis of acridine orange and Giemsa stains [37].
The acridine orange staining method requires less time and is more
sensitive under lower magnification than the Giemsa staining
method. The acridine orange staining method therefore provides an
alternative to Giemsa for malaria diagnosis in the field and laboratory
[38].
RDT dipstick test
The WHO said that the development of quality assured rapid diag-
nostic tests using a dip stick and a drop of blood necessitated a pol-
icy change. The tests can reliably demonstrate the presence or ab-
sence of malaria parasites in the blood and can be performed at all
levels of the health system, including community settings. Rapid di-
agnostic tests (RDTs), dipsticks or test strip bearing monoclonal an-
tibodies directed against the target parasite antigens are simple to
perform and to interpret. No electricity is required, nor special equip-
ment or training in microscopy. They may detect P. falciparum infec-
tion even when the parasites are sequestrated in the deep vascular
compartment and undetectable by microscopic examination of a pe-
ripheral blood smear [39].
They are, however, more expensive than microscopy. They can de-
tect antigens produced by gametocytes and can give positive results
in infections where only gametocytes are present. Gametocytes do
not cause any febrile condition and those of P. falciparum are not
affected by schizonticidal drugs. Hence, such positive results can
lead to erroneous interpretations and unnecessary treatment [15].
Quantitative buffy coat (QBC) test
This method for identifying the malaria parasites in the peripheral
blood was developed by Becton and Dickenson Inc. Test involves
staining of the centrifuged and compressed red cell layer with acri-
dine orange and its examination under UV light source. It is fast, easy
and more sensitive than the traditional thick smear film examination
[15].
Molecular method of diagnosis
The use of DNA hybridization probe for detection of P. falciparum
DNA in the blood affords the opportunity of increased sensitivity and
specificity in diagnosis of malaria [40]. The polymerase chain reaction
technique is even more sensitive and specific detecting as low as 5-
10 parasites/l of blood [41]. Although the turnaround time of these
tests may be long, the Real Time PCR method is a fairly rapid method
in the diagnosis of malaria [42].
Therapy of malaria
Drugs
Different methods of treatment of malaria has been reported previ-
ously and new methods of treatments are daily coming up due to
modern techniques of understanding drugs and the parasitized and
the parasites mode of resistance to these drugs continues daily.
i. Quinine which has been used for more than three centuries is
one of the four main alkaloids found in the back of cinchona
tree, and its the only drug which over a long period of time has
remained largely effective for treating the disease, partly be-
cause of undesirable side effects. It is used for treating severe
falciparum malaria [43].
ii. Chloroquine, first used in the 1940s shortly after the Second
World War is a low cost drug but very effective for treatment and
prophylaxis. It was used in curing all forms of malaria, with few
side effects when taken in the prescribed dose. Unfortunately,
most strains of falciparum malaria are now resistant to chloro-
quine [44].
iii. Fansidar is a combination drug, each tablet containing sul-
phadoxine 500mg and pyrimethamine 25mg. Resistance to Fan-
sidar is now widespread and side effects have been reported
[27].
iv. Maloprim is a combination of dapsone and pyrimethamine. Re-
sistance to this drug is now so widespread that its use is no
longer recommended [45].
v. Mefloquine (Lariam) was first introduced in 1971 and it is related
structurally to quinine. The compound was effective against ma-
laria. Its long life meant to serve as a good prophylactic increas-
ing resistance and together with undesirable side effects includ-
ing acute brain syndrome has resulted in a decline in its use [46].
vi. Halofantrin belongs to a class called the phenanathrene-meth-
anols. It is an effective antimalarial introduced in the 1980s, has
a short half-life and is therefore not suitable for use as a prophy-
lactic. Unfortunately, resistant forms are increasingly being re-
ported, and there is some concern about side effects such as
neuropsychiatric disturbances.
vii. Artemisinin is derived from a Chinese herbal remedy and covers
a group of products. The two most widely used are Artesunate
and Artemether. A high rate of treatment failure has been re-
ported and it is now being combined with mefloquine and other
antimalarials as Antimalarial Combination Therapy (ACT) for the
treatment of falciparum malaria [47]. The artemisinin derivatives
are the most rapidly schizonticidal antimalarial drugs known to
date, although they do not remain in the blood stream for long
[48]. It has relatively good safety profile despite initial anxiety
following pre-clinical findings and reduction in malaria transmis-
sion.
The factors that govern choice of drugs include parasite species, level
of resistance to drugs in location, patients general health and med-
ical history and availability of medication.
Vaccines
Many factors make malaria vaccine development difficult and quite
challenging. First the size and genetic complexity of the parasite
mean that each infection presents thousands of antigens to the hu-
man immune system. Secondly, the parasite changes through sev-
eral life stages even while in the human host, presenting a different
substance of molecules for the immune system to combat at each
stage [49]. Thirdly, the parasite has evolved a series of strategies that
allow it to confuse, hide and misdirect the human immune system.
To develop vaccines and drugs that exploit their vulnerabilities in the
parasites biology necessitates a complete understanding of the par-
asite and its complex relationship with its human and vector host.
This is where unravelling the genetic code of P. falciparum published
in 2002 presents a ray of hope as this has energized the malaria sci-
entific community and also served to attract a much broader range
of scientists to join the effort in discovering an effective vaccine. Sci-
entists have brought technologies such as gene chips, proteomics
and comparative genomics to research, though for now, no extraor-
dinary breakthroughs are forthcoming. Although no effective ma-
laria vaccine has been developed for human use, the rising funding
levels, promising scientific advances and heightened global aware-
ness of malaria have increased commitment to develop an effective
malaria vaccine as soon as possible. The malaria vaccine trial is the
Vol 2, No 3
most promising yet. The vaccine is directed against the sporozoites.
The Path Malaria Vaccine Initiative is very encouraging, as among the
under two years old studied, the vaccine was about 50% effective
against severe malaria [50].
Mosquito modification
Other genetic approaches include modifying mosquitoes to produce
offspring that cannot transmit disease but this failed because where
several species of vector are present, a separate transgenic must be
created for each one [28, 51].
Insecticides
Dichlorodiphenyltrichoroethane (DDT), an organochlorine pesticide,
became widely used in pest control after its discovery in 1972. Fear
of it being a potential human carcinogen has limited its use, how-
ever, some nations still effectively use DDT formulae control. Ecua-
dor, for example, has increased its use of DDT since 1993 and has
experienced the largest reduction of malaria rates in the world [52,
53].
Prevention and control of malaria
Measures necessary for the prevention and control of malaria include
the following:
i. Measures directed against the breeding of mosquito larva such
as flushing or draining of breeding sites, clearing vegetation and
spraying breeding sites with oil or chemicals;
ii. Measures directed against mosquito bites such as screening win-
dows and doors with fine mosquito netting, bed netting treated
with insecticides, wearing protective clothing, use of mosquito
repellant and insecticides;
iii. Preventive and creative measures such as early diagnosis and
treatment with drugs;
iv. Health education to the people and the community on malaria
control measures [47].
Studies have shown that rate of transmission of parasite causing ma-
laria differ depending on local factors such as rainfall patterns, the
proximity of mosquito breeding sites to people and the type of mos-
quito species in the area [54]. Malaria parasites are endemic in some
region, where there are fairly constant number of cases throughout
the year, while some region have malaria season mostly during
rainy season. World Malaria Report [55] shows that large and devas-
tating epidemic can occur when the mosquito-borne parasite is in-
troduced into areas where people had little prior contact with in-
fected parasite and have little or no immunity to malaria, or when
people with low immunity move into areas where malaria cases are
constant.
As malaria control intensifies, it is vital to monitor malaria burden,
trends and track the coverage and impact of interventions. While
malaria undoubtedly imposes a major public health burden, esti-
mates of the numbers of cases and death have been, for many coun-
tries too inaccurate to establish firm baseline against which to eval-
uate the success of control measures [56-58]. The study report of
Global Burden of Disease of WHO shows that non immune pregnant
women are at high risk of malaria which can result in high rate of
miscarriage and cause over 10% of maternal deaths, severe anemia
and impaired fetal growth [51]. Sickle cell disease, thalassemias and
other hemoglobinopathies are among the most common genetic
disorders of human [43]. Their high prevalence in malaria endemic
areas are considered to result from balancing selection, in that re-
duced fitness of affected individuals is counter balanced by some
mode of protection against malaria [27]. Vector control has saved
millions of lives worldwide, through indoor residual spraying, envi-
ronmental management to eliminate breeding sites and use of mos-
quito larvicides [59].
Indoors Resident Spraying (IRS) is one of the most effective methods
of vector control. In this method, the inside wall of houses are
sprayed with residual insecticides. When the mosquitoes rest on the
wall, they absorb the insecticides through their feet [30]. The pesti-
cides either kill them immediately or soon afterwards. Its cost, logis-
tical complexity and moderate efficacy make it poorly suited for con-
trolling malaria in rural areas of sub Saharan Africa.
Insecticide treated nets (ITNs) is another method of control with a
person sleeping under insecticide treated nets. The ITN works not
only by creating a barrier between the mosquito and the intended
meal, but also by killing the mosquito if it lands on the net [60]. Re-
duction of human-vector contact through insecticide-treated bed
nets is better suited for malaria control in Africa, it enjoys greater
community acceptance and is as efficacious as indoor residual spray-
ing. Although they are inexpensive and effective, fewer than 2% of
Africans sleep under them [29]. Massive campaigns to increase their
use are required as a matter of urgency especially in rural Nigeria.
Countries around the world use other methods of vector control with
varying degrees of success. These methods include larviciding, the
removal of breeding grounds by drying up wet lands or ensuring
that pools of standing water are drained or by using biological con-
trols such as fish that eats mosquito larvae [61]. The success of these
controls depends highly on the type of vector and its breeding hab-
itat, the geography of the area and the socioeconomic status of the
population at risk.
Other strategies include; intermittent preventive treatment (IPT) in
infants and pregnant women using existing drugs to protect them
from the worst effects of the disease. Infants receive an antimalarial
three times during the first year of life at the time of routine immun-
ization, whether or not they have malaria. IPT has the potential to
become a major tool for malaria control in Africa because it can be
delivered through the Expanded Program on Immunization (EPI),
one of the best functioning systems of regular health contact with
young children in Africa [62].
Conclusion
The current tools for combating malaria such as artemisinin-combi-
nation therapy can result in a major reduction in P. falciparum. The
use of insect repellent in addition to increasing coverage of long last-
ing insecticide treated bed nets will provide greater protection. Con-
trol of mosquito, vectors of malaria may be enhanced by newer
methods of bio-control such as bio-pesticides containing a fungus
that is pathogenic to mosquitoes, hence reducing malaria transmis-
sion. The effectiveness of an intermittent preventive treatment
against malaria in children may be hindered by high incidence of
malnutrition therefore adequate nutrition will help boost the im-
mune system and may help protect children from malaria. Existing
Programs such as Expanded Program on Immunization, one of the
best functioning systems of regular health contact with young chil-
dren in Africa should be strengthened by Government. The evolve-
ment of vaccines in developed countries against malaria parasites
should be welcomed and funded by Government in Nigeria.
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Open Access Review
2014 Irfan et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits
Cite this article as: Irfan A, Ahmed I: Hepatocellular carcinoma: Could stem cell therapy ever be a viable solution? El Mednifico Journal 2014, 2(3): 273-276.
Hepatocellular carcinoma: Could stem cell therapy ever be a viable solution?
Ahmer Irfan
1,2
, Irfan Ahmed
3

Introduction
Stem cells are described as the building blocks of specialized tissues
and have been heralded as the basis of personalized medicine and
possible biological insurance for human beings. However, this ther-
apy is still in its early stages of development and there is limited ev-
idence on which potential treatment regimes and research direction
can be formulated. There is great optimism towards the potential of
stem cell therapy with hopes that it will be able to create entirely
new organs as well as repairing damaged ones. It is important to
analyze any scientific evidence that supports this excitement before
any rash claims are made. The aim of this systematic review was to
see the evidence in medical literature for use of stem cells in HCC.
Liver cancer
The liver is the most metabolically active organ in the body and con-
sequently, susceptible to acute and chronic diseases. The incidence
and mortality of hepatocellular carcinoma (HCC) is increasing dra-
matically in western society while it remains one of the most preva-
lent forms of cancer in the eastern hemisphere. This may be primarily
linked to the rise in the incidence of liver cirrhosis (secondary to viral
hepatitis in eastern and alcohol abuse in the western societies), in
which HCC usually develops. The most recent statistics for the USA
predict approximately 30,000 new cases of HCC with an estimated
mortality of 22,000 [1]. The statistics for developing countries mirror
this alarming connection between incidence and mortality, with
440,000 new cases accounting for almost 355,000 annual deaths [2].
In part, due to the association with liver cirrhosis it is regarded as
more difficult to treat compared to some other cancers and is there-
fore one of the major causes of mortality in these patients [3]. In
HCC, mitosis is accelerated leading to a large and genetically unsta-
ble population of hepatocytes. At a cellular level this can lead to te-
lomere erosion, microsatellite instability and chromosomal structural

1
University of St Andrews, United Kingdom
2
University of Edinburgh, United Kingdom
3
University of Aberdeen, United Kingdom
changes [4]. Currently the potentially treatment options for HCC in-
clude transplantation and resection, which have favorable outcomes
in small carcinomas, achieved by early diagnosis [5]. Techniques such
as ablation, chemotherapy and chemoembolization are also used
but with limited long-term benefit and are deemed to be palliative
only [6].
The lack of definitive treatment options is due to the ineffectiveness
of the current alternative treatments. This may indicate the potential
role stem cell therapy may have as a future curative treatment with
regards to HCC, provided the diseased liver can be removed in its
entirety before metastatic spread occurs. However, the potential tu-
morigenic properties of stem cells may be enhanced, should they be
placed in an environment where proliferation is relatively uncon-
trolled. Therefore, stem cell therapy may instead be indicative for
supportive therapy, hastening liver regeneration after tumor resec-
tion. They may also be used to create replacement organs for trans-
plantation, but this is not yet a feasible technology.
There are a variety of stem cell types from various sources, each with
its own individual properties and merits. Consequently, only certain
stem cell lines have been sufficiently trialed, as they have been
deemed to be the most suitable for the requirements.
Stem cells
Stem cells are defined as clonogenic, undifferentiated cells. These
cells can differentiate into a variety of cell lineages or can otherwise
replicate indefinitely. These properties have been met with great ex-
citement and emphasis is being put on the potential of stem cell
therapy. There are a variety of stem cells that can be obtained from
various sources. These cells present with their own merits and disad-
vantages and their use in research varies around the globe. The dif-
ferentiation potential of various types of stem cells also varies and
Correspondence: Ahmer Irfan
Email: ahmerirfan@googlemail.com
Abstract
Over the years, stem cells have always been believed to have great potential and may eventually be common use in the treatment of a
variety of disease states. However, evidence of their use has only just started being collected and analyzed. We aim to review the evidence
in medical literature for the use of stem cell therapy in hepatocellular carcinoma (HCC). The incidence of HCC has been increasing in the
past 50 years, partly due to its association with cirrhosis. Current therapy has proved relatively ineffective and consequently there are no
definitive treatment options. It is hoped that stem cell therapy may provide more effective results and may be carried forward as frontline
therapy. Therefore, it is important to analyze the current evidence and to determine whether it supports clinical application of stem cell
therapy. A through literature search was carried out on PubMed and Ovid Medline and cross referenced in January 2013 to determine all
stem cell therapy trials in the treatment of liver disease. From this data, only those that focused on the treatment of HCC were included.
Only two trials were found to study the effects of stem cell therapy in the treatment of HCC. Both trials extracted hematopoietic stem cells
from the patients ileum. These were re-infused into the patient following portal vein embolization and liver regeneration noted. It was
found that this therapy increased liver regeneration when compared to the placebo group. These positive results do not explain the lack
of further research that has been carried out in this subject area and it would be impossible to draw valid conclusions on such a small
evidence base. However, the increased interest in other disease states may suggest that stem cell therapy may provide more
groundbreaking results and consequently the focus of research has shifted as such. (El Med J 2:3; 2014)
Keywords: Hepatocellular Carcinoma, Stem Cell Therapy, Hematopoietic Stem Cells, Clinical Trials
274 Stem cell therapy for hepatocellular carcinoma
Vol 2, No 3
can be classified into major groups. A totipotent cell has the ability
to differentiate into any cell type and therefore contributes to the
formation of the trophoblast as well as all three germ layers [7]. Plu-
ripotent stem cells can form the endoderm, mesoderm and ecto-
derm and consequently form all cell types that are derived from
these three blastodermic layers [8]. Multipotent stem cells are exclu-
sive to one germ layer and are thought to have the ability to replace
damaged cells within a specific tissue [9]. The various types of stem
cells currently in research are listed in table 1.
Table 1: Different types of stem cells
Type of Stem Cell Source
Differentiation
Potential
Embryonic Human embryos Pluripotent
Induced pluripotent
Reprogramming
human somatic
cells
Pluripotent
Hematopoietic Bone marrow Multipotent
Mesenchymal
Bone marrow
stroma
Multipotent
Hepatic progenitor
Human umbilical
cord blood
Multipotent
Endothelial progenitor Bone marrow Multipotent

Of all the stem cell types listed, only hematopoietic stem cells are
the only type that has currently being trialed. These cells are nor-
mally used in the treatment of blood disorders. Their multipotent
nature allows them to naturally differentiate to several lines within
the hematopoietic system making them theoretically ideal for such
a treatment [10]. Progression of research has shown multiple animal
models in which these cells have demonstrated the ability to differ-
entiate outside the hematopoietic system, including evidence high-
lighting their ability to differentiate into hepatocytes [11-13]. The ev-
idence of the cells ability to differentiate in humans is currently lim-
ited, forcing assumptions to be made based on the animal models
and carried forward practically.
Method
To obtain primary data, a literature search was carried out on Pub-
Med, Ovid and Google scholar. All the eligible articles were cross-
referenced. All the articles were read by both the authors (AI and IA)
prior to this review being written. This initial search was carried out
to determine all evidence of stem cell therapy in the treatment of
liver disease and this was later narrowed to only those studies focus-
ing on HCC (Figure 1).
Result
Only 2 clinical trials (Table 2) were found concerning the treatment
of HCC using supportive stem cell therapy [14, 15]. Both utilized the
same methodology, using portal vein embolization (PVE) initially and
subsequently monitored liver regeneration in both control and treat-
ment arms. Autologous hematopoietic stem cells, extracted from the
bone marrow at the iliac crests were then infused into the portal
system following PVE. Both studies reported an increase in liver re-
generation in those patients undergoing stem cell therapy when
compared to their counterparts in the placebo group.

Figure 1: Search strategy

Trials studying
non-cancer liver
disease
(n = 18)

Articles found
through keyword
search:
(n = 160)
Considered for
detailed analysis
(n = 22)
Excluded after full
paper analysis:
(n = 8)

Exclusive reasons:
Reviews only
No clinical
outcome
All Stem Cell Trials
in chronic liver
disease
(n = 20)

Considered for
Review:
(n = 14)

Obtained through
cross referencing
(n = 6)

Articles excluded
based on title or
abstract:
(n = 138)

Exclusive reasons:
Animal Trial
Reviews only
Irrelevant

Trials studying
Hepatocellular
carcinoma
(n = 2)

Irfan A, Ahmed I 275
Table 2: Stem cell therapy in the treatment of hepatocellular
carcinoma
Study Author Sample Size Author Conclusions
1
Esch et al,
2005 [14]
Active Treatment:
3 (1 male) Greater regeneration
in treatment group Placebo Treatment:
3 (2 male)
2
Furst et al,
2007 [15]
Active Treatment:
6 (3 male) PVE with HSC accel-
erates proliferation Placebo Treatment:
7 (4 male)

Discussion
It is plainly obvious that the evidence in this subject area is extremely
limited. It is difficult to draw conclusions from merely two papers
presenting primary data. There is also no reason to suggest why fur-
ther trials have not been carried out on this patient demographic
considering the results from the two initial trials. Clear demonstra-
tion of the potential safety and feasibility of the treatment option
should have theoretically sparked a greater interest. Both trials also
showed an increase in liver regeneration when compared to the pla-
cebo group highlight a clear area for exploration.
If the approach, which has been demonstrated in the trials, is carried
forward, only tumors, which can be resected can be treated and liver
recovery subsequently aided using stem cell therapy. However,
problems arise in carcinomas that are too large and where resection
is not a possibility. In these patients, the current stem cell therapy
we have at our disposal would be ineffective.
While this may be one drawback of this treatment approach, it still
does not fully explain the lack of further research that has been car-
ried out in this area. It may be possible that adverse effects were
detected beyond the follow-up period. However, due to the time-
scales these have not been followed up and reported. Stem cells
have thought to present with a risk of tumorigenesis, although there
is limited scientific data to definitively support or refute this claim.
Another possibility is that the enhanced regeneration effect pro-
vided does not support the economic burden that such a therapy
would place on the healthcare system. This practical hurdle was not
considered in these trials, they were run as feasibility studies to begin
determination of the absolute useful nature of this therapy. Such
economic studies are only carried out on established therapies and
therefore it would be impractical to suggest such an approach on a
treatment option that hasnt been proven effective. The problem lies
in the absence of literature to explain the halting of stem cell therapy
in HCC, an anomaly when compared to the results present.
Full organ recreation is an avenue for exploration in HCC treatment
if technology can be developed for such complex models. Following
this advancement, immediate organ transplantation could become
an option. The major problem highlighted with organ transplanta-
tion is the high levels of mortality suffered by patients on the trans-
plant list due to a worldwide organ shortage [16]. Those patients
awaiting transplantation may require hemodynamic, renal and res-
piratory support facilities which come at a huge cost to both the in-
dividual and the health system [17]. The elimination for the require-
ment for constant immunosuppression therapy, a major cause of
complications post-transplant would detract from likelihood of po-
tentially complex post-operative management. An ability to recreate
organs from stem cells would be a groundbreaking advancement
and stem cells could consequently be harvested and stored as bio-
logical insurance.
While stem cells, given time and adequate research, may be able to
solve some problems in the treatment of HCC, they still possess some
of the same drawbacks as current treatment. Those tumors that can-
not be treated through transplantation due to metastasis, unrespect-
able tumors and those patient unable to undergo surgery will not be
eligible for this treatment option. Therefore as with all cancer, early
diagnoses and action may be the most important tool we have in
adequate treatment.
It is still plausible that stem cell therapy may be effective supportive
therapy to resected HCC treatment. But the absence of data in the
past six years not only leaves a weak evidence base to establish such
conclusions on but also raises questions. There may be adverse ef-
fects that havent reached publication or it may be attributed to the
economic burdens when compared to the increased quality of life
this treatment appears to provide. Regardless, this treatment option
is a largely unexplored one and the recent surge in stem cell therapy
in other disease states may just suggest that resources are better
spent in other areas that may provide far clearer advantages when
compared to current practice, a factor which may not be relevant to
HCC treatment.
Conclusion
Due to the increasing incidence of HCC all over the world and the
problems present with current therapy, new treatment options
would be welcomed. Stem cell therapy initially showed promise,
with trials using autologous stem cells to hasten liver regeneration
after PVE. Only two trials have been found to study stem cell therapy
and both appeared to yield positive results. However, the lack of data
since suggests that there may be pitfalls that have not reached pub-
lic knowledge. While speculative, the surge in interest in stem cell
therapy in other areas suggests that major breakthroughs may be
more likely and consequently research and funding should be di-
rected accordingly.
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Open Access Case Report
2014 Sahu et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits
Cite this article as: Sahu L, Gandhi G, Bala N, Thakur P: Successful conservative management in placenta previa percreta involving urinary bladder. El Mednifico Journal 2014, 2(3): 277-281.
Successful conservative management in placenta previa percreta involving urinary bladder
Latika Sahu
1
, Gouri Gandhi
1
, Nalini Bala
1
, Priyanka Thakur
1

Introduction
Placenta percreta is a variety of placenta accreta (part of or the entire
placenta, invades and is inseparable from the uterine wall) where
there is invasion of the chorionic villi through the myometrium and
serosa, and occasionally into adjacent organs, such as the bladder [1,
2]. Placenta percreta is considered as severe pregnancy complica-
tion. It becomes problematic during delivery when the placenta does
not separate from the uterus and is followed by massive and poten-
tially life-threatening peripartum hemorrhage, leading to dissemi-
nated intravascular coagulopathy, the need for hysterectomy, surgi-
cal injury to the ureters, bladder, bowel, or neurovascular structures,
adult respiratory distress syndrome, acute transfusion reaction, elec-
trolyte imbalance and renal failure.
The average blood loss at delivery in women with placenta accreta
is 3,000-5,000 mL [3, 4]. Ninety percent of patients with placenta ac-
creta require blood transfusion, and 40% require more than 10 units
of packed RBC. Maternal morbidity had been reported to occur in up
to 60% and mortality in up to 7% of women with placenta accrete
[5]. The incidence of perinatal complications is also increased mainly
due to preterm birth and small for gestational age fetuses [6]. Ma-
ternal death may occur despite optimal planning, transfusion man-
agement, and surgical care [6].
The incidence of placenta accreta has increased and seems to paral-
lel the increasing caesarean delivery rate over the past 50 years [7].
In view of the fact that the indications for caesarean delivery seem
to be steadily expanding, including caesarean delivery on maternal
request, the incidence of placenta accreta is likely to continue to in-
crease [8]. Researchers have reported the incidence of placenta ac-
creta as 1:210 in 2006, 1 in 533 pregnancies for the period of 1982
2002 which has sharply increased from 1 in 4,027 pregnancies in the
1970s, increasing to 1 in 2,510 pregnancies in the 1980s, suggesting
that this increase is mainly the result of the increasing rate of caesar-
ean delivery [9, 10].

1
Department of Gynecology & Obstetrics, Maulana Azad Medical College and
associated Lok Nayak Hospital. New Delhi. India
Correspondence: Latika Sahu
Email: latikasahu@gmail.com
There are only a few cases reported of placenta previa percreta in-
volving urinary bladder in the literature available [11, 12] Here we
are reporting a case of placenta previa percreta involving bladder
managed conservatively with leaving placenta in situ during classical
caesarean section and followed by prophylactic bilateral uterine ar-
tery embolization (UAE), to highlight the catastrophic nature of this
clinical entity which can be predicted and managed conservatively.
Case Presentation
A 32 year old woman, gravida 4 para 2 abortion 1, with 38 weeks of
gestation with previous 2 lower segment caesarean section (LSCS)
with placenta previa was admitted in our hospital on 4
th
March 2013
for safe confinement. On admission, patient had no complaints. She
was a booked patient with Hb of 10.4g. USG showed: placenta ante-
rior covering internal os with a translucent line seen between pla-
centa and uterine wall (Figure 1).

Color Doppler revealed placenta was heterogeneous in echo pattern
with myometrial thinning posterior to urinary bladder with morbidly
adherent placenta (Figure 2). MRI pelvis showed placenta along right
lateral wall of uterus. Placental thickness was 5cm, with multiple het-
erogeneous hypointense areas within the placental parenchyma
showing placental lacunae. Interruption of myometrial line along the

Abstract
Background: Placenta Previa Percreta is a potentially life-threatening obstetric condition that requires a multidisciplinary approach to
management. The incidence of placenta accrete/percreta has been increased now and seems to parallel the increasing caesarean section
(CS) rate.
Case Presentation: This is a case of morbidly adherent placenta successfully managed conservatively. The patient was G3P2L2 with previous
2 lower segment caesarean sections (CS), antenatally diagnosed to be anterior placenta previa with placenta percreta. Elective classical CS
followed by post op bilateral uterine artery embolization was done for this case. She required only 2 blood transfusions peri-operatively.
The baby was fine. She required re-embolization after 5 weeks for hematuria due to bladder invasion of placenta percreta. Serum beta hCG
value became normal after 18-20 weeks. She is doing well with normal menstrual cycle 1 year after classical caesarean section.
Conclusion: Conservative management of placenta previa percreta, especially when involving bladder even if fertility preservation is not
the concern, should be preferred over caesarean hysterectomy if facilities are available. (El Med J 2:3; 2014)
Keywords: Placenta Previa Percreta, Conservative Management, Caesarean Section, Maternal Health

Figure 1: Antepartum ultrasonogram.
278 Placenta previa percreta involving urinary bladder
Vol 2, No 3
right lateral aspect in the region of placenta above the urinary blad-
der showing myometrial infiltration. There was loss of clear planes
with the bladder at points suggestive of morbidly adherent placenta
(Figure 3). Classical caesarean section was performed with uterine
incision given in upper uterine segment away from the placental
edge with bilateral tubal ligation under GA on 8
th
March 2013. Intra-
operative findings: placenta percreta confirmed, placenta seemed to
be invading through uterine serosa reaching up to bladder (Figure
4).

Baby was delivered as breech. Patient was observed till 20 min when
no active bleeding was observed and placenta didnt separate then
cord was cut and tied with suture and decision for placenta to be left
in situ was taken. Uterus closed in layers. Abdomen was closed in
layers and postoperatively no active vaginal bleeding seen. Patient
shifted for B/L uterine artery embolization prophylactically. Under
strict aseptic precaution bilateral uterine artery embolization was
done by PVA particles followed by gel foam (Figure 5). Triple antibi-
otics (ampicillin, gentamicin, and metronidazole) and weekly inves-
tigations - hemogram, urine C/S, and serum hCG - were done. Pa-
tient remained asymptomatic and postoperative course was une-
ventful and was discharged on day 18. USG was done for placental
size and vascularity. Beta hCG was 15400 IU/ml on 11
th
March, 4280
IU/ml on 7
th
May and 0.2 IU/ml on 7
th
August and 23
rd
December
2013.

Almost one month after discharge patient was readmitted with c/o
frank hematuria on 40
th
postop day (18
th
April, 2013). USG KUB &
cystoscopy was done. USG KUB showed: right kidney normal size
and echo texture, left kidney moderate hydronephrosis. Bladder
partially distended. One packed cell was transfused on 21
st
April,
2013. Coil re-embolization of feeder vessels was done on 22
nd
April,
2013 done. Patient was started on IV antibiotics according to urine
C/S report. Patient again had episode of hematuria on 4
th
May2013
for 2 days, managed conservatively. MR Urography and cystoscopy
was done. USG abdomen dated 29
th
April, 2013 showed both kidneys
had hydronephrosis with dilation of upper ureter measuring 1.2 cm.
Left ureter was dilated up to the pelvis. USG on 7
th
August, 2013:
uterus large 10x10x8cm with heteroechoic mass within completely
filling it. Myometrium thinned. Planes with bladder not maintained.
Internal vascularity is minimum [Figures 6(a), 6(b)].

Figure 2: Antepartum USG with color Doppler.

Figure 3: MRI picture with morbidly adherent placenta.

Figure 4: Intraoperative picture showing bladder involvement of placenta.

Figure 5: Bilateral uterine artery embolisation.

Figure 6(a): USG showing remaining placenta after 5 month.

Figure 6(b): Color Doppler showing reduced vascularity.
Sahu L, Gandhi G, Bala N et al 279
She started menstruating normally with average flow and regular cy-
cle. On 23
rd
December, 2013 her follow up scan revealed 6x8cm het-
eroechoic mass within completely filling uterus. Myometrium
thinned out and planes with bladder not maintained (Figure 7). She
had passed a bit of fleshy tissue of size 2x4cm not associated with
bleeding per vaginum on 23
rd
Jan 2014 and USG revealed 5x7cm
same placental mass. She has no other complain and is doing well 1
year after surgery with regular menstruation.

Discussion
Placenta accreta is currently the most common indication for peri-
partum hysterectomy. Risk factors of placenta accreta are those who
have myometrial damage caused by a previous caesarean delivery
with either anterior or posterior placenta previa overlying the uterine
scar. In the presence of a placenta previa, the risk of placenta accreta
is 3%, 11%, 40%, 61%, and 67% for the first, second, third, fourth, and
fifth or greater repeat caesarean deliveries, respectively [13]. Pla-
centa previa without previous uterine surgery is associated with a 1
5% risk of placenta accreta. Besides advanced maternal age and mul-
tiparity, other reported risk factors include any condition resulting in
myometrial tissue damage followed by a secondary collagen repair,
such as previous myomectomy, endometrial defects due to vigorous
curettage resulting in Asherman syndrome, submucous leiomyomas,
thermal ablation, and uterine artery embolization [14-16].
Antenatal diagnosis seems to be a key factor in optimizing maternal
outcome as it allows multidisciplinary planning to minimize potential
maternal or neonatal morbidity and mortality. All women at high risk
of placenta accreta should have routine placental localization at 20
weeks and follow-up scan at 32 weeks. The diagnosis is usually es-
tablished by transvaginal (TVS) and transabdominal (TAS) ultraso-
nography (USG) and occasionally supplemented by magnetic reso-
nance imaging (MRI). TVS is safe for patients with placenta previa
and allows a more complete examination of the lower uterine seg-
ment. A normal placental attachment site is characterized by a hy-
poechoic boundary between the placenta and the bladder. The ul-
trasonographic features suggestive of placenta accreta include irreg-
ularly shaped placental lacunae (vascular spaces) within the pla-
centa, thinning of the myometrium overlying the placenta, loss of
the retroplacental clear space, protrusion of the placenta into the
bladder, increased vascularity of the uterine serosabladder inter-
face, and turbulent blood flow through the lacunae on Doppler ul-
trasonography [17].
The presence and increasing number of lacunae within the placenta
at 1520 weeks of gestation have been shown to be the most pre-
dictive ultrasonographic signs of placenta accreta, with a sensitivity
of 79% and a positive predictive value of 92%. These lacunae may
result in the placenta having a moth-eaten or Swiss cheese ap-
pearance. Ultrasonography alone to diagnose placenta accrete car-
ries a sensitivity of 7787%, specificity of 9698%, a positive predic-
tive value of 6593%, and a negative predictive value of 98%. The
use of power Doppler, color Doppler, or three-dimensional imaging
does not significantly improve the diagnostic sensitivity.
MRI is considered an adjunctive modality and adds little to the diag-
nostic accuracy of ultrasonography except when there are ambigu-
ous ultrasound findings or a suspicion of a posterior placenta accreta,
with or without placenta previa. Gadolinium-based contrast en-
hancement enables MRI to more clearly delineate the outer placental
surface relative to the myometrium and differentiate between the
heterogeneous vascular signals within the placenta from those
caused by maternal blood vessels. However, the American College
of Radiology guidance recommends that intravenous gadolinium
should be avoided during pregnancy and should be used only if ab-
solutely essential [18].
In general, the recommended management of suspected placenta
accreta is planned classical caesarean section with placenta left in
situ because attempts at removal of the placenta are associated with
significant hemorrhagic morbidity, followed by caesarean hysterec-
tomy (ACOG) [5]. There are reports of conservative management
that includes ligating the cord close to the fetal surface, removing
the cord, and leaving the placenta in situ. However, this approach
should be considered only when the patient has a strong desire for
future fertility as well as hemodynamic stability, normal coagulation
status, and is willing to accept the risks involved in this conservative
approach. The patient should be counselled that the outcome of this
approach is unpredictable and that there is an increased risk of sig-
nificant complications as well as the need for later hysterectomy. Re-
ported cases of subsequent successful pregnancy in patients treated
with this approach are rare. This approach should be abandoned and
hysterectomy performed if excessive bleeding is noted. Need for re-
peated uterine artery embolisation may be required and these pa-
tients should be monitored under close supervision for successful
conservative management.
In order to avoid an emergency CS and to minimize complications of
prematurity it is acceptable to schedule caesarean at 34 to 35 weeks.
A multidisciplinary team approach and delivery at a center with ad-
equate resources, including those for massive transfusion are essen-
tial to reduce neonatal and maternal morbidity and mortality. Cae-
sarean hysterectomy is the preferable treatment. In carefully selected
cases, when fertility is desired, conservative management may be
considered with caution. Delivery planning may involve an anesthe-
siologist, senior obstetrician, pelvic surgeon such as a gynecologic
oncologist, intensivist, neonatologist, urologist, hematologist, and
interventional radiologist to optimize the patients outcome [19].
The delivery should be performed by an experienced obstetric team
that includes an obstetric surgeon, with other surgical specialists,
such as urologists, general surgeons, and gynecologic oncologists,
available if necessary.

Figure 7: USG showing remaining placenta after 9 months.
280 Placenta previa percreta involving urinary bladder
Vol 2, No 3
Because of the risk of massive blood loss, attention should be paid
to maternal hemoglobin levels in advance of surgery, if possible.
Many patients with placenta accreta require emergency preterm de-
livery because of the sudden onset of massive hemorrhage. Autolo-
gous blood salvage devices have proved safe, and the use of these
devices may be a valuable adjunct during the surgery [20]. The tim-
ing of delivery in cases of suspected placenta accreta must be indi-
vidualized, decision should be made jointly with the patient, obste-
trician and neonatologist. Patient counselling should include discus-
sion of the potential need for hysterectomy, the risks of profuse hem-
orrhage, and possible maternal death. Although a planned delivery
is the goal, a contingency plan for emergency delivery should be de-
veloped for each patient, which may include following an institu-
tional protocol for maternal hemorrhage management. However, the
results of a recent decision analysis suggested that combined mater-
nal and neonatal outcomes are optimized in stable patients with de-
livery at 34 weeks of gestation without amniocentesis [21]. The de-
cision to administer antenatal corticosteroids and the timing of ad-
ministration should be individualized.
The delivery should be performed in an operating room with the
personnel and support services needed to manage potential compli-
cations. Assessment by the anesthesiologist should occur as early as
possible before surgery. Both general and regional anesthetic tech-
niques have been shown to be safe. The judgment of which type of
technique to be used should be made on an individual basis. Pneu-
matic compression stockings should be placed preoperatively and
maintained until the patient is fully ambulatory. Prophylactic antibi-
otics are indicated, with repeat doses after 23 hours of surgery or
1,500 mL of estimated blood loss.
Preoperative cystoscopy with placement of ureteral stents may help
prevent inadvertent urinary tract injury. Some advice that a three-
way Foley catheter be placed in the bladder through the urethra to
allow irrigation, drainage, and distension of the bladder, as neces-
sary, during dissection. Preoperatively, the blood bank should be
placed on alert for a potential massive transfusion. Packed red blood
cells and thawed fresh frozen plasma and coagulation factors should
be available in the operating room and should be infused quickly as
necessitated. During surgical procedure patient should be in a mod-
ified dorsal lithotomy position with left lateral tilt to allow for direct
assessment of vaginal bleeding, provide access for placement of a
vaginal pack, and allow additional space for a surgical assistant. Be-
cause the procedure is anticipated to be prolonged, padding and
positioning to prevent nerve compression and the prevention and
treatment of hypothermia are important [22]. The choice of ab-
dominal incision usually midline vertical. A classical uterine incision,
often transfundal, may be necessary to avoid the placenta and allow
delivery of the infant. Ultrasound mapping of the placental attach-
ment site, either preoperatively or intra-operatively, may be helpful.
Because the positive predictive value of ultrasonography for pla-
centa accreta ranges from 65% to 93% it is reasonable to await spon-
taneous placental separation to confirm placenta accreta clinically.
Attempts at manual placental removal should be avoided. If hyster-
ectomy becomes necessary, the standard approach is to leave the
placenta in situ, quickly use a whip stitch to close the hysterotomy
incision, and proceed with hysterectomy. Whereas hysterectomy is
performed in the usual fashion, dissection of the bladder flap may
be performed relatively late, after vascular control of the uterine ar-
teries is achieved, in cases of anterior accreta, depending on in-
traoperative findings. Occasionally, a subtotal hysterectomy can be
safely performed, but persistent bleeding from the cervix may pre-
clude this approach and make total hysterectomy necessary.
Of the reported 26 patients treated with conservative approach, 21
(80.7%) successfully avoided hysterectomy, whereas 5 (19.3%) even-
tually required it. However, the majority of the 21 patients who
avoided hysterectomy did require additional treatment, including
hypogastric artery ligation, arterial embolization, methotrexate,
blood product transfusion, antibiotics, or curettage [23]. Current ev-
idence is insufficient to make a firm recommendation on the use of
balloon catheter occlusion or embolization to reduce blood loss and
improve surgical outcome, but individual situations may warrant
their use. Although some investigators have reported reduced blood
loss, there have been other reports of no benefits and even of signif-
icant complications [24, 25].
The folate antagonist methotrexate has been proposed as an adjunc-
tive treatment for placenta accrete but there are no convincing data
for the use of methotrexate for postpartum management of placenta
accreta. When the diagnosis of placenta accreta is suspected after
vaginal delivery, management options might include intrauterine
balloon tamponade, selective pelvic embolization in stable cases,
and emergency surgery.
In this reported case we have done elective classical CS with prophy-
lactic bilateral UAE and managed conservatively successfully though
she required once re-embolization for hematuria but injury to blad-
der/ureter, massive hemorrhage and severe morbidity were abso-
lutely avoided without any complication due to UAE.
So to conclude conservative management of placenta previa
percreta, especially when involving bladder even if fertility preserva-
tion is not the concern, should be preferred over caesarean hyster-
ectomy if facilities are available.
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Davis; 1972.
2. Tan CH, Tay KH, Sheah K, et al. Perioperative endovascular internal iliac artery
occlusion balloon placement in management of placenta accreta. American
Journal of Roentgenology.2007;189(5):11581163.
3. Faranesh R, Shabtai R, Eliezer S, Raed S. Suggested approach for management
of placenta percreta invading the urinary bladder. Obstetrics and Gynecology.
2007;110(2):512515.
4. Daskalakis G, Anastasakis E, Papantoniou N, Mesogitis S, Theodora M, Antsaklis
A. Emergency obstetric hysterectomy. Acta Obstetricia et Gynecologica
Scandinavica. 2007;86(2):223227.
5. ACOG COMMITTE OPINION n0529, July 2012Placenta Accreta.
6. Shellhaas CS, Gilbert S, Landon MB, Varner MW, Leveno KJ, Hauth JC, et al. The
frequency and complication rates of hysterectomy accompanying caesarean
delivery. Eunice Kennedy Shriver National Institutes of Health and Human
Development Maternal-Fetal Medicine Units Network. Obstet Gynecol
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7. Hamilton BE, Martin JA, Ventura SJ, Sutton PD, Menacker F. Births: preliminary
data for 2004.National vital Statistics Reports. 2005;54(8):117.
8. Warshak CR, Ramos GA, Eskander R, et al. Effect of predelivery diagnosis in 99
consecutive cases of placenta accreta. Obstetrics and Gynecology.
2010;115(1):6569.
9. Wu S, Kocherginsky M, Hibbard JU. Abnormal placentation: twenty-year
analysis. Am J Obstet Gynecol 2005;192:145861.
10. Stafford I, Belfort MA: Placenta accrete, increta, and percreta: A team-based
approach starts with prevention. Contemp Ob/Gyn April:77, 2008.
11. Yanagisawa T1, Furuta A, Egawa S, Tanaka T.A case report of placenta percreta
with bladder invasion. Hinyokika Kiyo Article in Japanese. 2012 Jun;58(6):283-
6.
12. Washecka R, Behling AUrologic complications of placenta percreta invading
the urinary bladder: a case report and review of the literature. Hawaii Med J.
2002 Apr;61(4):66-9.
13. Silver RM, Landon MB, Rouse DJ, Leveno KJ, Spong CY, Thom EA, et al. Maternal
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14. Al-Serehi A, Mhoyan A, Brown M, Benirschke K, Hull A, Pretorius DH. Placenta
accreta: an association with fibroids and Asherman syndrome. J Ultrasound
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15. Hamar BD, Wolff EF, Kodaman PH, Marcovici I. Premature rupture of
membranes, placenta increta, and hysterectomy in a pregnancy following
endometrial ablation. J Perinatol 2006;26:1357.
16. Pron G, Mocarski E, Bennett J, Vilos G, Common A, Vanderburgh L. Pregnancy
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2011;20:703.


2014 Akyol et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Akyol M, Gokdemir O, Ozturk T: Multimodality imaging features of Poland syndrome associated with cervical rib and elongated transverse process of cervical vertebrae. El Mednifico Journal
2014, 2(3): 282-285.
Multimodality imaging features of Poland syndrome associated with cervical rib and elongated
transverse process of cervical vertebrae
Muammer Akyol
1
, Onur Gokdemir
1
, Tulin Ozturk
1

Introduction
Poland syndrome (PS) is a rare congenital malformation occurring in
approximately one in every 30,000 to 100,000 live births [1]. It was
first described by Sir Alfred Poland in 1841 as complete unilateral
absence of the pectoralis major-minor, serratus anterior, obliquus ex-
ternus abdominis muscles with ipsilateral thoracic and upper limb
defects. But the term Poland Syndrome was first used in an article
by Patrick Clarkson in 1962 [2]. Clinical manifestations are extremely
variable and are rarely all seen in a single case. Most cases of PS re-
ported are sporadic; however, familial cases have been occasionally
described. The right side of the body is affected more often than the
left side, and a male to female ratio of 2:1 up to 3:1 can be found.
Reports of bilateral agenesis of the muscle have been infrequently
reported in literature [2, 3].
Cervical rib is a congenital anomaly which is usually located above
the first rib. It is seen bilaterally in 40% of cases and is found twice
as frequently in females than in males. Previous studies have re-
ported a wide range of values for the prevalence of cervical rib in
various human populations, from 0.05% to 3.0%, based on series us-
ing radiographs [4, 5]. Although typically asymptomatic, cervical rib
may cause thoracic outlet syndrome (TOS) in adults [4].
We encountered a patient with PS associated with right-sided cervi-
cal rib and left-sided elongated transverse process of 7
th
cervical ver-
tebrae. The association of PS with rib anomalies has been described
before. But to our knowledge, its association with cervical rib and
elongated transverse process of cervical vertebrae has not been re-
ported previously.
Case Report
A 25 year-old female presented to our outpatient clinic of the De-
partment of Plastic and Reconstructive Surgery with the complaint
of small left breast. No significant past medical or surgical history
was present. Physical examination showed depression of the left an-
terior chest wall with small left breast volume. The left nipple was
sited slightly higher compared to the contralateral side but was oth-
erwise normal (Figure 1). The patient had normal routine laboratory

1
Elazig Training and Research Hospital, Elazig, Turkey.
Correspondence: Muammer Akyol
Email: muammerakyol@gmail.com
values and was referred to the Radiology outpatient clinic with an
initial diagnosis of PS. Radiological examination, including ultra-
sound, computed tomography (CT) and magnetic resonance imag-
ing (MRI) revealed aplasia of the costosternal portion of the left pec-
toralis major muscle, left pectoralis minor muscle, left serratus ante-
rior muscle, left anterior intercostal muscles, hypoplasia of the left
latissimus dorsi muscle and reduced left breast tissue with right-
sided cervical rib and left-sided elongated transverse process of 7th
cervical vertebrae (Figure 2). These anomalies were compatible with
the diagnosis of PS.

Further systemic evaluation, including examination of upper-lower
limbs, did not show other anomalies. Cardiovascular and neurologi-
cal examination were normal. Renal ultrasound excluded important
anomalies which can occur in PS. She was within normal limits in
height, weight, and intelligence. The problem was aesthetic. Breast
augmentation was performed under general anesthesia with place-
ment of a 100 cc silicone implant (Figure 3). A small suction drain
was placed alongside the implant and she obtained a symmetric re-
sult. The post-operative period was uneventful and the patient re-
covered well. Three months following the surgery, she was asymp-
tomatic and was instructed to follow-up on an as-needed basis.

Abstract
Background: Poland syndrome (PS) is a rare congenital anomaly characterized by partial or complete absence of the major pectoral muscle
which is variably associated with ipsilateral thoracic and upper limb deformities.
Case Presentation: We present multimodality imaging features of PS associated with cervical rib and elongated transverse process of cervical
vertebrae in a 25 year-old female patient.
Conclusion: PS is a rare congenital disorder that has a wide spectrum of clinical presentations. The aim of our case report was to show
multimodality imaging features of the PS associated with cervical rib and elongated transverse process of cervical vertebrae. We could not
find any similar case reported in the literature. (El Med J 2:3; 2014)
Keywords: Cervical Rib, Computed Tomography, Magnetic Resonance Imaging, Poland Syndrome, Ultrasound

Figure 1: Frontal view of a 25 year-old woman shows depression
of the left anterior chest wall with small left breast. The left
nipple was sited slightly higher compared to the right side.

Akyol M, Gokdemir O, Ozturk T 283

Discussion
Classical PS is characterized by hypoplasia or aplasia of the pectoral
muscles variably associated with ipsilateral thoracic and upper limb
anomalies. Cardiovascular, genitourinary, spine and other abnormal-
ities sometimes coexist in this disorder, making it a polymorphous
syndrome with differing degrees of severity. The common features
of the syndrome are listed in Table 1 [6].
The etiology of this syndrome is still being discussed. Most reported
cases are sporadic, but the disease may be inherited as an autoso-
mal-dominant trait. The responsible gene has not yet been mapped.
Different etiologic factors of the PS are taken into account: genetic,
vascular disruption during embryogenesis and also teratogenic ef-
fect [6, 7].
Table 1: Common features of Poland Syndrome
Hypoplasia or aplasia of sternocostal head of pectoralis
major muscle
Hypoplasia or aplasia of pectoralis minor muscle
Hypoplasia or aplasia of latissimus dorsi, serratus anterior,
external oblique, infraspinatus, supraspinatus, deltoid and
intercostal muscles
Hypoplasia or absence of nipple and breast tissue
Bony dysostoses affecting hand (brachymesophalangy with
syndactyly, biphalangy, ectrodactyly), wrist, forearm, upper
arm, scapula
Axillary webs and absence of axillary hair; minimal
subcutaneous fat
Soft tissue syndactyly
Lung herniation
Scoliosis
Hypoplasia of hemithorax or ribs

Figure 2(a): Transverse ultrasound images of the chest wall show absence of
the pectoral muscles (arrows) and reduced breast tissue (calipers) on the left
side compared to the right side.

Figure 2(b): Axial non-enhanced CT scan reveals absence of the costosternal
portion of the left pectoralis major muscle, left pectoralis minor muscle, left
anterior intercostal muscle and reduced breast tissue compared to the right,
arrows: pectoralis major, arrowheads: pectoralis minor.

Figure 2(c): Axial non-enhanced CT illustrates aplasia of the left serratus
anterior muscle and hypoplasia of the left latissimus dorsi muscle, arrows:
latissimus dorsi muscles, arrowheads: right serratus anterior muscle.

Figure 2(d): Axial fast spin-echo T1-weighted image illustrates absence of
the left pectoral major-minor muscles, left serratus anterior muscle, left
anterior intercostal muscles, hypoplasia of the left latissimus dorsi muscle
and reduced breast tissue.

Figure 2(e): Axial fast spin-echo T1-weighted image demonstrates normal
development of clavicular portion of the left pectoralis major muscle and
aplasia of the left pectoralis minor muscle.

284 Multimodality imaging features of Poland syndrome
Vol 2, No 3

Depending on the physicians specialty and the referral pattern, a
variable incidence of the anomalous defects is recognized such as
rib defects (usually II-IV or II-V), absence of shoulder girdle muscles,
and breast hypoplasia or agenesis athelia, vertebral anomalies and
renal malformations [8]. Moreover, dextrocardia, situs inversus, lower
limb malformations, Mullerian duct anomalies, malignancies like
acute leukemia, non-Hodgkin lymphoma, lung cancer, and breast
cancer have been described in association with PS [6, 9].
PS has a wide spectrum of clinical presentations and corrective treat-
ment varies according to the case and surgeon. The operative recon-
struction of the chest wall is based on the anatomy, the degree of
severity and gender. Several treatment options have been described
for chest wall reconstruction in patients with PS, including the use of
breast implant or tissue expander combined with a flap, autologous
fat injection, a chest wall prosthesis, local or free flap reconstruction
such as a transverse musculocutaneous gracilis flap, latissimus dorsi
muscle transfer, a partial latissimus dorsi flap, a rectus abdominis
muscle transfer, a laparoscopically harvested omental flap, and the
use of a free anterolateral thigh perforator flap [9, 10].

Cervical rib is a supernumerary rib that usually arises from the sev-
enth cervical vertebrae. It is asymptomatic in 90% of the cases and
is associated with TOS in approximately 10% of the affected popula-
tion [5].
The criteria for cervical rib have been defined as follows [5, 11]:
1. The cervical rib must articulate with the C7 vertebrae with a well-
defined joint; if the rib was fused with the vertebra, it is consid-
ered an elongated transverse process.
2. The rib must not originate from the transverse process of the
first thoracic vertebra, but rather the 7
th
cervical vertebral trans-
verse process, which projects horizontally from the spine.
Embryologically, ribs arise from precursor sclerotome cells in the tho-
racic region and continued growth of these cells in the cervical spine
region may lead to the formation of a cervical rib. Mutations in Hox
genes (a group of related genes which are instrumental in regulating
body formation during development) have been shown to cause the
development of cervical ribs from the costal or ventral processes of
the primitive vertebral arches [12, 13].
The association of PS with rib anomalies has been reported as hypo-
plasia or aplasia of the ribs. But to our knowledge, its association with
cervical rib and elongated transverse process of cervical vertebrae
has not been reported previously in the medical literature. Thus, the
Figure 2(f): Axial maximum intensity projection CT shows right-sided
cervical rib with a well-defined joint and left-sided elongated transverse
process of the 7th cervical vertebrae.

Figure 2(g): Three-dimensional CT demonstrating
right-sided cervical rib and left-side elongated
transverse process.

Figure 3(a): Intraoperative view shows placement of silicone implant.

Figure 3(b): Axial post-operative CT scan reveals satisfactory position of the
breast implant.

Akyol M, Gokdemir O, Ozturk T 285
question arises as to whether this condition is a simple coincidence
or is an etiological association.
Conclusion
PS is a rare congenital disorder that has a wide spectrum of clinical
presentations. The aim of our case report was to show multimodality
imaging features of the PS associated with cervical rib and elongated
transverse process of cervical vertebrae. We could not find any simi-
lar case reported in the literature.
Consent: Written informed consent was obtained from the patient for publication
of this case report.
References
1. Ram AN, Chung KC. Poland's syndrome: current thoughts in the setting of a
controversy. Plast Reconstr Surg 2009;123:949-953.
2. Stylianos K, Constantinos P, Alexandros T, Aliki F, Nikolaos A, Demetriou M, et
al. Muscle abnormalities of the chest in Poland's syndrome: variations and
proposal for a classification. Surg Radiol Anat 2012;34:57-63.
3. Fokin AA, Robicsek F. Poland's syndrome revisited. Ann Thorac Surg
2002;74:2218-2225.
4. Gulekon IN, Turgut HB. The prevalence of cervical rib in Anatolian population.
Gazi Med J 1999;10:149152
5. Viertel VG, Intrapiromkul J, Maluf F, Patel NV, Zheng W, Alluwaimi F, et al.
Cervical ribs: a common variant overlooked in CT imaging. AJNR Am J
Neuroradiol 2012;33:2191-2194.
6. Mentzel HJ, Seidel J, Sauner D, Vogt S, Fitzek C, Zintl F, et al. Radiological
aspects of the Poland syndrome and implications for treatment: a case study
and review. Eur J Pediatr 2002;161:455-459.
7. Zhu L, Zeng A, Wang XJ, Liu ZF, Zhang HL. Poland's syndrome in women: 24
cases study and literature review. Chin Med J (Engl). 2012 Sep;125(18):3283-
7.
8. Galiwango GW, Swan MC, Nyende R, Hodges AM. Poland syndrome with
dextrocardia: case report. East Afr Med J 2010;87:469-472.
9. Cingel V, Bohac M, Mestanova V, Zabojnikova L, Varga I. Poland syndrome:
from embryological basis to plastic surgery. Surg Radiol Anat 2013;35:639-646.
10. Wechselberger G, Hladik M, Reichl H, Ensat F, Edelbauer M, Haug D, et al. The
transverse musculocutaneous gracilis flap for chest wall reconstruction in male
patients with Poland's syndrome. Microsurgery 2013;33:282-286.
11. Brewin J, Hill M, Ellis H. The prevalence of cervical ribs in a London population.
Clin Anat 2009;22:331-336.
12. Mangrulkar VH, Cohen HL, Dougherty D. Sonography for diagnosis of cervical
ribs in children. J Ultrasound Med 2008;27:1083-1086.
13. Galis F. Why do almost all mammals have seven cervical vertebrae?
Developmental constraints, Hox genes, and cancer. J Exp Zool 1999;285:19-
26.


2014 Prasad et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Prasad BK, Talwar R, Kumar M: Surgical approach in giant retrosternal goiter. El Mednifico Journal 2014, 2(3):286-287.
Surgical approach in giant retrosternal goiter
Bipin Kishore Prasad
1
, Rajnish Talwar
2
, Manoj Kumar
3

Introduction
Retrosternal goiter is the thyroid enlargement that, with stretched
neck, goes beyond superior thoracic inlet for at least 3 cm into the
mediastinum and that preserves, generally, the parenchymal or fi-
brous connections between the cervical and thoracic portions, main-
taining a direct vascularization supplied by thyroid arteries [1]. The
prevalence of retrosternal goiter is variable and fluctuates between
1.7% and 30% of all thyroid masses [2].
The treatment of retrosternal goiter is surgery as it inevitably be-
comes symptomatic. Although in most cases the excision of ret-
rosternal goiter can be done exclusively via a cervical collar incision,
the surgeon should be prepared for a thoracic approach in select
situations where removal is fraught with risk. Contrast enhanced CT
scan plays a key role in guiding the surgeon as it defines the size,
shape, extent and its relationship with vital structures in the medias-
tinum. Median sternotomy provides the most direct approach and
ensures resection in toto. The technique is safe, expeditious and ef-
fective. It is associated with minimal risk of blood loss from a major
vessel injury.
Case Presentation
A 49 years old woman was admitted with the complaints of short-
ness of breath, chest discomfort and occasional choking for 6
months. She also gave history of swelling in front of the neck for 16
years. She was diagnosed to be hypothyroid for past 4 years and was
on daily medication with 100 gm thyroxine. She was a bull necked
short stature obese hypertensive lady. Her respiratory rate was 20
per minute. Other vital parameters were normal. She used to become
breathless on lying supine and also on mild physical exertion. Her
face was puffy and lower eyelids were edematous. Trachea was de-
viated to the right. A 7x6 cm enlarged thyroid gland was palpable in
the neck, lower margin of which extended into the thorax through
thoracic inlet. She had bilateral jugular vein distension. The veins on
the superior thoracic wall were engorged and tortuous.
Intratracheal wheeze could be heard on auscultation. CECT scan of
neck and upper chest demonstrated a large mass replacing the nor-

1
Department of Ear Nose and Throat, Military Hospital, Kirkee, Pune, India
2
Department of Surgery, Army Hospital, New Delhi, India
3
Department of Ear Nose and Throat, Military Hospital, Roorkee, India
mal thyroid involving both lobes and isthmus. The mass was essen-
tially homogeneous with a few areas of calcification seen within. In
the neck, the right lobe measured 46x41 mm in cross section and
the left lobe measured 74x48 mm (Figure 1).

The mass extended inferiorly for a distance of 13 cm into the thorax
behind the manubrium and sternum, till the level of arch of aorta.
The arch was displaced posteriorly by the mass. There was severe
compression of superior vena cava and the brachiocephalic veins
(Figure 2). Prominent tortuous venous channels were seen in the su-
perficial planes of the neck, arms and upper chest. The azygos vein
was also unusually prominent. The trachea was compressed in an
antero-posterior axis with the diameter being reduced to 10 mm in
this axis. In the mediastinum the goiter measured 80x74 mm,
whereas the stalk connecting the cervical and mediastinal compo-
nent measured 40x32 mm, thus giving the goiter a dumbbell shape.
A final diagnosis of a giant dumbbell shaped goiter with huge ret-
rosternal extension, tracheal compression and superior vena cava
syndrome was made.
The patient was operated after necessary pre-operative evaluation.
Neck was opened with a lower collar incision and chest was opened
by a median sternotomy (Figure 3). There was a large multinodular
goiter measuring 12x10 cm in the neck with upper poles extending
superiorly up to submandibular glands. Middle stalk of this dumbbell
Correspondence: Bipin Kishore Prasad
Email: bipin1405@gmail.com
Abstract
Background: A retrosternal goiter occurs when thyroid enlarges downwards into the mediastinum. The natural history is of slow relentless
increase in size causing airway compression, venous compression and swallowing problem. The management of a retrosternal goiter,
symptomatic or asymptomatic and with or without suspicion of malignancy is surgical. Majority of benign retrosternal goiters can be delivered
and resected through a standard neck incision. Rarely, however, some cases require additional thoracic access.
Case Presentation: A case of giant dumbbell shaped benign retrosternal goiter meriting a planned median sternotomy is reported.
Conclusion: Careful evaluation of CECT scan and a planned cervico-thoracic exposure in select cases ensures safe resection of the tumor
avoiding major vascular catastrophe. (El Med J 2:3; 2014)
Keywords: Dumbbell Shaped, Retrosternal, Goiter, Superior Vena Cava Syndrome, Median Sternotomy, CECT Evaluation

Figure 1: CECT scan of neck and upper chest showing large goiter
involving both the lobes and isthmus. The right lobe measured
46mm x 41mm and the left lobe, 74mm x 48mm in cross section.
Prasad BK, Talwar R, Kumar M 287
shaped goiter at the level of thoracic inlet measured 4x3 cm. Lower
portion that extended down retrosternally into the thorax below the
brachiocephalic veins measured 8cx8 cm. Total thyroidectomy was
done preserving both parathyroid glands and recurrent laryngeal
nerves. The giant goiter was removed in toto (Figure 4).

Discussion
Most patients with retrosternal goiters have the clinical manifesta-
tions of cervical mass, dyspnea, hoarseness, superior vena cava syn-
drome, dysphagia, pericardial effusion, thyrotoxicosis caused by
toxic multinodular goiter and so on [3, 4]. Presenting symptoms are
generally related to the compressive nature of the mass on nearby
structures. Pre-operative evaluation includes thyroid function test,
chest radiography, fiberoptic flexible tracheoscopy and CT scan. In
selected cases, magnetic resonance imaging of the neck and medi-
astinum is useful for a better anatomic definition of the lesion, show-
ing its rapport with the aerial, digestive and vascular structures in
order to establish the most appropriate surgical approach [5].
Majority of retrosternal goiters are symptomatic and need surgery.
Asymptomatic mediastinal goiters also must be resected because all
of them will ultimately cause respiratory compromise. In addition
they also carry a risk of malignancy in a rapidly growing dominant
nodule in the mediastinal component, which cannot be otherwise
biopsied. Surgical options include subtotal thyroidectomy depend-
ing upon available normal tissue in the tracheo-esophageal groove
thus ensuring normal thyroid and parathyroid function or near total
thyroidectomy in the event of an anatomical finding of a ledge of
thyroid tissue around the berry ligament entrapping the RLN, just as
in any other benign multi nodular goiter. It has however been rather
logically suggested by many experienced thyroid surgeons that the
operation of choice in RSG should be near total/total thyroidectomy
thus reducing to zero the need for revision surgery due to regrowth
of retained thyroid tissue.
Since the retrosternal goiters derive their blood supply from cervical
vascular pedicle, despite the clinical and radiological evidence of
their large size and significant descent into the mediastinum, major-
ity of them can be delivered from the neck with a low collar incision.
Transcervical approach can be assisted by using traction on the me-
diastinal component and laryngeal nerve monitoring. The right
plane of dissection under the strap muscles makes the corner stone
of cervical delivery. CT scan is the most important investigation in
pre-operative planning in resection of a retrosternal goiter. Pub-
lished literature advocate additional surgical access in cases, where
the CT scan demonstrates: (i) more than 70% size of goiter below
the thoracic inlet, (ii) distal dislocation of the left brachiocephalic
vein, (iii) distal border of goiter below the level of aortic arch, (iv)
extension to posterior mediastinum or (v) size of the mediastinal
component larger than the thoracic inlet. This article stresses the
need for median sternotomy in cases of dumbbell shaped retroster-
nal goiters with a narrow stalk joining the cervical and thoracic com-
ponents.
There are many options for additional surgical access. Clavicular dis-
location or division to increase the space of the thoracic inlet has
been described to deliver large retrosternal goiter [6]. Anterior me-
diastinotomy preserving the costal cartilage and the internal thoracic
vessels for extra-pleural exploration of goiter has been advocated as
Morzouks procedure to avoid median sternotomy [7]. Partial mid-
line/anterolateral sternotomy or partial upper manubriotomy are
also considered in some cases. Median sternotomy is the only ap-
proach that permits widest exposure in cases of giant mediastinal
goiter, life threatening superior mediastinal compression and in ma-
lignant retrosternal goiters. It is easy and most direct access to ex-
plore retrosternal goiter.
Received: 6 February 2014 Accepted: 27 July 2014
References
1. Batori M, Chatelou E, Straniero A, et al. Substernal goitres. European Review
for Medical and Pharmacological Sciences 2005; 9: 355 359.
2. Porzio S, Marocco M, Oddi A, et al. Gozzo endotoracico: considerazioni
anatomo-cliniche e terapeutiche. Chir Ital 2001; 53: 453 460.
3. Melliere D, Saada F, Etienne G, et al. Goitre with severe respiratory
compromise: evaluation and treatment. Surgery 1988; 103: 367 373.
4. Moran JC, Singer AJ, Sardi A. Retrosternal goiter: a six year institutional review.
Ann Surg 1998; 64: 889 893.
5. Calo PG, Tatti A, Farris S, et al. Substernal Goitre; personal experience. Ann Ital
Chir 2005; 76: 331 335.
6. Picardi N, Di Rienzo M, Annunziata A, Bartolacci M, Relmi F. Transclavicular
approach for delivery of intrathoracic giant goitre: an alternative surgical
option. Ann Ital Chir 1999; 70 (5): 741 748.
7. Rathinam S, Davis B, Khalil-Marzouk JF. Marzouks Procedure: a novel
combined cervical and anterior mediastinotomy technique to avoid median
sternotomy for difficult retrosternal thyroidectomy. The Annals of Thoracic
Surgery 2006; 82: 759 760.

Figure 2: CECT scan of neck and upper chest showing large goitre
extending inferiorly for a distance of 13 cm into the thorax till arch of
aorta. The arch was displaced posteriorly by the mass.
Figure 3: Per-op photograph showing
the neck opened with a lower collar
incision and chest opened by a
complete median sternotomy.
Figure 4: Excised specimen of giant
dumbbell shaped goiter measuring 12cm
x 10cm in the neck, 4cm x 3cm middle
stalk at thoracic inlet and 8cm x 8cm
lower retrosternal component.

2014 Tugmen et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Tugmen C, Kebapci E, Sert I, Tanrisev M, Colak H, Pekcevik Y, Dogan SM, Olmez M, Karaca C: Kidney transplantation from a donor with nutcracker syndrome. El Mednifico Journal 2014, 2(3):
288-290.
Kidney transplantation from a donor with nutcracker syndrome
Cem Tugmen
1
, Eyup Kebapci
1
, Ismail Sert
1
, Mehmet Tanrisev
1
, Hlya Colak
1
, Yeliz Pekcevik
1
, Sait Murat Dogan
1
, Mustafa Olmez
1
,
Cezmi Karaca
1

Introduction
Nutcracker syndrome (NCS) is a rarely encountered condition. In its
well-known form, left renal vein is compressed between aorta and
superior mesenteric artery (anterior nutcracker). Rarely, left renal
vein can be compressed between aorta and vertebral bodies (poste-
rior nutcracker) [1, 2]. Pitotic position of the left kidney and abnormal
diverging angle of superior mesenteric artery from aorta are sug-
gested as the etiology [1, 2]. The compression increases the pressure
in left renal vein. Left kidney and left gonadal organs are also af-
fected because of their drainage into the left renal vein.
NCS may be seen in all age groups but its prevalence peaks at 2
nd

and 3
rd
decades [1, 3]. NCS may occur with clinical symptoms like
gross or microscopic hematuria, pain in left lumber and left lower
abdomen, orthostatic proteinuria, gynecological symptoms due to
pelvic congestion in females and varicosele in males. If NCS is sus-
pected, the diagnosis can be made by Doppler ultrasonography (US),
computed tomography (CT), and magnetic resonance imaging
(MRI). The treatment is determined according to the seriousness of
symptoms.
In this case report, we describe a 31 year old female who was referred
to living-donor kidney transplantation diagnosed with NCS during
preoperative investigations. Transplantation process and post-trans-
plantation course have been discussed according to literature.
Case Report
A 31 year old female was referred to our transplant center as a kidney
donor for her husband. Preoperative evaluation was performed. Bio-
chemical, immunological, and microbiological tests were acceptable
for both the recipient and donor. Renal failure etiology was unknown
in kidney recipient candidate. Donor and recipient had consanguin-
eous marriage. Tissue typing analysis revealed two-haplotype match.
The cross-match tests were negative. The donor had no complaints
to indicate the nutcracker syndrome.

1
Tepecik Training and Research Hospital, Turkey.
Correspondence: Ismail Sert
Email: drismailsertege@yahoo.com
In preoperative donor evaluation, both right and left kidney size and
parenchyma thickness of donor were similar in CT angiography (Aq-
uilion 64; Toshiba Medical Systems, Tochigi, Japan). In axial section
images, It was determined that left renal vein was compressed be-
tween aorta and superior mesenteric artery. The diameter of left re-
nal vein was 13 mm before the compression site and it was 3 mm in
compressed region. In sagittal plane images, aorta-mesenteric angle
(AMA) was measured as 24.2
o
[Figures 1(a), 1(b), 1(c)].
Abdominal US revealed that volume of left ovary was higher than
the right one and left ovary had a 2 x 3 cm complicated cyst. Micro-
scopic hematuria and proteinuria were detected in spot urine test of
the donor. In 24-hour urine collection of the donor, 440 mg/dl pro-
teinuria was detected. Glomerular filtration rate (GFR) was measured
as 96 ml/min. In order to evaluate functions of both kidneys, dynamic
kidney scintigraphy was performed. DMSA (dimercaptosuccinic acid)
uptake of left kidney was minimal non-homogenous and both kid-
neys functions were approximately equal. We decided to perform
left nephrectomy to the donor with available anatomo-pathological
imaging.
During the donor nephrectomy, mild dilatation was seen in renal
vein, left gonadal vein, left adrenal vein, and left lumbar vein. When
dissection was continued to where the renal vein pours into vena
cava inferior, the point where superior mesenteric artery had com-
pressed left renal vein was revealed and small regional varices were
observed (Figure 2). In order to not harm the kidney and the donor,
the dissection was finalized and the surgical procedure was com-
pleted after performing the transaction from the proximal site of
compressed renal vein. The other parts of kidney anatomy were nor-
mal. The removed left donor kidney was transplanted into right in-
guinal region of the recipient.
During the postoperative follow up of the donor, proteinuria and mi-
croscopic hematuria continued during the first and second week, he-
maturia disappeared in urinalysis of the donor. At first week, there

Abstract
Background: Nutcracker Syndrome (NCS) is a rarely encountered clinical condition. In NCS, due to the compression of the left renal vein
between aorta and superior mesenteric artery, outflow of the left renal vein is impaired. It may occur with the symptoms like hematuria,
proteinuria, pain on the left lumber, lower abdomen, varicocele and pelvic congestion or asymptomatic. In suspected cases, the diagnosis
can be established by the radiological imaging.
Case Presentation: In this case report, a 31 year old female who was referred to a live kidney donor diagnosed with NCS during preoperative
evaluation is described. Transplantation process and post-transplantation course have been discussed according to literature. This case
report is unique due to being the first report describing allogeneic kidney transplantation performed from a donor with NCS.
Conclusion: In nutcracker syndrome, surgical treatment is recommended for the patients with serious symptoms. Surgical interventions
and stenting are treatment modalities and this article suggests a new approach. It may be meaningful in terms of reporting the first
successful allogeneic transplantation performed from a donor with NCS. (El Med J 2:3; 2014)
Keywords: Nutcracker Syndrome, Kidney Transplantation, Living Donor
Tugmen C, Kebapci E, Sert I et al. 289
was 195 mg/dl proteinuria in 24-hour urine collection. GFR level de-
creased down to 55 ml/min. At second week, proteinuria was 127
mg/dl in 24-hour urine collection; GFR was 54 ml/min.

In preoperative evaluation of the recipient, proteinuria at nephrotic
syndrome level and hematuria was detected. At first week, pro-
teinuria in 24-hour urine collection sample decreased down to 950
mg/dl. GFR was 75 ml/min. At second week, GFR was 84 ml/min, he-
maturia was disappeared and 571 mg/dl proteinuria was detected in
24-hour urine collection. Glomerular, interstitium and tubular struc-
tures had ordinary morphology in analysis of 0 hour biopsy material
of the graft.
Discussion
Nutcracker syndrome had no self-specific symptoms. The most fre-
quent symptom is hematuria. Hematuria is generally microscopic
and induced by rupture of thin-walled varicose veins developed in
collecting duct system as a result of high pressure in renal vein [1, 2,
4]. Pain spreading from left lumbar to left inguinal region is a sec-
ondary frequent finding in this entity. The pain can be associated
with venous congestion, can also be secondary to hematuria in left
ureter and is aggravated by walking, sitting, standing and running
[5]. Depending upon the pelvic congestion, varicocele in males and
dyspareunia, dysuria, dysmenorrhea and polycystic ovary in females
can be detected. These findings are supported with varicose vein
structures that can be identified on left side of patient by the radio-
logical analysis [5, 6].
The proteinuria is the other possible clinical feature of the NCS. The
protein leak in calyceal system may occur depending on the in-
creased pressure and postural changes affect the degree of the pro-
teinuria [1, 2]. The prevalence of the proteinuria in NCS is 0.6-10.7%
[1, 2]. In this case, 24-hour urine collection revealed proteinuria over
400 mg/dl.
Low body mass index (BMI) is also correlated with NCS. Previously, it
has been reported that the due to intense loss of weight, decreasing
the retroperitoneal fat tissue causes the aorto-mesenteric angle
(AMA) to become narrower and as a result NCS may occur [1]. In our
case, BMI of donor was 19.
In NCS, the diagnosis is mainly established by imaging methods. Ra-
diological findings should be supplemented by physiological flow
information (ultrasound and/or catheter based venography). In Dop-
pler US flow patterns of main renal vein and collateral veins, varicose
formations, retrograde blood flows may be evaluated and vein diam-
eters measured [3]. In recent years, multi-detector CT angiography
and MR angiography images have been reported to be highly effi-
cient for diagnosis. If the rate is determined over 4:1 in axial sections
of CT when comparing proximal normal renal vein diameter and di-
ameter of narrow part and if the AMA measurement on sagittal
planes is narrower than 50
o
, then the diagnosis can be established
with the accompanying symptoms [7]. AMA is approximately 90
o
in
normal individuals [8, 9].
Kidney biopsy findings are usually normal or non-specific in NCS [6].
Hence, kidney biopsy is generally performed for differential diagno-
sis, to eliminate renal malignancies and other diseases associated
with hematuria-proteinuria. For symptomatic NCS patients treat-
ment is recommended. Treatment modalities include intravascular
stenting, left renal vein bypass, left renal vein transposition, superior
mesenteric artery transposition, renal to inferior vena cava shunt and

Figure 1(a): The compression of renal vein between superior
mesenteric artery and aorta is seen on axial section.

Figure 1(b): The image of compressed renal
vein and aorta-mesenteric angle measurement
on sagittal plane are monitored.

Figure 1(c): Left kidney and renal vein
compression was demonstrated on 3-dimension
image of CT imaging.

Figure 2: Left renal vein and left gonadal vein,
adrenal vein is ligated above. Superior mesenteric
artery is seen distally to renal vein (black arrow).
290 Kidney transplantation from a donor with nutcracker syndrome
Vol 2, No 3
auto-transplantation [1]. The aim is to correct renal vein blood flow.
After the treatment, hematuria disappears in a few days.
A patient with NCS for whom auto-transplantation is an alternative
for treatment can also be a kidney donor as in this case, where the
left kidney was chosen as a graft. If the donor is symptomatic, most
of the present symptoms will probably disappear after graft nephrec-
tomy as in this case. Because the phenomenon does not cause a
pathological problem at glomerular and tubular level in kidney, graft
function of the recipient will have optimal progression. As in our
case, GFR of the recipient is at a fairly good level. The proteinuria in
the recipient is expected to decrease as the time progresses. When
the current kidney function of the donor was evaluated, the hema-
turia had disappeared. The glomerular filtration rate is expected to
decrease and proteinuria is expected to decrease after completing
the compensation of the rest kidney.
Conclusion
In nutcracker syndrome, surgical treatment is recommended for pa-
tients with serious symptoms. Surgical interventions and stenting are
treatment modalities and this article suggests a new approach. It
may be meaningful in terms of reporting the first successful alloge-
neic transplantation performed from a donor with nutcracker syn-
drome.
References
1. Kurklinsky AK, Rooke TW. Nutcracker phenomenon and nutcracker syndrome.
Mayo Clin Proc 2010; 85: 552-9.
2. Kur E, Baturca H, Kanylmaz M, Sargn M, Sahin S. Nutcracker sendromu. Trk
Gs Kalp Damar Cerrahisi Dergisi 2013; 21(1): 146-150.
3. Venkatachalam S, Bumpus K, Kapadia SR, Gray B, Lyden S, Shishehbor MH. The
nutcracker syndrome. Ann Vasc Surg 2011; 25: 1154-64.
4. Beinart C, Sniderman KW, Saddekni S, Weiner M, Vaughan ED, Jr, Sos TA. Left
renal vein hypertension: a cause of occult hematuria. Radiology 1982; 145(3):
647-50.
5. Scultetus AH, Villavicencio JL, Gillespie DL. The nutcracker syndrome: its role
in the pelvic venous disorders. J Vasc Surg. 2001; 34(5): 812-19.
6. Chen YM, Wang IK, Ng KK, Huang CC Nutcracker Syndrome: An Overlooked of
Hematuria 2002 Oct; 25(10): 700-5.
7. Buschi AJ, Harrison RB, Norman A, Brenbridge AG, Williamson BR, Gentry RR,
et al. Distended left renal vein: CT/sonographic normal variant. AJR Am J
Roentgenol 1980; 135: 339-342.
8. Fu WJ, Hong BF, Xiao YY, et al. Diagnosis of the nutcracker phenomenon by
multislice helical computed tomography angiography. Chin Med J (Engl) 2004;
117(12): 1873-5.
9. Shokeir AA, el-Diasty TA, Ghoneim MA. The nutcracker syndrome: new
methods of diagnosis and treatment. Br J Urol. 1994; 74(2): 139-143.


2014 Faridi et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Faridi SH, Siddiqui B, Aslam M: Giant unilocular hydatid cyst of spleen. El Mednifico Journal 2014, 2(3): 291-292.
Giant unilocular hydatid cyst of spleen
Shahbaz Habib Faridi
1
, Bushra Siddiqui
1
, Mohammad Aslam
1

Introduction
Hydatid disease is caused by the tapeworm Echinococcus granulosus.
The most common site of disease is the liver (75%) which is followed
by the lungs (15%) [1]. Rare sites include kidney, bones, muscles and
brain [2]. Splenic hydatid disease has been reported to constitute up
to 4% of cases of abdominal hydatid disease [3]. Primary hydatid cyst
of spleen is even rarer. The rarity of splenic hydatid disease poses a
diagnostic challenge. Operator dependent radiological techniques
are usually unable to add to the diagnostic accuracy. In such cases,
exploration and per operative decisions are worth practicing. The
drug treatment is only adjunct to the surgery.
Case Report
A 45 year old female patient presented to the surgical out-patient
department with the complaints of low grade fever, dull dragging
ache and a lump in the left upper abdomen since 4 months. Physical
examination revealed a slightly pale, obese woman. The abdomen
was soft and there was a slightly tender lump present in the left hy-
pochondrium suggestive of splenomegaly. Rest of the physical ex-
amination was unremarkable. Ultrasonography of abdomen showed
presence of a large unilocular cystic mass inside the spleen. Contrast
enhanced CT scan of abdomen was suggestive of isolated cyst with
crumpled endocyst inside the cyst occupying almost whole of the
spleen (Figure 1). No other cyst was seen in other abdominal organs
or peritoneal cavity. Radiograph of the chest was found to be normal.
The patient was subjected to laparotomy by left subcostal incision.
Peroperatively there was a splenic hydatid cyst occupying almost
whole of the spleen. All the other organs were found to be normal.
Splenectomy was done and the hydatid cyst was removed (Figure
2). Histopathological examination showed characteristic cuticular
layer of the cyst wall in the form of amorphous densely staining lam-
inated chitinous material (Figure 3) and scolices were demonstrated
in the fluid from the cyst confirming the diagnosis of hydatid cyst.

1
JN Medical College, AMU, Aligarh, UP, India.
Correspondence: Shahbaz Habib Faridi
Email: shahbazfaridi@yahoo.com

Discussion
Hydatid disease is caused by the genus Echinococcus and it is en-
demic in Eastern Europe, Middle East, South America, North Africa,
Indian subcontinent, Australia and New Zealand [4]. Mean incidence
of splenic hydatid cyst in India is 4.3% with highest incidence in Cen-
tral India [5]. The disease affects all age groups and both sexes with
equal frequency. Dogs are the definitive host and human beings act
as an accidental intermediate host in the disease process.

Abstract
Background: Hydatid cyst of spleen is a very rare condition. It is usually secondary to spread of cysts from other regions. Primary hydatid
cyst of spleen without involvement of any other organ is even rarer. Here, we report a case of a giant unilocular hydatid cyst of spleen
without involvement of any other organ. The patient underwent laparotomy and splenectomy was done. This case report aims at reporting
a rare case of a primary giant unilocular hydatid cyst of spleen and describes its management.
Case Presentation: A 45 year old female presented to the surgical outpatient department with complaint of fever, dull dragging ache and
lump in the left upper abdomen. On examination there was a slightly tender lump in the left hypochondrium suggestive of splenomegaly.
Ultrasonography and computed tomography of abdomen were suggestive of a giant unilocular splenic hydatid cyst. The patient was
operated and splenectomy was performed. The patient was discharged on albendazole therapy and the follow-up was uneventful.
Histopathological examination of the specimen confirmed the presence of hydatid cyst.
Conclusion: Primary hydatid cyst of spleen is a very rare condition. Surgery remains the mainstay of treatment. The evolving concept is
towards splenic preservation surgery with cyst enucleation to prevent overwhelming post-splenectomy infections. (El Med J 2:3; 2014)
Keywords: Hydatid Cyst, Echinococcus granulosus, Splenomegaly; Splenectomy

Figure 1: Contrast enhanced CT abdomen showing splenic
hydatid cyst with calcification of the walls.

Figure 2: Cut section of the splenectomy specimen
showing cystic cavity.
292 Giant unilocular hydatid cyst of spleen
Vol 2, No 3

Splenic hydatid cyst has been classified in to ascending (immobile)
and descending (mobile) types by Dieulafoy (1898) and into cortical,
central and juxtasplenic types as per location of the cyst [6]. The larg-
est cyst ever reported was in Australia and it contained 57 litres of
fluid [7]. Approximately 30% of splenic cysts are asymptomatic and
detected incidentally. In addition, 40% have no detectable physical
signs [8]. Laboratory evaluation of patients with hydatid disease of-
ten yields non-specific data. Elevated levels of IgE levels are a non-
specific indicator of prior sensitization or active infection with para-
sitic organisms, while elevated levels of IgM classes specific to echi-
nococcal organisms may be a sensitive indicator or recurrent disease
[5]. Serum immunoelectrophoresis is currently the most reliable,
with a sensitivity of approximately 90%, with 1 year positivity after
the organism has been eradicated [9]. The Casoni intradermal skin
test, indirect hemagglutinition and ELISA had also been used. The
main problem in the diagnosis of splenic hydatidosis is in differenti-
ating it from other splenic cystic lesions, such as epidermoid cyst,
pseudocyst, abscess, hematoma, and cystic neoplasm of the spleen
[10].
More definitive diagnosis is based on abdominal ultrasound and CT
scan which have greater sensitivity and specificity [11]. On ultra-
sound scan of abdomen, splenic hydatid cyst may present as a soli-
tary unilocular or rarely multiple well defined anechoic spherical
cystic lesions or may demonstrate an anechoic spherical cystic lesion
with hyperechoic marginal calcification as seen in this case. CT ab-
domen confirms the cystic lesion with or without daughter cysts
within the spleen with attenuation value near that of water and does
not enhance after intravenous contrast administration. It is more sen-
sitive than ultra sonography in depicting subtle wall calcification
[12]. The treatment of hydatid cysts is principally surgical. Medical
treatment which comprises of albendazole (10 mg/kg/day for 6
months) can only complement surgery but cannot replace it.
However, pre-operative and post-operative 1-month courses of al-
bendazole and 2 weeks of praziquantel should be considered in or-
der to sterilize the cyst [13]. Intra-operatively, the use of hypertonic
saline or 0.5% silver nitrate solutions before opening the cavities
tends to kill the daughter cysts and therefore prevent further spread
or anaphylactic reaction.
Since 1980 there has been a trend towards splenic conservation to
avoid overwhelming post-splenectomy infection (OPSI) [14]. For
conservation of the spleen, enucleation of a unilocular cyst can be
done.
Conclusion
Isolated hydatid cyst of spleen in the absence of involvement of any
other organ is a very rare presentation. Surgery remains the mainstay
of treatment with medical treatment as the adjunct only. The evolv-
ing concept is towards splenic preservation surgery with cyst enu-
cleation to prevent overwhelming post-splenectomy infections. If
the cyst involves whole of the spleen or there are multiple cysts then
splenectomy is the only answer.
References
1. Kiresi DA, Karabacakoglu A, Odev K, Karakose S. Uncommon locations of
hydatid cysts. Acta Radiol 2003;44:622-36.
2. Engin G, Acunas B, Rozanes I, Acunas G. Hydatid disease with unusual
localization. Eur Radiol 2000;10:1904-12.
3. Celebi S, Basaranoglu M, Karaaslan H, et al. A splenic hydatid cyst case
presented with lumbar pain.Intern Med. 2006;45:10234.
4. Seymour I, Schwartz, Harold Ellis, Maingot's Abdominal Operations. Tenth
edition Vol II, 1534-45.
5. Bhandarwar AH, Katara AN, Bakhshi GD, Rathod MG, Quraishi AM. Splenic
Hydatidosis. Bombay Hosp J 2002;44:656-63.
6. Mills HW. Hydatid cyst of the spleen, with report of four cases. Gynaec Obst
1924; 38 : 491-505.
7. Manson-Bahr PEC, Apted FIC. Mansons Tropical Diseases, ELBS 18th edition,
1981; 245.
8. Qureshi MA, Haffner CD. Clinical manifestations of splenic cysts, study of 75
cases. Am Surg 1965; 31 : 605-9
9. Aquise M, Garca E, Aquise A, Pellicer MR, Pellicer JL. A Gyant Splenic Hydatid
Cyst Case Presented with Dyspnea and Fever. Medicrit 2009; 6(1):54-57.
10. Adas G et al. Diagnostic problems with parasitic and non-parasitic splenic
cysts. BMC Surgery 2009, 9:9.
11. Merino NH, Morte AJ etal. Splenic hydatid cyst. A report of 16 cases (Article in
Spanish). EV ESP Enferm Dig 1991;79:254-8.
12. Kalouidouris A, Pissilosis C, Pontifex G. CT characterization of multivesicular
hydatid cysts. J Comput Assist Tomogr 1984; 8:839-45.
13. Bildik N, Cevik A, Altinta M, Ekinci H, Canberk M, Glmen M. Efficacy of
preoperative albendazole use according to months in hydatid cyst of the liver.
J Clin Gastroenterol. 2007 Mar;41(3):312-6.
14. Ibrahim HH, Mustafa NA. Preservation of spleen in hydatid cystic disease
without intracavatory injection of scolecidal agents. Yemeni journal for
medical sciences (2009) 1(3).

Figure 3: Pictomicrograph shows characteristic cuticular
layer of the cyst wall in the form of amorphous densely
staining laminated chitinous material.

2014 Karaca et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Karaca F, Ozden F, Sert F: Merkel cell carcinoma of the head and neck: A case presentation in the light of literature. El Mednifico Journal 2014, 2(3): 293-295.
Merkel cell carcinoma of the head and neck: A case presentation in the light of literature
Feryal Karaca
1
, Ferhat Ozden
1
, Fatma Sert
2

Introduction
Merkel cell carcinoma was first identified by Toker as trabecular skin
disease seen in elderly Caucasians and having high risk for lymphatic
metastasis [1]. In 1983, Frigerio et al. reported 15 tumor cases de-
rived from Merkel cells of the skin [2]. Merkel cells are slowly acti-
vated neuroendocrine cells located in the dermo-epidermal junction.
Merkel cell carcinoma is a rare malignancy of the skin, having aggres-
sive course, high risk for local recurrence and distant metastasis and
low overall survival.
Merkel carcinoma of the skin, is also called trabecular carcinoma, cu-
taneous neuroendocrine carcinoma or Merkeloma. It is a rare highly
malignant skin tumors derived from Merkel cells located in basal
layer of epidermis. These cells are associated with sensory neurons
that serves as mechanoreceptors in dermal papillae. Merkel cell car-
cinoma is seen in elderly Caucasian with an equal male/female ratio.
Seventy eight percent of patients are over 59 ages old. Under the
age of 60 male/female ratio is almost the same but it usually occurs
in women over the age of 60 [3, 4].
50.8% of tumors are seen in head and neck and 33.7% of them in
extremities. Although the exact etiology is unknown, it is assumed
to be related with ultraviolet rays, immunosuppression and poly-
omavirus [5]. It has been shown to be related with immunosppres-
sion induced by polyomavirus. Immunologic course of Merkel cell
carcinoma is very interesting. In some cases complete remission has
reported [6].
Patients are treated according to favorable and unfavorable criteria.
Primary resection and adjuvant radiotherapy is the treatment for fa-
vorable localized disease. Age over 70, male gender, lesions on trunk,
head and neck (especially on lips), diameter of primary lesion >2cm,
first presentation with metastatic lymph node (especially >2 lymph
node metastasis), distant metastasis, small cell variant with high mi-
totic index, deeply located lesion, lymphovascular invasion, lesions
having infiltrative growth pattern are all unfavorable criteria and
those patients have aggressive disease course and poor survival [7].
To obtain long-term disease control, first surgical resection must be

1
Van Regional Training and Research Hospital, Van, Turkey.
2
Ege University Medical School, Izmir, Turkey.
Correspondence: Fatma Sert
Email: gracilis81@yahoo.com
made with negative margins. The initial approach for the primary
tumor is wide excision. It affects overall survival and disease free sur-
vival significantly (p=0.008) [7, 8]. Sentinel lymph node biopsy
should be taken before definitive local excision. Surgical resection
must be done with a tumor free margin of 1-2 cm. However, if it is
not possible cosmetically or functionally, surgery can be done with
close or positive margin. In these cases adjuvant radiotherapy should
be used after surgery. There exist false positive results in sentinel
lymph node sampling of the head and neck. More than one lymph
node sampling must be done because of different lymph node drain-
ages. Mainly immunohistochemical examination must be made for
the sentinel lymph node biopsies. Regional lymph node involvement
usually occurs early in the course. Lymph node involvement is seen
in 79% of patients throughout the disease. Sentinel lymph node sam-
pling must be done routinely during the operation even though no
lymph node positivity is detected clinically and radiologically.
Case Report
A 35 year old female patient presented with a growing lesion on the
right ear for about three months. After medical treatment, biopsy
was taken from the lesion. Merkel cell carcinoma diagnosis was given
and whole-body CT scans were ordered. A 5cm mass in the right
outer ear canal, millimetric reactive lymphadenopathies in right neck
and a lymph node in the right parotid gland were imaged. Also bi-
lateral ovarian cysts were reported (Figures include preoperative im-
ages). Right inferior 1/3 auricular resection, right superficial pa-
rotidectomy and right supraomohyoid neck dissection were per-
formed. Pathologic evaluation revealed Merkel cell carcinoma in the
outer ear canal and a 0.5 cm metastatic lymph node in right parotid
gland (Figure 1). Right neck level 1-2-3 lymph node dissections re-
vealed totally 37 lymph nodes with reactive hyperplasia. The patient
was evaluated as stage 3B and adjuvant radiotherapy was applied.
An adjuvant curative radiotherapy dose of 5600 cGY was given to
the patient. No pathological findings were observed in routine to-
mography during 18 months. However, whole-body tomography
was done because of abdominal pains and lobulated heterogeneous

Abstract
Background: Merkel cell carcinoma of skin is seen mostly in elderly Caucasians. Mortality and morbidity is very high. Treatment of these
cases is also quite difficult. Recommended treatment is primary total excision, sentinel lymph node dissection after sentinel lymph node
sampling and adding radiotherapy or chemotherapy according to stage.
Case Presentation: A 35 year old female patient had surgery because of an unhealed wound on the right ear. After giving adjuvant curative
radiotherapy the patient had been followed for 18 months. After 18 months of follow up, Merkel cell carcinoma metastasis was detected and
para-aortic metastatic mass was resected. The patient is being considered for chemotherapy.
Conclusion: Merkel cell carcinoma is an aggressive malignancy observed mostly in elderly Caucasians. Management consists of surgery with
adjuvant chemotherapy and/or radiotherapy in accordance with the stage. (El Med J 2:3; 2014)
Keywords: Merkel Cell Carcinoma, Head, Neck
294 Merkel cell carcinoma of the head and neck
Vol 2, No 3
soft tissue mass with a size of 10 cm axially and 12 cm cranio-caudally
was imaged (Figure 2). Tumor excision and bilateral oophorectomy
were performed. Pathology report revealed Merkel cell carcinoma
metastasis.

Discussion
Merkel cell carcinoma is an aggressive malignancy mostly seen in
Caucasian and in elderly immunocompromised patients in western
countries. Recent years have shown an increase in the elderly popu-
lation [9, 10].
Many surgeons think that aggressive surgical approach has an im-
portant role in long survival. There is no need for adjuvant radiother-
apy in patients who are operated with sufficient margin. Local recur-
rence rate is 39% and regional failure rate is 46% in patients treated
with local excision only. If patients are treated with wide local exci-
sion, prophylactic lymph node dissection and adjuvant radiotherapy,
there is less distant metastasis and overall survival increases [11, 12].
Patients who present with regional disease, chemotherapy and/or
radiotherapy can be given after wide local excision with lymph node
resection [13, 14]. Radiotherapy after surgery or chemotherapy is
highly effective [14, 15]. After chemotherapy protocol (cyclophos-
phamide, methotrexate and 5-fluorouracil), radiotherapy is proposed
to be given to patients with locally advanced disease.
The general approach is that external radiotherapy is given with a
standard dose of 1.8-2 Gy for 5-7 weeks by conventional method.
Altered fractionation is not recommended. Local recurrence rate is
8% even in a tumor of any localization resected with 2-5 cm surgical
margin. Even in patients operated with negative surgical margin,
sentinel lymph node excision or cervical lymph node dissection, local
recurrence rate is 11%. Lymph node involvement is detected in only
16% of patients with a 1.3cm primary tumor [16, 17]. Primary ap-
proach for Merkel cell carcinoma of the head and neck is wide local
excision followed by radiotherapy. Local control rates with surgery
only and surgery with adjuvant radiotherapy are 69% and 95% re-
spectively and p value is 0.020 [18].
Poulsen et al. gave carboplatin and etoposide with concurrent 50Gy
radiotherapy to 53 high-risk patients. Three-year loco-regional con-
trol outcomes were 71% and 45% respectively [19]. Fang et al. com-
pared radiotherapy only and radiotherapy fallowed by surgery in pa-
tients with clinically positive lymph node. In 2-year follow up, pa-
tients given radiotherapy only and radiotherapy followed by surgery,
loco-regional control rate in the arm was 78% and 73% respectively
(p=0.8).
Meeuwissen emphasized the importance of radiotherapy with sur-
gery in his series of Merkel cell carcinoma patients. All 38 patients
were treated with surgery only but recurrences occurred with an av-
erage of 5.5 months after the operation. On the other hand, 10 of
the 34 patients received radiotherapy after the surgery and the av-
erage recurrence time was 16.5 months [20]. Kuko et al. gave radio-
therapy to tumor bed after surgery in patients other than stage 1 or
2 but even so local recurrences occurred [21].
Lymphatic radiotherapy is recommended in case of sentinel lymph
node involvement or extracapsular invasion of sentinel lymph node.
If sentinel lymph node is not accessible or if there exists clinically
defined lymph node, lymph node radiotherapy is recommended by
National Comprehensive Cancer Network [22-24].
The role of adjuvant chemotherapy is limited. In many studies, chem-
otherapy is given alone or with adjuvant radiotherapy in primary
loco-regional high-risk disease. However, multivariate analysis show
that adding carboplatin and etoposide yields benefit to survival [25,
26].
In metastatic disease, treatment is palliative chemotherapy and radi-
otherapy. After surgical operation or in patients with unressectable
mass with distant metastasis, combined chemotherapies are recom-
mended. In metastatic disease, combined chemotherapy with etopo-
side, cisplatin, adriamycin and bleomycin may obtain complete re-
mission. However, in advanced disease other chemotherapy regi-
mens and long-term radiotherapy don't provide remission [14, 27-
30].
Conclusion
Merkel cell carcinoma is an aggressive malignancy observed mostly
in elderly Caucasians. Management consists of surgery with adjuvant
chemotherapy and/or radiotherapy in accordance with the stage.

Figure 1: Intraparotidal lymph node in axial slices of
computed tomography.

Figure 2: Abdominal mass in axial slices of computed tomography.

Karaca F, Ozden F, Sert F 295
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2014 Kayalvizhi et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Kayalvizhi G, Vishwas TD, Mahantesh R, Subramaniyan B: Dental management of severe early childhood caries. El Mednifico Journal 2014, 2(3): 296-298.
Dental management of severe early childhood caries
Gurusamy Kayalvizhi
1
, T D Vishwas
2
, R Mahantesh
3
, Balaji Subramaniyan
4

Introduction
Early childhood caries (ECC) is the rampant dental caries seen in in-
fants and toddlers. Early infection with mutans streptococci (MS) and
inappropriate feeding with a cariogenic diet are the main etiological
factors of ECC [1]. In children younger than 3 years of age, any sign
of smooth surface caries is indicative of severe early childhood caries
(S-ECC). From ages 3 through 5 years, one or more cavitated, missing
or filled smooth surfaces in primary maxillary anterior teeth or filled
score of >4 (age 3), >5 (age 4) or >6 (age 5) surfaces constitutes S-
ECC [2]. Its clinical appearance in 2-4 year old children is typical and
follows a definite pattern. There is early carious involvement of the
maxillary anterior teeth, the maxillary and mandibular first primary
molars, and sometimes the mandibular canines. The mandibular in-
cisors may or may not be affected [3].
It is one of the most difficult and challenging conditions confronting
the pedodontist from both a preventive and management stand-
point. The pedodontic treatment triangle plays a major role in suc-
cessfully performing full mouth rehabilitation in these children [4].
This paper presents oral rehabilitation of two severe early childhood
caries patients.
Case Presentation
Case 1
A 4 year-old boy accompanied by his mother reported to our depart-
ment with the chief complaint of pain in the lower left back tooth
region. Pain was dull and intermittent which aggravated on eating
food. Oral hygiene status of the child was poor. According to
Frankles behavior rating scale, he was rated positive. Medical his-
tory was unremarkable. Dietary interview was conducted wherein his

1
Department of Pedodontics and Preventive Dentistry, Indira Gandhi Institute of
Dental Sciences, Puducherry, India.
2
Department of Pedodontics and Preventive Dentistry, Hasanamba Dental College,
India.
3
Department of Pedodontics and Preventive Dentistry, Raichur, India.
mother was instructed to maintain a 7 day record of his diet, i.e. all
the food eaten at mealtime and between meals had to be recorded.
Diet chart evaluation showed high frequency of between meals
sweets/snacks intake.

Clinical examination revealed deeply carious tooth with pulpal in-
volvement in relation to 74 with an intraoral swelling. Root stumps
were present in relation to 52, 51, 61 and 62. Dental caries was pre-
sent with respect to 54, 64, 73, 72, 71, 81, 82, 83, 84 and 85 [Figure
1(a)]. Provisional diagnosis was made based on history, clinical ex-
amination as chronic periapical abscess in relation to 74, chronic ir-
reversible pulpitis in relation to 52, 51, 61 and 62. These findings
were further confirmed radiographically. With all the above data ob-
tained, diagnosis was confirmed as severe early childhood caries
[Figures 2(a), 2(b), 2(c)].
4
Sri Lakshmi Narayana Institute of Medical Sciences, Puducherry, India
Correspondence: Gurusamy Kayalvizhi
Email: drfisheyes22@gmail.com
Abstract
Background: Early childhood caries (ECC) is the new term given to dental decay in infants and toddlers. Severe ECC (S-ECC) is the most
devastating caries, which is typical and follows a definite pattern. It is diagnosed by its clinical appearance and history of the childs
nursing/dietary habits. This article focuses on complete oral rehabilitation of two S-ECC patients.
Case Presentation: Case 1: A 4 year-old boy accompanied by his mother reported to our department with the chief complaint of pain in
the lower left back tooth region. A diagnosis of S-ECC was made based on history, examination and radiographic findings. Preventive
regimens were enforced starting with parent counseling regarding oral hygiene. Case 2: A 6-year-old girl reported to our department with
the chief complaint of masticatory difficulty and food lodgment in the upper right and left back tooth region. With detailed history and
examination, a diagnosis of S-ECC was made. Again management was started by enforcing preventive treatment protocols with diet
counseling, oral hygiene and brushing instructions, use of fluoridated tooth paste and professional acidulated phosphate fluoride
application.
Conclusion: Successful dental treatment for S-ECC can be rendered if the parents and the child are motivated and counselled. Treatment
should be aimed at modifying all the four factors in caries tetralogy. Because of its aggressive nature, treatment should be specific for each
individual patient. (El Med J 2:3; 2014)
Keywords: Severe, Caries, Children, Behavior, Diet, Prevention, Treatment

Figure 1: FDI tooth numbering system showing affected teeth in S-ECC
patients. (a) Case 1; (b) Case 2.
Kayalvizhi G, Vishwas TD, Mahantesh R et al. 297

Treatment was planned with parental consent. Preventive regimens
were enforced starting with parental counseling wherein oral hy-
giene instructions were given along with dietary counseling. They
were advised to follow basic diet and reduce in-between meal
snacks/sweets intake. Lesion sterilization and tissue repair therapy
(LSTR) was done with respect to 74 and was sealed with glass iono-
mer cement (GIC), followed by composite resin [Figures 3(a), 3(b)]
[5, 6]. Pulpectomy was done and coronal access was sealed with GIC
in 51, 52, 61 and 62. Lesions were temporized in 54, 64, 75, 84 and
85. During further visits, temporized 54, 64 and 65 were replaced
with miracle mix and 75, 84, 85 with GIC. Composite resin restora-
tions were done in 71, 72, 73, 81, 82 and 83, 51, 52, 61 and 62. Deep
fissure in 55 was sealed with pit and fissure sealant [Figures 4(a),
4(b), 4(c)]. Every 3 month recall visits were planned and imple-
mented, during which the childs dietary habits and oral health sta-
tus improved.

Case 2
A 6-year-old girl [Figure 1(b)] accompanied by her mother reported
to our department with the chief complaint of masticatory difficulty
and food lodgment in the upper right and left back tooth region.
Detailed history revealed that the pain was dull and intermittent with
history of swelling which subsided on medication. Medical history
was non-contributory. Behavioral history based on Frankles behav-
ior rating scale was rated positive. Diet history revealed that the
patient was on high cariogenic diet and had night time bottle feed-
ing habit with poor oral hygiene.
Clinical examination revealed grossly destructed 54, 64, and dental
caries with respect to 55, 52, 51, 61, 62 and 65. Deep dental caries
were seen in 74, 75, 84, and 85. Radiographic examination revealed
periapical infection in 54 and 64, and chronic irreversible pulpitis
with respect to 74, 75, 84 and 85. Mandibular incisors (71, 72, 81 and
82) remained unaffected. With detailed history and examination it
was confirmed as severe early child-hood caries [Figures 5(a), 5(b),
5(c)].

Preventive treatment was initiated with diet counseling, oral hygiene
and brushing instructions, use of fluoridated tooth paste and profes-
sional acidulated phosphate fluoride (APF) application. Extraction of
54 and 64 were done under local anesthesia followed by the place-
ment of band and loop space maintainer. Instructions were given
regarding the maintenance of the appliance. Restoration of 55 and
65 were done with silver amalgam. Endodontic treatment was done
in 84, 85 and 75 and stainless steel crowns were placed. LSTR therapy
was done in 74 and the tooth was kept under observation till exfoli-
ation. Composite resin build up was done in 52, 51, 61 and 62 (Fig-
ures 6(a), 6(b), 6(c)]. Patient was kept under observation with 6
monthly application of topical fluoride. Assessment of oral hygiene
status and dietary condition was done every 3 months.

Discussion
Although the etiology of ECC is similar to that of other types of cor-
onal smooth surface caries, the biology may differ in some respects
[7]. An appropriate diet history and review of feeding practices may
help arrive at a definitive diagnosis [8]. The first step in treating chil-
dren with ECC is to identify the offending habit or cariogenic diet.
All four factors involved in the caries process (pathogenic microor-
ganisms, host susceptibility, fermentable carbohydrates and time/
frequency of exposure) should be examined and modified [9]. Moth-
ers have a major influence on the dietary habits and food choices of
their infants, toddlers and children. Parents are the promoters of oral
hygiene practices; thus, motivational interviewing may help direct
parents improve not only their oral health habits but also of their
children, which was done in our cases [10]. Our patients were on
highly cariogenic diet, but in case 2, history of nighttime bottle feed-
ing practice was elicited. Therefore dietary counseling was planned,
wherein parents were instructed to modify their childs diet. A series
of small changes over a period of time was given to our patients, as
it was usually more acceptable to the child and the parents.
Figure 2: Preoperative view (Case 1).
(a) Frontal view; (b) Upper arch; (c) Lower arch.

Figure 3: LSTR therapy in 74 (Case 1). (a) Before; (b) After.

Figure 4: Post-operative view (Case 1).
Figure 5: Pre-operative view (Case 2).
Figure 5: Post-operative view (Case 2).
298 Dental management of severe early childhood caries
Vol 2, No 3
During examination of a child, the cooperative behavior of the pa-
tient has to be taken into account because it is a key in rendering
treatment. Here in both the cases we had used the Frankles behavior
rating scale which is a popular research tool used for recording chil-
drens behavior in dental office. In both the cases behavior was rated
positive [3]. Based on the history and examination, they were diag-
nosed as S-ECC. Early counseling of parents can prevent S-ECC. The
best current preventive strategy for children susceptible to dental
caries is the frequent application of fluoride at home and in dental
offices. The effective concentration of fluoride is directly dependent
on the carious activity and therefore children with ECC may require
more frequent applications of fluoride [10]. APF gel application was
done in our patient. As the patient was at high risk for caries, pit and
fissure sealant applications were done in primary molars (case 2).
Owing to the destructive nature of S-ECC, treatment ought to be
specific for each individual patient [11]. In both our cases, treatment
was initiated with temporization of the lesions followed by pulpal
therapy and permanent restorations. Pulpal therapy treated teeth
were further reinforced with stainless steel crowns. Examination of
74 in both the cases revealed intraoral swelling with inter-radicular
bone loss. Considering their age, it was not advisable to extract their
teeth, so a new endodontic technique - lesion sterilization and tissue
repair therapy (LSTR) - was tried and the tooth was kept under ob-
servation till exfoliation. This technique was selected as it is simpler
and found to be successful in the treatment of infected primary teeth
[5, 6]. Within a week, resolution of signs and symptoms were ob-
served. In case 2, the teeth (54, 64) which could not be retained were
extracted and to prevent space loss problems, space maintainer was
given.
The foundation of any successful dental practice is the recare system,
wherein ongoing, continual attention is given to the patients by 3 or
6 month visits [3]. The recall/recare schedule is based on clinical find-
ings and the results of risk assessment. Therefore, based on the cri-
teria for recall schedule determination, visits were planned in our pa-
tients [12].
Conclusion
Severe early childhood caries can be prevented with early diagnosis
and the identification of risk factors. If left untreated, it would cause
severe destruction of teeth demanding comprehensive dental care
to be initiated at an early age. As physicians and pediatricians are the
first people to interact with the parents and child, parental aware-
ness regarding its risk and complications should be enforced
through them. Successful management of ECC depends on a coordi-
nated team approach among the pediatrician, pediatric dentist, par-
ents and child.
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2014 Nirmala et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Nirmala SVSG, Dadeepya R, Lalitha V, Sivakumar N, Sandeep C: A case of Stevens-Johnson syndrome. El Mednifico Journal 2014, 2(3): 299-300.
A case of Stevens-Johnson syndrome
S V S G Nirmala
1
, R Dadeepya
1
, V Lalitha
1
, N Sivakumar
1
, C Sandeep
1

Introduction
Stevens-Johnson syndrome (SJS) is named after Steven and Johnson
who coined the term in 1922. SJS is a severe hypersensitive reaction
that can be precipitated by infection, vaccination, systemic diseases,
physical agents, foods and drugs [1]. The drugs that cause SJS com-
monly are antibacterials (sulfonamides), anticonvulsants (phenytoin,
phenobarbital and carbamazepine), NSAIDs (oxicam derivatives) and
oxide inhibitors (allopurinol) [2]. This syndrome may present as a
nonspecific febrile illness (malaise, headache, cough, rhinorrhea)
with oral and perioral involvement, polymorphic lesions of skin and
mucous membrane characterized by acute blisters and erosions. It is
a rare condition with an incidence of 0.05 to 2 persons per million
populations per year [3].
Case Report
A male child of 8 years was referred to the Department of Pedodon-
tics and Preventive Dentistry, Narayana Dental College and Hospital,
Nellore with the chief complaint of ulcers in the mouth since 3 days.
Past medical history revealed severe drug reaction one month back,
for which the patient attended a pediatric hospital elsewhere, where
it was diagnosed as SJS and the treatment was given for the same.
The parents had photographs of the child taken before the treat-
ment (Figures 1 and 2). This was the first dental visit of the patient.
The child weighed 15 kg and had average build. The child looked
weak. Family history was not contributory. On extraoral examination,
skin lesions were healed whereas intraoral examination revealed
multiple painful ulcers on upper and lower labial mucosa (Figures 3
and 4). The ulcers were oval in shape with inflamed borders. Upper
lip showed healing lesion with crust formation. Excess salivary secre-
tion was evident and there was painful cervical lymphadenopathy.
His parents explained that the child had fever one month back and
had gone to local pharmacist for the medicine. However, the parents
were not able to not tell the details of the medicine taken. After the

1
Department of Pedodontics and Preventive Dentistry, Narayana Dental College &
Hospital Nellore, Andhra Pradesh, India.
Correspondence: S V S G Nirmala
Email: nimskrishna2007@gmail.com
child took the medicines, he developed severe itching and vesicle
formation followed by ulceration overall the body, without remission
from fever. His symptoms became worse including generalized
weakness and toxicity. They went to a pediatric hospital where the
child was diagnosed as having SJS and was treated for the condition.
After one month of treatment, the child was referred to our depart-
ment because of the persisting oral ulcers. The treatment consisted
of topical application of hexigel and multivitamin supplements were
prescribed. On follow up after 15 days, examination showed healed
ulcers. The patient fully recovered within a month.

Discussion
SJS had for years been considered an extreme variant of erythema
multiforme (EM), with toxic epidermal necrolysis (TEN) being a dif-
ferent entity. A group of experts proposed a new classification in

Abstract
Background: Stevens-Johnson syndrome (SJS) is an acute self-limited disease. The incidence of this disease is low, but there is a significant
impact on child as well as parents because of its extensive involvement of the body. This paper reports a case of SJS in an eight year old
male child along with the clinical features and treatment options.
Case Presentation: A male child of 8 years was referred with the chief complaint of ulcers in the mouth since 3 days. Past medical history
revealed severe drug reaction one month back, for which the patient attended a pediatric hospital elsewhere, where it was diagnosed as
Steven-Johnson Syndrome and the treatment was given for the same. After one month of treatment, the child was referred to our
department because of the persisting oral ulcers. On extra oral examination, skin lesions were healed whereas intra-oral examination
revealed multiple painful ulcers on upper and lower labial mucosa, with accompanying painful cervical lymphadenopathy. The treatment
consisted of topical application of hexigel and multivitamin supplements were prescribed. On follow up after 15 days, examination showed
healed ulcers. The patient fully recovered within a month.
Conclusion: Symptomatic management of the oral lesions is necessary in order to enable the patient to have oral feeds to maintain
nutritional balance. (El Med J 2:3; 2014)
Keywords: Drug Reaction, Stevens-Johnson Syndrome

Figure 1: Extensive involvement of the lower
part of the body.
300 A case of Stevens-Johnson syndrome
Vol 2, No 3
which SJS was separated from the EM spectrum and added to TEN,
thereby creating a new spectrum of severe drug-related diseases [4].
The criteria for diagnosis of SJS are epithelial detachment less than
10% of body surface area (BSA) and widespread erythematous or
purpuric macules of flat atypical targets. SJS and TEN are severe cu-
taneous disorders characterized by acute skin blisters and mucous
membrane erosions. In TEN, necrosis of the epidermis and other ep-
ithelia are seen. The distinguishing factor between the two is the
extent of skin involvement with it being <10% in SJS and >30% for
TEN.

More than 100 drugs have been associated with the development of
SJS/TEN in single case reports or retrospective studies [5]. SJS is a
severe adverse drug reaction characterized by widespread lesions af-
fecting the mouth, eyes, pharynx, larynx, esophagus, skin and geni-
tals. It almost invariably involves the oral mucosa. The spectrum of
severe cutaneous adverse drug reactions includes SJS or TEN, hyper-
sensitivity syndrome (HSS), anaphylaxis and angioedema, serum
sickness, and cutaneous vasculitis. One of the undesirable side-ef-
fects of highly active anti-retroviral therapy (HAART) in HIV manage-
ment is SJS [6]. Mycoplasma pneumonia infection has also been re-
ported in association with SJS [7]. An association between intake of
herbal drugs and onset of EM or SJS has been reported as an ex-
tremely rare occurrence [8]. A case of SJS secondary to use of diclo-
fenac for control of post-extraction pain has been described by
Shetty et al because it is uncommon [5].
In the oral cavity, SJS causes widespread ulcerative lesions. A pro-
drome occurs in about 30% of cases and may begin within 1 to 3
weeks of starting a new drug and lasts 1 to 2 weeks before the onset
of mucocutaneous manifestations, presenting with flu-like symp-
toms, sore throat, headache, arthralgias, myalgias, fever, bullous and
other rashes, pneumonia, nephritis or myocarditis. Ocular changes
such as dry eyes and symblepharon that resemble those of mucous
membrane pemphigoid may be noted. Balanitis, urethritis and vulval
ulcers may occur. SJS has to be clinically differentiated from viral sto-
matitides, pemphigus, EM, TEN and the sub-epithelial immune blis-
tering disorders like pemphigoid. SJS, its severe form TEN, and mu-
cous membrane pemphigoid (MMP) are the major autoimmune
causes of conjunctival scarring. The conjunctivitis varies from a pa-
pillary reaction with watery discharge to a membranous conjunctivi-
tis with sloughing of the conjunctival epithelium. Predilection of the
disease can be done with the following clinical picture of lesions on
the skin mucosa junction (pluriorificialis), on hands (dorsal surfaces)
and plantar surfaces of the feet.
Early diagnosis with the prompt recognition and withdrawal of all
potential causative drugs is essential for a favorable outcome. Intra-
venous fluid replacement must be initiated immediately upon ad-
mission using saline solution. Early initiation of massive oral nutrition
by nasogastric tube to minimize protein loss promotes healing and
decreases the risk of stress-induced ulcers. Corticosteroids have for
years been the mainstay therapy for SJS in most cases, as in our case.
They suppress the intensity of reaction, control the extension of the
necrolytic process, decrease the involved area, reduce fever and dis-
comfort, and prevent damage to internal organs when given at an
early stage and at a sufficiently high dosage. Topical antiseptics like
0.5% silver nitrate or 0.05% chlorhexidine are usually used for skin
lesions to prevent secondary infections. Complications such as
thromboembolism and disseminated intravascular coagulation and
damage to vital organs such as the kidney deteriorate the prognosis.
Conclusion
Symptomatic management of the oral lesions is necessary in order
to enable the patient to have oral feeds to maintain nutritional bal-
ance.
References
1. Roujeau JC. Steven-Johnson syndrome and toxic epidermal necrolysis are
severity variants of the same disease which differs from erythema multiforme.
J Dermatol 1997,24: 726-9.
2. Letko E, Papaliodis DN, Papaliodis GN, Daoud YJ, Ahmed AR, Foster CS. Steven
Johnson syndrome and toxic epidermal necrolysis: A review of literature. Ann
Allergy Asthma Immunol 2005, 94:419-36.
3. Yap FBB, Wahiduzzaman M, Pubalan M. Steven-Johnson Syndrome (SJS) and
Toxic Epidermal Necrolysis (TEN) In Sarawak: A Four Years Review. Egyptian
Dermatology Online Journal 2008, 4 (1): 1-13.
4. Stevens A, Johnson F. A new eruptive fever associated with stomatitis and
ophthalmia. Am J Dis Child 1922, 24: 526-533.
5. Shetty SR, Chatra L, Shenai P and Rao PK. Stevens-Johnson syndrome: a case
report. Journal of Oral Science 2010 , 52 (2): 343-346.
6. Balasundaram S et al. Oral lesions associated with nevirapine-related Stevens
Johnson syndrome: A report of four cases. J Oral and Maxillofacial Pathology
2011, 15(1): 39-45.
7. Saitoh A, Ohya T, Yoshida S, Hosoya R, Nishimura K. A case report of Stevens
Johnsons syndrome with Mycoplasma pneumoniae infection. Acta Paediatrica
1995, 37 (1): 113-115.
8. Chowdhury AD, Oda M, Markus AF, Kirita T, Choudhury CR. Herbal medicine
induced StevensJohnson syndrome: a case report. International J of Paed
Dent 2004, 14:204207.

Figure 2: Intra-oral picture of multiple ulcers on lower labial
mucosa.

Figure 3: Intra-oral picture of multiple ulcers on upper labial
mucosa.

2014 Aditya et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Aditya A, Waingade M: Concomitant occurrence of fibrous dysplasia and epilepsy: Report of an unusual case. El Mednifico Journal 2014, 2(3): 301-303.
Concomitant occurrence of fibrous dysplasia and epilepsy: Report of an unusual case
Amita Aditya
1
, Manjushri Waingade
1

Introduction
Fibrous dysplasia (FD) is an uncommon congenital developmental
anomaly of bone where normal bone is replaced by fibrous connec-
tive tissue. It has two clinical variants: monostotic and polyostotic
form. Craniofacial involvement in FD is seen in almost all cases of
polyostotic form and around 30% of the polyostotic form [1]. The
association between epilepsy and craniofacial fibrous dysplasia is un-
usual. Soler et al. have even reported epileptic seizures as the first
sign of fibrous dysplasia in one patient [2]. A clinician must be vigi-
lant and cognizant of this association so that a prompt referral and
treatment may be achieved. Also, thorough clinical and radiographic
examinations are essential prerequisites for the diagnosis of fibro-
osseous lesions.
Case Report
An 18-year-old male patient reported to the department with the
chief complaint of a swelling on the right side of the face since 4
years. The swelling was painless and had gradually increased to the
present size. He gave history of trauma to the secondary to a fall 4
years back. He had consulted a dentist then, however was not ren-
dered any treatment. Patient also complained of seizures since 2
years.
On extra-oral examination, a diffuse swelling was seen on the right
middle third of face extending medio-laterally from ala of nose to
outer canthal line, superiorly involving the zygomatic arch (Figure 1).
The swelling was bony hard and non-tender on palpation. Intra-
orally, swelling was seen associated with right buccal vestibule ex-
tending from right lateral incisors to second molar region, with nor-
mal overlying surface (Figure 2). The teeth present in the region ap-
peared to be normal.

1
Sinhgad Dental College & Hospital, Pune, Maharashtra, India.
Correspondence: Amita Aditya
Email: dr.amita30@rediffmail.com

Based on the history and clinical presentation a provisional diagnosis
of a benign lesion was made. Thorough radiographic investigations
were advised which included intra-oral periapical radiographs and

Abstract
Background: Fibrous dysplasia (FD) is a developmental anomaly in which normal bone is gradually replaced with fibrous connective
tissue. There are two variants: monostotic and polyostotic. The diagnosis of fibrous dysplasia is generally made on the basis of clinical and
radiographic findings. The association between epilepsy and craniofacial fibrous dysplasia is rather unusual. A case of fibrous dysplasia is
presented here which was seen co-existing with epileptic seizures.
Case Presentation: An 18-year-old male patient reported to the department with the chief complaint of a painless swelling on the right
side of the face since 4 years. He gave history of trauma secondary to a fall 4 years back and seizures since 2 years. On extra-oral
examination, a diffuse swelling was seen on the right middle third of face extending medio-laterally from ala of nose to outer canthal line,
superiorly involving the zygomatic arch. The swelling was bony hard and non-tender on palpation. Intra-orally, swelling was seen
associated with right buccal vestibule extending from right lateral incisors to second molar region, with normal overlying surface. Based
on the history and clinical presentation a provisional diagnosis of a benign lesion was made. Radiographic features were suggestive of a
fibro-osseous lesion, most probably fibrous dysplasia. Considering the fact that fibrous dysplasia may sometimes lead to epilepsy, patient
was referred for thorough neurological examination. A surgery was then planned for the patient for correction of the facial deformity.
However, the patient refused any further treatment.
Conclusion: A clinician must be vigilant and cognizant of this association so that a prompt referral and treatment may be achieved. (El
Med J 2:3; 2014)
Keywords: Fibrous Dysplasia, Epilepsy

Figure 1: Diffuse swelling on the right middle
third of face extending medio-laterally from
ala of nose to outer canthal line, superiorly
involving the zygomatic arch.

Figure 2: Swelling seen associated with right buccal
vestibule extending from right lateral incisors to
second molar region, with normal overlying surface.
302 Concomitant occurrence of fibrous dysplasia and epilepsy
Vol 2, No 3
panoramic radiograph. Computed tomography, although indicated,
could not be done due financial constraints. Intraoral periapical radi-
ographs showed diffuse radio-opacity in the periapical area with re-
spect to right canine to second molar region [Figures 3(a) and 3(b)].
Panoramic radiograph also showed similar diffuse radio-opacity in
the periapical regions of the associated teeth, extending superiorly
to involve the zygomatic bone (Figure 4). The radio-opacity showed
abnormal and irregularly shaped trabecular pattern with gradual
blending of lesion with the normal trabeculae.

The radiographic features were suggestive of a fibro-osseous lesion,
most probably fibrous dysplasia. Considering the fact that fibrous
dysplasia may sometimes lead to epilepsy, patient was referred for
thorough neurological examination. A surgery was then planned for
the patient for correction of the facial deformity. However, the pa-
tient refused any further treatment.
Patient was followed up telephonically up to 6 months after the ini-
tial visit. He was undergoing treatment for epileptic seizures at that
time.
Discussion
The term fibro-osseous lesion (FOL) is a generic designation of a
group of jaw disorders, characterized by the replacement of bone by
a benign connective tissue matrix. This matrix displays varying de-
grees of mineralization in the form of woven bone or of cementum-
like round acellular intensely basophilic structures [3, 4].
Fibrous dysplasia (FD) is a developmental anomaly in which normal
bone is replaced with fibrous connective tissue. As the lesion ma-
tures, the fibrous connective tissue is replaced with irregularly pat-
terned trabecular bone [5]. It is a localized abnormality, which can
involve one (monostotic) or multiple (polyostotic) bones. With initial
development of fibrous dysplasia, the patient usually reports facial
swellings and asymmetries. Although the lesion is usually asympto-
matic, encroachment on canals and foramina, as well as limitations
of movement, may lead to complaints of pain and discomfort [6]. In
general, males and females are thought to be affected evenly, alt-
hough recent research has shown a slight female preponderance.
The lesions of fibrous dysplasia are twice as common in the maxilla
as the mandible, and the posterior aspects of the jaw are more fre-
quently affected than the anterior.
Maxillofacial FOLs are of particular interest to the radiologist because
they emphasize the central role of the radiologist in the diagnostic
process. The late Charles Waldron wrote In absence of good clinical
and radiologic information a pathologist can only state that a given
biopsy is consistent with a FOL. With adequate clinical and radiologic
information most lesions can be assigned with reasonable certainty
into one of several categories [7].
The monostotic form accounts for 8085% of cases of FD. Although
the term monostotic can be readily applied to cases of FD affecting
the mandible alone, this is generally not so for FD affecting the max-
illa or face. There, FD can affect contiguous bones such as the zy-
goma and the sphenoid. These cases have been called craniofacial
FD [8].
The association of epilepsy and fibrous dysplasia is quite rare. Soler
et al in 1999 suggested that epilepsy might be an initial symptom in
fibrous dysplasia [2]. The mechanism for the production of epileptic
seizures may not be related to compression phenomenon or local
ischemia, but may be secondary to alteration in the mechanism of
cAMP as the secondary messenger of the cerebral cortex. However,
much needs to be explored in this field. Patients with fibrous dyspla-
sia hence should undergo neurological examination to rule out any
such possibility.
The diagnosis in this case was made based on the characteristic clin-
ical and radiographic features. Fibrous dysplasia may sometimes be
confused with other fibro-osseous lesions such as Pagets disease. In
addition to the predilection of Pagets disease for an older popula-
tion, certain radiographic and clinical features help to distinguish this
lesion from other radiographically similar lesions. These features in-
clude thickening of the cortices and cotton wool appearance of the
involved bone. The most useful clinical feature for distinguishing Pa-
gets disease from fibrous dysplasia is that the former tends to occur
bilaterally in the jaws, whereas the latter affects only one side.
A
B
Figure 3: Intraoral periapical radiographs showing diffuse
radio-opacity in the periapical area with respect to right
canine to second molar region.
Figure 4: Panoramic radiograph showing similar diffuse radio-
opacity in the periapical regions of the associated teeth,
extending superiorly to involve the zygomatic bone.
Aditya A, Waingade M 303
Treatment of fibrous dysplasia usually involves bony recontouring at
the affected site to improve aesthetics and function. The lesions can
show surprising growth potential if they are surgically altered during
their active growth phase [5].
Conclusion
A clinician must be vigilant and cognizant of this association so that
a prompt referral and treatment may be achieved.
References
1. Jhamb A, Mohanty S, Jhamb P. Craniofacial fibrous dysplasia. J Oral Maxillofac
Pathol 2012;16(3):465-9.
2. Soler R, Munoz-Torrero JJ, Barreiro P. Epileptic seizures as the first sign of
fibrous bone dysplasia. Rev Neurol 1999;28(10):976-8.
3. D.S. MacDonald-Jankowski. Fibro-osseous lesions of the face and jaws. Clinical
Radiology 2004;59:1125.
4. OHara BJ. Extragnathic fibro-osseous diseases. Oral Maxillfac Surg Clin Nor Am
1997;9:681-96.
5. Chandar VV, Priya, Amita. Bilateral fibrous dysplasia of the mandible in a 7-year
old male patient-A rare case. J Indian Soc Pedod Prevent Dent 2010; 2(28):126-
9.
6. Kanda M, Yuhki I, Murakami Y, Hasegawa Y, Kanki T. Monostotic front-orbital
fibrous dysplasia with convulsion. Neurol Med Chir 2001, 42:36-9.
7. Waldron CA. Fibro-osseous lesions of the jaws. J Oral Maxillofac Surg
1993;51:828- 35.
8. Waldron CA. Bone pathology. In: Neville BW, Damm DD, Allan CM, Bouquot JE,
ed. Oral and maxillofacial pathology. Philadelphia: WB Saunders Comp; 1995.
p. 460-91.


Open Access Opinion and Debate
2014 Erbay et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Erbay H: What if the patient says No! in the ambulance: An ethical perspective for assessment of capacity in the prehospital emergency setting. El Mednifico Journal 2014, 2(3): 304-306.
What if the patient says No! in the ambulance: An ethical perspective for assessment of capacity in the
prehospital emergency setting
Hasan Erbay
1

Introduction
Is it a crucial problem for an emergency team that when a patient to
whom an ambulance is called refuses emergency medical aid? In life-
threatening situations, it is not only a realistic matter of life and
death, but also an ethical challenge for prehospital emergency carers
(PECs) [1-3]. In the article, the term PEC refers to not only paramedics
but also registered nurses, emergency medical technicians and phy-
sicians working prehospital emergency care.
In emergency, does the patient who is thought having capable of
decision-making, have the right to refuse the treatment or medical
advice which has been proposed by PECs? In terms of human rights
and ethics, it is definitely yes in usual medical performance. Re-
spect for autonomy is one of the basic principles of modern bioeth-
ics. Also, according to World Medical Association (WMA): The pa-
tient has the right to self-determination, to make free decisions re-
garding himself/herself and a mentally competent adult patient
has the right to give or withhold consent to any diagnostic proce-
dure or therapy [4]. It is stated that it is all in the absence of any
contradictory evidence such as an advance directive. However, what
will happen, if it includes life-threatening situation for the patient?
Prehospital emergency care and ethical conflicts
Prehospital emergency care is unique and based on different set-
tings of classical health care systems. The differences are, resource
limited environment such as personnel, medicotechnical aids and in-
formation, caring where peoples normal living takes place, being on
public ground, being called to scenes where someone has called for
help, arriving at crime scenes, working tightly in a small team and so
on [5]. Most of ethical conflicts in prehospital settings are about in-
formed consent which includes refusal of treatment or transport,
conflict of hospital destinations, treatment of minors, and consent
for research [6]. Therefore, in prehospital setting, it is very important
to communicate effectively with patients. Moreover, if a patient is
unconscious or irrational, or an impenetrable language barrier exists,
explaining the necessary medical procedures becomes impossible or
more difficult [7].
It is worth thinking about refusal of treatment as an ethical conflict,
in emergency situations that PECs sometimes face in their practices.

1
Faculty of Medicine, Afyon Kocatepe University, Turkey
Correspondence: Hasan Erbay
Email: hasanerbay@yahoo.com
It could make a difference relatively, considering about conflicts and
challenges before they happen. Setting the principle standards in
advance is one of the ways to cope with these kinds of conflicts.
Considering all of these features of prehospital emergency field, we
ask the following crucial question: Will an adult patient to whom an
ambulance has been allocated to, have the right to refuse recom-
mended medical treatment, even if there is a life-threatening situa-
tion? It includes not only refusal of transport to hospital, but also
any medical treatment. It is also mentioned that the ambulance ser-
vice talked about on, is a governmental organization and there is no
need for health insurance of the patient.
It is required by law and medical ethics to obtain the informed con-
sent of the patient before initiating any medical intervention [8].
Contemporary jurists tell the medical community not to do anything
to a patient without gaining her/his informed consent, except emer-
gency situations. What are the emergency situations? This means al-
most everything PECs do as a professional. Undoubtedly, every case
is not a state of emergency in prehospital settings. However, a spe-
cial effort should be made to gain informed consent in all cases with-
out considering whether they are emergent or not. But sometimes,
it is too difficult to do so. If the patient is unconscious, consent is
presumed [9]. The reason is that PECs act to realize/do what the pa-
tient presumably wants as they know less (or nothing) about the
patient.
Therefore, it is considered that the unconscious patient would prefer
to live. In practice, making decision made in favor of preserving life
and ignoring the patient's expressed consent are justifiable [7].
Moreover, it is taught during training that health care professionals
have a duty of caring to act in the best interest of the patient. Hence,
health care professionals must act on the behalf of the patient when
the patients are not in a position to provide them with informed
consent or refusal. It seems to be a deontological attitude which in-
clines to ignore patients autonomy.
The expectation of society from organizations that provide emer-
gency medical care is a paternalistic approach where the emergency
medical staff eases the pain of suffering persons, thus, in other

Abstract
Is it a crucial problem for an emergency team that when a patient to whom an ambulance is called refuses emergency medical aid? In life-
threatening situations, it is not only a realistic matter of life and death, but also an ethical challenge for prehospital emergency carers. It is
impossible to contemplate and make recommendations in advance, for every possible situation that might arise in prehospital settings.
Thinking about the ethical challenges that may be encountered, ahead of time is necessary to provide appropriate attitude. (El Med J 2:3;
2014)
Keywords: Prehospital, Emergency, Ethics, Consent
Erbay H 305
words, performs an act of benevolence. This is more or less the same
with the relationship between the ongoing fire and calling the fire-
fighters. Why an ambulance is called for a person who does not need
an emergency medical aid? There is generally a preconceived belief
that the person in need of the emergency healthcare will consent
most of the procedures in advance.
On the other hand, what will happen if the patient has a plan to end
her/his life? Or, if the patient does not want to have any medical
intervention or refuses care. It causes an experienced ethical conflict
between patients autonomy and beneficence of the PECs in such
cases. Legal aspects of the issue vary from a country to another one.
There are also well-prepared laws and advisories on some aspects of
this topic in some countries [10, 11]. For example, in the U.K., The
Mental Capacity Act 2005 provides a statutory framework for people
who lack capacity to make decisions for themselves or who have the
capacity to make decisions for themselves but want to make prepa-
rations for a time when they may lack capacity to make decisions for
themselves in the future. The aim of the article is to think on ethical
aspects of the issue. As it is known that most of the healthcare pro-
fessionals are used to think legal aspects of the cases rather than
ethical aspects, however, it is important for PECs to think ethical as-
pects of refusing medical treatment.
When to assess capacity?
Because consent and refusal of treatment are closely related to each
other, they should be considered together. For a valid decision about
an informed consent or refusing the treatment, the following four
conditions must be provided:
1. The patient must possess the capacity to make the decision;
2. Medical personnel must disclose relevant information about the
risks and benets of the treatment in question;
3. The patient must comprehend the information
4. The consent must be completely voluntary and without duress
[12-14].
In fact, it seems the main solution point of the problem might have
been the assessment of the patient's decision-making capacity. The
term capacity refers to the ability to understand various treatment
options, risks, benefits, alternatives and the consequences of the
consent and/or refusal of treatment. Capacity is obviously, a clinical
term, whereas competence is a legal judgment. Any patient who
possesses decisional capacity has the right to make personal health
care decisions even if these decisions result in harm or death [15].
For PECs, the process for determining the decision-making capacity
does not need to include complex elements. Prehospital emergency
care field is required to think quickly and act serially. Therefore, PECs
should use quick and effective procedures to assess the patients de-
cision-making capacity. Even physicians could sometimes be unde-
cided about a patients decision-making capacity. Also, in the non-
emergency medical process in hospitals, many tests are sometimes
needed to be done for assessment the capacity of the patient. Then,
how will PECs decide?
How to assess capacity in prehospital emergency care
There are, unfortunately, no guidelines from medical societies for the
assessment of the patients capacity to consent to treatment for pre-
hospital emergency setting. However, the following six basic queries
could be made a significant difference for assessment of capacity in
prehospital emergency situations. If possible, relevant verbal com-
munication with the patient is very important in every stage of the
process:
1. Who has called the ambulance?
a. If the person calling the ambulance is the patient, it is clear
that he/she consents to the treatment. However, this is a
preliminary assumption. Consent to emergency treatment
should be taken at that time, and it is specific to each indi-
vidual case. Emergency care procedure should be just per-
formed depending on patient's consent as much as it is pos-
sible. Calling an ambulance is an individual choice (or expec-
tation) and it is in the patients best interest to treat.
b. If the person calling the ambulance is not the patient, but a
family member of the patient or someone else, it indicates
that there is an emergency situation there. But it doesn't in-
dicate the patient's consent. The person calling the ambu-
lance is not the patient, but it is mostly someone else [16]. It
is clear that there is no need for ethical discussion about the
treatment of the patient who is conscious and having deci-
sion-making capacity For PECs, it is the patient who is capa-
ble of making an informed decision and will decide his/her
treatment (or refuse the treatment) procedure, but not any-
one else.
2. Does the patient have disorientation? Is there any problem
about the awareness of the patient in three dimensions: time,
place and person? If there is any problem, decision-making ca-
pacity of the patient could have been affected. Especially, head
injury could cause disorientation. It should be examined more
carefully. Also patients with Alzheimers disease and other de-
mentias might have been affected decision-making capacity.
3. Does he/she have any information about whether he/she has
got any disease or not? It is important for analyzing the disease,
which could affect decision-making capacity. Effects of illness
could impair the function of mind. As such, psychiatric or neuro-
logical conditions are risk factors for impaired decision-making.
As many as 48% of inpatients with acute conditions have been
found to be incompetent to consent to medical treatment [17].
Refusal of treatment will be, of course, more complicated in the
presence of psychiatric illness. Psychiatric disorders, especially
schizophrenia, are associated with affected decision-making ca-
pacity [18].
4. Is the patient aware of what is going to be done after establish-
ing enough verbal communication with him/her? It is significant
that the patient is aware what will happen to him/her. Perhaps,
the patient has a needle phobia (or trypanophobia). Besides,
there could be a significant cultural or language barrier.
5. Does the patient admit the decisions of surrogates such as family
members? If the patient feels himself/herself inadequate to
make a decision, he/she may want his/her surrogates to make a
decision on behalf of him/her. However, in prehospital emer-
gency care, sometimes the patient is alone at the scene. When
surrogates make a decision, it is just their decision, not com-
pletely the patients own decision. The decisions of surrogates
306 Assessment of capacity in the prehospital emergency setting
Vol 2, No 3
generally do not accurately reflect patients preferences [19].
PECs should consider it in all the cases.
6. Is there any significance of drug abuse or alcoholism or so on
which may affect the decision-making capacity?
It could be said, of course, there are many proposals to determine
the patients level of consciousness. According to the answers to
these kinds of questions, prehospital emergency medical process is
more or less certain. Also, patients may refuse the treatment for
some reasons which are irrational reasons for PECs. It is, clearly not a
part of PECs job to judge the patients value. Some patients refuse
treatment for unusual or idiosyncratic reasons, but they are not irra-
tional when further evaluated [13]. Even the irrational choices of a
competent patient must be respected if the patient cannot be per-
suaded to change them [20]. Conversely, it might be criticized to
help patients to rationalize their decision [21]. Emergency medical
procedures, especially the ones related to religious issues, include
too many difficulties. For example, for 41.0% of the public and 30.6%
of the professionals, religious beliefs will be very important in guid-
ing their decisions about medical care if they were critically injured
[22].
An effective communication with the patient is necessary not only in
religious matters, but also in every dimension of refusal treatment in
prehospital emergency care. Refusal of treatment may vary accord-
ing to the cultural characteristics. For example, in a study from Tur-
key, paramedics were found to mostly try to persuade the patient
backing down from the refusal of treatment [23]. It should clearly be
stated that this should not be the duty of paramedics. According to
ethical issues, it is enough for PECs to tell medical situation and the
next process to the patient who has decision-making capacity. Para-
medics need to provide required information to the patient to help
him/her make a decision. It should include the benefits and risks of
the procedure and the potential outcomes of not accepting the
treatment. However, paternalistic decisions may frequently be made
by PECs. It is difficult to say if it is ethical to draw the patient into
treatment without his/her consent. It is also physically difficult to
treat a patient who does not want to be treated.
Conclusion
Prehospital emergency care is almost unique. Issues regarding the
consent and refusal for treatment are complex and challenging. It is
impossible to contemplate and make recommendations in advance,
for every possible situation that might arise in prehospital settings.
As a feature of ethical discussions, there could be different perspec-
tives of refusal of treatment country to country. The important thing
in these kinds of ethical issues about prehospital emergency care is
not answer all the questions, but it is crucial to generate ideas for
ethical conflicts and think on it. Thinking about the ethical chal-
lenges that may be encountered, ahead of time is necessary to pro-
vide appropriate attitude.
Received: 10 April 2014 Accepted: 26 July 2014
References
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the out-of-hospital setting. Acad Emerg Med. 1996;3(10):948-51.
2. Erbay H, Alan S, Kadioglu S. A case study from the perspective of medical
ethics: refusal of treatment in an ambulance. J Med Ethics. 2010;36(11):652-5.
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Fam Physician. 2001;64:299-306.
14. Appelbaum PS. Assessment of patients competence to consent to treatment.
N Eng J Med. 2007;357:1834-40.
15. Geiderman JM. Ethics seminars: consent and refusal in an urban American
emergency department: two case studies. Acad Emerg Med. 2001;8(3):278-81.
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1980;281(6233):121-3.
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M. Prevalence of mental incapacity in medical inpatients and associated risk
factors: cross-sectional study. Lancet 2004;364:1421-7.
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ill patients: a comperative empiricial study. Psychol Med. 2003;33:1463-71.
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Emerg Med. 2001;37(4):196-200.
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academic emergency medicine. Acad Emerg Med. 2000;7(10):1147-51.
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ambulance revisited. J Med Ethics. doi: 10.1136/medethics-2011-100079.
22. Jacobs LM, Burns K, Jacobs BB. Trauma death. Arch Surg. 2008;143(8):730-5.
23. Kadioglu S, Erbay H, Alan S, et al. Opinions of a group of ambulance staffs on
the right to refusing treatment. Oral presentation in Congress Book. 6th
Medical Ethics Congress, stanbul, 2010.


Open Access Opinion and Debate
2014 Shrivastava et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Shrivastava SR, Shrivastava PS, Ramasamy J: Scope of nutritional assessment in community and clinical settings. El Mednifico Journal 2014, 2(3):307-308.
Scope of nutritional assessment in community and clinical settings
Saurabh RamBihariLal Shrivastava
1
, Prateek Saurabh Shrivastava
1
, Jegadeesh Ramasamy
1

Opinion and Debate
The nutritional status of an individual is usually the result of multiple
factors which interact with each other in different proportions [1].
The consumption of adequate amount of food both in terms of
quantity and quality is one of the key determinants that have a sig-
nificant impact on the nutritional status [1]. Furthermore, the dietary
habits of an individual are the crucial factor that dictate the occur-
rence of a disease (viz. lifestyle disorders such as coronary heart dis-
ease, hypertension, stroke, diabetes mellitus, cancer), or an adverse
consequence (viz. low birth weight, malnutrition, disability, poor
quality of life, mortality) in both developed and developing countries
[2-5]. Acknowledging the role of diet in the onset of many diseases,
assessment of the nutritional status of an individual/family/commu-
nity is of extreme public health importance [1].
The nutritional assessment is done with an aim to obtain specific in-
formation about the prevalence and geographic distribution of nu-
tritional disorders in a given community/a specified population
group to identify nutritionally vulnerable high risk groups and to as-
sess the role of different epidemiological factors in the natural his-
tory of the nutritional deficiency disorders. Such nutritional assess-
ment has a significant role in the process of formulation of effective
policy/recommendations to rectify the problem, to project for the
financial allocations desired in the surveyed area to the program
managers and to finally evaluate the effectiveness of the imple-
mented corrective measures. Realizing the scarcity of resources, es-
pecially in developing nations and in poor resource settings, the aim
is to not to examine the entire population in a community, but to
restrict the survey to the representative group of the population only
so that the results of the survey can be generalized to the entire
community [1, 6, 7].
The comprehensive assessment of the nutritional status involves dif-
ferent methods which have been broadly categorized as direct (viz.
deal with the individual and measures the objective criteria) and in-
direct (viz. use community health indices that reflect nutritional in-
fluences) [6, 7]. These methods include clinical appraisal, anthro-
pometry, biochemical evaluation, functional assessment, vital and
health statistics, assessment of dietary intake and ecological studies

1
Department of Community Medicine, Shri Sathya Sai Medical College & Research
Institute, Kancheepuram, India
Correspondence: Saurabh RamBihariLal Shrivastava
Email: drshrishri2008@gmail.com
to cover all the phases involved in the natural history of disease. Each
of them has some advantages and limitations, and thus utilizing all
of them to assess the nutritional status gives a holistic picture [1].
1. Clinical appraisal: It is an essential feature of all nutritional sur-
veys as the primary aim is to assess levels of health of individuals
or of population groups in accordance with the type of food con-
sumed. The presence of two or more clinical signs characteristic
of a specific nutritional deficiency disorder increases the diag-
nostic significance. It can be applied to a large group of popula-
tion and usually it is not time consuming. However, its limitation
is that it cannot quantify the exact level of malnutrition just on
the basis of clinical signs, most of the deficiencies do not coexist
with clinical signs, lack of specificity and subjective nature of
most of the physical signs. For example, Bitots spots (vitamin A
deficiency), enlargement of the thyroid gland (endemic goiter),
etc [6, 8].
2. Anthropometric measurements: Anthropometric indicators
(viz. height, weight, skinfold thickness and arm circumference)
have a special role to detect any signs of undernutrition or over-
nutrition in population groups like newborn, under-five year
children and adults. Periodic anthropometric recordings can sug-
gest the patterns of growth and development, and deviations
from the normal range. The crucial aspect is that these measure-
ments can be done by trained non-medical individuals alone [1,
7].
3. Laboratory and biochemical investigations: These investiga-
tions are extremely helpful in detecting early changes in body
metabolism and nutrition even before the appearance of overt
clinical signs. In addition, the results obtained are precise, accu-
rate and reproducible. However, the limitations attributed to
them is that they are time consuming, expensive, cannot be ap-
plied on a large scale and essentially requires trained manpower
and infrastructure support [8, 9].
4. Functional indicators: Functional indices of nutritional status
are emerging as an important category of diagnostic tools and
support the biochemical investigations to a great extent. Some
of the commonly used functional indices are for hemostasis
(measure prothrombin time to check the adequacy of vitamin K)

Abstract
The nutritional status of an individual is usually the result of multiple factors which interact with each other in different proportions.
Acknowledging the role of diet in the onset of many diseases, assessment of the nutritional status of an individual/family/community is of
extreme public health importance. The nutritional assessment is done with an aim to obtain specific information about the prevalence and
geographic distribution of nutritional disorders in a given community/a specified population group, to identify nutritionally vulnerable high
risk groups and to assess the role of different epidemiological factors in the natural history of the nutritional deficiency disorders. To conclude,
the comprehensive nutritional assessment is an effective tool to assess the prevalence of nutritional disorders, to plan corrective measures
and simultaneously evaluate the effectiveness of the implemented strategies. (El Med J 2:3; 2014)
Keywords: Diet, Nutritional Assessment, Anthropometry, Clinical Examination
308 Nutritional assessment in community and clinical settings
Vol 2, No 3
and for nerve conduction (to assess the level of vitamin B12) [1,
9].
5. Vital statistics: Analysis of morbidity (viz. prevalence of protein
energy malnutrition/xerophthalmia/iodine deficiency disorders/
nutritional anemia) and mortality data (viz. infant mortality rate,
maternal mortality rate, under-five mortality rate etc) assist in
estimating the prevalence of the disease in the community and
even aid in identification of high risk groups. However, in con-
trast to the mortality data which do not provide a satisfactory
picture of the nutritional status of a population, morbidity data
(obtained either from a hospital or a community survey) are of
most public health importance and can help the policy makers
in giving more importance to a particular area [1, 6, 7].
6. Dietary intake assessment: Dietary intake is evaluated with the
help of a diet survey, which is the scientific assessment of pattern
of dietary intake, followed by the estimation of nutrient intake.
It is considered as the most essential component of the nutri-
tional assessment because only a dietary survey can detect
whether an inadequate dietary intake is the primary reason for
the observed deficiency as revealed by any other method of nu-
tritional assessment. Various methods are available to undertake
diet surveys in the different settings such as food balance sheet
(for the aid of program managers to decide the dietary needs of
a region or a state or a country), inventory method (institutions
with a homogenous group), weighment method (household
level), 24-hour recall method (household level) and food fre-
quency questionnaire method (to study the meal patterns and
dietary habits of people) [10-13].
7. Ecological factors: Occurrence of malnutrition is usually the fi-
nal event that results because of the interaction of different eco-
logical factors such as socio-economic factors (viz. family size,
occupation, income, education, customs, feeding practices of
children and mothers, etc.), quality, accessibility and availability
of health care services and infections (viz. parasitic, bacterial and
viral). It is extremely important to make an "ecological diagnosis"
(i.e. identification of the various factors that had affected the nu-
trition status of the community), as the malnutrition may precip-
itate again if these ecological factors are not controlled [1, 7].
Nutritional assessment is being used in different settings, for in-
stance, for evaluating the level of cognitive impairment in the el-
derly, in leukemia patients after hematopoietic stem cell transplan-
tation to find the possible nutritional risk of the patients during the
transplantation process, to assess the cardiovascular status of people
suffering from heart condition and to identify the prognosis of tu-
berculosis patients [8, 12-14].
To conclude, the comprehensive nutritional assessment is an effec-
tive tool to assess the prevalence of nutritional disorders, to plan
corrective measures and simultaneously evaluate the effectiveness
of the implemented strategies.
Received: 23 February 2014 Accepted: 26 July 2014
References
1. Park K. Nutrition and health. In: Park K, eds. Textbook of Preventive and Social
Medicine. 20th ed. Jabalpur: Banarsidas Bhanot, 2009:562-4.
2. Herder R, Demmig-Adams B. The power of a balanced diet and lifestyle in
preventing cardiovascular disease. Nutr Clin Care. 2004;7(2):46-55.
3. Price S. Understanding the importance to health of a balanced diet. Nurs
Times. 2005;101(1):30-31.
4. Shrivastava SR, Shrivastava PS. A longitudinal study of maternal and socio-
economic factors influencing neonatal birth weight in pregnant women
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5. Nucci LB, Schmidt MI, Duncan BB, Fuchs SC, Fleck ET, Santos Britto MM.
Nutritional status of pregnant women: prevalence and associated pregnancy
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6. Beghin I, Cap M, Dujardin B. A guide to nutritional assessment. WHO press:
Geneva; 1988.
7. World Health Organization. Field guide on rapid nutritional assessment in
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between cognitive impairment and nutritional assessment on functional status
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9. Bernstein LH. The increasing role for the laboratory in nutritional assessment.
Clin Biochem. 2012;45(15):1150-1.
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frequency questionnaire data by reference to a standard weighed diet survey.
J Hum Nutr Diet. 2000;13(3):219-24.
11. Wrieden W, Peace H, Armstring J, Barton K. A short review of dietary
assessment methods used in National and Scottish research studies, 2003.
Available from:
http://multimedia.food.gov.uk/multimedia/pdfs/scotdietassessmethods.pdf
12. Anyzewska A, Wawrzyniak A, Wozniak A, Krotki M, Gornicka M. Nutritional
assessment in Polish men with cardiovascular diseases. Rocz Panstw Zakl Hig.
2013;64(3):211-5.
13. Wang B, Yan X, Cai J, Wang Y, Liu P. Nutritional assessment with different tools
in leukemia patients after hematopoietic stem cell transplantation. Chin J
Cancer Res. 2013;25(6):762-9.
14. Miyata S, Tanaka M, Ihaku D. Full mini nutritional assessment and prognosis in
elderly patients with pulmonary tuberculosis. J Am Coll Nutr. 2013;32(5):307-
11.


Open Access Essay
2014 Rikani et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Rikani AA, Choudhry Z, Choudhry AM, Rizvi N, Ikram H: Spatial information processing by the human visual system. El Mednifico Journal 2014, 2(3):309-310.
Spatial information processing by the human visual system
Azadeh A Rikani
1,2
, Zia Choudhry
1,3,4
, Adnan Maqsood Choudhry
5
, Nasir Rizvi
5
, Huma Ikram
6

Behavioral approach of spatial information processing in
visual system
Ungerleider and Mishkin suggested the existence of two partly inde-
pendent visual streams in mammalian visual system. According to
their original account, a ventral stream originating from striate cortex
and finally terminating in infertemporal region is responsible for
identification of objects and, a dorsal stream also coming from striate
cortex and projection to posterior parietal cortex plays an important
role in localization of those same objects [1].
Most behavioral evidences coming from studies of neurological pa-
tients began to challenge Ungerleider and Mishkins what versus
where hypothesis. Studies that closely observe patients attempt to
make visually guided movement are particularly important. Close ex-
amination of patients with diffuse and profound damage to posterior
partial cortex homolog of dorsal stream in visual pathway, clinically
known as optic ataxia, showed that they were unable not only to
reach objects in right direction but also to appropriately adjust posi-
tion of their hands in space when grasping them [2]. Furthermore,
these patients were surprisingly still able to describe visual features
such as size, orientation and relative spatial location of different ob-
jects they were not able to reach [3].
Patients with damage to ventral stream, clinically known as visual
agnosia, had visual deficits and spared visual functions [4]. Selective
damage to object recognition areas in the ventral stream disrupts
patients ability to discriminate between objects based upon their
size, shape and orientation while these patients have no difficulty to
adjust their hands to the size, shape and orientation of those same
objects when they try to pick them up [2]. Calibrating accurate
grasping movements probably is due to intact dorsal stream playing
a critical role in pre-specification of movement parameters [5]. Be-
havioral studies of patients with visual agnosia and optic ataxia in
which ventral and dorsal stream are damaged respectively show
functional division between the ventral and dorsal stream [6]. Both
streams process visual inputs carrying information about orientation
and shape, and spatial characteristics of objects. However, each

1
Douglas Hospital Research Centre, Montreal, Quebec, Canada
2
Department of Psychiatry, McGill University, Montreal, Quebec, Canada
3
Department of Human Genetics, McGill University, Montreal, Quebec, Canada
4
Division of Research & Medical Education, International Maternal and Child Health
Foundation, Montreal, QC, Canada
5
Department of Neurology, University of Alberta Hospital, University of Alberta,
stream has different purposes and utilizes visual information in dif-
ferent ways [6]. Ventral and dorsal streams are dedicated to pro-
cessing visual features of the object for perceptual purpose and for
control of action, respectively.
Interestingly, the ventral stream transforms broader range of visual
features for perceptual purpose while the dorsal stream transforms
some of those visual features for actions [7]. In a study conducted by
Aglioti et al, healthy observers were tested with Ebbinghause illu-
sion. In this type of illusion, two target discs with the same size are
surrounded by two circles of different sizes [8]. One disc surrounded
by smaller circle seems larger than other one surrounded by larger
circle. When observers were asked to grasp the target discs, grip ap-
erture was very well adjusted proportional to actual size of disc not
unreal size. This study suggested that vision for perception tends to
be object-centered. Therefore, perceptual system needs to process
the size, shape, color, lightness and location of object with respect
to other, especially larger objects. This study also showed that unlike
perceptual system, visiomotor network has to be viewer-centered
and to compute absolute size of objects and their position relative
to observer [9]. While these findings refute separate streams for pro-
cessing of object vision and spatial vision, they support the idea of
transformation of spatial information for object perception and ob-
ject-directed grasping in two different streams.
Physiological approach of spatial information processing in
visual system
1. The Dorsal Stream
Since posterior parietal cortex major terminus for the dorsal stream
are highly involved in visual fixation, eye movement and visually
guided grasping and reaching, Andersen suggested that majority of
cells in this area "exhibit sensory-related and movement-related ac-
tivity [9, 10]. One study showed some cells in the dorsal stream are
visually sensitive. Fifty-five percent of cells classified as "hand-move-
ment-related neurons got stimulated during manipulation of ob-
jects in the dark. Most of the hand-movement-related neurons were
selective in type of manipulated objects. Of these, Sixty-nine percent
Edmonton, AB, Canada
6
Neuropharmacology Research Unit, Department of Biochemistry, University of
Karachi, Karachi, Pakistan 75270
Correspondence: Adnan Maqsood Choudhry
Email: am.choudhry@live.com
Abstract
Ungerleider and Mishkin suggested the existence of two partly independent visual streams in mammalian visual system. According to their
original account, a ventral stream originating from striate cortex and finally terminating in infer temporal region is responsible for identification
of objects and, a dorsal stream also coming from striate cortex and projection to posterior parietal cortex plays an important role in localization
of those same objects. What versus Where hypothesis has been center of investigators argument for years. In this review, considering
extensive behavioral and neurophysiologic studies, some new ideas about processing of spatial information in mammalian visual system are
briefly discussed. (El Med J 2:3; 2014)
Keywords: Spatial Information, Processing, Human Visual System
310 Spatial information processing by the human visual system
Vol 2, No 3
were affected by visual stimulus such as size, shape and orientation.
Based on these findings, hand-movement related neurons are asso-
ciated with visually guided hand movement particularly with adjust-
ing of hand movement to spatial features of manipulated object [11].
Motion sensitive cells have different subtypes in the dorsal stream.
Some of them continuously provide updated information about dis-
position and structural features of object and some other cells which
are direction and disparity sensitive participate in coding the direc-
tion of self-motion in environment [12].
Through extensive electrophysiology studies, Duhamel, Colby and
Goldberg showed that some neurons in posterior parietal cortex are
able to temporary change the receptive field even before saccadic
eye movement, so the stimuli will fit into receptive field and get pro-
cessed by neurons. The result of activity of these neurons is anticipa-
tion of shift in visual image on retina before an eye movement and
update of object representation relative to observes every time they
move [13]. In summary, role of posterior parietal cortex in processing
the immediate and ego-centric characteristics of objects is crucial for
skilled movement such as visually guided grasping [6].
2. The Ventral Stream
Cells which respond to similar visual features of the object are ar-
ranged in columnar region in infertemporal cortex. Each column re-
gion is considered as a unit for description of objects. Difference in
selectivity of cells in columns makes them similar to different ampli-
fiers representing difference within a group of features. Combination
of outputs of these amplifiers effectively describes different objects
in nature [14]. Electrophysiological studies also showed that unlike
to the dorsal stream, the ventral stream provides long term recogni-
tion memory of objects and events [15]. Compared to visual infor-
mation used in visually guided action, visual information used in per-
ception should be available over much longer time. Primary concern
of perceptual system is position of an object within the scene, not its
position with respect to the observer. Present perception of object
with stored information of previously recognized object contribute
to object recognition [7].
Conclusion
There is a growing body of behavioral and neurophysiologic evi-
dences explaining two streams of spatial information processing in
mammalian visual system. Although both streams receive infor-
mation about structural features and orientation of objects in nature,
they utilize quite different ways to process information. They also put
different sets of information into effect for different purposes. The
ventral and dorsal streams process structural features of an object
and its position relative to other objects and the observer, respec-
tively. Regarding the outputs of two streams, the ventral stream pro-
vides long term recognition of the object while the dorsal stream
provide instantaneous action relevant information.
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Single neurons in the medial thalamus of primates. Brain Res. 1993: 401-416.


Open Access Essay
2014 Elkadi et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Elkadi OA: Phage therapy: The new old antibacterial therapy. El Mednifico Journal 2014, 2(3):311-312.
Phage therapy: The new old antibacterial therapy
Omar Anwar Elkadi
1

Essay
Phage therapy is a microbial based therapy that utilizes the lytic life
cycle of bacteriophage to treat pathogenic bacterial infections. It is
the earliest antibacterial therapy in modern history. The early success
of phage therapy lost its luster after the development of the less
controversial antibiotic chemotherapies. However, in the context of
the advanced microbiology and biotechnology, phage therapy is re-
viving as an alternative for antibiotics chemotherapy, especially
against multidrug resistant (MDR) bacterial infections [1-3].
The discovery of bacteriophage was associated with its potential
beneficial effects. In 1896, Ernest Hankin described a filterable bio-
logical principle in Indian rivers, with antibacterial activity against
Vibrio cholera, thus, responsible for limiting the spread of Cholera
epidemics [2]. In 1917, Flix dHerelle officially discovered phage
with a more concise description. He described it as a veritable mi-
crobe of immunity and an obligate bacteriophage. He isolated it
from the stool of recovering shigellosis patients. This phage caused
lysis of Shigella bacilli culture, and DHerelle proved its clinical signif-
icance by satisfying some of Kochs postulates. DHerelle is the first
scientist to clinically use phage therapy in uncontrolled studies [1,
2]. After a number of unfavorable debates about the nature and ef-
ficacy of phage, together with the development of antibiotics, phage
therapy studies drastically declined especially in Western Europe and
USA. However, in uncontrolled studies, phage therapy continued to
show promising results in the former Soviet Union and Eastern Eu-
rope. With ineffective communication due to language and political
barriers, these promising results weren't shared with the rest of the
world [2].
A series of discoveries about the nature of phage helped in decreas-
ing the controversy about phage therapy. In 1925, Bordet and Bail
confirmed the viral nature of phage and described the phenomena
of lysogeny the ability of phage to infect bacteria without induc-
tion of lysis [2]. Later on, electron microscopy imaging of phage rev-
eled its detailed structure and diverse lifecycle lytic, lysogenic,
pseudo-lysogenic and chronic infection [4]. Till now more than 6000
different phages have been discovered from an estimate of 10
32

phages on the planet [2]. Animal studies (with various animal models
and various rout of administration) have tested diverse lytic phage
(virulent) in phage therapy leading to an increasing number of com-
mercial products in veterinary medicine and a number of controlled

1
Faculty of Pharmacy, Cairo University, Egypt
Correspondence: Omar Anwar Elkadi
Email: omar.elkadi@live.com
clinical trials, which started early in the twenty first century [5]. In
2009, the first controlled clinical trial of phage therapy published its
result. It showed the safety of a phage cocktail directed against E.
coli, S. aureus and Pseudomonas aeruginosa. Another controlled clin-
ical trial showed the efficacy of 6 phages against chronic Pseudomo-
nas aeruginosa induced otitis. More clinical trials are currently inves-
tigating the effectiveness of phage therapy [2].
Effectiveness of phage therapy is influenced by number of factors.
Generally, passive treatment, which involves using a sufficient con-
centration of phages ensuring that all bacteria are infected within a
short period, appears to be more effective than active treatment,
which uses low concentration depending on phages replication in
vivo [5]. Also, early intervention is more effective, and multiple doses
are better than a single dose. However, in late intervention there is
no significant difference between single and multiple doses. Envi-
ronmental factors are also considered important factors. For in-
stance, phage proliferation decreases with the decrease of PH, this
may lead to treatment failure of oral administration due to stomach
acidity (can be corrected by antacid neutralization or microencapsu-
lation) [5, 6]. Also, phages have limited diffusion in solid matrices
(such as in solid food [7]). Moreover, some proteins and immune
factors (such as those in raw milk) can protect bacteria from phages
[8]. As phages are immunogenic, it may be neutralized by the host
immune system. However, this is not a problem for initial treatment
due to the faster kinetics of phages than the immune system, but It
needs to be evaluated for second administration [5]. Although there
were doubts about the accessibility of phages to intracellular bacte-
ria, studies have shown effectiveness of phages against intracellular
bacteria such as Salmonella species and even obligate intracellular
bacteria, such as Chlamydia species [5, 9].
Besides treating MDR bacterial infection, phage therapy has other
potential advantages. For instance, phages can be developed for all
types of bacteria, can overcome biofilms, and is widely distributed
upon systemic administration (including the nervous system as it
passes the blood brain barrier). Thus, phage therapy can potentially
treat all bacterial infections [2]. Moreover, phage therapy has been
proven to be more cost and therapeutically effective than antibiotics.
Dose reduction (in terms of concentration and frequency of admin-
istration) is also possible due to the ability of phage to replicate at
the site of infection. Another potential advantage of phages is their

Abstract
Phage therapy is a microbial based therapy that utilizes the lytic life cycle of bacteriophage to treat pathogenic bacterial infections. It is the
earliest antibacterial therapy in modern history. The early success of phage therapy lost its luster after the development of the less controversial
antibiotic chemotherapies. However, in the context of the advanced microbiology and biotechnology, phage therapy is reviving as an
alternative for antibiotics chemotherapy, especially against multidrug resistant bacterial infections.
Keywords: Phage Therapy, Bacteriophage, Lysogeny, Lysis, Antibacterial
312 Phage therapy: The new old antibacterial therapy
Vol 2, No 3
possible ability to modulate inflammatory responses [2]. Phages
specificity to its bacterial host holds for us two main advantages.
Firstly, it is neutral and safe to patients cells: minimizing the poten-
tial of side effects. The other advantage is that it spares the existing
microbiome to perform its vital role for its host [1, 2].
However, this specificity from another point of view is considered a
limitation. It requires the knowledge of the exact etiological bacteria
before initiating the therapy. However, this problem could be solved
using phage cocktails (a mixture of phages) or polyvalent phages [1].
Another limitation of phage therapy is the heterogeneity of phages,
where lysogenic phages are much less effective than lytic phages. In
fact, lysogenic phages can cause spread of virulence factors and
pathogenicity determinants by transduction (transfer of genetic ma-
terial) [1, 2]. Thus, it is important to carefully select lytic phages in
phage therapy. Also, phage susceptibility to environmental condi-
tions (such as pH) is another limitation especially in its preparation
[2, 5]. Phage resistance is another problem facing phage therapy.
However, bacterial rate of developing resistance to phage is 10-fold
less than developing resistance to bacteria. Also, a new effective
phage can be selected much more rapidly (in a few days) than de-
veloping a new class of antibiotics [5]. Phages also have genes of
unknown function which could cause harmful side effects [2]. How-
ever, we are exposed to phages all the time, thus the patient is not
exposed to additional risks. Moreover, no phage therapies employed
in Eastern Europe have shown any significant adverse effect [2].
After decades of controversial investigation, phage therapy has
proven to have great potentials in the treatment of bacterial infec-
tion, and even phages are currently being employed in other thera-
peutic areas such as cancer treatment [10]. However, it needs more
controlled clinical trials to prove its efficacy, determine the optimum
doses and rout of administration for different phages. It also needs
further research and development on the molecular level to optimize
its therapeutic potential.
Received: 2 June 2014 Accepted: 26 July 2014
References
1. Sulakvelidze A, Alavidze Z, Morris JG, Jr.: Bacteriophage therapy. Antimicrobial
agents and chemotherapy 2001, 45(3):649-659.
2. Wittebole X, De Roock S, Opal SM: A historical overview of bacteriophage
therapy as an alternative to antibiotics for the treatment of bacterial
pathogens. Virulence 2014, 5(1):226-235.
3. Abedon ST, Kuhl SJ, Blasdel BG, Kutter EM: Phage treatment of human
infections. Bacteriophage 2011, 1(2):66-85.
4. Weinbauer MG: Ecology of prokaryotic viruses. FEMS microbiology reviews
2004, 28(2):127-181.
5. Ly-Chatain MH: The factors affecting effectiveness of treatment in phages
therapy. Frontiers in microbiology 2014, 5:51.
6. Jonczyk E, Klak M, Miedzybrodzki R, Gorski A: The influence of external factors
on bacteriophages--review. Folia microbiologica 2011, 56(3):191-200.
7. Guenther S, Huwyler D, Richard S, Loessner MJ: Virulent bacteriophage for
efficient biocontrol of Listeria monocytogenes in ready-to-eat foods. Applied
and environmental microbiology 2009, 75(1):93-100.
8. O'Flaherty S, Coffey A, Meaney WJ, Fitzgerald GF, Ross RP: Inhibition of
bacteriophage K proliferation on Staphylococcus aureus in raw bovine milk.
Letters in applied microbiology 2005, 41(3):274-279.
9. Sliwa-Dominiak J, Suszynska E, Pawlikowska M, Deptula W: Chlamydia
bacteriophages. Archives of microbiology 2013, 195(10-11):765-771.
10. Petrenko VA, Jayanna PK: Phage protein-targeted cancer nanomedicines. FEBS
letters 2014, 588(2):341-349.


Open Access Essay
2014 Zahid et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Zahid N, Ali A: Oral health and pregnancy. El Mednifico Journal 2014, 2(3): 313.
Oral health and pregnancy
Nida Zahid
1
, Anna Ali
1

Essay
Pregnancy is a very unique and precious experience in a womans
life. The progressive physiological changes that occur during preg-
nancy due to hormonal changes are necessary to support and safe-
guard the developing fetus and also to prepare the mother for par-
turition [1]. However, these systemic changes can also affect the fe-
males oral health, causing deleterious effects on the quality of life of
a female during pregnancy. Dental diseases such as deep dental car-
ies, dental erosion and periodontal infections can exacerbate during
pregnancy [2, 3]. Moreover, change in diet, nausea and vomiting dur-
ing pregnancy deteriorates oral health and increases the chances of
dental erosion and dental caries. Furthermore, during labor and de-
livery dislodged tooth and prostheses can cause complications [4, 5].
Dental problems not only causes severe pain and discomfort to the
pregnant females, but can also be a risk factor for preterm delivery
and low birth weight of the newborn [6]. We would like to highlight
the significance of management of oral health of a female during
pregnancy. Primary care for oral health during pregnancy would pre-
vent a female from undergoing through its deleterious complica-
tions [6]. Literature suggests that periodontal diseases may be asso-
ciated with prenatal mortality. The rate of prenatal mortality in Paki-
stan is 10-fold greater as compared to the developed countries,
which has exacerbated with the increase in periodontal diseases [7-
9]. In Pakistan not much emphasis is laid on oral health during preg-
nancy and therefore it is left untreated. A study from Pakistan re-
ported that 76% of females suffering from periodontal disease had
stillbirth, and chances of neonatal and perinatal death were also
higher among such females with a relative risk of approximately 1.3
[10].
Thus, healthcare professionals should recognize the importance of
good oral health and make certain recommendations for its preven-
tion during pregnancy. Although certain standardized guidelines
have been established for health care professionals for providing
standardized prenatal care, but unfortunately no such guidelines are
formulated with regards to prenatal maternal dental care. Studies
from various parts of the world suggest that majority of the health
professionals providing prenatal care rarely incorporate oral exami-
nation for pregnant woman as a part of standard prenatal care [11].

1
Department of Community Health Sciences, Aga Khan University, Pakistan
Correspondence: Nida Zahid
Email: nida.zahid@aku.edu
Hence we would like to recommend that the prenatal care provider
and dentists should be closely linked to each other. Moreover aware-
ness should be raised among the treating gynecologist regarding the
significance of oral health during pregnancy. Furthermore, aware-
ness should also be raised among the pregnant females regarding
the importance of their oral health through public health messages.
This can help in improving the utilization of dental services by fe-
males during pregnancy and thus will have profound effects not only
on the health of the expectant mother, but also on the health of their
newborns.
References
1. Carlin A, Alfirevic Z: Physiological changes of pregnancy and monitoring. Best
Practice & Research Clinical Obstetrics & Gynaecology 2008, 22(5):801-823.
2. P C: Bright Futures in Practice: Oral Health. Arlington, VA: National Center for
Education in Maternal and Child Health. 1996.
3. Gajendra S KJEB: Oral health and pregnancy: a review.Foreword to the
Supplement on Children and Oral Health. Ambulatory Pediatrics. N Y State
Dent J 2004, 70(1):40-44. 49.
4. Berkowitz RJ: Acquisition and transmission of mutans streptococci. Ontario
Dentist 2009, 86(1).
5. Douglass JM DA, Silk HJ. : A practical guide to infant oral health. Am Fam
Physician 2004(70(11):):2113-2120.
6. Pace M: Rationale for Implementation of Dental Care into Existing Maternal
Prenatal Care Standards.
7. UNICEF Regional Office for South Asia. Atlas of South Asian Women and
Children. Kathmandu, United Nations Childrens Fund. 1996.
8. Sachdev HPS: Low birth weight in South Asia." Malnutrition in South Asia: a
regional profile. ROSA Publication 1997(5): 23-50.
9. Mobeen N, Jehan I, Banday N, Moore J, McClure EM, Pasha O, Wright LL,
Goldenberg RL: Periodontal disease and adverse birth outcomes: a study from
Pakistan. American journal of obstetrics and gynecology 2008, 198(5):514.
e511-514. e518.
10. Wilder R, Robinson C, Jared HL, Lieff S, Boggess K: Obstetricians knowledge
and practice behaviors concerning periodontal health and preterm delivery
and low birth weight. American Dental Hygienists Association 2007, 81(4):81-
81.
11. Thomas KM: Nurse Practitioners, Physician Assistants and Certified Nurse
Midwives' Knowledge and Behaviors Regarding Periodontal Disease and Its
Impact on Adverse Pregnancy Outcomes: ProQuest; 2008.

Abstract
The progressive physiological changes that occur during pregnancy due to hormonal changes are necessary to support and safeguard the
developing fetus and also to prepare the mother for parturition. But these systematic changes can also affect the females oral health causing
deleterious effects on the quality of life of a female during pregnancy. Dental diseases such as deep dental caries, dental erosion, and
periodontal infections can exacerbate during pregnancy. Moreover change in diet, nausea and vomiting during pregnancy deteriorates oral
health and increases the chances of dental erosion and dental caries. Furthermore during labor and delivery, dislodged tooth and prostheses
can cause complications. (El Med J 2:3; 2014)
Keywords: Oral Health, Pregnancy, Womens Health

Open Access Essay
2014 Hazari et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Hazari MAH: Integrated teaching in medical curriculum in India. El Mednifico Journal 2014, 2(3): 314.
Integrated teaching in medical curriculum in India
Mohammed Abdul Hannan Hazari
1

Essay
The present medical curriculum utilizes a large part of the allotted
time frame in the form of didactic theoretical lectures while little
time is available for practical, clinical and behavioral skills acquisition
which is required of a basic doctor [1]. To stimulate students inter-
est, basic medical sciences may be pruned in terms of content and
duration to meet the requirements for a basic doctor whereas intern-
ship period may be increased to give more of clinical training. This
concept may not be relished by the teachers of both basic and clin-
ical sciences who may feel their interests to be in jeopardy.
In the west, there has been a shift from teacher-centered learning
to student-centered learning which is supplemented by regulations
and legislations laid down by the authorities governing higher edu-
cation. The globalization of education and health care and Indias
potential as a destination of choice for quality education and health
care has brought the issue into sharper focus. Worldwide attempts
made to stimulate student interest in medical subjects, particularly
basic sciences have resulted into two suggestions: (a) early exposure
to patients to create an awareness of the final objective of their
study; and (b) the use of integrated teaching [2].
Integration involves different subjects and specialties wherein indi-
vidual subject is subordinated to the main goal of training a compe-
tent physicians of first contact, a minimum target fixed by Medical
Council of India (MCI) [3]. At present, integration is done only in the
students' mind at widely dispersed times and dates which is not ef-
fective [2]. Curriculum integration usually involves both horizontal
and vertical integration, a pattern that is becoming widespread
throughout the world. Horizontal integration refers to learning
within the existing time frame i.e. I MBBS, II MBBS or III MBBS where
individual departments corroborate in a meaningful manner in the
development of the subject/concept. By this process, connections
are made between the different subjects and that learning is im-
proved by the interrelationships being made explicit. Vertical inte-
gration refers to combination of Pre, Para and Clinical sciences in
such a way that the traditional divide across years is broken down.
Hence, basic medical sciences are represented explicitly in the cur-
riculum within the clinical environments during all the years of MBBS
education and beyond into postgraduate training and continuing
professional development. This approach is realized to be more
meaningful and relevant to students. An integrated teaching offers
several advantages. Basic sciences are simplified without needless
details and taught along with clinical disciplines. Learning is short-
ened without repetition in different subjects giving a composite pic-
ture with concurrent clinical demonstration.
Integration therefore should be an official policy applicable to insti-
tution as a whole and cannot be implemented by individual subjects
or specialties. It requires freedom for each institution or university to
evolve its own methods at different levels in consultation with fac-
ulty. Keeping this in view MCI has incorporated use of integrated
teaching, both horizontal and vertical, in its policy document of VI-
SION 2015 with plans to restructure the curriculum and attain a bal-
ance between theoretical and practical hands-on learning [3]. Hin-
drances in its adoption are many fold, major being availability of
trained manpower, dissociation of hospital/clinical setup and class
room teaching, and the current evaluation and examination pattern
of the universities.
Curricular reforms and shift from traditional subject-based theoreti-
cal approach in a class room teaching to skill, competence and prob-
lem-based learning require appropriate mindset and capability on
part of the teachers. Teachers need to adapt to the reforms for which
appropriate training to be imparted to them. In this regard MCI has
initiated a faculty development program under its purview and
identified a number of medical colleges as regional learning facilita-
tion centers (RLFC) across the country [4].
Received: 20 April 2014 Accepted: 26 July 2014
References
1. Medical Council of India. Regulation on graduate medical education. New
Delhi: MCI, 1997.
2. Haranath P. Integrated teaching in medicine - Indian scene. Indian J Pharmacol
2013; 45(1):1-3.
3. Medical Council of India. Vision 2015-National meet on implementation of
reforms in UG and PG medical education. New Delhi: MCI, 2011.
4. Bhadra UK. Medical education in India: Current issues and challenges. J Indian
Med Assoc 2013; 111(2): 84-85.

1
Department of Physiology, Deccan College of Medical Sciences, India
Correspondence: Mohammed Abdul Hannan Hazari
Email: hannanhazari@deccancollegeofmedicalsciences.com

Abstract
The present medical curriculum utilizes a large part of the allotted time frame in the form of didactic theoretical lectures while little time is
available for practical, clinical and behavioral skills acquisition which is required of a basic doctor. Curricular reforms and shift from traditional
subject-based theoretical approach in a class room teaching to skill, competence and problem-based learning require appropriate mindset
and capability on part of the teachers. Teachers need to adapt to the reforms for which appropriate training to be imparted to them. (El Med
J 2:3; 2014)
Keywords: Integrated Teaching, Medical Education, Curriculum

Open Access Letter to Editor
2014 Mu et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits
Cite this article as: Mu J, Li X, Zhang J, Bo P: Renal transplant recipient undergoing cardiac surgery: Immunosuppressive management. El Mednifico Journal 2014, 2(3): 315-316.
Renal transplant recipient undergoing cardiac surgery: Immunosuppressive management
Junsheng Mu
1
, Xianshuai Li
1
, Jianqun Zhang
1
, Ping Bo
1

Introduction
An increasing number of renal transplants are being performed
world-wide. Many of them suffer from severe heart diseases which
require operative treatment. Such patients face a higher surgeon risk
compared to patients with normal renal function. In these patients,
appropriate immunosuppressive management is an important issue.
We present a case of aortic valve replacement for quadricuspid aortic
valve with regurgitation and stenosis in a renal transplant recipient,
and suggest a strategy to avoid organ rejection during the whole
perioperative period.
A 66-year-old woman presented to hospital with a 5-year history of
dyspnea on exertion, which had worsened over the past month. She
had received a kidney transplant 9 years previously. Physical exami-
nation revealed a blood pressure of 105/60 mm Hg and heart rate of
89 beats/min. Cardiac auscultation revealed a grade 2/6 systolic mur-
mur over the aortic area and a grade 3/6 diastolic murmur over the
left sternal border. Laboratory tests showed BUN 7.8 mmol/l, uric
acid 157.0 mol/l, and creatinine 57.7 mol/l, indicating normal renal
function. Electrocardiography showed sinus rhythm, left axis devia-
tion, and left ventricular hypertrophy and strain. Chest X-ray showed
left ventricular enlargement, slight widening of the ascending aorta,
and a cardiothoracic ratio of 0.56. Transthoracic echocardiography
showed severe aortic regurgitation and mild aortic stenosis. Color
Doppler flow imaging showed a large diastolic flow reversal signal
across the aortic valve, vena contracta 7.7 mm, and flow along the
anterior leaflet of the mitral valve, resulting in slightly reduced open-
ing of the anterior leaflet. Continuous wave mode imaging showed
increased forward flow velocity across the aortic valve with an aver-
age pressure difference of 21 mm Hg. There was severe left ventric-
ular enlargement but a normal ejection fraction of 57%, and widen-
ing of the aortic sinus (42 mm), ascending aorta (45 mm), and first
portion of the descending aorta (31 mm). Two- and three-dimen-
sional transesophageal echocardiography revealed an asymmetric
quadricuspid aortic valve (QAV) [Figures 1(a), 1(b)] and severe aortic
regurgitation due to incomplete leaflet coaptation.
Techniques
The patient was treated with inotropes, diuretics, vasodilators, and
other conventional treatment, resulting in improvement of her clini-

1
Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical
University; Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
Correspondence: Junsheng Mu
Email: wesleymu@hotmail.com
cal condition. She continued to take her long-term immunosuppres-
sant medication of cyclosporine 50 mg twice daily and mycopheno-
late mofetil 0.25 g twice daily. After all investigations were complete,
she underwent aortic valve replacement. Intraoperative observation
showed an enlarged left ventricle, widening of the aorta, an asym-
metric QAV, and severe aortic regurgitation [Figure 1(c)], which was
consistent with the preoperative transthoracic echocardiography
findings. She received a 25-mm bioprosthetic aortic valve (St. Jude
Medical Inc., USA).

Abstract
Cardiac surgery in renal transplant recipients has been become an important issue since it may have an impact on graft and patient survival.
In addition, a renal transplant recipient usually needs to take long-term immunosuppressive medication, which would increase the risk and
difficulty of cardiac surgical operation. We present a case of aortic valve replacement for quadricuspid aortic valve with regurgitation and
stenosis in a renal transplant recipient. We also suggest a strategy to avoid organ rejection during the whole perioperative period. (El Med J
2:3; 2014)
Keywords: Aortic Valve Replacement, Quadricuspid Aortic Valve, Renal Transplant, Immunosuppressive

Figure 1 (a): Two-dimensional transesophageal
echocardiography revealed a quadricuspid aortic valve.

Figure 1 (b): Three-dimensional transesophageal
echocardiography revealed a quadricuspid aortic valve.

Figure 1 (c): Intraoperative observation showed a
quadricuspid aortic valve.

316 Renal transplant recipient undergoing cardiac surgery
Vol 2, No 3
The patient was given oral cyclosporine 50 mg and mycophenolate
mofetil 0.25 g on the morning of surgery, intravenous methylpredni-
solone 500 mg during surgery, and intravenous methylprednisolone
150 mg/day for three days starting on the day of surgery. Oral cyclo-
sporine 50 mg twice daily and mycophenolate mofetil 0.25 g twice
daily were continued from the day after surgery. She was given
standard antibiotic prophylaxis, inotropes, diuretics, vasodilators,
and anticoagulants. Her renal function was monitored daily and re-
mained stable. She had an uneventful recovery with normal temper-
ature, stable cardiac function, and no obvious renal transplant rejec-
tion. On the 13
th
day after surgery, routine laboratory investigations
including renal function tests were within the normal range, echo-
cardiography and chest x-ray did not show any abnormalities, and
she was discharged from hospital.
Comment
The patient had received a kidney transplant 9 years previously, and
was taking long-term immunosuppressive medication, which in-
creased the risk and difficulty of the operation. We administered in-
travenous methylprednisolone, 500 mg during surgery and 150
mg/day for 3 days after surgery, to prevent rejection and provide
anti-inflammatory and anti-allergy effects. Obviously, the risk of re-
jection was not enhanced when immunosuppressive therapy was
maintained throughout the perioperative period.
With taking long-term immunosuppressive medication, infection
was the most worrying operation complication for a renal transplant
recipient. So controlling blood glucose well and rationally using an-
tibiotics was essential. Early ambulation and strengthening the man-
agement of respiratory tract was also very important. In order to pre-
vent the damage of cardiopulmonary bypass on transplant, we tried
to shorten the operation time in the condition of low temperature.
At the same time, we remained high perfusion pressure during the
bypass, ensuring that the patient maintained urine, and her renal
function was monitored daily after operation.
With careful use of immunosuppressive drugs, renal transplant rejec-
tion was avoided. The principle post-operation complications are
bleeding and infection and the overall mortality related to surgery is
8-10% [1]. Christoph Dresler reported that patients with functioning
renal allografts undergoing open heart operations have acceptably
low mortality and morbidity rates [1]. Cardiac diagnostic studies and
necessary open heart operations should be performed without delay
when cardiac symptoms occur. Renal transplant recipients should be
treated in the same manner as patients not having transplantation,
with particular attention to maintaining kidney graft function by con-
ventional therapeutic means.
In addition, QAV without hemodynamic abnormalities or clinical
symptoms does not need treatment, whereas QAV with severe val-
vular dysfunction requires aortic valve replacement or valvuloplasty
[2-3]. In this case, QAV resulted in severe aortic valve regurgitation
and mild aortic valve stenosis, compensatory hypertrophy of the left
ventricle, impaired left ventricular function, and obvious clinical
symptoms, indicating a need for aortic valve replacement. In this pa-
tient with QAV with regurgitation and stenosis and a history of renal
transplantation, aortic valve replacement was clearly indicated. And
the patients aortic wall was thin and fragile because of the long-
term use of immunosuppressive medication, resulting in general
seeping of blood through many points in the aortic wall during sur-
gery. A polyester sheet was placed around the aortic wall to achieve
hemostasis.
This is the first reported case of QAV with regurgitation and stenosis
in a patient with previous renal transplantation. This case provides
important insights into the immunosuppressive management of a
patient requiring aortic valve replacement after renal transplantation
during the perioperative period.
Received: 20 January 2014 Accepted: 27 July 2014
References
1. Dresler C, Uthoff K, Wahlers T, et al. Open heart operations after renal
transplantation. Ann Thorac Surg, 1997; 63(1): 143-6.
2. Schulze MR, Strasser RH. Images in clinical medicine. Uni-, bi-, tri-, and
quadricuspid aortic valves. N Engl J Med. 2006, 355(12):e11.
3. Formica F, Sangalli F, Ferro O, Paolini G. A rare cause of severe aortic
regurgitation:quadricuspid aortic valve. Interact Cardiovasc Thorac Surg. 2004,
3(4):672.


2014 Demirci et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Demirci H, Ermis F, Polat Z, Kantarcioglu M, Uygun A, Bagci S: Munchausen syndrome presenting with recurrent abdominal pain and coagulation disorder. El Mednifico Journal 2014, 2(3): 317-
318
Munchausen syndrome presenting with recurrent abdominal pain and coagulation disorder
Hakan Demirci
1
, Fatih Ermis
2
, Zulfikar Polat
1
, Murat Kantarcioglu
1
, Ahmet Uygun
1
, Sait Bagci
1

Introduction
Munchausen's syndrome is a psychological and behavioral condi-
tion, a factitious disorder, or mental illness, wherein the sufferer re-
peatedly acts as if he or she has a physical or mental disorder when,
in truth, he or she has caused the symptoms [1]. People affected by
this attention seeking syndrome feign disease, illness, or psycholog-
ical trauma to draw attention or sympathy to themselves. The name
of Munchausen syndrome derives from German aristocrat Karl Frie-
drich Hieronymus Freiherr von Mnchausen, who became famous
for telling tall tales about his exploits and past. Baron's fictional ex-
ploits, narrated mostly by himself, focus on his impossible achieve-
ments as a warrior, hunter, and traveler, including rides on cannon-
balls and trips to the Moon.
Munchausen syndrome is also known as MOON-chow-zun syn-
drome, hospital hopper syndrome, thick chart syndrome, or hospital
addiction syndrome. Some healthcare professionals refer sufferers of
this syndrome to as frequent flyers since they return to hospital just
as frequent flyers return to the airport. Asher was the first to name
this condition as Munchausen's Syndrome in his article published in
The Lancet in 1951 [2].
Typical characteristics suggesting the syndrome include deliberately
lying and pretending to be ill, intentionally taking drugs (insulin, war-
farin, laxatives, diuretics, vitamins, etc.) to induce adverse effects, re-
current abdominal pain, scars, rheumatologic, hematologic and var-
ious disorders [3]. People with this factitious disorder act this way
not to achieve a concrete benefit such as financial gain but to be
seen as injured or ill due to a deep inner motivation. They may even
pose serious health risks to themselves through undergoing painful
tests, investigations and operations just to get sympathy and utmost
attention given to those who are really ill. Some of the affected peo-
ple may even go further to self-injury, striving for causing signs like
cyanosis of a limb or blood in the urine.
Many of the sufferers have a comprehensive knowledge of proce-
dures and medical terms, thus are able to create plausible explana-
tions for their claims. Their portrayal of the symptoms may be so

1
Department of Gastroenterology, Gulhane Military Medical Academy, Turkey
2
Department of Gastroenterology, Duzce Medical Faculty, Duzce University, Turkey
Correspondence: Fatih Ermis
Email: fatihermis1@yahoo.com
convincing that it may be very difficult, labor intensive, expensive
and time consuming to establish the accurate diagnosis, and thor-
ough assessment with medical tests and investigations are usually
required to exclude possible underlying medical conditions.
The cause of Munchausen syndrome as yet remains obscure. There
is scant evidence about possible causes of the syndrome since many
sufferers refuse to comply with psychological profiling or psychiatric
treatment. Available theories about etiology of Munchausens syn-
drome include profound emotional traumas during childhood and
personality disorder. Management of Munchausen's syndrome re-
mains a formidable challenge since many of those affected refuse to
admit they have a serious problem and will probably not comply
with the recommended therapy. What adds a new dimension to
management of Munchausens syndrome is the irony that most suf-
ferers only admit to having a physical illness although they are gen-
uinely mentally ill. Psychiatric management includes psychoanalysis
and psychotherapy, family therapy and cognitive behavioral therapy.
In this case report, we describe a 28-year-old case (patient) with co-
agulation disorder caused by self-inflicted warfarin use admitting re-
peatedly to many different hospitals with abdominal pain.
Case Report
A 28-year-old woman presented to our outpatient clinic with com-
plaints of abdominal pain, fatigue, nausea and vomiting. She had a
history of many hospital admissions which failed to establish a spe-
cific diagnosis albeit various investigations were performed. The pa-
tient was referred to our inpatient clinic for further evaluation. De-
tailed history revealed that she had 6 operations including appen-
dectomy, Billroth II, right ovarian cyst rupture, right oopherectomy,
small bowel resections due to ileus, penicillin allergy, and fasciola
hepatica infestation.
She told that she was not using any drugs and she was working as a
medical secretary in a private hospital after leaving medical school
at the 4
th
year due to medical reasons. She explained her abdominal
pain as having a history of 2 years with a peak in severity recently

Abstract
Munchausen syndrome is a serious psychiatric factitious disorder, or mental illness, wherein sufferers feign disease, illness, or psychological
trauma in order to draw attention or sympathy to themselves. In this attention-seeking syndrome associated with severe emotional
difficulties, affected person repeatedly acts as if he or she has a physical or mental disorder when, in truth, he or she has caused the symptoms.
The atypical manifestations of Munchausen syndrome represent a broad spectrum of clinical findings and features. It may be very difficult,
labor intensive, expensive and time consuming to establish the accurate diagnosis. Herein, we report of a 28-year-old patient with coagulation
disorder caused by self-inflicted warfarin use admitting repeatedly to many different hospitals with abdominal pain. Thorough psychiatric
assessment and workup to shed light on the challenging clinical situation revealed the diagnosis of Munchausen syndrome for this patient.
(El Med J 2:3; 2014)
Keywords: Munchausen Syndrome, Warfarin, Psychiatric Disorder
318 Munchausen syndrome
Vol 2, No 3
and a significant increase in pain after eating. She told that she was
informed about having ileus-subileus attacks in her previous hospital
admissions and 2 years ago, anemia and elevated INR values were
detected when she presented with fatigue and epistaxis. The ele-
vated INR values caused her to be supported with fresh frozen
plasma when she had an operation 1 year ago. The patient described
all her complaints and medical history plausibly by her own hand-
writing on an information sheet. Physical examination revealed nor-
mal vital signs of 115/60 mmHg blood pressure, heart rate 100/mi-
nute, body temperature 36.6 centigrade degrees. Auscultation of
heart and lungs was normal. She had many scars in the abdominal
region along with gingival bleeding.
Detailed laboratory analysis revealed WBC: 6.2 10
3
/mm
3
(3.6-9.6),
hematocrit: 30.1% (36.4-43.9), hemoglobin: 10.3 g/dL, MCV: 69 fL,
Platelets: 340.000/mL, Fe: 40 g/dL (53-167), TIBC: 350 g/dL (155-
300), Ferritin: 11 ng/mL, PT-INR: 68-5.6, aPTT: 27 sn (14-41), sedimen-
tation: 17 mm/h, BUN: 13 mg/dL, creatinine: 0.61mg/dL, total biliru-
bin: 0.6 (0.2-1) mg/dL, SGOT: 25 (10-40) U/L, SGPT: 34 (10-40) U/L,
alkaline phosphatase: 119 (38-155) U/L, gamma-glutamyltransfer-
ase: 25 (10-49) U/L, albumin: 4.2 (3.5-5.5) g/dL, amylase: 68 (25-90)
U/L, Na: 139 mmol/L, K: 4.2 mmol/L, TSH: 2.58 U/mL, T3: 2.76
pg/dL, T4: 0.73 ng/dL, ANA negative, normal urinalysis.
Hematology consultation was requested regarding the prolonged
prothrombin time. Specific clotting factor levels were analyzed and
mixing test was performed. Significant decrease was detected in fac-
tors II, VII, IX and X levels.
Abdominal X-ray showed minimal gas shadows in pelvis. Ultrasound
scan of the whole abdomen revealed the absence of right ovary due
to an operation, 75x65 mm heterogeneous and hypoechoic image
with a thick wall in the left ovary suggesting a cyst with hemorrhage.
Abdominal CT scan and CT angiography showed a uniformly-
bounded high-density mass of 8x6 cm located in the right superol-
ateral vicinity of bladder. Ascending colon had an increased trans-
verse diameter of 7 cm in the largest part. Calibration of abdominal
aorta, celiac trunk, superior and inferior mesenteric arteries were nor-
mal. Gastrointestinal endoscopy revealed LA grade A esophagitis
and the Billroth II operation. Colonoscopy was normal. Small intes-
tine enteroclysis revealed minimally slow but unobstructed passage
in the distal jejunal and proximal ileal loops located in middle quad-
rant of abdomen.
Genetics analysis of autoimmune diseases (Hyper-IgD syndrome,
TNF-receptor associated periodic syndrome) and Familial Mediterra-
nean Fever to explain recurrent abdominal pain revealed no genetic
mutations. Due to the elevated INR values in close follow-up, the pa-
tient was given fresh frozen plasma when indicated.
Considering the inconsistent behavior of the patient and her non-
compliance to treatment, drug or substance abuse was suspected
and toxicological analyses were performed as part of patient evalu-
ation. Warfarin was detected in her blood which explained pro-
thrombin time prolongation. Contacting her family ascertained that
she had never received medical education. Psychiatric consultation
was made and the diagnosis of Munchausens syndrome was estab-
lished.
Discussion
Munchausen syndrome is an attention seeking syndrome in which
sufferers feign disease, illness, or psychological trauma to draw at-
tention or sympathy to themselves. Since patients usually have a
comprehensive knowledge of medical terms and procedures, they
may have plausible explanations for their claims which makes diag-
nosis difficult, labor intensive, expensive and time consuming.
Although a rare entity, Munchausens syndrome may have severe
presentations [4, 5]. With an inner need to get sympathy and draw
the most attention, sufferers mimic symptoms of diseases and seek
medical procedures and operations even at the expense of posing
serious health risks to themselves through causing signs like blood
in the urine or cyanosis of a limb, or intentionally taking drugs detri-
mental to their health [6]. Patients affected usually have adequate
knowledge of procedures, medical terms and their own medical his-
tory to create plausible explanations for their claims [7], like our pa-
tient working as a medical secretary with easy access to drugs.
Management of Munchausen syndrome is challenging. Sufferers
mostly admit to having a physical illness, when, in truth, they are
mentally ill. Psychiatric treatment is crucial for these patients. How-
ever, they seldom, if ever comply with the recommended therapy
very commonly leaving hospitals when final diagnosis is established
[8, 9].
A high index of suspicion by clinicians is required not to fail to notice
Munchausen syndrome particularly when the patient has a history of
repeated operations and hospital admissions without a distinct diag-
nosis, as in our patient.
References
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental
Disorders, 4th ed. Washington, DC: American Psychiatric Association;
1994:471472.
2. Asher R: Munchausen syndrome. Lancet 1951, 1:339-341.
3. Guggenheim FG. Somatoform disorders. In: Sadock BJ, Sadock VA, editors.
Kaplan and Sadocks Comprehensive Textbook of Psychiatry. 7th ed.
Philadelphia, PA: Lippincott, Williams and Wilkins; 2000:15141518.
4. Turner J, Reid S. Munchausen's syndrome. Lancet 2002;26: 346-349.
5. Robertson MM, Cervilla JA: Munchausen's syndrome. Br J Hosp Med 1997,
58(7): 308-312.
6. Eisendrath SJ: Current overview of factitious phsical disorders. MD Feldman,
SJ Eisendrath (eds): The Spectrum of Factitious Disordersda, American
Psychiatric Press Inc., Washington D.C., 1996, 21-36.
7. Rothenhausler HB, Kapfhammer HP: Munchhausen patients in general
hospitals--Clinical features and treatment approaches in C-L psychiatry
settings Rothenhausler HB, Kapfhammer HP. Psychiatr Prax 2002, 29(7): 381-
387.
8. Pope HG Jr, Jonas JM, Jones B: Factitious psychosis: phenomenology, family
history and long term outcome of nine patients. Am J Psychiatry 1982;
139:1480-1483.
9. Huffman JC, Stern TA: The diagnosis and treatment of Munchausen's
syndrome. Gen Hosp Psychiatry 2003, 25(5): 358-363.


2014 Kumar et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
Cite this article as: Kumar GNP, Manjunatha B, Rani S, Balaraj BM, Babu YPR: Traumatic asphyxial deaths. El Mednifico Journal 2014, 2(3): 319-320.
Traumatic asphyxial deaths
G N Pramod Kumar
1
, B Manjunatha
1
, Smitha Rani
1
, B M Balaraj
1
, Y P Raghavendra Babu
2

Introduction
Trauma related deaths are the third leading cause among all age
groups after cardiovascular and cancer related deaths. About 33% of
blunt force trauma victims, have an associated thoracic injury and it
is estimated that 25% of traumatic deaths are secondary to chest
trauma [1]. Traumatic asphyxia occurs when a heavy weight presses
down on an individuals chest or upper abdomen, making respiration
impossible [2]. It is termed 'traumatic' because gross mechanical
forces are usually the reason for fixation of the thoracic cage [3].
Traumatic asphyxia occurs when ventilation is compromised due to
external forces. It may be seen in building collapses, motor vehicle
collisions, avalanches and weekend car mechanics, who inexpertly
raise a car to work under it. In 1837, Olliver dAngers described these
findings in people trampled to death by crowds in Paris [4, 5]. This
syndrome has various other names such as acute thoracic compres-
sion syndrome, Oliver's or Perthes syndrome and ecchymotic mask.
It is a rare entity presenting with cervicofacial cyanosis and edema,
subconjunctival hemorrhage and petechial hemorrhages of the face,
neck and upper chest as a result of a compressive force to the
thoraco-abdominal region [1]. We report four cases of death due to
traumatic asphyxia involving victims of childhood and adolescent
age group.
Case Presentation
Case 1
A 19 year old male cadaver was brought with history of sliding of
mud over him while working in a pit of about 20 feet depth which
resulted in death at the scene of occurrence. On examination there
was distinct purplish discoloration of face, neck and the chest. The
area below the chest was pale with cyanosis of finger nails. Internally,
diffuse contusion of the posterior chest wall muscles was seen on
the right and left side corresponding to 5
th
- 7
th
ribs and 5
th
- 6
th
ribs
respectively. Trachea contained mud particles whereas both the
lungs showed diffuse contusion posteriorly. Petechial hemorrhages
were seen in brain.
Case 2
Body of male child aged 6 years was brought with history of acci-
dental fall of heavy stack of sugar cane over the child while loading
a lorry. Post mortem examination revealed intense congestion of the

1
Department of Forensic Medicine and Toxicology, JSS Medical College,
JSS University, Mysore, India.
2
Department of Forensic Medicine and Toxicology, Kasturba Medical College,
Mangalore, Manipal University, India.
part of body above the level of chest along with face (Figure 1). Mul-
tiple petechial hemorrhages were present on the chest. On internal
examination petechial hemorrhages were seen in white mater of
brain.

Case 3
Body of female child aged 4 years was brought with history of fall of
sugar cane load over the deceased while loading the lorry with sug-
arcane. Post mortem examination was conducted on next day. The
upper part of chest & face was congested. External examination
showed impact abrasions over chest & forearms. On internal exami-
nation brain showed petechial hemorrhages. Case 2 and 3 are from
the same incident.
Case 4
An 8 year old male was crushed under the debris of collapsed wall
while asleep at home with other family members. The face was con-
gested with purplish red discoloration. Collection of mud particles
were seen in both ears. On internal examination upper lobe of left
lung was contused.
Discussion
The syndrome of traumatic asphyxia is an uncommon one and pre-
sents with the classical triad of craniofacial cyanosis, petechial and
subconjunctival hemorrhages [6, 7]. Internally, the congestion is less
marked than on the surface, but the lungs are usually dark and heavy
Correspondence: Y P Raghavendra Babu
Email: bobs009@hotmail.com
Abstract
Asphyxial deaths are commonly encountered in forensic practice; however deaths due to traumatic asphyxia are uncommon. Traumatic
asphyxia is a type of asphyxia where death results from mechanical compression of the chest and/or abdomen. Four cases of accidental
traumatic asphyxia in pre-adolescent and adolescent age group are reported and discussed. (El Med J 2:3; 2014)
Keywords: Traumatic Asphyxia, Accident, Adolescents

Figure 1: Congestion of face and chest. Note the intense
discoloration of face.
320 Traumatic asphyxial deaths
Vol 2, No 3
and may well have subpleural petechial hemorrhages, the true 'Tar-
dieu spots'. There may be injuries to the chest wall from the trauma
of the fixating object [3].
In 1908 Bolt suggested that there were four principal factors in the
pathogenesis of traumatic asphyxia. These are deep inspiration, clo-
sure of the glottis, splinting of the thoracic and abdominal muscula-
ture and thoracic or upper abdominal compression. He postulated
that in order to produce the classical features of traumatic asphyxia
there must be a "fear response" in which the victim, apprehensive of
imminent injury, takes and holds a deep breath. This allows the gen-
eration of far higher thoracic pressures than compression alone [6].
Shapiro suggested that the pressure on the chest forces blood back
into the great veins and as the venous valves in the subclavian ves-
sels prevent displacement into the arms, the extra volume is forced
up the valveless jugular system to congest the head and neck [3].
Following a compressive force to the chest or upper abdomen posi-
tive pressure is transmitted to the mediastinum, forcing blood out of
the right atrium into the innominate and jugular veins. This leads to
an increase in pressure in the small venules and capillaries of the face
and head, causing petechial haemorrhages [6]. In some cases victims
who die of traumatic chest compression may not have petechiae.
This may be seen with chest compression that is great enough to
impair the left heart function as well as the right. Increased cephalic
venous pressure will not develop in this scenario because even
though the venous return is impaired, the input arterial pressure is
also compromised [4, 8].
Traumatic asphyxia is, for the most part, seen in children because of
their elastic walls [9]. As a result, fewer chest fractures and pulmo-
nary pathologies have been reported in children in contrast to adults
[1]. The amount of force required and duration of application to pro-
duce the typical manifestation of traumatic asphyxia is not known.
Weights ranging from 3000 pounds to several tons have been rec-
orded and the typical range of compression is between two and five
minutes [9].
Visit to scene of occurrence will help to corroborate the localization
of injuries on the victim. Eren B et al reported a case wherein the
victim was found compressed by rubbish container in the elevator
in an unusually awkward position of the block of flats where he was
working as doorkeeper. Death resulted from compression of thorax
without other fatal factors in which the force causing the chest com-
pression was distinctly determined by the autopsy and scene inves-
tigation as accidental traumatic asphyxia [5].
The four reported cases illustrate the classical features of traumatic
asphyxia. In all four cases there was marked congestion of face, con-
tusion of lung was seen in two cases, and 3 out of 4 cases showed
petechial hemorrhages in the brain (Table 1).
In patients with traumatic asphyxia, age and severity of trauma di-
rectly affect the outcome including morbidity and mortality. In case
of children being left unsupervised, it is necessary that parents
should be educated regarding such risks, so that proper preventive
measures are taken.
References
1. Uzkeser M, Aydin Y, Emet M, Cakir Z, Aslan S, Ozturk G and Akoz A. Traumatic
Asphyxia. Hong Kong j.emerg.med. 2011;18(5) :339-42.
2. DiMaio VJ, DiMaio D. Asphyxia In: Forensic Pathology.2nd edn. Boca Raton,
FL:CRC Press;2001:240-44.
3. Saukko P, Knight B. Suffocation and Asphyxia In: Knights Forensic Pathology.
3rd edn. London, United Kingdom: Edward Arnold Publishers,2004:363-64.
4. Gill JR, Landi K. Traumatic Asphyxial Deaths Due to an Uncontrolled Crowd.
Am J Forensic Med Pathol. 2004;25: 35861.
5. Eren B, Turkmen N, Fedakar R. An unusual case of thoracic compression. J Ayub
Med Coll Abbottabad.2008;20(1): 134-5.
6. Hewson GC, Egleston CV, Cope AR. Traumatic asphyxia in children. J Accid
Emerg Med 1997;14:47-49.
7. Sharma A, Rani A, Barwa J. Traumatic asphyxial deaths due to an uncontrolled
crowd at railway station: Two case reports. J Indian Acad Forensic Med 2010,
32(3): 254-6.
8. Ely SF,Hirsch CS. Asphyxial deaths and petechiae: a review. J Forensic Sci
2000;45(6):1274-1277.
9. Sarihan H, Abes M, Akyazici R, Cay A, Imamoglu M, Tasdelen I and Imamoglu I.
Traumatic asphyxia in children. Journal of cardiovascular surgery
1997;38(1):93-95.

Table 1: Profile of cases
Case Year Sex* Age (years) Cause of death Manner of death Place of incident History
1 2000 M 19 Chest compression Accidental Construction place Sliding of mud
2 2004 M 06 Chest compression Accidental Field Over turned sugar cane load
3 2004 F 04 Chest compression and aspiration Accidental Field Over turned sugar cane load
4 2005 M 08 Chest and abdomen compression Accidental Victims house Collapse of wall
*M: Male, F: Female


2014 Ulu et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits
Cite this article as: Ulu SM, Polat M, Altug A, Yuksel S: A fatal situation: Diabetes insipidus and superimposed acute polyuric kidney injury. El Mednifico Journal 2014, 2(3): 321.
A fatal situation: Diabetes insipidus and superimposed acute polyuric kidney injury
Sena Memnune Ulu
1
, Mehmet Polat
1
, Abdullah Altug
1
, Seref Yuksel
1

Introduction
Diabetes insipidus (DI) is a disorder due to lack of secretion or activ-
ity of antidiuretic hormone (ADH). It is characterized by polyuria [1].
Acute kidney injury (AKI) is defined as the increase in plasma creati-
nine levels at least 0.5 mg/dl or change in baseline serum creatinine
value as 50% or over. During the recovery period, polyuria may be
seen and sometimes urine output (between 3,000cc and 10,000cc)
may continue for 3-5 days up to several months. During this period,
the replacement of urine volume is crucial [2, 3].
Case Presentation
A 19-year-old male patient hospitalized by neurosurgery department
clinic due to head trauma, was referred to our clinic due to AKI. When
the patient was evaluated, BUN and creatinine values were found
increased (BUN: 22 mg/dL, creatinine: 0.9 mg/dL on hospitalization
day and BUN: 65 mg/dL, creatinine: 6.8 mg/dL in the control). The
oliguric patient was brought to our clinic with a diagnosis of AKI. In
the follow-up period, oliguria had remained, creatinine value
reached 7 mg/dl and uremic symptoms were seen and so hemodial-
ysis (HD) treatment was initiated. After 3 sessions of HD, his symp-
toms and general condition improved, urine output increased and
creatinine value decreased up to 0.8 mg/dL.
In the follow-up period, he developed polyuria and continued to re-
main polyuric. Urine output reached 23,000cc to 25,000cc/day and
continued for a long time (2 weeks). The patient had a history of
head injury, lower urine density (1.000-1.003) and lower urine osmo-
larity (216 mOsm/kg and 260 mOsm/kg) and was thought as central
DI. A test dose of nasal desmopressin (5g) was administered. After
a test dose of nasal desmopressin, urine output decreased and urine
osmolarity increased. He was diagnosed as a case of central DI and
superimposed polyuric AKI and continued on desmopressin. In the
follow-up, urine output decreased to 12,000cc and then up to
2,000cc/day. Any electrolyte abnormalities were not experienced
and laboratory results were in the normal range. The patient was
discharged with appropriate recommendations.
Conclusion
Diabetes insipidus is a disease leading to plenty of lower-density
urine. Different drugs are used in treatment, according to whether it
is central or nephrogenic. Desmopressin acetate is beneficial in cen-
tral DI treatment [4-6]. AKI is a disease characterized by a reduction
in glomerular filtration rate and can be seen with polyuria which may
cause serious fluid and electrolyte disorders [2, 3]. To date, renal DI
in the polyuric phase of AKI has been reported once but central dia-
betes insipidus and polyuric AKI characterized by severe polyuria has
never been reported [7]. Serious morbidity may result if the two en-
tities occur in combination, as in our patient.
In summary, this first case with AKI and superimposed DI has a major
clinical implication. In nephrology practice, if the disease duration of
a polyuric AKI patient lasts longer or a clinic incompatible with the
disease occurs, overlapping diseases should be kept in mind as in
this case.
References
1. Clancy Howard, Thomas Berl. Disorders of Water Balance: Hyponatremia&
Hypernatremia. Edgar V. Lerma, Jeffrey S. Berns, Allen R, ed. Nssenson Current
Diagnosis & Treatment Nephrology & Hypertantion. McGraw-Hill Companies
International Edition 2009: 22-31
2. Eldelstain CL,Schrier RW. Pathophysiology of ischemic acute RENAL failure. In:
Schrier RW, ed. Diseases of the kidney and urinary tract, vol 2,7th ed.
Philadephia: Lippincott Williams & Wilkins,2001:1041-1069
3. Bellomo R, Ronco C. Acute renal failure in the intensive care unit: adequacy of
dialysis and the case for continuous therapies. Nephrol Dial Transplant.
1996;11(3):424-8.
4. Seckl JR, Dunger DB. Diabetes Insipidus. Drugs 1992;44(2): 216-24
5. Maghnie M, Cosi G, Genovese E, et al. Central diabetes insipidus in children
and young adults. N Engl J Med. 2000;343(14):998-1007.
6. Fujisawa I, Nishimura K, Asato R, et al. Posterior lobe of the pituitary in diabetes
insipidus: MR findings. J Comput Assist Tomogr. 1987;11(2):221-5.
7. Mertz DP, Sarre H. Renal diabetes insipidus in the polyuric phase of acute renal
failure. Klin Wochenschr. 1962;40:23-32.

1
Department of Nephrology, Afyon Kocatepe University, Faculty of Medicine,
Afyonkarahisar, Turkey.
Correspondence: Sena Memnune Ulu
Email: drsenaulu@yahoo.com

Abstract
Diabetes insipidus occurs as a result of lack of secretion or activity of antidiuretic hormone. Polyuria may occur during acute kidney injury
follow-up period. Until now, these two diseases in which monitoring and replacement of fluid and electrolyte are crucial, have not been
reported together. In this report, a fatal situation, central diabetes insipidus and superimposed acute polyuric kidney injury is presented. (El
Med J 2:3; 2014)
Keywords: Diabetes Insipidus, Acute Kidney Injury, Polyuric

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provides a comprehensive list of reporting
guidelines.
More details on these and other reporting
guidelines are also available on the website
of US National Library of Medicine.
Human Subjects: Methods sections of pa-
pers on research using human subject or
samples must include ethics statements
that specify the name of the approving
institutional review board or equivalent
committee(s). If approval was not obtained,
the authors must provide a detailed state-
ment explaining why it was not needed.
Please note that the authors may be asked
to upload the documentation of approval.
Animal Research: Methods sections of
manuscripts reporting results of animal
research must include required ethics
statements that specify:
The full name of the relevant ethics com-
mittee that approved the work, and the
associated permit number(s) (where ethical
approval is not required, the manuscript
should include a clear statement of this and
the reason why)
Relevant details for efforts taken to reduce
animal suffering
Privacy and Confidentiality: Privacy is the
control over the extent, timing, and circum-
stances of sharing oneself (physically, be-
haviorally, or intellectually) with others.
Confidentiality pertains to the treatment of
information that an individual has disclosed
in a relationship of trust and with the ex-
pectation that it will not be divulged to
others without permission in ways that are
inconsistent with the understanding of the
original disclosure. Privacy and confidential-
ity must be maintained at all phases of the
research and the same must be stated in
the methods section of the manuscript.
Proper written, informed consent should be
taken where applicable, and the subjects
should be made aware of the complete

x

protocol and nature of dissemination of
data. The authors may be required to up-
load relevant documentation where appli-
cable.
Please refer to the Health Insurance Porta-
bility and Accountability Act (HIPAA) for
more information.
Types of Articles: EMJ welcomes following
types of articles:
Original articles (typically not longer than
5000 words): These are based on primary
observations. The results should not
have been published elsewhere either
fully or in part. An abstract (not longer
than 250 words) is required for submis-
sion.
Short Reports (typically not longer than
2000 words plus 4 figures/tables): Re-
ports of new and original work with sig-
nificance will be considered for publica-
tion. An abstract (not longer than 250
words) is required for submission.
Reviews (typically not longer than 6000
words plus 5 figures/tables): A review is a
well referenced, sharply focused, critical
assessment of literature provided by ex-
perts in the subject matter covered by
this review. Authors may and should ex-
press their individual opinion about a
topic of controversy or suggest new ap-
proaches for future research. It is re-
quired that these opinions are expressed
in a manner which makes them clearly
identifiable and distinguishable from lit-
erature data. An abstract (not longer
than 250 words) is required for submis-
sion.
Case reports (typically not longer than
1800 words plus 2 high quality fig-
ures/tables): Case reports describe clini-
cal case histories of interest. EMJ will
consider for publication case reports of
extraordinary significance with discus-
sion and case of very rare diseases with
review of contemporary literature for
educational purposes. An abstract (not
longer than 100 words) is required for
submission.
Opinions and Debates (typically not
longer than 1500 words plus 2 figures):
This section provides a possibility for
publishing opinions, perspectives and
debates. These articles present an argu-
ment that is not necessarily based on
practical research. They can report on all
aspects of the subject including sociolog-
ical and ethical aspects. Opinions and
Debates are published at the discretion
of the Editor-in-Chief and may undergo
peer-review. An abstract is not required
for submission.
Essays (typically not longer than 1000
words plus 5 references): This section is
reserved for students only. This section
provides a platform for students from all
disciplines of biology and medicine to
exhibit their creativity and writing skills.
Articles in this section include but are not
limited to stories from college life, elec-
tive reports etc. Essays are published at
the discretion of the Editor-in-Chief and
may undergo peer-review. An abstract is
not required for submission.
Letters to the editor (typically not longer
than 500 words plus 5 references). This
section only considers letters on articles
published previously in EMJ. Letters are
published at the discretion of the Editor-
in-Chief and may undergo peer-review.
An abstract is not required for submis-
sion.
In all cases manuscripts should be written in
clear and concise English. Every manuscript
should preferably include discussion of
most relevant and recent (recent 5 years)
literature related to the topic. The manu-
script should be written in font size 12-14,
double-spaced in all portions, abstract, text,
acknowledgments, references, individual
tables, and legends. Margins should be
about 2,5 cm (1 inch). All pages must be
numbered consecutively, beginning with
the title page. Please dont send the title
page as separate file.
Title Page: The title page should include
following information:
Article type: original article, short report,
review, case report, opinion, debate, es-
say, or letter to the editor.
Title of the article (bold letters, font size
14 or larger).
Authors list: Authors full names should
be given as first names followed by sur-
names, and should be clearly linked to
the respective institution by use upper
case Arabic numbers.
Affiliation(s)
Disclaimers (if applicable).
Corresponding author: The name, affilia-
tion, mailing address and e-mail address
of the author responsible for corre-
spondence about the manuscript on be-
half of all authors. The corresponding au-
thors e-mail address will be published.
The corresponding author is the guaran-
tor for the integrity of the manuscript as
a whole.
Source(s) of support in the form of
grants, equipment, drugs, or all of these
(if applicable).
A statement of financial or other rela-
tionships that might lead to a conflict of
interest.
Word count for the text (including ab-
stract, acknowledgments, figure legends,
and references).
Number of figures , Number of tables.
Abstract: An abstract should follow the title
page. It should not be longer than about
250 words and must reflect the content of
the article accurately. The abstract should
be structured as follows:
For original articles:
Background
Methods
Results
Conclusions
For short reports:
Background
Findings
Conclusions
For reviews:
A summary of the paper should be pro-
vided.
For case reports:
Background
Main observations
Conclusions
Key words: Following the abstract, provide
3 to 10 key words arranged in alphabetical
order. Terms from the Medical Subject
Headings (MeSH) list of Index Medicus
should be used; if suitable MeSH terms are
not yet available for recently introduced
terms, non-MESH terms may be used.

xi

Manuscript structure:
For original articles:
Background
Objective
Patients/Materials and Methods
Results
Discussion
Conclusions
Recommendations
For short reports:
Background
Methods
Findings
Conclusions
For case reports:
Introduction
Case report(s)
Discussion
Conclusions
For reviews: Review articles should be di-
vided into sections and sub-sections to
achieve highest possible text clarity.
References: References should be num-
bered consecutively in the order in which
they are first mentioned in the text. Identify
references in text, tables, and legends by
Arabic numerals in upper case. References
cited only in tables or figure legends should
be numbered in accordance with the se-
quence established by the first identifica-
tion in the text of the particular table or
figure. References to articles and papers
should mention: (1) name(s) initials of all
author(s), (2) title of paper; (3) title of the
journal abbreviated in the standard manner
(see Index Medicus); (4) year of publication;
(5) volume; (6) first and final page numbers
of the article (references to online articles
should have the same structure and addi-
tionally the appropriate web address fol-
lowing page numbers). (7) PMID number
(these numbers appear under each abstract
in PubMed). References which are not
PubMed indexed do not require a PMID
number.
Example: Lima XT, Abuabara K, Kimball AB,
Lima HC. Briakinumab. Expert Opin Biol
Ther. 2009 Aug;9(8):1107-13. PMID:
19569977

References to books and monographs
should include: (1) name(s) followed by the
initials of the author(s) or editor (s); (2)
chapter (if relevant) and book title; (3)
edition, volume, etc.; (4) place; (5) publish-
er; (6) year; (7) page(s) referred to.
Example: MacKie RM. Lymphomas and
leukaemias. In: Textbook of Dermatology
(Champion RH, Burton JL, Ebling FJG, eds),
5th edn, Vol. 3. Oxford: Blackwell Scientific
Publications. 1992; 2107-2134
Figures: Figures may be inserted into the
text file or may be uploaded separately as
additional files as JPEG or TIFF files. Manu-
scripts with low quality images will not be
considered for publication. Drawn Figures
will not be redrawn by the EMJ. Letters,
numbers, and symbols on Figures should be
clear and even throughout and of sufficient
size, that when reduced for publication
each item will still be legible. Figures should
be made as self-explanatory as possible.
Please provide Figure legends on a separate
page with Arabic numerals corresponding
to the illustrations. If photographs of pa-
tients are used, either the subjects must not
be identifiable or their pictures must be
accompanied by written permission to use
the photograph for publication.
Sending the Manuscript to the Journal: The
manuscript should be uploaded directly
onto the EMJ website. If you have any diffi-
culty with the above, the manuscript can be
sent by email to submit@mednifico.com.
Cover letter: Manuscripts submitted by e-
mail must be accompanied by a cover let-
ter, which should include the following
information.
A statement that the same or very similar
work has not been published or submitted
for publication elsewhere. A conference
presentation with a published abstract is
not considered a publication in this regard.
A statement of financial or other relation-
ships that might lead to a conflict of interest
A statement that the manuscript has been
read and approved by all the authors
In the case of manuscripts uploaded directly
to the EMJ website these statements will be
required by the uploading system. Any
additional information for the editor may
be provided in the Comments for the Edi-
tor box in Step 1 of the uploading proce-
dure.
Processing charges: There are no submis-
sion/per-page charges. However, the Board
may impose charges at a later point of time
in order to cover the fees associated with
open access publishing.
Submission Preparation Checklist: As part
of the submission process, authors are
required to check off their submission's
compliance with all of the following items,
and submissions may be returned to au-
thors that do not adhere to these guide-
lines:
The submission has not been previously
published, nor is it before another jour-
nal for consideration (or an explanation
has been provided in Comments to the
Editor).
The submission file is in OpenOffice,
Microsoft Word, RTF, or WordPerfect
document file format.
Where available, URLs for the references
have been provided.
The text is single-spaced; uses a 12-point
font; employs italics, rather than under-
lining (except with URL addresses); and
all illustrations, figures, and tables are
placed within the text at the appropriate
points, rather than at the end.
The text adheres to the stylistic and
bibliographic requirements outlined in
the Author Guidelines, which is found in
About the Journal.
If submitting to a peer-reviewed section
of the journal, the instructions in Ensur-
ing a Blind Review have been followed.
Copyright Notice
Authors who publish with this journal agree
to the following terms:
Authors retain copyright and grant the
journal right of first publication with the
work simultaneously licensed under a
Creative Commons Attribution License
that allows others to share the work with
an acknowledgement of the work's au-

xii

thorship and initial publication in this
journal.
Authors are able to enter into separate,
additional contractual arrangements for
the non-exclusive distribution of the
journal's published version of the work
(e.g., post it to an institutional repository
or publish it in a book), with an acknowl-
edgement of its initial publication in this
journal.
Authors are permitted and encouraged
to post their work online (e.g., in institu-
tional repositories or on their website)
prior to and during the submission pro-
cess, as it can lead to productive ex-
changes, as well as earlier and greater ci-
tation of published work (See The Effect
of Open Access).
Privacy Statement: The names and email
addresses entered in this journal site will be
used exclusively for the stated purposes of
this journal and will not be made available
for any other purpose or to any other party.

We accept Original Articles, Review Articles, Case Reports, Opinions and Debates, Essays, Letters to the Editor. There are no paper submission charges.
Submit your articles via the online system or send as an email to: submit@mednifico.com
We require editors, programmers, layout designers and proofreaders for our editorial staff. We also require avid medical bloggers for our sister website,
http://blogemia.com. We are also looking for journal representatives from different medical schools. To apply, send your CV to: apply@mednifico.com
El Mednifico Journal,
Address: El Mednifico Journal, Baba-e-Urdu Road, Karachi 74200 Pakistan. Email: editorial@mednifico.com. Phone: (92-334)2090696.

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