TheWestieHealthEBook

Commonhealthproblems,howtorecognizethemandwhattodo aboutthem JohnRobertson,VMDPhDandElizabethMcStay,BS VirginiaMarylandRegionalCollegeofVeterinaryMedicine(VMRCVM) VirginiaTech,Blacksburg,VA240610442 AboutthisEBook(electronicbook) WelcometothefirsteditionoftheWestieEBook,sponsoredbygenerous supportfromtheWestieFoundationofAmerica.Thiselectronicbookismeantto serveasasourceofinformationforWestieowners,breeders,veterinariansand foranyonewholovesWesties. TheEBook(reallyanelectronicwebsite)isorganizedbytopic.Alistoftopics followsandthenthelinkofthatportionofthesitewilltakeyoutherewithaclick ofabutton.Thematerialisorganizedbytopicsofgeneralinterest,andthenby specificdiseasesthatWestieseemmorepronetothanotherdogs.Undereach diseaseheading,isinformationintendedforallreaders.Therearethenareasof moredetailedcontent(forveterinariansandscientists),butallarewelcometo readthroughthismaterial.ReferencesusedtopreparetheEBookarelisted,as areshortsummariesofsomekeyarticles. Thisisaworkinprogress!Comments(wag,wag,wag!)andcriticisms(grrrr!) arewelcome!

Healthanddiseaseindogsabriefoverview Dogsareamazinglyheartyandhealthy.The ownerofanynewpuppyisamazedatthe numberofdelectableitemspuppieseatand howtheygrowandprosper. Thereareseveralthingsthatdeterminethe healthofalldogs.First,andforemost,dogs needanutritionallyadequateandcompletediet, plentyofclean,freshwater,andasafeenvironment(SeeDietand Environment,below).Second,dogsneedhumanattentiontotheirhealth problems.Ownersofdogsarethefrontlineinprovidingregularvisitstothe veterinarianforvaccinationsandphysicalexaminations(SeeYouandYour Veterinarian,below). Third,thebreedofdogscanhaveaverystrong influenceonthedevelopmentofsomehealthproblems.Weknowthatsome typesofhealthproblems,suchascancerorskindisease,aremorecommonin somepurebreddogbreedsthanothers.Oneexampleofthisisanincreased incidenceofbladdercancerinScottishterrierbreeds,suchastheScottieand Westie(SeeHowBreedInfluencesHealthinDogs,below)(referencehere).

DietandEnvironment RevisionbyKorrinSaker,DVMPhDDACVN Dogsprosperonmanydifferentdiets.Howcanyoubeassuredthedietyou choosewillprovideadequatenutritionforyourdog?AAFCO,theAmerican AssociationofFeedControlOfficials,hasdevelopedpoliciesforregulatingthe manufacture,labeling,distributionandsaleofanimalfeeds.TheNutritionClaim orNutritionStatementonallpetfoodlabelswillstateifandtowhatextentthe manufacturerhasfollowedAAFCOguidelinesintheformulationandtestingof thatdiet.Youwillbeabletoascertain,tosomeextent,ifthedietisappropriate foryourdogataparticularlifestage.Mostcommerciallyavailablediets(dry, semimoist,orcanned)areformulatedtoprovidecompletenutritionfora specificlifestage.Aseparatecategoryofcommercialdiets,termedtherapeutic orprescriptionareformulatedtoaddressspecifichealthconcerns.Dietsthatare formulatedtoprovidecompleteand/orbalancednutritiondonotrequire supplementationwithvitamins,mineralsorothernutrientsformaintaining adequatehealth.Someownersprefertopreparethedietfortheirdogfrom ingredientsfromthemarket.Homemaderecipeshavetheirplaceinpet nutrition,butcaneasilybeincompleteorunbalancedtherefore,itisimportant thatyoudiscussyourdogsdietwithyourveterinariantobesureitprovidesall thenutrientsthedogwillneedtomaintaingoodcondition.TheNational AcademyofSciencesmaintainsawebsiteforpetownersonthesubjectofdog andcatnutrition.Itcontainsinformationonnutrientrequirementsandnutrient problems.Thewebsite(calledPetdoor)isworthavisitifyouhavequestions aboutnutritionanddietsforyourWestie.ItisfoundatTheNationalAcademyof Sciences,BoardofAgricultureandNaturalResourcessite (http://www.dels.nas.edu/banr/petdoor.html). Ingeneral,mostdogsthriveonthesamedietdayafterday.Infact,some dogsdontdoverywelliftheirdietischangedfromonefoodtoanother,andwill sometimesgetstomachupsetsanddiarrheaiftheirdietchanges.Mostowners realizethattherearesomedietarynonostoomuchfood(exceedingbody needsandleadingtoweightgain),doggiejunkfoodandsnacks,andfatty scraps.Althoughtheylovethem,manydogswillgetupsetstomachsand diarrheaiftheyeatbones.Softbones,suchasthosefrompoultry,mayactually beadangertodogs.Thesesoftbonescanbebrokenintosharppiecesduring chewingandinjurethedigestivetractandmouthofdogs.Alloftheseshouldbe avoided. Numerouspetfoodcompaniesmaintainverygoodinformationondognutrition ontheirwebsites.Theyalsoprovideinformationfordogownersontheir products.Petfoodwebsitesandproductinformationcanbeobtainedby accessingtheAmericanAcademyofVeterinaryNutrition(AAVN)website( www.aavn.org).

Dogsneedclean,freshwater.Dogsshouldhavetheirwaterchangedseveral timesdaily,andregularlycheckedbytheirownerfordebris,cloudinessor discolorationthatmightindicatethewaterisunpalatableorpotentially contaminated.Waterbowlsmadeofstainlesssteelaregenerallyeasiertokeep cleanandtoresistchewingbyenthusiasticdogs.

Oneofthemostimportantthingsownerscandotoinsure thehealthoftheiranimalistokeepitinasafe environment.Dogsthatareallowedtorunfreemay encounterotherdogswithpotentiallyinfectiousdiseases. AlthoughWestieshavethecourageofAfricanlionsandwill standtheirgroundagainstmuchlargerdogs,theymayget severelyinjuredindogorcatfights.Dogsthatrunfree alsoruntheriskofbeingstruckbyautomobiles,ingesting dangeroussubstances(likeantifreeze,forexample),or beinginjuredfromfallsorfrommaliciousacts.So,keep yourWestiesafe!

YouandYourVeterinarian Youandyourveterinarianareateamdedicatedtomaintainingthehealthofyour Westie.Veterinarianstobetakefouryearsofclassesandmentoredpractice experiencesbeforetheytakelicensingexaminationsandbegintopractice veterinarymedicine.Mostnewveterinarianswillworkwithmoreseasoned practitionerstohonetheirskills.Someveterinarianswilltakeadditionalyearsof training(asinternsandresidents)tolearnaveterinaryspecialtylike dermatology,oncology(thestudyofcancer),ororthopedicsurgery. Ifyouare interestedinveterinarytrainingorinthescopeoftheveterinaryprofession, severalverygoodwebsitesaremaintainedbyTheAmericanVeterinaryMedical Association(www.avma.org)andtheAmericanAnimalHospitalAssociation (www.healthypet.com).Thesewebsitesalsocontainawealthofinformationon thehealthofcompanionanimals(suchasdogs,cats,andhorses)andyoumay wanttovisitthem. Regularvisitstoyourveterinarianarecriticalinmaintainingthehealthofyour Westie.Thesevisitsallowtheveterinariantogettoknowyourdogandtoknow you.Thevisitsallowyoutocommunicatetotheveterinarianwhataspecialdog youhaveandtoallowthedogtounderstandtheenvironmentandexamination procedures.Itiswellknownthatdogsthatknowtheirveterinarianandhis practiceenvironmentaremoreateasewithvisits.Thislowersthestresslevels yourdogmighthavewhengoingtoaplacewherethereareotherdogsandcats,

strangepeopleandstrangesmells.Regularvisitsalsohelptheveterinariandoa goodjobinassessingthehealthofyourdog,becausetheycandevelopa baselineofhealthandpotentialmedicalproblems,detectdiseasesatearly stages,and,mostimportantly,gainthetrustofyouandyourWestie. HowoftenyouandyourWestievisityourveterinariandependsontheageand thehealthofyourdog.Mostveterinarianswouldliketoseeyourdogfrequently (everyfewmonths)asapuppy,forvaccinationagainstinfectiousdiseases,to provideinformationondiet,todetectearlysignsofhealthproblems,andto assesswhetherornotyourpuppyisaffectedbyparasites.Whendogsbecome mature(between12years)visitstotheveterinarianmayonlybeneededevery 612months.Ofcourse,youandyourdogshouldalwaysseetheveterinarianif thereareanyhealthproblems,sotheycanbeaccuratelydiagnosedandtreated. MostdogsintheUnitedStatesarenowregularlymaintainedonmedicationto preventthedevelopmentofcanineheartwormdisease(dirofilariasis),adisease spreadfromonedogtoanotherbymosquitobites.Veterinariansmayalso recommendtheuseofmedicationsappliedregularlytominimizetheeffectsof fleasandticksondogsthatgooutdoors. Breeding,spayingandneutering Breeding,spayingandneuteringarecriticaltopicsfordiscussionbetweenyou andyourveterinarian. Ifyouareanexperienceddogbreeder,youhaveawealthofknowledge regardingbreedingperhapsmorethanyourveterinarian.Mostveterinarians willreadilyacknowledgethisandwillbehappytolearnfromyourexperiences. Theymayalsohavequestionsandobservationsthatwillfosterdialogue, includingoptimumtimingforbreeding,frequencyofbreeding,suggestionon nutritionfordam,sireandpups,vaccinationschedulesandprotocols(to optimizepuppyimmunity),andanumberofothertopics.Theoutcomeof breederandveterinariandialogueishappy,healthWestiepups,Westiemoms, andtheirhumanfamilies! Ifyoudonotintendtobreedyourdog,thenspayingandneuteringmayhave importanthealthconsequencesforyourdogandforthedogpopulationin general.Wearesuremostpeoplerealizethereisaseriousproblemofpet overpopulationintheUnitedStates.Althoughthisisrarelyaproblemfor Westies(becausetheyhaveverydevotedowners!),therearemanydogsthatdo nothavehomesandwhichmaystray.Petownerswhospayandneutertheir petsplayamajorroleinpreventingpetoverpopulation.

Spayingyourfemaledog(ovariohysterectomy)removestheovariesandthe uterusofthedog,sothatshewillnothavepuppies.Neuteringmaledogs removesthetestis,andthesedogsaresterile.Theseoperationsaredoneby yourveterinarianinhishospital.Veterinariansfirstexamineyourdogtobesure thatthedogishealthyenoughforsurgery,andthenscheduletheoperation. Dogsthatarespayed/neuteredaregivenageneralanesthesiaandpreparedfor sterile(asepticsurgery). Aftertheoperation,dogswillhaveaportionoftheirfur shaved,asutured/stapledsurgicalsite,andwillrequireobservationand aftercare.Thiswillallbediscussedwithyoubyyourveterinarian. Asnotedabove,thereareimportanthealthconsequencesofspayingand neutering.Severalstudieshavenotedthattheincidenceofuterineinfections (pyometra)andmammaryglandtumorsismarkedlyreducedinfemaledogs thathavebeenspayed.Thebeneficialeffectonthedevelopmentofcanine mammaryglandtumorsisseenindogsthatarespayedinthefirstyearoflife andsomewhatindogsspayedbetween12yearsofage.Femaledogsofany agehaveareducedriskofdevelopinguterineinfectionsandinflammation (pyometra),sincethespayingoperationremovestheuterus. Thebenefits(asidefrompreventingpetoverpopulation)ofneuteringmaledogs maybeareductionintheincidenceandgrowthofsometypesofskintumors (perianalglandadenoma),decreasedincidenceofperianalfistulaandon problemsassociatedwithbenignenlargementofthecanineprostate,including prostaticcystsandabscesses. Recentresearchhasnotshownthatneuteringof maledogsdecreasesprostaticcancerindogsinfact,somedatashowsthat neuteredmaledogsmaybeataslightlyincreasedriskfordevelopingthisvery uncommontumor. Theeffectofspayingandneuteringonthedevelopmentofotherdiseasesand onpetbehavior(suchasaggression)islessclearcut.Onceagain,adiscussion ofthesetopicswithyourveterinarianwillhelpyoumakeimportantdecisionson petbreedingandpetneutering. HowBreedInfluencesHealthinDogs Oneofthemanythingsthatareveryimportantindeterminingthehealthof everydogistheirgeneticmakeup.Eachcellineverydog(andpersonand everythingelse)containsablueprintforthecellandforthedog.These blueprintsaremadeupofDNA,formedintospecificgenescontainedin chromosomes.Theentiresetofgenesthatcontaintheblueprintforeach individualdogisknownasitsgenome.Thegenomespecifieshowcellsare made,howthecellsformtissues,andhowthetissues(liketheheartorskin) function.

Selectivebreedingofdogs,followingdomesticationfromwilddogsandwolves, hasresultedintheevolutionofspecificdogbreeds,liketheWestHighlandWhite Terrier.ThegenomeofoneWestieislikelytobeverysimilartootherWesties, becauseselectivebreedingoverseveralhundredsofyearshasfocusedthe genomeoncertaindesirablecharacteristicsthatmakethemWesties.For example,thepaleandwhitecoatcolorofWesties,theshapeoftheirbody,and eventhingsliketheirlifespanareencodedintheirgenome(Westiestendtolive longerthanGreatDanes!). ItisverylikelythatthedifferencesinthegenomeofWestiesfromotherdog breedsaresmallandcausedbythevariableexpressionofcertainkeygenes. Thesevariationsingeneexpressionaretermedmutationsorpolymorphisms bygenomicscientists.Manysuchvariationsinthegenomearegood,conferring selectiveadvantagesinappearance,performanceandhealth.Ontheother hand,somevariationsarenotadvantageousfordogs.Itiswellknownthat cancer,forexample,istheresultofmutationincertainspecificgenesthat controlcellgrowth,celldivision,andcelllifespan. Unfortunately,somebreedsofdogs,asaresultofselectivebreeding,develop diseasesthatareassociatedwiththeirbreed.Twoexamplesareshownbelowto illustratethis.Theinformationisalittletechnical,butithelpsshowstrong associationsbetweenbreedanddisease.HowthisallrelatestoWestiesfollows theseexamples.

Example:Breedpredispositionsasasignificantfactorinthe developmentofML GoldenRetrievers,incomparisontomanyotherdog breeds,aredisproportionatelyaffectedbyneoplasmsas causesofmorbidityandmortality. In1998,theGolden RetrieverClubofAmerica(GRCA)developedand distributedaquestionnairebasedhealthsurveytoClub members(Glickman,1998).Health,husbandry, morbidity,andmortalitydatawasreceivedfrom746dog owners,documentinginformationon1444dogs.Petownersconfirmed informationonmorbidityandmortalityofdogswithveterinarypractitioners. Theresultsofthissurveyindicatedthatapproximately61.4%ofalldeaths reportedinGoldenRetrieverswerecausedbyneoplasms.Indogsthatdied,the lifetimeriskofdevelopinganeoplasmwas1in2,withtheriskofdevelopmentof

hemangiosarcoma(themostcommontumor)being1in5,andofdevelopingML 1in8.Accordingtosurveyresults,onlyabout12%ofdogswhichdevelopedML werecuredbytherapy.MLrankedasthemostsignificantGoldenRetriever diseaseintermsofyearsofpotentiallifelostinthestudypopulation,andcaused roughly4timesmorepotentialyearslostthananyothersinglecauseof mortality. OtherdataalsoindicatesGoldenRetrieversmaybemorelikelytodevelopML thanotherbreeds.Thefivemostpopularbreedsofdogs(20034,indescending order)wereLabradorRetrievers,GoldenRetrievers,GermanShepherdDogs, Beagles,andYorkshireTerriers(Source:AmericanKennelClubregistrationdata, 2005).Thesebreedshavebeenamongthemostpopularformorethana decade.Theyaccountedfor15.6%,5.6%,4.8%,4.8%,and4.4%,respectively, ofthetotalof1,873,711purebreddogsregisteredinthoseyears.Ifallbreeds hadasimilarriskforthedevelopmentofML,onewouldexpectthatthe proportionofcasesofMLrecordedindatabaseswouldberoughlyproportional tobreedpopularity.Forexample,onewouldexpectthatLabradorRetrievers wouldcontributeabout3xmorecasesofMLtothedatabasethanGolden Retrievers. However,anexaminationofdataintheVCRdatabaseindicatesasubstantially increasedriskforMLinGoldenRetrievers.Currently,thereare1,141casesof MLinthedatabase(18%ofthetotalcases).LabradorRetrieversaccountfor 8.2%oftheMLcases,whileGoldenRetrieversaccountfor10.2%.Basedsolely onbreedregistrations(representingnumbersofpopularpurebreddogs)it appearsthatGoldenRetrieversmaybe3timesmorelikelythanLabrador RetrieverstodevelopML(Table,below).Unfortunately,actuarialdata, includingestimatesofthetotalatriskcaninepopulation,andreportsofcauses ofdeathdonotexist,makingcalculationofincidence,prevalence,orfrequency, difficultandimprecise. AKCreg. (%) 15.6 5.6 4.8 4.8 4.4 MLinVCR(%) 8.2 10.2 3.7 2.2 0.6 Obs/Exp 1.2 4.0 1.7 1.0 0.3

LabradorRetriever GoldenRetriever GermanShepherd Beagle YorkshireTerrier

Table.RepresentationofdifferentdogbreedsamongtotalAKCregistrations, andcasesofMLintheVeterinaryCancerRegistry.TheratioofobservedML frequencytoexpectedMLfrequency(basedonAKCregistration)isnormalized relativetoBeagle.

TheoverrepresentationofMLintheGoldenRetrieverbreedwasconfirmedina retrospectivestudyofMLatourinstitution.Threehundredninetyfive(395) dogswerediagnosedwithMLina15yearperiodofstudy(19862001).This comprised1.2%(n=32,823)ofallcanineadmissions.Morethan80breedsof dogwerediagnosedwithandtreatedforML.BreedsdiagnosedwithML included:MixedBreed(n=79),GoldenRetriever(n=38),LabradorRetriever (n=31),CockerSpaniel(n=23),Rottweiler(n=16),GermanShepherdDog (n=12),DobermanPinscher(n=11),Boxer(n=11),ShihTzu(n=11),andother breeds(n=157).Ofthetotalnumberofcasesinourstudypopulation,Golden Retrieversaccountedfor9.6%oftotalcasesseen,afigureclosetothat representedintheVCRdatabase. Itisentirelypossiblethatphenotypicselectionofdesirablecharacteristicsin somebreedsmayhavealsoselectedforgenomicabnormalitiesassociatedwith thedevelopmentofML.Aspreviouslynoted,thefundamentalbasisforall neoplasmsismutationofcriticalgenesthatcontrolgrowthanddifferentiation Conventionalpedigreebasedlinkagestudieshavebeenusedsuccessfullyto identifygenesthatareassociatedwithavarietyofcaninedisorders,includinga rarecancer(reviewedbySutterandOstrander,2004). References Glickman,L,Glickman,N,Thorpe,R,19981999GoldenRetrieverClubof AmericaNationalHealthSurvey,GoldenRetrieverClubofAmericaHealthand GeneticsCommittee,1998 SutterNB,EberleMA,ParkerHG,PullarBJ,KirknessEF,KruglyakL,Ostrander EA,ExtensiveandbreedspecificlinkagedisequilibriuminCanisfamiliaris, GenomeRes14:238896,2004 Example:Breedpredispositionsinthedevelopmentofbraintumorsin dogs Spontaneousprimarybraintumorsarecommonindogs, accountingfor13%ofalldeathsinageddogswhere necropsyisperformed(Koestner,etal,2002).Inonestudy, anincidencerateof14.5cases/100,000dogsatriskwas reported,althoughthismaybesomewhatimpreciseas actuarialdataisnotcollectedondogsatthetimeofdeath (Vandevelde,1984).Over70%ofprimarytumorsoccurin dogsaged6yearsormore,aperiodinlifespancomparable tomiddleageinhumans.Astrocytomas,oligodendrogliomas andmeningiomasaremostcommon,withastrocytomas accountingforapproximately10%ofprimarybraintumorsinsomeseries

(Luginbuhl,Hetal,1968).AstrocytomasclassifiedasgradesIIIVintherevised WHOClassificationsystemhavebeenrecognizedandreportedindogs,andare histologicallyidenticaltosimilarlygradedtumorsinhumans(Kleihues,Petal, 1993).Mostcanineastrocytomasoccurascorticallesions,withmanyformingin thetemporalandfrontalregions.Anincreasedincidenceofgliomashasbeen notedinbrachycephalicbreeds(BostonTerriers,Boxers,Bulldogs)(Summers, BA,etal,1995)aswellasintheGoldenRetriever,DobermanPinscher,Scottish TerrierandOldEnglishSheepdogbreeds(Summers,BA,etal,1991).Boththe clinicalpresentationandprogressionoftheseastrocytomasissimilartohumans (LeCouteur,RA,2001).Unfortunately,patternsofsurvivalarealsosimilar,likely acombinationoflimitationsinprovidingtherapytoveterinarypatientsand inherenttumorbehavior. Despitetheknownpredispositionofcertainbreedstospecifictumors,therehave beennodefinitiveinvestigationsofgeneexpressioninnormalcaninebrain tissue.Extrapolatingfromthehumanexperience,itispossiblethatsomedog breedshaveinheriteddefectsintumorsuppressorgenefunctionormaybe predisposedtooverexpressothercriticalgrowthregulatinggenes,eventually leadingtotumordevelopment. References Koestner,A,Higgins,RJ,Tumorsofthenervoussystem,inTumorsof th DomesticAnimals,4 ed.,Meuten,DJ(ed.),IowaStateUniversityPress,Ames, IA,2002,p.697 Vandevelde,M,Braintumorsindomesticanimals:Anoverview,Proceedingsof theConferenceonBrainTumorsinManandAnimals,ResearchTrianglePark, NC,September,1984 Luginbuhl,H,Fankhauser,R,McGrath,JT,Spontaneousneoplasmsofthe nervoussystemofanimals,ProgNeurologySurgery2:85164,1968 Kleihues,P,Burger,PC,Scheithauer, BW,ThenewWHOclassificationofbrain tumours,BrainPathology3:255268,1993 Summers, BA, Cummings, JF, De Lahunta, A, Tumors of the central nervous system, in Veterinary Neuropathology, MosbyYear Book Publishers, Inc., St. Louis,MO,1995,p.364 Summers,BA,Kornegay,JN,et.al,Analysis ofsurvivalinaretrospective study of86dogswithbraintumors,JVeterinaryInternalMedicine5:219226,1991 LeCouteur, RA, Tumors of the nervous system, in Small Animal Clinical rd Oncology, 3 ed., Withrow, SJ, MacEwen, EG, (eds), WB Saunders Co, Philadelphia,PA,2001

HowdoesthisrelatetoWesties? TherearesomediseasesthatoccurinWestiesthataremore commonthaninotherbreeds.Thereasonforthisis undoubtedlytiedupinthegenomeofthebreed.Selective breedingoverhundreds,ifnotthousandsofyears,has developedtheWestiewithcertaincharacteristicssuchas size,stature,colorationandevenpersonality.Atthesame timethatthesedesirablecharacteristicswereselectedbycarefulbreeding,other lessdesirablecharacteristicsalsodeveloped. Someoftheselessdesirable mutationswerelinked(literally,intheDNAandchromosomes)tomoredesirable breedcharacteristicssortofhitchingarideintheWestiegenomicpattern. Becauseoftheselinkedmutations,Westiesarepredisposedtothedevelopment ofsomediseases,justlikeGoldenRetrieversgetmoremalignantlymphomaand Bulldogsgetmorebraintumors. Weknowthatwhiledogsmaybepredisposed geneticallytodevelopingsomediseases,therearealsomanyidentifiedand unidentifiedenvironmentalinfluencesondiseasedevelopment,expressionand severity.Thiscomplexinterplaybetweengenomeandenvironmentisanareaof intensescientificstudy. Averygoodfirststepinmakingprogressinunderstandingwhichdiseasesare commonandforbeginningthestudyofgenomeenvironmentalrelationshipsare healthsurveys,conductedbytheWestieFoundationofAmericaandalsothe WestHighlandWhiteTerrierClubofAmerica.Theresultsofrecentstudiesarea kickingoffpointfordiscussionofdiseasesthatfollow. ItisnowourjobtofindthespecificgenesintheWestiegenomethatarerelated tocommondiseases.Oncethisisdone,moreeffectivetreatmentsforthese diseasescanbefound,andconcernedbreeders,owners,veterinariansand scientistscanworktogethertoeliminatetheseproblemgenes,whilemaintaining happy,healthypopulationsofWestiesforcenturiestocome. Withallthisbackgroundinformationdown,wearenowreadytodiscusssome CommondiseasesofWesties.Theinformationisorganizedbydiseasetopic. Beforeeachtopic,thereisabriefsummaryofinformationwhichmayhelp readersunderstandsomeoftheterminologyandconceptsusedinthe discussions. CommondiseasesofWesties TheWestieFoundationofAmerica(WFA)andtheWestHighlandWhiteTerrier ClubofAmerica(WHWTCA)haveeachconductedseveralsurveysofWestie

ownersandbreederstoidentifycommondiseases. Thefactthatownersand breedersrecognizediseasesthatoccurmorecommonlyinWestiesmeansthat therearelikelytobecomplexgenomicfactorsandenvironmentalfactorsthat interacttoproducedisease. In1999(andagainin2004)theWFAconductedahealthsurveyofWesties.The resultsofthe1999Surveywerebothinterestingandimportantintermsof focusingresearchonWestiehealthproblems.Ownersandtheirveterinarians wereaskedtoreportthediseasebothbyimportancetothemandprevalence.A responserateonthissurvey(27.1%)isconsideredlowforthepurposesof statisticalanalysis.Accordingtothe1999WFAWestieHealthSurvey DiseasesrankedbyimportanceasreportedbyWestieowners: 1. AtopicDermatitis 2. Pulmonaryfibrosis 3. CoppertoxicosisandLeggCalvePerthes(tied) 4. Addisonsdisease(hypoadrenocorticism) 5. Aggression 6. Diabetesmellitus 7. Whiteshakersyndrome 8. Dryeye(keratoconjunctivitissicca) 9. Allergies 10. Luxatedpatella 11. GloboidCellLeukodystrophy 12. Cancer Targeteddiseaseswererankedbyprevalence(mainlydiagnosedby veterinarians)asfollows: 1. AtopicDermatitis 2. Aggression 3. Luxatedpatella 4. Dryeye(keratoconjunctivitissicca) 5. LeggCalvePerthes 6. Cranialmandibularosteopathy 7. Pulmonaryfibrosis 8. Whiteshakersyndrome,diabetes,Addisonsdisease (hypoadrenocorticism)(tied) 9. Coppertoxicosis 10. Juvenilecataracts 11. GloboidCellLeukodystrophy 12. Deafness

AccordingtoWHWTCA,thefollowingdiseaseshavebeenidentifiedasof particularconcerntoWestieowners(thesediseasesarelistedalphabetically,not inorderofoccurrenceorimportance)(boldeditemsarediscussedinthisfirst draftoftheWestieEbook): AlphabeticallistingofdiseasesofconcerntoWestieowners Aggression Addison'sdisease(Hypoadrenocorticism) AtopicDermatitis BladderCancer(TCC) CleftPalate CopperToxicosis(CT) CraniomandibularOsteopathy(CMO) Deafness DiabetesMellitus EarInfections EpidermalDysplasia GloboidCellLeukodystrophy(GCL) HeartDisease HipDysplasia ImmuneSystem InflammatoryBowelDisease(IBD) Hernia(inguinalandumbilical) JuvenileCataracts KeratoconjunctivitisSicca(KCS,DryEye) KidneyDisease LeggCalvePerthes LuxatedPatella PortosystemicShunt PulmonaryFibrosis(WestieLungDisease) PyruvateKinase(PK)Deficiency Seborrhea,PrimaryandSecondary SkinandAllergyProblems TeethandGums WhiteShakersSyndrome CommondiseasesofWesties,categorizedbyBodySystem Alimentary(Digestive)System CleftPalate CopperToxicosis CraniomandibularOsteopathy DiabetesMellitus

InflammatoryBowelDisease(IBD) PyruvateKinase(PK)Deficiency TeethandGums CardiovascularSystem HeartDisease PortosystemicShunt PulmonaryFibrosis(WestieLungDisease) EndocrineSystem Addison'sdisease(Hypoadrenocorticism) ImmuneSystem LocomotorSystem HipDysplasia LeggCalvePerthes LuxatedPatella NervousSystem Aggression GloboidCellLeukodystrophy(GCL) WhiteShakersSyndrome SpecialSenses Deafness EarInfections JuvenileCataracts KeratoconjunctivitisSicca(KCS,DryEye) SkinandSoftTissue AtopicDermatitis EarInfections EpidermalDysplasia Hernia(inguinalandumbilical) KeratoconjunctivitisSicca(KCS,DryEye) Seborrhea,PrimaryandSecondary SkinandAllergyProblems UrogenitalSystem BladderCancer(TCC) KidneyDisease

CommondiseasesofWesties,categorizedbyunderlyingpathologic process Congenital/Developmental AtopicDermatitis CleftPalate CraniomandibularOsteopathy(CMO) Deafness GloboidCellLeukodystrophy(GCL) HeartDisease HipDysplasia Hernia(umbilical) JuvenileCataracts LeggCalvePerthes LuxatedPatella PortosystemicShunt Seborrhea,PrimaryandSecondary Hemodynamic Infectious EarInfections Inflammatory EpidermalDysplasia InflammatoryBowelDisease(IBD) KeratoconjunctivitisSicca(KCS,DryEye) PulmonaryFibrosis(WestieLungDisease) SkinandAllergyProblems(Atopicdermatitis) WhiteShakersSyndrome Metabolic/Endocrine Addison'sdisease(Hypoadrenocorticism) Neoplastic BladderCancer(TCC) Nutritional/Toxic CopperToxicosis(CT) DiabetesMellitus GloboidCellLeukodystrophy(GCL) PyruvateKinase(PK)Deficiency Other/Unknown

Aggression Hernia(inguinal) LeggCalvePerthes LuxatedPatella PulmonaryFibrosis(WestieLungDisease) TeethandGums WhiteShakersSyndrome

******************************************************** Specificdiseases ******************************************************** Topic#1:TheItchyFlakyDog DermatitisBasicsandAtopicDermatitisinWesties Dermatitis(inflammationoftheskin)isoneofthemostcommonmedical problemsindogs.Ithasmanycauses,cantakemanyforms,andisoften complicatedtodiagnoseandtreat. Manyownersexperiencethefrustrationof searchingforwhatiscausingtheirWestietoitchandscratchandforeffective meanstocontrolandcuretheproblem.Thisbriefoverviewdescribesthebasics ofdermatitis,causesofdermatitis,andhowveterinariansdiagnoseandtreat dermatitis.Adetaileddiscussionofatopic(allergic)dermatitisinWestiesis emphasized. Skinisacomplexorgan,consistingofseveraltypesofcellswithvariousjobsand theinflammatoryresponsemayinvolveallorjustsomeofthesecells. Inflammationisoneofthebodysmostimportantprotectiveresponsesto negativestimuliinitsenvironment.Infact,withouttheprotectionofferedby inflammation,peopleanddogscouldnotsurvivetheconstantassaultofcuts, bruisesandotherdailytraumas,aswellasexposuretoinfectiousorganismslike bacteriaandfungi.Commonsignsofacuteinflammationarefamiliarto everyoneandincluderedness,swelling,heatandpainatthesiteofinjury. Thereareanalmostinfinitenumberofthingsintheenvironmentthatthebody canperceiveasnegativestimuli.Thispaperwilldiscussthetypesofdermatitis (inflammationoftheskin)associatedwithreactionstofood,inhaledsubstances, parasites,hormonesandbacteria. Onetypeofdermatitisoftenseeninhumans,butuncommonindogsis urticaria,alsoknownashives.Dogswithurticariahavepatchesofskin (calledwheals)whichareitchyandelevatedandmayormaynotbereddened. Thesewhealsaredryandmaygrouptogethertoformlargerflattoppedpatches calledplaques. Inarelatedcondition,angioedema,thesepatcheswillbe moistandappearmoreswollen. Peoplewithsevereallergies(likeDr. Robertson!)tosomesubstanceslikebeevenom,willdevelopurticaria(hives) andangioedemawhenstung. Bothurticariaandangioedemaresultfromenvironmentalirritants,suchasfood, medication,insects,andplants,timeinthesunorextremehighorlow temperatures.Thebodymountsadefenseagainsttheirritantbyreleasing

histaminefromspecialcellsintheskincalledmastcells.Thepresenceof histamineoutsidethemastcellstriggersaseriesofeventsinthebodythat producethesignsofinflammation. Thetreatmentofurticariaandangioedemaideallyinvolvesavoidingthe offendingenvironmentalstimulusandmedicatingwithepinephrineor glucocorticoidsandpossiblyantihistamines. Canineatopicdermatitisisamore commondisorder,affectingatleast10%of dogs,withsomebreedsmoresusceptiblethat others,WestHighlandWhiteTerriersamong them.Canineatopicdermatitisisthedog versionofallergies.Dogsaremorelikelyto experienceallergiestothingsinthe environment,suchaspollensanddust.When exposedtotheseallergens,dogsaremore likelytodevelopitchyredpatchesontheirskin(likehives)thantoexperience sneezingandstuffyhead,likehumans.AWestiewithsevereatopicdermatitisis shownhere,inaphotographcourtesyofDr.WilliamMiller,NewYorkState VeterinaryCollegeatCornellUniversity. Dogswithatopicdermatitiswillusuallyscratchandlick themselvesenoughtocreateotherskinproblems, includinghairloss,hairstainingfromsaliva,elevatedor pussfilledlesions,darkorparticularlyroughorthickened patchesofskin(lichenification). Inthephotographatthe left(courtesyofDr.WilliamMiller,NewYorkState VeterinaryCollegeatCornellUniversity)areasof pigmentationandlichenificationareseeninthegroinand hindlegsofthisWestiewithseverelongstandingatopic dermatitis.Theseproblemsusuallyshowupontheface, paws,lowerlegs,elbowsandbelly.Somedogsmayalso experienceearinfectionsandhaveabadsmelltotheir skin.CanineatopicdermatitisisconsideredaTypeIhypersensitivity,meaning thattheonsetofsymptomsafterexposuretotheallergen(negativestimulus)is immediate. Thesymptomsofatopicdermatitisappearasaresultoftheinflammatory process.Thatprocessistriggeredbyexpressionofhypersensitivity(allergies)to particularallergens.Somedogs(likeWesties)aregeneticallyprogrammedtobe moresensitivetosomethingsintheirenvironments.

Itcanbeverydifficulttounderstandwhatiscausingatopic dermatitisorevenifadoghasit.Inthephotographon theleft(courtesyofDr.TomManning),adogwithnon specificbutatopic/allergicdermatitisisshown,with reddenedanditchylesionunderthefrontlegs.Theexact mechanism(underlyingprocessesthatproducethesigns ofdisease)ofatopicdermatitisisnotyetknown.Thecurrentunderstandingis thatwhenasensitivedogfirstinhales,ingestsorabsorbstheallergenits sensitiveto,itsbodymakesproteinstofightit,calledallergenspecific immunoglobulinE(IgE).OnsubsequentexposuresthatIgE,mastcells(a specifictypeofinflammatorycellcontaininghistamineandotherpro inflammatorymolecules),alongwithhighnumbersofcertainwhitecellscalledT lymphocytes(Tcells),causetheinflammatoryresponsetobeproduced.Current researchislookingintootherfactorsthatmayplayaroleinproducingthe inflammatoryresponse,includingothergeneticallyprogrammedimmune problemsandskinbarrierissues. Wenowknowthatupto90%ofcasesofcanineatopicdermatitiscanbe controlledwithappropriateandlongtermtreatment.Treatmentincludes avoidingcontactwiththeallergen,bathingwithmedicatedshampoo,andgiving somecombinationoffattyacidsinthediet,aswellasadministrationofanti histamines,glucocorticoidsandpossiblymorepowerfulimmunosuppressive drugslikecyclosporin. Allergiccontactdermatitis,orcontacthypersensitivity,differsfromatopic dermatitisinthattheallergencomesfromsomethingthathastouchedthedogs skin,suchasaplant,medicationorfabric.Allergiccontactdermatitisisrarein dogsbutwhenitispresent,theskinwillbereddenedandhavesmallflatlesions thatarecoloreddifferentlyfromnormalskinorsimilarlargerlesionsor,rarely, largefluidfilledlesions.Overtime,thistypeofcontactdermatitiscanproduce hairloss,greaterdiscolorationandraworthickenedskin.Theareasaffectedare commoncontactareas:thebottomsofpaws,thebellyandtheoutsidesofthe ears. Thechemicalandplasticscontainedinoldstylefleacollarsusedtobea commoncauseofthistypeofdermatitis,withlesionsappearingaroundthe neck,butnewertypesarelessliketoproducecontactdermatitisaroundthe neck.Patientsthatdevelopcontactdermatitismayormaynotbeitchy,andthis isveryspecificbothtothecontactallergenandtotheindividualdog. AllergiccontactdermatitisisconsideredaTypeIVhypersensitivity,whichmeans itisadelayedreactiontoanallergenandmaytakealongtimetodevelop(and toeliminate).Thecontactallergenisthoughttobeattackedbyspecialskincells calledLangerhanscells,whichthenpresentmoleculesoftheallergentoTcells, whichthenlaunchanimmuneandinflammatoryreaction.Moreresearchneeds tobedonetodeterminetheexactmechanismofthedisorder.Contactallergic

dermatitisistreatedbyavoidingtheallergen,ifitcanbeidentified,and medicatingwithglucocorticoids. Dogscanalsodevelopitchy,flakydermatitisfromfoodallergiesthisisknownas caninefoodhypersensitivity.Thisformofdermatitisprimarilymeansitchy skinfordogs,althoughsomemayalsohavemanydifferentkindsoflesionsor thickeningoftheskin,changesincoloring,scales,crustsorredness.Theears, rump,lowerlegsandgroinarethemostcommonlyaffectedareas. CaninefoodhypersensitivityisconsideredaTypeIhypersensitivity,producing immediatereactionstoingestedallergens.Commonfoodsthatproducethistype ofdermatitisarebeef,dairy,chicken,eggs,wheat,cornandsoyallnormal ingredientsofcommercialdogfoods,unfortunately.Foodadditiveshavenot beenshowntobeacontributortofoodallergies.Whentheoffendingfood ingredientisingested,abnormalitiesintheimmunesystemsimilartothose involvedinotherhypersensitivities,orinthegastrointestinaltractsbarrierallow ittopassintothebloodstreamratherthanbeattackedandeliminated. This exposurecanleadtomastcellsreleasingtheirhistamineandcausingan inflammatoryreactionintheskin.Futureresearchmaydeterminewhytheskin inparticularissoaffected. Likeallallergies,determiningtheallergenandavoidingitisanimportantaspect oftreatmentforcaninefoodhypersensitivity.Medicationstocontrolitchingmay alsobeemployed.Theotherpartoftreatmentisafoodchange,eithertoa commercialdogfoodmadewithproteinsthedogsimmunesystemdoesnthave asensitivitytoortoacustomhypoallergenicfood,onethatdoesntcontainthe offendingallergen,onceitisdetermined.Medicationwithglucocorticoidshas onlybeencompletelysuccessfulforcontrollingfoodhypersensitivitydermatitisin abouthalfofdogsandcatswithfoodallergies. Parasites,suchasfleas,ticksandotherinsectscanalsocausedermatitisin sensitivedogsfromtheirbites.Thisisknownasparasitichypersensitivityor morecommonlyfleaallergy.Dogswithfleasalivasensitivityareitchyand havelargerelevateddomeshapedorflattoppedlesionsontheirbacksbytheir tails,theinnerrearthighsandonthebelly.Tickbitescanproducedeadskin aroundthebiteandulcerationandpossiblyitchingaswell.Dermatitiscanalso occurinresponsetointestinalparasites,althoughthisisrare.Theredoesnot appeartobeanybreedpredilectionforparasitichypersensitivity. Whilethecompletemechanismofthisparasitichypersensitivitydermatitisis unknown,itisthoughttooccurinsimilarfashiontootherallergies,withthebody producingallergenspecificIgEandmountinganinflammatoryresponse.

Treatmentmeansparasitecontrol.Topicalfleaandtickpreventativesworkwell. Medicationwithglucocorticoidsmayalsobeadministered. Anotherrarehypersensitivityisrelatedtolevelsofsexhormonesandisreferred toashormonalhypersensitivity. Ninetypercent(90%)ofcasesofthisrare typeofdermatitisareseeninintactfemales.Patientsareitchyandhavesmall elevatedlesionsontherump,innerbackofthethighsandinthegenitaland analareas.Enlargementofthevulvaandnipplesiscommon. Howtheskinbecomesinflamedisunknownbuttreatmentbyneuteringisvery successful.Administrationoftestosteronetofemalepatientsandestrogento malepatientsisanotheroption. Finally,bacterialhypersensitivityisthelasttypeofdermatitisdiscussedhere. Dogswithbacterialhypersensitivityaresensitivetoagroupofbacteriaknownas Staphylococcus.Theirskinisitchyandhasdiscretepusfilledlesions.Your veterinarianmaysometimesrefertothisaspyodermaliterallytranslating frommedicaljargonintopusfilledskin. Again,themechanismisnotwell understood,althoughitisthoughttobeTypeIIIhypersensitivity,meaningitis immunesystemrelated.Thesepatientscanbetreatedwithantibiotics. Eachofthetypesofdermatitisdiscussedhereinvolveskininflammation,oftenin theformofvisibleskindisturbancesand,especially,itching.Dermatitisisthe resultofthebodysabnormaloroverlysensitivedefenseagainstirritantsor allergensintheenvironment.Someofthesesensitivitiesaregeneticallypassed onandcanbeavoidedbycarefulbreedingwhileallcanbeaddressedby avoidingspecificallergens. Treatment Atopicdermatitisisadifficultconditiontotreat.Thefirstfocusoftreatmentis usuallyonalleviatingthepatientsitching,andthentreatingsecondaryinfections andinflammation. Ifyourdogisdiagnosedwithatopicdermatitis,your veterinarianwilldevelopatreatmentplanwithyouthatmayinvolveseveral typesoftherapyincludingavoidanceofallergens,bathingwithmedicated shampoo,immunotherapy(allergyshots)andgivingsomecombinationoffatty acids,antihistamines,andglucocorticoids. Veterinarianscanuseskinteststodeterminewhich allergensadogisallergicto. Atypicalskintestfor adogisshowninthephotographontheleft (courtesyofDr.TomManning).Thebumpsseen hererepresentpositivereactionstosmallamounts ofinjectedallergens. Fleas,dustmitesandpollens

arecommonallergens.Ifwhatsbotheringadogcanbedetermined,avoiding thatsubstanceisthebestwaytotreatanyallergy.Therearemanywaysto controlyourdogsexposuretothesenegativestimuliandtheyaresimilarto measurestakenforpeoplewithallergies,likewashingallbeddingregularlyin hotwater,vacuumingallcarpetsandupholsteredfurniture,andkeepinggrass cutshort. Unfortunately,avoidingallergensisnotverysuccessfulasasoletreatmentfor dogswithatopicDermatitis.Theallergenscannotalwaysbedefinitively determinedandthesedogssystemsaresosensitivethatothermeasuresare usuallyneededforrelief.However,puttinginanefforttoavoidknownor commonallergensdoeslowertheloadforthedogandcanhelpincombination withothertreatments. Topicaltreatmentsarethenextlineofdefensefortheatopicdog.Regular bathingwithashampoowithantiitchormoisturizingpropertiesmaygoalong waytowardseasingyourdogsdiscomfort.Bathingnotonlyremovesdebrisand allergensfromcontactwiththeskin,butwateritselfcanbecoolingandsoothing toinflamedskin. Othertopicaltreatmentsincludefattyacidsandglucocorticoids(discussed below).Thesesubstancesmayalsobeadministeredorally.Fattyacids, specificallylinolenicacid(foundineveningprimrose)andeicosapentaenoic acid(fishoil),addedtothediet,havebeenshowntoimprovetheskincondition ofatopiccaninepatientsinseveralstudies.Itisnotknownexactlyhowthese fatsworkandthereisdebateoverthemostbeneficialdosebutitisthoughtthat theyaremetabolizedinthebodyintosubstanceswhichhaveantiinflammatory properties.Fattyacidsareavailableasdietsupplementsandcanalsobe includedincommercialdiets. Glucocorticoidsaredrugswhichhaveantiinflammatoryproperties.Theyalso acttosuppresstheimmunesystem(suppresscellactivityandantibody production)andinthiswaygotothesourceoftheproblemforatopicpatients, ratherthanjusttreatthesymptomsofinflammation.Prednisone,prednisolone andmethylprednisolonearecommonlyusedglucocorticoids.Cyclosporin, anotherimmunosuppressantdrug,hasalsorecentlybeenemployedfor treatmentofatopicdogs. Whilethesedrugscanbeveryeffectivefortreatingseveraldisorders,theyalso carryrisks,includingpancreatitis,gastrointestinalulcerationandmuscleandskin problems.Evendogsonshorttermglucocorticoidtherapycanexperiencesome sideeffects.Theywillusuallydrinkandurinateanddefecatemorefrequently andmayalsopantandexhibitbehavioralchanges.Becausethesedrugs suppresstheimmunesystem,dogsbeingtreatedwiththemaremoreproneto

gettingbacterialandotherinfections.Duetothesepotentialsideeffects, glucocorticoidsareusedwhenothertreatmentsarenotworkingandthenonlyin thelowestdosenecessary. Anotherroutefortreatmentofatopicdermatitisisimmunotherapy,whichuses vaccinesmadefromtheoffendingallergenstodesensitizethedogoveraperiod oftime.Vaccinesaregivenrepeatedlyatincreasingtimeintervals,gradually teachingthedogsimmunesystemtotoleratetheallergens.Immunotherapy, alsoknownashyposensitization,hasbeenacceptedasasafeandeffective treatmentforallergies,andhasbeenusedformanyyearsonhighlyallergic peopletolowertheirresponsetoallergens.Hyposensitizationtherapy(allergy shots)usuallyneedtobeadministeredregularly(weeklytomonthly)forthelife ofthedog,asthebeneficialeffectsmaydiminishifinjectionsarestopped. Finally,itiscommontoincludeantihistaminesinatreatmentplanforatopic dermatitis.Antihistaminesserveasantiitchmedications.Traditionalanti histaminesblockskincellsreceptorsforhistamine,thechemicalreleasedby mastcellsthatcaninitiatetheinflammatoryresponse.Unfortunately,anti histaminesarentthemosteffectivetreatmentandmayonlybeeffectivefor 10%ofdogswithallergies.Newerversionsalsoblockhistaminereleasefrom mastcellsinhumansbuthavenotbeenshowntobeparticularlyeffectivein dogsandtendtocostmorethanolderantihistamines.Alltypesofanti histaminescarrythesideeffectofmildsedationforthepatient. Whileproperlydiagnosingandtreatingatopicdermatitisisachallengefor veterinarians,thehardestpartoftreatmentistheburdenofcareitplacesonthe owner.Ownerofdogssufferingfromallergiesneedtounderstandthatcaring foranatopicdogisalifelongendeavorwhichwillinvolvetrialsofseveraldrugs anddoses,bathing,environmentalchangesandcost.Whatworksforyourdog inthewintermaynotbeenoughinthespring,whenallergensabound.Staying thecourseontherapiesyouandyourveterinarianagreeonwillbethebiggest determinantinyourdogsprognosisforhealthyskin. CurrentResearchonAtopicDermatitis(Furtherreading/Scientific backgroundliteratureandsummaries) Medicalresearchoncaninetopicdermatitisoverthelastfewyearshasfocused mainlyonanewunderstandingofthemechanismofthedisorderandnew treatmentoptions.Thetheorythatatopicdogshaveelevatedlevelsofallergen specificIgEhasbeenchallengedcontinuouslyandothertheories,especially thoseinvolvingskincelldynamics,aremovingtotheforefront.Whilewestill donthaveaperfectpictureofthemechanismofthedisorder,itappearsthat manymorefactorsareinplaythanwasoriginallythought.Treatmentwithfatty

acidshasgarneredalotofattentionaswell.Severalstudieshavealsolooked intothesafetyandefficacyofcyclosporineandotherdrugs. Whilemanystudieshavefoundthathypersensitivedogshavehighlevelsof allergenspecificIgE,otherstudieshavenotfoundacorrelationbetweendogs generalbloodlevelofIgEandskinhealth(Ledin,etal,2006).Someresearchers startedlookingintoIgG,anotherimmunerelatedprotein.Tworecentstudies concludedthatIgGlevelswerenotareliableindicatorofatopicdermatitis(Hou, etal,2006Hou,etal,2005).WhileitsstillcommonlyagreedthatIgEisplaying aroleintheskindisorder,itsbecomingclearthattheremaybeotherfactors alsoinvolved.AsinhumanAD,itseemsthatatopicdogstendtohavean imbalanceofimmunecellsandchemicals.Specialcellreceptors(CCR4),TARC (andimmunesystemchemical),increasedleukotrieneB4production,lysosomal enzymesandC3bhaveeachbeenfoundintheskinofatopicdogs(Maeda,et, 2004Maeda,etal,2005Breathnach,et,al,2006Marsella,etal,2006). Furtherresearchisthisareaofcellandchemicaldynamicscontinuestobedone. Acompleteknowledgeofthemechanismofatopicdermatitiswillleadtothebest andmosttargetedtreatments.Currenttreatmentscontinuetobeevaluatedfor theirefficacyandsafetywhilenewonesarebeingdeveloped.Manystudies haveshownfattyacidsupplementationtoimprovetheclinicalpresentationof theskinofatopicpatients(Mueller,etal,2004Saevik,etal,2004Abba,etal, 2005,Mueller,etal,2005). Researchhasfocusedontryingtounderstandthe mechanismbehindtheclinicalimprovement(Gueck,etal,2004)anddetermine thebestdosesandbalanceofomega3andomega6fattyacids.Onerecent studyconcludedthatneithertotalamountnorratiowasimportant.Fornow, fattyacidsremainavaluable,butmysterious,aidinthetreatmentofAD. Cyclosporine,asystemicimmunosuppressiveagent,hasrecentlybeencompared withmethylprednisolone(Steffan,etal,2004). Researchersfoundthatdogs treatedwithcyclosporinewerelesslikelytorelapseordidsoafteragreater amountoftimeafterstoppingtreatment.Severalotherstudieshaveshown cyclosporinetobeeffectiveandrelativelysafefordogs(Steffan,etal,2005 Guaguere,etal,2004Radowicz,etal,2005Burton,etal,2004,Steffan,etal, 2006).Itisthoughttohaveawidersafetymarginindogsthaninhumans, whereregularbloodtestsarenecessarytomonitorapatientshealth(Steffan,et al,2004). Onestudyshowed83.9%improvementindogssymptomsafter about40daysoftreatment(Burton,etal,2004).Thesideeffectsfoundhave tendedtobegastrointestinalinnature.However,allcurrentresearch recommendstheuseofcyclosporineforshorttermtherapyonly,uptoaboutsix months. Scientificsummariesofafewimportantreferencesonatopic dermatitisforveterinarians

Pathogenesis: IgE Ledin,A.,GenerationoftherapeuticantibodyresponsesagainstIgEindogs,an animalspecieswithexceptionallyhighplasmaIgElevels. HighIgElevels(totalserum)didnotcorrelatewithhealthstatus(atopic, healthy,parasites) Immunized9highIgEbeagleswithnewvaccinetoreducelevelwhich decreaseditby65%average.Maybehelpfultreatmenttolookinto further.

Marsella,Rosanna,Pilotinvestigationofamodelforcanineatopicdermatitis: environmentalhousedustmitechallengeofhighIgEproducingbeagles,mite hypersensitivedogswithatopicdermatitisandnormaldogs,2006 ThisstudyevaluatedthereactionofhighIgEbeagles,diagnosedatopicderma dogsandnormaldogstodustmites(sprayedonkennelfloor).Thedogswere subjectedtofourexposuresofdustmitesofincreasingconcentrationandtime. NormalandADdogswereusedascontrols.Thedogswereevaluatedfor erythema,macules,papules,excoriations,alopecia,lichenification,scalingand pruritis.Biopsieswerealsotakentoevaluatelesions.AllhighIgEdogsandall ADdogsdevelopedlesionsandpruritisafterexposurewhilenonormaldogsdid. Thestudyonlyincluded6IgEdogs,3ADdogsand3normaldogs. ThisstudywasuniqueinitsabilitytoproducepositiveAPT(atopypatchtests) anddermatitisinallIgEdogs.Theexperimentersthinktheirresultsaredifferent frompastexperimentsbecauseofthewaythedogswereinitiallysensitizedto dustmites(epicutaneously). Otherimportantpoints: Humiditylevelplaysaroleintheamountofmitesinanenvironment (higherhumidity=moremites) TheremaybemutationsotherthanhighIgEthatfacilitatethe developmentofskinlesions ReferencesWillemsesguidelinesfordiagnosingatopicdermatitis. CellDynamics MaedaS.,IncreaseofCCchemokinereceptor4positivecellsintheperipheral CD4cellsindogswithatopicdermatitisorexperimentallysensitizedtoJapanese cedarpollen.

CONCLUSION:TheproportionofCCR4+cellsinperipheralbloodCD4+ cellswasmeasuredindogswithallergicconditions.Thepresentfindings indicatethatCCR4+cellsmaybeinvolvedinthepathogenesisofallergy indogsasinhumans.

MaedaS.,Productionofamonoclonalantibodytocaninethymusandactivation regulatedchemokine(TARC)anddetectionofTARCinlesionalskinfromdogs withatopicdermatitis. ImmunohistochemicalanalysisusingthemonoclonalantibodyCTA1 demonstratedthatkeratinocytesweremajorTARCproducingcellsin lesionalskinofdogswithAD.

Breathnach,R.,IncreasedleukotrieneB4production,complementC3conversion andacidhydrolaseenzymeconcentrationsindifferentleucocytesubpopulations ofdogswithatopicdermatitis Thisstudymeasuredseveralmarkersoftheinflammatoryresponsein31atopic dogs,including6Westies.DogswithADhadallthreeenzymesmeasuredin increasedamountsvs.normalvalues.C3toC3bconversion(unlikeinhumans) andLTB4concentrationweresignificantlyincreasedinatopicdogs. ResultsindicateapotentiallysignificantroleforLTB4(inearlyphases), lysosomalenzymesandC3binthepathogenesisofAD Warrentsstudyingusingleukotrieneantagonistsfortreatment

Marsella,Rosanna,Cellularandcytokinekineticsafterepicutaneousallergen challenge(atopypatchtesting)withhousedustmitesinhighIgEbeagles. Thisstudylookedatthecellularandcytokinedynamicsofreactionsfromatopy patchtestingwithhousedustmitesin6highIgEbeagles.InhumanAD,itis currentlyacceptedthatimbalancesinlymphocytepopulationsandcytokine productionplayinimportantroleinthepathogenesisofthedisease. Eosinophilsshoulddominateanallergicreaction,notneutrophils. Resultsindicatethatthereisanimmunologicalresponseinwhich allergensappeartobeepicutaneouslycapturedbyepidermalLangerhans cellstriggeringaprogressiveinfiltrationofgranulocytesandlymphocytes. (116)HyperplasiaofLCoccurred(produceIL12maybeinvolvedin progressiontolaterphases) Cytokinespresentdependonageoflesions:earlylesionshad proinflammatorycytokines(IL6)andTh2cytokines(IL13),laterlesions

hadanincreaseinTh1cytokines(IL18)andincreasedmRNAexpression ofTARC TheauthorsconcludedtheyhadagoodmodelforhumanandcanineAD

AtopicdermatitisreferencesforownersandtheirveterinariansFor furtherreading AbbaC,MussaPP,VercelliA,RaviriG,Essentialfattyacidssupplementationin differentstageatopicdogsfedonacontrolleddietJournalofAnimalPhysiology andAnimalNutrition(Berl)89(36):2037,2005 BensignorE,OlivryT,Treatmentoflocalizedlesionsofcanineatopicdermatitis withtacrolimusointment:ablindedrandomizedcontrolledtrialVeterinary Dermatology16(1):5260,2005 BreathnachR,DonahyC,JonesBR,BloomfieldFJ,IncreasedleukotrieneB4 production,complementC3conversionandacidhydrolaseenzyme concentrationsindifferentleucocytesubpopulationsofdogswithatopic dermatitisVeterinaryJournal171(1):10613,2006 BurtonG,BurrowsA,WalkerR,RobsonD,BassettR,BrydenS,HillA,Efficacy ofcyclosporineinthetreatmentofatopicdermatitisindogscombinedresults fromtwoveterinarydermatologyreferralcentresAustralianVeterinaryJournal 82(11):6815,2004 CookCP,ScottDW,MillerWHJr,KirkerJE,CobbSM,Treatmentofcanine atopicdermatitiswithcetirizine,asecondgenerationantihistamine:asingle blinded,placebocontrolledstudyTheCanadianVeterinaryJournal45(5):4147, 2004 DeBoerDJ.,Canineatopicdermatitis:newtargets,newtherapiesTheJournal ofNutrition134(8Suppl):2056S2061S,2004 FarverK,MorrisDO,ShoferF,EschB,Humoralmeasurementoftype1 hypersensitivityreactionstoacommercialMalasseziaallergenVeterinary Dermatology16(4):2618,2005 FraserMA,McNeilPE,GettinbyG,ExaminationofserumtotalIgG1 concentrationinatopicandnonatopicdogsTheJournalofSmallAnimal Practice45(4):18690,2004 GuaguereE,SteffanJ,OlivryT,CyclosporinA:anewdruginthefieldofcanine dermatologyVeterinaryDermatology15(2):6174,2004

GueckT,SeidelA,BaumannD,MeisterA,FuhrmannH,Alterationsofmastcell mediatorproductionandreleasebygammalinolenicanddocosahexaenoicacid VeterinaryDermatology(5):30914,2004 HouCC,DayMJ,NuttallTJ,HillPB,EvaluationofIgGsubclassresponses againstDermatophagoidesfarinaeallergensinhealthyandatopicdogs VeterinaryDermatology17(2):10310,2006 HouCC,PembertonA,NuttallT,HillPB,IgGresponsestoantigensfrom DermatophagoidesfarinaeinhealthyandatopicdogsVetImmunologyand Immunopathology106(12):1218,2005 LedinA,BergvallK,HillbertzN.,HanssonH,AnderssonG,HedhammarA, Hellman,L,GenerationoftherapeuticantibodyresponsesagainstIgEindogs, ananimalspecieswithexceptionallyhighplasmaIgElevelsVaccine24(1):66 74,2006 MaedaS,OhmoriK,YasudaN,KurataK,SakaguchiM,MasudaK,OhnoK, TsujimotoH,IncreaseofCCchemokinereceptor4positivecellsinthe peripheralCD4cellsindogswithatopicdermatitisorexperimentallysensitizedto JapanesecedarpollenClinicalandExperimentalAllergy:JournaloftheBritish SocietyforAllergyandClinicalImmunology34(9):146773,2004 MaedaS,TsukuiT,SazeK,MasudaK,OhnoK,TsujimotoH,IwabuchiS, Productionofamonoclonalantibodytocaninethymusandactivationregulated chemokine(TARC)anddetectionofTARCinlesionalskinfromdogswithatopic dermatitisVeterinaryImmunologyandImmunopathology103(12):8392,2005 MarsellaR,NicklinC,LopezJ,AtopypatchtestreactionsinhighIgEbeaglesto differentsourcesandconcentrationsofhousedustmitesVeterinary Dermatology16(5):30814,2005 MarsellaR,NicklinCF,SaglioS,LopezJ,Investigationontheclinicalefficacy andsafetyof0.1%tacrolimusointment(Protopic)incanineatopicdermatitis:a randomized,doubleblinded,placebocontrolled,crossoverstudyVeterinary Dermatology15(5):294303,2004 MarsellaR,OlivryT,MaedaS,Cellularandcytokinekineticsafterepicutaneous allergenchallenge(atopypatchtesting)withhousedustmitesinhighIgE beaglesVeterinaryDermatology17(2):11120,2006 MarsellaR,OlivryT,NicklinC,LopezJ,Pilotinvestigationofamodelforcanine atopicdermatitis:environmentalhousedustmitechallengeofhighIgE

producingbeagles,mitehypersensitivedogswithatopicdermatitisandnormal dogsVeterinaryDermatology17(1):2435,2006 McEwanNA,KalnaG,MellorD,Acomparisonofadherencebyfourstrainsof StaphylococcusintermediusandStaphylococcushoministocaninecorneocytes collectedfromnormaldogsanddogssufferingfromatopicdermatitisResearch inVeterinaryScience78(3):1938,2005 McEwanNA,MellorD,KalnaG,AdherencebyStaphlococcusintermediusto caninecorneocytes:apreliminarystudycomparingnoninflamedandinflamed atopiccanineskinVeterinaryDermatology17(2):1514,2006 MuellerRS,FettmanMJ,RichardsonK,HansenRA,MillerA,MagowitzJ,Ogilvie GK,Plasmaandskinconcentrationsofpolyunsaturatedfattyacidsbeforeand aftersupplementationwithn3fattyacidsindogswithatopicdermatitis AmericanJournalofVeterinaryResearch66(5):86873,2005 MuellerRS,FieselerKV,FettmanMJ,ZabelS,RosychukRA,OgilvieGK, GreenwaltTL,Effectofomega3fattyacidsoncanineatopicdermatitisThe JournalofSmallAnimalPractice45(6):2937,2004 MuellerRS,VeirJ,FieselerKV,DowSW,Useofimmunostimulatoryliposome nucleicacidcomplexesinallergenspecificimmunotherapyofdogswith refractoryatopicdermatitisapilotstudyVeterinaryDermatology16(1):618, 2005 OlivryT,DeangeloKB,DunstonSM,ClarkeKB,McCallCA,Patchtestingof experimentallysensitizedbeagledogs:developmentofamodelforskinlesions ofatopicdermatitisVeterinaryDermatology17(2):95102,2006 OlivryT,JacksonHA,MurphyKM,TaterKC,RobertsM,Evaluationofapointof careimmunodotassayforpredictingresultsofallergenspecificintradermaland immunoglobulinEserologicaltestsVeterinaryDermatology16(2):11720,2005 PucheuHastonCM,ShusterD,OlivryT,BrianceauP,LockwoodP,McClanahan T,deWaalMalefytR,MattsonJD,HammerbergB,Acaninemodelofcutaneous latephasereactions:prednisoloneinhibitionofcellularandcytokineresponses Immunology117(2):17787,2006 PattersonAP,SchaefferDJ,CampbellKL,Reproducibilityofacommercialin vitroallergenspecificassayinimmunoglobulinEindogs.TheVeterinaryRecord 157(3):815,2005

RadowiczSN,PowerHT,Longtermuseofcyclosporineinthetreatmentof canineatopicdermatitisVeterinaryDermatology16(2):816,2005 SaevikBK,BergvallK,HolmBR,SaijonmaaKoulumiesLE,HedhammarA,Larsen S,KristensenF,Arandomized,controlledstudytoevaluatethesteroidsparing effectofessentialfattyacidsupplementationinthetreatmentofcanineatopic dermatitisVeterinaryDermatology(3):13745,2004 SchnablB,BettenaySV,DowK,MuellerRS,Resultsofallergenspecific immunotherapyin117dogswithatopicdermatitisVeterinaryRecord 21158(3):815,2006 SeidelA,GueckT,FuhrmannH,Theinfluenceoflongchainpolyunsaturated fattyacidsontotallipidfattyacidcompositiononacaninemastocytomacellline JournalofVeterinaryMedicine.APhysiology,Pathology,ClinicalMedicine 52(5):21924,2005 ShidaM,KadoyaM,ParkSJ,NishifujiK,MomoiY,IwasakiT,Allergenspecific immunotherapyinducesTh1shiftindogswithatopicdermatitisVeterinary ImmunologyandImmunopathology102(12):1931,2004 SimouC,ThodayKL,ForsythePJ,HillPB,AdherenceofStaphylococcus intermediustocorneocytesofhealthyandatopicdogs:effectofpyoderma, pruritisscore,treatmentandgenderVeterinaryDermatology16(6):38591, 2005 SteffanJ,FavrotC,MuellerR,Asystematicreviewandmetaanalysisofthe efficacyandsafetyofcyclosporineforthetreatmentofatopicdermatitisindogs VeterinaryDermatology17(1):316,2006 SteffanJ,HornJ,GruetP,StrehlauG,FondatiA,FerrerL,NoliC,Remissionof theclinicalsignsofatopicdermatitisindogsaftercessationoftreatmentwith cyclosporinAormethylprednisoloneTheVeterinaryRecord154(22):6814, 2004 SteffanJ,ParksC,SeewaldWNorthAmericanVeterinaryDermatology CyclosporineStudyGroup,Clinicaltrialevaluatingtheefficacyandsafetyof cyclosporineindogswithatopicdermatitis.JournaloftheAmericanVeterinary MedicalAssociation226(11):185563,2005 SteffanJ,StrehlauG,MaurerM,RohlfsA,CyclosporinApharmacokineticsand efficacyinthetreatmentofatopicdermatitisindogsJournalofVeterinary PharmacologyandTherapeutics27(4):2318,2004

SwinnenC,VroomM,Theclinicaleffectofenvironmentalcontrolofhousedust mitesin60housedustmitesensitivedogsVeterinaryDermatology15(1):316, 2004 TaiebA,HanifinJ,CooperK,BosJD,ImokawaG,DavidTJ,RingJ,GelmettiC, KappA,FurueM,deProstY,DarsowU,WerfelT,AthertonD,OranjeAP, th Proceedingsofthe4 GeorgRajkaInternationalSymposiumonAtopic Dermatitis,Arcachon,France,September1517,2005TheJournalofAllergy andClinicalImmunology117(2):37890,2006 ******************************************************** Topic#2:Understandingcancerindogs Weallknowwhatcanceris.Itisamongthemostfrighteningdiseaseswe encounterinourdogsandinourselves.Thetermcancerreferstothe progressive,relentlessanduncontrolledgrowthofcells.Amoreaccurateterm thatisnowusedbyscientiststocharacterizeuncontrolledcellgrowthis neoplasia.ThistermliterallytranslatesfromLatinasnewcells.Neoplasms (tumors)canbeeitherbenignormalignant. Allneoplasmsarecausedbymutationsinthegenomethegeneblueprintof cells,tissuesandindividuals.Thesemutationscanbeinheritedoracquiredby exposuretoviruses(wartsarecausedbypapillomaviruses),tochemical carcinogensintheenvironment,andbyexposuretoexcessiveamountsof radiation.Examplesofhowsomeformsofcancersseemtobeinheritedis discussedinExamples#1and#2,underDermatitis. Benigntumors,suchaswarts(officiallyknownascutaneouspapillomas),are characterizedbyexcessivecellgrowthinalocalarea.Many(butnotall)benign neoplasmsformdiscretelumpsandbumpsandthesearefrequentlytreatedby surgicalremoval,localchemotherapy,radiation,cryosurgery(freezing),or proceduresusingacombinationofthesetreatments.Benigntumorsusually respondverywelltotreatment,beingwellcontrolledforlongperiodsoftimeor curedcompletely. Showntotheleftisabenigntumoron theuppereyelidofan8yearold Westie.Thistumorgrewslowlyovera periodofacoupleofmonths,froma smallpinknoduletothisratherugly, raisedandulceratedmass.The surfaceofthemassisulceratednot coveredbynormalskincellsandis

mostlyhairless.Thistumorisalsoinflamed,probablybecauseitisbothinfected withbacteria(whichdidnotcauseit)andbecausethisdoghasbeenscratching it.Althoughitlooksprettynasty,itwasremovedbyveterinarysurgeonsandis veryunlikelytorecur.Thissurgicalsiteshouldhealinabout4weeks,with gradualreturnofhairtothesitethatwasshavedforsurgery.Thepathologist (drbob!)whoreadtheslideinterpretedthisasabenigncutaneoushistiocytoma, acommonandeasilytreatablebenigntumor.(PhotocourtesyofDr.Christine Sandberg). Malignantneoplasmsareadifferentstory. Malignantneoplasmsarethosetypes ofneoplasmsthatareofficiallycancers.Malignantneoplasmsfirststartas localuncontrolledcellclusters,butmayspread(infiltrate)intothetissuearound them.Malignantneoplasmsmayalsospreadtodistantsites,aprocesscalled metastasis,bywayofthebloodstreamandlymphaticchannels.Sometimes, veterinarianswillusethetermscarcinomaorsarcomawhendiscussing malignantneoplasms.Theseadditionaltermshelpdefinethetypeoftissuethat thecanceroriginatesfromandrelatestoterminologythatpathologistsusewhen describingbiopsies. Malignantneoplasmsaremuchmoredifficulttocontrolandtocureindogsand inpeople.Onereasonforthisisthatmalignantcellstendtoinfiltratenormal tissuesaroundthesiteoftumorgrowthearlyinthelifespanofthetumor.In fact,thewordcancerisderivedfromtheLatinwordforcrab,sincephysicians andveterinarians,hundredsofyearsago,recognizedtheinfiltrativegrowthof malignantcellsresembledthelegsofacrabprojectingfromthebodyofthe crab. Inanyevent,becausemalignantneoplasmsinfiltratetissue,theyaremuchmore difficulttoremovewithsurgeryorradiationtherapy.Malignantneoplasms frequentlyrequireextensivesurgicalresection,andthenadditionalradiationand chemotherapytocontroltumorgrowth.Unfortunately,manymalignanttumors arefoundaftertheyhavegrownforawhile,andtheymaybelarge,highly infiltrative,orhavealreadysentclustersoftumorscellstodistantsites,likethe lung,liver,brain,orbones(tumormetastases).Whenthesemalignanttumors arespread,theyaremoredifficult,ifnotimpossible,togetundercontrolandto cure. Westies,likeotherdogs,getalltypesofneoplasms.Asummaryoftumortypes wasobtainedinJune,2006fromtheVeterinaryCancerRegistrydatabase (www.vetcancerregistry.info).Thiselectronicdatabasecontainsrecordsof tumorsfromover6000dogsofallbreeds. HereiswhatwasintheneoplasmdatabaseforWesties:

Westies62totalcases(lessthan1%ofthetotalnumberofdogsin thedatabase) SexofWestieswithneoplasms Male(M)5dogs Female(F)7dogs Male,castrated(MC)20dogs Female,neutered(FN)30dogs

Ageofthedogatthetimeneoplasmwasnoticedandownersought veterinaryconsultation(agedatanotavailablefor2dogs) 12mo.2 1260mo.4 6172mo.5 73108mo.15* 109132mo.18* 133144mo.4 145156mo.6 157170mo.5 171194mo.1 *33/60(55%)ofneoplasmsoccurredindogsbetweentheagesof611 years Neoplasmsbysiteofoccurrence DigestiveSystem(7) Malignantlymphoma Papillaryadenocarcinoma Perianalcarcinoma Sarcoma Squamouscellcarcinoma(3) EndocrineSystem(1) Neuroendocrinecarcinoma EpithelialandMelanocyticTumorsoftheSkin(9) Adenocarcinoma Basalcellcarcinoma Carcinoma/adenocarcinoma Mastcellsarcoma(3) Pilomatricoma Squamouscellcarcinoma(2)

MesenchymalTumorsofSkinandConnectiveTissue(3) Fibrosarcoma Hemangiopericytoma Osteosarcoma MammaryGlands(5) Adenocarcinoma(2) Complexadenoma&ductalpapilloma Complexmammaryadenoma Invasivemammaryductularadenocarcinoma Hematopoietic/lymphoreticularsystemincludingmalignantlymphomas(14) Malignantlymphoma(12) Hemangiosarcoma(1) Histiocyticsarcoma(1) MaleGenitalSystem(2) ProstaticAdenocarcinoma NervousSystem(4) Granulomatousmeningoencephalitis Meningioma Neurofibroma Schwannoma RespiratorySystem(6) BronchialAdenocarcinoma Carcinoma(2) Nasaladenocarcinoma(2) Sarcoma UrinarySystem(11) TransitionalCellCarcinoma(11) SummaryofneoplasmsinWestiesbysiteofoccurrence(62animals total)(numberinparenthesesisthenumberofneoplasms) DigestiveSystem(7) EndocrineSystem(1) EpithelialandMelanocyticTumorsoftheSkin(9) MesenchymalTumorsofSkinandConnectiveTissue(3) MammaryGlands(5) Hematopoietic/lymphoreticularsystemincludingmalignantlymphoma(14) MaleGenitalSystem(2)

NervousSystemincludingeye(4) RespiratorySystem(6) UrinarySystem(11)

Themostcommontypesofneoplasms,basedonpercentageswere: Hematopoietic/lymphoreticularsystemneoplasmsincludingmalignant lymphoma(14/62=22.6%) Urinarysystemneoplasms(11/62=17.7%) AsimilartypeofanalysiswasdonefortwoothershortleggedScotsterrier breeds,ScottishTerriersandCairnTerriers. SummaryofneoplasmsinScottishTerriersbysiteof occurrence(97animalstotalsomewithmultiple tumors)(numberinparenthesesisthenumberof neoplasms) DigestiveSystem(17) EndocrineSystem(1) EpithelialandMelanocyticTumorsoftheSkin(8) MesenchymalTumorsofSkinandConnectiveTissue (18) MammaryGlands(5) Hematopoietic/lymphoreticularsystemincluding malignantlymphomas(22) FemaleGenitalSystem(1) NervousSystemincludingeye(6) RespiratorySystem(7) UrinarySystem(19) (PhotoofDuncan,ahappyandhealthyScottie,acourtesyofTheScottish TerrierClubofAmerica) Themostcommontypesofneoplasms,basedonpercentageswere: Hematopoietic/lymphoreticularsystemneoplasmsincludingmalignant lymphoma(22/97=22.6%) Urinarysystemneoplasms(19/97=19.6%) Digestivesystemneoplasms(17/97=17.5%) SummaryofneoplasmsinCairnTerriersbysiteof occurrence(33animalstotalsomewithmultiple tumors)(numberinparenthesesisthenumberof neoplasms) DigestiveSystem(5) EndocrineSystem(1)

EpithelialandMelanocyticTumorsoftheSkin(2) MesenchymalTumorsofSkinandConnectiveTissue(8) MammaryGlands(1) Hematopoietic/lymphoreticularsystemincludingmalignantlymphomas(8) MaleGenitalSystem(2) NervousSystemincludingeye(4) RespiratorySystem(4) UrinarySystem(1)

Themostcommontypesofneoplasms,basedonpercentageswere: Hematopoietic/lymphoreticularsystemneoplasmsincludingmalignant lymphoma(8/33=24.2%) MesenchymalTumorsofSkinandConnectiveTissueneoplasms(8/33= 24.2%) Digestivesystemneoplasms(5/33=15%) WhiletheinformationintheVeterinaryCancerRegistrydatabaseisveryuseful foridentifyingoveralltrendsintheincidenceofneoplasmsindogs,ithas limitations.First,onlyasmallnumberoftotalcasesaresubmittedforentryinto thedatabase,anditisverylikelythattherearemanymoredogswithtumors whoserecordsarenotsubmittedforinclusion.Second,onlycasesinwhich therehasbeenabiopsyconfirmationofthetumortypeareincludedmanydogs withsuspectmassesmaynotbebiopsiedandtheirinformationmaynotendup inthedatabase.Third,itisveryhardtotellifthenumberspresentedinthe VeterinaryCancerRegistrydatabaserepresentallofthedogsatrisk.Thereis nowaytoknowhowmanyWesties(orScotties,orCairns,ordogsofmixed heritage)areactuallyintheUnitedStatesandwecanonlymakerough estimatesofdogsatriskfordevelopingneoplasms.Theworkofbreedclubs liketheWFAinconductingsurveysofhealthproblemsinspecificbreedsisa greathelpinmakingmoreaccuratedataavailable.

BladdercancerinWestiesandScotties Onetypeofcancerthatisofveryseriousconcernto ownersofWestiesandScottiesisbladdercancer.The medicaldesignationofthistypeofmalignantneoplasmis transitionalcellcarcinoma(TCC)oftheurinarybladder. TCCcanoccurinanydogbreed,butismorecommonin ShetlandSheepdogs,ScottishTerriersandWesties.The medianageofoccurrencefordogsisaround8yearsold. ThereareseveralexcellentwebsiteswhichdiscussTCCindogs,howthistumor isdiagnosedandhowitistreated.Twosuchsitesare: www.petplace.com/dogs/urinarybladdercancerindogs/,asitethatis authoredbyDr.JeffreyPhilibert www.veterinarypartner.com,asitethatisauthoredbyDr.WendyBrooks. Onthissiteyouwillneedtosearchfordiseasesofdogsandthenlookfor urinarybladdercancer AbriefsummaryofimportantaspectsofthisdiseasewillhelptoalertWestie ownersthattheirdogmayhaveaproblem. Transitionalcellcarcinomaoftheurinarybladderdevelopsfromcellsthatline theurinarybladderandthekidney.Thereappeartobeanumberoffactorsthat influencewhetherornotthisneoplasmwilldevelop.Indogs,thegenome appearstoplayamajorrole,sincesomebreeds(theshortleggedScotsbreeds likeWestiesandScotties)seemtohaveahigherincidencepercapitathanother breedsofdogs.Thisincreasedbreedincidence,onceagain,suggeststhat duringthedevelopmentofthebreed,certainmutationsinthegenomewere acquiredandlinkedtodesirablebreedcharacteristics.Itisverylikelythatthere areseveralmutationsthatmaybepresentandresearchscientistsareactively lookingforthem,inordertoseewhatiscausingcancertodevelop.Remember, noteverydogwillinheritmutationsthatcanleadtothedevelopmentofcancer, anditmaytakethecomplexinteractionsofseveralmutationstoleadtothe initiationanddevelopmentofneoplasms. Oneotherimportantfactorinthe developmentofbladderneoplasmsinScotties isexposuretocertainenvironmental chemicals.Glickmanandhiscolleaguesat thePurdueUniversitySchoolofVeterinary Medicinehaveshownthatrepeatedexposure toonetypeofcommonlawnchemical phenoxyherbicidesmayleadtoan increasedriskfordevelopingbladdercancer.

(PhotoofRosie,ahappyandhealthyScottie,courtesyoftheScottishTerrier ClubofAmerica) HereisasummaryofimportantfindingsfromworkconductedatPurdue UniversitysSchoolofVeterinaryMedicine(From: http://www.vet.purdue.edu/news.html). HerbicideExposureandUrinaryBladderCancer InvestigatorsatthePurdueUniversitySchoolofVeterinaryMedicinehave recentlyconductedacasecontrolstudyinScottishTerrierstodeterminerisk factorsforthedevelopmentofurinarybladdercancer(transitionalcell carcinoma,TCC).Resultsofthiscasecontrolstudywererecentlypublishedin theJournaloftheAmericanVeterinaryMedicalAssociation(April15,2004 volume224pages12901297).ScottishTerriershavepreviouslybeenfoundto beathigherriskofTCCthanotherbreedsofdogs.Thestudywasperformedto determineifexposuretolawnchemicalsfurtherincreasestheriskofTCCinthis breedofdogs.Environmentalexposurehistorieswerecomparedbetween83 ScottishTerrierdogswithTCC(cases)and83ScottishTerrierdogsof approximatelythesameagewithotherhealthrelatedconditions(controls).A significantlyincreasedriskofTCCwasfoundfordogsexposedtolawnsor gardenstreatedwithherbicidesandinsecticidesorherbicidesalone,butnotwith insecticidesalone,comparedwithdogsexposedtountreatedlawnsorgardens. ThesefindingssuggestthatScottishTerrierdogs,aswellasotherdogsofhigh riskbreedsforTCC,berestrictedfromlawnstreatedwithherbicidesuntil additionalriskstudiesareconducted.Withthepublicationofourfindings,the largenumberofrequestsforinformationrelatedtothisstudyhasexceededour capacitytorespondonanindividualbasis.Furtherinformationcanbeobtained from:http://www.vet.purdue.edu/epi/herbicide_tcc_scotties.docorfrom http://clubs.akc.org/stca/TCCStudy_Page_1.htm. (Completescientificcitation:Herbicideexposureandtheriskoftransitionalcell carcinomaoftheurinarybladderinScottishTerriers,Glickman,LT,Raghavan, M,Knapp,DW,Bonney,PL,Dawson,MHJournaloftheAmericanVeterinary MedicalAssociation224:12901297,2004) Westieownersneedtounderstandthishasonlybeenwellstudiedin Scotties,butisthesubjectofveryintenseinvestigationbyseveralgroupsof researchscientists.Inhumans,occupationalexposuretoseveraltypesof chemicalssuchasdyesandplasticizershasbeenassociatedwithanincreased riskofdevelopingTCCoftheurinarybladder. Diagnosingurinarybladdercancer(TCC)indogs

Thefirstsignsthattheremayaproblemwiththehealthandfunctionofthe urinarybladdermaybeoneormoreofthefollowingclinicalsigns: difficultyurinating frequentattemptstourinate(achangeinthepatternofurination) dribblingurine lossofhousebreakinginadultdogs thepresenceofblood(hematuria)intheurine(seenaspinkorredspots onfloorsandcarpets) abdominaltenderness Ofcourse,thesesignsonlyindicatethereispotentiallyaproblemwiththehealth andfunctionofthebladderandarenotspecificforanydisease.Forexample, thesesignsmightindicatebladderinfection,thepresenceofstones,aneurologic problemleadingtoalteredbladderfunction,orthepresenceofaneoplasm, amongotherdiseases.TheimportantthingforWestieownerstonoteisthatif theirdogisdevelopingorhavinganyofthesesigns,theyshouldtaketheirdog totheirveterinarianforfurtherevaluation. Theveterinarianwillperformaphysicalexaminationofyourdog,andalso suggestsomeadditionalteststonarrowdownwhatiscausingyourdogtohave signsofbladderdisease.Duringthephysicalexamination,itisverylikelythe veterinarianwillgentlypalpatethedogsabdomen,payingattentionforsignsof tenderness,especiallyaroundtheareaoftheurinarybladder. Theveterinarianmaysuggestcollectingaurinesample,eitherbycatchingurine inapanoracupduringspontaneousurination(afreecatchspecimen),by passingacatheterintothebladder,orbytakingasmallsamplewithasyringe andneedle,throughtheabdominalwall(thisisknownascystocentesis).Urine samplescollectedbytheuseofacatheterorbycystocentesiscanbeusedfor bacterialculturetoseeifthereisaninfectionpresent.Urinesamplescanalso beanalyzedforthepresenceofbloodandtoseewhattypesofcellsandother suspendedmaterialsarepresent.Attimes,veterinariansandclinical pathologistscanseeclumpsofcellsthatmayindicatethepresenceoftumors. Itisverylikelythatyourveterinarianwillalsosuggestadditionaltests.Recently, atestcalledthebladdertumorantigentest(VBTA)wasdevelopedtohelp detectthepresenceofsomeuniqueproteinsassociatedwithTCCindogs.This maybeespeciallyhelpfulinscreeningforthepresenceofaneoplasm. Itisquitecommonnowforveterinarianstodoradiographs(theoldtermwasx rays)andtodoultrasoundstudiestolookformassesinthebladder.Shown belowisaradiographicoftheurinarybladderofaSheltiedogwhichwasseenby aveterinarianforbloodintheurine.Inthisradiograph,theurinarybladderhas

beenfilledwithacontrastdye.Thearrowinthisimagepointstoadarkmass (calledafillingdefect)isatransitionalcellcarcinomaprojectingintothecenter ofthebladder.Theseimagingstudiesareveryhelpfulindifferentiatingbetween stonesandtumors.

(RadiographcourtesyofDr.ChrisOber) Definitivediagnosisandoptionsfortherapy Ifthereisahighlikelihoodthatatumorispresent,yourveterinarianmaywant toperformasurgicalbiopsy.Thiswillinvolvegeneralanesthesia,anexploratory surgicalprocedureoftheabdomen,andopeningoftheurinarybladder.Some veterinarianswillremoveasmuchtumoraspossibleduringthisprocedure. Othersmaychosetotakeasmallbiopsytobesenttoapathologist,andthento treatthebladderwithoneormorechemotherapeuticagents. Chemotherapeuticdrugsusedtotreatcanceroftheurinarybladderindogsare identicaltodrugsusedtotreatthisneoplasminpeople.Allcancer chemotherapydrugsaregiventokilltumorcells.Theydothisinavarietyof ways,includinginterruptingtumorcelldivision,blockingtumorcellmetabolism, breakingdowntumorcellDNAandgenes,orpoisoningothertumorcell activities. Cancerchemotherapydrugsareusuallygivenbymouthorinjection,ora combinationofthesemethods.Treatmentmaycontinueformonths,depending ontheextentofthetumor,responseofthetumortotherapy,andtolerancefor thesideeffectsofthedrugs.Typicalunpleasantsideeffectsseeninsomedogs mayincludevomitinganddiarrhea,lossofenergy,changesinpatternsof urination,andpotentiallyincreasedsusceptibilitytoinfections.Itisvery importanttoknowthatveterinariansareveryexperiencedintreatingcancer, thattheyunderstandtheeffectsandsideeffectsofdrugtherapy,andthatthey

aretryingtohelpyouandyourpetovercomeaseriousdiseaseproblem.Most sideeffectsofdrugtherapyaretransientandtemporary,andcanbemanaged withsupportivecare.Youneedtodiscussthiswithyourveterinarianwhen decidingandiftotreatyourdog.Mostveterinarianswillalsodiscusstheuseof medicationstocontroldiscomfortandwillbecandidabouttheprobabilityofthe treatmentsbeingeffective. Theoutlook(prognosis)fordogswithbladdercancerisguardedanddepends agreatdealon: initialsizeandlocationofthetumor theamountofinvasionofthebladderwallandsurroundingtissuesinthe abdomen metastasisoftumorcellstolymphnodesandotherlocations ageandoverallhealthofthedog histologictypeoftumor,includingdegreeofdifferentiationandcellular patterning responseoftumorcellstochemotherapy toxicsideeffectsofchemotherapy AccordingtoDr.DeborahKnapp(TumorsoftheUrinarySystem,Chapter25in rd SmallAnimalClinicalOncology,3 ed.,Withrow,SJandMacEwen,EG,WB SaundersCo,Philadelphia,PA,2001)themediansurvivalofdogs(ofallbreeds) withtheearlystagesofTCCis218days.Fordogswithmoreadvanceddisease, thesurvivalisabouthalfofthatinterval.Ofcourse,theoutcomeforany individualdogishardtopredict,butTCCoftheurinarybladderisoneofthe mostserioushealthproblemsaffectingWestiesandothershortleggedScots breedterriers.

(ShortieTheScottie,courtesyofLisaandMichaelCerone,MinglewoodKennels)

Wecollectively(owners,breeders,veterinarians,andresearchscientists)needto putforthourbesteffortstoidentifythecausesandtofindeffectivetreatments forneoplasmsinourdogs.Weowethemthat.

******************************************************** Topic#3:IdiopathicPulmonaryFibrosisWestieLungDisease LungDisease Breathingproblemscanarisefromanumberoffactorsincludingdevelopmental problems,injury,obstructionofairways,circulationproblems,viral,bacterialand fungalinfections,andinterstitialdisease.Interstitialdiseaserefersto abnormalitieswithintheinterstitium,thestuffbetweentheairsacks(the alveoli)whichfunctioninbreathing.Thisinterstitiumismadeupofelastin, collagen,smoothmusclecells,mastcellsandafewothertypesoflesscommon cellsandgivesthelungsstructureandstrength.Pulmonaryfibrosis,alsoknown asWestieLungDiseaseoracuteinterstitialpneumonia,isadiseaseofthelung interstitiuminwhichthereisinjurytothosecellsandfibers.Asaresultofthis injury,scaringoccurs.Thescartissuedecreasestheabilityofthelungsto functionnormally,causingdifficultybreathingand,eventually,death. Fibrosis Wedonotknowwhatinjuryoriginallycausesthescaring,orfibrosis,totake place,sothediseaseisoftenreferredtoasidiopathicpulmonaryfibrosis. The wordidiopathicmeansthatonedoesnotknowwhatcausesthedisease.(Other formsofpulmonaryfibrosisoccurinhumans,buttheinjurycanbetracedto exposuretothingslikecigarettesmokeorminingdusts.)Itwasoncethought thatidiopathicpulmonaryfibrosiswasasortofinflammatoryreactiontoaone timeinjury.Itisnowunderstoodthatfibrosisismostlikelytobetheresultof repeatedinjurybysomeunknownagentoragents(perhapsacombinationof allergensintheair,pollution,andinfectiousorganisms).Thebodysnatural responsetoinjuryistoreplacedamagedcellsandfiberswithnewfibrous connectivetissue(scartissue).Whilethescartissuefillsinthespacewhere damageoccurred,itusuallyleavesthearealessflexibleandlessfunctional. Similartoascarontheskin,scartissueformationhealsthewound,butdoesnt leavetheareaquitethesame.Overactiveandrepeatedscarring,asin pulmonaryfibrosis,leavesthelungsinadebilitatedstate,unabletoexpandfully ortocontractproperly,andwithimpairedabilitytobringoxygenintothebodyor toexpelwastegases.Thereappearstobeageneticcomponenttopulmonary fibrosisandWestiesappear,inparticular,tobeatrisk. ClinicalSymptomsandDiagnosis Themajorsymptomofdogswithpulmonaryfibrosisisdifficultyinbreathinga clinicalsignknownasdyspnea.Somecaninepatientswillalsocough frequentlyandmayhaveafever.Thesedogstirequicklyandgetoutofbreath

fromthingstheyoncecoulddowithease(likerunningaroundorgoingupand downstairs).Lungsoundsheardthroughastethoscopeareabnormal.Asthe diseaseprogresses,patientswilldevelopenlargedhearts.Therightventricle,in particular,enlarges,asthisisthepartoftheheartthatpumpsbloodintothe increasinglyresistantlungs.Patientsmayalsohavecongestionintheirveins aroundtheirorgans,theresultoflowgradecirculatoryandcardiacdysfunction. Hypersensitivitypneumonitis,adisorderinwhichthepatienthasanallergic reactiontoinhaledorganicdusts,hassimilarsymptomstopulmonaryfibrosis andcanleadtochronicanddebilitatingscaringaswell.Aveterinarianwilluse theclinicalsignsandhistorytodiagnosepulmonaryfibrosis.Inthecaseof hypersensitivity,pulmonaryfibrosismaybepreventedbyeliminatingexposureto theallergen. Insomecases,skintestingmaybeusedtodetermineallergic sensitivity(seethesectionofthisEBookthatdiscussesAtopicSkinDisease) Lungfunctionstudiesandxrays(radiographs)arealsousedtomakethe diagnosis.Aveterinarianmaylookatthepatientslevelofoxygenintheblood, therespiratoryrate,howwelloxygenisbeingtakenin,andhowwellcarbon dioxideiseliminatedfromthebody.Chestradiographsfromthosesufferingwith pulmonaryfibrosisshowaparticulartypeofshadowinginbothlungsinsteadof clearairspace. Insomecases,veterinariansmayconsiderdoingalungbiopsy,tocollecttissue forhistologicinterpretationbyaveterinarypathologist. Abiopsyofthelung tissueisthegoldstandardusedtomakethediagnosisofidiopathicpulmonary fibrosisinhumans.Whilethisprocedureisinvasive(itrequires sedation/anesthesiaandsurgicalpreparation,ataminimum),itistheonlyway tolookattheactuallungcellsforabnormalchangesindicatingdisease. Veterinariansmayalsouseatechniquebronchiolarlavagetolookatother typesofcellsinvolvedinthediseaseprocess.Thisdiagnosticprocedureinvolves sedatingthedog,washingdilutephysiologicsterilesalinesolutionintothe patientslungs,andthensuctioningitoutwithasyringe.Whenthesaline sampleisthenretrieved,itcontainscellsanddebrisfromthelungsandairways. Experiencedveterinaryclinicalpathologistscanthenlookatthefluidandthe contentsofthefluidandmakeaninterpretationaboutthetypesofdiseasethat maybepresent,basedonthecontentsofthelavagefluid. TreatmentandPrevention Idiopathicpulmonaryfibrosisisaveryseriousandpotentiallyprogressivedisease inWesties. Preventionofthisdevastatingdiseasemaystartwithcareful breeding.Currentresearchislookingintoexactlyhowtodeterminewhich animalsoffspringareatrisk.Whilemostcaninepulmonaryfibrosisisidiopathic, smokingisacommoncauseofthediseaseinhumans(hotgasesfromcigarette smokedamagelungtissueandthisleadstoscarringandlungremodeling

emphysema).Livingwithahumanwhosmokeswilldramaticallyincreaseany dogsriskofdevelopingpulmonaryfibrosisandotherlungdiseases. Thereisnocureforpulmonaryfibrosisandtreatmentisdifficult.Currently, patientscanbehelpedbytheuseofcorticosteroids,tosuppresstheimmune systemandhelpinterruptthecyclethatleadstofibrosis. Systemicanti inflammatorytherapy(suchastheuseofdrugslikeaspirinoribuprofen)hasnot beenshowntobeparticularlyeffectiveintreatingthesignsofdiseaseor arrestingtheprogressivescarringassociatedwiththedisease.Withoutagood understandingofthecauseofthisdisease,therapiesarenotspecifictothe diseaseanddonotcompletelyalleviatesymptoms.Bronchodilatorsandcough suppressantsmayhelpmakesomepatientsmorecomfortable.Eachpatientwill haveadifferentresponsetotherapy.Casesdiagnosedinearlierstagesofthe diseasecanoftenbemanagedmoresuccessfullythancaseswhichhave progressedsignificantly. Dogswithlongstandingdiseasemaybeatriskfor heartproblemsandthese,too,willneedtobedetectedandmanaged. CurrentResearchinCanineIdiopathicPulmonaryFibrosisForfurther reading Idiopathicpulmonaryfibrosishasonlybeendiscoveredtoexistindogsinthe pastseveralyears.Mostliteratureonthesubjectiscasestudies,profilingdogs, oftenWesties,withthesymptomsandprogressionthatindicatepulmonary fibrosis.Veterinariansarestillsharingthistypeofinformationinthehopesof gatheringmoredatatoexplainthepossiblecausesandgeneticlink. In2005,astudywasrunwhichcomparedthefindingsinlungtissueofsix Westiesdiagnosedwithpulmonaryinterstitialfibrosistothosenormally associatedwiththehumanversionofthedisease,usualinterstitialpneumonia i (Norris,etal,2005). TheauthorsconcludedthatconcentricdepositionofECM [extracellularmatrix]aroundalveolarcapillaries(39)wasthemainfeatureof Westiechronicpulmonarydisease.Thismeansthatthetissuesshowedexcess buildupofconnectivetissuebetweenairsacksandbloodvessels.Theextra materialthickensthebloodairbarrier,makinggasexchangemoredifficult.The authorssawnoevidenceofdamagetobasallamina,whichisoneofthe hypothesizedsitesofrepeatedinjurywhichcanleadtofibrosis.Onlymild inflammationwasobserved,challengingthehypothesisthatfibrosisstemsfrom anoveractivefightagainstinfection.Theauthorssuggestedmoreresearchbe doneonabnormalcollagenregulation,asincreasedsynthesisofcollagenor decreaseddegradationofitmustbeplayingarole. Twootherrecentstudiesexaminednewwaystodiagnosepulmonaryfibrosis.In 2002,researchersusedakeyholebiopsymethodon13animalswithsuspected interstitiallungdisease(ILD)(Norris,etal,2002). Theypromotedthis

procedureasnecessaryindiagnosisofILDwhileotherdiagnosticsproveduseful inrulingoutinfectionorcancer.Complicationsfromthesurgeryincluded insufficientoxygenationoftheblood(hypoxemia),poorwoundhealinginthose patientstakingimmunosuppressants,airinthepleuralcavity(pneumothorax) andpulmonaryhemorrhage.Twodogsinthestudywereeuthanizedfollowing surgerybecausetheiralreadyseverecasesworsenedpostoperatively. Themostpromisingnewdiagnosticmaybethoracichighresolutioncomputed tomography(HRCT).HRCTusesatightlycollimatedxraybeamwithhigh spatialfrequencyreconstructionalgorithms(382)totakeimagesoftheareaof thelungs.A2005studyexaminedeightWestiesandtwoCairnTerrierswith symptomsindicatingcanineidiopathicpulmonaryfibrosis(IPF)(Johnson,etal, 2005). BycomparingHRCTimagesofcasesclassifiedasmild,moderateor severefromotherdiagnostics,theresearchersconcludedthatTHCTwasa superiorimagingtooltoradiographs.Withmoreresearch,itcouldbecomethe definitivediagnosticforIPFandreplacebiopsy. References Norris,AJ,naydan,DK,Wilson,DW,InterstitiallungdiseaseinWestHighland WhiteTerriers,VeterinaryPathology42:3541,2005 Norris,CR,Griffey,SM,Walsh,P,Useofkeyholebiopsyfordiagnosisof interstitiallungdiseasesindogsandcats:13cases(19982001),Journalofthe AmericanVeterinaryMedicalAssociation221:14531459,2002 Johnson,VS,Corcoran,BM,Wotton,PR,Schwarz,T,Sullivan,M,Thoracichigh resolutioncomputedtomographicfindingsindogswithcanineidiopathic pulmonaryfibrosis,JournalofSmallAnimalPractice46:381388,2005 ********************************************************

Topic#4:LeggCalvePerthesDisease(LCP)(Asepticfemoralhead necrosis) YoungWesties,andotherbreedsofpurebreddogs,candevelopadebilitating conditioninwhichthebonesthatformthetopofthehindleg(thefemurs) deteriorate.Thisconditionalsooccursinchildrenandwasfirstdiagnosedin 1910bythephysician/scientistswhothediseaseisnamedafter. Bonegrowthandskeletalmaturation Alldogsarebornwithanimmatureskeletalsystem.Healthydevelopinglong bones,likethoseinthelegs,growbywayofaprocessknownasendochondral ossification.Whenanimalsarefirstdevelopingtheirskeleton(thisoccurs duringgestation[pregnancy]),alloftheboneismadeentirelyofcartilage.As growthandmaturationoccur,thecartilagethatformsthemodelingstructures becomescalcifiedfromthecenteroftheboneoutward.Asthisoccurs,athin layerofboneislaidaroundtheoutsideoftheshaftofthebone(alsoknownas thediaphysis).Bonemarrow,containingstemcellsandmaturingbloodcells) developsinsidetheformingbone,asarebloodvessels.Eventually,immature boneisformedinasalacey,wovenmatrixforfurtherdevelopment.Thebone ends,orepiphyses,arestillmadeofcartilageandcontinuetogrow.Thearea wherethecartilageepiphysismeetstheboneydiaphysismeetisknownasthe growthplate.Thebonegrowsbywayofreplacingcartilagewithboneatthe growthplateandwithintheepiphysis,whichhasitsowncenterofbone development,orossification.Eventually,immaturewovenboneisremodeled intomatureregularbone. Whenthedogismature,thegrowthplatesslowdownorceaseactivity,and bonesstopgrowing.Dependingonthebreed,thismaturationoftheskeleton andbonesgenerallyoccursbetween12yearsofage.Itisimportanttorealize thatallbone,inanimalsofanyage,isalivemadeupofcells,usingnutrients andoxygenfromthecirculation,respondingtodemandsforsupportand strength,constantlyrenewingitself,andcapableofrepairinginjuries,like fractures. Bonegrowthisaverycomplexandwellregulatedactivity.Thegenomeofeach dogcontainsinstructionsforboneandcartilagecells,fortheorganizationof thesecellsintobones,andfortheorderlygrowthoftheskeletontosupportthe dogsactivities.Theproperformationofboneisheavilydependentonan adequatesupplyofnutrientssuchasprotein,calciumandseveralotherminerals, aswellastheactivityofoneormorevitaminsandhormones.Boneformationis alsocontrolledbythegrowthofbloodvesselsinandaroundboneandinthe coveringofbone,theperiosteum.

ThepathogenesisofLCPdisease Asnotedabove,boneisalivingtissueand,likeotherbodytissues,isvulnerable toallkindsofdiseases,rangingfromdevelopmentalandcongenitalproblemsto cancer,infection,metabolic,orbiochemicalproblems.LeggCalvPerthesis classifiedasadevelopmentalorthopedic(bonerelated)disease. Eachstageofbonedevelopmentrequireshealthybloodvesselstobring nutrients,includingoxygen,totheworkingcellsandcarrywastefromthose cells.InLCPdisease,bloodflowtodevelopingboneisdisrupted.Young cartilageandbonecellsdontgetthenutrientstheyneed,andconsequentlythey die.Asaresultofthiscelldeath(alsoknownasnecrosis),thehead(s)ofthe femursdonotproperlydevelopandareweak.Asaresultofthisboney weakness,theheadsofthefemursindogswithLCPmayfracture,evenwith normalactivity.Thebloodflowproblemthatseemtobetheincitingcauseof LCPappearstobetemporary,becausethebonewilleventuallyhealitselfand remodel.However,thisremodelingleavesthefemoralheaddeformedandleads todegenerativejointdiseaseandpainforthepatient. Itisnotknownexactlywhatcausesthedisruptioninbloodflowtothefemoral headregion,despitethefactthisdiseasehasbeenobservedinpeopleandin animalsfornearlyacentury.Theoriesincludedestructionofthegrowthplate, repeatedblockageofbloodflow,compressionoftheveins,effectsofsex hormones(inpeople,boysaremoreaffectedthangirls),infectionofthehipjoint orincreasedpressureinthejoint.Ageneticcomponentissuspectedbecause severalbreedsareoverrepresentedinpresentation,includingWesties. Clinicalsigns LeggCalvPerthesdiseasetypicallyaffectssmallbreeddogs.Onsetisusually betweenfourandelevenmonthsandmalesandfemalesareatequalrisk.Only 1216%ofdogshavebothlegsaffected.Patientsexperiencingthesebone changeswillbeirritable,maylimpandmaybeinpain.Asthedisease progresses,theglutealandquadricepsmusclesmayatrophy,makingthem appearsmaller.In68weeks,thepatientmaynotputweightontheaffected limbatall. Diagnosis TheprincipaldiagnostictoolforLeggCalvPerthesdiseaseisanxrayor radiograph. Veterinarianslookforincreasedjointspaceinthehipoftheproblem leg,decreaseddensityofthebone(givingagreyappearanceinsteadofastrong white),subtleorovertfractureoftheheadofthefemur,andpossibledislocation ofthehipjoint(subluxation). Inearlystages,patientswillexperiencepainwhen

aveterinarianmanipulatesthelimboutwardawayfromthebody(abductsthe limb),restrictedlimbmotion,andtheremaybeacrinklyorgratingfeelingor soundinthehipjoint(crepitus). Intheradiographicimageofadog,showntothe left,thereisaverygoodexampleofaseptic necrosisofthefemoralhead.Thisradiographis froma10montholddog(notaWestie)withthe typicalradiographicsigns.Atthearrow,thereis degenerationofthetopofthefemurand detachment(subluxation)fromthehipsocket. (ThisradiographiscourtesyofDr.ChrisOber). Treatment/Prognosis/Prevention TheacceptedtreatmentforLeggCalvPerthesis surgicalremovalofthefemoralheadandneck,the sectionofbonerightunderthehead.Oncethe surgeryiscompleted,aftercareinvolvesexercisingthedogslegswithagentle programofexercisethatmayincludewalking,andthenrunningandswimming. Theexerciseencouragesthegrowthofafibrousfalsejoint,alsoknownasa pseudoarthrosis.Scartissueactuallytakestheplaceoftheheadofthefemur andfitsintothehipbone.Whilethisproceduremayseemprettydramatic, patientscanhavefulluseoftheleginaslittleasfourweeks.Thisisdependent, however,onthedegreeofbonychangesinthefemurandhipbeforesurgery, andmayvarybyindividuals.Surgeryrelievesthepainandlamenessindogs sufferingfromLeggCalvPerthesin84100%ofcases,regardlessofthe progressionoftheconditionorageofthepatient.Propersurgicaltechniqueis criticalmanyveterinariansareveryexperiencedwiththeprocedureoffemoral headresection. Withoutsurgery,dogswithLCPdiseasepatientscanbekeptcomfortablewith rest,thejudicioususeofantiinflammatorydrugsandmedicationtocontrolpain, andattentionpropernutrition(topromotenaturalhealing).Lamenessresolves withthiscourseoftreatmentinlessthan25%ofpatients. RecentResearchonLeggCalvPerthesDisease Unfortunately,therehasnotbeenmuchresearchoncanineLeggCalvPerthes diseaseinrecentyears.Itwasdiscoveredtoexistindogsinthe1960s,butonly ahandfulofstudieshavebeendonetoexplorethecausesandtreatmentsfor theconditioninthelastdecade.

Asrecentlyas2002,researcherslookedattheprevalenceofdevelopmental orthopedicdisordersindogsforthefirsttime.Byexhaustivelyreviewing veterinaryteachinghospitalmedicalrecordsfrom1986to1995,veterinary researcherswereabletoranksusceptibilityofbreedsforbeingdiagnosedwith twelvedevelopmentalorthopedicdisorders.WestHighlandWhiteTerriersare 33.2timesmorelikelytohaveLeggCalvPerthesthanmixedbreeddogs.Of thebreedsthathadbeendiagnosedwiththecondition,Westieswerethe seventhmostrepresentedbreed.Whilebreedsusceptibilitysuggestsagenetic componenttoanydisease,theresearcherspointedoutthattheultimate methodtocharacterizegeneticetiologyforadiseaseisthedeterminationofits heritabilityandmodeofinheritance(Lefond,etal,2002).Thismeansthat mappingthegenomeofWestieswouldgiveusthebestopportunitytoseewhat mutationsareassociatedwiththedevelopmentofthediseaseandhowitis inherited. LeggCalvPertheshasbeenlinkedtooveractivebloodclottinginhumans. Clottedbloodcancreatethrombosis,atravelingclotthatblocksbloodvessels andcausesthetissuesaroundtheblockareatogowithoutnutrientsanddie.A 1999studyexaminedtheclottingfactorsin18dogswithLeggCalvPerthesbut foundclottingtobeentirelynormal(Bertram,etal,1999).Basedonthiswork, itappearsthatfactorsotherthanclottingarecontributingtotheconditionin dogs. ApromisingnewdiagnostictoolforearlydetectionofLCPdiseasehascomeout ofhumanmedicine(Isola,etal,2005).Dualenergyxrayabsorptiometryisa techniqueforimagingprecisebonemineraldensity.Itcanbeusedforhumans anddogs.Quantifyingbonemineraldensityallowsveterinarianstotrackthe progressofboneweakeningdiseasesandpotentiallydiagnosesuchproblems earlier.A2005studyfoundnosignificantdifferenceinmineraldensitybetween dogsgoodandbadlegs,butattributedthistoboneremodelinginthebadleg. Boneremodelingmaynotbeeasilyseenwithconventionalradiographicmethods usedinroutineveterinarypractice. AbetterunderstandingofwhypatientswithLeggCalvPertheshavebloodflow disruptionscouldpotentiallygreatlycontributetoourabilitytotreatthedisorder inalessinvasivewaythansurgery.Moreresearchintheareaofgeneticsand genomicswouldpotentiallyhelpuswipeoutthedisorderandkeepWestiesfrom experiencingthepainassociatedwithit. ReferencearticlesonLCPdisease,withselectedshortsummaries, Forfurtherreading

Bertram,B,Leeb,T,Jansen,S,Kopp,T,Analysisofbloodclottingfactor activitiesincanineLeggCalvePerthesDiseaseJournalofVeterinaryInternal Medicine13:570573,1999 Basedonthetheorythatischemiaresultsfromvascularcompressionorocclusion andthelinktohypercoagulabilityinhumans,researcherslookedatmediatorsof thrombosis.Alldogs(18)studiedhadnormalplasmaclottingfactorsand clottingactivity.Theresultsofthisstudyappeartoindicatethat hypercoagulability/thrombosisisnotaprimaryfactorinthedevelopmentofLCP diseaseindogs. Demko,J,McLaughlin,R,DevelopmentalorthopedicdiseaseTheVeterinary ClinicsofNorthAmericaSmallAnimalPractice35:1111135,2005 Overviewofseveraldiseases,welllaidoutfordifferentialdiagnoses. ThisworkdefinesLCP(avascularnecrosisofthefemoralhead)asadiseaseof youngdogs,411monthsoldatthetimeofonset,andasabilateral(bothhips) diseasein1216%ofdogsstudied. ThisworkalsosummarizescurrenttheoriesandpossiblecausesofLCPdisease: Compromiseofvesselsenteringepiphysis, Synovitis Sustainedabnormallimbpositionleadingtoincreaseinintraarticular presscollapsingveins Transientvascularproblembecauseofcyclicalreparativefibrosisand osteoblasticactivityafterinitialphase. Theseauthorsalsooutlinedcurrenteffectsandoutcomesoftreatment. Conservativetreatment:rest,painkillers,goodfood.Lamenessassociatedwith diseaseresolvesinlessthan25%ofdogsmanagedconservatively.Surgery relievespainandlamenessin84100%regardlessofprogressionandage. Propersurgerytechniqueiscritical.Agoodreferenceradiographofanaffected animalisshownonpg.1121ofthisreference. Isola,M,Zotti,A,Carnier,E,Baroni,E,Busetto,R,Dualenergyxray absorptiometryincanineLeggCalvePerthesDiseaseJournalofVeterinary Medicine52:40710,2005 Useddualenergyxrayabsorptiometry(recentadvancementinimagingfor precisebonemineraldensitymeasurementforhumansanddogs)toquantify bonechangesproducedbyosteonecrosisintheproximalfemurontheaffected andunaffectedside.Describesradiographicsigns/stagesusedfordiagnosis. Foundnodifferencesbetweengoodandbadlegsandconcludedthatevenwhen

radiographicchangesareseen,theoverallmineraldensityisnotaffected.This couldbeduetoboneremodelingthatcantbedetectedinanxray. LeFond,E,Breur,G,Austin,C,Breedsusceptibilityofdevelopmentalorthopedic diseasesindogsJournaloftheAmericanAnimalHospitalAssociation38:467 477,2002 Epidemiologicalstudyonbreedriskfor12developmentalorthopedicdiseasesin dogs.Examinedmedicalrecordsfromveterinaryteachinghospitalsforthe periodof19861995. Differentialanalysisofbreedsusceptibilitysuggests geneticpredisposition.Westieshaveoddsratioof1,313/1forcraniomandibular osteopathy,theonlybreedtohaveahigherincidenceofthatdisease.They th haveanoddsratioof33.2/1forLeggCalvePerthes,the7 highestratioforthat disease.Theyhavea1.7/1ratioforpanosteitis(acquiredselflimiting inflammatoryconditionofundeterminedcausethataffectsthediaphysealand metaphysealregionsoflongbonesinyoungdogs)and1.8/1forpatellaluxation. Theultimatemethodtocharacterizegeneticetiologyforadiseaseisthe determinationofitsheritabilityandmodeofinheritance. Liu,S,H,T,TheroleofvenoushypertensioninthepathogenesisofLegg PerthesDiseaseTheJournalofBoneandJointSurgery73A(2):194200,1991 Thisstudyexamined32humanpatientswithLeggPerthesandlookedatthe venography,intraosseousandintraarticularpressures,arthrographyandbone imaging.Theydeterminedthatthedifferenceinarterialbloodflowbetween goodandbadfemoralheadswasnotstatisticallysignificant,butthattherewasa markeddisturbanceofthevenousdrainage,and,higherintraosseouspressure andintraarticularpressureinthebad(affected)hipcomparedtononaffected hips. Othergeneralreferencearticles: FujikawaK,Comparativevascularanatomyofthehipoftheminiaturedogand ofthenormalsizemongrel38(3):15965,1991 NaitoM,SchoeneckerPL,OwenJH,SugiokaY,Acuteeffectoftraction, compression,andhipjointtamponadeonbloodflowofthefemoralhead:an experimentalmodelJournalofOrthopedicResearch10(6):8006,1992

Topic#5:Craniomandibularosteopathy(CMO)inWestiesandother Scottishterrierbreeds Theabilitytoeatandtodrinkisessentialtostayingalive!Eatinganddrinking arecomplexactivities,dependentoncoordinationoftheprocessesofhunger andthirstbythebrainandalsoonthefunctionofnose,mouth,esophagusand gastrointestinaltract. Thebonesoftheskull(thetemporalbone, temporomandibularjoint,tympanicbullae,andmandible),musclesofchewing (temporalmuscles,primarily),attachedligaments,andtendons,allowdogsto holdandchewtheirfoodeffectively. Malfunctioninanypartofthe eating/drinkingsystemisserious. Whendiseasedevelops,itcanaffectthe dogsabilitytoeat,gainweight,grow,andinextremecases,tolive. WestHighlandWhiteTerriersareveryhighlyaffectedwithcraniomandibular osteopathy(CMO),anonneoplastic(notatumor)diseasealteringformand functionofthebonesoftheskullandmandible(jawbone). Thisdiseaseis knownbyseveralsynonyms,suchasmandibularperiostitis,Westiejaw, Scottiejawandlionsjaw(Alexander,1983). OtherScottishterrierbreeds (ScottishTerriersandCairnTerriers)areaffectedmorecommonlythanother breedsofdogs,suchasIrishSetters(TronwaldWigh,G,etal,2000),Labrador Retrievers(Alexander,etal,1975),DobermanPinschers(Watson,ADJ,etal, 1975),EnglishBulldogs(Hathcock,1982),PyreneanMountainDogs(Franch,et al,1998),andShetlandSheepdogs(Taylor,etal,1995). CMOwasfirstrecognizedinEnglandin1958((Littlewort,MC,1958)andthe pathologyofthediseasewasstudiedextensivelybyWayneRiserandhis colleaguesattheUniversityofPennsylvania.Drs.RiserandNewtonhavewritten averyextensivereviewofCMO.Youcanreadthisreviewonlineat http://www.ivis.org/special_books/ortho/chapter_54/ivis.pdf(RiserandNewton, 1985).InadditiontothisWebcitation,therehavebeenexcellentreviewsofthis subject,andthesearelistedinReferencesforthisTopic(Alexander,JW,wtal, 1983Watson,ADJ,etal,1995LaFond,etal,2002,Schwarz,T,etal,2002). TheincidenceofCMO:NotrareinWesties! InareviewofliteratureonCMO,Watsonandcolleagues(Watson,etal,1995) foundreportsof81affecteddogs:44of81dogswereWestHighlandWhite Terriers,22/81wereScottishTerriers,2/81wereCairnTerriers.Takentogether, thesethreeScottishterrierbreedscomprised about84%ofcasesdescribedin literaturereviewed. Inaverylargestudyofinformationondevelopmental orthopedicdiseasesindogscontainedinmedicalrecords,andcollectedovera tenyearperiodoftime,LaFondandcolleagues(LaFond,etal,2002),foundthat WestiesweretheonlybreedwithCMO.Theyidentified35casesofCMOamong 24,373recordsofdogsofallbreedswithdevelopmentalorthopedicdiseases.It isclearthattheincidenceofCMOamongdogsislow,butasignificantproblem forownersofWesties(seemorebelow).

Onsetandclinicalsigns CMOisadevelopmentaldisease,primarilyaffectingtheformandfunctionof bonesoftheskullofyoungdogs. Whenwesaythediseaseisdevelopmental wemeanthatthereisageneticpredispositiontothediseaseinsomedogs,and itusuallybecomesaproblemataparticularstageoflife. Inthiscase,CMO usuallybeginstodevelopbeginningaround6monthsofageandmaybefully developedinaffecteddogsby18monthsofage(seetheTable1,foundbelow, fromWatson,etal,1995,modifiedslightlyforthisTopic). DatafromthisTable showthatslightlymorethan90%ofdogswithCMOdevelopthediseaseby1 yearofage. Table1.Ageatdiagnosisof153dogswithcraniomandibularosteopathy includedintheVeterinaryMedicalDataBase(VMDB)atPurdueUniversity Percentageoftotaldogsindatabase(modifiedfromoriginaltextfigure) Breed Age26 Age612 Age12 Olderthan category months months years 2years Terriers 37.9% 33.3% 3.3% 3.9% Otherbreeds 9.2% 10.5% 1.3% 0.6% Total 47.1% 43.8% 4.6% 4.5% (Reference:Watson,ADJ,Adams,WM,Thomas,CB,Craniomandibular osteopathyindogs,CompendiumVetMedSmallAnimal(July):911922,1995) InconsideringthedatacontainedinTable1,itisimportanttounderstandthat whileyoungWestHighlandWhiteTerriersandotherScottishterriersare predisposedtodevelopingCMO,thediseasecannotbeconsideredcommonin dogsasaspecies.ThedatasummarizedinthisTableincluded153affected dogs,butthisdiseaserepresentedaverysmallfraction(0.014%)ofthe 1,080,396canineentriesintheVMDBatthetimethetablewascompiled. Similarly,LaFondandcolleaguesonlyfoundCMOin35Westiesinastudyof 300,122VMDBrecords(19861995)(anincidenceof0.01%).Thefactthatthis particulardiseaseisveryuncommonhasimplicationsforresearch,discussed later(SeeResearchandAdditionalInformation,below). Individualdogsmayvarywidelyintheseverityofdisease,thetimeofonset,and therateofprogression(moreonthisbelow).Inonereview,therewasnosex predispositionnoted,withmalesandfemalesbeingrepresentedinapproximately equalnumbers(Watson,etal,1995). Thislackofgenderpredispositionhas beenconfirmedbyothers(LaFond,etal,2002). Thediseasecanaffectseveralindividualdogsinthesamelitter(TronwaldWigh, etal,2000).Astudyofthegeneticsofthisdisease,usingretrospectivepedigree

analysis,conductedbyPadgettandcoworkers(Padgett,etal,1986)hasshown thatthediseaseisinheritedasasimpleautosomalrecessivecharacteristic.As breedersknow,thismeansthatthebreedingofdogsthatmaypossessthe geneticmutationcausingCMO,butnotshowingsignsofdisease(carriersofa defectivegene),arethesourceofdisease. Diseasescausedbytheexpression ofrecessivegenesoccurwhendogsacquiremutatedgenesfrombothparents. ThediagnosisofCMO ThefirstsignsofCMOnotedbyownersofaffecteddogsaredifficultyeating (grasping,holdingandchewingfood),drooling,andswellingofthefacearound thejaw.Someaffecteddogsmaydisplaysignsofpainwhenthemouthis opened,andtheremayberestrictionintheamountthejawscanopen. Padgett andMostosky(Padgett,GA,etal,1986)reportthatpalpationofthejawand temporomandibularjoint,withpainonpalpation,isadependablemethodthat canbeusedclinicallytodiagnosedogswithCMO. Fevermayormaynotbe present.Affecteddogsmayshowswellingofthefaceoverthejaw,atthejointof thejawandtheskull(thetemporomandibularjoint),andatthebaseoftheskull. Thisswellingisduetotheproliferationofdisorganizedbone(seebelow). Laboratorytestsforserumandhematologic(blood)abnormalitiesarenotuseful indiagnosingthisdisease.Analysisofindicatorsofboneremodelingor proliferation,suchasseruminorganicphosphorusoralkalinephosphatasegives inconsistentresultsamongaffecteddogs.Definitivediagnosisisusuallymade bycharacteristicradiographicchanges,describedbelow(Schwarz,etal,2002). Radiographs(xrayimages)ofthetemporalbonesandmandibleofdogswith CMOshowdisorderlyproliferationonbonesurfaces,compromisingthefunction ofthejointlinkingthesebones(thetemporomandibularjoint)(Figures13, courtesyofDrs.GregDanielandMarthaMoonLarson,VirginiaMaryland RegionalCollegeofVeterinaryMedicine[VMRCVM]).Thisproliferationofbone isnotatumor(neoplasm).

Otherbonesinthebody,includinglongbonesinlegs(radiusandulna)mayalso showsimilardisorderlyproliferations,althoughthisisnotcommon(Padgett,etal, 1986). Insomedogs,bonychangesmaybepresentonradiographs,butdogs donotdisplaytypicalclinicalsignsthisisuncommon.

Figure1.DrawingsoftheskullofadogwithCMO,lateralandventralviews. Arrowsanddarkenedlinesshowsitesofbodyproliferationinmandible,temporal bones,tympanicbullaeandtemporomandibularjoints.(FigurecourtesyofDr. GregDaniels,VMRCVMallrightsreserved)

Figure2.Lateralradiographicviewofthedisorderlybonyproliferation(white arrow)onthemandible(lowerjaw)ofadogwithCMO. Thetopoftheskullisat thetopofthefigure,andtheteeth/toothrootsclearlyvisibleforreference.(Figure courtesyofDr.GregDaniel,VMRCVMallrightsreserved)

Figure3.RadiographofanesthetizeddogwithCMO,withmouthopenandview takenfromthenosetowardthebackofthemouth.Anendotrachealtubecanbe seeninthemouth(center,lower).Bilateral(bothsides)disorderlybonegrowth onthemandiblesandtemporomandibularjoints(whitearrows)canbeseen.The growthofthisbonelimitsopeningandclosingofthemouth,abilitytoeat,is associatedwithpainandcanbeirreversible.(FigurecourtesyofDr.Martha MoonLarson,VMRCVMallrightsreserved) Proliferatingbonemaydecreasemovementofthetemporomandibularjoint, limitingtheabilityoftheaffecteddogtoopenitsmouth,graspandholdfoodand tochew.Inveryseverecases,dogswithCMOcanonlyopentheirmouthtoa limiteddegreeandexperienceverysignificantpainwhentryingtograspfoodand chew. Dogsexperiencingpainandlimitedmobilityofthejawmaydevelop secondaryatrophy(shrinkage)ofthemusclesthatallowchewing,duetodisuse. Thislossofmuscleintheheadandjawmayfurthercompromisetheaffected dogsabilitytoeat. Riserandcolleaguesdescribedhistologicbonychangesasbonyproliferation, boneremodeling,increasedconnectivetissuewithinandsurroundingbone,and variabledegreesofinflammationinandaroundbone(Riser,etal,1967). The inflammationseenmayplayaroleinthedevelopmentofdisease,perhaps supplyinggrowthfactorsstimulatingbonegrowth.Itisprettyclearthattreating dogswithantiinflammatoryagentsmayhelpcontrolpain,fever,andperhapsthe progressionofdisease(SeeTreatmentofCMO).

Bonylesionsprogressatdifferingratesfordifferentdogs.Insomedogs,lesions areminimalandcauseonlyminimallossoffunction.Inmoreseverelyaffected dogs,bonychangesmayfusethebonesofthejawtothoseoftheskull. These severelyaffecteddogsrarelyshowimprovementclinically. Yourveterinarianneedstoconsideravarietyofpossiblediseaseswhen presentedwithaWestiewithdifficultyeatingandwithmouthpain.Agood sayingtorememberisCommonthingshappencommonlyandthatalthough Westies,asabreedaremostlikelytodevelopCMO,itisarelativelyrare condition.Somepossiblecausesofdifficultyeatingand/ormouthandjawpain are(innoparticularorder): Badteethandbadgums Strains,sprainsandfracturesduetotrauma Mouth,noseandthroatinfections Tonsillitis Tumorsofsofttissuesandbonesoftheskullandjaw Inflammationofthemusclesoftheheadandneck Sprains,strainsandfracturesoftheneck Palatabilityoffooditemsoffered Oralulcersorulcerselsewhereinthedigestivetract Exposuretotoxinsinthedietorenvironment Andmanyothers. Itsveryimportanttoseeyourveterinarianifyounoticepoorweightgain,trouble eating,pain,ordrooling. TreatmentofCMO ThereissomecontroversyregardingtheprogressionofCMO.Riserand colleagueswritethatthediseaseisselflimiting(slowsandstopswithadvancing age),oftenregressesandattimescompletelyresolves(Riser,etal,1967). Alexandernotedalotofvariationintheprogressionofdisease.Hefeltthat somedogsmightbeminimallyaffectedandthediseaseonlyseenwith radiographs.Somedogs,unfortunately,hadvariableamountsofbonyfusionof thetemporomandibularjointandseverelyaffecteddogswereeuthanized. Alexander,too,concludedthatinmostcases,CMOwasselflimitingandthatas dogsmatured,thediseasestoppedprogressing(Alexander,1983).Padgett statedWithcorticosteroidtreatment(orsometimesspontaneously)remodeling occurs,thenewboneisremovedandthejawlinereturnstoanormalornear normalappearance(Padgett,etal,1986).Intheirreview,Watsonand colleaguesnotethatbonyproliferationsmayshowsmoothingandremodelingin somebonesofsomedogs(Watson,etal,1995).Mostauthorsagreethatthe useofantiinflammatoryagentscanbehelpful(seeTreatmentofCMO). ManyoftheauthorscitedinthisTopicadvocatetheuseofantiinflammatory drugstohelpcontrolpain,feverandswellingindogswithCMO.Thejudicious

useofthesedrugs(bothcorticosteroidsandnonsteroidaldrugssuchasaspirin) allowsaffecteddogstoeatanddrink.Severalarticleshavesuggestedtheuseof thesedrugsmayinterferewithprogressionofdisease,butaccordingtoRiserand NewtonMostanimalscanbemadecomfortableusingaspirinorcorticosteroids however,treatmentdoesnotresultincure(Riser,etal,1985). Therehavebeenscatteredreportsofattemptstosurgicallyfreeupbonyfusions inthetemporomandibularjointofseverelyaffecteddogs.Thisdoesnotappear tohelp. ItisveryclearthatthebesttreatmentforCMOinWestiesispreventionby selectivebreeding. CurrentresearchandadditionalInformation Thisdiseaseattractedconsiderableattentionbetween1958,whenitwasfirst described,and2002.SomeofthefeaturesofCMOinWestiesresembled skeletaldiseasesseeninotherdogbreedsandinpeople. AdiseaseofBullMastiffs,knownasidiopathichyperostosisorcalvarial hyperostoticsyndrome(CHS),causesasymmetricalthickeningofsomebones oftheskullsinyoung,maledogs(Pastor,etal,2000). McConnellandco workers(McConnell,JF,etal,2006)describedmagneticresonancefindingsin twodogs,oneofwhichhadbonyproliferationinthefemur(sometimesseenin severalskeletaldiseases,includingCMO).Huchkowsky(2002)successfully treatedCMOlikesyndromeina6montholdBullMastiffwithantiinflammatory drugs. WhilesomeoftheproliferativebonylesionsseeninCHSofBullMastiffs aresimilarhistologicallytoCMOinWesties,thereareimportantdifferences includingthesexofaffecteddogs(onlymaleBullMastiffsgetCHS,whileboth sexesofWestiesgetCMO),andthebonesaffected(CHSinBullMastiffaffects frontal,temporalandoccipitalbonesasymmetricallyCMOinWestiesaffectsthe mandibleandtemporalbones,andusuallysymmetrically).Acomparisonofthe underlyinggenomicmutationscontrollingeachofthesediseases(CHS,CMO) shouldbedonetoassesspotentiallinksandpossiblemoleculartherapies. CMOwasdescribedaspartofacomplexpatternofdiseasein12dogsfrom6 littersofIrishSetters(TronwaldWigh,etal,2000).Allofthesedogssuffered fromaprimarydiseaseconditionknownascanineleukocyteadhesion deficiency(CLAD).Allofthedogswerelessthan15weeksoldwhenthey developedavarietyofinfections,includingbone(osteomyelitis)andmouth (gingivitis)infections.Thesusceptibilityofthesedogstoinfectionwasdueto thefactthattheirwhitebloodcells(leukocytes)didnotfunctionproperlyto protectagainstinfectiousagentslikebacteriaintheenvironment.Elevenof12 dogsstudieddevelopedproliferativebonygrowthonmandibles,withthe characteristiccobblestoneappearanceofCMOin5/12dogs.Histologicsections ofboneshowedincreasedactivityofboneremodelingcells,bonedeath,and inflammation.Theresultsofstudyingthesedogsisofsomeinterest,since

inflammationisarelativelycommonfeatureinCMOandonecannotexcludethe possibilitythatoneinitialtriggerforCMOmightbeexposuretoinfectiousagents. ThishasrelevancetoobservationsofpeoplewithPadgetsdisease(seenext paragraph). SomeaspectsofthedevelopmentofCMOinWestieshaveinterested researchersstudyinghumanbonediseases.Forexample,Padgetsdiseaseisa relativelycommonnonneoplasticproliferativebonedisease,generallyseenin olderpeople(Inzucchi,2006).Theradiographicandhistologicappearanceof newlyformedanddisorderlyboneinpeoplewithPadgetsdiseaseresemblesthe appearanceofnewlyformedboneinCMO.Inpeople,thebonygrowthoccursin theskull,pelvisandlongbonesofthelegsandarmssomewhatsimilarin locationtothelocationofCMOinWesties.Someresearchdoneonpeoplewith Padgetsdiseasehassuggested,butnotproven,thataviralinfectionmight triggerthebeginningofthedisease.AroleforviralinfectioninCMOhasnot beenstudied. Anotherhumandisease,infantilecorticalhyperostosis,resemblessomeaspects ofthedevelopmentofCMOinWesties.Itisageneticdiseaseanautosomal dominantdisease,whichresultsinnonneoplasticbonyproliferation(Padgett,et al,1986). Foodforthought ItsprettyclearthatCMOisaWestieproblem.Weunderstandthegeneticsofit andhowtodiagnoseit.Weknowthatselectivebreedingcanreducethe incidenceofthedisease.Whatwedontknowiswhatifthekeyproblemwiththe genome(oneormoremutations)whichtriggeritandallowdevelopment. Understandingthiscouldbeimportantnotonlyfordiagnosisandtreatment,but alsotoseeifsomeofthesesamegenomicmutationsmightbeassociatedwith otherWestieanddogdiseases.Unfortunately,therarityofthisdiseaseamong dogsandtheabsenceofanidenticaldiseaseinpeoplemeanthatCMOisnot likelytogetstudiedmuch.Veterinariansandresearchersmaythinktheyhave thecompletestory.WethinkthebookonCMOandothergeneticdisordersmay onlybeopenbeonthefirstpage! Acknowledgements TheauthorsthankDrs.MarthaLarsonandGregDanieloftheDepartmentof SmallAnimalClinicalSciencesattheVirginiaMarylandRegionalCollegeof VeterinaryMedicine,VirginiaTech,Blacksburg,Virginia,forimagesprovidedto illustratethisTopic.

References Alexander,JW,Kallfelz,F,AcaseofcraniomandibularosteopathyinaLabrador Retriever,VetMedSmallAnimalClinician70:560563,1975 Alexander,JW,Selectedskeletaldysplasia:Craniomandibularosteopathy, multiplecartilaginousexostosis,andhypertrophicosteodystrophy,VetClinNorth America:SmallAnimal13:5570,1983 Franch,J,Cesari,JR,Font,J,CraniomandibularosteopathyintwoPyrenean mountaindogs,VetRec142:455459,1998 Hathcock,JT,CraniomandibularosteopathyinanEnglishBulldog,JournAmer VetMedAssoc181:389,1982 Huchkowsky,SL,Craniomandibularosteopathyinabullmastiff,CanVetJourn 43:883885,2002 Inzucchi,SE,Diseasesofcalciummetabolismandmetabolicbonedisease, AmericanCollegeofPhysiciansACPMedicine2006,Dale,DC,Federman,DD (eds.),NewYork,2006,p.681 LaFond,E,Breur,GJ,Austin,CC,Breedsusceptibilityfordevelopmental orthopedicdiseasesindogs,JourAmericanAnimalHospAssoc38:467477, 2002 Littlewort,MC,Tumourlikeexostosisonthebonesoftheheadinpuppies,Vet Rec70:977978,1958 McConnell,JF,Hayes,A,Platt,SR,Smith,Calvarialhyperostosissyndromein twoBullmastiffs,VetRadiolandUltrasound47:7277,2006 Padgett,FA,Mostosky,UV,Animalmodel:Themodeofinheritanceof craniomandibularosteopathyinWestHighlandWhiteTerriers,AmerJMed Genetics25:913,1986 Pastor,KF,Boulay,JP,Schelling,SH,Carpenter,JL,Idiopathichyperostosisof thecalvariainfiveyoungBullMastiffs,JournAmerAnimHospAssn36:439 445,2000 Riser,WH,Parkes,JL,Shirer,BS,Caninecraniomandibularosteopathy,JAm VetRadiolSoc8:2331,1967 Riser,W,Newton,CD,Craniomandibularosteopathy,inNewton,CD, Nunamaker,DM(eds),TextbookofSmallAnimalOrthopedics,LippincottCo, Philadelphia,PA,1985pp.621626

Schwarz,T,Weller,R,Dickie,AM,Konar,M,Sullivan,M,Imagingofthecanine andfelinetemporomandibularjoint:Areview,VetRadiolUltrasound43:8597, 2002 Taylor,SM,Remedios,A,Myers,S,CraniomandibularosteopathyinaShetland Sheepdog,CanVetJourn36:437439,1995 TronwaldWigh,G,Ekman,S,Hansson,K,Hedhammar,A,Hard,C,Segerstad, AF,Clinical,radiographical,andpathologicalfeaturesin12IrishSetterswith canineleukocyteadhesiondeficiency,JSmallAnimalPractice41:211217, 2000 Watson,ADJ,Huxtable,CR,Farrow,BR,Craniomandibularosteopathyin DobermanPinschers,JSmallAnimPract16:1119,1975 Watson,ADJ,Adams,WM,Thomas,CB,Craniomandibularosteopathyin dogs,CompendiumVetMedSmallAnimal(July):911922,1995

Topic#6:LuxatingPatella Thebasicspatellarluxation(dislocatedkneecap) Aluxatingpatella,ordislocatingkneecap,isacommoncauseoflamenessin smallbreeddogs,includingWesties. Mostpatellarluxationsaremedial, meaningthatthekneecaphasbeendislocatedtowardstheinsideofthejoint (andleg)versuslateral,whenthekneecaphasmovedtowardstheoutsideof thejoint. Whileatraumaticevent,likeafallorbeinghitbyacar,candislocate thekneecap,patellarluxationisusuallycausedbymuscleandskeletalproblems thatdogsmaybebornwith. Needlesstosay,theconditioncanbepainfuland beacauseoflameness. Fortunately,itcanbediagnosedandtreatedeffectively inmostdogs. Howdoespatellarluxationhappen? Thebonesofthekneejointincludethethighbone(thefemur),theshinbones (thetibiaandfibula),andthekneecap(thepatella),whichsitsinagrooveinthe femurcalledthetrochleargroove.Ligamentsconnectallthesebonesandserve tostabilizethejoint. Thequadricepsmusclesareasetoffourmusclesthatlie onthefrontofthefemurandallcometogetheraroundthepatellatoformthe patellarligament,whichcaneasilybefeltrunningfromthepatellatoacreston thetibia(thetibialtuberosity)overthefrontoftheknee. Thequadricepsmuscles servetoextend,orstraighten,theknee,whilethepatellaactsasaleverarmfor thequadricepsandalsocreateseventensionfromthemusclesonthepatellar ligament. Healthykneejointsworkbecauseallofthesecomponentsarelinedupproperly. Incongenitalcasesofpatellarluxation,dogsmaybe bornwithordevelopmalformationordysfunctionofone ormoreofthecomponents(bones,ligaments,tendons, muscles)ofthekneejoint. Ofcourse,manydogsmay developthisconditionlaterinlife,duetothingslike traumaoracombinationofinheritedkneejoint malformationandsubsequentwear. Dogswithluxating patellamayhaveoneorseveralofthefollowing abnormalities:poorangleoftheheadofthefemur, medialdisplacementofthequadriceps,lateraltwistingof thelowerfemur,lateralbowingofthelowerfemur,a shallowtrochleargroove,oramedialdisplacementofthe tibialtuberosity(Figure1,right,courtesyofDr.Daniel Degener,AuburnHillsHospital,AuburnHills,Michigan, diagrammaticallyshowsnormalcomponentsinthe diagramontheleft,withthepatella(smallmaroonoval) underthequadricepsfemorismuscleandattachedbythe patellarligamenttothetibia. Ontherightsideofthe

figure,thepatellaandquadricepsaredisplacedaclassiccaseofpatellar luxation). Veterinarianshavemultipletheoriesastowhichtypeofdeformity initiatestheproblem andcauseprogression.Themostwidelyacceptedtheoryis thatabnormalangulationbetweentheheadofthefemurandtheshaftofthe bonecausesthequadricepsmuscletomovemediallyandpullthepatellawithit. Othertheoriessuggestthathormonalinfluencesonboneformationandgrowth leadtothedevelopmentofashallowtrochleargroove, orthathipproblems causedogstowalkabnormally,makingthekneecompensateinappropriately,or thattheexistenceofmuscleattachmentsinthewrongplaceonbonespullthe patellamedially. Noonetheoryexplainsallcases. Nomatterwhatinitiatespatellarluxation,thereareseveralconsequencesifitis leftuntreated.Withthepatellaoutofplace,thecartilageonthesurfaceofthe patellaandotherbonesgetsworndown,causingpainandrestrictingmovement, eventuallyleadingtoarthritis.Otherproblemsthatmaydevelopincluderupture ofthecranialcruciateligament,aligamentthatattachesthefemurtothetibia. Thisligamentcanbestretchedtoofarandbreakifthepatellaisdisplaced. Therearespecialconsequencesofpatellarluxationfordogswhicharestill growing.Anypreexistingbonedeformitythatmaybecausingtheluxationwill onlyworsenwithoutcorrectionasthebonescontinuetogrow.Also,without normalwearfromthepatella,thetrochleargroovewillnotappropriatelydeepen, eventuallyleavingittooshallowtoholdthepatella,evenifitispoppedbackinto place. Itisveryimportanttogetagooddiagnosisandfollowupwithtreatmentin dogsofanyage,butespeciallyinyoungdogs. Signsandappearanceofpatellarluxationtheseveritygradingsystem Dogswithluxatingpatellaewillhavevarioussigns,dependingontheseverityof theproblem.Veterinarianshavedesignatedfourgradesofsigns,fromthemild casesofGradeItotheseverecasesofGradeIVluxations. GradeIluxationsareusuallyonlydiscoveredinpatientsduringroutine physicalexaminations.Thepatellacanbeforcedoutofplacemanually butrarelymovesoutofplaceduringregulardailyactivity. Allthe componentsofthekneediscussedearlierarenormalsopatientswith GradeIluxationswillappeartotallynormalandhealthywithnolameness. GradeIIluxations,however,arecharacterizedbysomesortofmild femurbonedeformity. Againthepatellamaybeluxatedmanually,but alsomaymoveonitsownoccasionally.Somepatientswillbeableto replacethepatellathemselvesthroughnormalmovementofthejointand somewillneedthepatellamanuallyreplacedforthem. Thesepatientswill occasionallyskipwhentheyrewalkingorrunning,wheneverthepatella hasmovedoutofplaceanduntiltheycanpopitbackin. GradeIIIluxationsaremoresevereandusuallyremainluxatedmostof thetime,althoughthepatellacanoftenbemanuallyreplaced.The

quadricepsmusclesofthesepatientsarealsodisplacedmediallyand therearebonedeformitiesaswell. PatientswithGradeIIIluxationsmay skiplikethosewithGradeIIluxations,althoughmorefrequently.Ifthe patellaisluxatedmoreoftenthanitisnot,theywilldevelopaweight bearinglameness,meaningthattheywillputsomeweightonthebadleg butwalkwithalimp. GradeIVluxationsarethemostsevere.Thepatellaisalwaysluxated andcannotbereplacedmanually.Therearesignificantdeformitiesofthe bonesandothercomponentsinvolvedinthejoint. Thesepatientswill walkwiththehindlegscrouchedinapermanentlyflexedposition.They areunabletoextendtherearlegsduetothepermanentluxationofthe patella.

Diagnosis Thediagnosisofaluxatingpatellaaloneissimple,asthepatellacanbefeltor movedoutofplaceduringaphysicalexamination. Radiographswillrevealjoint deformitiesandhelpdeterminethegradeoftheluxation.Yourveterinarianwill lookintootherproblemsthatoftenoccursimultaneouslywithluxatingpatellae, suchashipdysplasia,cranialcruciateligamentruptureandLeggPerthes disease(seethisTopicintheEBook). Treatment Recommendedtreatmentdependsonthegradeoftheluxationandthepatients age. Dogswithnoovertsignsoflamenesscansimplybemonitoredforany changesthatwouldindicateanincreaseintheseverityoftheluxation. Surgery isnotrecommendedforthesepatients. OlderpatientswithGradeIluxationsdo finewithoutanyinterventionaswell. Surgeryisrecommendedforanydogwhich islameandespeciallyforthosewhosebonesarestillgrowing. Thegoalofanysurgery foraluxatingpatellaisto putthepatellabackinits properplaceandrealign theotherkneejoint componentsinorderto keepitthere.A veterinarysurgeonwill useacombinationofthe followingvarious techniquesand procedures:recentering thepartofthetibia(shin) bonethatthepatellar ligamentattachesto,

cuttingorreinforcingtheligamentsonthesidesofthejoint,deepeningthe trochleargrooveonthetibiainwhichthepatellaissupposedtosit,and shorteningandrealigningthetibiaandorfemurbones. (Figure2,above, courtesyofDr.DanielDegener,AuburnHillsHospital,AuburnHills,Michigan, diagrammaticallyshowsthegoalsandresultsofpatellarluxationcorrective surgery). Aftersurgery,patientswillhavetobeleashwalkedonlyforuptosixweeks,in orderforthejointtorecover.Afterthat,patientsshouldbebroughtbackupto theirregularspeedslowly,soasnottoreinjurethearea. Surgeryisusuallyvery successfulinrestoringpatientswithGradesIIIIluxationsbacktonormalactivity. Assmalldogs,Westieshaveanadvantageinhealingandtendtohaveahigher successratethanlargebreeddogs. GradeIVluxationsmaynotdoaswell,even aftersurgery. Asmanyas50%ofallpatientsmayhaveGradeI,orincidental, luxationsafterthesurgery.Arthritiscannotbeavoidedcompletelybysurgery, butitmaynotbeassevereasifthepatellahadremainedluxated. Veterinarians mayprescribeantiinflammatorydrugstohelpcontrolpainfollowingsurgery. Currentresearchonluxatingpatella Therehasnotbeenasignificantamountofresearchonpatellarluxation, especiallyinrecentyears.Whiletheexactcausesofthisconditionremaina subjectofdiscussionanddebate,treatmentinmanycaseshasbeensuccessful andthereisnotastrongincentivetopreventpatellarluxation.Mostofthe researchthathasbeenpublishedonthematterfocusesontreatment.Itis largelyacceptedthatacombinationofsurgicaltechniquesproducesthebest outcomeforpatients,andcurrentresearchhasconfirmedthisbyexaminingand quantifyingthebenefitsoftheavailabletechniques.Overlappingwiththe surgicalfocus,therehasbeeninterestinunderstandinghowsurgeryand differentsurgicalproceduresinparticular,mayormaynotincreasetheamountof degenerativejointdiseaseapatientwillexperienceposttreatment.Othertopics includefrequencyanddistributionofthediseaseindifferentbreedsandre examiningsomeassumptionsaboutthepathogenesis. Surgeryandpathogenesis. Publicationsonnewsurgicaltechniquesandon quantifyingthevalueofexistingtechniqueswerethefocusonrecentresearchon surgicaltreatmentofpatellarluxation.A2004studypresentedanalternativeto existingsofttissuecorrection.(Bevan,etal,2004)Theauthorsadvocated arthroscopicreleaseofthemedialfemoropatellarligamentinsteadofthemedial retinaculumorjointcapsule.Thefollowingadvantageswerecitedbythese authors:lesstissuetrauma,quickerhealingtime,rapidreturntofunctionwith significantuseoflimbin45days,andnormalusein10days(althoughthe authorsrecommend6weeksofrestrictedexercise). Theoutcomewassimilarto thatoftraditionalsofttissuetechniquesandthemaincomplicationwasfluid extravasationintomedialsubcutaneoustissueofthestifleinall5casesreported.

Anothernewsurgicaltechniquewasexaminedinrecentstudies.Trochlear blockrecessionwasadvocatedoverotherwedgerecessiontechniquesinan articlepublishedin2000(Talcott,etal,2000). TheauthorsstateRectangular recessiontrochleoplastyissimpletoperform,achievesadequatetrochleardepth andwidth,resultsinmaximalpreservationofhyalinearticularcartilageand utilizesandosteochrondralautograftthatissecurelypressfitintorecipient subchondralbone.A2001study,usedcadavermodelstocomparetrochlear blockrecession(TBR)andtrochlearwedgerecession(TWR).(Johnson,etal, 2001)Theauthorsusedcomputedtomographyandbiomechanicalevaluationof 12largebreedcadaverhindlimbstodeterminethatTBRincreasesproximal patellardepth,increasespatellararticularcontactwiththerecessedproximal trochlea,recessesalargerpercentageoftrochlearsurfacearea,andresultsina greaterresistancetopatellarluxationinanextendedpositionascomparedwith TWR. Tworecentstudiesevaluatedseveralsurgicaltechniques.Aretrospective medicalrecordstudydetailedthecomplicationsexperiencedby109dogswith luxatedpatellas(Arthurs,etal,2006). Theauthorsfoundthefrequencyof patellarrelaxationtobeonly8%,muchlessthantheaccepted50%reportedby otherstudies.Complicationsweremorelikelyforlargerdogs(over20kg)than smallerdogsandfordogswithhighergradesofluxation.(Anotherrecentstudy similarlycorrelatedgradewithoutcomeofsurgery(Alam,etal,2007)).This paperreportedthatwhiletrochlearsulcoplastyandtibialtuberositytransposition resultedinlowerfrequencyofpatellarrelaxation,retinacular/capsularrelease actuallyresultedinhigherfrequencyofmajorcomplications.Theauthors attributedthisresulttoreducedsofttissuesupport. A2005prospectivestudyusedradiographicandcomputedtomographicimages totakemeasurementsoneightluxatedpatellas,beforeandimmediatelyafter surgery(Towle,etal,2005). TheauthorsofthisstudystatedRadiographic measurementsincludedangleofinclination,Norbergangle,quadricepsangle (QA),anteversionangle,ratioofthelengthofthepatellartendon(PT)tothe lengthofthepatella,andchangeinpatellatendonangle.CTmeasurements includedangleofinclination,Norbergangle,QA,anteversionangle,depthofthe femoraltrochleargroove,ratioofthemiddlefemoraltrochleargroovedepthto thepatellathickness,andtibialcrestalignment.Theauthorsconcludedthat surgeryrestoredthealignmentofthequadricepsandadequatelydeepenedthe femoraltrochleargroove.Tibialcresttranspositionresultedincaudalizationofthe patellatendonandlateralizationofthetibialtuberosity,butthattheconformation ofthehipjointwasnotaffectedbysurgery. TheresultsoftheTowlestudy(Towle,etal,2005)generallysupportandamplify thoseofa2001studyinwhichusedmagneticresonanceimageswereusedto takemeasurementsofluxatedstifles.The2001studyconcludedthattheAT angle[anteversionangle]ofthefemoralneckdoesnotinfluencepatellar instability.(Kaiser,etal,2001)

Degenerativejointdisease(DJD)aconsequenceofpatellarluxation KnowingthataluxatedpatellacancausesignificantDJD,itisassumedthat surgicallyreducingthepatellawouldhelpavoidsomeoralloftheassociated painanddamage.SparingpatientsDJDhasbeenoneofthemotivatingfactors inpromotinghyalinecartilagesavingsurgicaltechniquesovertraditional trochlearrecessiontechniques.Astudyconductedin1999examinedthe cartilageofninedogsthathadundergonecorrectivesurgeryforluxatingpatellas inthepastandcomparedittotwohealthydogscartilage(Wander,etal,1999). Theseauthorsfoundtherewasnocorrelationbetweengradeofluxationand healthofcartilagebutthesurgicallytreateddogscartilagedidshowsomecell lossinsuperficiallayersoftheircartilage,anearlysignonosteoarthritis. This findingleadstheauthorstorecommendhyalinecartilagesavingsurgical techniquesovertraditionaltechniques.Thestudymentionedabove,whichused cadaverstocomparetrochlearblockandwedgerecessions,recommendedthe blockrecessiontolimitthedevelopmentofDJDforsurgicallytreated dogs.(Johnson,etal,2001)Thisworkshowedblockrecessiontogiveagreater proximaldepthtothetrochlea,makingluxationlesslikelyintheextendedlimb positionandthereforemakingDJDlesslikely. In1992,researcherspublishedAretrospectiveevaluationofstifleosteoarthritis indogswithbilateralmedialpatellarluxationandunilateralsurgicalrepair.(Roy, etal,1992)Theyfoundthatboththesurgicallycorrectedandotherstifleshad developedcomparableDJD.Thegradeofluxationdidntseemtomattereither inhowmuchDJDhaddeveloped.Ageatsurgerywastheonlypositive correlationwithprogressionofosteoarthritisthattheauthorsfound.Thisleadto theirconclusionthatInthisstudy,surgerysignificantlyimprovedlimbusein dogswithlamenesscausedbymedialpatellarluxationHowever,surgical correctiondidnotpreventprogressionofosteoarthritisinstiflesofdogswith medialpatellarluxation. Frequencyanddistributionofpatellarluxationindogs Recentstudieshaveverifiedacceptedideasaboutthefrequencyandbreed distributionofpatellarluxation.A1994paperexaminedthemedicalrecordsof 124dogswithpatellarluxation.(Hayes,etal,1994)Theauthorsfoundthat98% ofpatellarluxationsinsmallbreeddogsweremedial.Lateralluxation,although lesscommonthatmedialwasmorefoundmoreofteninlargerbreeddogs. Anotherstudypublishedin2007confirmedthesefindingsafterexamining134 cases(Alam,etal,2007). ResearchersinIndianareportedonthebreedriskfor severaldevelopmentalorthopedicdiseasesindogsin2002(LaFond,etal, 2002). Theyusedoddsratiostodescribethefrequencyofadiseaseina particularbreedtothatamongmixedbreeddogs.Westieswerereportedto havea1.8:1oddsratioforpatellaluxation.Whilethisissignificant,itisamuch

smalleroddsratiothatotherbreeds,suchasGreatPyrenees(64:1)and Pomeranian(18.6:1). Referencesusedandfurtherreading AlamMR,LeeJI,KangHS,KimIS,ParkSY,LeeKC,KimNS,Frequencyand distributionofpatellarluxationindogs134cases(2000to2005)Veterinary andComparativeOrthopaedicsandTraumatology20(1):5964,2007 Arthurs,GI,LangleyHobbsSJ,Complicationsassociatedwithcorrective surgeryforpatellarluxationin109dogsVeterinarySurgery35(6):55966,2006 BevanJM,Taylor,RAArthroscopicreleaseofthemedialfemoropatellar ligamentforcaninemedialpatellarluxationJournaloftheAmericanAnimal HospitalAssociation40(4):32130,2004 HarasenG,Patellarluxation:pathogenesisandsurgicalcorrectionThe CanadianVeterinaryJournal47(10):10379,2006 HayesAG,BoudrieauRJ,HungerfordLL,Frequencyanddistributionofmedial andlateralpatellarluxationindogs:124cases(19821992)Journalofthe AmericanVeterinaryMedicalAssociation205(5):71620,1994 HulseDA,TheStifleJointin:OlmsteadMLed.SmallAnimalOrthopedicsSt. Louis:Mosby,1995:395404 JohnsonAL,ProbstCW,DecampCE,RosensteinDS,HauptmanJG,Weaver BT,KernTL,Comparisonoftrochlearblockrecessionandtrochlearwedge recessionforcaninepatellarluxationusingacadavermodelVeterinarySurgery 30(2):14050,2001 KaiserS,CornelyD,GolderW,GarnerMT,WolfKJ,WaiblH,BrunnbergL,The correlationofcaninepatellarluxationandtheanteversionangleasmeasured usingmagneticresonanceimagesVeterinaryRadiologyandUltrasound 42(2):1138,2001 LaFondE,BreurGJ,AustinCC,BreedSusceptibilityforDevelopmental OrthopedicDiseasesinDogsJournaloftheAmericanAnimalHospital Association38:467477,2002 RoushJK,CaninepatellarluxationTheVeterinaryClinicsofNorthAmerica. SmallAnimPractice23:855868,1993 RoyRG,WallaceLJ,JohnstonGR,WickstromSL,Aretrospectiveevaluationof stifleosteoarthritisindogswithbilateralmedialpatellarluxationandunilateral surgicalrepairVeterinarySurgery21(6):4759,1992

TalcottKW,GoringRL,deHaanJJ,Rectangularrecessiontrochleoplastyfor treatmentofpatellarluxationindogsandcatsVeterinaryandComparative OrthopaedicsandTraumatology13:3943,2000 TowleA,GriffonDJ,ThomasMW,SiegelAM,DunningD,JohnsonA,Preand postoperativeradiographicandcomputedtomographicevaluationofdogswith medialpatellarluxationVeterinarySurgery34(3)26572,2005 WanderKW,PowersBE,SchwartzPD,Cartilagechangesindogswith surgicallytreatedmedialpatellarluxationsVeterinaryandComparative OrthopaedicsandTraumatology12:1837,1999 deBruinT,deRoosterH,vanBreeH,CoxE,Interleukin8mRNAexpressionin synovialfluidofcaninestiflejointswithosteoarthritisVeterinaryImmunologyand Immunopathology108(34):38797,2005

Topic#7:Addisonsdisease(Adrenalglandinsufficiency) ThebasicsofAddisonsaproblemforWestiesandpeople Addisonsdisease,alsoknownashypoadrenocorticism,isanuncommon conditioninwhichthepatientsadrenalglandsnolongersupplythebodywith veryimportanthormones,calledglucocorticoidsandmineralocorticoids. These hormoneshelpregulatemetabolismandelectrolytebalanceinthebody. AccordingtotheMerckVeterinaryManual(Merck,2005)thisdiseasedevelops withnonspecificsignsofgastroenteritis(vomitinganddiarrhea),lossofbody condition,lethargyandweakness,andinabilitytorespondtostressinmany affecteddogs. Addisonswasfirstreportedinadogin1953butisthesameconditionashuman Addisonsdisease. Itisadifficultconditiontodiagnose,asthesymptomscan indicatemanypossiblediseases.However,whenitisproperlydiagnosed, effectivetreatmentisavailableanddogswithAddisonscanleadhealthynormal lives. Howdoesthisdiseasedevelop? Theadrenalglandsarecomplicated,multifunctionalorgans.Therearetwo adrenalglands,oneontopofeachkidney(adrenalnearthekidney).The outerlayerofthegland(thecortex)producesthreetypesofhormones: glucocorticoids,mineralocorticoidsandsmallamountsofsexhormones.The probleminAddisonsdiseaseisalackofproductionoftheglucocorticoidsand mineralocorticoids. Basicphysiologyofhormonereleasefromtheadrenals Inthehealthyanimal,glucocorticoidproductionisregulatedbythebrain.The hypothalamusinthebrainproducesahormonecalledcorticotrophinreleasing hormone(CRH)whichstimulatesanotherpartofthebrain,thepituitarygland,to releaseahormonecalledadrenocorticotrophichormone(ACTH).ACTHtravels totheadrenalglandsinthebloodandstimulatesthemtoreleaseglucocorticoids intheformofcortisol.Whenthereisahealthyamountofcortisolcirculatingin theblood,thebrainstopssendingtheCRHandACTHtostimulatethe productionofcortisol.Thisiscalledanegativefeedbacksystem.(Thehealthy levelofcortisolinthebloodisanegativeinfluenceontheproductionofmore CRHandACTH.)Whentheresnotenoughcortisolintheblood,the hypothalamusandpituitarygladarestimulatedtomakemoreCRHandACTH, respectively,andthatproductionstimulatestheadrenalglandstoproducemore cortisoluntilthebloodlevelsreachahealthyvalue. Incontrast,mineralocorticoidsarenotregulatedbythebrain,butareinstead controlledbyasystemthatstartswithspecialcellsinthekidneys,called

juxtaglomerularcells.Thesespecialcellscansensewhenbloodpressureistoo low,primarilybydetectingtheamountofsodiumandoxygenatedbloodnear them. Whenthesecellsdetectinadequateflowandchangesinblood composition,theywillproduceachemicalcalledrenin,anenzymewhichthen reactswithanotherchemicalintheblood,calledangiotensinogen,andconvertsit toangiotensinI.Withsomehelpfromthelungs,angiotensinIisconvertedto angiotensinIIanditisangiotensinIIwhichstimulatestheadrenalglandsto producemineralocorticoidsintheformofaldosterone. (Activatedformsof angiotensinareveryimportantinregulatingbloodpressure.Theynotonly stimulatemineralocorticoidsfromtheadrenalglands,butalsocancausearteries andarteriolestoconstrict,raisingbloodpressure.Itisprettyobviousthat maintainingtherightbloodpressurehelpsdogsandpeoplestayalive!) Addisonsdiseasecanbeeitheraprimaryorsecondaryadrenalinsufficiency.In secondaryadrenalinsufficiencycases,themainproblemstartsinthebrain,with insufficientproductionofeitherstimulatinghormone,CRHorACTH.Without enoughCRHorACTHtoencouragetheadrenalglandstoproducecortisol,the glandsthinkitsnotneededandtheywillbegintoatrophy(shrinkinsizeand reducefunction). However,mostcasesofAddisonsareprimaryadrenal insufficiency,meaningthattheadrenalglandshavebeendamagedsomehow andarenolongerabletomakecortisolandaldosterone,evenwhenstimulated byCRH/ACTHandangiotensinII,respectively. Mostveterinariansand physiciansthinkthatanautoimmuneprocessisresponsiblefordestroyingthe adrenalglandsincanineandhumanpatientswithAddisons.Thatmeansthat thepatienthasdevelopedantibodies(likethosethatarenormallyusedtofight diseasesliketheflu,etc.)whichattackanddestroytheirownadrenalcells. The triggersforthedevelopmentofthisautoimmuneattackontheadrenalsarenot known,butarethesubjectofactiveresearch(seebelow). Whileautoimmunediseaseisuncommon,itismorelikelyinfemalesfemales aretwiceaslikelytodevelopAddisonsasmales. Unfortunately,Westiesseem tobeatahigherriskthanotherbreedsfordevelopingAddisons,sothereis likelytobesomegeneticcomponenttothedisease,ashasbeenshowninother breeds.Veryrarely,otherevents,suchasgranulomatousdiseases(aspecial typeofchronicinflammation),hemorrhagicinfarctions(bloodclotsformingand lodgingintheadrenalsandothertissues),canceroftheadrenalsornearly tissues,andtraumacaninduceenoughdamagetotheadrenalglandstocause Addisons. WhatarecommonclinicalsignsofAddisonsdiseaseinWestiesandother dogs? ThetypicalcanineAddisonspatientisyoungtomiddleaged(averageageis45 yearsold)andfemale.Themostcommonsignthatdogsshowislethargy. Affecteddogsmayseemlistless,reluctanttoexerciseorevendonormal activities,andmayseemmoretiredandsleepythantheypreviouslydid. Many

ofthesignsofAddisonsarenotspecifictothediseaseandallrelatetothe deficienciesofglucocorticoids(cortisol)andmineralocorticoids(aldosterone). Becausecortisolisimportanttothebodysmetabolism,cortisoldeficiencyoften manifestsinalossofappetite,vomiting,stomachpain,weightlossandlethargy. Aldosterone(theprimarymineralocorticoid)enablesthekidneystoretainsodium andexcretepotassium,balancingthebodyselectrolytesandmaintainingproper bloodpressure. Withtoolittlealdosterone,duetoAddisonsdisease,thereistoo littlesodiuminthebloodandbloodpressuredropsduetoinsufficientcirculating bloodvolume.Lowbloodpressuremeansallthepatientsorganswontreceive enoughnutrientsandwillsuffer.Thiseffectisespeciallyaproblemforthe kidneys.Patientswithlowbloodsodiummayloseweight,feelweak,have smallerthannormalheartsandproducedilutelookingurineeventhoughthey maybedehydrated.Highlevelsofpotassiuminthebloodcancauseheart rhythmproblems(calledarrhythmias),whichcanbelifethreatening. Addisonsdiseaseisusuallyaslowlyworseningproblem thatmayappeartowax andwane.Earlycasesmayonlybecomeevidentwhenthepatientisstressed, suchasfromundergoingsurgery,beingsickorevenboardingorshowing.Other casesmaymanifestsuddenlyasanAddisoniancrisisduetosevere dehydration(signsofkidneyproblems)orheartproblems. HowisAddisonsdiseasediagnosed? Addisonsdiseaseisadifficultdiseasetodiagnosebecauseofthemyriadof signsdogscanhave,andthesesignsarenonspecificandcanoccurinmany otherdiseasesbesidesAddisonsdisease. Bloodtestscaneasilyindicate whetheradoghaslowsodiumandhighpotassium,whichwouldraisethe suspicionofAddisons.WhenaveterinariansuspectsAddisonsdisease,heor shecanrunotherfairlysimplebloodteststoconfirmit.First,abaselinecortisol levelismeasuredintheblood.Then,theveterinarianwillgivethedogthe hormoneACTHtomimicthepituitaryglandssecretionofACTH.Healthy adrenalglandsshouldrespondtotheACTHliketheywouldtonaturallyoccurring ACTHfromthepituitaryandproducecortisol,raisingthelevelofcortisolinthe blood.Thecortisollevelinthebloodismeasuredagainonehourafter administrationoftheACTH.Iftheadrenalglandshavenotrespondedtothe ACTHbyraisingthebloodcortisollevel,adiagnosisofAddisonsismade. While theACTHstimulationtestonlytestscortisollevels,itisconsideredtoindirectly assessaldosteronelevels,sincedamagetotheadrenalcortexshouldeffect productionofbothhormonessimultaneously. Unfortunately,theACTH stimulationtestdoesnotdistinguishbetweenprimaryandsecondaryadrenal insufficiency.Patientswithsecondaryadrenalinsufficiencymayeventually respondtoenoughACTHgivenbytheveterinarian,whilethosewithprimary adrenalinsufficiencywillnot.Veterinariansmayalsouseradiographsand electrocardiograms(measurementsoftheheartselectricaloutput)tohelpmake adefinitivediagnosisofAddisonsdisease.

Treatmentcurrentthinkingandsuccesses Fortunately,Addisonsdiseaseincanbeeffectivelytreatedsimplybygiving patientsthehormonestheycantproducethemselves.Glucocorticoidscanbe replacedwithprednisone(amanufacturedformofthehormone)tabletsgiven orallyeveryotherday.Mineralocorticoidscanbereplacedeitherwithan injectabledrugcalleddesoxycorticosteronepivalate(DOCP)orfludrocortisone pillsgiventwicedaily.DOCPrequiresatriptothevetsofficeaboutoncea month,whilefludrocortisonemaybegivenathome,likeprednisone.While fludrocortisoneismoreconvenientforowners,itdoescarrysomesideeffects, suchasincreasedurination,drinking,andpossibleincontinence.Itisvery importantthatownersofWestieswiththisdiseaseprovideanadequatesupplyof drinkingwatertomeettheneedsofthedog.Thismayrequirefrequentrefilling ofwaterbowlsorprovidingadditionalwaterbowls.Likewise,youandyour veterinarianwillhaveadiscussionoftherightdiet,andespeciallytheright amountofmineralslikesalt,thatyourdogwillneed. Workingouttherighttreatmentforeachdogandownerisaprocessthatmay involveafewmonthsoftweakingdosesandmakingsurethedogsbloodwork lookshealthy.Fludrocortisone,whilemainlyamineralocorticoidalsohassome glucocorticoideffectsandsomepatientsmaynotneedadditionalglucocorticoid replacementwhileonfludrocortisone.Medicationswillneedtobeincreased duringtimesofstressforpatients,suchasboardingandtravel. TreatingAddisonsdiseaseinyourdogisalifelongcommitment.Patientswith thisdiseasearedependantontheirownersandveterinarianstoprovidethe hormonestheirbodiesneedtosustaintheirmetabolismandelectrolytebalance, whichareessentialtolife.ThegoodnewsisthatoncepatientswithAddisons arestabilizedandproperlydiagnosed,theycanleadhealthyandnormallives. TheaveragelifespanafterdiagnosiswithAddisonsdiseaseisapproximately sevenyears(thereissomeindividualvariation)aboutatypicallifeexpectancy. CurrentresearchonAddisonsdisease RecentresearchonAddisonsdiseasehasfocusedonfourareas:neurologic complicationsoftreatmentofAddisoniancrisis,thegeneticcontributiontothe disease,newtoolsfordiagnosisandmaintenance,andreviewingtreatment options. NeurologiccomplicationsofAddisonsdisease Treatinghyponatremia(lowserumsodium)isoneofthemajorgoalsof addressingahypoadrenocorticismemergency,oranAddisoniancrisis. When dogsexperienceacrisis,theyhaveveryabnormalbloodelectrolytelevelsand thiscanbelifethreatening,especiallyintermsofcardiacandrenalfailure. Severalrecentcasestudieshaveillustratedthedangersofoveraggressive

treatmentofdogsincrisisandrapidbloodsodiumlevelcorrection.Onerecent paperdescribedacaseofa3yearoldmixedbreeddoginAddisoniancrisis whichwastreatedtorestorecardiovascularstabilityandserumelectrolyte balance.Duringtreatment,thisdogdevelopedsevereneurologicsignsfrom rapidincreasesinserum sodium (Brady,etal,1999). Thedogeventually recoveredfully,butbrainlesionsweredemonstratedevenat23weeksafterthe initialpresentation.Anothercasestudyfollowedthetreatmentofan18month oldWestiewhichwasdiagnosedwithmyelinolysis(breakdownofthematerial thatcoversnervesinthebrainandspinalcord)causedbyrapidadministrationof IVfluids(MacMillan,2003).Thisstudynotedthatexistingliteraturevariedon recommendationsforelectrolyterestorationandprovidescalculationsfor determiningasaferrestorationrate.Areviewarticlepublishedin2007 recommendscorrectingserum sodiumataratenofasterthan12mEq/L (milliequivalents/liter)perday(Meeking,2007).Theauthorrecommended withholdingmineralocorticoidadministrationuntilserumelectrolytebalancehas beenrestored,soasnottoincreasetherateofcorrection. NewresearchintothegeneticsofcanineAddisonsdisease OneofthemainareasofinterestincanineAddisonsdiseaseisthesuspected geneticinheritabilityofthedisease.Recentresearchhasindicatedthatthe diseaseishighlyheritableinBeardedCollies(Oberbauer,etal,2002)andin StandardPoodles(Famula,etal,2003).Anotherstudyproposedagenetic comparisonofAddisonsdiseaseinthePortugueseWaterDogtotheanalogous diseaseinhumans(Chase,etal,2006).Theseauthorsdescribethegenetic aspectascomplexandsimilarinhumansanddogs. Whenwespeakabout inheritabilityweneedtomentionthatamongthepotentialfactorsthatmightbe inherited(passedinthegenome)are: Oneormoremutationsofgenescontrollingbasicphysiologicfunctionof thebrain(hypothalamusandpituitary)andadrenalglands Oneormoremutationscontrollinghormonesecretionfromthese endocrineglands Oneormoremutationscontrollingtissuesensitivitytohormoneeffects Oneormoremutationscontrollingthestructureofglandsandtissuesthey effect Oneormoremutationsthatpredisposeindividualdogstodeveloping automimmunedisease Andothereffectsnotlistedhere! Geneticresearchforcaninediseaseisarapidlyemergingfield,nowthatthe entirecaninegenomehasbeenmapped.AtthetimeofpublicationofthisTopic, The WestieFoundationofAmericaisseekinggeneticsamplesfromWestiesto contributetoresearchonthegeneticheritabilityofAddisons(andother diseases)inthebreed.SeetheFoundationswebsiteformoreinformationon thisandotherstudies.Understandingtheroleofthegene(s)thatmaycontribute

tothedevelopmentandprogressionofAddisonsdiseaseinWestiesandother dogbreedswillhelpbreedersandveterinarianspreventthedisease. AdvancesindiagnosingAddisonsdiseaserespondingtothechallenge Aswehavementioned,makingthediagnosisofAddisonsdiseasecanbea challengeforveterinarians.Thesignsarenotpathognemonic(absolutely indicativeofaparticulardisease)andvaryfromindividualtoindividual.New toolsfordiagnosishavebeenamajorinterestincurrentresearchonAddisons andwillhopefullycontributetoeasierrecognitionofthedisease. Arecentpaperreportedontheultrasonographicevaluationofadrenalglandsin healthyandAddisonspatients(Hoerauf,etal,1999). Theauthorsfoundthat Addisonspatientshadshorterandthinneradrenalglandsthanhealthydogs, whenexaminedwithultrasonography,andthatthesedifferenceswere statisticallysignificantintheleftadrenalglands.Inthesameyear,aseparate studyexaminedimagingofotherorgansinAddisonspatients(Melian,etal, 1999). Melianandcoauthorsquantifiedthepresenceofradiographic abnormalitiesindogswithAddisonsdisease,usingavarietyofmeasurement andcomputationalmethods.Accordingtotherereport,81.8%ofuntreateddogs withprimaryhypoadrenocorticismhadoneormoreradiographicabnormalities. Theseincludedsmallheart,smallcraniallobarpulmonaryartery,smallvena cavaandsmallliver. RenalbloodflowmayalsobeanothertoolforbothdiagnosisofAddisonsand managementofthedisease,sincethekidneysareultimatelyresponsiblefor balancingserumelectrolyteslikesodiumandpotassiumandalsoinsuringthe stateofbodyhydration.Kochandcoauthorsmeasuredintrarenalbloodflowin aTibetanterrierwithAddisonsusingduplexDoppler(Koch,etal,1997),an imagingmethodthatallowsvisualizationandmeasurementofbloodflow.They reportthat,usingaresistiveindexsystem,bloodflowcanbeusedtoevaluate propercontrolofAddisonsdiseasepatientswithpharmaceuticals.Oncethe diseasewasproperlycontrolledwithtreatment,thepatientsresistiveindexfell withinanormalrange. Traditionally,thedefinitivediagnosisofAddisonsismadebymeasuringblood cortisollevelsbeforeandafteradministrationofACTH.Aldosteroneisnot typicallymeasuredbutisassumedtobeindirectlyaccountedforasmostpatients withhypoadrenocorticismhaveuniformdamagetotheadrenalcortexwhich affectstheproductionofbothhormonessimultaneously.However,Thompson andcoworkers,inastudyon46dogswithhypoadrenocorticism,determinedthat 35(76%)weredeficientinbothglucocorticoidsandmineralocorticoidsandthat 11(24%)wereonlyglucocorticoiddeficient.Theseresultsindicateahigherthan expectedpresenceofpatientswithonlyglucocorticoiddeficiency.TwoWesties wereamongthe11patientswithprimaryglucocorticoiddeficiency(Thompson,et al,2007).

Similarly,apaperbyJavadi,etal,offeredanewsetofparametersforassessing Addisonsindogs(Javadi,etal,2006)Thisstudymeasuredthetraditional plasmaconcentrationofcortisolandofACTHbutalsomeasuredthe concentrationofaldosteroneandrenin.Theauthorsfoundthatwhilethese valuesoverlappedwiththoseofhealthydogs,thecortisoltoACTHratioand thealdosteronetoreninratiodidnot.Theseratiosdefinitivelyseparatedthetwo groupsofdogs,allowingthespecificdiagnosesofprimaryhypocortisolismand primaryhypoaldosteronism. MakingprogressinthetreatmentofAddisonsdiseaseindogs Researchtodevelopnewtreatmentsforaffecteddogshasbeenveryactivefor overadecade.KintzerandPetersonpublisheddataonthelongtermtreatment of205dogswithAddisons(Kintzer,etal,1994).Accordingtotheseauthors, 190dogswereinitiallytreatedwithfludrocortisoneacetateandtreatmentlasteda medianof2.6years.Twentyseven(27)ofthesedogswereswitchedtoDOCP duetoadverseeffects,poorresponseorfinancialconsiderations.Median treatmentwithDOCPwas3.5years.200dogsweretreatedwithprednisonebut treatmentwasstoppedin22dogsduetoadverseeffects.Thegoodnewsisthat 80%ofcaseswerefoundtohaveagoodtoexcellentresponsetotherapyand themediansurvivaltimewas4.7years,withchoiceoftreatmentmakingno difference.Unfortunately,31%ofcaseshadoneormoresignsofiatrogenic (causedbymedicaltherapy)hyperadrenocorticismbuttheseweregenerally resolvedbydecreasingorstoppingprednisoneorbyswitchingtoDOCP. ResearchersinNewZealandmaybeofferinganewtreatmentforAddisons: licorice. Licoricecontainsglycyrrhizinicacidanditsmetabolite,glycyrrhetinic acid,canincreasemineralocorticoidactivity,ashasbeenshowninhumans.At thetimeofpublication,theresearchershadhadsuccesswitha4yearoldmale withAddisonsbutwereseekingparticipantsforalargerstudy(Jarrett,etal, 2005) Insummary Addisonsdisease(hypoadrenocorticism)maybedifficulttodiagnoseinearly stagesofdisease,duetorelativelynonspecificclinicalsigns.However,once detected,itcanbeeffectivelymanagedthroughacombinationofhormone replacementtherapy,diet,goodhusbandry,andregularveterinarycare.We needtofindoutwhyWesties,asabreed,seemtobemorepronetodevelopthis diseasethanmanyotherdogbreeds,butwearenowusingpowerfuldiagnostic andgenomictoolstodothis. ReferencesandResources

BradyCA,ViteCH,DrobatzKJ,Severeneurologicsequelaeinadogafter treatmentofhypoadrenalcrisisJAmVetMedAssoc.215(2):2225,210,1999 ChaseK,SarganD,MillerK,OstranderEA,LarkKG,Understandingthe geneticsofautoimmunedisease:twolocithatregulatelateonsetAddison's diseaseinPortugueseWaterDogsInternationalJournalofImmunogenetics 33(3):17984,2006 FamulaTR,BelangerJM,OberbauerAM,Heritabilityandcomplexsegregation analysisofhypoadrenocorticisminthestandardpoodleJournalofSmallAnimal Practice44:8,2003 FeldmanEC,NelsonRW,Hypoadrenocorticism(Addisonsdisease)inCanine rd andFelineendocrinologyandreproduction.3 ed.Philadelphia.WBSaunders Co.,2004394439 GrecoDS,HypoadrenocorticisminsmallanimalsClinicalTechniquesinSmall AnimalPractice22(1):325,2007 HoeraufA,ReuschC,Ultrasonographicevaluationoftheadrenalglandsinsix dogswithhypoadrenocorticismJournaloftheAmericanAnimalHospital Association35(3):2148,1999 JavadiS,GalacS,BoerP,RobbenJH,TeskeE,KooistraHS,Aldosteroneto reninandcortisoltoadrenocorticotropichormoneratiosinhealthydogsanddogs withprimaryhypoadrenocorticismJournalofVeterinaryInternalMedicine 20(3):55661,2006 JarrettRH,NormanEJ,SquiresRA,LicoriceandcanineAddison'sdisease NewZealandVeterinaryJournal53(3):214,2005 KintzerPP,PetersonME,Diagnosisandmanagementofprimaryspontaneous hypoadrenocorticism(Addison'sdisease)indogsSeminarsinVeterinary MedicineandSurgery(SmallAnimal)9(3):14852,1994 KintzerPP,PetersonME,Treatmentandlongtermfollowupof205dogswith hypoadrenocorticismJournalofVeterinaryInternalMedicine11(2):439,1997 KochJ,JensenAL,WenckA,IversenL,LykkegaardK,DuplexDoppler measurementsofrenalbloodflowinadogwithAddison'sdiseaseTheJournal ofSmallAnimalPractice38(3):1246,1997 MacMillanKL,Neurologiccomplicationsfollowingtreatmentofcanine hypoadrenocorticismTheCanadianVeterinaryJournal44(6):4902,2003

MeekingS,TreatmentofacuteadrenalinsufficiencyClinicalTechniquesin SmallAnimalPractice22(1):369,2007 MelianC,StefanacciJ,PetersonME,KintzerPP,Radiographicfindingsindogs withnaturallyoccurringprimaryhypoadrenocorticismJournaloftheAmerican AnimalHospitalAssociation35(3):20812,1999

th MerckVeterinaryManual,9 edition,Kahn,CM,Line,S,(eds.),Merck&CO, WhitehouseStation,NJ,2005,p.436437

OberbauerAM,BenemannKS,BelangerJM,WagnerDR,WardJH,FamulaTR, InheritanceofhypoadrenocorticisminbeardedcolliesAmericanJournalof VeterinaryResearch63(5):6437,2002 RiesenSC,LombardCW,ECGoftheMonth.Atrialfibrillationsecondaryto hypoadrenocorticismJournaloftheAmericanVeterinaryMedicalAssociation 229(12):18902,2006 ThompsonAL,ScottMoncrieffJC,AndersonJD,Comparisonofclassic hypoadrenocorticismwithglucocorticoiddeficienthypoadrenocorticismindogs: 46cases(19852005)JournaloftheAmericanVeterinaryMedicalAssociation 230(8):11904,2007

gut,aninfectiousagent,oradogwiththeequivalentofhyperactivitydisorder. (WearesurethislasttheoryappliedstrictlytoJackRussellterriers,notWesties). (WeapologizetoownersofJackRussellterriersforthisjokeattheirexpense. JRTsarewonderfuldogs!). Currently,itisunderstoodthatIBDisanimmune relateddisorder. Inahealthydog,thesmallandlargeintestines,whichincludesthecolon,have theirownlocalpartoftheimmunesystem. Thisgastrointestinalportionofthe immunesystem ismeanttoprotectthebodyfromviruses,bacteriaorother antigens(unwelcomeoutsiderproteinsandcomplexmolecules)thatmaybe consumedinfoodandwater. Thehealthyintestinaltractis,fortunately,inhabited byfriendlybacteriaatalltimes.Thisfriendlybacteria,ornormalflora,helpkeep antigensoutsimplybyoccupyingallthegoodlivingspaceintheintestines. Undernormalcircumstances,theintestinalimmunesystemdoesnotreacttothe friendlybacteria,allowingthemanyspeciesofthesebeneficialbacteriaan environmentdototheirjob. ItisthoughtthatinanimalswithIBD,aproblemhasdevelopedinoneofthree areas:thelocalintestinalimmunesystemoritsregulation(thebodymaybe attackingitselforfriendlybacteria),theintegrityoftheintestinesthemselves (throughsomeinjury),orthedisruptionofthebalanceofnormalflorainthe intestines. Anyoneoftheseproblemscantriggeranunwantedimmune responsethatgetsoutofcontrolandbecomesselfperpetuating. Muchofthe currentresearchinthepathogenesis(whatcausesIBDandhowitdevelops)is devotedtounderstandingtheroleoftheimmunesystem(SeeCurrentresearch inthepathogenesisandtreatmentofIBD,below) WhatarethesignsthatIBDmaybedeveloping? ThemajorclinicalsigninIBDissmallboweldiarrhea.(Yes,veterinarianscantell fromdiarrheaiftheresaproblemwiththesmallorlargeintestines.)Ifitsthe earliestpartofthesmallintestinesthatsaffected,vomitingmaybethemost prominentsignandtheremaybenodiarrheaatall. DogswithLPCwillsuffer fromlargeboweldiarrhea,developingsoftstoolswhichmayhavebloodor mucusinthem. Oftenthesignscomeandgoseeminglyrandomly.Inearly stagesofIBD,dogsmayappearperfectlyhealthyexceptforachangeinstool consistencyandfrequency. Astimegoesonandifthediseaseisundiagnosedorleftuntreated,somedogs maylooseweightbecauseofthelossofnutrientsinthestool. Eventually,any patientcandevelopvitaminandmineraldeficiencieswhichmanifestas malnutrition.Anotherlongtermproblemthatcanoccurislymphangiectasia(the dilationoflymphaticvessels)whichcaneventuallyresultinthedevelopmentof oneormoremassesintheaffectedarea.

HowisIBDdiagnosed? IBDisadiagnosismadebyrulingoutotherdiagnoses.Dogscanexhibitsimilar signs(vomitinganddiarrhea)fromproblemswithintestinalparasites,food allergies,dietarychanges,stressesassociatedwithmoving/traveling/boarding, andevenchangesinhouseholdoccupants(likethearrivalofnewbabies). In manyaffecteddogs,adefinitivediagnosisofIBDismadebyexaminingasection orsectionsoftheintestinestakenfromabiopsy. Theseproceduresaretime consuming,requiresedation/anesthesia,areinvasive(biopsiesaresnipped fromthesurfaceofthegastrointestinaltract),andcanbeexpensive(Allenspach, etal,2004). Veterinarypathologistsexaminethesectionsforanoverpopulation ofimmunecells.Unfortunately,thedeterminationoftoomanyimmunecellsisa subjectiveoneandcanbeconfusedwithlymphocyticlymphoma,aformof intestinalcancer. WhenaveterinariansuspectsIBD,heorshemayperformanumberof diagnosticteststoruleoutotherdiseases. Afecaltestwillhelpruleout parasites. Bloodworkwillrevealahighcountofimmunerelatedcells,indicating inflammation.Insomecases,xraysmaybetakenafterthepatienthasreceived abariumenema,whichwillhighlightthecolononthexray. Ultrasoundand regularxraysarenot usuallyashelpfulin thediagnosisofIBD, butmayrevealother problems.Themost importantdiagnostic testisathorough examinationofthe intestineswithan endoscope.An endoscopeisa camerathatcanbe insertedintothe intestinesofapatient inordertoallowa veterinariantoview thehealthofthe intestinaltissueand totakeabiopsy,if necessary. Shownin Figure1,Dr.MichaelLeib,anexpertinthediagnosisand therapyofsmallanimalgastrointestinaldiseases,examinetheinsideofadogs colonwiththeendoscopeinhislefthandandlookingatthemonitorontheright of Figure1..

Figure2,ontheleft,showsanendoscopicviewof inflamedintestine(redspotsandroughsurface).The endoscopistmaybiopsytheseareasthroughthe endoscopeandputthesesmallbiopsypiecesin fixativeforpreparationofmicroscopeslides.A veterinarypathologistwillexaminethebiopsysample underamicroscopeanddeterminewhattypeof diseaseprocessisgoingon.Anunexplained inflammatoryprocessislikelytobeIBD.Amajor differentialdiagnosisindogswithsomeofthesesigns isintestinalcaninemalignantlymphoma,andit requiresaskilledpathologist,workingwiththeclinicalveterinarian,tobesurethe correctdiagnosisismade.Theappearanceofintestinalcaninemalignant lymphomainendoscopicbiopsiesisanincreasednumberofabnormal lymphocytespresent.AmajordifferentiatingfeatureofIBDisthepresenceof mixedpopulationsofnormallymphocytes,plasmacells,andsometimescellslike neutrophilsandeosinophils(Craven,etal,2004).Ifthereisanydoubtaboutthe diagnosis,itisanexcellentideatorequestasecondopiniononthebiopsy diagnosis. AveterinarianmayalsoemploythecanineIBDactivityindex(CIBDAI)toscore apatientsclinicalsignsanddeterminetheseverityofthedisease(Jergens Jergensetal,2002,2003,2004). Theveterinarianassignsanumberfromoneto threetoeachofsixclinicalsigns:attitude/activity,appetite,vomiting,stool consistency,stoolfrequencyandweightloss.Thescoresareaddedupandthe totaldeterminesifthediseaseisconsideredclinicallyinsignificant,mild, moderateorsevere.ThisindexisbasedonothersdesignedtoquantifyCrohn's diseaseinhumansandcanbeusedtoassestheprogressapatientismaking. SimplebloodtestsgenerallyarentveryhelpfulfordiagnosingIBDspecifically. However,averysmallnumberofaffecteddogs(2.5%inonestudy)had decreasednumbersofcirculatingplatelets(Ridgway,etal,2001).Treatmentof thesedogsforIBDresolvedthisproblem(thrombocytopenia).Anothercase reportstudyfoundtwodogswithanemia,presumablyduetobloodlossthrough thegastrointestinaltract(Ristic,etal,2002). Fosterandcoworkers(Foster,etal,2003)studiedserumantibodies(IgEand IgG)inthreepopulationsofdogsnormaldogs,dogswithallergiesanddogs withoneoffourtypesofgastrointestinaldisease.Thefourtypesof gastrointestinaldiseaseweresmallbowelbacterialovergrowth,IBD,food responsivedisease,andinfectiousdiarrhea. Theyfoundnodifferencein antibodylevelsbetweendogswithanyofthetypesofgastrointestinaldisease buttherewasastatisticallysignificantincreaseinIgGlevelsofdogswith gastrointestinaldisease,comparedtoeithernormaldogsorthosewithallergies.

TreatmentofIBDsometimesfrustratingforowners Unfortunately,thereislittledataontheeffectivenessofparticulartreatmentsfor IBDsotreatmentisbasedonempiricalevidenceandtheclinicalexperienceof theveterinarian. TreatmentofIBDisusuallymultifacetedandwilllikelyincludea combinationofdietchange,antibioticsandimmunosuppressivedrugs,including theuseofcorticosteroidssuchasprednisone,alldescribedinmoredetailbelow. Managementwithdrugsaloneisnotrecommendedandusuallyhaslimitedvalue instoppingIBD. Diet. InitialtreatmentofanacuteboutofIBDmayrequirecompleterestingof theintestinesbywithholdingfoodandprovidingIVnutrients.Forlongtermcare, feedingaspecialdietisoneofthemostimportantthingsthatcanbedoneto manageIBD.Anidealdietshouldincludelimitedsourcesofhighlydigestible proteinandcarbohydrates.Often,itisnecessarytoprovideanovelprotein source,onetheanimalhasnthadbeforeandsowillnothavedevelopedan allergyto.Aveterinariancanexplain howtocreateanappropriate homemadedietandsome commercialprepareddietsmaywork aswell. (Figure3.atlefthome cookingofdietsmaybeausefulpart ofmanagingIBD). Commercialdiets withhydrolyzedproteins(proteins withamolecularweightsmallerthan isthoughttoberecognizedbythe bodyasanantigen)arenow availablebutlittledataexistsasto theireffectiveness. Otherdietchangessuchasincreasingfibercontent(to decreasediarrhea),changinglevelsofomega3andomega6fattyacids(to reduceinflammation),andfeedingprobiotics(suchasLactobacillus)mayalsobe tried. Averycomprehensivereviewofnutritionaltherapyingastrointestinal diseaseindogswasrecentlypublished(Zoran,2003). Antibiotics.Antibioticsarethoughttosuppressthenumbersbothfriendlyand unfriendlybacteriaintheintestines.Alowerednumberofbacteriaandthe antigensassociatedwiththem arethoughttoallowthepatienttoreduceits immuneresponsetobacterialantigens,reduceinflammationandreducesigns associatedwithIBD.Formanyyears,themostcommonlyusedantibioticin casesofIBDhasbeensulphasalazine(Azulfidine)becauseitisthoughttohave bothantibioticandantiinflammatoryproperties.Themostcommonsideeffect from theuseofsulphasalazineisdryeyes. Othercommondrugsusedincluded theantibioticsmetronidazoleandtylosin(Craven,etal,2004). Immunosuppressivedrugs. Corticosteroidsaregiventosuppresstheimmune system,butcarrydangerouspotentialsideeffectswhengivenoverlongperiods

oftime,suchashyperadrenocorticism,gastrointestinalulcerationand pancreatitis. Azathioprine,animmunosuppressivedrugsometimesusedtotreat autoimmunediseasesandcancer,isoftengiveninconjunctionwith corticosteroidsinordertoreducethedosesofcorticosteroidsneededandavoid sideeffectsasmuchaspossible. Bonemarrowsuppressionisthemost commonsideeffectofazathioprine. ManagingcanineIBDrequiresalifelongcommitmentfromowners. The prognosisforadogwithIBDdependsontheseverityofthediseaseandthe progressionatthetimeofdiagnosis. Achangeindietandclosemonitoringof thepatientmaybeallthatsneededtomanagemanycasesofIBD. Forothers, onlyminimalmedicationmustbeadded.However,ifananimalisinverypoor bodycondition,itisharderforittorecover. DogswithLPCdobetterthanthose withLPEanddogswithgranulomatousenteritis/gastritisarethoughttonotfare well,althoughnotmuchdataisavailable. Thegoodormoderatelygoodnewsisthatwithacombinationoftherapies,many dogswithIBDwillimprove.Datapublishedinaretrospectivecasestudyreview of80dogswithIBD,byCravenandcoworkers(Craven,etal,2004)showedthe following: 21/80dogswentintodiseaseremissionwiththerapy(medianobservation time14months) 40/80dogshadintermittentsignsofdisease(medianobservationtime17 months) Unfortunately,theseauthorsalsofoundintheirstudythat3/80dogshaddisease thatcouldnotbecontrolledbytherapyand10/80dogswereeuthanizeddueto failuretoimprove.Goodfollowupwasnotfoundontheremainderofdogsin thisstudy. CurrentresearchinthepathogenesisandtreatmentofIBD MuchofthecurrentresearchonIBDisfocusedintwomainareas: understandingcharacteristicsandfunctionsofimmunecellsfoundin biopsiesofdogswithIBD noveldiagnosticmethodstodetectIBDorresponsetotherapyofIBD testingofnewtherapiesfortreatmentofIBD Characteristicsandfunctionsofmucosalimmunecells Inaseriesofpapers,Allenspachandcolleagues,(Allenspach,etal,2004, 2006a,2006b,2006cLuckschander,etal,2006)lookedformarkersofimmune cellactivityorresponsivenessindogswithIBD.Theyfoundthatroughlyhalfof dogsstudiedhadcirculatingperinuclearantineutrophiliccytoplasmicantibodies (PANCAs)intheirserum,indicatingreactivitytoinflammatorycells.These antibodieshadbeendetectedinpeoplewithIBD,ulcerativecolitis,andalsoin

thosewithsystemiclupuserythematosus.Theylookedforantibodiesagainsta commonyeast(Saccharomycescerevisiae)(ASCAs),whichareknowntobe seeninpeoplewithCrohnsdisease,andfoundthemin17/39dogsstudied. TheydidnotconsiderthelevelsofASCAssignificantinIBDdogs.Theyfound thatdogswithIBDthathadrelativelylowlevelsofacellularprotein,p glycoprotein(pgp),weremorelikelytorespondtodrugtherapythandogswith highlevelsofpgp. Germanandcoworkers(German,etal,2000a,2000b,2001,2003)studied biopsiesfromtheduodenumfromdogswithIBD.Theyfoundincreasednumbers ofIgG+plasmacells,CD3+tlymphocytes,CD4+lymphocytes,macrophages andneutrophils,usingavarietyofspecialcellstains.Ofinterest,theynoteda decreasednumberofmucosalmastcells,thisdifferingfromfindingsofLocher andcoworkers(Locher,etal,2001).Germanandhiscolleaguesfoundthatin Boxerdogswiththehistiocyticvariantofulcerativecolitis,therewerealso increasednumbersofIgG+plasmacells,CD3+tlymphocytes,andperiodicacid Schiffspositivemacrophages.Notonlywereincreasednumbersofimmune effectorcellspresent,butinflammatorycytokines(IL2,IL5,IL12p40,TNF alpha,andTGFbeta)producedbythesecellswereseenoverexpressedin GermanShepherddogswithIBD.However,McCannandhiscoworkers (McCann,etal,2007)didnotfeelthatserumTNFalphalevelsweregood indicatorsofdiseaseseverityinIBD. Gregerandhiscolleagues(Greger,etal,2006)alsonotedincreasedexpression ofperoxisomeproliferatorassociatedreceptoralpha(PPARalpha)inmucosal samplesofdogswithIBD.Theyinterpretedthisasanindicationofincreased nuclearreceptoractivitymediatingmucosalinflammation. Likewise,Spichiger andcoworkers(Spichiger,etal,2005)foundincreasedexpressionofgrowth hormonereceptors,IGF1,andIGF2insamplesofinflamedgastrointestinal tract.They,too,feltthatthepresenceofthesemediatorswasindicativeof cyclesofinflammationandhealingindogswithIBD. Noveldiagnosticmethods Gaschenandcoworkers(Gaschen,etal,2005)usedDopplerbloodflow measurementsoftwoofthemainarteries(theceliacandcranialmesenteric arteries)thatsupplybloodtothegastrointestinaltract.Ofsignificantinterest, theyfoundattenuatedbloodflowduringseveralfastingandfeedingintervalsin dogswithIBDnotseeninnormaldogs.Thismayindicatethatchangesinblood flow,coupledwithchangesinmotilityofgutsegments,maycontributetothe developmentandprogressionofIBDandsignsassociatedwithit. NewtherapiesforIBD SomedogsdonotrespondwelltotherapiesforIBD.Dogstreatedwith corticosteroidslikeprednisonearepronetodevelopmentofgastriculcersandto

Topic#8:InflammatoryBowelDisease(IBD) Thebasicsthedogwithvomiting,diarrhea,weightloss,andunhappy owners Inflammatoryboweldiseaseisanimmunerelateddisorderinwhichtheintestines arechronicallyorintermittentlyinflamed.Asynonym,withthesameabbreviation (IBD),isirritableboweldisease.Caninepatientsmayexperiencevomiting, diarrhea,weightlossoracombinationofany(orall)ofthesesigns. Thereisa greatdealofindividualvariationintheseverity,duration,responsetotherapy, andlongtermeffectsofhavingIBD. IBDcancomeindifferentforms,butthemostcommoniscalledlymphocytic plasmocyticenteritis(LPE)andisnamedforthemainimmunecelltypesthatare foundinbiopsiesoftheaffectedsectionsofthesmallintestine.Alsovery commonisaforminwhichtherearemixedinflammatorycells(Craven,etal, 2004). Lymphocytesarecellsthattypicallyfunctiontodetectandkillviruses, fungi,andeventumorcells.Whentheyareexposedtoinfectiousagents, includingbacteriaandsomecomplexmoleculeslikeforeignproteinsand complexcarbohydrates,theycantransformintoantibodyproducingplasmacells. Lymphocytesalsointeractwithotherimmuneandinflammatorycellstocreatea veryactivedefensesystemofthebody,protectingpeople,dogs,andother animalsagainstdisease. OthertypesofIBDincludelymphocyticplasmocyticcolitis(LPC),whichprimarily affectsthecolon(aportionofthelargeintestine)andgranulomatous enteritis/gastritis,wheretherecanbelesionsinthesmallintestinesand/or stomach.Granulomatousenteritis/gastritisisveryrare. CanineIBD,especiallygranulomatousenteritis/gastritis,issimilarinsome respectstothehumandisorder,knownasCrohnsdisease. Humansexperience manyofthesamesymptomsasdogswithIBDandareoftencaredforwiththe sametreatments.MuchofourveterinaryknowledgeofIBDcomesfrom researchonCrohnsdiseaseusingdogsandotheranimalswithspontaneous andexperimentaldiseaseastranslationalanimalmodels.Crohnsdiseaseis thoughttohaveageneticcomponentandresearchersarelookingintothis possibilityindogs. HowdoesyourdogdevelopIBD? Itisnotfullyknownwhysomedogsgetinflammatoryboweldiseaseandsoitis anotheridiopathiccondition.(Arunningjokeamongmedicalandveterinary medicalprofessionalsisthatidiopathicreallymeanstheidiotstreatingmedont haveaclueaboutwhyImsick!). Differenttheoriesonthecauseofthisdisease havebeenpopularovertime,includingpreexistingproblemswithbloodvessels causingdisruptionintheintestines,overproductionofmucus,asimplyoveractive

haveexcessivethirst(polydipsia),excessiveandsometimesuncontrolled urination(polyuria)andexcessivehunger(polyphagia).Longtermuseof corticosteroidsisassociatedwithincreasedchanceofinfectionandmayincrease theriskfordevelopingcancer(thishasbeenshowninpeople).Veterinarians havelookedfornewdrugstohelpdogsthatmaynottoleratecorticosteroids. Allenspachandcoworkers(Allenspach,etal,2006)administeredthe immunosuppressivedrug,cyclosporineA,todogsnotrespondingwellto corticosteroidtherapy.Improvementinclinicalsignswasseenin12/14dogs treatedandbiopsiesoftheintestinaltractshoweddecreasedmucosalt lymphocytesinrespondingdogs. Tumultyandcolleagues(Tumulty,etal,2004)studiedtheeffectofthecentrally actinghormonemediator,budesonide,onclinicalsignsindogswithIBD.No beneficialeffectofthisdrugwasseen. Insummary,researchintothecausesandtreatmentsofIBDisveryactiveinthe pastfewyears.Anincreasingunderstandingofthecriticalrolethatimmune reactivityplaysinthedevelopmentofIBDispossiblewithnewmolecular techniques.Thisknowledgewillhelpinthedesignofmoleculartherapiesinthe neartermandunderstandingwhyWesties,asabreed,maybepredisposedto developIBD. Referencesusedandresourcesforfurtherstudy AllenspachK,BergmanPJ,SauterS,GrneA,DoherrMG,GaschenF,P glycoproteinexpressioninlaminaproprialymphocytesofduodenalbiopsy samplesindogswithchronicidiopathicenteropathiesJournalofComparative Pathology:134(1):17,2006a. AllenspachK,LuckschanderN,StynerM,SeiboldF,DoherrM,AeschbachD, GaschenF,Evaluationofassaysforperinuclearantineutrophiliccytoplasmic antibodiesandantibodiestoSaccharomycescerevisiaeindogswith inflammatoryboweldiseaseAmericanJournalofVeterinaryResearch: 65(9):127983,2004. AllenspachK,RfenachtS,SauterS,GrneA,SteffanJ,StrehlauG,Gaschen F,Pharmacokineticsandclinicalefficacyofcyclosporinetreatmentofdogswith steroidrefractoryinflammatoryboweldiseaseJournalofVeterinaryInternal Medicine:20(2):23944,2006b. AllenspachK,SteinerJM,ShahBN,BerghoffN,RuauxC,WilliamsDA,Blum JW,GaschenF,Evaluationofgastrointestinalpermeabilityandmucosal absorptivecapacityindogswithchronicenteropathyAmericanJournalof VeterinaryResearch:67(3):47983,2006c.

CaveNJ,Chronicinflammatorydisordersofthegastrointestinaltractof companionanimalsNewZealandVeterinaryJournal:51(6):26274,2003 CaveNJ,HydrolyzedproteindietsfordogsandcatsVeterinaryClinicsofNorth America.SmallAnimalPractice:36(6):125168,2006. CravenM,SimpsonJW,RidyardAE,ChandlerML,Canineinflammatorybowel disease:retrospectiveanalysisofdiagnosisandoutcomein80cases(1995 2002)JournalofSmallAnimalPractice:45(7):33642,2004. FosterAP,KnowlesTG,MooreAH,CousinsPD,DayMJ,HallEJ,SerumIgE andIgGresponsestofoodantigensinnormalandatopicdogs,anddogswith gastrointestinaldiseaseVeterinaryImmunologyandImmunopathology:92(3 4):11324,2003. GaschenL,KircherP,LangJ,GaschenF,AllenspachK,GrneA,Pattern recognitionandfeatureextractionofcanineceliacandcranialmesentericarterial waveforms:normalversuschronicenteropathyapilotstudyVeterinaryJournal: 169(2):24250,2005. GermanAJ,HallEJ,DayMJ,Chronicintestinalinflammationandintestinal diseaseindogsJournalofVeterinaryInternalMedicine:17(1):820,2003. GermanAJ,HallEJ,DayMJ,Immunecellpopulationswithintheduodenal mucosaofdogswithenteropathiesJournalofVeterinaryInternalMedicine: 15(1):1425,2001. GermanAJ,HallEJ,KellyDF,WatsonAD,DayMJ,Animmunohistochemical studyofhistiocyticulcerativecolitisinboxerdogsJournalofComparative Pathology:122(23):16375,2000a. GermanAJ,HelpsCR,HallEJ,DayMJ,CytokinemRNAexpressioninmucosal biopsiesfromGermanshepherddogswithsmallintestinalenteropathies DigestiveDiseasesandSciences:45(1):717,2000b. GregerDL,GroppF,MorelC,SauterS,BlumJW,Nuclearreceptorandtarget genemRNAabundanceinduodenumandcolonofdogswithchronic enteropathiesDomesticAnimalEndocrinology:31(4):32739,2006. JergensAE,Clinicalassessmentofdiseaseactivityforcanineinflammatory boweldiseaseJournaloftheAmericanAnimalHospitalAssociation:40(6):437 45,2004 JergensAE,Underestimatinggastrointestinalinflammationimplicationsfor therapyJournalofFelineMedicineandSurgery:4(3):17982,2002.

JergensAE,SchreinerCA,FrankDE,NiyoY,AhrensFE,EckersallPD,Benson TJ,EvansR,Ascoringindexfordiseaseactivityincanineinflammatorybowel diseaseJournalofVeterinaryInternalMedicine:17(3):2917,2003 LocherC,TipoldA,WelleM,BusatoA,ZurbriggenA,GriotWenkME, QuantitativeassessmentofmastcellsandexpressionofIgEproteinandmRNA forIgEandinterleukin4inthegastrointestinaltractofhealthydogsanddogs withinflammatoryboweldiseaseAmericanJournalofVeterinaryResearch: 62(2):2116,2001. LuckschanderN,AllenspachK,HallJ,SeiboldF,GrneA,DoherrMG,Gaschen F,Perinuclearantineutrophiliccytoplasmicantibodyandresponsetotreatment indiarrheicdogswithfoodresponsivediseaseorinflammatoryboweldisease JournalofVeterinaryInternalMedicine:20(2):2217,2006. McCannTM,RidyardAE,ElseRW,SimpsonJW,Evaluationofdiseaseactivity markersindogswithidiopathicinflammatoryboweldiseaseJournalofSmall AnimalPractice:Jun302007[Epubaheadofprint]. PetersIR,HelpsCR,CalvertEL,HallEJ,DayMJ,CytokinemRNA quantificationinduodenalmucosafromdogswithchronicenteropathiesbyreal timereversetranscriptasepolymerasechainreactionJournalofVeterinary InternalMedicine:19(5):64453,2005. MnsterM,HraufA,BilzerT,[Assessmentofdiseaseseverityandoutcomeof dietary,antibiotic,andimmunosuppressiveinterventionsbyuseofthecanine IBDactivityindexin21dogswithchronicinflammatoryboweldisease]Berliner undMnchenertierrztlicheWochenschrift:119(1112):493505,2006. RidgwayJ,JergensAE,NiyoY,Possiblecausalassociationofidiopathic inflammatoryboweldiseasewiththrombocytopeniainthedogJournalofthe AmericanAnimalHospitalAssociation:37(1):6574,2001. RisticJM,StidworthyMF,Twocasesofsevereirondeficiencyanaemiadueto inflammatoryboweldiseaseinthedogTheJournalofSmallAnimalPractice: 43(2):803,2002. RudorfH,vanSchaikG,O'BrienRT,BrownPJ,BarrFJ,HallEJ, Ultrasonographicevaluationofthethicknessofthesmallintestinalwallindogs withinflammatoryboweldiseaseTheJournalofSmallAnimalPractice: 46(7):3226,2005. SpichigerAC,AllenspachK,OntsoukaE,GaschenF,MorelC,BlumJW,Sauter SN,AbundanceofmRNAofgrowthhormonereceptorandinsulinlikegrowth factors1and2induodenalandcolonicbiopsiesofdogswithchronic

enteropathiesJournalofVeterinaryMedicineA,Physiology,Pathology,Clinical Medicine:52(10):4917,2005. StrombeckDR,ChronicinflammatoryboweldiseaseIn:StrombeckDR,(ed.) SmallAnimalGastroenterology,Davis,CA:StonegatePublishing,1979:240 261. TumultyJW,BroussardJD,SteinerJM,PetersonME,WilliamsDA,Clinical effectsofshorttermoralbudesonideonthehypothalamicpituitaryadrenalaxis indogswithinflammatoryboweldiseaseJournaloftheAmericanAnimal HospitalAssociation:40(2):1203,2004. ZoranD,NutritionalmanagementofgastrointestinaldiseaseClinical TechniquesinSmallAnimalPractice:(4):2117,2003.

Topic 9: Juvenile Cataracts in West Highland White Terriers Lindsey Buracker and John Robertson Introduction to this Topic To be able to prosper in their environment, dogs need healthy eyes. Evolution has provided dogs with a very keen sense of vision and the ability to see in extreme conditions of light and darkness and to be highly perceptive of movement. Although we generally dont think of them as primal predators, every Westie is born with this in their blood, and predators need sharp vision. At times, injuries to the eye and the surrounding lids and gland, or disease, will disrupt vision. Unfortunately, highly complex structures such as the eye, may also suffer from defects in ocular development, such as the formation of juvenile cataracts. Simply defined, a cataract is an irregularity and opacity in the lens. It may be helpful to readers to give a few short definitions that will help when reading material included in this Topic. Most cataracts are seen in older dogs. If the cataract forms as a result of disease (like infections or diabetes mellitus), exposure to some chemicals and intense irradiation (cataracts are an unwanted side effect of radiation therapy of the head and neck), or injury, the cataract is considered to be acquired as a result of the injurious process. A juvenile cataract is one that has formed before birth (congenital juvenile cataract) or which develops shortly after birth, as the eyes of the dog mature (a developmental juvenile cataract). Juvenile cataracts may be caused by the expression of defective genes and/or problems affecting the dam during gestation. In some breeds of dogs, the incidence of cataracts increases with age and is considered hereditary (inherited as a genetic disease from one or both parents). The outcome of all is the same a decrease in visual acuity for the dog. The anatomy of the eye and the phenomenon of vision The parts that make up the eye are shown in the figure appearing below (Source: The School of Biomedical Engineering at Georgia Tech). The eye is essentially made up of two connected parts. The smaller part, called the anterior chamber, is bounded by the transparent cornea at the front of the eye and the lens. The larger part of the eye, the posterior chamber is formed externally by the tough white part called the sclera, and contains the lens, the gelatinous vitreous humor, and the neural receptor membrane of vision, the retina. The eye is composed of several layers of cells, blood vessels (in the uveal tract), and connective tissue. The lens is a living tissue. It is a tight clustering of specialized cells, enclosed in a capsule, located behind the iris and in front of the vitreous body, and is held in place by fibers, the anterior vitreous face, and the iris

(Magrane, 1972). The lens is normally quite flexible. Tension and relaxation on the edges of the lens, controlled by the small muscles and fibers, alters lens shape. By changing its shape, the lens can alter its refractive power. As a living tissue, the lens grows with advancing age, needs nutrition (acquired by diffusion through the aqueous and vitreous humors, can be damaged by injury and disease, and can show limited healing. Lens shape varies throughout life. Lets discuss a few important points about the lens, since cataracts form within the lens. The capsule, surface layer or epithelium, and fibers are the three main parts components of the lens. The capsule is a thickened smooth membrane made of collagen and produced by the lens epithelium and fibers. It completely surrounds the lens and possesses elastic properties, so when not under tension, the lens assumes a rounded shape. The epithelium is comprised of cells that elongate over time and are eventually transformed into lens fibers, which contain high concentrations of the protein crystallin (which help the lens to refract and transmit light). These fibers are tightly packed and extend the full length of the lens. Continual growth of the lens adds more elongated cells and fibers and produces an arrangement similar to the layers of an onion (Magrane, 1972). Damage to any of the components of the lens can result in formation of a cataract. One final point the formation of the lens helps orchestrate the overall development of the eye. The lens forms relatively early during the development of the eye and helps induce the formation of both chambers and many of the components of the eye. This pivotal role of the lens in controlling development of the eye is important for several reasons. First, if the lens does not properly form, this can affect the development of other components of the eye. Second, disease or defective gene expression that occurs during pregnancy can significantly affect lens formation and, by extension, the development of healthy eyes. Third, the presence of cataracts at the time of birth clearly indicates problems with lens development, but also may signal the potential for problems elsewhere in the eye. Finally, it is important to remember that puppies are born with incompletely matured eyes and some of the process of development takes place after birth. A good rule of thumb is that formation of the eye is complete by about 12 weeks of age, in most breeds of dog. Dogs should have good visual acuity by this age. Normal vision summarized! Light energy from the surroundings produces electrochemical changes in specialized nerve cells (the rods and cones) in the retina. These changes result in the generation of signals (called nerve action potentials) that are relayed to the brain, where they are processed and consciously appreciated as a vision (Magrane, 1972). The lens is a key part of the system that focuses and transmits light to the retina so that signals that eventually produce vision are received on the retina.

Examination of eyes you and your veterinarian Owners and breeders are often the first to detect a problem with the eyes and vision. Some common signs that something is not right include: The eyes, lids, and membranes of the eye just dont look right; there may be discoloration, irregularities in shape and size, or perhaps the eyes are inappropriately proportioned to the size of the head. Shown at the right is the eye of a dog in which there is a cataract, causing the lens to appear milky white/opaque, and in which the pupil is dilated. Puppies may bump into things in their path (this has to be differentiated from just clumsiness or poor coordination), Puppies appear reluctant to move about or are overly shy (most Westie puppies are pretty affable and playful), Puppies are reluctant to go in to darkened areas during exploration, Puppies appear to cue interactions based on hearing rather than on both hearing and seeing (that is, they may search for sounds instead of searching visually). If a problem with vision is suspected, you should take your Westie to your veterinarian. All thorough physical examinations of dogs include an evaluation of the eyes. Most evaluations by veterinarians have common elements, and some of the routine evaluation is done with simple tests: Evaluation of the gross appearance of both eyes, comparison of one eye with the other and with the head in terms of size, shape, coloration, tonicity (see below), and integration with facial shape, Detection of visual signal processing: the veterinarian will shine a light in one eye and then the other to see if there is constriction of the pupils in response to light. This is actually a simple test of a complex process, since it tests whether light is focused on the retina, which then creates a visual signal that is then transmitted on nerve fibers to the brain. There the signal is interpreted as vision, at the same time that automatic mechanisms in the central nervous system regulate the size of the pupils, (Figure, right, [not a Westie!] The ability to track movement in a lighted area is assessed by the response of the dog to hand movements near the eyes. In many examinations, the veterinarian will see if the dog will blink in response to movement near the eyes assessing both visual perception and the automatic blink response, Tonicity (firmness) of the eyes can be first evaluated by gently applied pressure to the eyes through the lids. Most dogs do not mind this part of

the examination and it helps determine if the eyes are firm, but not too firm, and if there are irregularities or pain, Ophthalmic evaluation of the anterior chamber, posterior chamber, and intraocular structures (lens, iris, pupil, retina).

Many eye problems can be detected with these simple tests. In some cases, owners and veterinarians may wish to seek out a specialist (a veterinary ophthalmologist) for further testing. Specialists commonly see patients by referral and have specialized equipment and facilities for examination and treatment of eye diseases. Many specialists are certified by examination boards after years of advanced training on treating diseases of the eye. Shown at the right, Dr. Phillip Pickett, a board-certified veterinary ophthalmologist, and his veterinary ophthalmology technician, Ms. Betsy Midkiff, perform an examination of a Golden Retriever service dog, using an external lens and light source, which allows the retina to be more closely examined. In the next figure, shown below, left, a hand-held ophthalmoscopic evaluation is conducted. The device being used is a more sophisticated version of the ophthalmoscope used by most veterinarians and has increased magnification to allow detection of smaller defects. The value to Westie owners in seeking regular evaluations of their dogs should be evident. Health problems can be detected, diagnosed and many (most) are treated effectively. When more complex treatments, such as surgery, are needed to treat problems and to correct defects, it makes sense to seek the services of a specialist. These specialists may have facilities and tools for treatment and, since they concentrate exclusively on treating diseases of the eye, they are generally more practiced (have seen more cases and more difficult cases), and may have access to the latest research findings and tools.

Cataracts - An Overview A cataract is an opacity occurring in the lens, usually appearing as a cloudy white discoloration, and is a site of injury and cell death within the lens. Unfortunately, cataracts are one of a number of diseases that Westie owners have to consider when breeding and when raising Westies. Cataracts can affect only one or both eyes. Cataracts are among the most common intraocular lesions and are a

leading cause of vision loss in dogs. They can be classified according to several criteria: age at presentation, localization, etiology (cause), appearance, and stage (Adkins, et al., 2005). In the diagram at the lower right (Source: http://www.animaleyecare.net/diseases/cataract.htm) several different types of cataracts are diagrammed. In the eye shown, a small, focal, incipient (developing) cataract is shown. Unfortunately, the position of this cataract, in the center of the lens, will interfere with the direct path of light energy to the retina at the back of the eye, and will interfere with visual acuity. Also in this figure are simplified diagrams of immature and mature cataracts. These terms, immature and mature, refer to the developmental stage of the cataract. Immature cataracts are newly formed and may occupy only a portion of the lens; mature cataracts have been present longer and may involve the entire lens. In some mature cataracts, the cells in the lens have degenerated and liquefied. This debris is held within the lens capsule, a membrane that surrounds the lens. Cataracts are more common in adult dogs than young dogs. Common causes of cataracts in adult dogs include direct penetrating trauma to the eye that damages the lens capsule and lens cells, ocular diseases that interfere with nutrition of the lens (such as glaucoma) or inflame the eye (including panophthalmitis and uveitis, see following), and some systemic diseases such as diabetes mellitus. Cataracts diagnosed in younger dogs (usually less than 6 months old), called juvenile or congenital cataracts, can be hereditary or occur as a result of problems during gestation. Cataracts may also be acquired in association with viral infections during gestation or in newborns In many species (including people and dogs), cataracts can be associated with other ocular congenital abnormalities. These include coloboma, which present as holes or craters in the posterior lining of the eye; retinal dysplasia, or failure of the retina to mature; and aniridia, when the iris fails to develop normally (Magrane, 1972). Exposure to chemical substances (both local and systemic exposures), radiation, and electricity have been known to cause cataracts (Magrane, 1972). Uveitis, an inflammation of the vascular (uveal) layer of the eye, can be caused directly by degeneration of the lens, in some cases. With the formation and

disruption of mature and hypermature cataracts, lens protein can leak from inside the lens capsule into the anterior chamber, spontaneously or as a result of trauma, and induce severe inflammation. The relationship between glaucoma and cataract formation is complex. Glaucoma is a disease condition characterized by elevated intraocular pressure. In some cases of glaucoma, interference with the production and drainage of fluids within the eye is the primary disease process that increases intraocular pressure. The increased pressure within the eye may interfere with lens health, resulting in the formation of cataracts. In other cases, cataracts and other lens diseases may be a cause of glaucoma. For example, lenses with cataracts may become dislodged from their normal fibrous connections and migrate into the pupil, occluding fluid flow from the posterior chamber to the anterior chamber. This essentially plugs up the drainage of fluid and pressure increases within the eye, resulting in glaucoma. Juvenile Cataracts As previously stated, some juvenile cataracts are hereditary, passed on as one or more mutated genes. If the genomic abnormality is a recessive gene, this means that both parents could carry a single defective copy of one of a number of genes that regulate lens development, but show no signs of juvenile cataract formation. However, breeding this pair can produce puppies that have juvenile cataracts, when copies of the defective recessive gene are combined from the normal parents with the single recessive mutation (see figure below) (Gelatt, et.al., 1983).
Father = Carrier J j + Mother = Carrier J j

J J No cataract gene

j J Carrier

J j Carrier

j j AFFECTED

J = dominant gene, no cataracts j = recessive gene, can express cataracts JJ = no recessive cataract gene present J j = carries the cataract gene but is not expressed j j = CATARACTS This means that if both parents are carries of the disease 1 in 4 of their puppies will have juvenile cataracts.

Causes of juvenile cataracts Recent studies in several breeds of dogs, and in people, have identified multiple defective genes that may participate in the generation of cataracts, suggesting

that in some cases the development of cataracts has a complex mode of inheritance (that is, it is a polygenic trait). Gelatt and coworkers (2003), and others (Gelatt, et. al., 1985; Barnett, et.al., 1985, Leppanen, et. al., 2001; Mellersh, et. al., 2006; Starr, et.al. 2007; Muller, et.al, 2008) noted that in the 300 breeds of dogs, 20 are known to have hereditary cataracts and the presence of defective genes leading to cataract formation is suspected to affect another 125 breeds, making hereditary/congenital cataracts one of the most common genetic diseases in dogs. Commonly affected breeds are shown in Table 1, found near the end of this chapter. Hejtmancik (2008) recently reviewed the molecular genetics of congenital cataracts in people. In people, congenital or infantile cataracts are those that occur within the first year of life, and juvenile cataracts are defined as those occurring up to age 10. Approximately 8-25% of congenital cataracts were considered to be inherited the result of transmission and expression of faulty genes. Mutations in 26 specific genes have been identified as causes of human congenital cataracts, with about half of the mutations affecting the development of lens crystallin proteins, and the remainder affecting expression of connexins, heat shock proteins and other structural proteins. Hunter and coworkers (2006) took a first step to identify linkages between breed and cataract formation in dogs, using a highly complex genomic analysis, known as radiation hybrid mapping. Their preliminary work allowed them to locate 21 canine homolog regions to human cataract gene defects and to begin analysis of these homolog regions for specific defects. This work is ongoing. Several groups of researchers have conducted genetic and genomic analyses on dogs to see if similar mutations cause juvenile cataracts. In an early study, Zhang and coworkers (1991) were unable to find mutations in key genes encoding lens crystallins in Miniature Schnauzers. More recently, Sidjanin and coworkers (2005) were unable to identify mutations in a human gene linked to congenital cataracts (galactokinase-1) in a pedigree of Labrador Retrievers affected with juvenile cataracts. Mellersh and coworkers (2006) were able to identify mutations in genes regulating heat shock proteins (HSF4) in Staffordshire, Bull, and Boston Terriers affected with hereditary cataracts. However, Muller and coworkers (2008) were not able to identify mutations in HSF4 in Dachshunds or Enttlebucher Mountain Dogs with hereditary cataracts. Clearly, the search for the complex mix of genes responsible for causing hereditary cataracts in dogs must continue. This is not going to be a trivial (or inexpensive) task. Havanese dogs are a toy breed variant of the Bichon breed that have multiple congenital abnormalities, including cataracts, liver shunts, heart murmurs, and a high incidence of osteochondrodysplasia. Gelatt and

coworkers (2005) noted an incidence of hereditary cataracts in over 11% of Havanese dogs, a figure substantiated by the breed club. Starr and coworkers (2007), using a canine specific microarray, found 113 differentially regulated genes in this breed and now are attempting to determine the single, multiple and linked expressions that may be responsible for the multiple congenital anomalies. Given a cost of about $1000 per analysis using the Affymetrix Canine GeneChip 2.0, it may take time to sort this out. Prevention of Cataracts Since we know that some types of cataracts have a hereditary basis, its essential for dog breeders to keep thorough records of litters and diseases affecting each pup. Breeders should keep in regular contact with the owners of pups from their litters throughout the life of the dogs. The presence of cataracts in young dogs (less than 6 months old) and in multiple dogs from the same breeding is very suggestive of an underlying genetic problem. One caveat if, during gestation, there is evidence of ill-health in the dam, cataracts may be the result of damage to the developing puppies. Most experienced breeders are very aware of the need to keep pregnant dams well-nourished and free from exposure to potentially damaging viruses and chemicals in the environment. In the event that a litter is delivered and one or more pups develop cataracts, the breeder has a responsibility to 1) seek veterinary diagnosis and discuss treatment options for affected pups, 2) examine the breeding and pedigree of both dam and sire for similar problems (or the presence of other congenital defects from this paired breeding), and 3) refrain from breeding either sire or dam until the relationship of breeding to cataract development can be clearly determined. As noted above, hereditary cataracts were identified as a significant problem in the Miniature Schnauzer breed in the 1970s and 1980s. Following the leadership provided by breed associations, veterinarians and research scientists, this autosomal recessive trait was identified and bred against, resulting in a substantial decrease in the incidence of the disease in Miniature Schnauzers today. By identifying those dogs that are carriers of the disease and not breeding them, juvenile cataracts can be controlled and eventually eliminated. The importance of keeping accurate breeding records and long-term follow-up on litters cannot be understated. Potential owners need to do an extensive background check before purchasing a Westie from a breeder. These potential Westie owners need to be sure there are accurate records for each damn and sire, a solid bloodline, and no overt problems or diseases noted in each litter from the time of whelping. If Westie owners and breeders work together, this disease will eventually be eliminated from breeding stock.

Treatment of Cataracts Although there is no cure for cataracts, treatment can be highly successful and is recommended for two reasons. First, the presence of cataractous lenses can lead to the development of serious eye diseases such as glaucoma. The breakdown of cataracts can cause inflammation in the eye (panophthalmitis), which leads to squinting, tearing or watering of the eye, and increased redness of the conjunctiva, the white part of the eye. Both glaucoma and panophthalmitis can be serious and progressive problems, potentially leading to blindness. Second, the presence of even small cataracts can lead to losses of visual acuity for affected dogs. In many cases, dogs will learn to compensate for small visual defects by head turning and memorizing their environment. Well-compensated dogs may not need to have treatment for their small cataracts. However, if there is evidence that dogs with cataracts cannot find their way in the environment (bumping into objects, reluctance to walk or run, difficulty in finding sources of food and water), consultation should be sought with your veterinarian. Surgery to remove lenses with cataracts and replacement with artificial lenses is a common and effective method of treatment for dogs with cataracts. Surgery can be performed to remove the cataract, as long as the rest of the eye is healthy and the dog is healthy enough to undergo general anesthesia (although cataract removal in humans does not require general anesthesia, canines must be completely anesthetized for lens removal/replacement). A good outcome of surgery is dependent upon the selection of the patient, surgical technique, and perioperative (referring to the time period surrounding surgery, before, during, and after) screening and therapy. Patients are selected based on a number of different criteria including age, health, and progression of the disease. As with any procedure, the risk of failure for the operation increases with age. Increased age makes surgery slightly more risky because it will be harder for the animal to tolerate anesthesia and for the body to recover and heal itself post operatively. In order to prepare for surgery, your veterinarian may want you to administer a few medications to your pet. These could include a topical non-steroidal antiinflammatory agent or corticosteroids, placed on the eye, and you could be asked to give aspirin orally to reduce the pain (Na-Young, et al., 2006; Kecova, et al., 2004. Your veterinarian will also be likely to perform a complete ophthalmic examination, collect blood for a complete blood count and serum chemistry profile (to help evaluate anesthetic risk), and urinalysis, in order to determine that your animal is healthy enough to undergo surgery (Adkins, et al., 2005). An electroretinogram (ERG) may be obtained by the veterinary ophthalmologist before cataract surgery is performed. This measurement involves placing one or more sensors on the head of the dog and then stimulating the visual pathway (generally with variably pulsed light). The dog is generally sedated while this procedure is done, to minimize movement, allow placement of sensors, and to maximize transmission of light to the retina. The reason that the ophthalmologist

may recommend an ERG is to be sure that the dog has an intact vision system and that the only significant ocular problem is the presence of the cataract. Dogs that have other eye problems (such as glaucoma with retinal degeneration leading to retinal blindness) will not have significant improvement in vision after cataract surgery. However, if the lens with cataract is an element in causing glaucoma, lens extraction may be helpful in preserving the eye, even with limited or no vision. Several different surgical treatments are used for cataracts. Typically, dogs are anesthetized and prepared for surgery. The pupil is dilated with drugs and topical anesthetics and anti-infective are placed on the surface of the eye. Then, the surgeon will make a small incision that will allow access to the inside of the eye. For some dogs, the surgeon will then extract the lens (and cataract) by cutting any ligament connections to the lens, holding the lens capsule, and gently removing the lens, taking care not to disturb fluids in the posterior portion of the eye. Depending on the dog and surgeon, a prosthetic lens (see figure on the right) may then be implanted and the surgical site closed with very fine suture. (Source of this figure: http: //www.animaleyecare.net/ diseases/ cataract.htm Phacoemulsification refers to a type of cataract surgery in which the lens is emulsified (essentially liquefied) with an ultrasonic instrument, and then the lenticular debris is removed from the eye. After the removal of all the residual debris from the emulsified lens, an intraocular prosthetic lens is implanted, in order to reduce the possibility of the patient suffering from extreme farsightedness. The surgical site is sutured after lens replacement. In some cases, owners and surgeons may elect not to have a prosthetic lens implanted. Dogs without a functional lens are unable to focus light on the retina, and will only be able to perceive vague patterns due to variations in light and darkness. While this may seem to be very undesirable to us (people are very visual), many dogs can get along well with limited vision. In fact, one of the coauthors of this Topic (JR) has examined dogs in his clinical practice and found them to be blind without owners knowing this! These dogs, if blindness has had gradual onset, compensate with memory and other senses. With every surgery there is a risk, and cataract surgery is no exception. The prognosis for a return of some degree of visual acuity after surgery is normally very good (approximately 90%) depending on the stage of the cataract and other concurrent findings. Complications of surgery may include (Williams, et al., 1996):

Post-operative pain and infection (diligent aftercare of the affected eye is needed for several weeks) (see below), Glaucoma, uveitis or panophthalmitis, or keratitis, Retinal detachment

Post-operative care is very important in the healing process. The eye will be bandaged in order to immobilize the eye, provide added warmth (conducive to healing) and prevent infection. In some cases, the veterinarian may temporarily suture the eyelid closed to provide additional protection to the eye during healing. Your veterinarian may ask that you apply eyedrops, ocular lubricant, or other topical treatment to the eye following surgery. Oral corticosteroids and antibiotics may also be given for a short time after surgery. A week following surgery, the eyelid suture (if used) will be removed. Owners must be cautious in handling their dogs and may wish to use a protective collar to prevent the dog from scratching at the eye. They should also restrict movement and lessen excitement during the first week prior to surgery (Na-Young et al., 2006). Cataract surgery has significantly improved over the past few decades. At first, surgeons simply removed the intracapsular lens and used irrigation-aspiration techniques to extract any remaining lens cortical material. Recently, phacoemulsification and aspiration have become common methods for lens extraction. New surgical instruments have also been developed that allow surgeons to choose from a one-handed or two-handed system for fragmentation and aspiration. An operating microscope allows the surgeon to perform delicate work on the eye and lens fragments during surgery (see below). (Source: http:// www.spokesmanreview.com /stories/2005/dec/15/cit_cataracts.IMG_12 -15-2005_8F69DK0.jpg Research is currently underway to develop ocular surgery lasers which optimize cutting, welding, and coagulation during surgery. Not only would this make cataract surgery more precise, but it would decrease the chances of certain post-operative complications. Research is also being done to compare the different types of intraocular lenses available. These include acryl foldable, silicone, and polymethylmethacrylate (PMMA) (Na-Young, et al., 2006). Developing the best surgical technique, as well as material for the intraocular lenses, will be significant steps in ensuring cataract surgery will be even more successful and cause fewer problems in the future.

New techniques for cataract surgery are currently being tested to minimize the size of the incision and create a more accurate suture placement. Wilkie and colleagues (2008) have modified the current approach for suture fixation of an intraocular lens (IOL) implant in canines. This new technique uses smaller suture needles in order to suture the IOL into the eye and position it appropriately. Surgeons, using an intraoperative microscope, could visualize the suture and needle during the entire procedure, and, using a foldable IOL, implant the lens through the small incision, creating less trauma and complications. Though there is a concern that this new technique, which uses two sutures, could have complications, Wilkie et al. (2008) report no instances of suture slippage or instability to date in cases followed for many months. In an attempt to find an alternative to ultrasonographic phacoemulsification, several researchers have been investigating the use of visible, ultraviolet, and infrared radiation to remove the cataractous lens. With each of these methods, certain complications and risks arise. For example, UV radiation is potentially carcinogenic and mutagenic, and infrared lasers can result in a larger area of damage. Duran and Zato (2001) found that by using an Erbium YAG infrared laser they could obtain optimal cutting, welding, and coagulating qualities because the wavelength of the Erbium laser is strongly absorbed by the water contained in biological tissue. When clinically tested against phacoemulsification there was no significant advantage found; both methods showed improved visual acuity. Duran et al., (2001) stated that there are certain disadvantages to using the Erbium laser. For example, the laser does not penetrate very deeply and therefore creates narrow furrows. Because the laser has a low aspiration rate, removal of the flaky nuclear material can be hazardous and time-consuming. More research is needed to improve the laser technique in order for it to surpass the current phacoemulsification procedure for cataract surgery. Prevention There is no real way to prevent cataracts unless they are known to be hereditary (inherited as recessive genes). If that is the case, breeding is not recommended to ensure the disease will not be passed on within the breed. The Canine Eye Registration Foundation (CERF) (http://www.vmdb.org/feb01.html#dxspot) warns breeders against using those dogs affected with cataracts and also those that are carriers of the disease. Table 1. Inherited cataracts in the dog may occur independently or in association with other ocular diseases. The breeds that appear to develop inherited cataracts along with their age of onset are listed below. If a dog is diagnosed with

inherited cataracts, the dog should obviously not be used for breeding because of the likelihood of perpetuating the disease in the offspring. (Source: http: //www.peteducation.com /article.cfm?cls=2&cat=1606&articleid=407
Breed
Afghan Hound American Cocker Spaniel Boston Terrier Chesapeake Bay Retriever German Shepherd Golden Retriever Labrador Retriever Miniature Schnauzer Old English Sheepdog Siberian Husky Staffordshire Bull Terrier Standard Poodle Welsh Springer Spaniel West Highland White Terrier

Age of Onset
6-12 months 6 + months Congenital 1 + years 8 + weeks 6 + months 6 + months Congenital or 6 + months Congenital 6 + months 6 + months 1 + years Congenital Congenital

If cataracts are seen in young dogs (less than 6 months old and more commonly at an early age) the prudent approach is to assume cataracts to be hereditary. These dogs should not be bred, except in unusual cases specifically known to be associated with other causes. As long as owners and breeders work together juvenile cataracts could be controlled and even eliminated in some breeds. Currently genetic research is being done in order to identify those dogs that carry the recessive gene for juvenile cataracts. If all goes well there will be a simple DNA test that can be administered to determine which dogs are affected by the disease and therefore should not be bred. This research is being conducted by the Veterinary Genetic Services (VetGen) collaboration (http://www.vetgen.com). They are currently obtaining samples of DNA (via swab) from the families of dogs where two or more siblings are affected with the disease. By creating a large database with affected dogs in comparison to members of their family that are not affected with the disease it will be possible for VetGen to identify the gene that causes juvenile cataracts. References for this Topic Adkins E, Hendrix D, Outcomes of Dogs Presented for Cataract Evaluation: A Retrospective Study, Journal of American Animal Hospital Association 41: 235240, 2005

Andley UP, Crystallins and hereditary cataracts: molecular mechanisms and potential for therapy, Expert Rev Mole Med 8: 1-19, 2006 Barnett, K, Startup, F, Hereditary cataract in the Standard Poodle, Vet Rec 117:15-16, 1985 Duncan, M, Kozmik, Z, C, Cveklova, K, Piatigorsky, J, Cveki, A, Overexpression of PAX6(5a) in lens fiber cells results in cataract and upregulation of 51 integrin expression, Jour Cell Science 113: 3173-3185, 2000 Duran, s, Zato, M, Erbium:YAG laser emulsification of the cataractous lens, J Cataract Refract Surg. 27:1025-32, 2001 Gelatt, K, Samuelson, D, Bauer, J, Das, N, Wolf, E, Barrie, K, Andresen, T, Inheritance of congenital cataracts and microophthalmia in the Miniature Schnauzer, Amer J Vet Res 44: 1130-1132, 1983 Gelatt K, Wallace M, Andrew S, MacKay E, Samuelson D, Cataracts in the Bichon Frise, Vet Ophth 6:3-9, 2003 Gelatt, K, MacKay, E, Prevalence of primary breed-related cataracts in the dog in North America, Vet Ophth 8: 101-111, 2005 Hejtmancik, J, Congenital cataracts and their molecular genetics, Sem Cell Dev Biol 19:134-149, 2008-09-21 Hunter, L, Sidjanin, D, Johnson, J, Zangerl, B, Galibert, F, Andre, C, Kirkness, E, Talamas, E, Aclund, G, Aguirre, G,Radiation hybrid mapping of cataract genes in the dog, Mol Vision 12:588-596, 2006 Kecova H, Necas A, Phacoemulsification and Intraocular Lens Implantation: Recent Trends in Cataract Surgery, Acta Veterinarian Brno 73: 85-92, 2004 Leppanen, M, Martenson, J, Maki, K, Results of ophthalmic screening examinations of German Pinschers in Finland a retrospective analysis, Vet Ophth 4:165-169, 2001 Magrane, W, Canine Ophthalmology, 2nd ed. Lea and Febiger, Philadelphia, 1972 Mellersh, CS, Pettitt L, Forman OP, Vaudin M, Barnett KC, Identification of mutations in HSF4 in dogs of three different breeds with hereditary cataracts., Vet Ophth 5: 369-378, 2006

Mller C, Whlke A, Distl O, Evaluation of canine heat shock transcription factor 4 (HSF4) as a candidate gene for primary cataracts in the Dachshund and the Enttlebucher Mountain dog, Vet Ophth11: 34-37, 2008 Na-Young Yi, Shin-Ae Park, Man-Bok Jeong, Won-Tae Kim, Se-Eun Kim, Je-Min Chae, Kang-Moon Seo, Phacoemulsification and acryl foldable intraocular lens implantation in dogs: 32 cases, Journ Vet Science 7: 281-285, 2006 Sidjanin, D, McElwee, J, Miller, B, Aguirre, G, Cloning of canine galactokinase (GALK1) and evaluation as a candidate gene for hereditary cataracts in Labrador Retrievers, Animal Genetics 36:265-266, 2005 Starr, A, Famula, T, Markward, M, Baldwin, J, Fowler, K, Klumb, D, Simpson, N, Murphy, K, Hereditary evaluation of multiple developmental abnormalities in the Havanese dog breed, Jour Heredity 98:510-517, 2007 Williams DL, Boydell IP, Long RD, Current concepts in the management of canine cataract: a survey of techniques used by surgeons in Britain, Europe and the USA and a review of recent literature, Vet Rec 138: 347-353, 1996 Wilkie, D, Gemensky-Metzler, A, Stone, S, Basham, C, Norris, K, A modified ab externo approach for suture fixation of an intraocular lens implant in the dog, Vet Ophth 11:43-48, 2008 Zhang, R, Samuelson, D, Zhang, Z, Reddy, V, Shastry, B, Analysis of eye lensspecific genes in congenital hereditary cataracts and microophthalmia of the Miniature Schnauzer dog, Invest Ophth Vis Science 32:2662-2665, 1991

Topic 10: White Shaker Disease Syndrome Lindsey Buracker and John Robertson Introduction and Overview White Shaker Disease Syndrome (WSDS) is a neurologic disease seen primarily in dogs with white coats, particularly in West Highland White Terriers, Maltese Terriers (Bagley, et al., 1993), and Samoyeds (Cummings, et al., 1986). The disease presents with a very unique generalized tremor, in young (5 months to 3 years old) dogs of either gender (Yamaya, et al., 2004). The National Institutes of Neurological Disorders and Stroke defines tremor as unintentional, somewhat rhythmic, muscle movement involving one or more areas of the body: (Source: http://www.ninds.nih.gov/disorders/tremor). There have been numerous cases of WSDS in breeds of dogs without a white coat (Dachshund, among others) (Yamaya, et al., 2004), and in the adult years of their life. Therefore, the terms shaker dog syndrome, white shaker disease and little white shaker dog have been used as synonyms of WSDS (Yamaya, et al., 2004). The cause of the disease is not known and there is little research being done on this condition in any breed. Because there are several neurologic and neuromuscular diseases that can produce tremor and incoordination, it is essential that the Westie owner immediately get a thorough evaluation of their dog and that an accurate diagnosis is made. Symptoms and Diagnosis WSDS is characterized by a relatively sudden onset of constant tremors over the entire body, which includes the head and eyes. A tremor is a characteristic, abnormal set of repetitive movements that occurs when opposing muscle groups alternately contract and relax (Smith and Thacker, 2004). Uncontrolled eye movements, referred to as opsoclonus, consist of rapid, involuntary, multidirectional (horizontal and vertical) rapid eye movements. The tremors are exaggerated by excitement, handling, forced locomotion, and high levels of stress (Summers, et al., 1995). Although some dogs with WSDS may have constant tremors, they are alert and responsive to their owners and environment. These dogs generally show no deficit in cranial nerve function, such as facial touch sensation or dilation/constriction of the pupils. In some instances, tremors may be severe enough to cause an ataxic or wobbly uncoordinated gait, or cause hypermetria, shown as overreaching with the legs when walking forward (a form of ataxia)(Smith and Thacker, 2004). There are other diseases that can manifest as tremors, all of which must be ruled out before appropriate treatment can be administered (Smith and Thacker, 2004). Exposure to toxic substances such as moldy food, lead

poisoning, organophosphate poisoning, various inflammatory or infectious diseases of the nervous system, and epileptic patients can all show signs of tremors. These possibilities are ruled out by performing an electrophysiological evaluation of nerve function and nerve biopsy. After a variety of baseline tests are performed to eliminate the aforementioned possibilities, those dogs with normal test results and typical signs are diagnosed with WSDS. Occasionally, a head tilt may be seen. Unfortunately, head tilt is seen with other central or peripheral neurologic disorders and can even be seen with ear problems. The association of head tilt and WSDS should be established by thorough examination and by elimination of other potential causes (Smith and Thacker, 2004). Westies also suffer another neurologic disease that is not related (as far as we know now) to WSDS and which must be considered in the differential diagnosis since it may present as tremors at a young age. Krabbe disease, or globoid cell leucodystrophy (GCL), is a neurologic disease in which nerve cells accumulate material inside of the cells, due to a deficiency of a specific enzyme, needed for normal cell metabolism. West Highland white and Cairn terriers are the two breeds most affected by GCL, which is inherited as an autosomal recessive trait (Parker, et al., 1995, Wenger, et al., 1999). Clinical signs tend to appear beginning around 3 months of age. Dogs may die from the disease in less than a year or may be euthanized due to poor quality of life (Parker, et al., 1995). Common clinical signs include ataxia of the hindlimbs, muscle wasting, head and body tremors, and even blindness. In many dogs, there is also a substantial degenerative change in the peripheral and autonomic nervous systems (Summers, et al., 1995). In the brain of affected dogs, pathologists have noted gray discoloration, firmness of the cerebral cortex, and ventricular dilation, reflecting tissue loss (Summers, et al., 1995). The brains of affected dogs appear reduced in size, with a notable decrease in the amount of white matter (Summers, et al., 1995). GCL is one of a number of diseases called storage diseases in which intermediate metabolites build up within cells. GCL is caused by deficient galactocerebrosidase activity (GALC), and is a severe disorder of the peripheral and central nervous system. When the enzyme GALC is defective, psychosine, a metabolite highly toxic to myelin-forming oligodendrocytes and Schwann cells accumulates. Myelin makes up most of the white matter in the central nervous system and is also present in the peripheral nervous system. Myelin is essential for normal functioning of nerve fibers in both systems; hence the neurological deterioration from myelin breakdown found in this disorder. This leads to severe neurological symptoms such as progressive blindness, seizures, and eventually death.

Deficiency of galactocerebrosidase has been demonstrated not only in the brain but also the liver and kidneys of affected dogs (Fletcher et al., 1972, Yunis, et al., 1976, Wenger, et al., 1999). To determine if a dog is affected with GCL, a blood sample is collected and analyzed by polymerase chain reaction (PCR) for the enzyme deficiency (Cifti, et al., 2000). Although not done commonly, examination of a nerve biopsy using electron microscopy may aid in reaching a diagnosis and MRI can also be useful (Cozzi, et al., 1998; Wenger, et al., 1999). Krabbe disease has been reported in humans, dogs, mice, monkeys, and sheep (Fletcher, et al., 1972). In humans diagnosed in infancy, death usually occurs before 2 years of age, but the disease has also been identified later in life. Canine GCL most closely resembles the late-onset form in human patients and unfortunately there is no effective treatment (Yunis, et al., 1976).

(Source: www.westierescueca.com/ images/health2_sm.jpg) The diagnosis of WSDS is generally made by history, age at onset and symptoms. Blood cytology, chemistry and x-rays, as well as a physical exam, are usually normal and have not proven valuable to aid in a diagnosis. A sample of cerebrospinal fluid may be collected for analysis, since an increase in the number of lymphocytes has been noted in some cases (Smith and Thacker, 2004). WSDS is rarely a fatal disease. Causes Though the exact cause is not yet known, WSDS is most often associated with a mild central nervous system inflammation (nonsuppurative encephalomyelitis) (Smith and Thacker, 2004). The cerebellum is commonly affected and dysfunction of this part of the brain could be one of the initiators of the tremor. It is not known if the inflammation is the true cause or if there is an associated neurotransmitter abnormality in those dogs with WSDS. Further research should be done to rule out that possibility as well as an underlying virus as the cause of the tremors. There has also been some speculation that WSDS can be congenital in some breeds (West Highland White Terriers, Maltese Terriers, and Samoyeds).

Treatment and Prevention Early diagnosis is beneficial in treating dogs with WSDS, as many will respond in a few days to immunosuppressive levels of corticosteroids (anti-inflammatory drugs) (Yamaya, et al., 2004). Corticosteroids suppress the underlying disease process, whatever its origin. The tremors can be reduced with diazepam (Valium), which is used to diminish anxiety or modify behavior, as a muscle relaxant, or an anticonvulsant (Smith and Thacker, 2004). In some cases, dogs will have to remain on a low dose of corticosteroids for the duration of their life in order to remain free of signs of the disorder. There are a few adverse affects that can occur from taking high doses of corticosteroids. Some of these include vomiting, gastrointestinal bleeding, ulcers, and diarrhea (Smith and Thacker, 2004). Even though the complications can be serious most can be managed clinically. Unfortunately, since the underlying cause of WSDS is not yet known, there is no way to prevent the disease. Some dogs experiencing tremors may convulse, and just before seizures may refuse to eat or seem disconnected with their environment. Affected dogs may need to be encouraged to eat and drink. Some owners have noted that hand feeding and raising food and water bowls off the floor is helpful (Swingle, C, 2008). Symptoms can lessen or resolve when the dog is relaxed or sleeping (Summers, et al., 1995). Some dogs respond well to being crated in a minimally dark room that is quiet during times of high stress. In summary, WSDS is a disease that affects primarily white-coated dog breeds, including Westies. Clinical signs, including involuntary tremor, are seen in young dogs. An accurate diagnosis is essential in order to help affected dogs, which can be sustained with treatment. Further research is needed to determine the cause(s) of WSDS. References Bagley, R, Kornegay, J, Wheeler, S, Plumer, S, Cauzinille, L, Generalized tremors in Maltese: clinical findings in seven cases, Jour Amer Anim Hosp Assoc 29: 141-145, 1993 Ciftci K, Trovitch P, Applications of genetic engineering in veterinary medicine, Elsevier Science, Philadelphia, 2000 Cozzi F, Vite C, Wenger D, Victoria T, Haskins M, MRI and electrophysiological abnormalities in a case of canine globoid cell leucodystrophy, Journ Small Anim Pract 39: 401-405, 1998

Cummings, J, Summers, B, DelaHunta, A, Lawson, C, Tremors in Samoyed pups with oligodendrocyte deficiencies and hypomyelination, Acta Neuropath 71: 267-277, 1986 Fletcher, T, Kurtz, H, Animal model for human disease: Globoid cell leukodystrophy, Am J Path 66: 375-378, 1972 National Institute of Neurological Disorders and Stroke NINDS Tremor Information Page/Tremor Fact Sheet http://wwwninds.nih.gov/disorders/tremor/tremor.htm Parker, A, "Little white shakers" syndrome: generalized, sporadic, acquired, idiopathic tremors in adult dogs. In J.D. Bonaguara and R.W. Kirk (eds) In J.D. Bonaguara and R.W. Kirk (eds) Kirk's Current Veterinary Therapy XII Small Animal Practice. pp. 1126-1127. W.B. Saunders Co., Toronto., 1995 Smith, K, Thacker, L, Generalized temors: Identifying a White Shaker dog, http://www.addl.purdue.edu/newsletters/2004/spring/tremors.htm Summers, B, Cummings, J, DelaHunta, A, Degenerative diseases of the central nervous system, in Veterinary Neuropathology, Mosby-Year book, St. Louis, MO, 1995 Swingle, C , White Shakers Syndrome, Westie Club of America, http://www.westieclubamerica.com/health/whiteshaker.html. Wenger, D, Victoria, T, Rafi, M, Luzi, P, Vanier, M, vite, C, Patterson, D, Haskins, M, Globoid cell leukodystrophy in Cairn and West Highland White Terriers, J heredit 90: 138-142, 1999 Yamaya, Y, Iwakami, E, Goto, M, Koie, H, Watari, T, Tanaka, S, Takeuchi, A, Tokuriki, M, A case of Shaker Dog Disease in a Miniature Dachshund, J Vet Med Sci 66: 1159-1160, 2004 Yunis, E, Lee, R, The morphologic similarities of human and canine leukodystrophy, Am J Path 85: 99-114, 1976

Topic 11: Canine Breeding and Perinatal Care, 2008 Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT Baker Institute, College of Veterinary Medicine, Cornell University, Ithaca, NY There are many recommendations that can be made to guide breeders in the important task of breeding dogs that will produce the next generation of the breed. The following is an outline of some practical considerations, remembering that if we want to produce the best dogs in the breed, we should start with the best dogs we have and continue to choose the best. This is true for genetic traits that are important in the show ring as well as those that control reproductive success. CHOOSING THE BREEDING PAIR, FROM A REPRODUCTIVE POINT OF VIEW Choosing a stud dog: Remember that a foundation male, the male that is the principal founder of a line, will contribute a significantly large proportion of his genetic makeup to the dogs in that line. There should be some evidence that he has valuable genetic characteristics to contribute to the breed, such as being certified clear of mutations for inherited eye disorders by yearly CERF examinations. In breeds where hip dysplasia is a problem, it is desirable for a foundation sire to have Grade Excellent hips, as certified by OFA or PennHIP evaluation. He should not be affected with any inherited disorders that are known to occur within the breed, as determined by specific testing, such as DNA testing. In addition to having the traits that you want to pass on to your line, a stud dog will transmit those that affect reproductive success. Some of these traits affecting reproduction are not obvious, and require some investigation into health history. First, he should be in good reproductive health and have a good personal and family history of reproductive success. Second, the average litter size produced by the prospective stud dog, his father, or full brothers should meet or exceed the breed average. The stud dog you choose must have two testicles in the scrotum. Inquiry into the family history should include whether the prospective stud dog, his father or any of his full brothers had cryptorchidism (failure of one or both testes to descend into the scrotum) or delayed testis descent. If they have, this is a concern, as infertility and testicular tumors are frequent consequences of cryptorchidism. Therefore, one should avoid propagation of this trait. Confirm, if possible, that both testes of the prospective stud dog were descended into the scrotum before 6-8 weeks of age. The size of the testes is a good indicator of sperm production capacity, with larger testes being capable of producing more sperm than smaller ones. For the adult stud dog (older than 2 years of age), the size of his testes (Figure 1) and his sperm count should be within the normal range for his body weight. For example, for fertile dogs weighing 10 to 34 pounds, the total scrotal width ranges between 33-40 mm, and the total sperm count between 290-510 million per ejaculate (Amann 1986). For dogs weighing 35-59 pounds, the total scrotal width ranges between 49-52 mm, and the total sperm count between 990-1250 million per ejaculate (Amann 1986). For dogs weighing 60-84 pounds, the total scrotal width ranges between 54-58 mm, and the total sperm count between 970-1890 million per ejaculate (Amann 1986).

Figure 1: Method for measuring canine total scrotal width, as an indicator of testis size. The width across both testes at their widest point, shown here as the distance between the yellow dots, is measured with a caliper. (photo copyright Dr. Vicki Meyers-Wallen, Cornell University)

To be certain that the semen quality is sufficient for reproduction, a complete semen evaluation performed by a veterinarian is recommended for all dogs before they contribute to a breeding program. While males frequently have sperm in the ejaculate before 1 year of age, one should evaluate them after they have become an adult in order to be sure that a representative semen sample is being obtained. A complete semen evaluation should minimally include three criteria: the total number of sperm in the ejaculate (an actual sperm count), the percentage of progressively motile sperm, and the percentage of normal and abnormal sperm morphology (Figure 2). Semen evaluations to determine a stud dogs average semen quality are recommended by the time he is 2-3 years of age. Further semen evaluations should be performed if any bitches bred to him fail to become pregnant or if litter size is smaller than average for the breed. If banking frozen semen is being considered, it is best to freeze semen when the semen quality is excellent. Semen collections for this purpose should be performed when the dog is a young adult (2-4 years old for most dogs). Semen quality in older dogs, or those in failing health, is often poor.

Figure 2: High power microscopic images showing canine sperm morphology (original magnification1000x). Normal sperm are shown on the left. The sperm with abnormal morphology (coiled tail) on the right would be unable to swim sufficiently to reach the oviduct, and is thus unlikely to participate in fertilization of the oocyte. (photos copyright Dr. Vicki Meyers-Wallen, Cornell University)

If the semen quality is poor, the semen evaluation should be repeated after the male has become accustomed to the collection procedure. Furthermore, it takes approximately 2 months for a whole new population of sperm to be produced in the ejaculate, which includes the time for completion of one spermatogenic cycle in the testis and sperm transit to the tail of epididymis where sperm are stored. Therefore, semen evaluations taken at least 2 months apart are needed to determine whether the semen quality has changed (for better or worse). Recovery after an insult to spermatogenesis can take at least 4-6 months (2 or 3 spermatogenic cycles) before a significant change in sperm quality and quantity in the ejaculate can be clearly identified. Choosing a breeding bitch: In addition to having the traits that you want to pass on to your line, the bitch will transmit those that affect reproductive success. Therefore she should be in good reproductive health and have a good personal and family history of reproductive success. There should be some evidence that she has valuable genetic characteristics to contribute to the breed. In addition, she should not be affected with any inherited disorders, such as inherited eye disorders, as documented by yearly CERF examination, or specific DNA testing for example. In breeds where hip dysplasia is a problem, she should be evaluated (OFA or PennHIP) and cleared for breeding. Inquiry into the family history should determine whether the average litter size produced by the prospective bitch, her mother, or full sisters meets or exceeds the breed average. Inquire whether she, or any of these close female relatives, have had difficulty in becoming pregnant or maintaining pregnancy, difficulty giving birth without assistance, had episodes of uterine or breast infections (pyometra or mastitis), had problems producing sufficient milk for the litter, or had difficulty in raising pups to weaning age. If many of these problems are present in females of the line, consider changing to a different female. The bitch should have a history of regular cycles (see below, stages of the estrous cycle). For example, the period of vulvar swelling and bloody discharge from the vulva that is followed by receptivity to mating (heat or estrus) generally lasts less than 3 weeks, and appears at regular intervals (7 months on average for bitches in general). Therefore for the average bitch, regular cycling would be the occurrence of an estrous period approximately every 7 months (interestrus interval). Each bitch will have her own average for this interval. The bitch should have good conformation in the reproductive organs. The vulva should be located in the normal position (below the rectum, not tilted, not tucked up in skin folds). Before her first breeding, she should be examined by a veterinarian to determine whether there are any internal structural abnormalities that may interfere with breeding, artificial insemination, or vaginal delivery of pups. Ideally, each mammary gland should each have a single, round nipple that can easily fit in a pups mouth. BREEDING MANAGEMENT Although some dogs can breed successfully by allowing nature to take its course, it is best to monitor all stages of the breeding program and have a backup plan ready to go in case complications in breeding, pregnancy, delivery or puppy care are encountered. There are methods now available to accurately identify the period of peak fertility. Thus ovulation timing (see below) is now used to time insemination or natural breeding, as well as to calculate whelping date (parturition date, day of birth). Precise timing can substantially reduce anxiety for the breeder and the veterinarian when unexpected events or complications arise, as well as providing the best chance for a good outcome for the bitch and pups. While proceeding through

the breeding management process, it is important that the breeder keeps accurate records on all aspects of the program for the bitch, the stud dog, and the pups produced. Recording cycles: Record every season (estrus) that the bitch has, whether or not you plan to breed her on that season. Make sure that you check your bitch at least once or twice weekly for evidence that she may be coming into proestrus: swelling of the vulva or bleeding from the vulva (see below). Also record when she apparently went out of season - so that you can identify the average length of her proestrus and estrus periods. Consistently use measures that are evident to you for a particular bitch, such as the day she no longer was attractive to males, the day that she quit flagging, or the day all vulvar swelling and bleeding disappeared. Stages of the canine estrous cycle There are four stages of the canine estrous cycle, which have these characteristics: Proestrus- The vulva swells and there is a blood-tinged to bloody vaginal discharge and cornified cells begin to appear in vaginal cytology (Figure 3). Average duration is 9 days. Figure 3: Swelling of the vulva at proestrus (left): Bloody discharge from the vulva is characteristic at this stage but is not appreciable in this picture. Mostly noncornified epithelial cells are present in the vaginal cytology (right), but cornified cells start to appear (right upper corner). (copyright Dr. Meyers-Wallen, Cornell University) Estrus- The bitch is receptive to mating. Ovulation normally occurs once during this period. The vulvar swelling is still present at this stage and the bloody vaginal discharge has subsided or may be scant. However, bloody vaginal discharge continues during estrus in some bitches. Greater than 90% cornified cells are present in vaginal cytology (Figure 4). Average duration of estrus is 9 days, but at the extreme of normal, it can be 21 days. (If it is nearing 21 days of estrous behavior without beginning to wane, consult your veterinarian.) Figure 4: Appearance of the vulva at estrus (left): Note prominent swelling of the vulva. Bloody discharge from the vulva is usually decreased by this stage. Greater than 90% of the epithelial cells are cornified in the vaginal cytology (right). Cornified cells are large, flat cells having angular cell borders and have a small nucleus or no nucleus. (copyright Dr. Meyers-Wallen, Cornell University).

Diestrus- No external signs are generally shown, but over 1-2 days as estrus subsides, vaginal cytology changes back to predominantly noncornified cells. Vulvar swelling subsides. In pregnant dogs, this stage ends at whelping. In nonpregnant dogs this stage may last over 60 days. In the diestrus stage, serum progesterone (P4) concentrations are normally elevated, whether the bitch is pregnant or not. That is, there is no significant difference between the P4 levels in pregnant or nonpregnant diestrus dogs, except before whelping, when the P4 falls significantly in pregnant bitches, after which it remains low. In nonpregnant bitches the P4 decreases slowly at the end of diestrus. Therefore serum P4 is not useful as a canine pregnancy test Anestrus- After a pregnant diestrus, the bitch will lactate for several weeks. After a nonpregnant diestrus, some lactation may occur for a short period, but otherwise no external signs are associated with anestrus. During this period of reproductive rest, concentrations of ovarian hormones in the serum fall to low (baseline) levels. This stage should last at least 3 months, but can be longer. The variable length of anestrus accounts for the difference in the length of estrous cycles between bitches. For example, if anestrus is long, the interval between estrous cycles (interestrus interval) will be greater than the average 7 months. Ovulation timing Ovulation is the term used to indicate the release of the eggs (oocytes) from the ovarian follicles. All oocytes released from both ovaries enter the oviducts (Figure 5) where they mature and become capable of being fertilized. This period where they are capable of fertilization (period of peak fertility) lasts a few days in the bitch. If the oocytes are not fertilized during this period, they degenerate. Although healthy canine sperm from a fresh ejaculate can live a few days in the oviduct, waiting for the oocyte, sperm will degenerate if they do not participate in fertilization. Apparently, sperm from frozen semen insemination do not live as long in the oviduct as freshly ejaculated sperm. To maximize the chances of fertilization and pregnancy, it is important to time the insemination such that healthy sperm are present in the oviduct at the same time as healthy oocytes. Even though a single natural mating performed several days before ovulation or several days after ovulation can occasionally result in pregnancy, the resulting litter size is generally small. With such poorly timed breedings there is also a good chance that pregnancy will not be achieved because either the sperm or the oocytes have degenerated to the point that they cannot produce a healthy embryo. Thus ovulation timing is used to identify the period of peak fertility because it is the best time for insemination, providing the best chance of achieving pregnancy and a normal litter size.

Figure 5: An ovulated canine oocyte (round structure on left) within the oviduct. The oocytes remain in the oviduct, where they are fertilized during the period of peak fertility. (copyright Dr Meyers-Wallen, Cornell University)

Although there are many ways to time ovulation, some are more accurate than others. For example, serum progesterone (P4) can be estimated with various kits [enzyme linked immunoassay (ELISA) tests], but these are not as accurate as quantitative laboratory tests for progesterone concentrations [chemiluminescent immunoassay (CLIA) or radioimmunoassay (RIA) tests]. On the other hand, an ELISA kit that measures LH, can provide a good estimate of d0, provided it is used daily according to the manufacturers directions. The LH peak The signal for ovulation is a hormone secreted by the brain (pituitary) that is delivered through the blood stream to the ovaries. As a result, all the oocytes from both ovaries are released at the same time. This signal for ovulation is luteinizing hormone (LH). In the bitch, serum LH concentrations reach a peak sufficient to induce ovulation over a 24 hour period. We call the day upon which this occurs day 0 (d0). In order to detect this LH peak, blood samples must be collected every day during proestrus and estrus until d0 is detected (Figure 6).

Figure 6: Example of serum LH measurement on an ELISA test (Witness LH, Synbiotics, CA). Blood samples were taken daily, but only samples from 3 days are shown. A) No LH peak is detected. Well 1 is the negative control: it should always be blank. Well 2 is the test well: a prominent colored line will occur here when LH is elevated, but only a faint line is present here. Well 3 is the positive control well: a colored line as shown here should always be present in well 3 if the test is working properly. B) Note that a prominent colored line appears in well 2, and is more prominent than the positive control (well 3). This indicates that the LH peak occurred on the day this blood sample was drawn, which would be day 0 (d0). C) On d1, the line in well 2 is very faint, indicating that the LH peak has subsided. This series of results illustrates why the blood samples for this test must be taken daily in order to accurately detect the LH peak. (copyright Dr. Vicki Meyers-Wallen, Cornell University).

The progesterone (P4) rise Fortunately in the bitch, a rapid rise in P4 begins on the same day as the LH peak, after which P4 continues to rise. Therefore for practical reasons, day 0 is most frequently calculated from this initial P4 rise for the purpose of ovulation timing (Figure 7).
8 6 4 2 0 bitch 1 bitch 2 bitch 3 0.6 0.4 0.9 -6 -5 -4 -3 0.5 1.2 -2 -1 0.9 2 d0 d1 d2 d3 3.3 3.9 5.6

0.5 0.9 0.8 1.2 2.1 3.1 5.6 7.1

days from d0

Figure 7: Serum progesterone (P4) concentrations observed on samples taken daily from bitch 1 and every other day from bitches 2 and 3 during proestrus and estrus. Day 0 (d0) is identified as the day that serum P4 concentrations rise to 1.5-2.5 ng/ml. In normal bitches, one can obtain an accurate estimate of d0 from the P4 concentration by taking blood samples every other day, provided that they are assayed by CLIA or RIA. Although these curves look very similar, variation in P4 concentrations after d1 can be significant between bitches. Therefore, d0 should not be estimated from P4 values obtained late, in other words if you start sampling after d1 has already occurred (Kutzler et al 2003a). (copyright Dr. Vicki Meyers-Wallen, Cornell University) Because the time of ovulation cannot be reliably estimated from the onset of proestrus or estrus, even when judged by vaginal cytology, it is best to start the ovulation timing process within 2-3 days after the first signs of proestrus are noted (vulvar swelling and/or bloody discharge). Regardless of whether d0 is calculated from the LH peak (by the ELISA test) or the initial P4 rise (by CLIA or RIA), all subsequent events are calculated from d0. Identifying d0 is very important because all timing for the breeding and the pregnancy thereafter depends upon accurately identifying it! Therefore it is important to start taking samples BEFORE d0. Starting after d0 has already occurred, and then estimating backwards, is inaccurate (Kutzler et al 2003a).The following protocol can be used when P4 samples are collected every other day and measured by CLIA or RIA. Vaginal cytology and a serum P4 are first taken within 2-3 days after the first signs of proestrus are noted to confirm that she is in proestrus or estrus and that she has not yet ovulated. Then blood samples are taken every other day to identify when serum P4 begins to rise (1.5-2.5 ng/ml), which is day 0 (d0). This can be identified if sampling is done at least every other day (Figure 7). Because we need to confirm that the P4 continues to rise after d0, P4 sampling is continued every other day until the P4 concentration exceeds 3-5 ng/ml. Vaginal cytology is usually taken on the same days as blood sampling to help determine that the cycle is proceeding normally. Counting from d0:

Ovulation occurs on d2. Natural breeding or intravaginal AI (fresh semen in the vagina) should be performed every other day, at least twice (d3 and 5, or d4 and 6) because this is the when the oocytes are mature and capable of fertilization (period of peak fertility). Frozen semen insemination (intrauterine deposition of the semen) is usually performed on d5, but this can vary depending upon the protocol recommended by the company that originally froze the semen. Ultrasound examination for pregnancy diagnosis should be performed between d28-30. Whelping should occur at d65 +/-2 days (between d63-67, with the majority occurring on d65.)

Note: no matter when the natural matings or inseminations were performed, you should expect the whelping date to be within the d63-67 interval. Remember that the embryo is timing gestation according to the oocyte, and it starts counting from the day of ovulation, not from the day of insemination. Thus when estimating the whelping date by this method, it is important to count from the d0 you obtained during ovulation timing and not from the day of breeding or insemination. For example, if you counted from any one mating to the day of whelping, the dog could whelp anytime between 57-72 days (at the extremes), depending upon if that mating was performed several days after ovulation (d57 whelping) or several days before ovulation (d72). However, for the same pregnancy, the whelping date counting from d0 would occur between d63 to 67.) PREGNANCY Pregnancy diagnosis Pregnancy can be identified by palpation (examination by the veterinarian d28-35), a serum relaxin test (after d28), or ultrasound examination (Figure 8). After d44, fetal skeletons can be detected on a radiograph (Figure 9). Ultrasound examination can be used to monitor the fetuses anytime after the initial pregnancy diagnosis. Each method has an optimum time for pregnancy diagnosis, but I prefer ultrasound (US) examination between d28-30 because: gestation is sufficiently advanced to conclude whether the bitch is pregnant or not this is the ideal time to measure fetuses during the ultrasound exam and estimate gestational age (i.e., to compare the gestational age estimated by the US fetal measurements with the estimate obtained by progesterone estimate of d0). The two methods should agree within one day if fetuses are growing normally. fetal heart beats should be present at this time, an indicator that pups are alive fetuses can be counted at this stage more easily than at later stages fetal resorptions can often be identified at this stage, as well as later Although pregnancy can be diagnosed by ultrasound at other times during gestation, the most accurate estimations of gestational age from fetal measurements taken during US examination were obtained at d30. Even at this age, correction must be made for the body weight of the dam (Kutzler et al 2003b). Other investigators use mathematical formulas to estimate gestational age from fetal ultrasound measurements in early gestation with similar accuracy (Beccaglia and Luvoni 2006). 8

Gestational age could not be accurately estimated by the ultrasound method for fetuses older than d39 in our studies (Kutzler et al 2003b). The reason is that fetal growth is exponential after d30, but fetuses in toy breeds grow more slowly and are significantly smaller, while those of giant breeds grow more rapidly and are significantly larger.

Figure 8: Ultrasound examination of a pregnant bitch at d28. Yellow dots mark the limits of the gestational sac. The fetus is the white object lying in the fluid (black) within the gestational sac. (copyright Dr. Meyers-Wallen, Cornell University)

Figure 9: Radiograph taken in late gestation showing complete fetal skeletons. (photo copyright Dr. Vicki Meyers-Wallen, Cornell University)

CARE DURING PREGNANCY Feeding the bitch A high quality diet (adult maintenance quantity) should be started well before the bitch enters proestrus and then continued until pregnancy is first diagnosed (d28-30). The same diet should be maintained after pregnancy diagnosis. However in the last 3 weeks of pregnancy (after d44), the fetuses grow rapidly. To accommodate this growth, the bitch will require increased intake of a high density, easily digestible diet (growth or puppy type diet). This type of diet is usually maintained after whelping until the pups are weaned. Underfeeding before and during pregnancy will result in pups with low birth weight and poor survivability. On the other hand, obese bitches can have difficult deliveries, particularly if they have also received little exercise. Medications and supplements Remember that something that seems harmless to humans or adult dogs may be detrimental to growing canine embryos, fetuses, or newborn pups. Vaccinations should be given well before the bitch enters proestrus, and not during pregnancy. Furthermore, no supplements or drugs should be given during pregnancy unless required to maintain the bitchs health, as discussed with your veterinarian. Consult your veterinarian before giving any type of medications or nutritional supplements, whether they are given by mouth, placed on the skin, or given by injection. This includes medication for itching skin, hormonal preparations, or insect control. For example, your veterinarian can advise you regarding the safety of using specific heartworm preventatives, flea/tick medications, or insecticides during pregnancy. Milestones in pregnancy: Period of the embryo Preimplantation (up to approximately d19)- Fertilization occurs in the oviduct (d3-6) and the zygote begins to develop into an early embryo in the oviduct. By the blastocyst stage the embryos are floating freely in the uterus. Embryos emerging from each oviduct can migrate to either uterine horn (transmigration), then space themselves evenly along the uterine horns. Postimplantation (approximately d20-d34) The embryos attach to the uterine wall (implantation). The placenta develops. This is the period at which most organ systems are being formed, and when embryos are most susceptible to environmental insults (teratogens, viral infections, drugs). Period of the fetus (approximately d35-65) Most organ systems have developed and now begin to enlarge and/or refine by further differentiation. A notable exception is the eye, which continues to develop even after birth. PERINATAL AND PUPPY CARE: Perinatal Observation of the Bitch By d58 (one week before the estimated d65 due date) Set up a clean whelping box, complete with bedding (papers for example) and a heat lamp located over one corner of the box (not over the middle of the box). Introduce the bitch to the box and let her get used to it. Start taking the bitchs rectal temperature once a day. Clip hair away from the breasts and the vulva.

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Starting by at least day 62 Take the bitchs rectal temperature twice a day: For those that are 100F in late gestation, the temperature may fall to 98-99F about 24 hours before whelping (Figure 10). However, not all bitches have a temperature drop before they whelp. Observe for signs of labor (nesting, not eating that day, vaginal discharge, increased activity such as digging or pacing) Observe breasts for presence of milk Ensure that the heat lamp is on and located only over one corner of the box so that pups and bitch can move away if they get too warm. Make sure it is placed high enough that the bitch will not be burnt by it or chew on the electrical cord. Check the whelping box temperature directly under the lamp with a thermometer (8085F maximum) and raise or lower lamp as required. Ensure fresh bedding (clean and dry) is in the box. Assemble clean whelping materials: such as bath towels to dry and rub pups, sterile suture or white cotton thread, sterile scissors, latex gloves, Karo syrup, milk replacer. Between d63-67 (estimated whelping date from d0, average is d65) Check the bitch several times during the day and night for signs of labor.

103 102 101 100 99 98 97 96

d63 am

d63 pm 100

d64 am

d64 pm

d65 am

d65 pm

d66 102

rectal temp (F) 99.9

99.8 98.6 98.6 days from d0

Figure 10: Example of significant rectal temperature drop in a bitch before whelping. Whelping occurred on the evening of d65 and the temperature was not taken at that time. Note that the temperature drop occurred approximately 24 hours before whelping and rebounded on the day after whelping. Not all bitches will exhibit a temperature drop. (copyright Dr. Vicki MeyersWallen, Cornell University) Guidelines - when to call the veterinarian (from Schweizer and Meyers-Wallen 2000): Although it is possible that the bitch may normally whelp as late as d67, the veterinarian should be informed if the bitch has reached d65 and there are no signs of a temperature drop or labor. She/he may wish to check fetal viability by ultrasound examination.

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If a temperature drop has occurred (Figure 10), but no signs of labor are seen within 24 hours. If there is a black-green vaginal discharge (same color as the placenta) but no pups have yet been delivered. If the bitch has shown signs of labor (restlessness, nesting), but after 6-8 hours the bitch has not proceeded to the pushing (second) stage of labor. If the bitch has been actively straining (pushing) for more than 20 minutes or has weak contractions for an hour and has not expelled a pup, or only the fetal membranes are showing through the lips of the vulva. If it has been an hour since delivery of the last pup but there are no further signs of active straining (pushing). Most bitches give birth to one puppy per hour on average, but some are faster or slower. In general, if the time between pups is increasing and it is a large litter, the pups at the end may be weak upon delivery. Call your veterinarian if pups are becoming increasingly weaker by birth order.

On the Day of Whelping: If there is any question whether all the pups have been born or not, call the veterinarian. If the bitch does not promptly remove the fetal membranes over the mouth and nose, do it for her and resuscitate the pup as follows. Wipe pups nose with clean towel, then stimulate it to breathe by rubbing it along both sides. Pause to see if it takes a few breaths. Repeat until it is breathing regularly and the gums or footpads are pink. Dry the pup well, then return it to the whelping box, under the lamp. Observe every few minutes to be sure breathing continues to be regular and gums are pink. If not, rub pup again, remove any fluid in nose, keep it warm and stimulate it. Trim umbilical cord to a length of approximately one half inch. Tie it about one quarter of an inch from the body with sterile suture or white cotton thread. Trim suture ends well so that the bitch will not chew the suture. Place each pup on a breast to nurse within the first 8 hours after birth so that they can absorb colostrum. Make a separate record for each pup to record all findings below. Note sex, distinguishing marks, obvious external characteristics: color, rear dew claws, etc. Check for problems like cleft palate, umbilical hernia, open fontanelles (hole in the top of the skull bone). Check pups for suck reflex, noting if strong or weak. Using a warm, moist cotton ball, stimulate urination and defecation. Weigh all pups, including stillbirths. Use a scale that reads in grams, as it is more useful for the small weight changes that occur in small pups. Check the bitch and write in her record: total number of pups whelped (live and stillborn), color and consistency of her vaginal discharge, number of breasts producing milk, any abnormalities in mothering (failure to remove fetal sacs, chewing of umbilical cords too close to body, not lying down with pups so they can nurse, excessive carrying of pups, traumatizing pups, etc.).

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On Days after whelping, until weaning: Bitch- record all observations in her record Check vulvar discharge, general health and appetite. On the day after whelping the vaginal discharge may still be black to green (like the placentas), but after that it should become reddish brown. Take the bitchs rectal temperature daily for the first 3 days after whelping. It may go up to 103F on the day after birth, but should fall to 101-102F after that. Note milk quantity and quality in the first 3 days by gently getting 1-2 drops from each breast. Gently feel the breasts- they should be spongy and pink. If any are firm, reddened, or painful, check the rectal temperature and call the veterinarian, as this could be an indication of mastitis (breast infection). The bitch will require increased food intake for at least 3 weeks during the period that pups are nursing and rapidly gaining weight. The amount may be 2 to 4 times her normal ration, depending upon the litter size. For large litters, if the bitch does not have sufficient milk, it will help to start supplementing pups. First, in addition to allowing them to suckle, bottle feed them with a commercial canine milk replacer, at room temperature or warmed to be comfortable by testing on your wrist. As they approach 3 weeks of age, offer them moistened puppy food mixed with the milk replacer. Signs of hypocalcemia (milk fever, low serum calcium) are trembling of the muscles that progresses to stiff limbs and can look similar to a seizure except that the bitch appears conscious. Most cases occur within 3 weeks after giving birth. In this disorder, the muscles continuously contract, so the body temperature becomes dangerously high. Call your veterinarian if there is any question, as this is a medical emergency that can lead to death of the bitch. Pups- record all observations in each pups record From birth to 3 weeks of age: Weigh pups daily and assess their skin turgor as a measure of hydration. After 3 weeks of age, you can weigh pups every few days or weekly if they are doing well. Smallest pups or those on supplemental formula should be weighed more frequently. Normal pups gain steadily from first nursing or lose less than 10% of their birth weight in the first 48 hours. Pups should double their birth weight in the first 7 days of life. So if the pup is 300 grams on the day of birth for example, it should be 600 grams by day 7. (which means it should gain about 300/7 = 42 grams per day.) If any pup fails to gain, see feeding below. Allow pups to stay with their mother as much as possible, even if they are being fed by bottle, as the mother gives them warmth, cleans them, and so forth, which is just as important as being fed. Healthy pups should be either eating or sleeping quietly. Pups that are continuously crying and moving around are of concern- check whether they are too cold, too hot, hungry, sick, or the mother is not attending to their elimination needs (urination & bowels). 9 If it is too cold, the pups are usually piled up on one another. Check whether the whelping box temperature is too cold and make sure the box is dry and clean.

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9 If it is too hot, the pups are generally spread out and moving away from the heat source. Make sure they can get away from the heat lamp. Check the temperature under the lamp. It is better for them to be a little cool than too hot. 9 Check the mother for problems (breasts, vaginal discharges, rectal temperature). Check each pup- for example: the umbilicus for infection, the color and consistency of the stools. Feeding/Nursing If bitch is not lying down to nurse the pups very well, try gently lying her down while pups nurse for 15-20 minutes at a time (Figure 11). (If there are very small pups, or pups are not able to nurse well right away for any reason, supplement the pups in addition to allowing them to nurse from the mother. It is all right to feed a 10% sugar solution in a baby bottle for a day or two if there is a delay in getting canine formula. You should use 1 part clear Karo syrup plus 9 parts of warm water in a baby bottle. Mix well and check solution temperature on your forearm before feeding.) 9 On the first day that a pup fails to gain weight- it should be supplemented! 9 Check suck reflex, color of gums or footpads, activity level, rectal temperature. Rectal temperature in first week of life should not be lower than 98F. If colder, warm up by holding pup on your skin (your tummy is a good place). 9 Check the bitch- especially her milk and rectal temperature. A pup that fails to gain (or loses weight) should be supplemented frequently each day with formula until it gains consistently every day. If it continues to lose weight, call your veterinarian. Figure 11: Example of a bitch that is lying in a position that allows pups to easily suckle. The bitch is quiet and comfortable and lifting one rear leg to accommodate the pups. In the background note the ledge on the inside of the whelping box wall that helps prevent the bitch from inadvertently injuring a pup by squeezing it between herself and the wall. (copyright Dr. Meyers-Wallen, Cornell University)

References Amann RP. 1986. Reproductive physiology and endocrinology of the dog. In: Morrow D (ed), Current Veterinary Therapy 2, WB Saunders Co., Phila., pp. 532-538. Beccaglia M and Luvoni GC. 2006. Comparison of the accuracy of two ultrasonographic measurements in predicting the parturition date in the bitch. J Small Animal Practice 47:670673.

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Kutzler MA, Mohammed HO, Lamb SV, Meyers-Wallen VN. 2003a. Accuracy of canine parturition date prediction from the initial rise in preovulatory progesterone concentration. Theriogenology 60:1187-1196. Kutzler MA, Yeager AE, Mohammed HO, Meyers-Wallen VN. 2003b. Accuracy of canine parturition date prediction using fetal measurements obtained by ultrasonography. Theriogenology 60:1309-1317. Schweizer CM and Meyers-Wallen VN. 2000. Medical management of dystocia and indications for Cesarean section in the bitch. In: Current Veterinary Therapy XIII, Bonagura JD (ed), WB Saunders Co., Phila., pp. 933-939.

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Topic 12: Aggression in dogs: What does it mean for Westie owners? John Robertson One of the most controversial issues for owners, breeders, veterinarians, and the public is canine aggression. This Topic is written from the viewpoint of both a dog owner and veterinarian. It is, unfortunately, also written with personal insights; I was 11 years old when severely mauled by a German Shepherd Dog. This Topic is not written by an animal behavior expert, but contains the current thinking of a number of behaviorists. One point needs to be emphasized Westies, as a group and statistically, are not a breed of dog for which there are profound public concerns over aggressive behavior! In a word (see photo right, courtesy of the Chapmans) Westies are solid and predictable canine citizens. Problem dogs An old adage is that there are no bad dogs, only bad owners. However, each year, millions of dogs are surrendered at shelters and many/most of these dogs are euthanized. According to shelter managers, dogs are surrendered to them primarily for one of four reasons: Dogs are aged or ill, or both, Dogs are homeless/ownerless, There was a weak bond between the dog and owner (the dog did not fulfill the expectations of the owner), Dogs are not good pets because of behavioral problems (40% of dogs surrendered). There have been major strides in reducing the number of unwanted animals surrendered to shelters. Public education and outreach campaigns by animal welfare organizations, veterinarians, and governments have raised public awareness about pet animal overpopulation and the need for neutering pet animals. However, even as these campaigns succeed, many dogs are still taken to shelters. In a survey conducted at 12 animals shelters, adolescent and young adult dogs comprised a significant proportion (29-31%) of the dogs surrendered (Arkow, 1991). While many dogs surrendered at shelters are of mixed parentage, roughly 30% of dogs are purebred animals. Many professionals and concerned groups note that even if pet overbreeding and overpopulation were virtually eliminated, many dogs would still end up in shelters and would be destroyed. Shelters receive ownerless dogs from animal control officers and from the public. Homeless dogs may be strays (have escaped from owners), abandoned, or may be truly feral (breeding and roaming without human intervention or ownership). Dogs that roam individually or in groups are problematic. These dogs may suffer from starvation, disease and trauma. Ownerless dogs may harbor infectious diseases that can spread to other ownerless dogs or to pet dogs. Ownerless dogs may predate wildlife, livestock and pet animals while searching for food or raid waste bins. In many cases, ownerless (feral) dogs may avoid human contact like other wild animals such as coyotes. At times, ownerless dogs may threaten or attack humans or pet animals. The public health problem associated with biting dogs is discussed more fully below.

In a study of socialized pet dogs presented at 12 humane shelters, Salman, et.al. (2000) noted that there were several common behavioral problems that were the cause of surrender. Most common was inappropriate elimination (dogs resist learning or observing housebreaking and soil the home). Dogs that could not be housebroken were seven times more likely to be taken to shelters than other dogs. Some dogs displaying inappropriate elimination may, in fact, be marking territory within homes. This normal behavior, while completely appropriate out-ofdoors, is definitely not desirable indoors. Canine aggression was the second most common behavioral problem that resulted in dogs being surrendered for adoption or euthanasia at shelters (Salman, et. al., 2000). Ten percent (10%) of all dogs relinquished had displayed aggression toward people and of the dogs surrendered, 69% had bitten at least one person. Eight percent (8%) of all dogs relinquished displayed aggression toward other animals. A number of studies have shown that approximately 40% of dogs presented for evaluation and treatment of behavioral problems at veterinary practices are dogs displaying aggression, with a majority of dogs showing aggression toward people. Dogs that bite people are a significant public health problem. According to information published by the Centers for Disease Control in 2003 (the latest published and summarized data available) 4.7 million dog bites occurred in 1994. It is pretty clear that this number has increased substantially since then. Approximately 799,700 people required medical care for bites in 1994 (CDC, 2003). Dog bites are both a financial and legal burden for owners of dogs that inflict the bites. In 2001, an estimated 368,245 people sought acute treatment for dog bites at hospital emergency rooms. The rate of injury and the severity of injury were highest among children aged 5-9 years old. Forty-two percent (42%) of dog bites occurred in children less than 14 years old. The incidence rate was significantly higher in boys than in girls, probably a reflection of outdoor and unsupervised contact. The injury rate declined with increasing age; adults are much less likely to be bitten than children. For persons over 15 years old, there was no difference in incidence between males and females. Cases increased slightly in the warmer months (April to September, peaking in July). Between 4-7% of dog bite-related injuries were work-related (delivery and service people, staff and professionals involved in animal care) (CDC, 2003). The most common sites of injury included bites to arms and hands (45% of all injuries), legs and feet (26%) and head and neck (23%). The majority (65%) of the injuries to children less than 4 years old were head and neck injuries. The incidence of extremity injuries increased with age. The types of injuries inflicted included punctures, lacerations, contusions and hematomas, infections, and crush/amputation injuries, and fracture/dislocations (CDC, 2003). About 98% of all people seeking care at emergency departments for dog bites are treated and released. Between 1979 and 1996, more than 300 people were killed as a result of unprovoked dog attacks, according to data collected by the Humane Society of the United States (Sacks, et. al., 2000). In a study of 227 human fatalities for which breed information and attack data was available (1979-1998), Sacks and co-workers were able to demonstrate that 25 breeds of dogs (including crossbreds but with a predominating phenotype) were involved. Pit Bull Terrier/Pit 2

Bull Type dogs, Rottweilers and German Shepherd Dogs accounted for 147/227 fatalities. In the 20-year study period, there was one fatality due to a West Highland White Terrier. Single fatalities were also recorded for Yorkshire Terriers and Dachshunds. A majority of deaths (58%) involved an attack by an unrestrained dog on the owners property. Most fatalities (160/227) were caused by an attack from a single dog. A trend was noted in the number of attacks and breed popularity. When Rottweilers and Pit Bull Terrier type dogs increased in breed registrations, the number of attacks attributed to these dogs went up. (Photos above, left, courtesy of the Sarasota County Sheriffs Department; subjects are all listed as aggressive dogs on a public warning list). The contribution of dog genetics to behavior is discussed below. Nature versus nurture: Is there a genetic connection to behavior? I think there is a popular perception that dog behavior can be predicted fairly well by the breed of the dog. Jack Russell Terriers are feisty, Golden Retrievers are great with children, and Rottweilers are stalkers. And as everyone knows, Westies are Lovers! (Photo courtesy of the Chapmans) Lets take a look at evidence and opinions about breeds and behavior. The influence of genetics and breeding on canine aggression and other behaviors has been studied for thousands of years. It is very clear that domestication of dogs was a process of selecting not only desirable body shape and size, but also selecting useful behaviors including guarding, hunting and herding. Roughly 100 years ago, scientists began to collect observations and perform studies to determine potential genetic links to behavioral characteristics. As early as 1921, MacDowell noted differences among litters of Dachshund puppies in reactivity to visual and auditory cues. Whitney (1926) noted that some behaviors were characteristic of certain breeds and that these behaviors were inherited independently from phenotype (physical appearance). Some of the traits studied included shyness, intelligence, levels of energy and aggression (defined as a tendency to bite). Whitney concluded that while some behavioral traits seemed to show classic patterns of inheritance (caused by expression of dominant and recessive genes), many traits were complex and probably inherited as expressions of multiple genes. Mahut (1958) studied the differences in emotional responses in 10 breeds of dogs. In a standardized test setting, young dogs were evaluated for curiosity, response to teasing (approaching and pawing/mouthing objects), approach-avoidance (excitement at seeing objects and stalking them), wariness (tensing and trembling, growling), and frank avoidance. She classified dogs studied as belonging to one of two groups. Fearful dogs (Collies, German Shepherds, Poodles, Corgis, and Dachshunds) had high scores for wariness and avoidance. The other group was classified as fearless based on low scores of wariness and avoidance. Fearless dogs included fighters, ratters, and killers such as Boxers, Boston Terriers, Bedlington Terriers, and Scottish Terriers. Mahut found that the environments dogs were raised in significantly affected the display of behavioral traits. Animal behaviorists consider the work of Scott and Fuller (1965) to be a cornerstone of our understanding of the genetic basis of dog behavior. Work they conducted in a very controlled environment, over decades, showed that within each breed of purebred dog studied, there is a 3

wide variation in emotional responses to various stimuli. They suggested caution in accepting the idea of a breed stereotype of emotional behavior. Many other studies (too numerous to list here) on heritable behavioral characteristics in purebred dogs have yielded contradictory and sometimes confusing results. Studies of lineages and pedigrees of several breeds of dogs have appeared to clearly demonstrate a heritable link of aggression. This was shown in studies of Golden Retrievers (Van den Berg, 2006), Cocker Spaniels (Podberscek, et. al., 1996) and English Springer Spaniels (Reiner, et. al., 2005). While some authors believe that there is a heritable tendency toward excitability, fear, or nervousness in some dog breeds, other authors feel that factors such as length of time puppies stay with dams, sex of dogs, and early experiences are just as important as parentage. The influence of early socialization cannot be underestimated. A significant number of dog breeders feel that the more time a puppy can spend in the controlled environment of the breeder, the more predictable the puppys behavior will be. There is ongoing (and probably unresolvable) debate about the optimum age for puppy adoption. Many breeders believe that adoption between 6-8 weeks does not allow for adequate dog:dog and dog:human socialization. It would seem clear that delaying adoption of puppies might allow breeders to more easily identify puppies with potential behavior problems and to decide how best to manage these dogs. On the other side of the debate, many veterinarians and some behaviorists believe that an optimum time for bonding of puppies with their new owners and environment is between 6-8 weeks. This debate is not going to be settled unless there are objective research studies that demonstrate how best to socialize puppies. Additional thoughts on this are to be found below where prevention of aggression is discussed and also in Dr. Meyers-Wallens topic on breeding practices. Pfleiderer-Hogner (1979) analyzed the heritability of performance from records of 2046 evaluations conducted on a total of 1291 German Shepherd Schutzhunden (photograph of Schutzhund Schatze, right, courtesy of Dr. Mark Plonsky). Dogs were evaluated with the standard measures of Schutzen performance, including tracking, obedience, man-work and character. A correlation was found between man-work (such as guarding and commanded confrontation) and character, but not other traits. She concluded that there is little heritable basis for performance and that early evaluation of dogs for performance could not predict behavior. The very comprehensive review authored by MacKenzie, et.al., (1986) exhaustively covers these controversies. Hart, et.al., (1985a, 1985b) discussed behavioral profiles of 56 dog breeds and factors which might influence selection of purebred dogs as pets. A panel of 96 authorities (48 small animal veterinarians and 48 obedience trial judges) expressed opinions that were used to score breeds of dogs on 13 traits, including such things as excitability, snapping at children, watchdog barking, and affection demand, among others. A very complex scoring system was developed and tested statistically for validity. Authorities were asked to determine a predisposition to excitability based on the following statements A dog may normally be quite calm but can become very excitable when set off by such things as a doorbell ringing or an owners movement toward the door. This characteristic may be very annoying to some people. Rank these breeds from least to most excitable. 4

Data collected on Westies is interesting, for a number of reasons. First, Westies ranked highly as a breed in terms of excitability. In contrast, Bloodhounds, Bassett Hounds and Rottweilers ranked lowest in terms of excitability. Second, a separate behavioral category, watchdog barking, was analyzed. To assess this behavior, the following statements and scenario were given as a definition Now we would like to find out your opinion regarding watchdog capabilities of these breeds. A woman living alone in a city wants a dog that will sleep by her bed and frighten intruders by barking if anyone breaks into the house in the middle of the night. Rank these breeds from least to most as to which will most consistently sound an alarm when it hears something unusual and will bark at intruders. Westies were ranked in the most effective watchdog category (with Rottweilers, German Shepherd Dogs, Doberman Pinschers, and Scotties). Taken together, one might well argue that high scores in terms of both excitability (alertness) and watchdog barking, are a desirable combination in some circumstances (family protection) but a detriment in others (continual barking at sounds in an apartment environment). In terms of housebreaking (a measure of trainability), Westies scored in the middle of the rankings. Hart and co-workers (1985b) used their data to create behavioral profiles of breeds, based on scoring in all 13 categories. Using statistical tools including cluster and principal component analysis, they created a scheme that classified different dog breeds. Needless to say, their work suggested very strongly that although there were variances in individuals within breeds, there were inherited behavioral predispositions in breeds. They specifically concentrated on reactivity, aggression, and trainability to cluster breeds. Reactivity was defined by the aggregate scoring of dogs in the following categories: affection demand, excitability, excessive barking, snapping at children, and general level of activity. Aggression was defined by the aggregate scoring of dogs in the following categories: territorial defense, watchdog barking, aggression to dogs, and dominance over owner. Finally, trainability was defined by the aggregate scoring of dogs in the following categories: obedience training and housebreaking ease. Based on the analysis of all data, Westies were placed in a cluster of very high aggression, high reactivity, and medium trainability. Other dog breeds in this cluster were Cairn Terriers, Scottish Terriers, Airedales, Miniature Schnauzers, Dachshunds and Fox Terriers. By contrast, German Shepherd Dogs, Akitas, Doberman Pinschers, and Rottweilers formed a cluster characterized by very high aggression, very high trainability, and very low reactivity. We have to remember that this is an artificial system of data classification, based on interviews with authorities and their subjective experiences and opinions with these breeds. Hart and co-workers (1985b) also analyzed the effects of gender on behavioral characteristics. Not unexpectedly, they found several measures of aggression (snapping at children, territorial defense, aggression toward other dogs and dominance over owners) higher in intact male dogs than in intact female dogs. They felt that their data demonstrated that neutering of male dogs altered hormonally-driven behaviors (mounting, urine marking, and aggression) in about half of dogs in which these undesirable behaviors created problems for owners. Neutering did not appreciably alter other behaviors such as playfulness, destructiveness, snapping at children, and territorial defense.

Scientists are just beginning to understand the relationship of brain anatomy and chemistry to behavior and aggression in dogs. Jacobs and his colleagues (2006) found actual differences in the centers in the brain that regulate emotion and reaction when they compared tissue samples from aggressive and non-aggressive dogs. Reisner and co-workers (1996) also found differences in neurotransmitter metabolites in aggressive and non-aggressive dogs, perhaps indicating a higher potential level of reaction to stimuli in aggressive dogs. This area of neurobiology is rapidly evolving. We can expect that more study of the triggers of dog behavior will lead to a better understanding of genetic factors controlling brain development and metabolism. This may lead to the development of drug and behavioral therapies for problem dogs (See below). What is canine aggression? Aggression is broadly defined as a behavior that is manifested as growling, snarling, baring of teeth and biting (Scarlett, et.al., 2002). There are times (see below) when aggression in dogs is appropriate and times when it is not. Haug (2008) stated that there were three underlying reasons for canine aggression: fear; resource-guarding (territory, owner and other animal protection); and predation. There are not clear boundaries between these reasons and some dogs may display aggression for several reasons. Haug further noted that aggression may be normal and functional, or it may be normal but inappropriate or considered unacceptable, or it may be a frank behavioral abnormality, with dogs acting completely inappropriately in many situations. It is possible to distinguish several forms of appropriate and predictable aggression. First, as shown in the figure at the left (Tank and Bruiser Robertson, age 7 weeks!), puppies will play out aggression as they become socialized in litters. Much of this controlled and playful aggression serves multiple purposes. Most breeders will readily acknowledge that dogs quickly establish a hierarchy within litters for attention, for access to food, water, toys, and for the most desirable places to sleep. In the past, this was broadly classified in terms of seeking and learning dominance. Playful aggression is a component of socialization during the critical period of 4-14 weeks of age, when dogs learn about their relationships with other dogs (adults and littermates) and people (Scott, 1950). It is during this critical period of development that puppies also learn (in general terms) what they need to fear and what they do not need to fear. As discussed later, many animal behavior specialists and veterinarians now believe that the basis for much of the inappropriate aggression shown by dogs is fear-based, not dominance-based (Tynes, 2008). It is critically important to assure adequate socialization of dogs between 4-14 weeks of age and to help them overcome fear and anxiety. A study by Roll and Unshelm (1997) showed that about half (44%) of dogs that were aggressive to other dogs had not had a significant amount of contact with other dogs between the ages of 5 weeks and 5 months old. Dogs that fail to understand their hierarchical position with owners, familiar and unfamiliar people, and other animals during the critical period of socialization may develop unacceptable behavior later in life. This is discussed more fully in terms of leader recognition later in this Topic. Unfortunately, no one really knows how much early socialization is optimal for any individual dog.

Second, there are appropriate and acceptable forms of aggression shown by adult dogs. A major value of dogs after domestication must have been protection of people and livestock from marauding animals and from unfamiliar people (resource-guarding). Warning humans, by barking, of impending threats and also displaying more direct forms of aggression (biting) was highly desirable (and rewarded) behavior. Shown to the lower right (photograph of Schatze courtesy of Dr. Mark Plonsky) a well-trained Schutzhund is displaying normal, trained and highly desirable but highly controlled aggression in response to commands at a field trial. Aggression displayed in these circumstances is normal and is expected, based on training. It is critically important to understand that such aggression terminates on command and is therefore not problematic. Haug (2008) specifically notes, All forms of aggression are modified by learning. In fact, if working dogs do not display aggressive performance, according to training and on command, they are considered to be behaving abnormally. Animal trainers and behaviorists disagree about the source of aggression in working dogs. Some believe that some dog breeds possess inherited behavioral tendencies to aggression that can be exploited and controlled by training. This would appear to be in agreement with studies by Scott and Fuller (1965) and multivariate cluster analysis developed by Hart and co-workers (1985). Pfleiderer-Hogner (1979) was not able to show this with Schutzenhunden. Some trainers of protection dogs feel that aggressive tendencies are more individualized. There is virtually no disagreement that dogs of any breed, subjected to unexpected stimuli that cause fear can create stress for the dog. Likewise, dogs that are abused learn to be fearful and learn aggression. Inappropriate and unpredictable aggression: familiar and unfamiliar people, dogs, and situations Haug (2008) wrote a comprehensive review of canine aggression directed to unfamiliar people and dogs. Fear of unfamiliar stimuli (people, dogs, situations) was considered the most common cause of aggression (also see Luescher and Reisner [2008], below). The proximity of the stressful stimulus may be a factor. Some dogs will be observant and mindful when unfamiliar or unexpected stimuli are far from them, their owners, and their territory, but may become increasingly fearful as the stimulus moves closer. Haug notes that some dogs may display aggressive reactions (posturing, snapping, barking) while leashed or restrained, but not otherwise. Fear-related aggression may be well-developed by about 6 months of age, and this helps to differentiate it from territorial guarding and aggression that may not occur until at least 6 months of age or at a time of social maturity. Luescher and Reisner (2008) reviewed the complexities of canine aggression to familiar people and situations something of the greatest concern to owners and breeders. They note that the domestication of dogs and wolves from a common ancestor (roughly 12,000 years ago) was based on selection of many different traits. In terms of behavior, they believe dogs were selected to retain characteristics as adults that generally are seen in immature wolves. These immature characteristics include playful behavior, the need for extensive physical contact, and highly social interactions (barking, pawing, licking and nuzzling). Adult wolves form structured hierarchical packs in which body language and conflict avoidance is important (feral dogs do not form such packs). 7

These authors (Luescher and Reisner) define many different types of aggression, including: Fear-induced aggression Resource guarding aggression Conflict-related aggression (dominance) Territorial aggression to unfamiliar people and animals Predatory aggression Play-related aggression (see photo of Tank and Bruiser, above) Excitement-induced aggression Pain-induced aggression Maternal aggression Disease-associated aggression (with brain tumor growth, for example) Many people (including veterinarians, owners, and breeders of dogs) believe that dogs that bite owners or family members do so to assert dominance, potentially challenging the owner for leadership. Luescher and Reisner question this. Citing data from a number of studies, they found that in many cases of aggression in young adult (2-3 year old) dogs, aggressive behaviors emerged in puppies and became amplified as the dogs aged. In many cases, early aggressive behavior was correlated to fearfulness and resource guarding, not to the evolution of social bonds and relationships that appear to form after 6 months of age. Guy (1999) extensively studied aggressive behavior toward familiar people and other dogs (termed household aggression). This study found that approximately 40% of dogs presented to veterinary practitioners for evaluation of inappropriate behavior had growled at family members, 20% had growled and snapped when owners tried to remove food or toys from the dog (characteristic of resource guarding aggression), 15% of dogs had bitten owners, and 12% had bitten with sufficient force to leave a bite mark or penetrating wound. For most dogs, conflict management and avoidance is important. Body cues that signal stress and conflict may include repetitive yawning (not related to sleepiness), gazing and gaze avoidance, and changes in body posture. Erect, heightened and rigid postures may be signs of stress, fear, and potential conflict. Play bows, rolling, licking, whining, and submissive urination all may be strategies for avoiding conflict. Luescher and Reisner (2008) advise owners, breeders and others in contact with known or potentially aggressive, stressed and fearful dogs, to watch for changes in body language that may indicate thoughts of conflict are escalating or that conflict is imminent. Dogs that display overt signs of offensive aggression (erect body posture, erect tail and ears, lip curling with display of canine and incisors) are sending clear signals that they may act out and bite in a short period of time. Many veterinarians and behaviorists note that confident, offensively aggressive dogs will stare at a potential target before initiating an attack. Dogs that display defensive aggression appear to have different body language; this is usually seen in fearful dogs, placed in unpredictable situations (veterinary clinics, unfortunately). Defensively aggressive dogs may withdraw, lower their hindquarters and overall body position, and may lip curl, displaying many teeth. It is important to lower levels of stress and fear and these dogs, to prevent escalation of aggressive behavior.

Prevention and treatment of aggressive canine behavior

Veterinarians and other professionals who deal with inappropriate aggressive canine behavior feel it is challenging to treat and that the prognosis for controlling or eliminating aggression is guarded. Prevention of the development of aggressive behavior is critical for puppies and should be of great concern to breeders. Luescher and Reisner (2008) offer some guidelines and suggestions for development of well-adjusted puppies (growing, hopefully, into well-adjusted dogs). These guidelines include: Provide a safe, comfortable, and predictable environment, free of intense stimuli (noise would be one example) that might induce fear and stress, Handle frequently, Wean at an appropriate time; early weaning may induce stress and fear, Be aware of health issues; some work has shown that early, severe illness can lead to fearfulness in adults, Encourage controlled socialization and exposure to diverse, safe environments that will help puppies understand and overcome fear, Be consistent in interactions and training, Punishment-based training may induce fear and later aggression: physical punishment may have poor outcomes; when puppies are punished, and suffer physical discomfort, they may become more fearful and frustrated - an overview of effective training strategies can be found at http://veterinarymedicine.dvm360.com/Punishment, (cited in Tynes, 2008) Regular meal feeding, regular interactions with humans, and regular exercise set the stage for good human-dog interactions.

You and your veterinarian must be a team when trying to help treat a dog with aggressive behavior. Some general guidelines for evaluation and treatment of canine aggression are outlined by Luescher and Reisner (2008) and Tynes (2008) and are to be found below. First, it is important to determine the basis for aggression in an individual dog, and not to assume its just something in this breed. In some cases, physical ailments (thyroid disease, inflammation and tumors in the brain, liver failure, infectious agent [rabies, for example]) may be a cause of aggressive behavior. A recently published study of 238 dogs examining potential links between itchiness (pruritis) and either anxiety or aggression found no relationship (Klinck, et. al., 2008). These authors did find that dogs treated with glucocorticoids (cortisone) were more likely to be anxious and reactive when confronted by loud noises (thunderstorms or other noise). It is essential to diagnose these problems with a thorough case history, physical examination, and laboratory tests (hematology, serum chemistry, and urinalysis). Second, if aggression appears to be a primarily behavioral problem, veterinarians specifically trained in dealing with behavior should be consulted. Several professional organizations, including the American College of Veterinary Behaviorists (www.dacvb.org) and American Veterinary Society of Animal Behavior (www.avsabonline.org) can provide recommendations for certified veterinary behaviorists to help deal with problem dogs. Not all veterinarians in clinical practice are interested in or trained to treat behavior problems. It is very important for owners and breeders of problem dogs to find a qualified person to help.

Third, owners and breeders should realize that problem behaviors like aggression develop and persist for many reasons (genetics, brain chemistry, fear, environment, and so forth) and that controlling the expression of behavior is not a simple matter of giving a pill (discussed below) or subjecting the dog to training. Everyone should be wary of any person who represents themselves as a dog trainer who can break an aggressive dog and whether they can actually achieve a positive outcome. I personally would advise caution in simply seeking someone who trains dogs in dealing with an aggressive dog. I think there is a world of difference between teaching a well-adjusted pet to play Frisbee and taking an offensively aggressive dog and transforming them to a well-adjusted and predictable pet. Fourth, veterinary behaviorists usually approach the treatment of aggressive dogs in a threepart approach (Luescher and Reisner, 2008). I: Take a general history and assess normal environment and management of the problem dog. Perform physical examination and laboratory studies to detect underlying physical problems that may cause fearfulness and aggression II: Take a history that assesses how the dog interacts in the environment, with familiar and unfamiliar people and situations, and attitude toward major daily events III: Study the actual aggression problem: when does it occur, how often, what triggers it, what does it look like, what has been attempted to treat it Once the nature of aggression is assessed, several approaches can be taken that seem to help. First, the dog has to have as much predictability in their environment as possible. For example, dogs should be fed regular meals twice daily rather than having unlimited access to food at all times. The setting of a regular mealtime creates predictability and structure for the dog. Second, a commitment must be made on the part of the owner to regularly (at least twice daily) exercise the dog in a safe manner. It seems pretty obvious that owners should not take dogs that are aggressive to unfamiliar people and other dogs to places where they will encounter unfamiliar people and dogs! Many behavior specialists recommend walking the dogs with a head halter leash, which encourages owner control and dog attentiveness. Third, dogs that are aggressive should be kept in environments that do not encourage fearful or territorial aggression. Some behavior specialists have noted that crating dogs may both prevent aggressive episodes and allow security for the dog. Crating should be used ONLY for limited periods of time each day and should not be used as a form of isolation and punishment. Fourth, there is broad, uniform agreement that physical punishment is not effective in modifying the aggressive behavior of dogs. It should be avoided. Veterinary behavior specialists (Yin, 2007) acknowledge that traditional training methods based on the concept of dominance and submission are outdated and may, in fact, make aggression worse, due to fear, frustration, and inconsistency. Instead, many advocate a system of rewarding desirable behaviors and not rewarding less desirable conduct. A bond between dog and owner is based on reward, trust, and a lack of fear of punishment (domination). As with all training methods and theories, it only works if the owner and dog work at it consistently, constantly, and to successful goals. Displacement and desensitization training, done by capable professionals and committed owners, can help control aggressive behaviors of dogs. In this type of training, small changes are made in the environment or triggers that help dogs become less reactive. Luescher and Reisner (2008) discuss how dogs that act aggressively when food is offered or withdrawn can 10

be subjected to gradual behavioral modification. One method discussed, is simply placing food in a room without the dog being present, allowing the dog into the room to eat, and then removing the dog from the room after eating. This is thought to break down a connection of possession guarding (food) and the owner. Another method involves gradual feeding from a long-handled pot, so that the dog cannot attack the owner nor will it be able to guard its food. Once again, behavioral modification is a job for trained behaviorists. Finally, lets discuss drug therapy. It is well known that humans suffering from anxiety and depression can, in many cases, be treated effectively (clinical signs of illness decrease) with a combination of psychotherapy and drug therapy. In some cases, drugs alone can significantly help. We are just beginning to understand the complex neurochemistry associated with behavior in dogs. Several studies in this area were noted above. We are also just beginning to understand that some drugs, especially drugs known as selective serotonin reuptake inhibitors (SSRIs) may help modify the behavior of some dogs in some situations. For example, there have been some preliminary studies done that support the use of the drug fluoxetine for treating anxiety disorders in some dogs. There is a presumption that this drug, given to some dogs, will modify the levels of critical neurotransmitter chemicals in the brain (serotonin), helping to calm dogs and decrease inappropriate behavior. There have been no carefully controlled clinical trials of this drug and it should not be viewed as a known effective treatment, especially for canine aggression. There is a difference of opinion among animal behaviorists about the effectiveness of antianxiety drugs, like diazepam, in managing canine aggression. Some behaviorists, based on observations of individual dogs, have seen improvements in behavior. Other professionals caution that by changing an anxiety threshold (essentially removing anxiety that is blocking behavior), such drugs might make aggression worse in some dogs (Crowell-Davis, et. al., 2006). In a recently published study (Herron, et. al., 2008), diazepam was judged only minimally to modestly effective in controlling some anxiety-associated behaviors and was often discontinued by owners who were unhappy with side effects (sedation, agitation/hyperactivity, increased appetite). Bottom line: there is a lot of work still to be done before effective drug therapy for canine aggression can be prescribed. In summary Canine aggression is a significant problem. The contributions of genetics, environment, upbringing and training are discussed in this Topic. Dog breeders should be aware that there is a complex interaction between inherited breed traits, environment of adult and young dogs, active socialization, and learning that will create adult dog behavior. Responsible breeders should be alert to signs of fearfulness in puppies and to understand that the current thinking on canine aggression is that much of it is fear based. Several research studies have been able to link inappropriate adult behavior with specific breeding animals, but this is a largely unexplored field. Nonetheless, it is very important that breeders regularly follow-up with owners of dogs they have bred to see if there are physical and behavioral problems that emerge in some litters and from some pairings. Dog breeders, dog owners, and veterinarians should be knowledgeable about the importance of body language and conflict avoidance for dogs. Dogs displaying body language of offensive or defensive aggression should not be pushed to a point of acting out their aggression. By the same token, potentially aggressive dogs should not be physically punished, since this may actually heighten levels of fear and foster biting. Recent studies have noted that dogs may be 11

acutely sensitive to human body language and even to human odors associated with emotional behavior. At times of potential conflict, humans should not escalate human behaviors that inappropriately aggressive dogs find threatening. Problem dogs should be examined by veterinarians and by qualified animal behaviorists. Physical problems that may be associated with aggression should be actively investigated. With overtly healthy aggressive dogs, the dog, the owner, and the behaviorist all have to commit the effort needed to help the dog. It is absolutely mandatory that once an owner identifies an aggressive or potentially aggressive dog, they must control this dog so that it does not injure people or other animals. There are no magic pills or quick training methods for treating overcoming canine aggression. The science of using drugs to modify dog behavior and perception is in its infancy and it may take many years of study before drugs to predictably modify behavior are available. Dog owners should understand that there may be significant limitations of behavioral training in eliminating aggressive behavior. As concerned dog owners and breeders, it is our responsibility not to create fearful, aggressive dogs, and to reach out and educate the public about proper dog behavior and upbringing (Reisner, et. al., 2008). Lets try to be sure that, within our power, we raise great pets and not subject any more children to dog bite scars for life (see left).

(John, Tank, and Bruiser Robertson at the Dog Walk Against Cancer, October 11, 2008. The Boys will be 3 years old on December 25, 2008))

References Arkow, P, Animal control laws and enforcement, Journ Amer Vet Med Assoc 198:1164-1172, 1991 Centers for Disease Control, National Dog Bite Prevention Week, September 30, 2008 (http://www.cdc.gov/ncipc/duip/biteprevention.htm) Crowell-Davis, S, Murray, T, Benzodiazepines, In Veterinary Psychopharmacology, CrowellDavis, S, Murray, T, (Eds.), Blackwell Publishing, Ames, IA, 2006 Guy, N, Canine household aggression in the caseload of general veterinary practitioners in Maritime Canada, Master of Science thesis, Atlantic Veterinary College, University of Prince Edward Island, 1999 12

Hart, B, Miller, M, Behavioral profiles of dog breeds, Journ Amer Vet Med Assoc 186: 11751180, 1985a Hart, B, Hart, L, Selecting pet dogs on the basis of cluster analysis of breed behavior profiles and gender, Journ Amer Vet Med Assoc 186:1181-1185, 1985b Haug, L, Canine aggression toward unfamiliar people and dogs, Vet Clin NA Small Animal 38: 1023-1041, 2008 Herron, M, Shofer, F, Reisner, I, Retrospective evaluation of the effects of diazepam in dogs with anxiety-related behavior problems, Journ Amer Vet Med Assoc 233: 1420-1424, 2008 Jacobs, C, Van Den Broeck, W, Simeons, P, Increased volume and neuronal number of the basolateral nuclear group of the amygdaloid body in aggressive dogs, Brain Res 170: 119-125, 2006 Klinck, M, Shofer, F, Reisner, I, Association of pruritis with anxiety or aggression in dogs, Journ Amer Vet Med Assoc 233: 1105-1111, 2008 Lue, T, Pantenburg, D, Crawford, P, Impact of the owner-pet and client-veterinarian bond on the care that pets receive, Journ Amer Vet Med Assoc 232: 531-540, 2008 Luescher, A, Reisner, I, Canine aggression toward familiar people: A new look at an old problem, Vet Clin NA Small Animal 38: 1107-1130, 2008 MacDowell, E, Heredity of behavior in dogs, in Dept. of Genetics Report 101-56, Davenport, C (Ed.), Carnegie Institute, Pittsburgh, PA Mackenzie, S, Oltenacu, E, Houpt, K, Canine behavioral genetics a review, Appl Animal Behav Science 15: 365-393, 1986 Mahut, H, Breed differences in the dogs emotional behaviour, Can Journ Psychol 12: 35-44, 1958 Mendocino Coast Humane Society, Pet Information Sheets: dog aggressive behaviors, (http://mendocinohumane.org/html/aggressive.html) Moffat, K, Addressing canine and feline aggression in the veterinary clinic, Vet Clin NA Small Animal 38: 983-1003 MMWR, Nonfatal dog bite-related injuries treated in hospital emergency departments, United States, 2001, MMWR Weekly 52(26): 605-610, 2003 (http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5226a1.htm) Pfleiderer-Hogner, M, Moglichkeiten der Zuchtwertschatzung beim Deutschen Schaferhund anhand der Schutzhundenprufung (Doctoral Thesis), Ludwig-Maximilians-Universitat, Munich, FDR, 1979 Podberscek, A, Serpell, J, The English Cocker Spaniel: preliminary findings on aggressive behavior, Appl Anim Behav Sci 47:75-89, 1996 13

Reisner, I, Mann, J, Stanley, M, et. al., Comparison of cerebrospinal fluid monoamine metabolite levels in dominant-aggressive and non-aggressive dogs, Brain Res 160: 57-64, 1996 Reisner, I, Houpt, K, Shofer, F, National survey of owner-directed aggression in English Springer Spaniels, Jour Amer Vet Med Assoc 227:1594-1603, 2005 Reisner, I, Shofer, F, Effects of gender and parental status on knowledge and attitudes of dog owners regarding dog aggression toward children, Journ Amer Vet Med Assoc 233: 1412-1419, 2008 Roll, A, Unshelm, J, Aggressive conflicts amongst dogs and factors affecting them, Appl Animal Behav Science 52: 229-242, 1997 Sacks, J, Sinclair, L, Gilchrist, J, Golab, G, Lockwood, R, Breeds of dogs involved in fatal human attacks in the United States between 1979 and 1998, Journ Amer Vet Med Assoc 217: 836-840, 2000 Salman, M, Hutchinson, J, Ruch-Gallie, R, et.al., Behavioral reasons for relinquishment of dogs and cats to 12 shelters, J Appl. Animal Welfare Science 3: 93-106, 2000 Scarlett, J, Salman, M, New, J, Kass, P, The role of veterinary practitioners in reducing dog and cat relinquishments and euthanasias, Journ Amer Vet Med Assoc 220: 306-311, 2002 Scott, J, Marston, M, Critical periods affecting the development of normal and maladjustive social behavior in puppies, Journ Gen Psychology 77:25-60, 1950 Scott, J, Fuller, J, Dog behavior The genetic basis, Univ of Chicago Press, Chicago, IL, 1965 Tynes, VV, Debunking 10 behavior myths, Vet Med 103: 504-514, 2008 Van den Berg, L, Genetics of aggressive behavior in Golden Retriever dogs, Doctoral Thesis, Utrecht University, 2006 Yin, S, Dominance versus leadership in dog training, Comp Vet Med (July): 414-417, 432, 2007

14

Topic 13: Canine Diabetes Mellitus Stephanie Shrader and John Robertson Introduction and Overview Diabetes mellitus is a complex endocrine metabolic disorder which results in hyperglycemia (abnormally high blood glucose [blood sugar]) and glycosuria (glucose in the urine). The primary cause of the disease is a lack of activity of the hormone insulin. Two main forms of diabetes mellitus are recognized. Type I diabetes is characterized by an inability of the beta cells of the pancreas to produce insulin (see below). In people, Type I diabetes mellitus is also known as juvenile onset diabetes since it may be seen in young people. Type II diabetes mellitus is caused by resistance to the activity of insulin at the cellular level. In people, this may also be known as adult onset diabetes and is the most common form of diabetes in humans. The underlying causes of most cases of diabetes mellitus are not known. However, some known factors can trigger the onset of diabetes including exposure to some drugs, abdominal tumors, pancreatitis and surgical procedures. According to a 2004 survey completed by the makers of Vetsulin (the only FDA-approved veterinary product for the treatment of diabetes mellitus in both dogs and cats), approximately 1 in every 500 dogs suffers from diabetes mellitus. Survey results also showed that of the more than 200 veterinarians polled, 70% had between one and 10 diabetic canine patients, while 26% noted that they had 11 or more diabetic canine patients. West Highland White Terriers are one of the breeds predisposed to develop diabetes mellitus, so it is important for the owner to understand the signs and symptoms of the disease, the disease process, and treatments available. The Relationship between the Pancreas and Insulin The pancreas, an elongated organ located near the beginning of the small intestine (at the duodenum), has both exocrine and endocrine functions. This topic does not involve the exocrine pancreas, but know that it does play a vital role in digestion such as the secretion of substances into the duodenum that aid in digestion, such as bicarbonate ions and digestive enzymes. The endocrine pancreas is where we will focus our attention. Its function is to synthesize and secrete various hormones. This portion of the pancreas is made up of clusters of cells termed the Islets of Langerhans which can easily be recognized in histological preparations (Figure 1 left ). The islets are made up of three major cell types (alpha, beta, and delta cells) which secrete specific hormones. The alpha cells secrete glucagon (which raises blood glucose levels), the beta cells secrete 1

insulin (which lowers blood glucose levels) and the delta cells secrete somatostatin (which inhibits the secretion of other hormones). Insulin is the key player in diabetes mellitus, so it is the target of our discussion. Insulin is synthesized and secreted only by the beta cells of the pancreas. During synthesis, insulin mRNA is translated as a precursor called preproinsulin, and removal of its signal peptide during insertion into the endoplasmic reticulum (ER a site in each cell where proteins are made) generates proinsulin. Proinsulin is made up of three parts: a carboxy-terminal A chain, an amino-terminal B chain, and a connecting chain in the middle, C peptide. The proinsulin is exposed to several endopeptidases (types of intracellular digestive enzymes) within the ER which excise the C peptide. This excision generates the mature, active form of insulin. Insulin and free C peptide are packaged in the Golgi apparatus (a subcellular organelle) into secretory granules which accumulate in the cytoplasm. When pancreatic islet beta cells are stimulated (by elevated blood glucose levels) the insulin and C peptide are excreted via exocytosis. Insulin can then regulate blood glucose levels. C peptide is currently known to have no biological function. This process is diagrammed below, Figure 2.

Figure 2. Cellular events in the production and secretion of insulin. Source: Journal of Transitional Medicine, Ren, 2007.

Physiologic Role of Insulin Lets suppose your Westie just ate a huge meal, rich in carbohydrates (like Thanksgiving Dinner!). How does his/her body utilize the nutrients (especially the carbohydrates) as an energy source and how is insulin involved? First, the body is going to liberate the glucose from the carbohydrate molecules by the process of digestion in the small intestine via a chemical reaction known as hydrolysis. This liberated glucose is then absorbed by the blood. As the blood glucose level rises, the release of insulin is triggered. Insulin, through activity at the surfaces of most cells, then causes cells in the body to take up and use glucose or store glucose as glycogen. Skeletal muscle and fat cells readily use glucose immediately; liver cells may process it for storage (in the form of intracellular glycogen) or convert it. The overall effect of the uptake and storage of glucose from the blood is a decrease in the blood glucose level, mediated at the cellular level by the activity of insulin. Insulin has a variety of functions in the body related to glucose, the main role being the transmembrane transport of glucose and amino acids. It is also vital to glycogen formation in the liver and skeletal muscle, conversion of glucose to triglycerides, nucleic acid synthesis, and protein synthesis (Cotran, et al, 1999). With insufficient amounts of insulin being produced (Type I diabetes mellitus) or when insulin cannot trigger glucose uptake (Type II diabetes mellitus), the body cannot metabolize glucose as a source of energy. Unused glucose will accumulate in the circulation (hyperglycemia fasting blood glucose above 70110 mg/dl). To compensate for the lack of intracellular glucose, the body and its cells will first go through a metabolic process known as glycogenolysis, which liberates glycogen stores for use as energy. When these stores are used up, the body begins a process known as lipolysis (the breakdown of fats) in order to obtain energy for proper functioning. While this is initially beneficial, fat metabolism in diabetics can progress to ketoacidosis. Ketoacidosis results from high concentrations of ketone bodies, formed by the deamination of amino acids and the breakdown of fatty acids. Diabetes mellitus and resultant ketoacidosis, if left unchecked, can cause an acidification of the blood (blood pH drops) and eventually even death. Diabetes mellitus, if unmanaged, can be life-threatening. It is a paradox of this disease nutrients are available to cells in the circulation, but without insulin, the cells are starving. Starvation at the cellular level may be associated with increased appetite and eating (polyphagia). Long-term, poorlycontrolled diabetes may actually waste away as body stores of calories are used up. Type I Diabetes Mellitus This form of diabetes mellitus is the most common form found in dogs. In human medicine, it was once known as juvenile diabetes or insulin-dependant diabetes. It is the result of insulin deficiency, caused by the destruction of the pancreatic beta cells (Cotran, et al, 1999). This destruction of beta cells is likely 3

due to the combination of autoimmunity, genetics and environmental factors. It has been known for decades that dogs (and people) will develop immune reactivity to pancreatic islet proteins, and immune/inflammatory cells may destroy islets, resulting in diabetes. The observation that some breeds, including Westies, have a higher risk of developing diabetes mellitus indicates there may be multiple, currently undefined, genetic factors leading to spontaneous destruction of pancreatic islets. The fact that both WHWT and Cairn Terriers have an increased risk of developing diabetes mellitus is more proof of a genetic linkage, since these Scottish terriers are ancestrally related. The role of diet composition, obesity, and environment may be very significant, but poorly understood (Greco, et. al., 1995, Rand, et. al, 2004). Although any dog can develop diabetes mellitus, dogs that are middle aged or intact bitches, or of certain breeds are at greater risk. According to the Intervet website (http://www.caninsulin.com/Diabetes-mellitus-in-dogs.asp), breeds that are prone to developing Type I diabetes include: Keeshond Poodle Samoyed Dachshund Alaskan Malamute Miniature Schnauzer Chow Chow Beagle Doberman Pinscher Labrador Retriever Puli Old English Sheepdog Golden Retriever Miniature Pinscher English Springer Spaniel Rhodesian Ridgeback Schipperke Finnish Spitz West Highland White Terrier Cairn Terrier

Signs of Type I diabetes include polyuria (frequent urination), polydypsia (increased thirst), polyphagia (increased hunger), weakness, weight loss, increased susceptibility to infections (such as skin infections or urinary tract infections), depression and potentially loss of vision due to cataract formation. As already discussed, if left undiagnosed, diabetic ketoacidosis can develop. This is now a medical emergency that will require intravenous fluids and fast acting insulin (http://www.caninsulin.com/Diabetes-mellitus-in-dogs.asp). In order for the veterinarian to diagnose Type I diabetes mellitus, urinalysis and serum chemistry analysis will be performed. A blood sample and urine sample will be collected to do these tests. Laboratory findings typically focus on detecting hyperglycemia (elevated blood glucose) and glucosuria (glucose in the urine, which is never normal). Abnormal values can also include hypercholesterolemia, increased serum alkaline phosphatase (ALKP), and alanine aminotransferase (ALT) (resulting from hepatic lipidosis, ketonemia, and ketonuria).

In a normal patient, glucose filtered by the kidney glomeruli is reabsorbed by the proximal tubules. In a diabetic patient, however, the increased amount of glucose exceeds the reabsorptive capacity (renal threshold) of the kidney, resulting in excretion of glucose in the urine, glucosuria. Normal glucose values (Meyer, 1992): Serum chemistry Renal threshold 60-110 mg/dL 180 mg/dL

When you and your veterinarian meet to discuss the results of their examination of your Westie, they will not only review laboratory results, but will also examine the signs and symptoms to be sure of the correct diagnosis. For example, there can be other causes for hyperglycemia besides diabetes mellitus and these need to be considered. According to Meyer (1992), these include: Postprandial hyperglycemia (increased blood glucose levels following a meal) Exertional epinephrine release due to stress (common in cats) Increased glucocorticoids (caused by stress, administration of corticoids or ACTH, hyperadrenocorticism) Acute pancreatitis Drug induced-thiazide diuretics, morphine, intravenous fluids with glucose, accidental exposure to ethylene glycol (anti-freeze) Glucagon-secreting pancreatic tumor Once the veterinarian has established that your dog has Type I diabetes mellitus, he/she will discuss treatment with you. The goals in treating diabetes mellitus are to supply enough insulin (by injection) to minimize the clinical signs of diabetes, the risk of hypoglycemia, and the development of long-term complications. Establishing the amount of insulin your pet may need and how often your Westie needs to be treated may require several weeks. The veterinarian is likely to have to make adjustments to the initial dosage based on clinical signs, urinalysis results, and glucose curve values until he/she feels that adequate blood glucose control is established. According to the Vetsulin website (http://www.vetsulin.com/vet/DosingOverview.aspx), in a US clinical study, blood glucose control was considered to be adequate if: An acceptable blood glucose curve was achieved (that is, a reduction in hyperglycemia and a stable levels of 60160 mg/dL achieved) Clinical signs of hyperglycemia (polyuria, polydipsia, and ketonuria) improved Hypoglycemia (blood glucose <50 mg/dL) was avoided

Many owners initially find the administration of insulin (insulin shots) to be an unnerving task. Really, its not that bad! In addition to your veterinarian going over the steps and giving you paperwork, there is a wonderful online tutorial by Auburn University, College of Veterinary Medicine that goes through each step of the dosing process, storage and handling procedures. It is a great aid for those of you who just learned that you have a diabetic pet and a good refresher for those of you who are seasoned veterans. Here is the website: Diabetes Mellitus: How to Administer Insulin Properly (http://www.vetmed.auburn.edu/sac/mededu/diabetes/home.html. Type II Diabetes Mellitus This form of diabetes mellitus is much less common in dogs and thus will only be briefly discussed. In human medicine, it is also known as adult-onset or noninsulin-dependent diabetes. It develops when the body becomes resistant to insulin or when the pancreas stops producing enough insulin. The exact cause is unknown, but excess weight and inactivity seem to be important factors. As with Type I diabetes, if left undiagnosed, the results of Type II diabetes can be fatal. There is no current cure, although it can be prevented and managed by eating healthy, exercising, and maintaining a healthy weight (See information at www. MayoClinic.com). Complications of Untreated and Poorly Managed Diabetes Mellitus One of the most common complications of untreated diabetes in dogs is the development of cataracts (this topic is discussed more fully elsewhere in the Westie Health E-Book). These usually have rapid onset due to the change in osmotic environment of the lens. In a non-diabetic patient, glucose diffuses from the aqueous humor into the lens and is metabolized to acetic acid. In the uncontrolled diabetic patient this system becomes saturated. Glucose then becomes metabolized via an alternative sorbitol pathway leading to high concentrations of sorbitol and ultimately fructose within the lens. Glucose is freely diffusible from the lens but sorbitol and fructose are not. These solutes are highly osmotic, which means they draw water into the lens causing it to swell, leading to lens fiber disruption and irreversible cataract formation (Hardy). Another complication of diabetes mellitus is glaucoma. This arises because of damage to the optic nerve caused by increased intraocular pressure, as illustrated in Figure 3 to the left (Image is from The New York Times, 2007). Glaucoma can have many causes but it is usually caused by a narrow or obstructed drainage 6

angle (a structure in the front of the eye, under the clear cornea) through which the aqueous humor should flow. Glaucoma can lead to intense ocular pain, decreased vision, lots of money spent on veterinary bills/medications and eventually blindness. Stephanie adopted a diabetic dog a few years ago with severe glaucoma. She was able to treat the diabetes, but unfortunately his glaucoma was too far advanced. He required about $150 worth of ocular medications per month, none of which seemed to relieve the pain. Just about the time I decided to have an enucleation performed, his eyes began to atrophy and he became less painful. This is a picture of Rudy Shrader, as his intraocular pressure regressed. Dont let this happen to your dog! If you suspect your dog may be diabetic, get him/her to the veterinarian immediately because there can be severe consequences if left untreated.

Summary and important points Diabetes mellitus is a relatively common metabolic and treatable disease in dogs, including West Highland White Terriers. The causes are unknown but include pancreatic disease, genetics and possible environmental factors. Common signs are increased thirst (polydipsia), increased urination (polyuria), and appetite (polyphagia). Simple blood and urine tests can be used to diagnose the disease. Treatment usually involves monitoring blood glucose and giving daily injections of insulin that are sufficient to meet daily metabolic needs. If left untreated, diabetes mellitus can cause significant spikes in blood sugar, ketoacidosis and coma, cataracts, glaucoma and even death. Properly treated dogs can live relatively normal lives.

Additional resources for owners and veterinarians Websites cited in the text of this topic: http://www.vetsulin.com/ Vetsulin Veterinary Market Survey, 2004. http://www.vetmed.auburn.edu/sac/mededu/diabetes/home.html http://www.vetinfo.com/ddiabt.html http://www.vetmed.wsu.edu/ClientEd/diabetes.aspx Other references for owners and veterinarians: Davies, M, Diabetes mellitus in Canine and Feline Geriatrics. Wiley-Blackwell Publishers, New York, 1996. German, AJ, "The growing problem of obesity in dogs and cats." Journal of Nutrition 136: 1940S-946S, 2006 Greco, DS, Peterson, ME, Diabetes mellitus, in Veterinary Clinics of North America, 25: 3. Philadelphia: Saunders, 1995. Levin, CD, Dogs, diet, and disease an owner's guide to diabetes mellitus, pancreatitis, Cushing's disease & more. Oregon City, OR: Lantern Publications, 2001. Rand, JS, Fleeman, LM, Farrow, HA, Appleton, DJ, Lederer, R, "Canine and feline diabetes mellitus: nature or nurture?" Journal of Nutrition 134: 2072S080S, 2004. References and general background information Canine Diabetes Mellitus." Managing Diabetes Mellitus in Cats and Dogs. Intervet/Schering-Plough Animal Health. 3 Mar. 2009 http://www.caninsulin.com/ Dogs: Vetsulin dosing and administration." Vetsulin. Intervet/Schering-Plough Animal Health. May 29, 2009 <http://www.vetsulin.com/vet/default.aspx>. Cotran, RS, Kumar, V, Collins, T, Robbins, SL, . Robbins Pathologic Basis of Disease. Philadelphia, Saunders, 1999. P. 914. Glaucoma. The New York Times. 2007. The New York Times. 20 May 2009 <http://www.nytimes.com/imagepages/2007/08/01/health/adam/9349Glaucoma.h tml>. 8

Glaucoma: what is it?" MyDr.com. MIMS Consumer Health Group. 20 May 2009 <http://www.mydr.com.au/eye-health/glaucoma-what-is-it>. Hardy, RM, Diabetes Mellitus in the Dog. Rep. St. Paul: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Minnesota. Meyer, DJ. Veterinary laboratory medicine interpretation and diagnosis. Philadelphia, Saunders, 1992. Ren, J, Jin, P, Wang, E, Liu, E, Harlan, DM, Li, X, Stroncek, DF, "Pancreatic islet cell therapy for type I diabetes: understanding the effects of glucose stimulation on islets in order to produce better islets for transplantation," Journal of Transitional Medicine 5: 2007. Type 2 diabetes." MayoClinic.com. 23 May 2009. Mayo Clinic. 29 May 2009 <http://www.mayoclinic.com/health/type-2-diabetes/DS00585>.

Topic 14: Keratoconjunctivitis sicca (Dry eye) Stephanie Shrader and John Robertson Keratoconjunctivitis sicca (KCS) is a disease of the eyes, characterized by inflammation of the cornea and conjunctiva, secondary to a deficiency in the aqueous (watery) portion of the tear film (Cote, 2009). This leads to dry, irritated eyes. It is more commonly known as dry eye or in veterinary terminology, xerophthalmia. KCS is often seen in West Highland White Terriers, but is also common in the Lhasa Apso, English Bulldog, American Cocker Spaniel, English Springer Spaniel, Pekingese, Pug, Chinese Shar Pei, Yorkshire Terrier, Shih Tzu, Miniature Schnauzer, German Shepherd, Doberman Pinscher, and Boston Terrier. According to Cote, there is an increased predisposition reported for both neutered male and female dogs, and for female West Highland White Terriers, in particular. The current incidence of KCS across all dog breeds ranges between 1% and 2%, depending on which research article is referenced. Understanding Tears The tear film that covers the eyes is made up of three distinct layers (see Figures 1 and 2 below). The outermost layer is made up of oils, which are secreted by the Meibomian glands, located along the edge of the eyelid. This lipid layer provides protection against evaporation and cohesive properties that prevent tears from simply pouring out over the lower eyelid onto the face. The middle layer is the aqueous layer, produced by the lacrimal glands. In the dog there are two lacrimal glands; one is located just above and slightly lateral to the eye, and the other is located medially by the third eyelid (also known as the nictitating membrane). The aqueous layer contains mostly water, along with important proteins and enzymes that help to maintain proper osmolarity and protect against infection by viruses and bacteria. The innermost layer of the tear film is the mucin layer. This hydrophilic layer is produced by tiny secretory cells in the conjunctiva known as goblet cells. Being that this is the innermost layer, it is what immediately bathes and protects the cornea. Figure 1. Cross sectional view of the composition of tears [Source: http://www.optrex.co.uk/healthcare_professi onals/refresh_your_knowledge_on_dry_eye s.php]

Figure 2: The location of the lacrimal (tear producing) apparatus in dogs. Source http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/30101.htm

What causes keratoconjunctivitis sicca? According to Kirk Gelatt (2005), a noted veterinary ophthalmologist, the failure of tear production and corneal lubrication, due to lacrimal gland hyposecretion, may result from a single disease process or a combination. The potential causes for KCS, listed in the Clinical Veterinary Advisor (Cote. 2009), are presented below, with in depth explanations for each. Immune-mediated adenitis Immune-mediated adenitis simply means that the bodys own immune system is causing abnormal inflammation of a lymph node or gland; in this case, the lacrimal gland. According to the Merck Veterinary Manual (2009), this is thought to be the most common cause of KCS in dogs. What triggers immune-mediated adenitis is currently not known. Congenital acinar hypoplasia (congenital alacrima) Alacrima (literally no tears) refers to a variety of lacrimal secretory disorders that are mostly congenital (genetic) in origin. This is an autosomal recessive trait a recessive allele carried on the non-sex determining chromosomes. If two animals mate, each having the recessive trait for alacrima, there is a 25% chance that the offspring will 2

inherit the disorder. Breeding dogs with congenital disorders is problematic - this continues the disease in future offspring. WHWT breeders must appreciate this when selecting mating pairs so as not to propagate this genetic problem. Most breeders will also monitor the health of litters they have sold, in order to detect the emergence of this problem in litters or breeding stock. For potential buyers of WHWT from unknown sources, there is an old Latin saying, Caveat emptor Let the buyer beware. Get the bitchs and sires history and health records before purchasing your new pet. Dont rely on a verbal assurance that the puppy is pure bred. Dealing with well-established breeders will help prevent heartache and medical bills. Drug and anesthesia induced KCS Certain drugs/anesthetics can produce either temporary or permanent KCS. Transient KCS is sometimes noted following anesthesia and surgery but the exact relationship between anesthesia and KCS is unknown. It is important for all veterinarians to provide a lubricating ointment or fluid to protect eyes during surgery to prevent transient KCS. Iatrogenic KCS Iatrogenic means a medical problem may develop as a result of or associated with a physicians/veterinarians treatment. For example, removal of the gland of the third eyelid (nictitans gland) to correct a disease problem can increase the risk of a dog developing KCS, since tear-production is associated partially with the nictitans. Years ago, a condition known as Cherry Eye (inflammation and proliferation of lymphoid tissue near the nictitans) was often treated by removal the gland of the third eyelid. It was common to have chronically dry eyes after this procedure. Today, the importance of this gland is understood, and instead of removal, it is medically and surgically reduced if protrusion occurs. Infectious diseases The most common viral disease in dogs, canine distemper virus, is often associated with KCS. Typical ophthalmic complications associated with canine distemper virus infection include conjunctivitis, chorioretinitis (retinal inflammation) and acute KCS (Gilger, 2009). Canine distemper virus (CDV) is a highly contagious disease that is typically spread via aerosolized respiratory secretions. In most cases, the virus first attacks the respiratory system, and then spreads to the gastrointestinal and nervous systems. When the virus colonizes sensitive glands of the eye, including the cornea, this can lead to KCS. In this instance, KCS is caused due the virus attack on lymphoid tissue (leading to immunosuppression) and ocular epithelial cells. Metabolic diseases/disorders 3

Systemic metabolic diseases associated with the development of KCS include hypothyroidism, diabetes mellitus, hyperadrenocorticism (Cushings disease), atopy, and dysautonomia (Kaswan, et al, 1998). Each of these diseases represents a chapter of its own, so it will suffice to mention them in passing. Just be aware that KCS is a possible complication in each of these diseases. Neurologic Parasympathetic innervation to the lacrimal glands is provided by cranial nerve VII (facial nerve). Damage to this nerve, either due to disease or trauma, can result in KCS by decreasing the amount of tear film produced. One could also have loss of sensory innervation to the ocular surface if there is damage to cranial nerve V (trigeminal nerve) (Gelatt, 2005). The ophthalmic branch of the trigeminal nerve provides innervation to the lacrimal gland, conjunctiva, and upper eyelids. Damage to this nerve, either by disease or trauma, could result in KCS. How is KCS diagnosed? Dogs with KCS are often presented to the veterinarian because they have red/irritated eyes, are pawing at their eyes because they itch and/or hurt, and may have a thick ocular discharge that can range from off-white to green in color. Upon physical examination, the doctor may also notice that the third eyelid is protruded, that the cornea is no longer shiny in appearance, that there is corneal keratitis (inflammation) present. In advanced cases of disease, corneal scarring may lead to potential vision loss. In order to differentiate KCS from other ocular disorders, the veterinarian will do a comprehensive eye exam that will include a Schirmer tear test (STT), fluorescein staining of the cornea, and evaluation of the intraocular pressures (to see if there is glaucoma). Schirmer tear test (see Figure 3 below) The Schirmer tear test is designed to quantify the amount of tear film produced by the eye. It is a painless procedure (but looks yucky). The veterinarian will place a thin strip of paper (about an inch long and quarter of an inch wide) just under the eyelid for one minute. This piece of paper has a small scale on it. During this time period, the tear film will wick up the paper. When the minute is over, the tear production can be quantified, based on mm/min.

Figure 3. The Schirmer tear test. Calibrated paper strips are placed under the eyelid for a short period of time to quantify tear production. Normal and abnormal values for canine tear production are found below (these values can vary slightly depending on which text is referenced): Normal: 15 mm/min Early KCS: 11-14 mm/min Mild/moderate KCS: 6-10 mm/min Severe KCS: 5 mm/min Application of fluorescein stain (see Figure 4 below) Fluorescein is a bright yellow/orange stain that is used to detect corneal ulceration. The veterinarian will place a few drops of the stain in the eye, turn off the exam room lights, and use the ophthalmoscope to determine if corneal ulcers are present. In dogs with KCS, it is not uncommon to also find corneal ulceration because of the chronic irritation.

Figure 4: Photograph of the eye of a dog with a corneal ulcer (arrow) highlighted by the application of fluorescein dye during ophthalmic examination. Source: http://www.animal-eye-specialists.com/exam.htm Examination of intraocular pressures The veterinarian will assess the intraocular pressure of each eye by using a handheld device known as a tonometer. It is a quick and painless 5

method to determine whether the ocular disorder experienced by your dog is something other than KCS (such as glaucoma). Typically three measurements are obtained for each eye and averaged together. Normal intraocular pressure for dogs is 15-25 mmHg. The image below is one example of a handheld tonometer.

Treatment of KCS There are various types of medical treatments that can be used to treat KCS in dogs. Your veterinarian will select the type of therapy that is best for your Westies situation. Common drugs used are listed below (Gelatt, 2005). Topical antimicrobial agents: Topical ophthalmic anti-bacterial drugs typically include a combination of bacitracin, neomycin, polymyxin, dexamethasone, and/or hydrocortisone. These medications are manufactured as ointments and solutions; your veterinarian will determine which medication is best for your dog. Common brand names include Terramycin and Neo Poly Bac. Anti-inflammatory drugs Topical corticosteroids can be used to decrease ocular inflammation and pain associated with KCS. One of the common agents used today is Cyclosporin A (CsA) (an immunosuppressive drug). The exact mechanism of CsAs action is unknown, but it appears to have immunomodulatory (meaning an agent that modifies the immune response) and lacrimostimulant effects (Beranek, 2006). Another immunomodulatory agent used for treatment of KCS is Tacrolimus; a more recent medication that belongs to a group of drugs called calcineuron inhibitors (Fourney, 2009). In simplistic terms, Tacrolimus blocks the proliferation of T lymphocytes and cytotoxic cells (Forney), thereby decreasing the immune response that may be an underlying cause of glandular inflammation and decreased tear production. Tear substitutes (lacrimomimetics) Tear replacement solutions are typically a combination of ingredients that replace one or more components of the tear film. There are many different tear replacement medications and your veterinarian will prescribe one or more to help control the signs associated with KCS. Many of these agents

have a relatively short duration of activity and it may be necessary to reapply them several times a day. For some feisty dogs, application of topical medications to the eye can be challenging, since these dogs may have pain associated with KCS and corneal inflammation. They undoubtedly will initially resent you holding their eye open to put drops in. Fortunately, with effective management, pain may decrease and both dog and owner will accept the routine of putting medications in the eyes. Providing rewards as positive reinforcement may help. Surgical Intervention (Parotid Duct Transposition) Some dogs with very severe KCS, which is unresponsive to medical treatments (listed above), may require surgery. When this is the case, there is a surgical procedure that involves moving the parotid salivary duct from over the masseter muscle to a spot on the eyelid (the conjunctival fornix). The goal of this surgery is to provide a source of lubricating and antibacterial fluid to the surface of the eye in dogs with KCS. The parotid gland is the largest salivary gland, lying just below the ear, beneath the skin. Its duct leads to the oral cavity, providing secretions that aid in chewing and lubricating food and swallowing. Saliva and tears have very similar physiologic properties, thus making parotid duct transposition a very successful solution to severe KCS in dogs. The regular secretion of saliva from the gland reaches the surface of the eye through the transposed duct. There is normally intermittent production of saliva from this gland, with the majority of secretion coming in response to eating. The image (Figure 5. left) below shows how this surgical procedure is accomplished. F Figure 5. Parotid salivary gland duct transposition for treatment of clinical signs of KCS. Source: http://www.eyedvm.com/eyeinfo-kcs.html After surgery, your Westie will take several weeks to heal and for you and your veterinarian to see if the procedure is working. Sometimes, the parotid duct is damaged or kinked during transposition and the amount of fluid produced is not sufficient. Veterinarians with experience doing this procedure routinely are most likely to have a successful outcome.

And, by the way, dogs have lots of salivary glands and plenty of secretions. Moving this duct around should not create problems with eating or digestion. Summary The basic problem with keratoconjunctivitis sicca (KCS dry eye) is a lack of effective tear production. There are many known causes, but the role of genetics and autoimmune disease are still being studied. Affected dogs may have painful, red, dry eyes that are constantly inflamed and irritating for the dog. Untreated KCS can lead to a variety of problems with the cornea, since tears are needed to lubricate the cornea. These problems can include corneal inflammation, erosion, ulceration, chronic scarring and potentially loss of vision. Both medical and surgical treatments are available to manage KCS. References "Alacrima: eMedicine Ophthalmology." EMedicine - Medical Reference. 15 July 2009 <http://emedicine.medscape.com/article/1210539-overview>. "Animal Ophthalmology Clinic: KCS Dry Eye." Animal Ophthalmology Clinic, Ltd. 13 Aug. 2009 <http://www.eyedvm.com/eyeinfo-kcs.html>. Beranek, Jiri. "Keratoconjunctivitis Sicca - WSAVA 2006 Congress." Veterinary Information Network (VIN) - For Veterinarians, By Veterinarians. 12 Aug. 2009 <http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2006&PID=1588 0&O=Generic>. "Canine Distemper, What you should know about." American Veterinary Medical Association. 25 July 2009 <http://www.avma.org/animal_health/brochures/canine_distemper/distemper_bro chure.asp>. Cote, Etienne. Clinical Veterinary Advisor Dogs and Cats. St. Louis: Mosby, 2006. "Examination Procedures." Animal Eye Specialists Home Page. 20 July 2009 <http://www.animal-eye-specialists.com/exam.htm>. Forney, B, "Tacrolimus For veterinary use." Avastin, Trilostane, Trimix:Wedgewood Compounding Pharmacy & Veterinary Pharmacy. 12 Aug. 2009 <http://www.wedgewoodpharmacy.com/monographs/Tacrolimus.asp>. Gelatt, KN, Keratoconjunctivitis sicca, in Essentials of Veterinary Ophthalmology. Ames: Blackwell, 2005.

Gilger, BC, "Waltham - OSU Symposium." Veterinary Information Network (VIN) For Veterinarians, By Veterinarians. 12 Aug. 2009 <http://www.vin.com/VINDBPub/SearchPB/Proceedings/PR05000/PR00526.htm >. Kaswan R, Pappas Jr. C, Wall K, Hirsh SG. Survey of canine tear deficiency in veterinary practice. In Sullivan et al. (eds): Lacrimal Gland, Tear Film, and Dry Eye Syndromes 2. New York: Plenum Press, 1998. Pp. 931-939. "Merck Veterinary Manual." The Merck Veterinary Manual. 20 July 2009 <http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/30107.htm>. "Optrex Eye Care Advice: Healthcare professionals dry eye information." Optrex We understand the language of eyes. 20 July 2009 <http://www.optrex.co.uk/healthcare_professionals/refresh_your_knowledge_on_ dry_eyes.php>. Additional Resources American College of Veterinary Ophthalmologists (ACVO). http://www.acvo.com/ American Society of Veterinary Ophthalmology (ASVO). http://www.asvo.org/ Crispin, Sheila M. Notes on Veterinary Ophthalmology. Grand Rapids: Blackwell Limited, 2005. Grahn, Bruce H. Veterinary ophthalmology essentials. Philadelphia, Pa: Butterworth-Heinemann, 2004. Veterinary Information Network. http://www.vin.com Veterinary Ophthalmology Services. http://vos-tn.com/index.php http://www.vetmed.ucdavis.edu/courses/vet_eyes/default.html

Topic 15: Copper toxicity in the canine liver Stephanie Shrader and John Robertson Introduction The 19th century American philosopher, William James, once said, Is life worth living? It all depends on the liver. And he was right. The liver is a vital organ that performs many biological functions (about 1200, actually). The major functions include: protein synthesis, detoxification, glycogen storage, hormone production, red blood cell decomposition and the production of bile. The liver is the major organ controlling digestion and distribution of nutrients (carbohydrates, fats, and proteins) for every cell in the body. Liver disease reduces or eliminates one or more of these functions most of which are critical to life. There are many disease processes that can affect the liver, each one deserving of its own chapter. This chapter will focus on copper toxicity and its effect on hepatic function. In order to fully appreciate coppers role in this diseased state, it is important to understand coppers role in daily biological functions, the dietary needs of canines, and finally the pathophysiology, clinical signs and treatment of copper toxicity. Coppers Role in the Body Copper is an important trace mineral that plays a role in various metabolic processes. Its main function is to act as a cofactor for enzymes, meaning that through binding, it enables the enzymes to properly carry out biological activities. Below are some of the processes in which copper is a key player: Energy Production (ATP Synthesis) Copper is a component of cytochrome c oxidase, a large protein found in the mitochondria in cells. This membrane protein is a component of the electron transport chain that functions to create a proton gradient that is used to synthesize ATP, the bodys energy source. Thus, an acute copper deficiency (usually due to a lack of copper in the diet), causing decreased ATP production, would result acutely in fatigue and impaired brain function. Longstanding copper deficiency, which compromises energy production in many cells, can be life-threatening. Below is a diagram (Figure 1) depicting cytochrome c oxidase and its role within the electron transport chain thats produces energy for cells.

Figure 1. Complex intracellular energy-producing reactions, dependent on the activity of cytochrome c oxidase (an enzyme) and metabolic copper. Elimination of Free Radicals Copper serves as a cofactor (along with zinc) for regulating the activity of superoxide dismutase (SOD), an enzyme that is important for the removal of peroxide free radicals from the body. These free radicals are reactive oxygen molecules that are produced during normal metabolic processes. If not removed quickly, however, they can damage cell membranes. Without copper in the diet, SOD would not be able to act as an antioxidant, weakening the bodys response to various disease processes such as cancer. According to Sigma-Aldrich, SOD is shown to suppress apoptosis (programmed cell death) by preventing the conversion of NO to peroxynitrate, an inducer of apoptosis. The diagram on the next page (Figure 2) depicts how the copper-dependent enzyme SOD functions to prevent oxidative damage in the body.

Figure 2. Key biochemical reactions mediated by the copper-dependent enzyme, superoxide dismutase. This enzyme prevents free radical damage to cells. Source: Sigma-Aldrich, 2009 (http://www.sigmaaldrich.com/lifescience/metabolomics/enzyme-explorer/cell-signaling-enzymes/superoxidedismutase.html) The Role of Copper in Facilitation of Iron Uptake Copper is a component of ceruloplasmin, a transport protein in blood serum, that also functions as an enzyme for catalyzing the oxidation of minerals such as iron. This oxidation is necessary for iron to be bound to its transport protein (transferrin) and distributed to various tissues in the body. Irons crucial roles in dogs include: being a key component of the heme group that makes up hemoglobin, being a component of other heme groups in the body (e.g. myoglobin, an oxygen-carrying protein in muscle), participating in DNA synthesis and cell division, maintenance of the immune system, and neurotransmitter functionality. Both copper deficiency and hepatic disease can lead to the same outcome iron deficiency. Without copper, ceruloplasmin cannot be synthesized by the liver, and without a healthy liver, plasma protein synthesis in general will be decreased.

Copper Plays a Key Role in Pigmentation Copper is a cofactor component of tyrosinase, an enzyme that catalyzes the synthesis of tyrosine to melanin, the key protective pigment in skin. Lack of the tyrosinase enzyme or lack of functionality of that enzyme results in albinism, an inherited recessive genetic disorder. The diagram below (Figure 3) depicts the complexity in the melanin biosynthetic pathway:

Figure 3. Copper plays a key role in the activity of the enzyme tyrosinase needed to produce the pigment melanin. Melanin protects skin from damage by ultraviolet radiation. (Ando, et al, 2007) In summary, copper directly or indirectly controls many important functions in the body. Too little copper may lead to a loss of key activities such as the control of free radical damage, loss of immune functions, and impairment of iron transport and function. However, too much copper is also bad and is described more fully below. Copper in the Diet According to the National Research Council (1985), the recommended daily intake of copper for growing dogs is 0.16 mg/kg/day and for maintaining health in adult dogs is 0.06 mg/kg/day. The major dog food companies have spent millions of dollars formulating foods that contain the correct ratios of nutrients for growth, maintenance, or even for dogs suffering from disease. It is very likely that if your Westie is fed one of these commercial diets, it is getting the proper amount of nutrition. With that said, we have read some conflicting reports stating that many dog foods provide excess copper. A quick perusal down the dog food isle and examination of the nutrition labels was fruitless; the copper content is often not listed. We were also unable to determine the copper content of some commercially available dog foods by searching company websites. If you are interested in how much copper is in your dog food and the information is not provided on the label, do not hesitate to contact the company. They are usually more than happy to provide nutritional information. 4

Please note!: Dogs that are fed home-made rations run the risk of developing nutrient imbalances and associated disease processes. Some owners who formulate these homemade diets may not properly balance nutrients. It is important to discuss diet and dietary change with your veterinarian, whether you are using a commercial diet or one you concoct at home. Dietary sources of copper include fish, some mollusks, cashews, sesame seeds, liver, legumes (beans), raisins (not especially good for dogs), cocoa (definitely a no-no for dogs), olives, and avocados (another no-no). Copper absorption occurs throughout the intestinal tract, but as with most other nutrients, the majority of the absorption occurs in the small intestine. Once absorbed, copper is stored mainly in the liver, with lesser amounts being stored in muscle, kidneys, brain, and heart. Hepatic concentrations of copper reflect an animals intake and copper status (Gross, et. al., 2000). In healthy dogs, if amounts of copper are excessive, it is normally excreted in the bile. Copper Toxicity Pathology and Clinical Signs Accumulation of toxic levels of copper in the liver is a heritable trait that can be seen in many animals, including dogs. The inherited problem is either an inability to properly metabolize copper or is the result of a copper storage disease. The end result is the same for all - chronic liver failure. Most research lists the Bedlington Terrier as the most susceptible dog breed, but according to Dr. W. Jean Dodds, other predisposed breeds include the West Highland White Terrier, Skye Terrier, Doberman Pinscher, Labrador Retriever, Keeshond, and American Cocker Spaniel. Normal dogs have a mean copper concentration in the liver of 200-400 ppm on a dry weight basis. Levels greater than 2000 ppm are considered toxic; dogs with copper toxicosis can have concentrations of copper up to 10,000 ppm (Dodds, 2009). Dogs with this heritable trait start to accumulate copper early in life and show no clinical signs at first. During this early stage, the copper concentration in the liver can quickly reach 1500 ppm, a level bordering on toxicity. If the veterinarian suspects copper toxicosis, due to clinical signs of liver failure, they may take a biopsy of the liver. A histological preparation of biopsied tissue (stained with rhodanine and hematoxylin) would begin to show

copper deposition. The image below (Figure 4, above) shows copper granules stained red-brown by the rhodanine stain. Source: Rosai: Surgical Pathology 9th edition, 2004. Copper levels will continue to rise in the second stage of the disease. Concentrations at this point will be around 2000 ppm and hepatitis (liver inflammation, scarring and cell loss) is obvious. Laboratory findings can include increased alanine aminotransferase (ALT) and alkaline phosphatase (ALKP) (liver enzymes), increased bilirubin, hypoalbuminemia, and anemia - all related to decreased liver function. As the copper concentrations rise beyond 2000 ppm, the liver is no longer able to function and portions become necrotic (dead). An animal at this stage may present with loss of appetite, depression, abdominal pain, vomiting, increased thirst and urination, jaundice, and weight loss (Dodds, 2009). Unfortunately, these clinical signs may be seen with many other diseases as well, so your veterinarian will have to take a thorough history and run some laboratory tests to properly diagnose copper toxicosis. As noted above, it may be necessary to do a surgical biopsy of the liver to make a definitive diagnosis of copper toxicity Treatment Options The goals of treatment for copper toxicity in dogs are: to reduce further absorption of copper from the gastrointestinal tract, to promote copper excretion, and to preserve liver function and encourage liver healing. This can be achieved by feeding a diet low in copper, combined with supplements and medications that reduce copper absorption and enhance its secretion (Filippich, 2009). The first step is a dietary change. Your veterinarian will either prescribe or help you formulate a diet low in copper. Do not do this yourself as it can lead to other nutrient deficiencies/toxicities! Simultaneously, the veterinarian may decide to decrease intestinal absorption of copper by the oral administration of zinc, a competitor for uptake of metals in the diet. The dosage is 10 mg of zinc acetate/kg, twice a day for 3 months followed by a maintenance dose of 5mg/kg, twice daily (Boothe, 2001). Again, do you not take it upon yourself to go to the pharmacy and get a zinc supplement it can cause serious gastrointestinal upset and hemolytic anemia if zinc toxicosis occurs. In conjugation with diet and mineral supplementation, your veterinarian may also prescribe a chelating drug, such as d-penicillamine (trade names are Cuprimine and Depen). Chelators are chemicals that form complex molecules with certain metal ions, thereby inactivating the ions so that they cannot react detrimentally

with other chemicals to produce precipitates. Once the d-penicillamine binds to copper, the chelated complex that is formed can be excreted in the urine. DPenicillamine is to be taken orally at a dosage of 10-15 mg/kg, 30 minutes before a meal, every 12 hours. Following treatment, you should return to your veterinarian for regular check-ups, including blood work, to be sure that hepatic function is returning to normal and that there are no adverse reactions to the medications. The liver, as a tissue, has a lot of reserve capacity and the ability to heal through regeneration. In response to disease, lost cells may be quickly replaced (within a matter of hours to days). However, and this is a big however, if there is a lot of damage to the blood supply or bile channels, and/or a lot of scar formation, healing does not proceed well. Chronic copper toxicity is a disease that can cause a lot of liver scarring and severely affected dogs are unlikely to regain full function from a permanently damaged liver. These dogs may have continued problems with digestion, maintaining condition, susceptibility to infections and decreased immunity, and with blood clotting (the liver makes important clotting proteins). It is very important to get an accurate diagnosis of copper toxicity in early stages of the disease to prevent significant (and often permanent) liver damage. One final note: It is currently thought that most cases of copper toxicity are due to inherited defects in copper metabolism. Affected dogs should not be bred so that this defect is not passed to future generations. References Ando, et al. J Investigative Dermatology 127: 751761, 2007. doi:10.1038/sj.jid.5700683; published online 11 January 2007 http://images.google.com/imgres?imgurl=http://www.nature.com/jid/journal/v127/ n4/images/5700683f1.jpg&imgrefurl=http://www.nature.com/jid/journal/v127/n4/fi g_tab/5700683f1.html&usg=__SKRcZi5uUD_txBdINFHzmKPXtPM=&h=233&w= 420&sz=55&hl=en&start=2&tbnid=VzB3zxspG5EhRM:&tbnh=69&tbnw=125&pre v=/images%3Fq%3Dmelanin%2Bpathway%26hl%3Den Boothe, DM, Small Animal Clinical Pharmacology and Therapeutics. Pg 510. Philadelphia: Saunders, 2001. Print. "The crucial role of iron in the body." Department of Chemistry. 2004. Web. 11 Sept. 2009. http://www.chemistry.wustl.edu/~courses/genchem/Tutorials/Ferritin/IronBody.ht m Dodds, WJ, "Copper toxicosis/chronic active hepatitis." 2005. Web. 10 Sept. 2009. http://www.geocities.com/rottndobie/coppertoxicosis.html

"Enzyme Explorer Product Application Index for Superoxide Dismutase." Sigma Aldrich Home. Web. 11 Sept. 2009. http://www.sigmaaldrich.com/lifescience/metabolomics/enzyme-explorer/cell-signaling-enzymes/superoxidedismutase.html Filippich, L J, Hyun, C, "What is canine copper toxicosis." The University of Queensland, Australia. 1999. Web. 11 Sept. 2009. http://www.uq.edu.au/~aplfilip/copper/b03.htm Gross, KL, Wedekind, KL, Cowell, CS, Schoenherr, WD, Jewell, DE, Zicker, SC, Debrakeller, J, and Frey, RA, Nutrients in Small animal clinical nutrition, 4th ed., Marceline, MO (ed): Walsworth Publishing for Mark Morris Institute, pp. 66-68, 2000 National Research Council Nutrient requirements of dogs. Washington, D.C: National Academy, 1985. Print. Rosai, J, Rosai and Ackerman's Surgical Pathology. 9th ed. Edinburgh: Mosby, 2004. Print. Additional resources for the interested reader Ackerman, LJ, Canine nutrition what every owner, breeder, and trainer should know. Loveland, CO: Alpine Publications, 1999. Print. American College of Veterinary Nutrition: http://www.acvn.org/ American Veterinary Medical Association: http://www.avma.org/ Canine Nutrition: http://www.caninenut.com/ Eukanuba: www.eukanuba.com/ Food and Drug Administration: http://www.fda.gov/AnimalVeterinary/default.htm Hills Pet Nutrition: www.hillspet.com/ Purina: www.purina.com/ National Resource Council: http://sites.nationalacademies.org/NRC/index.htm Wortinger, A, Nutrition for Veterinary Technicians and Nurses. Grand Rapids: Blackwell Limited, 2007. Print.

Topic 16: Complementary and Alternative Medicine (CAM) Stephanie Shrader and John Robertson Introduction Complementary and alternative medicine (CAM) has been practiced in various forms for thousands of years, originating in ancient Asian and Indian cultures. Through trans-oceanic exploration and colonization, non-traditional medical treatments eventually spread to Western civilizations. Many of these therapies were, and still are, practiced by folk healers. The use of CAM therapies has become an emerging niche in the fields of human and veterinary medicine in the past 30 years. In 1982 Carvel G Tiekert, DVM, established the American Holistic Veterinary Medical Association (AHVMA). According to the charter of the AHVMA, holistic veterinary medicine combines conventional and complementary (or alternative) modalities of treatment. Diagnoses and treatments are based on physical examination, behavioral history, medical and dietary history, and consideration of the animals environment (including diet, emotional stresses, etc.). CAM therapies are considered to be so important in human medicine that one branch of the National Institutes of Health the National Center for Complementary and Alternative Medicine (NCCAM) was founded specifically to study them. The National Cancer Institute maintains an Office of Cancer Complementary and Alternative Medicine. The Basics of Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) defines CAM as a group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine (also known as allopathic medicine). Complementary medicine, by definition, is used in conjunction with conventional medicine, while alternative medicine is used instead of conventional medicine. CAM can be divided into four general categories: mind-body medicine, biologically based practices, manipulative and body-based practices, and energy medicine. These are discussed below. Mind-Body Medicine The first category, mind-body medicine, includes prayer, mental healing, and therapies that utilize creative outlets such as art, music, or dance. Oriental practices, such as tai chi, qi gong, meditation, and relaxation techniques are included in this category as well. This category has little practical relevance to the veterinary profession, although there is some research that supports the use of music to ease canine anxiety. One such study was conducted in Belfast, Ireland by Dr. Deborah Wells (Wells, et. al., 2002), a psychologist and animal

behaviorist. The study focused on the influence of five types of auditory stimulation: human conversation, classical music, heavy metal music, pop music, and a silent control (no music at all). Results revealed that classical music had a calming effect on dogs in animal shelters when compared to the other types of auditory stimuli. One of us (JR) has successfully used classical music therapy, in his practice, for dogs with obvious anxiety disorders, including dogs that are severely reactive to loud, sudden sounds (Fourth of July fireworks, for example). It is known that dogs have a considerably larger frequency range and increased perception of sounds compared to humans. Exposing dogs to regular, rhythmic, and complex sounds (symphonies, for example) at the same time that they are being rewarded and comforted, allows dogs, over time, to associate the music with positive and relaxing experiences. Playing music at times when dogs are experiencing stress (Fourth of July fireworks!) will relax them and also dilute perception of any sudden or unexpected background sounds. This type of therapy is inexpensive and allows owners alternatives to the uses of sedative, tranquilizers, and antidepressants for calming anxious dogs. A web search reveals a number of companies that make and market CDs specifically for dogs that experience anxiety problems. Here is one such companys website: http://www.throughadogsear.com/music_behavior.htm. Biologically Based Practices Herbal medicine (also known as phytomedicine) has been used for thousands of years in the prevention and treatment of human disease. In recent years, it has become accepted as standard allopathic therapy to make use of substances found in flowers, roots, berries, and herbs. Many potent and effective therapies, in common use, were derived from plants. For example, corticosteroids were derived from the molecule diosgenin, originally isolated from wild yams (Dioscorea villosa). The cancer chemotherapy agent, vincristine, is derived from compounds found in periwinkles. Aspirin, a non-steroidal drug, is a salicylate related to compounds found in willow tree bark and cambium. Quinine, a preventative for human malaria, was also derived from Cinchona tree bark (Chevallier, 1996). Antibiotics, such as penicillin and streptomycin, came from molds and fungi. The drug digitalis, from purple foxglove (Digitalis purpurea), is a mainstay of therapy in dogs and people for treatment of heart failure. It should be pretty apparent that substances derived from plants can also be extremely toxic. A small dose of aspirin may lower the body temperature in a person with a fever or help prevent blood clots from forming by keeping blood platelets from becoming sticky. Two or three times that small dose may cause heartburn, stomach ulceration, and bleeding tendencies. We pointed out (above) that some very common and useful antibiotics are derived from growing molds. The growth of other molds, like the fungus Aspergillus flavus on peanuts and

grains, can produce mycotoxins which are capable of causing cancer (aflatoxin B) or destroying brain tissue (Fusarium toxin fumonisin). Methylxanthines found in chocolate (derived from the cocoa plant Theobroma cacao) are very toxic, even in small amounts for dogs. Dog owners should understand that the metabolism of dogs and people are very different. Herbal remedies that may be relatively safe for people, may not be safe for dogs. The doses of drugs used to treat disease in humans and dogs have been established through scientific studies. The doses of herbs for treatment of disease in dogs have not been well-studied. According to the World Health Organization (WHO), in some Asian and African countries, 80% of the population still depends on traditional medicine for primary health care. The WHO also notes that herbal medicine is the most popular worldwide form of complementary and alternative medicine. Herbalists seek to treat a variety of human conditions, including arthritis, depressed immunity, Alzheimers, asthma, depression, fatigue, skin problems, and a host of others. Three common herbal remedies used in both humans and animals are St. Johns wort, ginseng, and echinacea. St. Johns wort (Hypericum perforatum) is used in humans as an analgesic, anesthetic and an anti-inflammatory agent. In dogs, it has been used to treat obsessive problems such as lick granulomas, aggression, barking, jumping, scratching, chewing and separation anxiety. Its use is contraindicated with antidepressant drugs. Ginseng root, from the plant Panax ginseng, is native to North America and China. In Chinese, the word ginseng means the essence of man. This is because it has been used to treat a wide variety of ailments. In humans, Ginseng is administered to treat fatigue and headaches, stimulate the appetite, and to increase both vitality and immune function (Kim, et.al., 1990), especially in older individuals. It is marketed to treat many of the same conditions in both dogs and cats. Ginseng, when chemically analyzed, is shown to contain over 35 distinct chemical compounds (ginsenosides, triterpenoid saponins, [anaxans, sesquiterpenes) that may have medicinal actions for humans (Chevallier, 1996; Blaylock, 2003). Studies have shown that ginseng will inhibit human tumor cell growth in tissue culture (Shinkai, et. al., 1996). Whether these findings can be extrapolated to dogs would require further studies. Echinacea is a wildflower (Echinacea angustifolia and E. purpurea) native to the central United States. Its main uses are to improve the function of the human immune system, especially against the common cold and influenza. It can also be used to help wounds heal faster and decrease inflammation. In dogs,

echinacea has been used to bolster the immune system, aid in the treatment of viral infections, and prevent cancer. And now, a final word of caution and warning about herbal remedies and phytotherapy for your Westie. While plants and herbs have been used for literally thousands of years as folk remedies in humans, much less is known about the effects of plant-based compounds as therapies for disease in dogs. Before beginning any herbal remedy with your pet, always consult your veterinarian first. When in doubt, leave them out - as therapy for sick dogs. Manipulative and Body-Based Practices The use of chiropractic/osteopathic manipulation and massage are well-known forms of manipulative and body-based CAM therapies. Osteopathic manipulation is used by osteopathic physicians, combined with physical therapy, in order to shorten patient recovery time. Reflexology, Tui Na, rolfing, the Bowen technique, Trager bodywork, and many other techniques are also included in this category. Most of these therapies are impractical for veterinarians and their patients, but there is a growing chiropractic movement within the veterinary field. Formal animal chiropractic education began in 1989 with the formation of the American Veterinary Chiropractic Association (AVCA). The first courses were taught by the founder, Dr. Sharon Willoughby, DVM, DC. She began the practice of teaching Doctors of Veterinary Medicine and Doctors of Chiropractic side by side. Doctors of Veterinary Medicine receive a foundation of chiropractic theory and technique, and Doctors of Chiropractic learn common animal diseases, zoonotic diseases, comparative anatomy, and animal handling techniques. The AVCA has a multi-tiered mission: to provide a professional membership group, to promote animal chiropractic, and provide certification for doctors who have completed animal chiropractic training. The AVCA also seeks to provide the public with access to doctors trained in animal chiropractic. Animal chiropractors treat many different animals and a wide array of problems. Cats, dogs and horses are the most common patients, but chiropractic medicine is also used to treat zoo animals, wildlife, and exotics. A chiropractic exam includes evaluation of the patients history (including prior radiographic results), a full neurological exam, and finally the adjustment of vertebral joints, extremity joints, and cranial sutures. Animal chiropractic has been used in the treatment of neck, back and extremity pain, muscle spasms, injuries, internal medicine disorders, and temporomandibular joint (TMJ) syndrome. To find out more information or to locate an AVCA certified veterinarian, review the following website: http://www.AnimalChiropractic.org. Most Westie owners know that their dog enjoys being petted and held. Some dogs seem to particularly enjoy massage, if they are acclimated to it and

rewarded for participation. Dogs that have suffered injuries may be painful and resentful of manipulation and massage, but may benefit from the gradual introduction of common-sense physical therapies, including gentle massage and range-of-motion exercise, warm and cool compresses and even hydrotherapy. Most veterinarians receive little, if any, training in physical therapy and rehabilitation of their patients. However, they may work with you and local physiotherapists to custom design programs for dogs with injuries that would be helped by therapy. This should be discussed with your veterinarian. Energy Medicine Energy medicine, perhaps the least studied and least understood of all the CAM therapies, involves manipulation of the energy fields that purportedly surround living beings and the use of electromagnetic fields for therapeutic outcomes. Energy medicine includes Reiki, Therapeutic Touch therapy, light and sound therapy, qi gong, homeopathy, acupuncture, and a host of other treatments. Although we have known some pet owners to practice Reiki and Therapeutic Touch therapy, the most common energy medicine techniques practiced by holistic veterinarians (and endorsed by AVHMA) is homeopathy and acupuncture. Homeopathic remedies date back to the time of Hippocrates, and include the use of plants, minerals, drugs, viruses, bacteria and/or animal substances to treat illnesses. Homeopathy involves treating an ill patient using a substance that can produce, in a healthy individual, symptoms similar to those of the illness. This substance is created through serial dilution of the normally toxic agent. For example, snake venom, poison ivy and opium have been used to make homeopathic remedies, but in high enough concentrations can cause serious problems. Homeopathy has been used to treat a wide range of problems in both humans and animals, but has not been studied scientifically to prove effectiveness or safety. Acupuncture, by definition, is the Chinese practice of piercing specific areas of the body along peripheral nerves with fine needles to relieve pain, induce surgical anesthesia, and for therapeutic purposes (Dorland's Pocket Medical Dictionary, 25th ed. W. B. Saunders Co., 1995). Acupuncture dates back thousands of years and is considered part of traditional Chinese medicine. According to traditional Chinese medical theory, the qi (life force) flows through various meridians (channels) throughout the body. When this flow is disrupted, it manifests as pain, and other ailments. In the United States there are currently more than 50 schools and colleges of human acupuncture and Oriental medicine. Many offer masters degree programs and are accredited by or have been granted candidacy status by the Accreditation Commission for Acupuncture and Oriental Medicine (ACAOM). Here is a website for finding out more about the acupuncture schools in the United States and the programs they offer: http://www.acupunctureschools.com/.

The National Cancer Institute website for complementary and alternative medicine (http://www.cancer.gov/cancertopics/treatment/cam) provides a wonderful overview of the use of acupuncture as a treatment for individuals (humans) with cancer or cancer-related side-effects. Research supports acupuncture as an effective complementary therapy to reduce nausea and vomiting after surgery and chemotherapy, as well as an effective pain inhibitor. There are many studies currently underway involving acupuncture and its ability to relieve lower back pain, breast cancer, limb pain, menopausal symptoms, nausea, dry eye, and the list goes on, and on. One of us (JR) has undergone acupunture treatment of painful lower back spasms (due to disc prolapse) and will personally attest to its effectiveness! A full list of current clinical trials involving human acupuncture can be found at: http://clinicaltrials.gov/search/open/intervention=acupuncture. There are a growing number of veterinary acupuncturists. According to the AVHMA, the main goal of veterinary acupuncture is currently to strengthen the body's immune system. The etiology of acupunctures therapeutic effects, however, is not well understood. As you might imagine, dogs that are going to be acupuncture subjects may not understand what you and the acupuncturist are trying to accomplish or how you are doing it. It takes little imagination to realize that your Westie might not think it is such a good idea to get stuck with one or more long needles and then to hold still for the therapy to work (5-30 minutes). It is probably a very good idea, if you are considering acupuncture therapy for some painful condition, to discuss this with your veterinarian and the veterinary acupuncturist. It may be worthwhile to get the names of clients who have had dogs treated with acupuncture and to contact them to see how the therapy worked. Remember: dogs dont seem to experience a placebo effect there is no amount of talk that will convince the dog it is going to feel better! To contact and/or locate a holistic veterinarian who practices homeopathy or acupuncture, check out the websites listed at the end of this chapter. A personal view of CAM John Robertson Imagine for a minute that you are sick. Perhaps suffering from arthritis and the ravages of age on our bones and muscles. How do you view your disease and suffering? The result of normal wear and tear? Perhaps the result of injuries sustained many years ago? Bad diet? Not enough vitamins? Poor posture, a bad mattress or old shoes? It is very hard to say if any or all of these factors are the cause of your current disease, but you know you want some relief. What are some things that might be effective? Anti-inflammatory drugs (cortisone, non-steroidal drugs like aspirin) to decrease joint inflammation and potentially slow the progression of disease

Anti-inflammatory drugs to decrease pain, allowing more normal mobility and better quality of life, with normal daily activities Application of topical heat to sore joints and muscles, with or without application of heating and cooling topical gels and ointments Vitamin and mineral supplements, including calcium and magnesium, to help rebuild and maintain bone Vitamin supplements, including chondroitin-glucosamine, for helping the healing process A balanced program of exercise, perhaps including exercise in water, and stretching to gain/regain mobility, decrease stiffness, and increase a feeling of well-being New mattress and new shoes Better diet, coupled with sensible weight loss (if overweight) Rest in a comfortable place when tired Avoid repetitive injury than makes the arthritis worse

If you did all the things (ten of them) on the list, do you think you would feel better, especially if you did them over and over? At least 80% of the items on the list (the bottom 8 items) are not a pill prescribed by your doctor. Each, however, would be complementary to the occasional use of drugs (steroids and nonsteroidal anti-inflammatory drugs). Complementary therapy provides a system of holistic healing, optimizing diet, exercise, and judicious use of drugs that have been proven to be effective. This would work for you and for your dog. And (I hope) you would accept that neither strict medical therapy (the drugs alone) nor the combination of medical and complementary therapies are going to cure your arthritis. Suppose, now, that your dog has developed a serious cancer, such as malignant lymphoma. Malignant lymphoma is one of the most treatable forms of cancer in dogs. With multiagent chemotherapy, many (over 50%) dogs, even those with moderately to markedly advanced cases, may live 1-2 years. The drugs, however, do not cure the cancer, and virtually all dogs diagnosed with malignant lymphoma will succumb to the disease or complications of the disease. We know this from studying the outcomes of treatment of thousands of dogs that have developed malignant lymphoma. In general, about 10% of dogs getting chemotherapy (the treatment of choice for malignant lymphoma) will develop treatable side effects during therapy, including vomiting and diarrhea. Dogs with moderately to markedly advanced malignant lymphoma that do not receive multiagent chemotherapy rarely live more than a few months. What do you do? Treat? Not treat? Hard choices. Life and death choices. Some owners, concerned with the potential suffering that their dog might have, decide on humane euthanasia, and this is both a personal and rationale choice. Some other owners might decide to go ahead with chemotherapy, realizing it is expensive (perhaps $3,000 to $6,000), and that they may prolong life, good quality life, for up to a year or two. And that your dog is going to very likely die as

a result of the cancer. For most owners, making this decision if very difficult and there is almost always sadness and frustration for your canine friend and companion having an incurable disease. But, there are two rational choices euthanize or treat. In trying circumstances, some owners may reject rational choices, feeling that traditional allopathic and complementary medicine has failed them and their pet. When they ask the veterinarian to cure the incurable and treat the untreatable, they indicate that current medical and surgical practice has failed them. They may wish to avoid well-documented and supportive therapies in favor of treatments whose value, effectiveness, and safety have not been established. While it is quite normal to feel frustrated that our pets get ill and eventually die, it is not rational to reject proven therapies for unproven alternative therapies. Ive lost eight dogs and as many cats to disease. As much as I hoped I could fix them, in the end I could not. There were no magic medicines, no secret herbs, and no intervention that would keep them with me. Ive reflected on my limitations and failings quite a bit. In the end, I always come back to the same answer. As pet owners, as veterinarians, as scientists, we owe our pets the best possible life we can provide for them and we need to constantly work harder to make the years they have with us quality time, free of disease. We need to understand disease and develop better treatments, not harbor resentment over the limitations we now experience. In the end, its all about understanding more and doing more, not rejecting treatments that arent perfect or foolproof. In summary There are many forms of complementary and alterative medicine that have a place with common and traditional medical and surgical therapies in treating disease in dogs. There is a lot of information available (see below) describing some tested and helpful therapies. Westie owners should be cautious about subjecting their dogs to unproven therapies and should reject stuff that promises unrealistic results (like curing or preventing cancer). Do not use toxic and potentially deadly plant/herb products. Contact a Practitioner of Complementary and Alternative Medicine http://ahvma.org/ http://www.ivas.org/ http://www.holisticvetconsult.com/ http://www.holisticvetpetcare.com/ http://www.petsynergy.com/ http://www.AnimalChiropractic.org. Further Resources for Owners and Veterinarians

Biddis, KJ, Homoeopathy in Veterinary Practice. Boston: C.W. Daniel Company, Limited, 1987. Blaylock, R, Natural Strategies for Cancer Patients, Kensington Publishing, NY, 2003 Chevallier, A, The Encyclopedia of Medicinal Plants, Dorling Kindersley Ltd. London, 1996 Day, CE, The Homoeopathic Treatment of Small Animals. Boston: C.W. Daniel Company, Limited, 1990. Devi, L, Flower Essences for Animals : Remedies for Helping the Pets You Love. Grand Rapids: Beyond Words, Incorporated, 2000. Goldstein, R, Broadfoot, PJ, Palmquist, R Integrating Complemetary Medicine into Veterinary Practice. Malden: Wiley-Blackwell, 2008. Grosjean, N, Veterinary Aromatherapy. Boston: C.W. Daniel Company, Limited, 1994. Holloway, S, Animal Healing and Vibrational Medicine. Grand Rapids: Blue Dolphin, Incorporated, 2001. Kim, JY, Germolec, DR, Luster, MI, Panax ginseng as a potent immunomodulator: studies in mice, Immunopharm Immunotox 12: 257-276, 1990 Ramey, DW, Complementary and Alternative Veterinary Medicine Considered. Iowa State Press, 2004. Shinkai, K, Akedo, H, et. al., Inhibition of in vitro tumor cell invasion by ginsenoside Rg3, Japan J Cancer Res 87:357-362, 1996 Shojai, AD, New choices in natural healing for dogs & cats : over 1,000 at-home remedies for your pet's problems. Emmaus, Pa.: Rodale P, 1999. Stein, D, Natural Remedy Book for Dogs and Cats. New York: Crossing P, 1994. Tilford, GL, Wulff-Tilford, M, All You Ever Wanted to Know about Herbs for Pets. New York: BowTie P, 1999. Wells, DL, Graham, L, Hepper, PG "The Influence of Auditory Stimulation on the Behavior of Dogs Housed in a Rescue Shelter." Animal Welfare 11: 385-93, 2002 Wynn, SG, Fougere, BJ, Veterinary Herbal Medicine. St. Louis: Mosby, 2006.

Related Websites for Additional Information National Center for Complementary and Alternative Medicine http://nccam.nih.gov/ Alt Vet Med, Complementary and Alternative Veterinary Medicine http://www.altvetmed.org/ Academy of Veterinary Homeopathy http://www.theAVH.org American Academy of Veterinary Acupuncture http://AAVA.org Veterinary Botanical Medicine Association http://VBMA.org British Association of Veterinary Homeopathic Surgeons www.bahvs.com/ World Health Organization http://www.who.int/mediacentre/factsheets/fs134/en/

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******************************************************** TheWestieEBookTeam

John(drbob)Robertson,VMD,PhDisaProfessorof PathologyandistheDirectoroftheCenterfor ComparativeOncologyatVMRCVM.Priortohis employmentatVirginiaTech,heworkedinthe pharmaceuticalindustrydevelopingnewhumanand animaldrugs,andwasanAssociateClinicalVeterinarian atMediaVeterinaryHospitalinMedia,Pennsylvaniafor 16years,attheSpringfieldAnimalHospitalinSpringfield, Pennsylvaniafor3yearsandasareliefveterinarian.He liveswithhiswife,Sue,twopuppiesofuncertainparentage,12cats,sixgeese andtwoducksinFloyd,Virginia.HehasownedthreeWestiesandasaperson ofScottishancestry,appreciatesthebreedimmensely.

Elizabeth(Betsy)McStaygraduatedfromConnecticut Collegein1998withmajorsinSociologyandWomen Studies.Herworkoftenfocusedonthesociological aspectsofmedicalresearch.Afterseveralyearsworking inhealthrelatedlegislativeresearch,shebeganpursinga careerinveterinarymedicine.Elizabethsexperience includesworkingasaveterinarytechnicianatasmall animalhospital,participatinginbehaviorresearchatthe NationalZooandworkingwithlocalanimalshelters.She isnowinhersecondyearatVirginiaMarylandRegional CollegeofVeterinaryMedicine.Herunusualbackground foravetstudenthasgivenheracriticalperspectiveonthemedicalcommunity andfocusedherpursuitofherdegreeontheholisticwelfareofherfuture patients.Elizabethviewsthecommunicationbetweenanimalownerand veterinarianasthemostimportantaspectinprovidingthebesthealthcarefor pets.

Stephanie Shrader graduated from Wilson College in 2006 with a B.S. in biological sciences. At Wilson, she completed a research project and thesis entitled Calcium Oxalate Urolithiasis in Oryctolagus cuniculus. Upon graduation she began working for Charles River Laboratories as a Research Associate, developing morphometric techniques to assist in the pathology portion of various studies. Stephanies experience also includes many years working as a veterinary nurse/technician at a small animal practice. She is currently in her second year at Virginia-Maryland Regional College of Veterinary Medicine. Stephanie enjoys working in the corporate research environment and aspires to become a board certified veterinary pathologist.