by PD Mulkern · 1962 — As long as the treatment continued the catarrh was controlled, nocturnal nasal obstruction disappeared and there were no further infections of the throat or ears.
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THECATARRHALSTATEP.D.MULKERN,M.R.C.S.,L.R.C.P.RomfordItwasduringthemeaslesepidemicoftheautumnof1951tothespringof1952thatIblundered-forthereisnoothermoresuitablewordtodescribemyshamefulandunscientificempiricism-onausefultreatmenttocontrolthecatarrhalstate.Frequentupperrespiratorytractinfections,otorrhoea,sinusitisandtonsillitisbecametheacceptedaccompanimentofconvalescencefrommeaslesinthisworking-classpractice.QuiteanumberofadultswereknowntohavequiescenttuberculosisandIwasanxiousthatchildrendebilitatedbymeaslesshouldnotinadvertentlybecomeinfectedbyneighboursastheyplayedinotherhouses.Soitbecamearoutinetousethejellytestfortuberculinsensitivityduringthe6monthsafterrecoveryinanychildrenwhoappearedtobeundulydebilitated,pronetofrequentcoldsandcatarrh,orwhosufferedmultipleattacksofupperrespiratorytractinfectionofonekindoranother.Ifoundquiteanumberofpositivereactors,althoughonlookingroundIcouldnevertracethesource.NorcouldIdetectanyphysicalsignsofaprimaryfocusbyclinicalorradiologicalexaminations.Nevertheless,Idecidedtotrytheeffectofrimifononthesechildrenwhowereunderweight,fullofcatarrh,wouldn’teat,hadnoenergyandwhowerealsopositivereactorstothejellytest.Tomysurpriseanddelighttheyappearedtomakeverysatisfactoryprogressandtheirmotherswouldcomeagainandagainforthe”vitamintablets”.Aslongasthetreatmentcontinuedthecatarrhwascontrolled,nocturnalnasalobstructiondisappearedandtherewerenofurtherinfectionsofthethroatorears.Ifthetabletswerediscontinuedthecatarrhalstatewouldsoonrelapse.Insomecasestreatmentwasusedcontinuouslyorwithintervalsofabstinenceforperiodsofayearortwowithsatisfactoryresults.AssoonasIwasconvincedoftheusefulnessofrimifon,Idecidedtouseitonallcasesofcatarrhandupperrespiratorytractinfectionsregardlessoftheresultofthejellytestanditbecameevidentthatthistestwasnotconnectedwiththeefficacyofrimifon.AsIdevelopedthistherapy,Iincludedpara-aminosalicylicacidanditslessunpleasanttastingderivativesJ.COLL.GEN.PRACT.,1962,5,218
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withevenbetterresults.Inacuteinfectionsofbacterialtypeimposedonabackgroundofcatarrh,Iusedquarterstrengththerapeuticdosesofantibioticstoactinsynergismwithrimifon.Meanwhile,certaininvestigationsandmuchcorrespondencehadfoundthejellytesttobeinaccurate’.IwasrecheckingmyjellypositiveswiththesamethoughtinmindandwasfindingthemnearlyallnegativetoMantoux1:1000.OneyearaftertheoriginaltestswithjellyIwastofindamajoritywereagainnegativereactorstojelly.Somyblunderingresearcheshadgoneinalong,uselesscircle;.butonthewayIhadpickedupaveryusefulempiricaltreatmentwhichhasprovedaboontomostpatients,oldandyoung,whosufferwithcatarrhandsecondaryinfectionsfromanymucousmembraneofthebody.Theexplanationofthissuccessfulempiricismwasapuzzle.Couldtuberculosisexistinalatentformwhichdidnotprovokeahypersensitivityreaction?OrcouldthebacillusofKochhaveotherlifecyclesthantheclassicalone,whichcouldbetrans-mittedtothedescendantsofsufferersfromtuberculosis.IknewthatmostofthefamiliesIlookedafterwouldnothavetolookfurtherthanparentsor.grandparentstofindadeathfromtubercu-losis.Supposingthetuberclebacilluscouldbecomegranularorvirusinformand,escapingthroughthemeshesoftheplacenta,becomeresidentinthefoetalliverandspleen,causingonlyminordisorderssuchasneonataljaundice,difficultyinthrivinganddelicacyinchildhood?Andsupposingthatthesechildrengrowingupwithacatarrhaldiathesisproducedbythepresenceofsuchafactoractingasadepressanttothedefensivestatus,couldcontinuetotransmitagranularformacrosstheplacentalbarrier,yetwitheachgenerationthisinfectiongrewweakerandweakerastheoppor-tunityforthisformtometamorphoseintotherodbacillusenclosedinitsresistantlipoidcapsulefailedtoappear,thentheconstitutionwouldbecomestrongerastheatypicalandgranularformofthetuberclebacillusgrewweaker.Ifsomesuchthesiswerepossibleitwouldexplaintheresponseofthecatarrhalstatetoanti-tuberculousdrugs.SurveyofLiteratureDuringtheworldpandemicofinfluenzain1918,anumberofresearchworkershadattemptedtoprovethattheinfluenzaviruscausingthisepidemicwasconcealedbylatencyintheinfluenzabacillusandthatbysuitableculturetechniquesthelattercouldbepersuadedtoproducethevirusinvisibleformagain2.Theseobser-vationshavefallenintoneglectandevenintodisgracebecauseotherworkersusingothertechniquescouldnotrepeatthem.Thesameworkerswhoassertedthattheinfluenzaviruswasapartofthelifecycleofthebacillusofinfluenzawerealsoabletodemon-THECATARRHALSTATE219
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strateanultraviruswhichemergedfromthebacillusofKochwhenspecialculturetechniqueswereapplied3.Theoppositiongroup,againusingadifferenttechniquewereunabletoconfirmtheseviews.In1933,M.C.Ninniwasabletodemonstratenon-acidfastatypicalbacilli,bothinmicro-culturesandinvivoafterinoculationoffiltratesfromtuberculousmaterialandfromcultures.Healsofoundsimilarimmaturebacilliinthespleensandlymphaticsystemsofnewbornguinea-pigswhosemothersweresufferingfromactiveandgeneralizedtuberculosis.Theseatypicalformssometimesbecameacid-fastbutdidnotcausetuberculosisnordidtheycauseasustainedhyper-sensitivityreactiontotuberculin.Buttheycausedadiseasewhichhasvariouslybeentermedabortivetubercu-losis,pre-bacillary,granulaemicorbacilloseinfection4.Morerecently,in1953,NegryandBreteyhaveagainexaminedthefactsregardingthetransmissionofastateofdiseasebysomeagentseparatedfromtuberculousmaterialbyafilterorthroughaplacentaandtheyhaveconfirmedsomeoftheearlierwork.Theydenythatanyvirusispresent,buttheyfindevidenceforimmaturebacillipassingthesebarriers.Theyconfirmthattuberculosisdoesnotdevelopbutthatabenignself-limitingdiseaseoccursinguinea-pigsinoculatedwiththeexcretaandbloodofinfantsbornoftuberculousmothersandfromtheumbilicalveinbloodofthemothersfilteredthroughChamberlandL3atmorethan50mm.mercurypressure.Thisstateofdiseasedoesnotprogressandisnottransmissibleinguinea-pigs5.DownieandMeissnerrepeatedsomeofNinni’sworkin1934.Theyfoundthatfiltratesfromvarioustypesoffiltersometimescausemildabortivepathologiesinguinea-pigsandthatpassagingmaterialfromtheseanimalssometimesresultedinthedevelopmentoftuberculousdiseaseandpositiveculturesevenwhentheoriginalfiltrateshadapparentlybeennegativemicroscopicallyandonculture.Inotherexperimentsacertainnumberofanimalsdiedofpneumonianotassociatedwithtuberculousinfectionandanevenlargernumberdiedofacuteintercurrentdisease,usuallypneumonia,whilebeingusedaspassageanimalsinserialinoculationsoffiltratesfromotherguinea-pigs.Theyconcludedthatdefectivefilterswillallowscantynumbersofimmaturebacillitopass,butthatefficientfiltersneverdoso”.Ninnididnotfindasinglefiltratetocontainmatureandpathogenictuberclebacilli,nordidheobservecongenitaltuberculosis.ModernAmericanopinionacceptsthebeadingfoundincertaintuberclebacilliasbeingcomposedoflivingelementscapableofdevelopingintoacid-fastbacilliinvitroandofcausingtuberculosisinexperimentalanimals7.M.C.Kahndescribesthedevelopmentoftuberclebacillitogetherwithnon-acid-fastgranulesandrodsinculturecolonies.Hehasalsodescribedhowthegranules220’P.D.MQULKERN
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canbeobservedinsingle-cellsuspensionsunderahighpowermicroscopetoelongatetorodsandtomaturetoacid-fasttuberciebacilli8.OntheotherhandCooperandPetrofffailedtofindanylivingagentintheirfiltratesfromtuberculousmaterialwhichwouldgrowonculturemediumorcauseanydiseaseintheirinoculatedanimals9.ButNinni,whowasconsistentlysuccessfulinproducingactivepathogenicfiltrates,insistedthatcrudesalinefiltrateswouldneverbepathogenic.Ineffect,heanticipatedthetissueculturemediumnowusedtopropagatevirusesbyrenderinghisfiltratesactivewiththeuseof5%salineandemulsifiedfreshliverandspleenpulpfromhealthyguinea-pigfoetuses.Noonerepeatedhistech-niquesatthattimeanditisthereforenotsurprisingthathissuccess-fulresultswerenotrepeated.ThiswasprobablythereasonforthefailureofDownieandMeissnertoconfirmNinni’sworkbecausetheyusedonlynormalsalinefiltrates.However,in1949DrBrieger’0,workinginthePapworthHospitalnearCambridge,reportedsomeveryinterestingexperimentsusingmoderntissueculturetechniquestodeveloptuberclemycobacteriafromalmostinvisiblegranulesfoundincaseouslesionsfromguinea-pigspleens.Theanimalshadpreviouslybeeninoculatedintra-splenicallywithalargedoseofvirulentaviantuberclebacilliandallowedtorecover.Theseanimalswerethensacrificedatintervalsofmanyweekssubsequenttotheinoculation.Thelesionswereexaminedhistologicallyandbacteriologically.Veryscantyoroccasionalmycobacteriawerefoundafterprolongedsearch;noculturewaspositive.Yet,withinafewdaysofinoculatingthematerialintotissuecultures,filamentous,mycelial,andfinallytypicalacid-fastrodformsoftheavianM.tuberculosisdeveloped.Inotherwords,M.tuberculosisdisappearesinoneenvironmentbutcanbepersuadedtore-appearinanother.ThisfullyconfirmstheresearchesofM.C.Ninni.Finally,in1960,anAmericanbacteriologistreportedthatmicewhichhadbeeninfectedbyhumantuberclebacilliandhadreceivedtreatmentwerefreefromviabletuberclebacilliwhensacrificedattheendofa90daycourseofanti-tuberculousdrugs.However,whenkeptforafurther’threemonthstuberclebacillicouldberecoveredbyculturefromsacrificedanimalsintheabsenceofanylesionsorofobvioussourcesofbacillaryinfection”.Tosummarizethiswork;thereisacaseforsuspectingthatthebacillusofKochiscapableofmorethanonemodeofrep’roductionaccordingtotheenvironment.Inamilieufavourabletorapidgrowththeacid-fastbacillaryrodsegmentandthesebyfissionbecomegranularandpossiblyultra-microscopic.Thisamorphous,non-acid-fastmateriallaterbecomesfinerodsandonlywhentheTWECATARRHAI,STATEF221
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environmentisinimicaldotheserodsacquirecapsulesandacidfastness.Intissueswhicharenothypersensitive,immatureatypicalformswouldpropogate.Inordertotransposethisexperimentaldatatoclinicalform,itissuggestedthattheatypicalrodsorgranularformsarepassedbythemotherwithactivetuberculosisthroughtheplacentatothefoetalliverandspleen.Thefemalessoinfectedmaypassthesameformtoanewgenerationwhentheybecomeparturientandsoon.Ineachgenerationacertainnumberwilldevelopprimaryendogenoustubercularfociifthegranularformmaturesinthespleenandentersthegeneralcirculationtoformemboliinthelungs.Intheremainder,thepresenceofthegranularformconfinedwithintheliverorspleendepresseshepaticfunctionandisassociatedwithastateofcatarrhinthehost.AccordingtoallexperimentalevidencethepresenceoftheatypicalbacillaryorthegranularformdoesnotprovokeahypersensitivereactiontotuberculinandtheMantouxorHeaftestremainsnegative.Itshouldbeclearlystatedthatthishypothesisdoesnotaffecttheclassicalmodeoftransmissionofmaturetuberclebacillidirectfromhosttohostresultingintheprimary,secondary,andtertiaryphasesoftubercu-losisandaccompaniedbytheconversionoftissuesensitivitytotuberculo-protein.Publishedexperimentalworksupportsahypothesisconcerningthegenesisofthecatarrhalstatebyreferencetoalatenttubercleinfectionofatypicaltype.Isuggestthatempiricaltherapywithanti-tuberculousdrugscausesareversalorsuppressionofcatarrh.Idonotintendtoidentifycongenitalhepaticandsplenicinfectionbyattenuatedatypicalviralparticlesortuberclebacilliastheonlycauseofcatarrh.Anyagent,whetherprenatal,neonatal,orinlaterlife,whichdepresseshepaticfunctionwillinitiatethecatarrhalstate.Alcoholcausescirrhosisoftheliveraccompaniedbygastritis,oesophageal,pharyngeal,andbronchialcatarrh.Tobaccosmokingissometimesassociatedwiththesecatarrhalmanifestations.Cessa-tionofsmokingresultsinanincreaseinappetiteandmarkedweightgain;thiscouldbeduetoimprovedhepaticfunction.Theinhalationofimpureairisknowntobeassociatedwiththecatarrhalstate.Itispossiblethattheagentsinhaledarefilteredoffintheliver(themajororganofdetoxification),thuscausingslowbutincreasinglossofliverefficiency.Thestateoflassitude,anorexia,anddepres-sionensuingafteranillness(especiallywhenofviralorigin)maywellindicateadepressedhepaticfunctionnotdiscerniblebyourcrudebiochemicaltests.Catarrhisanexcessofmucoproteinnormallyexcretedbyendo-thelialmembranesexposedtotheenvironmentofthebody.Shouldtheefficiencyofthelivertode-aminiseproteinandtodisposeoftheproductsbereduced,itispossiblethatthesemembranesareusedas222P.D.MULIKERN
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anaccessoryorganofexcretion.Thatthismaybesoissuggestedbyobservingthereactionsofnew-bornbabiestotheirmilk.Certaininfantsearlymanifestthecatarrhalstate.Thefirstoccurrenceisthe”stickyeye”ofcatarrhalconjunctivitis,localizedtotheinnercanthusofoneeye.Otherscommencewithnasalobstruction,naso-pharyngeal,orpharyngo-oesophagealcatarrh.Alittlelaterthesebabiesregurgitatefeeds,retchmucousfluid,orfranklyvomit.Analysisoftheirfeedinghabitswilldisclosethatthecalorieintakeisexcessive,orthat,althoughthecalorie/weightratioiscorrect,theyaremuchoverweight.Ashortfastfollowedbyadjustmentofthefeedscausesaregressionofthecatarrhalstate.Nodrugtherapyisnecessary.Isuggestthatthecatarrhalstateisanexpressionofpoorhepaticfunctionassociatedwithproteinmetabolism.Itfollowsthatanybiologicalorchemicalagentwhichdepressesliverfunctionwithreferencetoproteineconomyanddisposalmayproducethecatarrhalstate.Atypicaltuberculosiscanbeinheritedoracquired;itischieflythoughttoinfecttheliver,spleen,andlymphadeno-matoussystemsandbythismeanstodepresstheliverfunctionandcausecatarrh.TheClinicalPictureIngeneralitisaconditionofsubnormalhealthverycommonlyseeningeneralpracticewhichdevelopswhenthelevelofhealthfailstobemaintained.Thebodyde-encesarere-alignedonanewbasistoresistfurtherdeteriorationresultinginastateofcatarrhdevelopingatvariousweakenedareassituatedonthemaincanalsofthebody-thegut,therespiratory,orthegenito-urinarysystems.Descentintothecatarrhalstatecommencesintheautumnandemergenceoccursinthespring.Catarrhislikesyphilisinthatitcanaffectallagesandmanysystems;syphilisisaspirochaetemiawithhepaticandsplenicinfectionwhichaccordswellwiththehypo-thesisexpressedinthispaperconcerningatypicalgranularhepaticinfectionbythebacillusofKoch.Thesymptomsofcatarrharenumerous,butthesignsarescanty.Theclinicalsymptomsdefineastateofpoorphysiologicalfunctionaccompaniedbymuco-proteinhypersecretioninendothelialmembraneswhichareliabletoacuteexacerbationthroughbacterialinfection.TherespiratorytractTheprimarycatarrhalsyndromeisacoldantiphlogisticaffair,therebeingnofeverandnotumescence.Butear,nose,andthroatareasareveryliabletodevelopsecondaryinflammatoryreactions.Bronchialcatarrhandbronchitis,atelectasisandpneumonitis,sinuscatarrhandsinusitisareexamplesofthisdualcoldandhotpathology.Obstructivenasalcatarrhextendingtotheeustachiantubescausestinnitus,impairedauditionandpainsbeneaththeearcanals.ATHECATARRHALSTATE223
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specificpathology,congestiveinflammationofthemucosa,andmultiple,localadenitisisanotherpossibleexpressionofthecatarrhalstate.Manysufferersfromchronicconstipationandspasticcolonpainbecomefrankcasesofmucouscolitis,whichissurelyanotherformofthesamecatarrh.Allthesestatescandevelopatanyagefrombirthonwards,appearingandregressingfromseasontoseasonandinaccordancewiththegeneralhealthofthepatient.Theytendtoprevailatthechangeoftheseasonswhensucharedescribedas”chills”,orfollowingcircumstanceswhichcausenervousorphysicaldepressionofthepatient’svitality.Thesyndromemaybeobservedtotravelfromthemouthtotheanusasinterruptedepisodestakingyearstoextendtootherareasandoftenrecurringrepeatedlyatonesitebeforeaffectinganewregion.Itseemslikelythatthevaguesymptomsofpainintherightiliacfossa,constipation,anddyspepsiawhichhasbeencalled”grumblingappendicitis”arecausedbycatarrhandmusclespasmofthecaecumandappendix.Shouldahotinflammatorydefencereactionbeinitiatedbybacterialinfectionthenacuteappendicitisoccursandthelocalcatarrhalstateisliquidated.ThereproductivesystemCatarrhofthevulvaandvaginaisnotuncommoninyoungchildrenandisreportedbythemotherswhoareworriedbyfindingstainsonundergarments.Leucorrhoeaofcatarrhaltypecommencesafterthemenarche,butinmultiparousfemalesisaccompaniedbysecondarybacterialinfectionfollowingtraumatothecervixduringabirth.Theendometrialproliferationwhichisoftenfoundtoaccompanycervicitismayindicateacatarrhalmetritis.Thesymptomsassociatedwithsuchapathologyarepolymenorrhoea,menorrhagia,dysmenorrhoea,andchronicsacraldiscomfort.Sometimespainlessbladderfrequency,precipitantmicturition,orcoughincontinenceindicateastateoftrigonecatarrh,whilefrankattacksofcystitisarecausedbytheusualsecondaryinfectioninvadingamucousmembranealreadyweakenedbycatarrh.Suchpatientsoftenexhibitmultiplesymptomssuggestingageneralloweringofvitalityusuallycallednervousdebility.Thereisepi-gastricemptinessandunusuallyrapidsatiationatmealssothatal-thoughfeelinghungryafewmouthfulssatisfiesthem.Theycomplainofcentralabdominalbloatingcausingthemtocastoffcorsets.Theyaremoody,irritable,perpetuallytired,yetunabletosleepsoundly.Theyarepronetomiscarriageandaccidentalhaemorrhageinpregnancy;manyarerelativelysterile.GeneralaidstodiagnosisWhereverthecatarrhalstateismanifest,thereonefindslocallymphglandhypertrophyandtenderness.Thecervical,themesen-tericandtheinternalchainofiliacglandsareallpalpableiftheTHECATARRHALSTATE225
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catchmentorgansareaffectedbycatarrh.Thereisalsoatendencyforinflammationduetoknownpathogenicbacteriatodevelopatanysitesickwithcatarrhwheresuchorganismsaresaphrophyticorcangainaccess.Suchaduelpathologyisillustratedbytonsillitis,sinusitis,andotitismediaintheupperrespiratorytract;bybron-chitis,bronchopneumonia,andpneumonitisinthelowerrespiratorytract;byinfantilegastro-enteritisandbysomecasesofulcerativecolitis;byvaginitis,cervicitis,andcystitisinthegenito-urinarytract.Itissuggestedthatsomestatesofcatarrhandsecondarybacterialinfectionresultfromexcessivesecretionofmucoproteininitiatedbyageneraldecreaseinhepaticfunction.Ingeneral,thesepatientsaretenseandirritable.Theytireeasilybutsleeplightly.Theycannotfaceanymealbeforemiddayandalthoughfeelinghungryasmallmealsatisfiesthem.Headachesareacommonoccurrence.Amongparouswomenenquirywillelicitmenstrualirregularities.Adolescentandyoungadultmalesareimmuneexceptforthedigestivetract.Perhapstheexperimentalworkdescribedinthispaperhasbeenignoredormisunderstoodbecausethephenomenaobservedinexperimentalanimalsdidnotappeartorelatetoanydiseasesorsyndromesdescribedinman.Pioneersreportfactsforposteritytointerpret.IfthesuccessorsandstudentsofKochhavereportedsomepartofthetruthwhentheyobservedthatthefoetusesandyoungofguinea-pigsinfectedbyhumantuberclebacilliwerenothealthybecauseofliverdamage,thenwemustlookforasimilarsyndromeinhumans.Thesyndromewearelookingformaybethecatarrhalstateandthisstatemaybeanoccultdefectinproteinmetabolism.REFERENCES1.LENDRUM,J.D.(1951),Brit.med.J.,2,148-51.2.LENDRum,J.D.(1952),Brit.med.J.,2,649-51.3.CROFTON,W.M.,Thetruenatureofviruses.London.Chap.III,p.51.4.CROFTON,W.M.,Thetruenatureofviruses.London.Chap.I.5.NINNI,M.C.,PASTEuR,A.R.,Inst.S.India,1933.6.NEGRYandBRETEY.(1953).Amer.Rev.Tuberc.68,467.7.DOWNIE,A.W.andMEISSNER,G.(1934).Zbl.Bakt.,1.Abt.Orig.130,465.8.RICH,A.R.,PathogenesisofTuberculosis.Oxford,1951.Chap.III.p.96.9.KAHN,M.C.(1936).Amer.Rev.Tuberc.34,36110.KAHN,M.C.(1923).Amer.Rev.Tuberc.18,815.11.CoopER,F.R.andPETROFF,S.A.J.Infect.Dis.43,200.12.BRIEGER,E.M.,Tubercle,Vol.XXX,248.London.13.SIMoN,H.J.(1960).AttenuatedInfection.Montreal.175.226P.D.MULKERN
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