A

l\l|A ffieL MARINEMEDICAL SOCIETY

(RegdF-3611)

President Surg VADM JC SHARMA VSM, PHS DGMS(NAVY)

VicePresidents Surg RADM VK PAHWA SurgRADM HP MUKHERJEE VSM CMO WesternNaval Command CommandinsOfficer.INHS Asvini

ExecutiveCommittee Surg Cmde PS VALDIYA Surg Cmde SP MALHOTRA DirectorINM DMS (P&M) NavalHeadquarters Surg CmdeWP THERGAONKAR SurgCmde BPS Rawat, VSM CMO, EasternNaval Command CMO,SouthemNaval Command Surg Cmde ML GUPTA VSM Surg Cmde AK CHAUDHARJ DentalAdv. (Navy) DMS (H& S) Naval Headquarters Surg Capt S NANGPAL Surg Cdr D D'COSTA Sr.Adv MarineMedicine INS Vajrabahu Surg LCdr S BHANDARI Surg LCdr GD BHANOT SHO(Mumbai) INS Abhimanyu Secretary Surg Cdr KBS CHEEMA Treasurer Surg Capt GS GREWAL Addressfor Correspondence Secretary MARINE MEDICAL SOCIETY Instituteof NavalMedicine, Colaba,Mumbai 400 005.INDIA Fax:022-2150670 E-mail: [email protected] JOURNAL OF MARINE MEDICAL SOCIETY

JULY-DEC1999

PublishedBiannually

Chief Editor SUTgRADMVKPAIIWA

Editor Surg Capt S NANGPAL

Co Editors Surg Capt RATAN SINGH SuTgCdTGIRISHGUPTA

Sub Editors Naval Headquarters SurgCdTAAHIJJANM Western Naval Command Surg Cdr D D'COSTA Eastern Naval Command Surg Cdr VRG PATNAIK Southern Naval Command SuTgCdTMJJOHN Editorial AdvisoryBoard SurgCmde (D) MLGUPTA,VSM Surg CmdeRTAWASTHI CoIHSPRUTHI SurgCaptRAMESHKLIMAR Surg Capt KK DUTTA GUPTA SurgCdrB SUDARSAN

Addressfor Correspondence Editor JOURNAL OF MARINE MBDICAL SOCIETY Instituteof NavalMedicine, Colaba.Mumbai 400 005. Telefax:022-215 0670 E-mail: [email protected]

Printed and Publishedby Surg Cdr KBS Cheemaon behalf of Director Generalof Medical Services(Navy) and printed at Typo Graphics,Mumbai 400 103 and publishedat Instituteof Naval Medicine, Colaba,Mumbai 400 005. Editor: Surg Capt S Nangpal - t orix REi JOURNAL OF MARINB MEDICAL SOCIETY MU CONTENTS Surg From The Editor's Desk 6l Surg

NEW FRONTIERS ABSl Advancesin MolecularBiology' BeamonAgarwal Apn malar The PolymeraseChain Reaction and8 SurgI't cdr H Mani, surg Lt cdr cN chaudhari, surg cdr RN Misra, surg capt MK Gupta above beenr Infectioushoteinaceous Particles - Prions 69 Lt Col SPMittal, SurgIs Cdr Mohit Goel KEY

ORIGINAL ARTICLE INTI Resurgenceof Malariaat Mumbai 'tl CantonmentDuring 1998-99 Or SurgCapt KK Dutta Gupta,Surg MDM VK Pahwa, SurgLt Cdr S Bhandari, in l9i Surgls Cdr M llankum/zren hogr Blood PressureProfile Under Hyperbaric Conditions globa SurgCdr MJ John, SurgCapt S Nangpal count HyperbaricOxygen for IndustrialMedical SerUp 83 ticida SurgLt P Gokulakrishnan under (NMr QualityAssurance of Regenerativechemical Being used in submarineEscape Set dence SurgGdr B Sudarsan,Surg Cdr MJ John, SurgCapt S Nangpal yearI SexualDimorphism in CoronaryArtery Disease: AnatomicalFactors result UshaDhall, BasantLal duetr Managementand Visual Outcomeof Patientswith OpenGlobe Injuries 95 Th S Natarajan, ShyamaSatyan differ Roleof SerumThyroglobulin in The Managementof Well DifferentiatedThyroid Cancer 98 specil SurgCdr B Fanthome,Sandeep Sebastian troopl Challengesin BurnShock Resuscitation 103 befro SurgCdr YPMonga risk r becon An Analysisof HundredSuccessful Pregnancies in Infertilecouples 106 SurgCdr SushilKumar, SurgCmde RT Awasthi, Surg L CdrA Kapoor, froml Surg L Cdr S Sinivas, P Verma additi onlee Alcohol in The MedicolegalRegister u0 SurgCdr Alh^adAnant Pawar A notic( GrowthPattem in The Frist Six Monthsof Life A Semi-longitudinalStudy tt4 to the SurgLt Cdr S Narayan,Surg Cmde WP Thergaonkar, Surg CdrT Nagaraja locall SerumPotassium kvels in Beta-2Agonist Nebulisation of Asthmaticchildren 120 surg L cdr s Das, surg capt KS Bawa, P Agarwal, surg cdr s Mathai, surg cdr G Gupta *Sr.Ar Mumbr

Jour.t .t.q.sn RBPoRT Congenital Malaria - A Report on Two Cases 128 Surgls Cdr S Narayan, SurgLt CdrV Hande, SurgLt Cdr N Nath Congenital Cyst of The Spleen - A CaseReport 130 lt Col G Ravindranath, VSM, Surg Capt Ramesh Kumar, Surg Cdr G Gupta, Dr. TanveerA Majeed A Case of Natal Teeth 132 Surg Lt (D) SS Chopra, Surg Lt CdrV Hande, Surg lt Cdr S Narayan . BOOK REVIEW 134

JOURNALWATCH 135 , GUIDELINESTO AUTHORS t37 From water bottles to wind-up to)4s

Frommugs to milk pouches

From jars to juicers Reliancetouches eve$odyrslife. From pipes to packaging

From gas-masksto garbagecans

From bottles to bathtubs

,As 6e f.got p"fytto manufac'tnerin dre country, Relianceprovides the raw materialsfo making alrrost eveaykind of plastic youlve seen.This has enabld Relianceto touch the lives of millions for the better.Not just brough the plastic prodrrts that it helps qeate but also becausealt ReliancepLstics ale recyclableand eco-friendly,

a A Reliance Inftrolrleb Llmlted o I --M;i;;-Actt|tbfre F zP -A -'I. 6-:; /o-- r\ /**\ \:--:7 -:!zz

HiBb Ddsity tirrdldD.Bity bl)ryinyl Chlorid. Folypopylcm Fobrthylcnc Folycthy'cm blpthy{cnc (F/C) (PP) T@phthaL!. (}IDPE) OIDPE) (PET) - FROM THE EDITOR'SDESK

The releaseof this issuecoincides with the NationalConference on Marine Medicinebeing held pt Mumbai. This is alsothe last issue of theJournal in thismillennium. Just as this last issue of themillennium contains threearticles from eminentcivilian doctors, we aresure that the Journal will continueto receivearticles from our civilian counterpartson a regularbasis. Dr. S.Natrajan an eminent and renowned vitreo retinal surgeon shares his experiencein themanagement ofopenglobe injuries ofthe eye.Hyperbaric facilities at variousindustrial set ups may help in treatingseveral occupationaldisease and this is the recommendationgiven by SurgLt. Gokulkishnanin his articletitled "HyperbaricOxygen for Industrialsetup". Advancesin molecularbiology, the inventionof the polymerasechain reaction and discovery of Prions havebeen some of the advancesin the field of basicmedical sciences. Their contributiontowards finding the causeof diseaseand suggesting remedies for the sameh3ve been major achievements. Three articles in the currentissue highlight these advances. "Sexualdimorphism in coronaryartery disease - anatomicalfactors" an articleby Dr. Dhall et al. makes interestingreading. That there are structural (both gross and microscopic) differences between the coronaries of malesand females has been emphasised by theauthors. They conclude that narrowercoronaries in relation to heartsize and thicker tunica intima in malesmay be someof the anatomicalfactors making them more susceptibleto coronaryartery disease. Hitherto,the staiusof borderlinehypertensives especially in divers,submarines and patients undergoing hyperbaricoxygen therapy was not clear,as literature was scanty even on theinternet, but thearticle "Blood pressureprofile underhyperbaric condition" by SurgCdr MJ Johnet al in thecurrent journal deals with this issuecomprehensively. Havingsaid all this,it is our solemnduty to onceagain remind ourselves of the supremesacrifice by the valiantmembers of the ArmedForces who laid downtheir lives in the defenceof our country'sborders in the recentconflict. l.et us observea minute'ssilence and rededicate our selvesto the causeat handin the comingmillennium. JaiHind!

NANGPAL)

Jour. Marine Medical Society,July-Dec 1999,Vol. I, No.2 6I Qrtlunefl ast V ompliments

ftom

IryS.IESICA CHEMICALS

ByramjiMansion, lst Floor, SirPM Road,Fort, 'Mumbai40000l. Phones:266 4052,2660574,2666283 New Frontiers ADVANCESIN MOLECULARBIOLOGY

BEAMON AGARWAL

INTRODUCTION Cell adhesion

1.s molecularbiology relevantto us? Molecular Cell adhesion acts as a contact inhibitor of cell questionshow a normal human proliferation. are I biology ma- The main adhesionmolecules the I-chine worksbiologically and at whatprecise site lectins, selectinsand the cadherins.Deregulated cell a disorderin this machineresults in disease. adhesionleads to proliferation of cells which is not physiological. Mediators of cell adhesionhelp us in The basic advances recently occurring are in the genesisof tumour development. embryogenesis,cell cycle, cell adhesion,cell com- explaining munication, signal transduction and cell death or Cell defence ' apoptosis.To beginwith, how doesa humanevolve? We all have been programmed with a software - The moment an organismis born it entersinto the DNA on which we develop our phenotype. The Darwinian survival for existence.Even the smallest evolved human body hasbeen granted a neuroendo- organism is met by numerouspathogens which can crine control which regulatesour progam. destroy it. The one that is able to survive is depend- ent on cell immunity. Malfunction of this leadsto Cell cycle autoimmunityor immunodeficiency.The majorhis- After conceptioncell proliferation leadsto differ- tocompatibility complex or the HLA system has provided ent stagesof embryogenesis..Each system is devel- been on nearly all cells which acts as oped from individual collection of cells. The cell identificationmarker unique to an individual. Any cycle hasmainly four stagesGl, G2, S andM. In the pathogenattacking the body but having a different cell cycle the principal regulators are the cyclins - antigenstatus is recognisedby the immune cells B cdkl, cdk2, cdk4 and p21. Improper activationof and T. The T cells with the help of macrophages pathogen. theseresults in unregulatedcell growth-hyperplasia/ ultimately led to cytotoxic death of the neoplasm.Understanding about the loss or disorder This is regulated by IL-l and IL-Z. HLA system of a cyclin in individual tumour helps us in under- forms the basis of transplant.That a mother is able standing the biology of tumours. to hold another organism for approximately 290 dayswithout rejection can also be explained.Hyper- Cell communication active rejectionleads to hypenensitivity or the so - Why does one cell work in co-ordinatedmanner called allergicdisorders. with other cells? If all the cells startedfunctioning Cell cytoskeleton simultaneouslyor randomly- what would resultwill be akin to heaped up cars on a race track. Cells It is responsiblefor the spatialorganisation ofthe communicatewith eachotherthrough chemical me- cells. The three major types of fibres are the micro- diators. They receive signalsby cytokines/ inter- tubules, actin filaments and the intermediate fila- leukins - which is the languageof communication ments.The microtubulesare used for intracellular of the cells. Interleukinsplay an importantrole in transport.The actin filaments areresponsible for cell cell stimulationand the defenceof the cell immu- mobility and shape.The intermediatefilaments are nology. responsiblefor giving tensilestrength to the cells. The intermediatefilaments are keratin in epithelial cells. vimentin in fibroblastsand desmin in muscle

Tata Memorial Hospital, Dr. Emest Borges Marg, Mumbai - 400 012.

Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 63 fibres. area combinationof immunologicalassay and mo- lecular genetictechniques. The initial setup is ex- Cell growth factors pensivebut with gradualautomation of all techno- Stimulation and inhibition of releaseof growth logicalprocesses this problemis now circumvented. factor is responsiblefor cell growth and cell death. The main techniquesare flow cytometry, immuno- Releaseof thesegrowth factorsis also responsible histochemistry,Insitu hybridisationand the polym- for the differentiation during embryogenesis.The erasechain reaction. principle growth factors are the EGF (epidermal The basic reason for understanding molecular growth factor), PDGF (platelet derived growth fac- biology is to stimulateour minds to answer why tor), FGF (fibroblast growth factor) and TGF (trans- things work. This is best understood in a reverse forming growth factor). processby studying individual diseases.Finding a Cell receptors particular fault in a profile of a diseasehelps in The growth factors and other signals act on cell elucidatinga causefor thedisease. Once we areable receptorswhich belong to mainly threeclasses : G to answerit's aetiologywe can think of repairingor proteins, steroid receptor family and the enzyme modifying it. The whole scienceof pharmacology receptors.The G proteinscontain seven transmem- 'replacingor the treatment of diseaseby drugs is based on - brane proteins. It consistsofthree subunitsa, p and or controlling a biochemical mediator y. The enzymelinked receptorsare tyrosinekinase, enzyme,ion or hormone.Deeper understanding of tyrosine phosphateand the serene/ threoninerecep- the processhelps in preciselocalisation of the mal- - tors. function replacementof themediator by an equiva- lent drug and finally treatment.Besides infectious Cell regulation and signal transduction diseasewe rarelycure a diseaseby drugs.It is more The cellsare mainly regulatedby thenervous and palliative. Vaccinesdevelopment occurred by un- the endocrinesystem. The nervoussystem regulates dentandingor isolatingthe toxic geneof the organ- through neurotransmitters, while the endocrine ism - it's pathwayor cycle in the human organism regulatesthrough the horrnones.All theseact on cell and building up a prepareddefence against it. receptorswhich act through the camp or the Ca++ Finally as every era of journalists prophesise - activation tyrosinekinase activation causing regu- aboutthe eradicationofdiseases and a diseasefree lation of cell processes.Disorders of hormone regu- world. medical scientistsknow better. The emer- latory transmitter leads to endocrine diseasesand genceof prion associateddiseases (bovine spongio- disorderof neurotransmittersto mainly the psychi- form encephalopathy),HIV relatedsyndromes and atric disease. the resurfacingof the dormant diseaseslike TB and Cell death shigellosiskeep informing us about our inadequate understandingof diseases. Apoptosis is recognisedas the mechanismby which unwantedcells are tidily eliminatedwith no What liesin thefuture is thefield of neurobiology messyconsequences such as inflammation.This is which will help in understandingthe pathogenesis important in the immune systemwhich is typified of the neurologicaldiseases, which till date are a by overproductionof all sortsof cells, particularly conglomerationof clinical and pathologicalfind- self-reactivelymphocytes which would be a severe ings and medicalcure is availableonly for epilepsy embarrassmentto the organism if not removed. and a few other diseases. Autoimmunity and cancerare the consequencesof REFERENCES not having enough apoptosis.Apoptotic mecha- l. Heldin CH. Dimerizationof cell surfacereceptors and signal nisms also play a role in killing of target cells by transduction. Cell 1995:.80 : 213. immuneeffector cells suchas cytotoxic T cells. 2. Ihle JN. Cytokine receptor signalling. Nature 1995:.3'17 : Molecular biologr techniques 591.

Briefly moleculartechniques rely on the repro- 3. Feig LA. The many roads that lead to ras. Science 1993 duction of the invivo biochemicalreactions. Thev 2N :767.

64 Jour. Marine Medical Society, July-Dec 1999, Vol. 1, No.2 THE POLYMERASECHAIN REACTION

Surg Lt Cdr H MAM'|', Surg Lt Cdr CN CHAIJDHARI*, Surg Cdr RN MISRA+, Surg Capt MK GUPTA#

(PCR) llolymerase chainreaction is a common allowedto cool,then complementary base pairs can (renature 'Anneal') lrmethod of creatingcopies of specificfrag- reform or andthe originaldou- L mentsof DNA. PCRrapidly amplifies a sin- ble helix is restored. gle DNA moleculeinto manybillions of molecules The polymerasechain reactionis a test tube in a few hours.When the polymerase chain reaction systemfor DNA replicationthat allows a "target" was introducedto the scientific communityat a DNA sequenceto be selectivelyamplified, or en- conferencein October1985, scientists, quick to riched, severalmillion fold in just a few hours. embracethe new technique, were surprised (with the Withina dividingcell, DNA replicationinvolves a wisdomthat accompanies hindsight) that no one had seriesof enzymemediated reactions, whose end thoughtof it earlier.The credit for this flash of resultis a faithfulcopy of theentire genome. During insightgoes to Kary Mullis,a scientistworking for cellularDNA replication,enzymes first unwindand theCetus Corporation. Dr. Mullis wasdriving along denaturethe DNA doublehelix into singlestrands. a mountainroad in NorthernCalifornia with his Then,RNA polymerasesynthesizes a shortstretch mindon a problemof nucleicacid biochemistry. He of RNA complementaryto oneof the DNA strands wasstruggling to devisea simplemethod for deter- at the startsite of replication.This DNA/RNA het- miningthe identity of a specificnucleotide along a eroduplexacts as a "primingsite" forthe attachment stretchof DNA. Whathe hit upon,however, was not of the DNA polymerase,which then producesthe a solutionto his originalproblem, but one of even complementaryDNA strand. greatersignificance. He had just conceivedof a Within a testtube, PCR uses just oneindispensa- simple methodfor producingvirtually unlimited ble enzyme- DNA polymerase- to amplify a spe- copiesof a specificDNA sequencein a testtube - cific fractionof thegenome. PCR will allow a short thepolymerase chain reaction. Cetus rewarded Kary stretchof DNA (usuallyfewer than 3000 base pairs) Mullis with a $10,000bonus for his invention,and to be amplifiedto abouta million fold so that one later, during a corporatereorganization, sold the candetermine its size,nucleotide sequence, etc. The patentfor the PCR processto the pharmaceutical particularstretch of DNA to beamplified, called the companyHoffmann-La Roche for $300 million! targetsequence, is identifredby a specificpair of The popularityof PCR continuesunabated. As of DNA primers,oligonucleotides usually about 20 the end of 1998.PCR hasbeen referenced in well nucleotidesin length.During PCR,high tempera- over20,000 scientifi c publications. ture(about 9fC) is usedto separatethe DNA mole- The Mechanismof PCR culesinto singlestrands, and synthetic sequences of single-strandedDNA (20-30nucleotides) serve as Thechemistry of PCR,as with muchof molecu- primers.Two differentprimer sequences are used to lar biology, dependson the complementarityof bracketthe target region to beamplified. One primer DNA bases,by whichadenine and guanine in one is complementaryto oneDNA strandat the begin- stand bind complimentarilyonly to thymine and ningof thetarget region; a secondprimer is comple- cytosineof the oppositestrand by hydrogenbonds. mentaryto a sequenceon the oppositeDNA strand Whena moleculeof DNA is sufficientlyheated, the at the end of the targetregion. The annealingof hydrogenbonds holding together the doublehelix primers 'Dena- to the ends of the target sequencesis are disruptedand the moleculeunzips or achievedby cooling.The solutionin the tubesto tures'into singlestrands. If the DNA solutionis

*GradedSp Pathology;+Classified Sp Pathology;#Sr AdviserPathology; INHS Asvini,Colaba, Mumbai - 400 005.

Jour. Marine Medical Society,July-Dec 1999,Vol. 1, No.2 65 lowertemperature (55-6f). Duringthis cooling it is lyze their own DNA and seefor themselvestheir possiblethat the originaltwo strandsof DNA may uniquegenetic heritage ! annealtogether thereby not providingthe target site The actual procedure for annealingof the primers.This problemis over- comeby puttingan excess of primersin thesolution, To performa PCRreaction, a smallquantity of thusincreasing the chancesof 'hits' by the primers thetarget DNA is addedto a testtube with a buffered on the target.Also, the primersequences are much solutioncontaining DNA polymerase,oligonu- smallerthan the original complementarystrand of cleotideprimers, the four deoxynucleotidebuilding DNA, thusfacilitating preferential annealing of the blocksof DNA, andthe cofactor MgCl2. The PCR primersto the targetsequence of interest.Now the mixtureis takenthrough replication cycles consist- DNA polymerasecomes into play. In the presence ing of : of this enzyme,additional nucleotides are added on l. One to severalminutes at 94-96 degreesC, to the now annealedprimer sequences,(an event duringwhich the DNA is denaturedinto single 'Extension'), termed at temperaturesof about72t. strands; The sequenceof this 'polymerization'of individual 2. Half to oneminute at 50-65degrees C, during nucleotidesto form a chain is determinedby the whichthe primershybridize or anneal(by way complementarysequence of the targetDNA. Thus, of hydrogenbonds) to their complementary if thesequence in thetarget DNA is -TAACTG-the sequenceson eitherside of thetarget sequence; DNA polymerasewill add - ATTGAC- to the and lengtheningnew strand, and so on till theend ofthe DNA strand.This completesone PCR cycle. As the 3. Half to one minute at 72 degreesC, during cyclesare repeated through sequences ofdenatura- whichthe polymerase binds and extends a com- tion, annealingand extension, more and more of the plementaryDNA strandfrom eachprimer. targetDNA sequencewill begenerated till thereac- Thus, the three stepsin the polymerasechain tion undergoessaturation as substrateand enzyme reaction- theseparation ofthe strands,annealing the getsused up. primer to the template,and the synthesisof new - In the earlydays, PCRs used to be carriedout in strands take lessthan two minutes.Each is carried waterbaths of differenttemperatures. Since DNA outin thesame vial. At theend of a cycle,each piece polymeraseis an enzyme,it wasfound to be labile of DNA in thevial hasbeen duplicated. As amplifi- at the high temperaturesrequired for denaturation, cation proceeds,the DNA sequencebetween the andthe enzyme had to beadded afresh for eachnew primersdoubles after each cycle. But the cycle can cycleof extension.Not only wasthis cumbersome, be repeated30 or moretimes. Each newly synthe- but the increasedhandling also increasedthe sizedDNA piececan act as a newtemplate, so after chancesof 'contamination'.Two importantinnova- 30 cycles,one billion copiesof a singlepiece of tionswere responsible for automatingPCR.First, a DNA canbe produced! Taking into accountthe time heat-stableDNA polymerasewas isolated from the it takesto changethe temperatureof the reaction bacteriumThermus aquaticus, which inhabitshot vial,one million copies can be ready in aboutthree springs.This enzyme,called the Taq polymerase, hours. remains active despite repeatedheating during The intentof PCRis to basicallyamplify target manycycles of amplification.Second, DNA thermal DNA of interest.Now detectionof this targetse- cyclerswere invented that use computer software to quencein solutionsenriched with thetarget DNA is controlthe repetitivetemperature changes required easier.This detectionis carriedout throughelectro- for PCR.Automated DNA thermalcyclers are be- phoresison agarosegels. While suchamplifications comingless expensive, and may soon cost about the areimpressive, the importantpoint to rememberis sameas microcentrifuges,which are increasingly that the amplificationis selective- only the DNA foundin teachinglaboratories. A DNA thermalcy- sequencelocated between the primersis amplified cler enablesthe instructorto takefull advantageof exponentially.The restof the DNA in the genome PCR'scapabilities, including the amplificationof is not amplifiedand remainsinvisible in the gel. humanDNA. PCRcan even allow students to ana- SincePCR amplifications can generatemicrogram

66 Jour. Marine Medical Society,July-Dec 1999, Vol. I, No.2 quantitiesof product(which is a greatdeal of DNA), and held at a temperatureabove the threshold amplifiedfragments can be visualized easily follow- of non-specificbinding of primerto template. ing stainingwith a chemicalstain such as ethidium All thePCR reaction components are added for bromide,methylene blue, or carolinablue (TM) the extensionreaction except one critical re- DNA stain. Ethidium bromide is the stain most agent(usually the thermostablepolymerase). commonlyused because of its sensitivityto DNA Justprior to thecycling, the missing component and the speedof staining.Drawbacks include the is addedto allow the reactionto takeplace at costinvolved for its visualization(it requiresa UV highertemperature. Due to lackof non-specific light source),and its suspectedcarcinogenicity. The hybridizationof primersto template,the ampli- low concentrationsrequired for stainingcan be used fied DNA bandstend to becleaner; the primen safely, however,by wearing rubber gloves and don't havea chanceto annealnon-specifically. workingin a sink. e. RT-PCR- Reversetranscription PCR is an in- Variations on the theme directmethod of detectingRNA sequences.In the normal cell, DNA codesfor RNA by a Numerousmodification of this basic protocol processcalled transcription. RNA viruseslike have been devisedfor certain specialsituations. . HIV andHepatitis C containreverse transcrip- Someof thesevariations are: tase,an enzyme that forms DNA from RNA. A a. NestedPCR - Here,the PCR product is subject similar principleis usedin the laboratoryfor to a secondround of PCR usingfresh primers detectionand amplification of messengerRNA for smaller sequencesof interestwithin the whereinin the first step the RNA is reverse majortarget sequence. This thereforeincreases transcribedto complementaryDNA (cDNA). thesensitivity and specificity ofthe reactionby This cDNA is thenamplified by PCR. approachingthe final DNA sequenceof interest f. MultiplexPCR - This involvesadding multiple in two phases. setsof primersin the sametest tube. These b. TouchdownPCR - TouchdownPCR involves multipleprimer sets increase the sensitivityof decreasingthe annealingtemperature by one detectionof a targetsequence. degreeC everysecond cycle to a 'touchdown' annealingtemp which is thenused for l0 or so The applicationsof PCR cycles. It was originally intendedto bypass Theapplications of PCRare extensive including more complicatedoptimization processes for : molecularbiology, environmental science, foren- determiningoptimal annealingtemperatures sicscience, medical science, biotechnology, micro- for eachreaction. This thereforehelps enrich biology, the food industry, diagnostic science, the correct productsover incorrectproducts, epidemiology,genetics, gene cloning and many since lowering the annealing temperature more.The main applicationsin clinicalmedicine makesthe reaching more specific. Another use pertainto infections,malignancies, genetic disor- for this procedureis in determiningDNA se- ders,tissue typing and forensics. quencefor a known protein,that is, working Infectionscan be diagnosedby identifyingspe- backwards. cific DNA sequencesof microorganismsin tissues c. AP-PCRor RAPD PCR - Arbitrarily primed andbody fluids wherethe numbersof microbesare PCR(AP-PCR) or randomamplified polymor- too smallto allowdetection by routinemethods (e.9. phic DNA (RAPD) are methodsof creating tuberculousmeningitis) or routinemethods are not genomicfingerprints of specieswhere little is easilydone (e.g. chlamydial infections). Further, known abouttarget sequence to be amplified. PCRmay allow monitoringof treatmentresponses, DNA amplifiedin this mannercan be usedto especiallyin thecase of viruseslike HIV andhepa- determinethe relatednessof species. titisC. d. Hofstart PCR - "Hot-start"PCR is a method In the field of oncology,not only do PCR-based that generallyproduces cleaner PCR products. methodsgive information on geneticpredisposition TemplateDNA andprimers are mixed together to cancer(e.g. BRCA-l genein breastcancer), but

Jour.Marine Medical Society, July-Dec 1999, Vol. l, No.2 67 also allow specifictyping and classificationof tu- The ability of PCRto utilize degradedDNA samples mours(e.g. specific translocation and other molecu- is of great interestto forensic scientistswho must lar eventsin hematolymphoidmalignancies), and sometimeswork with human cells in very poor help maketherapeutic decisions (e.g. detection of condition.The techniquehas provided conclusive minimalresidual disease and molecular staging). identificationsin caseswhere conventionalDNA Genedisorders can be identifiedwhere the spe- typing has failed. Ironically, the greatestconcem cific geneis known in disease(e.g. cystic fibrosis, aboutthe widespreaduse of PCR in forensicmedi- Duchenne'muscular dystrophy, hemochromatosis). cine is the technique'sexEeme sensitivity! Even PCRhas proven a quick, reliablemethod for detect- minisculeamounts of DNA left overfrom previous ing all mannerof mutationsassociated with genetic amplificationscan be reamplified,leading to an disease- from insertions,to deletions,to point mu- inconclusiveresult, so-called'contamination'. And tations,and most genetic testing may soon be PCR- finally, PCR relatedtechniques are being widely based. Tissue typing by serologic methods is usedin the questfor mappingthe humangenome wroughtwith pitfallsespecially in thecase of HILA andother medical research. class-ll. PCR amplificationand use of sequence REFERENCES specific probeshave tremendouslyimproved the specificityof donor-recipientmatch and graft sur- l. Mullis KB. The unusual origin of the polymerascchain vival in transplantation.Applications in forensic rcaction.Scientific Anerican l99O;262 : 5G65. medicineare obviousand includeparentage deter- 2. PCR Protocols.A guide to methodsand applicatims. MA minationand DNA identificationat crime scenes. Innis el aJ,eds,, Academic Press, New York, 1990.

68 Jour. Marine Medical Society,July-Dec 1999,Vol. 1, No.2 INFECTIOUSPROTEINACEOUS PARTICLES . PRIONS

Lt Col SP MITTAL*, Surg Lt Cdr MOHIT GOEL+

ABSTRACT Stanley B Prusiner of United Staies of America was awarded the Nobel Prize in 1997 in medicine for his commendablework leading to the discoveryof PRIONS, an entirely new genreof diseasecausing biological agents, other than known infectious agents including parasites, bacteria, viruses and fungi. Stanley and his colleagues started work in l92.ln 1982they isolatedsuccessfully from hamstcr's brain a single infectious agent which was found to be comprising of a single protein. Stanley called it Prion. In 19E4,Stanley and his colleaguesisolated a prion geneprobe and showedthat ihis genecode is present in gll enimals, including man. Subsequently,Stanley found two types of prions, Scrapie type (PrPSc) and cell type (PrPc). Prions were demonstrAtedto be species specific. Stanley and other workers cloned the prion geneand showedthat prion @rPc) is present in many cells in the body and ls abundant in nerve cells in brain. Stanley and his colleaguesalso successfullydemonstrated in 1992that prion encodinggene is required for infection with PrPSc in animal models. KEY WORDS : PRIONS.Slow virus.

INTRODUCTION enablesdisease causing prion proteinsto interact with oneanother forming nconventionalslow viruseswere believed, threadJikestructures and ag$egatesthat till lately to be the causativeagents of non- uniformlydestroy nerve cells. The basisof this proteinaggregation inflammatoryneurologic diseases. The in- andtheir cumula- tive destructivemechanism cubationperiod of suchdiseases is variablefrom is not clear.Prions are speciesspecific Theseparticles manymonths to years.No singlevirus property can []. aresupposed to progressing be assignedto theseunconventional transmissible causeseveral slowly brain diseases, bothin humans agents,suggesting these could be different from andanimals. conventionalviruses. Out of many theoriesabout Infectedbrain areas by prionsimpart vacuolation 'sub- the natureof theseinfectious agents, one postulate andspongy appearance and henceare called wasthat these agents lack nucleic acid, a sensational acutespringiform viral encephalopathies'.Now vi- hypothesissince till todate all known infectious ral word appearsto be a misnomerbecause of dis- agentscontain DNA or RNA. Stanleyet al, success- covery of prions as causativeagents of these fully isolateda singleinfectious agent from experi- encephalopathies.There is associatedextensive mentaldiseased hamster brain and found that this nervecell death. agentwas comprisedof a single protein.Stanley calledthis.agent PRION as an operational name for Genetic determinants and prion formation this putativeinfectious agent. hion is definedas a Stanleyet al in 1984isolated a geneprobe for smallproteinaceous infectious particle that is resis- prionand showed subsequently that this geneprobe tantto inactivationby mostof proteasesthat modify for prion wasfound in all animals,including man. nucleicacids. But how are theseprions harmless in animalsand manwhen these are normallybeing formed in the Pathogenicity of prions body?Prion protein (hP) may be presentin two Prionsare much smaller than viruses. As prions distinct conformations,one that causesdisease, arenatural proteins, no immuneresponse is present Scrapietype (PrPSc)and other normal i.e. cellular againstprions. They arenot poisonous,but become type(PrPC). Scrapie was the beststudied disease in harmful only by convertinginto a structwethat whichsurface membrane prion protein - PrPScwas

*Classified Specialist (Medicine); +Graded Specialist (Medicine); INHS Sanjivani, Naval Base, Cochin.

Jour. Marine Medical Society,July-Dec 1999,Vol. I, No.2 69 thought to be involved in the development of this of mutationof humanhPc encodinggene. It is disease.This hPSc was not found in normal brain. primarilyan infectionof thalamusregion. It was shown that PrPScprion protein had infectious (d) Creutzfeldt- JakobDisease : Involvespre- properties and could initiate a gene based chain dominantlycerebral cortex. ln 85-90Voof the cases reaction so that PrPC is also converted into a more ofdiseaseoccurs spontaneously. Ten to fifteenper- stable PrPSc form. PrPSc is more stable and is cent of CJD werecaused by the mutationof PrPc resistant to proteolysis, organic solvents and high encodinggene and rarely CJD occursdue to infec- temperature. During incubation period PrPSc can tion. A new variantof CJD wasidentified through accumulateto a level that results in brain damage. BSE-transmission.These patients present with Stanley et al cloned the prion gene and demon- psycologicalsymptoms and motor system involve- stratedthat PrPc is an ordinary componentofleuco- ment. cytes and many other tissuescells. PrPc is abundant (e) Thereare indicationsthat dementialike ill- on the surface of nerve cells in the brain. Stanley nesse.g. Alzheimer's disease are caused when cer- found that prion diseases,Creutzfeldt-Jakob disease tain, non-prion,proteins (CJD) and Gerstmann-Straussler-Scheinker(GSS) undergoa confirmational changethat leads to theformation and deposition of diseasewere due to mutation in the prion gene.The harmfulplaques in conceptof mutation was unravelled in experimental or deposits the brain. (mice mice where prion knock-out mice in which Future outJook of prion diseases prion gene encoding prion protein was abolished) were resistantto infection when exposedto disease The discoveryof prionsand their role in causa- causing PrPSc. When gene encoding PrP was rein- tion of variousdiseases, the so called slow virus troduced in these mice they became susceptibleto diseases,now preferablycalled prion diseaseshas infection with hPSc. The role of PrPc in brain and openedthe field for betterunderstanding of these other tissuesremains unsolved. diseasesand search forprion specificpharmacologi- Specific mutations within the prion gene gives cal agents.The discoveryof prion encodinggene rise to structurally variant disease-causingproteins. mayhelp in thebetterunderstanding of is functional The variant PrPSc proteins may be preferentially modification.The dementia like diseases e.g. Alzhe- accummulatedin various parts of the brain, thereby imer'sdementia, can be better understood in light of prions. manifestingclinically with different incubationpe- discoveryof For example,Alzheimer's de- mentiais causedwhen certain, non-prion, proteins riods [,2]. undergo configurationalchanges and lead to depo- (a) Bovine spongiform encephalopathy(BSE) : sitionof harmfulplaques in the brain. It is transmittedto cows through feedssupplemented with products from scrapieinfected sheeps.Primar- REFERENCES ily brain stemis infectedin this PrPScvariant. l. Donald HH. Robert GJ. Viral diseasesof central nervous (b) Kuru and GSS : These predominantly infect system : Aseptic meningitis and ecphalalitis. In: Harrison's cerebellum. Kuru was shown to be transmitted Principles of intemal medicine. International edition : New through cannibalistic rituals in some tribals of New York Mc Graw Hill Inc l99l; 2031-38. Guinea.GSS is a hereditarydementia resulting from 2. hice RW. Slow virus infection of the nervous system. In : mutation of gene encoding human PrPc. Cecil's Text Book of Medicine; Philadelphia WB Saunders (c) Fatal familial insomnia : It is another variant Company 1985;2203-7.

70 Jour. Marine Medical Society,July-Dec 1999, Vol. l, No.2 ' e Original Articles RESURGENCEOF MALARIA AT MUMBAI CANTONMENTDURING 1998-99

Surg Capt KK DUTTA GUPTA*, SurgRADM VK PAHWA+, 6l SurgLt Cdr S BHANDARI#,Surg Lt Cdr M ILANKUMARAN**

ABSTRACT 6'1 A proforma basedepidemiological investigation of malaria cases(slide positive)was carried ouL 371 casesof malaria occurredfrom Sep.98 to Mar. 99. Benigntertian malaria and malignanttertian malaria caseswere 289 65 and 82 respectivelyout of a total of 371 malaria cases.Four casesdied due to malignant tertian malaria during abovestudy period.The result ofthe studyalong with suggestedmeasures to reducethe incidenceofmalaria have beendiscussed in this paper. 69 KEY WORDS: Malaria.

INTRODUCTION malariacases in the "A" ward of Mumbai Municipal 1l Organisedmalaria control effortsstarted in India Corporationwhere Mumbai Cantonmentarea is lo- cated. in 1953with launchingof NationalMalaria Control Programme. Encouraged by initial successand MATERIAL AND METHODS 76 globalcall for malariaeradication, large areas of the A proformabased epidemiological investigation country were brought under in-door residualinsec- of all admitted malaria cases(slide positive) was ticidal spray. Modified plan of operation(MPO), 83 carriedout by SHO (MB) staff for patientsadmitted under national malaria eradication programme at INHS Asvini. Daily admissionstate and malaria (NMEP) was successfulin keeping malaria inci- 86 parasitereport register formed the source of infor- denceto around 2-3 million casesannually. In the mation aboutoccurrence of a case.Comprehensive year 1994,largescale epidemics broke out in India investigationincluded detailed history, clinical pic- 92 resulting in an increasein morbidity and mortality ture,species ofmalarial parasiteby peripheralblood dueto malaria []. smear/ bonemarrow examination,movement to or 95 The control of malaria in armedforces assumes from endemicarea and treatmentgiven. Mixed in- different dimensionbecause of certainpeculiarities fectionhas been included in malignanttertian (MT) 98 specific to armed forces.Due to strategicreasons, malariafor the purposeof analysis. troopsare moved from oneplace to anotheri.e., may RESULTS 103 be from low malariarisk/non endemic region to high risk maiaria region and vice versa.These troops The first caseof malignanttertian (MT) malaria becomea reservoirof infectionwhen was admitted on 18 Sep. 98. The distribution of 106 they moveout from high malariarisk areaafter a specifictime. In casesof malaria(BT and MT) from Sep.98 to Mar. addition,there is a constantmovement of personnel, 99 is givenin Table l. on leave/dutyencouraging transport of malaria. Out of 371 malariacases, I 15 (3l%o)cases were il0 A marked increasein the number of caseswas not admittedin the hospitaland hencenot investi- noticedfrom Sep.98 till endof Mar.99 ascompared gated.This wasevident from laboratoryreport book n4 to the sameperiod in earlieryears. Information from and admission/dischargebook of the hospital. local healthauthorities indicated an upwardtrend of The distributionof BT malaria casesfrom Sep. t20 *Sr. Adviser, Prev and Social Medicine; +Command Medical Officer, Western Naval Command, Mumbai; llOfficer-in-chiuge, SHO, Mumbai: **PG Traineein Prev.Med.

Jour. Marine Medical Society,July-Dec 1999,Vol. I, No.2 7I TABLE1 r rl Mdarla (BT and MT) casesln armedforces personnel and their familiesat Mumbai

Month Sep.98 Oct.98 Nov.98 Dec.98 Jan.99 Feb.99 Mar.9 Total

Naval personnel 23 t7 l8 10 t4 l3 t8 ll3 Navalfamilies l3 l5 05 05 02 0l 05 46 Army personnel ll 08 06 05 03 03 03 39 Army families 03 08 04 03 0l 0l 20 Othersr l0 08 06 08 02 0l 03 38 Not admiaed 39 l8 t6 05 20 l0 o7 l15 Total 99 74 55 36 42 28 37 371

i Ohcrsincludcd air forcespersonnel and their families, personal servants and ex-service personnel.

TABLE 2 Benigptertian (BT) malartacases

Sep.98 Oct.98 Nov.98 Dec.98 Jan.99 Feb.99 Mar.99 Total

l. Admitted 46 3l 24 23 2l l5 30 190 i) t ocal 34 l8 l8 l3 05 06 23 lt7 ii)Imported t2 l3 06 02 02 04 39 iii) Relapse 08 t4 05 o7 34 2. Not admitted 30 t4 l3 05 20 l0 07 99

Total 45 37 28 4l 25 37 289

TABLE3 Malignant terdan (MT) malaria cascs

Sep.98 Oct.98 Nov.98 Dec.98 Jan.99 Feb.99 Mar. 99 Total

Admined t4 25 l5 08 0l 03 6 Locd 07 t2 08 & 'l 01 33 Imported 06 09 (X 03 0l 23 Relapse 0l (X 03 0l 0l l0 I Not admitted 09 M 03 l6 t Total 23 29 l8 08 0l 03 82 ( s

a 98 to Mar.99 is shownin Table2. local, 10 (l5.2%o)cases relapsed and 23 (34.8Vo) Outof 289cases of BT malaria,99(343%) cases were importedcases. Mixed infectionshave been werenot admitted hencecould not be investigated. includedin malignanttertian malaria cases. Four Out of 190 investigatedcases, 34 (17.97o)were casesout of aboveended fatally. A surveycarried relapsecases, l17 (6l.6vo)cases were local and39 out revealedlids to over-headwater tanks miss- (20.5%)were imported cases. ing/brokenin 407otanks. The distribution of MT malariacases from Sept OBSERVATIONS 98 to March99 is shownin Table3. The following significant observationswere Therewerc 82 casesof MT malaria.16 (I9.5%) made. caseswer€ not admittedand hencewere not inves- . The transmissionof malariain Mumbai had tigarcd.Out of 66 investigatedcases, 33 (50%)were increasedwith increasein MT cases.

Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 l,argenumber of caseswere diagnosed as clini- to sub-centrelevel as given in Table5 [2]. cal malariaas repeated blood slides were nega- , tive for MP. They aremostly treated with only TABLE 5 chloroquine. Presumptlve treatment of malaria in high risk areas 3 Large numberof slide positivemalaria cases Age Firstday Secondday Thirdday 5 (in years) Chlor oq uinePr imaq uineChloroquine Chloroguine ) were not adminedin the hospital.They were (mg) (mg) (mg) (mg) ) treatedas OPD patientsand it was not clear <- I year 75 Nil 75 37.5 l whether these patients received radical treat- I -4 yean 150 7.5 150 ?5.0 5 mentor not. 5-8yean 300 15.0 300 150.0 I o The numberof relapsecases was 4 (I7.2%) 9 - 14 years 450 30.0 450 225.0 indicating failure of treaunent / inadequate > 15years 600 45.0 600 300.0 treatrnentresistance to drugs. o Due to constructionalactivities. man made Recommendedpresumptive treatrnent in resis- mosquitogenicenvironment is prevalent in tant areasinclude sulphalene/ sulphodoxine+ mostaneas. pyrimethamine(1500 mg + 75 mg respectively)as " Improperly fitting/mi-ssingover headtank lids a singledose [2,3]. Chloroquine resistance has been ^ (, resultedin breedingof vectorspecies. docunientedin manyareas in our country[4]. The 7 r Insecticidalresistance, inadequate manpower WHO classificationof in vivo resisianceis graded ) with stationhealth organisationsand lack of from RI (blood film becomesclear of parasitesby I community participation are also contributory oneweek but relapses by four weeks),to R II (partial ) to the increasedincidence of malaria. responseat one week) and R III (no significant responseat oneweek) At presentserious efforts 9 o Penonalprotective measures (especially use of [3]. mosquitonets / mosquitorepellants / improper arenot b€ing made to determinein vivo chloroquine mosquitoproofing) to preventmosquito bite resistancestatus. Presently recommended 13 bloods werenot takenby mostof the individuals. slideexamination in four weeksto determineearly recrudenceand late recrudence may not bepractica- SUGGESTEDSOLUTIONS TO TIIE - ble.It will be worthwhile to carryout in vivo study PROBLEM andformulate a viableprotocol in the follow-upof malariacases with the help of peripheralblood ) a) Casedetection of malaria cases l smear. l Emphasisshould be to detectmaximum cases ii) Radical treatment J throughsick bays, MI roomsand hospital OPD's by I examinationof blood smearfor MP of all fevei It hasbeen seen that most of the admittedcases ,_ cases.NMEP guidelineto stainthe slidewith JSB of malariahave been treatedwith chloroquine/ stainand examineat least 100 fields which takes primaquinecombination, but some slide positive BT aboutfive minutesshould be followed.[n serious malariacases have been treated with chloroquine/ 87o) andcomplicated MT cases,density of parasitesper metakalfincombination. There is a needto stand- )een 100fields should be assessed. NMEP envisages that ardisethe treatmentprotocol. All rour microscopically all positiveblood smearsand l0% of all negative positivecases of malariaare to be given radical ried ones to be crosschecked by a seniorlaboratory treatrnentwith primaquinefor its gametocidaland riss- technicianor pathologist[2]. anti relapseproperties. This ensurescure from ma- laria and makesthe patientnon infective b) Treatment of cases to mos- quito. Radicaltreatment of P. Vivax, P. Malariae i ) p resumptiv e t reqtment andmixed infection is 15 mg primaquinedaily for Presumptivetreatrnent in low risk areascom- 5 days[2]. prisesof a singledose of chloroquinephosphate in Reviseddrug policy undermalaria action pro- the doseof 10 mg/kg body weight.NMEP recom- grammerecommends treatment of MT caseswith a mendspresumptive treatment in high risk areasup combinationof sulphalene/ sulphodoxine(1500

Yo.2 Jour.lQarine Medical Society, July-Dec 1999, Vol. I, No.2 73 mg) andpyrimethamine (75 mg) asa singledose for area, overheadtanks are important source of mos- the stanr adultfollowed by 45 mg primaquine(single dose). quito breeding.During January to May every year, usedin t Thesedrugs should be givenwith cautionas sulpha all overheadtanks should be made mosquito proof / drugs and primaquineare known to precipitate repaired.Terrace / Roof top drainageoutlets should MATEI haemolyticcrisis in sensitivecases with G6PDde- be checked,so that there is no stagnation of water Thel ficiency.In cases,which are resistant to abovedrugs on rooftop. Construction activities create excellent ing para and severeand complicatedmalaria with P. falci- breedingcondition for anophelesstephensi. Several parum infection, quinine 10 kg out breaksof malaria have causedby water sulphate mg/per been the TABLE1 body weightthrice daily as intravenousinfusion in storage/ stagnationconsequent to construction and Physicalr 57odextrose / glucoseover 4 hoursis given.Later other developmental activities. Engineers can en- samedose schedule is given orally to complete7 sure that mosquitogenicenvironment is not created. S.No. T1 daystreatmentl2,3), This can be achievedby simple methods like land t. C( filling, proper drainage and observanceof dry day iii) Useof newanti-malarials st( at unit level. Newerdrugslike mefloquine,artemisinin and its 2. Cr derivativescan be usedin the managementof P. vi ) Anti-larv al measure s falciparumresistant to chloroquineby medicalspe- Various studies indicate that antilarval insecti- a) cialist supportedby a laboratoryreport issued by a cides like Fenthion and Temephos are effective b) pathologistindicating that thereare P. falciparum against mosquito larvae. Temephos at I ppm and c) ringsin theperipheral blood f2,3,51. Acombination Fenthion I mglL are effective against mosquito d) of sulphamethopyrazine/ sulphamethoxazole+ larvae[8]. e) pyrimethamine(Metakelfin) may be used in chloro- 0 Biocidesnamely Bacillus sphericus and Bacillus quineresistant malaria. 3. Si thuringiensis are now recommended for malaria a) iv) Chemoprophylaxis control only in specialsituations. SHO (Class- I) periodically A good suppressivedrug shouldbe fast acting can monitor susceptibility of various h' againsterythrocytic stages, should have long half- insecticidesand proposethe useofalternative insec- c) /' life andshould not betoxic. In armedforces chloro- ticide / biocides if situation demands.In addition to gambusia, other locally available fish, which are .j quineis starteda weekbefore departure to hyper-en- 0 larvivorous. can be used in fire tanks and static demicarea and terminated 4 to 6 weeksafter leaving 4.D the area.The recommendeddose is l0 mg/kgbody tanks. weight as loading dose and 5 mg/kg at weekly vii Anti -adult measures interval. In moderatechloroquine resistant area, ) B Since annual parasite incidence (API) is more a. proguanil100 mg is given daily. Drug compliance D than2Toat Mumbai, plasmodiumfalciparum (MT) will be poor in view of daily requirement.Both c chloroquineand proguanilcan be takenfor a con- cases are being diagnosed and four deaths due to d tinuousperiod of five years without apparentill malaria have taken place during period under study, e I, effect[6]. Betterefficacy of 600mg chloroquineas it will be worthwhile to carry our insecticidal spray, building wise This block sprayingdesign has chemoprophylaxishas been reported for controlof [9]. a (Feb. - malariain P. falciparumresistant area where other beentried in naval residqntialareas Mar.99) b malariacontrol measures are not feasibleor practi- at Mumbai and found to be effective and can be F cal anddiagnostic therapeutic facilities are not eas- implementedas a regular spraying practice. ily available b [7]. viii) Impregnatedbed nets 1 v) Role of administration,engineers and a Deltamethrin emulsifi able concentrate25Vo can t resident'sas sociation be usedfor impregnationof bed nets.Nylon netsare ( Thereis now increasingrealisation that involve- preferredover cotton nets becauseofdurability and ( mentof the community,engineers and administra- they arequicker in drying after impregnation.Insec- I torsand a multi sectoralapproach are essential com- ticides stay longer on the surface of nylon fibres. ponentsof the malariacontrol strategy.In urban When not washed, the impregnated net will have

74 Jour.Marine Medical Society, July-Dec 1999, Vol. l, No.2 Jour. lt bfficacyfor six months.SHO (MB) hasimpregnated tor measur€swill go a longway in reducingmorbid- netswith deltamethrinfor navalestablishments at ity and mortality due to malaria. Mumbai.The efficacyof deltamethrinimpregnated REFERENCES netsis beingassessed. l. NeerajDhingra DhillonGPS, Shivlal. Processindicaton for ix) Personalproteetive measures malariacontrol, J ComnunDis 1998;30 (3): 209-28. It includesuse of mosquitonet, long trousers, 2. DirectorateGencral of Health Services.Govt. of India Mr- rolleddown full sleeveshirt from duskto dawn.The man Bhavan,New Delhi. OperationalManual, Malaria Ac- sizeof theopening of thenets should not exceedI .2 tion ProgramnreGovt. of India, Delhi (1995) p 18-29. mm in anydimension. Screening of houseswith nets policy with similar dimensiongives excellent protection. 3. Dhillan GPS,Shivlal. Revised drug undermalaria eradicationpro$amme. J CommunDis 1997:n Repellentslike Odomosand DMP whichare avail- Q):2@- 17. able with Material Superintendentas patterned item canbe usedduring night duty. 4. SharmaVP. Reemergenceof malariain India. krdian Jour- rul of Medical Research 1996;103 : 26-45, CONCLUSION 5. Wilkinson RI, DavidsonRN. Drug therapyof falciparum Thereis no doubtthat malariahas come back to malaria practicc and futu€ prospects.Bombay Hospital stay with us. The failure of efforts to control the Joumal 1996t3E.l :63-7. vector speciesand increasingnumber of plasmo- 6. Weip WRC. Thc chcmoprophylaxisof malaria practical dium flaciparumcases make it unlikelythat signifi- consideration.Bonbay Hospital Jounul 1996;38.1 : 6f'-7O. cant declinein incidenceof casescan take place until andunless there is co-ordinationbetween cli- 7. Agarwal VK SharmaRC, Ctalaabarty PK. Malariaconuol nician,pathologist, public health workers and com- amongsttroops involved in counterinsurgency. Operation munityin particular.A quick diagnosisand prompt in resistantplasmodium flacipaum arca.MJAFL 1998; 54 (2): treatmentwould be facilitated if reliableand careful 105-6. reporting of malarial parasite smear was widely 8. Shivlal, PhukanPK SharmaSN, Kaul SM, SaxenaNBL. available.A synchronizedfalciparum infection may 'Anti-malaria Month' A step forward in multisectoralcol- sequesterinto deep tissuesleading to a negative laborationand community involvement in malariaconuol. ./ smear.Therefore repeatedblood smeartesting is CommmDis 1998;30 (2) : 93-101. necessaryin P. falciparuminfection. The enthusias- 9. Park K. Text book of Prcventivcand Social Medicine. lv{/s tic useofpersonal protective measures and anti-vec- BanarasidasBhanot. Iabalpur, lsth Ed 1997,196.

Jour. Marine Medical Sociery,July-Dec 1999,Vol. I, No.2 75 Original Articles BLOOD PRESSUREPROFILE UNDER HYPERBARICCONDITIONS

Surg Cdr MJ JOHN{', Surg Capt S NANGPAL+

ABSTRACT This study investigates biood pressure and heart rate values at 10 minuie iniervals using a computerized ambulatory monitor in patients undergoing hyperbaric oxygen therapy and divers / submariners brething compressedair at depths varying from 2.2 ATA to 2.EATA as compared to thelr values at normal atnmpheric pressuFes.Its nim was to detect how cardiovascular rhythms behave under changed / increased ahospheric pnessunecondltions which may have implications for patients who arrcundergoing hyperbaric oxygen therapy and for divers in their long tenn carrer. The study was proposed as no data on thesc aspectswas available in literature. Blood pressurt and heart rate were measurcd using a hon invasive ambulatory computcrized monitor at l0 minutes interval and statfutically analyzedby conventionalprocedures. All men,of meanage of 32 yrs were studied. They underwent exposurc to higher barometric pressunesof 2.2 ta 2.E ATA for duration of 6t0minutes to 80 minutes. The results were compared to their valuesunder normal afuospheric pnesisure. a) Iherr is a statistically significnnt reduction in the systolic,diastolic and mean arterial pressurts and pulse rate during stay at high barometric prlessune. b) Therc is an increase ln the mean systollc, diastolic, mean arterial pnessuneand pulse rate during the prrcssrrrizationand de pressurization schedules c) Atthough the difference in blood pressurevalues ofdivers (under the presentstudy with no cardiovascular risk fac'tors) measurcd with a mercury blood pnessureapparatus and mean of the resting blood pressurc under nonnobaric conditions using ambulatory btood pnessunemonitor was not statisdcally sipificant it indicahs the pmsibte use of ABP monitor ln assessingwhite coat hypertension in professionaldivers. The observedchanges may be reflecting a tonic modulation of blood prcssure and heart ratc rhythm which allows the cardiovascular apparatus to adapt itself without imposing an extra load on its function in normotensive subjecG.But the zurge of thesevalues during prtssurization and de-pressurizationschedule in an hypertensive/ taclycardia padent / individual may be deleterious and henceprior to hyperbaric oxygen therapy / diving, the blood prcssurc and pulse rate should not exceed140/90 mm Hg. KEY WORDS : Ambulatory Blood Pressurc,Hyperbaric chamber

INTRODUCTION preventedits introductionworld wide, on invasive ambulatory blood pressure Portablenon-invasive computerized units auto- monitoringhas been developed over the past maticallyinflate a conventionalarm cuff at pre-set two decadesand offers considerable advan- intervalsand measure blood pressure either by aus- tageover conventional clinical blood pressure moni- cultatoryor by oscillometricmethods via a micro- toring. The concept originated after the phone transducerstrapped over brachial artery. developmentof intra-arterialblood pressuremoni- Most presentday unitshave facility for bothmeth- toring in the UK. The accuracyand reliability of ods of recordingand oscillometricmethod is used theseinvasive units were excellent,but fears of asan automaticback up in caseof enoneousread- suddendistal ischaemiaor a major haemorrhage ings.The primaryadvantage offered by monitoring

*ClassifiedSpecialist in Marine Medicine,Diving School,Kochi; +SeniorAdviser in Marine Mcdicine, Institute of Naval Medicine, Mumbai.

76 Jour. Marine Medical Society,July-Dec 1999,Vol. 1, No.2 overlong perid aremultiple readings rather than a factorssince experienced divers are difficult to one time measurementand avoidanceof possible comeand thereis considerableinvestment in erron associatedwith conventionalmeasurements. them., Twenty four hour measurementsplay an important b) Is it safeto accepthypertensive patients (who role in diagnosingand treating patients with border are poorly controlled) for hyperbaric oxygen line hypertensionmany of whommay have normal therapy(since any way the bloodpressure will ambulatoryblood pressures. It is estimatedthat ap- decreaseunder higher partial pressures) proximately207o of thosediagnosed with hyperten- c) Is theeis a scopeto eliminate sionby conventionaloffice bloodpressure readings "white coat hy- pertension"among who were "white coat hypertensive".These personnel divers have no other cardiovascularrisk factors and therebysave can avoid beingdiagnosed with hypertensionand unnecessarytrained man power loss. can avoid the associatedcost of treatmentand un- necessaryjob restrictions. MATERIAL AND METHOD In addition,use of ambulatoryblood pressure The equipment monitoringcan provide informationregarding re- The mainequipment used was BR 102ambula- sponseof cardiovascularsystem to differentenvi- tory tomputerized blood pressure recorder of ronmentalconditions like space,extreme cold cli- Schiller I It is a menuguided, user programmable mates(like in Antarctica),travel across several time I ]. unit, enablingboth individualand long pres- zonesetc. term sure measurementsat pre-setintervals around the Diving bradycardiais a well known entity.But clock for severaldays. All recordedmeasurement review of literature revealed that blood pressure dataare stored in its internal memory.It hasa serial responseunder hyperbaric conditions are scantily interfacewhich canbe linked with peripheralunits studied.In facta searchover the National Library of like a printer for print out of a "blood pressureheart Medicine,USA, revealed489 indexedarticles pub- rate protocol" of a long term measurement;to a PC lishedon ambulatoryblood pressure monitoring, but for storageand analysis of measurementdata; and noneunder hyperbaric conditions. to a modem for transferringmeasurement data Basedon thesereports, there have beenrecom- througha phoneline. mendationsof allowing experienceddivers to con- The subjects tinuewith diving activity evenwith bloodpressure The subjecs were male divers/submarinersand recordingsof 150/95mm Hg sincea decreaseof patientsundergoing hyperbaric oxygen therapy at blood pressurewas expectedunder dived condi- the Hyperbaricoxygen therapyfacility of Institute tions.Also no reasonableguidelines were available of NavalMedicine. All subjectsalso under went a regardingblood pressure readings ofpatients under- restingECG, X-ray chest PA andfasting blood sugar goinghyperbaric oxygen therapy who are otherwise aspart of thestudy and only subjectshaving normal hypertensiveand poorly controlled. valuesfor each of theseinvestigations were in- Also, in the past,a numberof diven had to be cluded.A cardiovascularrisk profile questionnaire withdrawn from diving cadre becauseof "labile to evaluateobese, current smoken, exercising fewer hypertensionI gradeI hypertension"without any than 20 minutesthree times a week and having cardiovascularrisk profile at all. family history of hypertensionwere also drawn. Hence the following questionsremain unan- Subjectswere explainedthe study involved and sweredas far asdiving andblood pressure readings providedwith a sheetof paperfor recordingtheir areconcerned. activities. a) Is the decreasein bloodpressure and pulse rate Study design underdived conditionsuniversal and if so can The proposedstay under pressureand depth of we accepta higherblood pressure recording of dive werepredetermined (as for a hyperbaricoxy- 150195mm Hg as the limit valuefor experi- gentherapy schedule / normaldive profile) so that enceddiven without anv cardiovascularrisk the controlmeasurement time could be calculated.

Jour.Marine Medical Society, r*-Orc 199, Vol.I, No.2 The blood pressurecuff of the BR 102equipment TABLE2 wasplaced on the nondominant arm of the subject. Cardiovascularrisk factors(n = 52) Patientdata is thenentered into therecorder and Risk factor No. of subjects the measurementparameters are defined. l. Historyof family 4 The subjectis explainedthe procedureand in- illnessof cardiovascular formedabout the time whenthe measurementswill diseases ) begin.He is advisednot to movehis arm whenthe 2. Obesity measurementis beingrecorded and preferably keep 3. Smoker ll 4. lrss exercise lt it at heartlevel. 5. None 24 Control readings The subjectis kept inside the chamberfor the TABLE3 calculateddive period.The recorderrecords blood Catepryof subjects(n = 52) pressureand heart rate every l0 minutes.Since the Categoryof subjects subjectswere kept insidethe chamberat this stage, it excludedany environmentai bias (other than high Divers / submariners t4 pressure)and hence these readings acted as controls HBOT patients 38 for the study.Three manual readings using mercury blood pressureapparatus were recorded at the be- TABLE 4 ginning period. of rest Mean restlng BP and heart rate rcsponsesamong divers / Thechamber pressure is thenraised to thedesired zubmariners(n = 14) level (2.2ata to 2.8 ata)and maintained for 60 to 80 Values No. of subiects minutes.After this the pressureis reducod,subject is takenout from thechamber and the measurement Meansystolic pressur€ 128 is terminated. Mean diastolicpressure 77 Mean arterial pressure 92 Data retrieval Meanpulse rate 69 The dataon the recorderis thentransferred to a computerdata base. BR 102software was usedto TABLE 5 facilitatedata sorting and correlation with theactiv- Mean BP and heart rate responsesamong divers / subma- ity log sheetregarding depth and time. Initial experi- riners during pressurisation (n = 14) mental readingswer6 read out serially from the recordersince the presentsoft ware was not then Values No. of subjects available.Enoneous blood pressure readings as in- Meansystolic pressure 138 dicatedby recorderwere omitted. Meandiastolic pressur€ 97 Meanarterial pressure ll0 RESULTS Meanpulse rate 102

TABLE I Age distribution (n = 52) TABLE 6 Mean BP and heart rate nesponsesamong divers / subma- Age group No. of subjects riners during de-pressurisatlon(n = 14) <20 I Values No. of subjects 2t-30 27 3l-40 15 Meansystolic pressure t42 4l-50 6 Meandiastolic pressure 9'l 5l-60 7 Mean arterial pressure t12 61-70 I Meanpulse rate 98

78 Jour. Marine Medical Society,July-Dec 1999, Vol. 1, No.2 TABLE 7 TABLE 12 Mean BP and heart rate responsesamong divers / subma- Mean resting BP and heart rate responsesamong patients riners 20 minutes aft€r stay at bottom (n = 14) of HBOT during depressurisation(n = f,g; Values No. of subjects Values No. of subjects Mean systolic pressure tt7 Meansystolic pressure 156 Mean diastolic pressure 68 Meandiastolic pressure 102 Mean arterial pressure 84 Mean arterialpressure t20 Mean pulse rate 62 Meanpulse rate 106

TABLE 8 TABLE 13 Mean BP and heart rate responsesamong divers / subma. Mean resting BP and hesrt rate responsesamong patients riners after 30 minutesstay at bottom (n = 14) of HBOT at 20 minutesstay at depth (n - 38)

Values No. of subjects Values No. of subjects

Meansystolic pressure 118 Meansystolic pressure ll8 Meandiastolic pressure 68 Meandiastolic pressure 78 Mean arterial pressure 84 Mean arterialpressur€ 83 Meanpulse rate ffi Meanpulse rate 70

TABLE 9 TABLE 14 Mean BP and heart rate responsesamong divers / subma- Mean resting BP and heart rate responscsamong patients riners sfter 40 minutes stay at depth (n = 14) of HBOT at 30 minutes stay at bottom (n = 38)

Values No. of subjects Values No. of subjects

Mean systolic pressure ll8 Mean systolic pressure lt8 Mean diastolic pressure 67 Mean diastolic pressure 74 Mean arterial pressure 84 Mean arterial prcssure 88 Mean pulse rate 60 Mean pulse rate 60

TABLE IO TABLE 15 Mean resting BP and heart rate responsesamong patients Mean resting BP and heart rate responsesamong patients of HBOT (n = 38) of HBOT at 4{) minutes stay at bottom (n = 38)

Values No. of subjects Values No. of subjects Mean systolic pressure r32 Mean systolic pressure 120 Mean diastolic pressure 86 Mean diastolic pressure 1J Mean arterial pressure l0l Mean arterial pressure 88 Mean pulse rate 78 Mean pulse rate 68

TABLE 11 DISCUSSION Mean BP and heart rate respons€samong patients of HBOT during pressurisation(n = 38) Ambulatory blood pressure monitoring began with intra-arterialdevices developed in the UK. The Values No. of subjects accuracy and reliability of the unit was excellent. Meansystolic pressure 151 The investigatorsclaimed that their device was rea- Mean diastolicpressure r02 sonably comfortable and safe. But, fears of sudden Mean arterial pressure u8 distal ischaemiaor a major haemorrhageprevented Meanpulse rate ll0 its introduction and use in the USA. Portablenon invasive monitors becameclinicallv

Jour. Maine Medical Society,July-Dec 1999,Vot. l, No.2 79 availablein the USA in 1978.These units automat- monitoringequipment during spaceflights on the ically inflated a conventional arm cuff at preset NASA shuttle. intervalsand measuredblood pressureby ausculta- pressure tion of Korotkoff soundsvia a small microphone Ambulatory blood monitoring during transducerstrapped over the brachialartery. To ex- fiights acrosstlme zones clude inaccuraciescaused by adventitioussounds, Fogeri R et al [4] reportedthe effectsof a west- chestleads (to facilitateR wavegating) ensured that wardtransmeridian flight acrosssix time zoneson only true Korotkoff soundswere being measured. blood pressureusing ambulatory blood pressure Oscillometryoffen analternative non invasive tech- monitoringequipments in normotensivesubjects. nique. This involves direct palpationof brachial The resultof the studyindicated that thereare no artery fluctuations through the arm cuff. The unit significantchanges in blood pressureacross time measuressystolic and mean blood pressures directly zonesflights and the only decreasenoted was during (on the basisof the width of thepulse pressure) and sleepand that it wasthe resultof sleepitself. usesan algorithm to calculatethe diastolic pr€ssure. pressure Becausethis doesnot requirechest leads, this tech- Ambulatory blood monitoring at niqueuses a smallerand simplerunit thanthe aus- Antarctica cultatorydevices. Cugini P et al [5] reportedtheir study in the Aviation SpaceEnvironment Medicine regarding How reliable are theseunits investigationson the blood pressureand heart rate JM Neutel[2],studied the relationshipbenreen valuesin clinically healthysubjecs adapted to liv- bloodpressuremeasured by a mercurysphygmoma- ing in Antarctica,as compared to their coevalsub- nometerand an oscillometric or auscultatorydevice jectsliving in theirhome country using ambulatory in 25hospitalizedpatients andhas shown significant blood pressuremonitoring equipment.The nor- correlation(p < 0.001)in thesystolic diastolic meas- motensivesubjects living in Antarcticawere seen to urements.He observedthat thesedevices tend to showsignificant changes in the daily meanlevel of lose accuracyif the patientis excessivelyactive systolic blood pressure(increase) and heart rate duringmonitoring. This is oneof thedisadvantages (decrease)as compared to theircontrols. But despite of non invasiveBP measurementscomparcd to in- the permanentsolar lighl they were seento show tra-arterialtechniques. blood pressureand heartrate circadianrhythms to be perfectlysynchronized to the 24 hour cycle (as Mc KenzieI [3], of theRoyal Air ForceInstitute of AviationMedicine, Farnborough, UK, evaluated an effectimposed by the routinesof their local life ambulatorymonitoring apparatusagainst meariure- style. mentstaken intra arterially. It wasfound that ambu- Ambulatory blood pressure monitoring among latory blood pressureequipments tend to underesti- Military Aviators mateboth systolic and diastolic blood pressures but correlateswell with intraarterial line measurements. StewartJC, [6] after studyingblood pressure In general,the slope of the relationshipbetween problemsin aerospacemedicine identified a subset ambulatoryblood pressuremonitoring equipment of flien with "offrcehypertension" who may be on andintra arterialvalues were close to unity. medicationneedlessly. He discussesthe advantages of homeblood pressure recording and24 hour am- Ambulatory blood pressure monitoring in bulatory blood pressuremonitoring over routine spacemedicine blood pressurechecks and five day blood pressure (the Non invasivetechniques were initially devel- examinations standardpractice in the United opedin the USA to monitorblood pressure during StatesAir Forcetill then). spaceflight. In the 1960's,NASA madein-flight Recentlythere has been increasingnumber of measurementsinjet aircraftandduring Mercury and reports on studies carried out on blood pressure Gemini flights using the cuff technique and profiles using ambulatoryblood pressuremonitors Korotkoff sounds.In the early 1980'sashonaut - and a specialgroup of office / white coat hyperten- physicianWilliam Thornotonwore bloodpressure siveshave been identified. hesentlv the ambulatorv

80 Jour.Marine Medical Society, July-Dec': 1999, Vot. t, tlo,.Z blood pressure moniton are increasingly being unlikely,however, with thetherapy cunently avail- used. able,that theserisks can be reducedto a negligible a) to identify borderline hypertensionwith target level.Because of this,the presentrecommendations organdamage of an upperlimit of arterialblood pressureof l,t0/90 b) evaluationof drugresistance mm Hg should remain the standardfor entry into c) episodichypertension diving. d) hypotensive symptoms on antihypertensive Thequestion is thatofan experienceddiver who medications subsequentlydevelops borderline hypertension. Ac- e) office / white coathypertension cording to RD Greenand R lritch [7] one is reluc- f) evaluationof BP changesin noctumalangina tant to lose the servicesof a'skilled diver who is g) autonomicdysfunction's expensiveto train.According to them,although this h) carotidsinus syncope and pacemaker syndromes individual has an increasedrisk of mortality and i) exclusionof placeboreactors when determining morbidity, for thosewith a blood pressurebetween efficacyof antihypertensivedrug therapy in control- 140190mm Hg,and150/95 mm Hg it is not exces- led clinical trials. sive.They believed that the riskscan be minimized Ambulatory blood pressure monitoring of (but not entirelyeliminated) by ensuringthat asso- personnel under high pressure envlronments ciatedcardiac pathology, such as ischaemicheart diseaseor ventricular hypertrophyis excluded. During diving, the responseof blood pressure Hence in their paper they had recommendedto will result from a combination of the effects of considerdivers with blood pressurebelow 150195 diving environmentand the associatedphysical ac- mrn Hg andno associatedcardiac pathology should tivity requiredto perform the dive. No datais avail- beallowed to continuein diving with closemonitor- able detailing the effects of exercisein water on ing andyearly reviews. borderlinehypertensives. The presentstudy has revealed that evenin indi- The present study vidualswith perfectlynormal blood pressureand no cardiovascularrisk factors, is There were randomly sampled52 subjects,14 there a surge in the systolic,diastolic and mean arterial pressures diven / submarinersand 38 patientsof hyperbaric during pressurizationas well as oxygentherapy for the study.Their agedisribution during de-pressurization. In deeperdives and is depictedat Table 1. 28 subjectshad one of the saturationdives with long last- ing decompression cardiovascularrisk factorspositive. There is statis- times thesechanges maybe sus- tainingproducing deleterious tically significant difference(paired t test) between effectsin the long run. the blood pressureand pulse responsesduring rest Unless detailed evaluationsarc carried out under will prudent perid and during pressurization/ depressurisation theseconditions, it be not to allow even experienced with pressure /rest period at 40 minutesin both categoryof sub- divers blood of over 140/90mm Hg to carryout diving. jects. The differencein thesevalues during rest perid on surface measuredwith mercury blood REFERENCES pressureapparatus (average of three readings)and l. Schiller.Ambulatory blood pressurerccorder BR 102;users averageof valuesmeasuredby ABP monitorhasnot guide version2.2 L98,6. (paired beenstatistically significant t test). 2. Ncutcl JM. Role of whole day ambulatoryblood prassure Borderlinehypertensives have an increased mor- monitoring in the managementof hyperrcnsion,Amcrican tality overthe general population. For instance,a 35 Journal of Nephrotogy1996; 16 : 202-9. year old male with an initial blood pressureof 3. MckenzieI. Non-invasiveblood pressuremeasu€rnent un- $?'/95 mm Hg hasa 3Voless chance of surviving der G; Royal Air ForceInstitute of Aviation Medicine,UK, overten yearswhen compared to a 35 yearold with SAFEJ l99l:21 (l) :2630. an initial BP of l4U9O mm Hg. This increased 4. Fogari& LusardiP,Tappi A. "Effectsofa westwardtrans- mortality,although significant, is not excessiveand meridianflight on ambulatoryblood prcssuremonitoring in with monitoringof the individual and appropriale normotcnsivesubjects". J Hypcnens Feb. 1997; 15 (2) : therapyis potentiallyreducible. It would appear t43-6.

Jour.Marine Medical Sociery, July-Dec 1999, Vol. l, No.2 8I 5. Cugini P, CamillieriG, AlessioL, ChristinaG, Petrangeli 6. Stewart JC. "Office hypertension in the Military aviators", CM, CapodaglioPF,Ambulatory blmd pressurcmonitoring Aviation SpaceEnviron Med 1998; 59 (8) : 778-9. in clinicallyhealthy subjecrs adapted to living in Anrarctica; 7. Green RD, Leitch DR. Blmd prcssur€ and dling, Joumal Aviat SpaceEnviron Med 1997l'8: 795-801. of Royal Navy Medical Semices 1986; 72 : l5-9.

W. napher keep him smiling.

TVe help her protect him ftom ThaCs Hocclst - carc ft,r 1ou. fever, allergiesand a wide spectrum lvlaking our dpcrtirc Fo&a ',orn of lih-dueatening infectiors. most valuablc assct- ),our hcaltL Why do drousandsof doctorsuust our medicines?Simply because)'ea$ of rescarchhave helped us produce qr:ality medicineswtrich ue saft and efficacious.No wonder most of ow phannaceutical produce arc well-knoyo names, especially.our anugyreucs, anhhritamlnes, antisoasmodics and of coursc antibiotics.Each product backcd by the brmidable research skills of Hoedut AC, Germany. And our conccm hr your health goes mudr bcyond developingand medioncs. We even ensure drat our Rabies vacrine readrespatiens without a break in dre cold cluin - so cnrcial o the potencyof the vaccine. . _l HOeCnSr

Hocchst Marion Roussel Hoechlt llrrion RousselLimiled Thc Phermrceutical Compeny of Hocchst

82 Jour. Marine Medical Society,July-Dec 1999, Vol. I, No.2 HYPERBARICOXYGEN FOR INDUSTRIAL MEDICAL SET-UP

Surg Lt P GOKULAKRISHNAN

ABSTRACT Hyperbaricoxygen administered in arecompressionchamber inan industrialhospitalcan be used as a therapeutic adjunct in various settings. The article highlights the clinical usefulnessof hyperbaric oxygen in industries. KEY WORDS : Hyperbaric OxygenTherapy, Industrial Medicine

n industrialmedical set-up is differentfrom of oxygenunder pressure is thatnot only full hemo- a communitymedical set-up. Peculiarities globinsaturation is achievedbut alsosome amount suchas exposureto harmful and injurious ofoxygendissolves in theplasma causing enhanced substances,physical accidents, exposure to tissueoxygenation []. The mechanismof actionof heaVfire/highpressure are dauntingprospects for HBO is becauseof : any industrialworker. Added to it is the fact that l. Directbactericidal action on anaerobicand mi- industriesare often far from cities,located close to croaerophilicorganisms and inhibition of their highwaysand nodal points and are seldom near good toxins[2,3]. medicalcentres. These reasons make the industry's 2. Stimulatingneo-angiogenesis and osteogenesis ownmedical centre a vital link to its worker'shealth. [4,5]. An industrialhospital must be well equippedto 3. Vasoconstrictiveeffect of HBO which reduces handle cornmon emergencies,routine illness compartmentpressures and oedema amongstthe workersand some rare "strictly for the [6]. book" disorders.Ask Samir,23 yrs., a patientof 4. Immunomodulationand potentiation of certain carbon tetrachloridepoisoning contracted at his chemotherapeuticagents and antibioticslike paint and solventwarehouse; or Amar, 29 yrs., a trimethoprimand sulfonamides [7]. patient sequelaeto a com- of chronicosteomyelitis 5. Greaterleucocyte killing ability[8]. poundfracture he sustainedat theheavy machinery industrywhere he works. For Samirhyperbaric oxy- 6. Mitigation of air embolus/bubblevolume due genwas life savingwhen other therapeutic modali- to raisedpressure and outward diffusion of ni- tieshad proven futile. On Amar his diseasehad left trogen. only a minimalscar on his leg thanksto hyperbaric The foundationsof therapeuticrecompression oxygen(HBO). The highlighton thesetwo patients and hyperoxygenationare dictated by well known is not only that HBO hasbeen beneficial but also physicalprinciples such as Boyle'slaw, Charles' thattheir diseases happened to havebeen contracted law,Dalton's law and Henry's law. Not surprisingly at industries. the individualsfirst subjectedto an environmental pressure Hyperbaric medicine deals with the medical changeon surfacein an RCC were not patients. problemsand therapeutic applications of barometric diversbut pressuregrcaterthan sea level. Hyperbaric oxygena- Today RCC is utilised by divers all over the tion is achievedby havingthe patient breathe 1007o world to conductthousands of simulatedpractice Oxygeneither by mask,head tent or endotracheal dives, and HBO is used routinely to shortenthe tubein a recompressionchamber (RCC). The effects post-divedecompression period. The HBO stateof

SubmarineMedical Officer. INS Sindhuratna.

Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 83 the art of presenttimes is a spin off from research oxygen.Fire hazardin oxygenrich chamberenvi- and developmentwork related to diving indushry ronmentis alsoto be counteredeffectively. andhyperbaric medicine. Overthe yean the empha- A baromedicalunit shouldbe an integralpart of sis has slowly moved away from strictly diving every large industrial medical set-up.Industries relateddecompression to I.IBO for clinical therapy, . with theiravailable resources, latest technology and notsurprisingly because ofthe variedand seemingly commitmentto healthof their workerswould cer- endlesslist of indicationsfor its use.RCC in an tainly benefitfrom the myriaduses of a multiplace industrialhospital would help the organisationtreat RCC. With hyperbaricoxygen as a part of their somecommon industrial hazards such as : [9,10,1U repertoireindustrial hospitalscan act as a meeting Decompressionsickness in marine and caisson groundbetween conventional medicine and hyper- workers. baricmedicine. Carbsnmonoxide poisoning REFERENCES Osteoradionecrosisand soft tissue radionecrosis 1. Kivisaari J, Niinikoski L Effects of hyperbaricoxygenation amongstradiation workers andprolonged hypoxia on thehealing ofopen wounds. Acta ChirScatd 1975:l4l : 14. Crush injury with traumaticischaemia, compart- ment syndromeor nerveinjury 2. Tally FP, Stewart PR, SutberVL, RosenblattJE. Oxygen toleranceof freshclinical anaerobicbacteriu J Clin Micro- Cyanidepoisoning biol1975:.l: 16l-4. Severethermal burns. 3. Gonlieb SF. Effecs ofhypcrbaric oxygen on microorgan- Acutehydrogen sulfide poisoning. isms.Am RcvMicrobiol l97l:225: lll-52. Acutecarbon tetrachloride poisoning. 4. Kerchum.SA,III, ThomasAN, Hall AD. Angiographic studies of the effects of the hyperbaric oxygen on burn Chronicnon-healing ulcen. woundrevascularisation. Proceedings of the fourth intema- Methaemoglobinaemiain aniline poisoning. tional congresson hyperbaricmedicine. Edited by J Wada andIwa Sapporo: IgakuShoin Ltd. 1970;388-94. Severeanaemia with bloodbeing non-available. 5. Niikoski Jr, HuntTK. Oxygentensions in healingbones Szrg Problemwounds. GynObstet 1972:134 t74650. Hyperbaricoxygenation administered by RCCof 6. SukoffMH, Holli SA, JacobsonJH, tr. The protectiveeffect an industrialhospital can alSo be used to serveneedy of hyperbaricoxygenation in experimentallyproduced cerc- and sick generalpopulation of the locale. Ingisti- bral oedemaand comprcssion. Surgery 1967;62 (l) : 4G6. cally too RCC makessound financial sense as it is 7. GottliebSF, Solosky JF, Aubrey R, NcdeloffDD.Synerges- much cheaperthan transportingthe patientVother ' tic actionofincreased oxygen tensions and PABA-Folic acid costlytherapeutic agents over large distances. antagonistson bacterial growth. Aerosp Med 1974;.45 : But HBO is not entirely a bed of roses.The 829-33. adverseeffects ofHBO areoxygen induced seizures 8. MaderJT, BrownGL, GuckianJC, et aL A mechanismfor at higherpartialpressures [3] andpulmonary oxy- the amelioration by hyperbaric oxygen of experimental gentoxicity whenthe durationof HBO application staphylococcalosteomyelitis in rabbits.J Infect Dis l98O; exceedsthe safe limit of 6-8hours. Iarge multiplace r42 (6\ :915-22. chambersare expensive,so they arc few and far 9. Myen RAM, SnyderSK, Emhoff TA. Subacutescquelae of between.Seriously ill patientscannot be provided carbonmonoxide poisoning. Arn EmergMed 1985;14:- criticalmonitoring in monoplacechambers. Patients I 163-?. areoffered HBO generallyafter all othertherapeutic 10. Marx RE. JohnsonRP. Kline SN. hevention of osteora- modalitieshave failed or when the patientis criti- dionecrosis: A randomisedprospective clinical trial of hy- cally ill. Ideally HBO is given early and energeti- perbaricoxygen versus penicillin. J Am DentalAssoc 1985; cally for best results.Used last and late it is least lll:49-54. effective.It is alsoimportant to identify the health ll. ZamboniWA, Brown R, Roth AC, Mathur A. Effect of hazardsfaced by the in chamberattendants due to hyperbaricoxygen on peripheralnerve rcgeneratron, Under- repeatedexposures to higher partial pressuresof seaBiomed Res l99l; 18(Suppl.) :43.

84 Jour. Marine Medical Society, July-Dec 1999, Vol. I, No.2 t2. Riddick MF, Ianey SC, Nunky C. Hyperbaricoxygen ther- 15-6.. apy in acurcand delayed sternal wound infections and dehis- 13. Bert P. Barometricprcssur€ : Rescarchesin expcrirnental cences: An analysisofthis modality s effect on length of physiology.Translated by MA Hitchcockand RA Hitchock. stay,utilisation of resourcesand morbidity in coronaryartery Colombus:Colombus Book Co.. l%3. bypassprocedurcs. Undersea BiottcdRas 1988;15 (Suppl.)

97o"n )onate) 6y

KRISHNAN KUMAR Jaipur (Rai).

Jour. Marine Medical Society,JuIy-Dec 199, Vol. 1, No.2 85 QUALITY ASSURANCEOF REGENERATIVECHEMICAL BEING USEDIN SUBMARINEESCAPE SET

Surg Cdr B SUDARSAN*,Surg Cdr MJ JOHN+, Surg Capt S NANGPAL#

ABSTRACT Granularform of Regenerativechemical (Kz Oz)is usedin the submarineescape set for absorbingCO2 and moisture in the exhaledair and to regenerateequal amountof oxygenfor inhaling. Various lirms are manufac- turing the regenerativechemical which shouldbe testedbefore acceptance. A usertrial ofindigenousregenerative chemical was conductedto ascertain the quality of this regenerativechemical. Efforts were made to formulate the standardsof regenerativechemical, so that newlymanufactured chemical can be testedby usingthese parameters. KEY WORDS : SubmarineEscape set, Breathing apparatus, Oxygen regenerative chemical

INTRODUCTION The canister (Fig. 2) of breathing apparatus is filled with oxygen regenerative(03) chemical for (ISP-60)(Fig. ubmarineescape set l) is used absorbing carbon-di-oxide and moisture in the ex- for escapingfrom a sunkensubmarine upto a haled air and to regenerateequal amount of oxygen (IDA- deathof 120mtrs. Breathing apparatus for inhaling. Various firms are manufacturing the part 59) is a of submarinerescue outfit andis used regenerativechemical. User trials are required to be for breathingduring ascent from sunkenSubmarine conductedto ascertainthe quality of newly manu- andalso while carrying out damagecontrol in sub- facturedregenerative chemical by comparing it with marinecompartments.

-I re I rt$ MT FM Lil n

Submarine escapesuit Fig. 2 : Re-generativecanister

*Classified Specialist in Marine Medicine, INS Satavahana,Visakhapatnam - 14; +Classified Specialist in Marine Medicine, INS

Jour. Marine Medical Society,July-Dec 1999, Vol. 1, No.2 mos- 'the standardregenerative chemical which is being A. Physical characteristics year, usedin the submarineescape set. The escapeset wasused by differentdivers for roof/ 2ll2hrs andafter everyll2 hr the sampleof regen- hould MATERIAL AND METHODS from water erativechemical was takenout the canister. procedureadopted is outlinedin thesucceed- Physicalproperties of the chemicalobserved are ellent The ing paragraphs: shownin Tablel. :veral water TABLE I n and Physical characteristics of regenerativechemical during trials n en- :ated. S. No. Type of test Result Remarks r land l. Conditionof No dents/corrosion/ Watertightness y day storagecannisters Peeling of paint checkedby Hermetically sealed. immeningin water Colourchanges Pale white Ash Black 3O%of cream chemicalcolour secti- a) Initial t00% 9"t changedinto white/graylblack. )ctive b) After l/2 hr rffi% 1 and c) After I hr 94% i* 2% quito d) After I '/z hr 90Vo 5% 5% e) After 2 hr 80% t0% 8-r0% r-2% f'1After2tlzfu 65-70% 6% t5% 'raL cillus Sizeand shape of granules alaria a) Initial Rough cylindrical shaped Averagesize o rs-l) granules with averagesize of granulesshould I mm dia and l-2 mm length not passthrough rious t/z b) After hr No change 30 guazestrainer. nsec- c) After I hr Minimal lump formation 2-3% ionto d) Afterl/z hr Lump formation 5-7% h are c) After 2 hr -do- f) After 2 r/z hr -do- static Dustcontent r-2% Ideally powder content should be <5% Brittleness Tested by finger more a) Initial, Firm in consistency. pressing. -do- (MT) b) After'/z hr c) After I hr -do- lueto d) after I and r/z hr -do- ;tudy, c) After 2 hr -do l/z ipray, f) After 2 and hr -do- n has Weightof 03 chemicalin canister. a) Before use. 1.8kg r.99) b) Aftcr use 1.7kg an be 7. Resistanccofcanister with 03 chemical filled a) Beforeuse 16mm of HzO b) After use 2l mmof HzO Temperatureof03 chemicalin canister a) Initial -- 300c lo CAn b) Afterr/2 - g00c )tsare c) After I hr -- logoc l/z y and d) After I hr -- ll50 c e) After 2 hr -- 1300c nsec- r/2 f) After 2 hr -- 1300c ibres. have

, No.2 Jour. Marine Medical Society,July-Dec 19919,Vol. I, No.2 87 't.ABI B. Chemical characterlsdcs mixture cylinder was with charged air. Result The chemical characrcristicsof regenerative -On fint day of trial, six diversbrcathed through S. chemicalwere determinedby using : the set eachfor 30 minutes.Thus the set was used by different diven for threehn. a) Calcimetryanalysis toestimate oxygen capac- ity and carbondioxidecontent. -On subsequenttwo days one diver breathed through the breathingset for 2ll2 hrs (i.e. till the b) Chemicalanalysis to ascertainits composition. Fit" enduranceofthe set)and on next day anotherdiver L The chemicalcharacteristics observed during the repeatedthe same. trails arc given in Table 2. --Samples , of 03 chemicalwere collected every '/z .2. C. Trials on surface h and tested for oxygen and COz con8entby

calcimetryanalysis. While taking out samples,the J. The nials on surface with brcathing apparatus following procedurewas adopted: werecarried out by usingsix diversas experimental -Gas samplesfrom breathingbag were collecrcd .4. subjects.The undermentionedprocedure was fol- in rubber bagsfor analysingthe Oz and COz con- lowed: tents every half hourly except when the samples 5. -The breathingset wasmodified so asto collect weretaken for chemicalanalysis the canisterswere 6. gassamples from brcathingbag. The canislerof the keptin closedposition. set was chargedwith 03 chemical. Resultsof the trials recordedare shownin Table Secol -Oxygen cylinder wascharged with oxygenand 3 andthe calcimetricanalysis are shown in Figs 3, l.

TABIJ2 Chemtcal chsnctcrlstlcr ol 03 rcgeneradvechemlcel

S.No. Typcofanalysis Rcsult

Cdclmetry rndysls Oxypn Crrbon.dl-odde a) Bcfore usc mVgm Aveihgc nVgrn Average 203 3 Thin 188 5 l. r& 183 65 t79 5 l8l 6 b) Aftcr usc i) Surfacctrials 158 7 123 7 r73 142,5 7 1.2 t25 7 133 8 143 7 ii) RCC trials 141 4 r20 3 120 135 4 4,5. 145 4 130 4 D.1 150 5 1 ChcmicalAnalysis As pcr ER.DLspecifications a) PotassiumSuperoxidc 82.0r 0.8 brei b) Magnasiumoxide 5.5r 0.05 tive c) Calciumoxi& 10.0r 0.10 ase d) Asbestospow&r 2.5r 0.(n5 tive Catalystson loading a) Copperoxychlcidc 0.15r 0.0015 saIT b Cobalt chlaidc 0.30* 0.m3 oft c) Manganasc(tr) sulpharc 0.10r 0.001

88 Jour. Marhe Medical Society,July-Dec 199, Vol. I, No.2 Jou )enlnr Resultsof thesedays surface trials. thmugh S. Name of diver Time B*"th!!9.93:__ Calcimetry Temp03 asused Exhale Inhale Chemical o.---Td o;--i.o Oz COz reathed %%%% mVgm mVgm till the Firrt day erdiver L Diver No. I 0 hrs -2033 188 5 tg6 d every 'lztn 2. Diver No. 2 6 0.5 54 0.9 t7t 5 tent by 179 5 't4.3 les,the 3. Diver No. 3 lhr 70 -1827 183 6 'lzln illected 4. DiverNo.4 -l8l 7 )z con- r73 6 -1637 amples 5. Diver No. 5 2hr 62 65 168 7 rs wel€ 6. Attheend 2tlzhr 70 68 -1587 of trial t23 7 nTable Secondday 'lztn Figs3, l. Sinelediver breathed 59 0.8 74 0.4 t7l 7 tkJughthesetfor 2tlzfu lhr 54 0.5 60 0.4 163 6 162 7 |lzhr | 5l 0.8 61 0.3 l6t 8 100 163 6 2hr 54 0.9 67 0.4 151 153 r20 2tlztr 57 0.9 72 0.6 r73 135 t25 Third day l. Sinslediver breathed 0hr 70 0.1 85 0.1 179 5 l/2 thro-ughthe set for 2 hr l8l 6 'lzln 88 0.6 97 0.8 178 7 90 r72 6 lhr 93 0.8 99 0.8 163 6 100 t62 5 r/z I hr 88 0.9 92 0.4 161 6 I 15 163 7 2hr 82 1.1 82 1.0 153 8 130 t43 7 2ttzIu 67 t.2 61 1.0 133 8 130

4,5. depthfor 30 min. D. Trials in RCC b) At 50 m depth,after the diver has been at that depthfor l0 min. The trials in recompressionchamber by using breathingapparatus filled with standardregenera- c) At 60 m depth,after the diver hasbeen at that tive chemicalwere carried. Three divers were used depthfor 5 min. asexperimental subjects. During the trials regenera- The resultsof the RCCtrials are shown in Table tive 03 chemicalsamples from canisterand gas 4 andthe calcimetric analysis are shown Figs. 6,7. samplesfrom breathingbag werecollected at each of thefollowing depth: DISCUSSION a) At 30 m depth,after the diver hasbeen at that A usertrial of indigenouschemical 0-3 usedin

I, No.2 Jour.Martne Medical Society, July-Dec 1999, Vol. I, No.2 89 TABLE4 Resultsof two daysRCC tdrls lr t- S. No. Name of diver Depth Bottom Total 03 Chemical Mtrs. Timc Duration 1' Min of Dirre tr] Min Oz COz Oz COz Oz COz l % % %% mVgm mUgrn ,.J

First day trl l. DiverNo.I 30 l0 34 39 l.l N 0.9 188 5 l 183 6 I trl 193 5 I t DiverNo.2 50 l0 36 36 l.E 3l 0.E I I 3. DivcrNo.3 60 5 ,t{) 25 1.6 26 0.6 t47 4 I "1 t20 3 t20 4 olI Total duration ofdive: ll0min Secondday l "] l. DiverNo.I 30 t2 22 24.4 0.9 25 0.8 188 5 I 183 6 193 5 "l I 2. DiverNo.2 50 l0 42 23 t.4 u 1.6 ,; 3. Divcr No. 3 60 5 38 25 1.6 26 1.8 145 4 t30 4 150 5 Fig.5: Totalduation: 102min

ffiqw :ffiqw -Mffi ..---mffi ID Dr -1. ts l@ -l

:ro t{ I I ila t! :l {,' il !'' I l', T i 5T ':l I ol

{ "J "l l l l D] ! t r a! u i. . G a, 1... t . o-:.-' a - -'c i-o--_..1.. -..--1... " i..." """"" ""'""' ol 0 oullJ'2!! 06rl52Bt - mnffi . lun@

Fig. 3 : Surfacetrial first day - Calcirnetryanalysis Fig. 4 : Surfacetrial secondday - Calcimetryanalysis Fig.I escapesets was canied out to determinevital pa- bials to simulatereal time situations.The oxygen rametersof the chemical. content, CO2 content, physio-chemical charac- The chemicalwas subjected !o extensivedetailed teristics of this chemical werc found to be well

90 Jour.Marhe Medical Society, July-Dec 199, VoLI, No.2 Jou ,. _Gdllr -Mffi ..---ffiffi .-...ffiffi

retry I

Coz r I mUgm lh l ! 5 6 T. 5 l't I I I ln T 4 gr t 3 a 4

6 5

osrlStat I 4 TlMllxE(m 5 Fig. 5 : Surfaceuial third day. Calcimetryanalysis Fig.7 : RCCtriat seconaaay' Calcimetry analysis

-Mffi .....cAMffi within the acceptablelimits tll. The indigenisationeffort of the industry proves that the indigenouschemical can be usedto substi- tute the importedmaterial Thetrial wascarried outtoensurethatthis chemi- cal will passall standardlests, because individual escapesets are the only meansof survivalin caseof mishap[2] The escapeset is life supportingand as such, it is absolutelyessential to maintain the quality of breathingequipment, gases and chemical 0-3. Efforts havebeen made to standardizethe indige- nouschemical0-3and laydown the parameters with which all new suppliescan be calibrated.

REFERENCES

l. BR self containedbreathing apparatus IDA 59. 0 flWNf,OW 2. INBR manualof medicaland dental administration, chapter Fig. 6: RCC trial fint day. Calcimetryanalysis s on submarineescaPe 473-8. oxygen charac- rc well

9I l, No.2 Jour.Marhe MedicalSociety, July'Dec I99,Vol. 1, No,2 SEXUAL DIMORPHISMIN CORONARYARTERY DISEASE : ANATOMICAL FACTORS

USHA DHALL, BASANT LAL*

ABSTRACT

Coronarl arteries were studied in 50 human hearts (25 male, 25 female) in the age range of 20-40 years to find out anatomical factors that could explain the sexdifferential in coronarl artery disease(CAD). No six difference was observedregarding lhe number, origin, branchingpattern ofcoronary arteriesor incidenceofmyocardial bridges. The incidenceof short stemleft coronary artery was higher in femalesbut this doesnot help in eiptaining thesexdifferential in CAD. Lumen diameterofcoronary arteries was found to bemoreinmen, butwhen compared to heart weigh! coronarieswere found to be wider in femalessuggesting better coronaryflow in them. Histomor. phometry revealedthat tunica intima wasthicker in malesas comparedto femalesnot only in absoluteterms but also in relation to tunica media and lumen diameter, making men more prone to atherosclerosis,primarily a diseaseof tunica intima. Key Words : Coronary Arteries, Male, Female

INTRODUCTION Heartswere fixed in lOVoformaldehyde. Gross anatomyof coronaryarteries oronary artery disease(CAD) is a major was studiednoting their number,origin, pattern causeof human mortality and morbidity. branching and occur- renceof myocardialbridges. The prevalenceof significantcoronary ar- tery diseaseis lower in womenthan in men and For histomorphometrytissue pieces from coro- singlevessel disease is morecommon in women narieswere taken from the following sites: thanin men[]. Thereasons for this sexdifferential l. Stemof left coronaryartery (LCA). in CAD arenot fully understood. Femalehormone 2. Rightcoronary artery at its origin (RCA-I). estrogenhas beenspeculated to be the protective factor as it favourably affecs lipid 3. Right coronary artery 2.5 cm from origin metabolism (RCA-rr). slowingdown the processof atherogenesis[2]. The presentstudy is aimedat analysinganatomical fac- 4. Left anteriordescending 5 mm from origin tors which may contributeto the understandingof (LAD). sexualdifferences in CAD. 5. Circumflexartery 5 mm from origin (CI). Sevenmicron MATERIAL AND METHODS thick transverseparaffin sections wereprepared from eachsite and stained with Ver- Fifty humanhearts (25 male,25female) obtained hoeffs stainto demarcatethe intemalelastic lam- from medicolegalautopsies done in this institute ina. Threesections from eachspecimen were sub- werestudied. The age ofsubjects varied between 20 jectedto histomorphometry.Using a microprojector and40 yearsto avoidmajor cardiac pathology. The and a grid, the thicknessof tunicamedia, tunica causeofdeath was accident and therefore, occurred intimaand lumen diameter were measured by linear suddenly.Heart weight was recordedand hearts interceptand point-counting techniques [3]. weighingmore than gms 370 in malesand 280 gms Theresults were statistically analysed using stu- in femaleswere excludedfrom the studyto avoid dent's't'test, the possibilityof hypertensivecases. Hearts show- ing obviouschanges of atherosclerosiswere also OBSERVATIONS excluded. Followingobservations were made.

*Forensic Dept of Anatomy and Medicine, ft BD SharmaPost GraduateInstitute of Medical Sciences,Rohtak.

Jour.Marine Medical Society, July-Dec 1999,Vol. l, No.2 1. The mean heart weight in males and females 7. Tunicaintima was thickerin malesthan in was 262.6 + 8.4 gms and 220.3 + 6.7 gms femalesnot only in absoluteterms but also respectively. relativeto tunica mediaand lumen diameter, 2. Nothing abnormal was noted regardingthe ori- particularlyin RCA-II, LAD and CI arteries gin and number of major coronary arteries. (Figs.1-3). In otherwords tunica media relative to tunicaintima was thicker in females. 3. Right coronarydominance was seenin 84Voin both sexes. DISCUSSION 4.ln23 heartsthe left coronary artery had a very The observationsofpresent study point to some short stem and it bifurcated just beyond its anatomicalfactors which can explain, at least to origin. This pattern was observedmore often in someextent, the sex differentialin incidenceof females(9 male, 14 females). CAD. 5. Myocardial bridges over different arterieswere It hasbeen reported that in a greatproportion of observedin 2l hearts(10 male, I I female). r.::t MALE 6. Mean lumen diameterof all the vesselsstudied 7- FEMATE was greater in males. This difference was sta- tistically significant for LAD. However, in re- lation to heart weight (diameter : heart weight) all the arterieswere wider in femalesOable l).

TABLEI Lumendiameter in relationto heartweight 00 Anery Diameter (um) Diameter : Heart weight Male Female Male Female

LCA 2117.5 2rr6.3 8.0 9.6 RCA-r 1600.8 1501.6 6.1 6.8 RCA-rr r&75 1425.6 6.1 6.5 cI 1628.0 1463.2 6.2 6.6 LAD 1805.0 1640.0* 6.9 7.4 *P < 0.05 Fig. 2 : Thicknessoftunicaintima

I:I MALE Z FEMALE fj:r MALE = F M FEM^LE = t- !2 z z 9 : z & 3 u.l F F UJ = U 6 = z, z[! = F J

CORONARYARTERIES CORONARYARTERIES Fig. I : Lumendiameter of tunicaintima Fig.3 : Ratioof tunicamedia : Tunicaintima

Jour. Marine Medical Society,July-Dec 1999, Vol. 1, No.2 93 patientswith left bundle-branchblock, the left coro- malesmay be someof the anatomicalfactors mak- nary artery had a very short stem [4] It was suggested ing menmore susceptible to CAD. that in such cases,the initial part of the LAD was REFERENCES exposedto unusualstress from systolickinking. As a result this artery could be particularly liable to l. Chaitman BR, BaurassaMG, Davis K. Angiographic preva- intimal changesand atherosclerosis.In the present lence of high risk coronary artery diseasein patients subsets study, however, short stem of left coronary artery (CASS). Circulation l98l;64 : 360-7. was seen more often in females as compared to 2. Walsh BW, Schiff I, Rosner B, Greenberg L, Ravinkar V, malesand so could not be heldresponsible for higher SacksFM. Effects of postmenopausalestrogen replacement incidenceof CAD in males. on the concentration and metabolism of plasma lipo-pro- teins. N Engl Med l99l;325 : ll9Gl?M. The lumen diameter of coronary arteries was J found to be smallerin femalesas compared to males 3. Aheme WA, Dunnill MS. Morphometry. London : Edward consistentwith the earlierreports [5,6]. This differ- Amold. 1982;155-7. encein lumen diameterdid not persistwhen coro- 4. Lewis CM, DagenaisGR, FriesingerGC, RossRS. Coronary nary size was adjustedfor heartweight [7] or body arteriographic appearances in patients with left bundle surfacearea [5]. branch block. Circulation 1970:'4l :299-309.

Dodge et al 16l reported that women had nar- 5. Mac Alpin RN, Abbasi AS, Grollman JH, Eber L. Human rower coronary arterieseven after normalisation of coronary artery size during life : A cinearteriographic study. body surface area. However, the results of present Radiology1973; 108 :56'l-76. study showed that relative to heart weight the coro- 6. Dodge JT, Brown BG, Bolson EL, Dodge HT. Lumen di- naries were wider in females.This shows female ameterof normal human coronary arteries;Influence of age, heartswere better perfusedthan male heartsmaking sex, anatomic variation and left ventricular hypertrophy or women lessprone to CAD. dilation. Circulation 1992: 86 : 232-46.

In thepresent study, in general,tunica intima was 7. Robert CS, Robert WC. Cross sectional areaof the proximal found to be thicker in males not only in absolute portions of the three major epicardial coronary arteriesin 98 terms but also relative to tunica media and lumen necropsypatients with different coronary effects : Relation- size. Thicker intima in males has been reported in ship to heart weight, are and sex. Circulation 1980; 62 : fetuses,newborns, adolescents and adults t8-101. 953-9. On the other hand,absence ofconsistent sex differ- 8. Dock W. The predilection of atherosclerosisfor the coronary encesin intimal thicknessare also reported I I I ]. The arreries.JAMA 1945: l3l : 39-50. finding of thickertunica intima in malesseems to be importantin relationto higherincidence of CAD in 9. Vlodaver Z, Kalin HA, Neufeld H. The coronaries in early men which is usually due to atherosclerosis,a dis- life in three different ethnic groups. Circulation 1969t 39 : 541-50. easethat primarily involves tunicaintima. Interest- ingly women are reported to be more prone to 10. Velican D, Velican C. Comparative study of age related nonatheroscleroticCAD i.e. angina pectoris, as changes and atherosclerotic involvement of the coronary comparedto men [2]. The presentstudy revealed arteries of male and female subjects upto 40 years of age. that women had thicker tunica media relative to Atherosclerosisl98l; 38 : 39-50. tunicaintima, thus perhaps making them more liable ll. Moon HD. Coronary arthries in fetuses, infants and juve- to coronary spasm. niles. Circulation 195'l: 16 :263-9.

It may be concluded that nanower coronariesin 12. Douglas PS. Heart disease in women. Philadelphia, FA relation to heart size and thicker tunica intima in Davis Company,1969; 144.

94 Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 MANAGEMENTAND VISUAL OUTCOMEOF PATIENTSWITH OPENGLOBE INJURIES

S NATARA.IAN, SHYAMA SATYAN

ABSTRACT We analysedpatients of open globeidury referred to our vitreo retinal centre with or without intraocular foreign body. Casesvaried from simple retinal detachment to total retinal detachment,PVR with intra'ocular foreign body. Visual acuity varied from best correctedvision 6/9 to no PL and dependedon the type ofinjury, time of presentationand promptnessofmedical (primary or secondary)procedure done. KEY WORDS : PVR, PL, Eye Injuries

INTRODUCTION Woundlength and location were noted down care- raumais oneof the mostimportant prevent- fully.'Finalvisual outcome was graded as very good (> able causesof blindnessin all age groups. 6136),good (6/60 or better),poor (PL) or no (NI-P). The aim of our studvwas to determinethe perception optimal managementand visual outcomeof open RESULTS globeinjuries. Approximarcly 75Vo of peoplewith traumainduced visual improvementare monocu- Preoperativevisual acuity in 15 patientswas perceptionof light with no projectionof light, five larlyblind [1]. patientshad perceptionof light with accuratepro- The usualmanagement of an openglobe injury jectionand rest five patientshad vision ofcounting caseis repairof ocularwounds surgically, whatever fingerat onefoot or more.Wound was corneal in I I theinitial vision and extent of injury.Many of these cases,comeoscleral in ninepatients and scleral with eyesare either enucleated to avoidthe development its posteriorend anterior to equatorin five patients. of sympatheticophthalmia or lossof visionforever. Penetratingeye trauma occuned more frequently This study is an attemptto correlatethe final in men(72Vo) and in youngerage group (80Vo <40 visualacuity with preoperativeclinical parameters : yearsof age).Initial visualacuity, wound location initial visual acuity,wound locationand length, andextent and mechanism of injury wereimportant mechanismof injury, perforating (through and prognosticfactors. In contrastage and sex were not through)versus nonperforating ocular wound and significantpredictor. presenceof an introcularforeign body. In threepatients injury was due to fire cracker, MATERIAL AND METHODS 13 patientshad injury with bluntobject and 9 pa- We retrospectivelyanalysed a consecutiveseries tientshad injury with sharpobject like knife, sickle of 25 eyesof 25 patientswith open globe injury etc. Intraocularfqreign body was presentin five associatedwith posterior segmentcomplication cases. who presentedto our hospitalbetween October 98 Surgicalprocedure varied depending upon extent andMarch 99. Clinical features, including age, sex, of damage.All the patientsunderwent vitrectomy initial visualacuity, final visualacuity, mechanism surgery,which was limited to anteriorvitrectomy in of injury, whethervitrectomy was performed, pres- five cases.In thesefive casestranscleral IOL fixa- ence of intraocular foreign body, perforating tion wasdone alongwith anterior vitrectomy. Seven woundsand lengthof followup wereobtained. All patients(287o) underwent vitrectomy with scleral patientshad at leastthree months of followupdata. buckling with perflucropropanegas injection

AdityaJyot Eye Hospital, Aashirwad, 168-D, Vikas Wadi, Dr. AmbedkarRoad, Dadar TT, Mumbai- 400014.

Jour. Marine Medical Society,July-Dec 1999,Vol. I, No.2 95 (C3F8), five patients (207o) underwent vitrec- De Juan et al reportedthat only 47o of eyes with tomy/lensectomyalongwith silicon oil injection.In woundsextending posterior to the equatorachieved anotherfive patients(207o)l-nnsectomy and Vitrec- final visual acuity of better than 5/200 which was tomy was done alongwith intraocularforeign body consistentwith our findings [5]. removal.Two patients(87o) underwent lensectomy In our study patientswith only comeal wounds and Vitrectomy. One casewas managedon the line and lens damageattained postoperative visual acu- of endophthalmitiswith lensectomyvitrectomy and ity of > 6/36 with transscleral fixation of IOL at the intravitrealantibiotic injection. samesetting. We managedthese type of caseswith The final visual acuity achievedwas 6/36 or more combinedsurgery at thesame setting. The introcular in l0 patients(24Vo). In anotherfourpatientsvision lens implantation was done by anterior segment was 1124-1160.In 8 patientsvisual acuity was count- surgeonsand followed by vitrectomy by posterior ing finger at one foot. Out of thesetwo caseshad segment surgeons.In eyes with corneal wounds cornealopacity (healedcorneal wound) obstructing alongwith intraocularforeign body, postoperative vision. Thesepatients underwent penetrating kera- visual acuity was finger count - 2 feet, and in one toplastywith the final visual acuity 6/36. Five pa- casethere was no PL. This finding was inconsistent tients lost vision. Out of thesethree eyes became with the finding of Gilbert et al Ul. They have phthisical. One case could not get useful vision reported 2012W or better final visual acuity inl3%o becauseit was a case of penetratinginjury with of corneal wounds.The reasonbehind this is that intraocular foreign body. Surgery performed was evenif the entry woundsis cornealand small in size vitrectomywith lensectomywith intravitrealantibi- the velocity and infectious nature of the foreign otic injection.Peroperatively, retina was found to be body which can destroyboth mechanicallyand by plasteredwith organisedexudates which wasimpos- infection leadsto poor visual prognosis.But cases sible to clean.The casewas abondoned.In the fifth with penetratingwound of corneawith no foreign case(a 4 year female) there was a penetratinginjury body attainedreasonably good, postoperative usual with no perceptionof light. She was operatedbut acuity. becauseit was a corneoscleraltear involving the Esmaili et al have fourtd age as a significant eiliary region,the patient developed iris cystwith no factor in predicting the outcome,i.e. younger age perceptionof light due to amblyopia. group (< 12 yrs) attainedbetter postoperativevisual DISCUSSION acuity due to sharpnature of the penetratingwound [8]. But in our study,results were poor in younger Consistentwith previously reportedclinical se- agegroup that could be due to amblyopia [8]. ries of ocular trauma, we found that penetratingeye Blunt and missile injuries resultedin markedly traumaoccurs predominantly in youngmales [2-4]. Preoperativevisual acuity is an important predictor worse final visual acuities which was consistent with the findingsof Esmaeliet aI andother investi- of postoperativevisual outcome[5-7]. gators.In our study presenceof intraocularforeign Despiterecent surgical advances, the incidence body indicatedpoor visual outcomewhich was in of visualloss in eyeswith posteriorsegment injuries contrastto the findings of Esmaeli et aI l8l. The role remainshigh. Eight out of 25 eyesin our studyhad of vitrectomy in treating penetrating trauma has postoperativevision 6/36 or more. Site of perfora- beenconsidered a major advancein the last decade. tion in four caseswas corneal and remainingfour caseshad corneascleralwound. Five patients(207o) CONCLUSION hadno perceptionoflight. Out ofthesefive patients, The standardpractice by most Ophthalmoligists threepatients had comeoscleral tear with intraocular hasbeen to surgicallyrepair the eyes, whatever their foreign body. initial vision and extentof injury. Our dataindicate Gilbert et al found that 907oof eyeswith wounds that all type of injuries can be subjectedto surgery extendingposterior to the rectusmuscles were enu- (Vitrectomy)and enucleationis not a must.But the cleated[7]. In our studyno eyewas enucleated even visual improvement dependson size and site of in the eyeswhich had undergonephthisis. perforation, presence of foreign body, extent of

96 Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 -i -' damage whether transsceleral,IOL fixation was tratingeye injuries in thc wortphca Thonational eyc trauma possible or not and chancesof developing am- systemrcgistry, A rch Ophtlnbat 192; I lO : 843-8. blyopiai.e. youngerage etc. 5. De luan E Ir, StembergPk, Michels RG, Penetratingocular REFERENCES injuies. Tlpes of injurics andvisualrcsits.OpluMmology 1983:90:l3l8-22. l. National societyto preventblindness. Operational rescarch dept. vision problemsin thc US. New Yck : The society, 6. StcrnbergP Jr, De JuanE Jr, Michels RG, Auer C. Multi- 1980. variateanalysis of prognosticfactors in perrtrating ocular 2, Klopfer J, Tielsch JM, Vitale S, er aJ.Ocular traumain the injwies.AmJ Ophth1984;98 :46i1-72. United States.Eye injuries resultingin hospitalization,1984 7. Gilbert CM, SoongHK, Hirst LW. A rwo year prospcctive ttuotrgh l98T. Arch Ophtdmol 199? l l0 t 83842. study of penerratingocular trauma* thc Wilmer Ophthal- 3. White MF Ir, Mqris & Fcist KM, et al. Eyc injury : mologicalInstitutc, Am OphtMnol 1987; 19 : 10&6. prevalenceand prognosisby *ning. SouthMed.I 1989;E2 8, BitaEsmaeli,SusanaElner, Authony SchorkM, aal, Visual : l5l-8. outconre and ocular survival after penetrating tauma. 4. DannenbergAL, ParverLM, BrechnerRJ, Khool L. Penc- OphtW 195; 103 : 393-400.

lour. Marhe Medical Society,July-Dec 1999,VoL I, No.2 97 ROLE OF SERUMTHYROGLOBULIN IN THE MANAGEMENT OF WELL DIFFERENTIATEDTHYROID CANCER

Surg Cdr B FANTHOME*, SAI{DEEP SEBASTIAN+

ABSTRACT Thyroid carcinoma is an uncommon malignancy. In the vast majority of patients, if treated appropriately, it is associatedwith a benign clinical course.The diseasehowever is not totally benign, being associatedwith an overall l0Tomortality.ln30%o-40%oof patientsthe diseasepersists or recursafter the lirst surgicaltreatmenl Consider- able controversyexists regarding the extentofsurgery and the follow up protocol recommended.This study has analyzedthe sensitivityand specilicityofthyroglobulin assayin thedetection ofresidual, recurrent and mer'static well-differentiated thyroid carcinoma as compared to clinical examination and whole body scans. KEY WORDS : Thyroid carcinoma,Thyroglobulin, Sensitivity and Speciticity

INTRODUCTION age of patientswith thyroid carcinoma.TSH ele- vatesthe level of thyroglobulinby increasingits canceralthough a relativelyrare tu- 4-lhyroid mRNA transcription.Because thyroglobulin is re- mour is the mostcommon cancer of the en- I leasedinto the serum from thyroidcancer cells it can I- docrine glands and includestumour types be usedas a monitor for recurrentor metastatic rangingfrom amongthe mostindolent to the most diseasefollowing treatment.A high serumthyro- virulenthuman malignancies. Though some patients globulinlevel during thyroid hormone suppression may outlive their physicians,there is significant '" afteroperation or I therapyusually reflects me- mortalityand morbidity associated with thisdisease, tastaticdisease or recurrentprimary tumour. More- with an overall death rate of L0Voat ten years. over, immunohistochemicalstudies of recurrences Besides,in 30Voto 40Voof thyroidcancer patients, andmetastases in differentiatedthyroid carcinomas the diseasepersists or recursafter the first surgical havedemonstrated a positivecorrelation between treatment.Good result of treatmentin thyroidcancer circulatingthyroglobulin levels and estimated total is aidedby theability ofthyroid cellsto concentrate tumourmass iodineand the availability of serumthyroglobulin as [-3]. a markerfor recunence. This studywas undertaken to studythe sensitiv- ity andspecificity of serumthyroglobulin assay in Thyroglobulinis an importantprotein that is the detectionof residual,recurrent and metastatic uniqueto the thyroidgland. It is the mostabundant well differentiatedthyroid carcinoma. proteinin the thyroidand provides a matrixfor the synthesisof thyroidhormones. In humans,the thy- MATERIAL AND METHODS roglobulingene resides on thelong arm ofchromo- Thepatient population comprised forty consecu- some8, distilledto thec-myc oncogene. It is made tivepatients with well differentiatedthyroid cancer up of two monomericpolypeptide chains of 660kd. managedwith totalor neartotal thyroidectomy. This Humanthyroglobulin has many auto antibody epi- retrospectiveanalysis covered a three-yearperiod topesand high titers ofanti-thyroglobulin antibodies 1995-98.Histological verification of thediagnosis are found in approximately70Vo of patientswith of well-differentiatedthyroid was from Hashimoto'sthyroiditis, in607o of thosewith newly cancer made tissueobtained at surgery. diagnosedidiopathic hypothyroidism, in 30Voof thosewith gravesdisease as well asa smallpercent- Following recoveryfrom surgery all patients

*Classified Specialist in Surgery and Oncosurgeon;+Postgraduate Student, INHS Asvini, Colaba, Mumbai - 400 005.

98 Jour. Marine Medical Society,July-Dec 1999, Vol. I, No.2 were discharged receiving no thyroid hormone re- tial competitiveradio immuno-assaydesigned for placementtherapy. They returned in four weeks for the quantitativemeasurement of thyroglobulin in a thyroid scanto evaluateresidual functioning thy- serumand plasma.It is intendedstrictly for in vitro roid tissue.Any resi_dualthyroid tissueneeding less use as a complementto radioiodine scanningand than 250 mCi tf ll3l *u, ablatedwith appropriate other techniquesfor identifying the presenceof dosesof sodiumiodide. Subsequently patients were functioningthyroid tissue.The sampleis first,incu- put on a regimenof thyroid suppressivetherapy with bated with anti-thyroglobulinanti serum. l^'" la- levothyroxinesodium. beledthyroglobulin then competes with thyroglobu- The first follow up visit was scheduledafter six lin in the patient'ssample for,antibody sites. After months and if it demonstratedresidual, recurrentor incubation for a fixed time (4'lz hours), separation metastatic disease, patients were treated and re- of bound from free thyroglobulin is achievedby the evaluatedsix months later. If no residual or metas- polyethyleneglycol accelerateddouble antibody tatic thyroid tissuewas detectedat thefirst visit then method.Finally the antibodybound fraction is pre- patientswere seenyearly. cipitatedand counted.Patient's sample concentra- tions are read from a calibration curve. Patientswere advisedto discontinuelevothyrox- ine sodiumfour weeksprior to a follow up visit. On .In patientswith no known thyroid diseasethe follow up, patients were evaluated for suspicious referencerange is; non-detectableto 52 ng/ml, with featuresin the patientshistory, physical examina- a medianof 7.4nglml; the central(957o) range is up tion, indirectlaryngoscopy, and chest X-ray. Imme- to 2l ng/ml. In patients who have undergone total diately prior to dosing with 4 MCI sodium iodide thyroidectomy or radioablation therapy, circulating l3l for thewhole body scan,the patient's blood was thyroglobulinlevels should be undetectable.A level collectedfor T3, T4, TSH and Thyroglobulin esti- of greater than l0 ng per ml in such patients is mation.It is importantto obtainthyroglobulin meas- usuallyconsidered indicative of residual,recurrent urementsbefore administeringI"' for scanning, or metastaticdisease. since the scan may result in the releaseof large In order to compare the efficacy of clinical ex- amountsof thyroglobulinfrom evena smallnumber amination,whole body scan(WBS), andserum thy- of cells. roglobulin assay (Tg), in the detection of recur- The presenceofresidual, recurrent or metastatic rencesand metastases, patients were divided into the thyroid cancerin all caseswas establishedby clini- following four groups: cal, radiologicaland/or biopsy findings. L Group I : Patients with residual or recurrent Whole body scanswere performed 96 hours after thyroid cancer(thyroid bed activity on scan). dosing.Depending on the extentofresidual, recur- 2. Group II : Patientswith local metastasesto rent or metastaticdisease, patients received appro- lymph nodesin the neck. priateablative doses ofsodium iodide l3l. Patients 3. Group III : Patientswith distantmetastases. needingmore than 250 MCI of Il3l for locoregional diseasewere taken up for surgery.Patients having 4. Group IV : Patientswithout residual,recurent metastaticdisease or no uptakeon whole body scan or metastaticdisease. were either treatedsurgically or referredfor extemal OBSERVATION AND RESULTS beam radiotherapy.Following completionof treat- ment, patientswere put on thyroid suppressivether- Age incidence apy with levothyroxinesodium. The peak incidenceofdifferentiated thyroid car- Euro/DPC's (Diagnostic hoduct Corporation, cinomain this serieswas seenin the agegroup of 3l 5700West 96th Street,Los Angles)double antibody to 40 years accountingfor 45Voof all cases.The thyroglobulinkit was usedfor measurementof thy- youngestpatient was 9 yearswhile the oldest was roglobulin levelsin serum. 70 years.Mean 40.75 years(SD ! 13.76years).

Principle of the procedure Histology Double antibodythyroglobulin is a Il25 sequen- The commonesthistological type in this study

Jour.Marine Medical Society, July-Dec i,999, VoL 1, No.2 waspapillary carcinoma accounting for 75Voof all TABLE4 patients Detectionof metastasisby wholebody scen Wholc body scan Metastasis(HPE) TABLE I Total FEdi-----Ts€nt Age incidence +ve 20 20 0 Age group Number Percentage -ve 20 & l6 0-10 I 2.5 t6 tt-20 I 2.5 2t-31 4 l0 3l-40 l8 45 TABLE5 4l-50 4 l0 Detectionofmetastases by serumthyroglobulin assay 51-60 8 20 6t-70 4 l0 Serumthyroglobulin Metastasis(HPE) Total ffisent--5Gii 40* 100 > l0 nglml 24 22 2 * 22 males,18 females < l0 ng/ml l6 2 l4

TABLE2 Histologt TABLE 6 Histologicaltype Numberof Percentage Predictive value of dfugnosdcmodalities patients Group Clinicalexam Whole body Scrum Papillary carcinoma 30 75 scan thyroglobulin Purepapillary 26 65 +'te-3 +v;---6 +ve---a Follicularvariant 4 l0 I (N=9) 0 0 9 100 7 77.77 Follicular carcinoma l0 25 tr (N=8) 5 62.5 6 75 8 100 Total 40 100 trI (N=?) 7 100 5 7r.4 7 100 IV (N=16) l6 100 l6 100 t4 87.5

TABLE3 Detectionof metastasisby clinlcd examlnatlon FromTables 3, 4, 5 and6 it is evidentthat clinical predictor Clinicalexamination Metastasis examinationis an excellent of diseasein for metastasis ConfirmedbyHPE GroupIII and GroupIV patients.Il3l whole body Present Abscnt scanis an excellentpredictor of diseasein GroupI and GroupIV patients,while serumthyroglobulin +ve t2 12 0 predictor -ve 28 t2 l6 assayis an excellent of diseasein Group II and Group[I[ patients. Total ,10 24 l6 Amongthe three diagnostic modalities evaluated whole body scanand clinical examinationhad the

TABLE 7 Statistical analysis of diagnootic testsin the evaluation of recurrrnces and metastasis

Diagnostic Specifrcity Sensitivity Accuracy Positive Negative test predictivevalue predictivevalue

CE 100 50 70 100 51.r4 WBS 100 83.3 90 100 80 Tg 87.5 91.6 90 91.6 87.5

t00 Jour. Marine Medical Society,July-Dec 1999,Vol. I, No.2 highestspecificity while serumthyroglobulin assay 6. Occasionallyimmunometric assays may fail to hadthe highestsensitivity in the detectionofrecur- detectextremely high serumTg levels,which rencesand metastases. canbe avoidedby dilution of the serumspeci- men. DISCUSSION The presenceof significantamounts of residual The meanage incidence of differentiatedthyroid thyroidtissue after surgery can interfere and reduce cancer(DTC) in thisstudy was 40.7 years (Table l). thereliability of thyroglobulinestimation. Once the The mean age for men was 42.2 yearsand for thyroid gland has been completelyresected and women38.8 years. The ageincidence in this series ablatedwith radioiodine,serum Tg concentrations is comparableto reportsfrom AIIMS (Delhi),PGI shouldapproach the limits of assaydetectability. (Chandigarh),SGPGI (Lucknow) and TMH (Mum- Duringfollow up of patientsthe Tg level may take bai).All studiesconfirm a lower mean age incidence oneor moreyears to declineto anundetectable nadir for women [4-7]. followingpri.ary therapy.3 The incidenceof thyroid cancerin womenhas An importantfactor in the interpretationof Tg beenuniversally reported greater in women This [7]. concentrationsis the concurrentlevel of TSH. The studyhas revealed a higherincidence in men(M:F sensitivityofTg assayto detectrecurrent cancer is - l:0.81).The male predominance is explainable by enhancedby the elevationof TSH during levothy- a selectionbias sincethis seriesis drawn from a roxinewithdrawal lrvothyroxine withdrawal referralhospital, having a significantlyhigher per- [3,9]. is routineprior to WBS andas such was followed in centageof malepatients. all thecases studied. False negative results can occur Papillarycarcinoma accounted for 757oof all in patientswith smallnodal metastases of papillary casesin this study.The histopathologicalprofile of carcinoma,or in a settingto tumourdedifferentia- our patientsis similarto the profile in otherstudies tion [9]. from non-endemicareas [4-6]. Whereasa detectableTg level signifiesdisease, Of the forty patientsin our study,24 (607o)had theabsence of detectableTg duringTSH stimulation evidenceof residual,recurrent or metastaticdisease. suggeststhe absenceof disease.Serial estimations Of these24 patients, clinical examination was posi- of serumTg aremore useful than a singlemeasure- tive in 12(SOVo). Whole body scan was positive in ment.Progressive elevation of serumTg suggests (83.3Vo), 20 patients sincefour patientshad non-io- progressivedisease [3]. dine concentratingtumours these were not visual- Despitethe enhancedsensitivity of currently isedon scan.Serum thyroglobulin assay was posi- availableTg immunoassays,problems remain in tivein22 patients(9lvo). their clinical application.In immunometricassays Two patientshad positive whole body scans but reportedTg concentrationscould be falsely lowered negativethyroglobulin values, which couldbe due by autoantibodiesthat bind Tg andprevent antigen to oneof thefollowing reasons [3,8,9] : interactionwith the assayantibodies. For DTC pa- l. Thyroid tissue is absentbut scan artefactis tientswith anti Tg autoantibodies,serum Tg levels present. mustbe interpretedwith caution,or not usedat all 2. A normalthyroid remnant is suppressedby T4. in patientmanagement. 3. The presenceof anti thyroglobulinantibodies Theoreticexplanations for the occurrenceof a artificiallylowers the levelon radioimmunoas- negativewhole body scanwith an elevatedthyro- say. globulinseen in two patientsin this seriesinclude thefollowing [3,8,9]. 4. The thyroidcancer has lost its capacityto syn- thesiseor releasethyroglobulin. l. Tumourtoo smallto be pickedup on WBS but secretingdetectable amounts of Tg. 5. Thethyroid tissue releases an immunologically modified thyroglobulinmolecule that is not 2. Tumouris unableto trapor organifyIl3l but is detectedin a given thyroglobulinradioimmu- ableto synthesiseand release thyroglobulin. noassay. 3. The stableiodine pool is expandedby recent

Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 I0I exogenousiodine administration. 1996:25:159-78. 4. Endogenousthyroid stimulatinghormone lev- 2. Miller FR, Nenerville JL. Surgical managementof thyroid elsare adequate to allowthyroglobulin release and parathyroiddisorder.Medical Clinics of North America. but inadequateto promoteil31'uptake. 1999;83:24'l-59. 5. A circulatingantibody against thyroglobulin 3. Sherman SL Adjuvant therapy and long-term management resultsin falselyelevated values in a given of differentiated thyroid carcinoma. Seminars in surgical radioimmunoassay. oncology. 1999; 16 : 30-3.

6. Non-thyroidal tissue is producing thyro- 4. Chumber S, Mathur A, Thomas Z. Thyroid cancer-AIIMS. glogulin. Institutional experience. In : Mishra SK, editor. Thyroid Useof sensitivepolymerase chain reaction meth- cancer : hoceedings of the Indo-Japaneseworkshop on odsallows the detectionof messengerRNA for Tg thyroid cancer. Japan Intemational Co-operative Agency circulatingin the peripheralblood of patientswith 1997:.177-8. thyroidcancer, presumably contained within circu- 5. Behara A, Gupta NM, Kataria RN, Singh R, Sharma AK. lating tumourcells. The immediateadvantage of Thyroid cancer- A retrospectiveanalysis ofa single surgical suchan assaywould be bypassingthe problemof unit, PGI, Chandigarh. In : Mishra SK, editor. Thyroid anti thyroglobulinantibodies interfering with im- . cancer : Proceedings of the Indo-Japanese workshop on munoassaytechniques. Whereas preliminary re- thyroid cancer. Japan International Co-operative Agency ports suggestexcellent sensitivity for such ap- 1997r19l-3. proaches,m RNA basedTg assaysare not yet clini- 6. Agarwal G, Agarwal A, Mishra SK. Surgical management callyavailable. of thyroid cancer at SGPGIMS, Lucknow. In : Mishra SK, Following successfulthyroidectomy and abla- editor. Thyroid cancer : hoceedings of the Indo-Japanese tion of residualnormal or canceroustissue by ra- workshop on thyroid cancer. Japan Intemational Co-opera- dioiodine,thyroglobulin is in the athyreoticrange. tive Agency 1997; 195-8. Levelsabove athyreotic range are indicative ofper- 7. Rao DN. Epidemiological observationsof thyroid cancer.In sistentfunctioning residual thyroid tissue or carci- : Shah DH, Samuel AM, Rao RS, editors. Thyroid cancer : noma.If thereis detectableserum thyroglobulin in An Indian perspective.Quest Publications 1999; 3-16. the circumstanceof suppressivethyroxine therapy, 8. Ashcraft MA, Van Herle AJ. The comparative value of it is a trueindicator of persistentor recunentthyroid serum thyroglobulin measurements and iodine l3l total carcinoma.The testis moresensitive in the setting body scan in the follow up study of patients with treated of thyroidhormone suppressive therapy withdrawal differentiated thyroid cancer.Arze rican Joumal of Medicine andfrank hypothyroidism. l98l:71 :86O-74.

This studyhas shown that of thethree diagnostic 9. Kumar A, Shah DH. Serum thyroglobulin : Tumour marker modalities,serum Tg assayprovides the highest in thyroid carcinoma. In : Shah DH, Samuel AM, Rao RS, diagnosticyield with a sensitivityof 9l.6Vo.Similar editors. Thyroid cancer: An Indian perspective.Quest Pub- highsensitivities have been reported by a numberof lication 1999; l10-35. otherauthors [3,9- I I ]. Thevalidity and reliability of 10. Fraker DL, Skarulis M, Livolsi V. Thyroid tumours. In : serumthyroglobulin measurement is centralto ac- Devita VT, Hellman S, Rosenberg SA, editors. Cancer : curatediagnosis and cost effective management of Principles and practice of oncology, Philadelphia : Lipin- patientswith differentiatedthyroid carcinoma. cott-Raven 1997: 1629- 52.

REFERENCES I 1. SpenccrCA, Wang CC. Thyroglobulin measurement: Tech- l. Boyd CM, BakerJR. The immunologyof thyroidcancer. niques, clinical benefits and pitfalls. Endocrinology and Endocrinologyand metabolismclinics of North America. metabolism clinics of North America 1995:24 : 841-63.

r02 Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 I cuer-LENGESIN BURNsHocK RESUSCITATIoN netrv SurgCdr YP MONGA CO: ml/gm INTRODUCTION o Systemic antibiotics administereddepending ll patientssustaining majorburn injuries suf- upon the antibioticpolicy. o Analgesicsadministered as required. o ferfrom shock necessitating energetic resus- ) citationto achievesurvival. In the past, o Bladder catheterisedto monitor hourlv urine hypovolemicshock and renal failure were the lead- output. 4 ingcauses ofdeath in thesepatients. Today, with our o Patientplaced on a steriledressing table. Burnt 3 currentknowledge of the massivefluid shifts and 4 clothes were carefully removed. Burn wounds vascularchanges that occur during burn shock, mor- cleanedand topical antimicrobial agents ap- tality dueto burninduced volume loss has decreased plied. The patient is then shifted back to the considerably.Vigorous approach to fluid therapy - 5 resuscitationroom. 6 resultsin fewerdeaths in the first 24-48hours post burn.However, a largenumber of deathsstill occur Fluid therapy within first 10 days,following bum injury from a a. Fluids in first 24 hours as follows : 4 multitudeof causes,one of the most significant i. Adults : Ringers lactate 4 mlkg/Vo 4 being inadequateor improper fluid resuscitation Burns SurfaceArea (BSA) 5 therapy. ii. Chifdren: Ringers lactate 4 mlkg/Vo BSA. The purposeof this study was to review our experiencein burn shockresuscitation and discuss + 100 ml/kg (first l0 kg body weight) thechallenges involved. + 50 ml/kg (secondl0 kg body weight) (third MATERIAL AND METHODS + 20 ml/kg l0 kg body weight) Children require additional amount of fluids be- Patients cause of their large body surface area and higher 372 patientsadmitted with burn injuriesto the metabolic requirements.Additional fluids may be Bum'sCentre, were managed according to thelaid given as glueose- salinesolutions because children down protocol for fluid resuscitationand results havepoor glycogenreserves. analysed. b. Fluids in second 24 hours (the same for both Emergencyresuscitation adults and children) : - Immediatelyon arrival of a patientwith major i. Colloid : Plasma 0.3 to 0.5 mllkgl%oBSA or - burninjuries, resuscitation was started as follows : 57oAlbumin lgkglday. o Ensureadequate airway and breathing. ii. Evaporative loss : 57odextrose + water- o Vascularaccess obtained by placinga wide I to 2 mVkg/7oBSA. borecannula into oneof theperipheral veins or c. Fluids after 48 hours doingvenesection. i.Electrolyte Ringer'slactate - 1500to o Extent and depth of burnsassessed and sites maintenance: 2000 ml/m' affectedcarefully recorded diagrammatically. ii. Evaporativeloss : 57odextrose + water- . Any associatedinjuries recorded. ls I to 2 ml/kg/7oBSA . Body weightrecorded. iii. ColloidsPlasma or 57oalbumin to maintain oxygen . Tetanusprophylaxisadministered. serumalbumin3 g%o. charac- le well ClassifiedSpecialist Surgery and Reconstructive Surgery, INHS Asvini,Colaba, Mumbai - 400005.

I, No.2 Jour. Marine Medical Society,July-Dec 1999,Vol. I, No.2 103 iv. Blood to maintaina haematocritof35-4OVo. 40 ndding viabilit d. Monitoring: 30 variour o Hourly urine output(adults - 0.5 to 1 ml/kg/h, edema children- I ml/kg/h). volumt Rateand amountof fluidto be administered was 15 fluid s, 10 tailoredevery hour accordingto urineoutput. to Reducr o Vital parameters. chemir o iFk pressar o Sensorium. o-10 11-20 21-30 31-40 41-50 51-60 6.t-70 71_80 81-90 9.t_1oo injurier o Peripheralcirculation. , EXTENTOF BURNS prs alsobe o CVP monitoringwas done when indicated. INo oF EaNo oF pra D|ED4oH L-No oF prs otED 7D Fig. I : Burnshock resuscitation statistics - 1994 Proble d. Modifications in fluid therapy Maj i. Patientssustaining high voltagecontact burns 50 massiv with massivemyo-necrosis were administered volumr excessiveamounts of fluid upto 7 ml/kg/body eningi weighU%oof BSA, along with soda-bicarb(to necess alkalanizeurine) and mannitolto ensureurine admini outputof 1.5to 2 mVkg/hour,to preventblock- tonicc ageof renaltubules with myoglobins. Col ll, Elderlypatients or thosesuffering from cardio- amino pulmonarydisorders were administeredcol- o-10 11-20 21-30 31-40 41-50 51-80 81-70 71-80 81-90 91-100 lowing loids after 12 hoursto reducethe amountsof EXTENTOF BURNS oA fluids requiredto be administered,but need INo oF prs INo oF pts DIED48H ENo oF prs orEo7D cit very carefulmonitoring and tailoring of fluid Fig. 2 : Burnshock resuscitation statistics - 1995 'Br requirementsaccordingly. qr lll. Amountof fluids to be administeredwas indi- rIn patient'sresponse. For- vidualizedaccording to rM mula quoted above is used only as a rough The guideline. rD, OBSERVATIONS AND RESULTS ca a. Total no of patientstreated at Burn's Centre th duringthe threeyears viz. 1994-1996. oC, in (Figs.l-3) 372 o-10. 1t-20 21-30 3t-40 41-50 51-00 61-70 71-80 8t-90 91-100 The b. No. of patientswith morethan 307o burns t57 EXTENTOF BURNS prs prs prg someI c. Mortality in the first 7 dayspost-burn INo oF ENo oF DrEo4aH ENo oF DrEo7D - capilla 23(6.187o) Fig. 3 : Burnshock resuscitation statistics 1996 Var d. Most of the patientswho diedduring the first 7 Thereis lossof microvascularintegrity resulting in with2 days had 907o burns with severeinhalation escapeofproteins and fluids into interstitial spaces. hypert injury. Threeinfants who died with lesserex- Oedemaalso occurs in non-burnedtissues in major oll tentof burnshad positive blood culture. bum injuries.Capillary permeability is slowly re- rRr DISCUSSION storedto normal,starting from 12 to 24 hoursafter in Thermalinjury resultsin markedchanges in mi- burn injury and with this, thereis shiftingback of dr cro-circulation.These changes are mediated by re- fluids into intravascularcompartment. Burn edema Thr leaseofvaso-active substances, such as leukotriens, canreduce tissue oxygenation, whic.h may result !n oTl prostaglandins,free oxygenradicals and histamine. loss of some viable epidermalelements, thereby AC

104 Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 Jour.Iv ^adding to the depthof burn wounds.Loss of tissue o Earlyadministration of hypertonicsaline while viability makesthem prone to infection.The role of . the capillariesare leaky will resultin hyperos- variousbiochemical mediators in thegenesis of burn molarityof fluidsin interstitialspaces and cause edemais not fully understood.Loss of intravascular cellulardehydration. volumeresults in hypovolemia,which is causedby Therefore,it is betterto avoid administrationof fluid sequestrationin the interstitialcompartment. hypertonicfluids during first 12-18hours post-burn Reducedtissue perfusion results in pnd organis- injury. Carefulmonitoring of serumelectrolytes is chemiaand metabolicacidosis. A myocardialde- mandatorywhen this is undertakento avoidserious pressantfactor has been demonstrated in severeburn problemsof hypernatremia. k injuries.Changes in cell membranepotential have In the presentstudy, no patientswere adminis- alsobeen recorded in burninjured tissues. teredhypertonic fluids, as this would requiresfre- Problems in burn shock resuscitation quent and accuratemonitoring of serumelectro- Major burn injuries necessitatetransfusion of lytes. massiveamount of fluids to restoreintravascular Patientswho weremore than 60 yearsold were volume[], which at the sametime, leadsto wors- administeredcolloids early after first 12 hours,'in eninginterstitial fluid sequestration.Therefore, it is ordgrto reducethe requirement of amountof fluids. necessaryto carefullyselected the type offluid to be Onepatient, although 30 year'sold, a known case administeredi.e. crystalloidsor colloidsand hyper- of rheumaticheart disease with mitral stenosiswas tonicor isotonicfluids [1,2]. similarly administeredcolloids after 18 houn in Colloidscommonly used are fresh frozen plasma, order to a avoid fluid over-load.These patients I5, aminoacid solutionor dextran.They havethe fol- requiredmore careful monitoring and CVP monitor- 91-100 lowing advantages: ing alsohad to be done. o A lesservolume of fluids is requiredfor resus- l7D citation. CONCLUSION o Bettermaintenance ofrenal perfusionand ade- Severalformulas and regimenshave beende- quateurine output. scribedin the literaturefor resuscitationof acutely . Improvedcardiac output. burnedpatients [3,4]. No formulais a licenceto put thepatients on autopilot.Fluid requirement in every o Minimal fluid sequestration. patient has to be individualisedconsidering the The disadvantagesofcolloids are: problemsof age,preexisting cardiopulmonary dis- o During first 12-18hours post-injury, leaking orders,presence of inhalationinjury or otherasso- capillariesresult in loss of colloids making ciatedinjuries. Beneficial properties of crystalloids themineffective. andcolloids must be appropriately utilised. Amount o Colloidstrapped in interstitialspaces will result of fluidsadministered has to betailored on thebasis S,ll in retentionof waterand hence increase edema. 91-100 of physiologicalmonitoring of thepatient, including Therefore,administration of colloidswould be of hourlyurine output, and the amountof fluid calcu- someuse only after 12-18hours post-injury when :D70 latedby anyformula is only a roughguideline. capillarypermeability starts returning. Varioushypertonic formulations have been used REFERENCES rltingin with 240-300mF4 of Na+/ litre. The advantagesof l. DemlingRH. Fluid replacementin bumedpatients. Surg spaces. hypertonicfluids are: Clin NorthAm 1987:67 : 15-30. nmajor . They causeless edema. 2. Warden OD. Burn shock resuscitationWorld J Surgery wly re- o Reducedamount of fluid administeredresults 1992:16:1G23. rrsafter in lessrisk of overloading,reducing the inci- 3. HemdonDN. Total burn care.WB SaundersCompany Ltd., backof denceof cardiacand pulmonary complications. t996. ,edema Their disadvantagesare: 4..Barry Prcss.Thermal, electrical and chemicalinjuries in esultin . Theycan cause complication of elecfiolyteand Grabband Smith Plastic Surgery. Lippincott - LavenPub- thereby acidbase imbalance, as well ashypematremia. lishers,hfth ed. 197: 16l-89.

. l, No.2 Jour.Marine Medical Society, July-Dec 1999, Vot. I, No.2 AN ANALYSIS OF HUNDRED SUCCESSFULPREGNANCIES te IN INFERTILE COUPLES b. Is th pl Surg Cdr SUSHIL KUMAR*, Surg CmdeRT AWASTHI+, st Surg LCdr A KAPOOR**, Surg LCdr S SRINMS{"t, OI PVERMA#* c. \\ in ABSTRACT SL m Onehundred pregnanciesoccurring in 226infertilecouples between lstJan.95 to30 Apr.99 wereanalysed. Gross pnegnancyratc of 44.27owas obtained in brief follow up of six months to two years.Etiological factors responsible d. Ir for infertility were - anovulation43.E7o, unexplained infertility 197o,seminal deficiency 187o, endometriosis 57o, is tubal factor 1I 7oand uterine and vaginal Tactors3 7o. Polycysticovarian disease(PCOD) and hyperprolactinaemia is were found to be commonestcause of anovulation, and pregnancy rates in thcse two conditions were 47Vo anll ir 617o respectively. Most commonly used drugs for induction of ovulation were clomiphene citrate and bro- tt mocriptine. No difference in pregnancy raies was observed in casesof unexplainsd infertility, with or without treahenl In patients with seminaldeficiency, intrauterine insemination(IUI) wasfound to be marginally superior Fur to no treatnent at all. Among the patients with bilateral tubal block (conual), good results were obtained with well i conrual implantation (pregnancy rate 75 Vo). from KEY WORDS : Infertility, Anovulatory infertility, IntraUterine insemination, Cornual implantation, truegl Male infertilitv. whofr partsI gener, (Intra INTRODUCTION Though expensive,ICSI cytoplasmic sperm REFE] themain stav of treatmentfor adventof newerdiagnostic technologies fflhe il5:ti:ll,fiibecome 1.Pa I andrefined therapeutic armamentarium have ric I renderedmanagement of infertility simple, By andlarge, the current technological sophisti- m( lessinvasiveandextremelyrewarding.Theconven-cation enjoyed by the reproductivephysicians and 2.M tionaldiagnostic methods such as tubal insufflation surgeonsimmensely benefit the infertile couples by S. and D and C (dilatationand curettage)have been meansof moreeffective treatment through less in- Dt we havemade an replacedby moreobjective and less invasive meas- vasiveapproaches. In this study 3. Gl urese.g. laparoscopy, hysteroscopy and trans - vagi: attemptto shareour experiencein treatmentof in- mr nal sonography (TVS). Laparoscopic and fertility. hysteroscopicsurgery with the help of TV mon" MATERHL AND METHODS has almost completelyreplaced conuentionat i"- parotomiesin treatmentof infertility. Newerthera- One hundredinfertile coupleswho conceived piesin theform of GnRhanalogues (gonadotrophin betweenlst Jan.95 to 30thApril 99 wereanalysed. releasinghormone) and pure FSH (follicular stimu- Duringthis period total252patients were registered lating hormone)made by recombinantDNA tech- for infertility treatment.Twenty six patientswere nology have made ovulation induction more lost in follow-up. 226 coupleswere investigated, successfuland predictable.Assisted reproductive treatedand followed-up for a periodvarying from technologies(ART) like IUI, GIFT,IVF havecome six monthsto 24 months.Infertility wasdefined as a long way sincethe birth of LouiseBrown in 1977. failure to conceiveafter one year of unprotected Todayit is morereadily available and has been able intercourse.Treatment independent pregnancy was to achievehigher pregnancyrates. Treatment of definedas pr€gnancywhich occurredwithout any male infertility has also been revolutionised. specifictreatment or threemonths after stoppage of

r06 Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 Jour. -)nedical treatmentor 12months after surgical treat- nation with tamoxifenor dexamethasonewas re- ment.After registration,history was taken and ex- sponsiblefor 44Vopregnancies in this group and aminationperformed. The diagnosticevaluation in- bromocryptinefor 32% pregnancies(Table 3). cluded hormonalprofile (Day 3 - FSH, LH, ho- Amongthe 20 conceptionsrecorded in unexplained lactin, Testosterone,Esftogen, T3 T4 TSH) and infertility patients,10 pregnanciesoccurred in pa- (Day 2l - Progesteronelevels), hystero-salpingog- tientswho were given some form of treatmentwhile raphy (HSG), diagnosticlaproscopy and hystero- rest were treatment independentpregnancies. scopyin somecases. Seminal deficiency was diag- Among male factor infertility patientspregnancy nosedas per WHO recommendation(Sperm count rate(PR) of 39% wasachieved with treatmentand < 20 x l0o per rnl) tll. Patientswith azospermia 307owithout treatrnent. (Table 3). Pregnancyrate of were not includedin this study. Ovulatorydefi- 36.3Vowas obtainedwith the use of IUI in these ciency was diagnosedby serialultrasound (USC) patients. monitoringof developingfollicle andby serumpro- gesteronevalues < 7 nglrnlon day 2l ofthe cycle. TABLE2 The tubal factor wasdiagnosed by abnormalHSG Anovulatory infertllity (distribution of patients and preg. nanclesas per dlqgosis) andlaparoscopy in somecases. Endometriosis was diagnosedby laproscopy.Couples with no abnor- Diagnosis Noofpatients Pregnancieshegnancy mality were classifiedas unexplainedinfertility rate group. Polycysticovarian 39 l8 47% disease OBSERVATIONS Hyperprolactinaemia 26 16 6l% In thepresent study 100pregnancies occurred in Congenitaladrenal 3 26% 226 coupleswith overallpregnancy rate of 44.2Vo. hyperplasia(adult onset) Hypogonadotrophic 2 r 50% Thecommon causes for infertility wereanovulation hypogonadism (43.87o),male infertility (l8%o),tubal factor (llVo), Prematureovarian 4 nil nil endometriosis(SVo) and unexplainedinfertility failure (l9%o).Maximum number of pregnancies(50, Preg- Anovulationwithout 26 13 50% nancyrate 5O.5Vo),occurred in anovulatorygroup apparentcause and the minimum pregnancyra;te (28Vo) was ob- tainedin tubalfactor group (Table 1).

TABLEI In 25 patientssurgical treatrnent was required. Etlologr oflnfertility ln 226 couplesand distribution of Cornualimplantation was done in fourpatients(PR preglanciec rmong them 757o).18 patients had tubal factor involvement as a Clinical diagnosis No. ofpatients No. of Pregnancy causeof infertility. Of these12 patientswerc sub- (% oftotal patients) pregnancies rate jectedto surgeryand 50% of themconceived. Four patientswith uterinefactors were subjectedto sur- Anowlatory 99(43.8%) 50 50.5% gery Unexplained 43(r9%) 20 46.5% andonly oneofthem conceived.In threepa- Seminaldeficiency 40(r8%) t5 37.5% tientsvaginal septum was found to bethe only cause Endometriosis 12(05%) 05 4r.6% of infertility, two of themconceived after division Tubal factor 25(rr%, o7 28% . of the septum.(Iable 5). Uterine and vaginal o7(o3%\ 03 42.8% factor DISCUSSION 226(rwo) 100(100%) Infertility is seldom,if ever,a physicallydebili- tatingdisease. It may however,severely effect the couple'spsychological harmony, sexual life and Amongthe 50 conceptionsrecorded in anovula- socialfunction. Insler in an infertility surveyfound tory subjects,18 (36Vo)occurred in PCODsubjects the incidenceof infertility to be about16.77o, with and 16(327o)in hyper-prolactinaemic patients (Ta- about90 million infertilecouples around the globe ble 2). Clomiphenecitrate, either alone or in combi- [2]. Factorsresponsible for infertility wereanovula-

Jour.Marine Medical Society, July-Dec 1999, VoL 1, No.2 107 TABLE3 Trestmentmodalities uscd and pnegnancyrates in anovulatoryinfertility andunexplained lnfertility

Type of owlation induction Anovulatoryinfertility pregnancies/ Unexplainedinfertility pregnancieV Protocol no. of patients no. of patients

Clomiphene l?21 (3-6Cycles) 5/10(3-6 Cycles) Bromocriptine r6t26 Nil Clomiphene+ Tamoxifen 7/16(3 cycles) Nil Clomiphene+ Dexamethasone 3/5 (3-6Cycles) Nil HMG+HCC 4/10(One Cycle) 2/4 (One Clcle) Gn Rh + HMG + HCG 2/5 (OneCycle) Nil Clomiphene+ IUI Nil 2/6 (3-6Cycles) HMG +HCG+ IUI Nil l/3 (OneCycle) Treatmentindependent 6n6 10t20 pregnancies

TABLE 4 4-SToandmalefactor26.2to46.6%.Westudied226 Treatment modalities used and pregnancy rates ln Male in- couplesand as:shown in Table1, the distributionof fertitity thesepatients are similar to the figurescited above. Treatment modality No. of Pregnancies Pregnancy Disturbanceof ovulation(99 patients)was the patients rate leadingcause of infertility. Among the common Clomiphenecitrate l0 3 30% causesof anovulationwere PCOD - 39 patients Tamoxifen 3 2 6.6% (pregnancyrate 47%), hyperprolactinaemia- 26 Pentoxyphylline 4 2 50% patients(pregnancy rate 617o) (Table 2). Many ruI lt 4 36.3% authorstoday agreethat the common_estcause of Treatmentindependent t2 4 30% pregnancies anovulatoryinfertility is PCOD]3]. Treatmentof hyperprolactinaemiawith bromocripine wasfound l5 375% to be one of the most effective treatmentof anovu- lation. Rajan also found hyperprolactinaemic TABLE 5 anovulationmost amenable to treatment[4]. In nor- Modalities of surgicsl treotment and pregnancy rstes moprolactinaemicpatients, we inducedovulation with eitherclomiphene citrate or clomiphenecitrate Treatmentmodality No. of Pregnancies Pregnancy patients rate in combinationwith tamoxifenor dexamethasone. Pregnancyrate of 57.IVo,43.75Vo, and 6O7o were Comual implantation 4 3 75% obtained.Clomiphene citrate is the mostcommonly Tubo-tubalanastomoses 3 1 33.3% used drug for induction of ovulation, with 507o Laparoscopicadhesiolysis 2q% 5 pregnancyrates reported in literature The com- Myomectomy 2 Nil Nit [5]. Hysteroscopicdivision 2 | 50% bination of clomiphenecitrate and tamoxifen was of adhesions first used by Sugiami who found it effective in Divisionofvaginal 3 2 6s% patients,resistant to clomiphenecitrate alone 61. s€ptum Our studyshows that clomiphene citrate either alone Treatrnentindependent 6 I t7% or in combinationwith otherdrugs was responsible pregnancy(tubal factor only) for 22 of 34 (65Vo)pregnancies in normoprolacti- Total - Tubal + Uterine 25 naemicanovulatory patients. It can thereforebe + Vaginal concludedthat bromocryptineand clomiphehecit- rateforms the mainstayof treatrnentfor anovulatory infertility.These are relatively cheaper drugs, there- tion 42Vo,tubal ll-l6Vq uterinefactor 3.2 - 4.8Vo, fore adequatetrial must be given before venturing unexplainedinfertility 3.5 - 22.lqo,endometriosis

108 Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 into expensivemodalities of treatment. 5). High pregnancyrate (75Vo)was observedin Unexplainedinfertility was diagnosedin 43 patientswho had undergonecornual implantation (l9%o)patients. Total 20 pregnanciesoccurred in for bilateralcornual block. This was in contrastto this group,ten of themwere treatment independent lower successrate (35-69Vo)obtained by other pregnancieswhile other l0 occurredas a resultof workers[0]. someform of treatmente.g. clomiphene citrate IUI, REFERENCE.S in variouscombinations HMG, GnRh analogues l. WHO laboratorymanual for examinationof humansemen (Table 3). This studyshows that thereis no differ- andsperm cervical mucous interaction, 3rd ed. 1992. encein pregnancyrates with or withouttreatment. Fujii in his most recent study did not find any 2. InslerV, LuenfieldB.Infertility : Tlredimension of problem, Infertility : Male andfemale, 2nd ed. 1993;3-7. increasein pregnancyrates with useof clomiphene citratein unexplainedinfertility patients[7]. How- 3. SperoffL, RobertH, GlassNG. Femaleinfertility, clinical ever in absenceof any specific treatment,many gynaecologicalendocrinology and infertility, 5th e4 1994; cliniciansstill preferto usethis drug and claim better 809-19. pregnancyrates [8]. 4. RajanR. Infertility survey,postgraduate reproductive endo- Amongthe 40 patientswith seminaldeficiency, crinology,4th ed.Jaypee Bros. 461-6. 15 pregnanciesoccurred. Twenty eight of these 5. GyslerM, March CM, Mishell DR. A decadeexperience patientswere administered some form of treatment, with an individualizedclomiphene treatment. Fertil Steril resultingin 1I pregnancies(Pregnancy rate 39Eo) 1982137 : l6l. while 307opregnancy rate was obtainedin 12 pa- 6. Suginami H, Kitagava H, NakahashiN, Yano K. A tientswithout any treatment (Table 4). Glanzeret al clomiphenecitrate and tamoxifen combination therapy - also reported3070 spontaneous pregnancy rate in Noveltherapy for ovulationinduction, Fertil Sterill993;59 womenwhose male partners were oligospermic [9]. (5):97G9. High pregnancyrate was obtainedwith the useof 7. Fujii S, Fuki Y, Kagia A, SatoS, Saito Y. The effectsof tamoxifenbut the numberof patientswas too small clomiphenecitrate on normally ovulatorywomen. Fertil to drawany conclusion. This studyshows that there Steil 1997: 68 : 997-9 . is no statisticallysignificantdifference in pregnancy 8. CheckJH, DaviesE, AdelsonH. A randomizedprospective rates,with or without treatment,in malefactor in- studycomparing pregnancy rates following clomiphene cir fertility. rate and human menopausalgonadotrophin therapy. Harn In 25 patientssurgical treatment was required. Reprodl992i7:801-5. Eighteenpatients had tubal factor involvement as a 9. GlanzerCMA, Kelly NJ,Weir MJA. Thediagnosis of male causeof infertility. Twelve were subjectedto sur- infertility : Prospectivetime specificstudy for conception geryand 507o of themconceived, four patientswith ratesrelated to semenanalysis, Hum Reprod1987; 2 (8) : uterinefactor were subjected to surgery,only oneof 6r.5. them conceived,in three patientsvaginal septum 10. Musich JR, Behraman SJ. Surgical management of tubal wasfound to be the only causeof infertility,two of obstruction at uterc.tubal iunction. Fenil Steril 1983: zl0 : themconceived after division of the septum(Table 423.

Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 109 ALCOHOL IN THE MEDICOLEGAL REGISTER

SurgCdr ALHAD ANANTPAWAR

ABSTRACT The purpose of this study was to find out the incidenceof alcohol consumption among naval personnel who are sent for medicolegd examination, through the medicolegalregister. Available medicolegalregisters for the period 1995- lgyl were studied and the report of the doc'tor in recording alcohol consumption was noted. In such cases where alcohol consumption was recorded an attempt was made to correlate it with the reason for medicolegal exarninationand with the lindingp of the docior. Findings reveal that alcohol consumptionis associatedwith about hrenty percent of all medicolegalcases especially those reporting on issuedays. Seldomwas further investigation carried out to rule out alcohol dependenceand institute necessarTtreahent for the sarne.It is recommendedthat investigation into alcohol consumption be made a routine part of all periodic medical examination. KEY WORDS : Alcohol, Medicolegal register.

INTRODUCTION this hasnot beeninvestigated in the servicesetting. onsumptionof alcoholhas been traditionally MATERIAL AND METHODS associatedwith thedefence services. Stories perid andpoems of drunkensailors abound in the Available medicolegalregisters for the 1995 - 1997 were studied.The numberof cases westemliterature []. The civilian lookswith envy at the man in uniform who gets his liquor at a where alcohol consumptionwas recordedwere cheaperrate. Traditionally a land ofprohibition,in noted.Such case reports were studiedfurther and which alcoholconsumption was frownedupon by attemptswere made to correlatethe findingscf the the govemmentafter independence,the situation medicalofficer with the reasonfor the medicolegal today hasundergone a seachange in the country. examination,the age of the patient,the time of Alcoholis now freelyserved in retailoutlets, adver- reporting for medicolegalexamination and the tised in the numeroustelevision channels. Excise branchofthe sailor.Disposal ofthe caseand the fact whetherthe doctorhad made any attemptto inves- figures put the $owth rate at fifteen percentannu- ally. tigatefurther the patient'sconsumption of alcohol, wasalso recorded. Thatalcohol plays a role in accidentsand crimes is well known.It is estimatedthat a goodpercentage RESI.JLTS of patientsadmitted to medicaland surgical wards A totalof 386cases were studied in the medico- havean alcoholrelated disability. The preoccupa- legal registersfor the period 95-97.Alcohol con- tion of doctors with clinical care and treatment sumptionwas recorded in eightytwo cases(21.2Vo). makesthem disinclined to investigatealcohol abuse In 1995,out of 60 cases,alcohol was recordedin anddirect such cases for necessarytreatment, thus, sixteen(26.7%) (Table l), whereasin 1996it was preventinga potentialtragedy. twentyone (257o) out of 84 casesand in 1997it was It is difficult to estimatethe amountof alcohol fortyfive (22.3Vo)outof 202cases. Most of thecases consumedin the society,as peoplewho drink are occurredamongstjunior sailors for all the yearsof adeptin concealingthe amount consumed. Ordinary the study(Fig. 1).The mostcommon reason for the surveysare notoriouslyunreliable and what is re- presentationwas fights followed by road traffic latedis the tip of the iceberg.A potentialsource is accidents(Table 2). A significantpercentage(8.5Vo) themedicolegal register where alcohol consumption of thecases were those who hadconsumed alcohol is recorded.To the bestof the author'sknowledge, while on duty and were refened for medicolegal

ClassifiedSpecialist (Psychiatry), INHS Sanjivani,Naval Base, Cochin. u0 Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 examination.Surprisingly many cases were referred for medicolegalexamination without a reasonbeing recorded by the investigatingofficer. An attempt was also made!o conelateconsumption of alcohol with liquorissuedays i.e. Wednesday,Saturday and Sundayand a majority (62%) were found to have to ,z beenreferred on suchdays (Fig. 2). 15 TABLE1 10 Propordon of olcohol rrlatcd medlco-legalcases* 5 Totd Alcoholrelated Percentageof 0 medicolegal cases alcoholrelated 1995 - ca6es ' calgs 1996 Yoar 1995 60 l6 26.7 1996 U 2l 25 Fig. I : Distribution of MLC casesby rar* 1997 m2 45 22.3 The proportionofjunior sailorsfar outweighsall other ranksin alcoholrelated caseb. *Thenumber ofcases scem to beless in 1995and 1996. This is dueto thefact that some ofthe registerswere not available.

TABLE2 hcsentadonof alcoholrelated medicolegat cases

Quarrels/ RT^N On duty No Total Fights reasongiven

1995 5 4 t616 1996 9 2 2821 t997 19 6 41645 Fig. 2 : Alcohol consumptionlinked to issuedays Most of the alcoholelated medicolegal cases occurrcd In most ofcases consumingalcohol presented with fightdquar- on dayswhen liquor wasissued. rels and in a significant numberthe reasonwas not given.

DISCUSSION ICD 10 in addition to the conceptof dependence and intoxication also infioduces the concept of harmfuluse which refersto a maladaptivesubstance usewhich impain health in a broadsense. Alcohol consumptionis reportedlyhighest from mid twen- tiesto theforties with a lifetimerisk of l47oto207o [2,3].Asians and orientals are said to beat a reduced risk due to the variant in the enzymealcohol dehy- drogenase[4]. However going by the increasing consumptionpattem in our country this does not seemto be the case.There is a generalpattem of heavydrinking in the latetwenties leading to serious difficultiesatworkin 1' themid thirties.This couldnot fig. : Alcoholconsumptionbranchdistribution be correlatedin our studybecause in manycases the i | agewas not recorded.Mostof the casesin this study group of twenty to thirty. Studies in the UK and USA occuned among the junior sailors i.e. in the age reveal that alcohol consumption is associatedwith

Jour.Marhe MedicalSociety, July-Dec 1999, Vol. 1, No.2 111 forty percent of all road traffic fatalities. In the abusein clinical settings[7-9]. Somerecommend presentstudy only onecase of a "broughtin dead" routinescreening for all personspresenting for pe- wasassociated with alcoholconsumption though a riodicmedical examinations [0]. Thiscan be easily total of twelve cases(26.7Vo) presented with evi appliedin the servicesetting where all personsre- denceof havingbeen involved in roadtraffic acci- port to the medical officer for routine half yearly dents. medical,leave medical, promotion medical etc. Though it may be arguedthat the meresmell of In themedicolegal setting such screening should alcoholin thebreath is notevidence ofalcohol abuse be thoroughlydone especially on weekendswhen or dependence,it may be notedthat in the service abuseof alcoholis very common. settingwhere the amountof alcoholconsumed is In the clinical setting,historical factors which restrictedand punitive action taken to curb misbe- indicatean alcohol induced problem include insom- haviour,the presenceof smell of alcohol in the nia,headache, dyspepsia, diarrhea, palpitations, mo- breathis a significantfinding. Often such cases were tor vehicleaccidents and multiple emergency visits sentfor medicolegalexamination after the evalu- for anyreason. Important physical factors indicating ationby thepolice is over,a period,which may take analcohol induced problems are cirrhosis, hyperten- severalhours, allowing the alcohol to burnout ofthe sion, unexplainedtachycardia, tremulousness and present, system.At no facilitiesexist to detectblood smellof alcoholin the breath.The findingsof this alcohollevels to determinethe level of intoxication studywas that the majorityof casespresented with or to estimateserum GGT levels to screenout fights or quanels(4O.2Vo) followed by road traffic chronic alcohol abuseon a routine basisin most accidents(l4.6Vo). Unfortunately in36.5%o cases no servicehospitals. Evidence of drunkennessis pre- reasonwas given for sendingthe case for medicole- dominantlydetected by an investigationand the gal examination.This caneasily be rectifiedby the performed medicolegalexamination to rule out any medicalofficer insistingon the reason,in all cases positive underlyingmedical condition. A findingof refenedfor medicolegalexamination. Our findings drunkenness by suchan investigationinvites disci- thatthe incidence seems to be increasingamong the plinaryaction. Seldom aresuch cases referred to the seamanand communicationcadre (Fig. 3) needs psychiatrist for evaluationof alcoholabuse. verificationby further studies.Significantly not a Alcohol abusegoes undetected not only because singlecase of alcoholconsumption was admitted for alcoholicshide their drinking but becausedoctors evaluationof alcohol abuseor dependence.As fail to recognisethis possibilityand screen for this statedearlier the category of harmfuluse in theICD disorderby askingthe right questions.A simpleand 10gives a widelatitude foradmitting such cases and a quick way to askthe CAGE questionnaire.In this preventinga potentialmishap. only four questionsare asked i.e. CONCLUSION Haveyou everbeen asked to Cut down on your drinking? The abuseof alcoholby the individualnot only impairs his health but also adverselyaffects his you get you Do Annoyedif someonetells that family. In addition,such individualsby virtue of you drink too much? their dependenceon liquor can compromisethe Do you feel Guilty aboutyour drinking? safetyof the ship andcolleagues especially during Do you needan Eye - openeri.e. a drink in the periodsof long sailingwhere forced abstinence is morning? the norm. The traditionof overlookinga drunken episodeneeds to beavoided and such persons should positive A answerto any oneindicales the need be thoroughly evaluated.Screening for alcohol for evaluationand two or more positiveanswers shouldbe a routinein all periodicmedical examina- indicatethat the patientis dependenton alcohol.A tions. numberofgroups in theUSA includingthe National Instituteof Alcohol Abuseand Alcoholism. the In- REFERENCES stitutethe Medicine and the US heventive Task l. BoydstunIA, PerryIGC. Military psychiatry.In comprehen- Force recommendroutine screeningfor alcohol sive text book of psychiatry. Third edition. Editors HI

112 Jour. Marine Medical Societt,July-Dec 1999,Vol. I, No.2 Kapla$ AM Frccdman"Bt Sdoch Wilians and Wilkins. intoxicatio addictim.193; E8 :3l.fl. Bdtimcc 1980;3:2E9. 6.7tuk TS, ermt BF, Stincdr fS, ncrtOuocl D. Alcohol 2. Rcgicr DA, Nanow WE, Rac DS, ct al.Tto'dc faclo' US involvenrcnt in fatrl traffic crashcsin thc United Statcs : rnental and addictivc disodcrs scrvicc systcrn ArcNvcs ol 199-190; Addiction 194; 89 : ?21-31. Gcneml Psychbry 1994;50: E5-9. 7. US Departmcntof Hcalth and Humrn Scrvices.Thc physi- 3. Kcssler RC, McGquelc KA, Zhao S, et al. Lifctim and cians gui& o hclprng pcoplc with alohol pr,oblcns.NIH hrrelvcnronth prevalcnccofDSM Itr psychiatricdismdcrs Publicationno.95-3?69, Washington DC, US. Dcpartmcnt inthc Unitcd Starcs:results fromtheNational CoMorbidity of Healthand HumanScrviceq 195, Survcy.Arcfu'vcs of Geural Psychiatry 1994;51 : &a), 4. WaUTL, ThomacsonIIR, Schukit MA EhlereCL. Subjcc- 8. In*ina of Mcdicinc: Broadeningthe bascof trcarrcnt fq tivc foclings of alcohol intoxicatio in Asisns with geuic alcoholpoblans. WashingtonDc N*iod Aca&my Prcss vrriations of ALD H2 allelas.Alcohol Clinical andExpcri- 1990. mcntalRcscarch l9X2: 16:991-5. 9. US prcvcntivetast fscc : Gui& to clinical ard prcventive 5, NaranjoCA, BremnerKE. Behaviouralconelatcs ofalcohol scrvices2nd cdition, Baltimore.Williams andWilkins 196.

Jour. Mhrine Medical Society,JuIy-Dec 1999,VoL 1, No.2 II3 GROWTHPATTERN IN THE FIRSTSIx MONTHS OF LIFE A Semi-longitudinalstudy

SurgLt Cdr S NARAYAN*,Surg Cmde WP TIDRGAONKAR+, SurgCdr T NAGARAIA#

ABSTRACT A two year prospective semi-longitudinal study of the growth pattern of full term healthy infants of service pensonnelwas carried oul A total of 221 infants were assessedfor weight length and head circumference at half-monthly intcrvals for the first six months of life. The mean body weight increasedfrom 2930 gm at birth to 7260 gm at six months; an averageincrease ol72l.5 gm per month. There was a total increaseof 15.6 cm in the mean crown-to-heel length in the first six months and during this period, head circumferencegrew by 9.4 cm from a mean 34.4 cm at birth. Growth curves drawn for theseparameters reveal the growth of the population under study to be better than the growth pattern of infants delineatedby most earlier Indian studies and comparable with those of recent studies. The weight of infants in this.study was consistently less than the NCHS standards thoughthe length and headcircumference were comparable to theNCHS standards. Howeverr larger, multicentric studies from various service hospitals would provide the correct growth curves for the truly mixed population that is only seenin the Armed Forces. KEY WORDS : Growth, Growth curves,Weighl Length,Head circumference.

INTRODUCTION The resultsthus obtained are presentedand com- pared with the results of author's works rowth chartingis theonly methodavailable other on growth patternsofvarious groups oflndian children to monitorthe of children[]. Given $owth as well as with the NCHS standards. the vastsize ofour countrvand the diverse ethnicand socio-culturalgroups therein, it is little MATERIAL AND METHODS wonderthat disparity is observedbetween different This study was conductedbetween April 1995 studieson the physicalgrowth of childrenin India. andMarch 1997in the Departmentof Pediatricsof Despitenumerous individual and collective efforts, INHS Kalyani. we havenot beenable to obtaina suitableNational GrowthCurve for usein our country[2]. A totalof 221infants; 125 male and 96 female qualifiedfor this study.Subjects included babies present The ArmedForces a uniqueopportunity bornin thishospital as well asbabies bom elsewhere peoplesfrom various parts of vast to study our butattending Well BabyClinic in thishospital. country but with similarity in socio-economic status,standard of living andaccess to healthcare. The criteria for exclusionfrom this study in- Against this background,a two-year,prospective cludedone or moreof the following factors: semiJongitudinalstudy was undertakento define a. Prematurity the growth parametersof full-term healthyinfants b. Intrauterinegrowth retardation of servicemen. c. Any majorillness requiring hospitalization This study was conductedwithin the available resourcesof the pediatricdepartment of a medium d. Any pre-existingmalnutrition sizedservice hospital with a singlepediatrician, the This studyis semi-longitudinalbecause not all aim being easy reproducibilityin other centres the parameterswere recorded for all the subjectsat throughoutthe ArmedForces. everymeasurement interval.

*Graded Specialist (Pediatrics) INHS Dhanvantari, Port Blair - 744 L02; +Command Medical Officer, Eastern Naval Command, Visakhapatnam - 5; #Officer-in-charge, Station Health Organization, Visakhapatnam- 5.

I14 Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 Mothers were given appointmentby dates to drawnand the results of thepresent study compared bring their babiesfor measurements.Records were with thefindings of othersuch studies. maintainedin the departmentitself. All measure- RESULTS mentswere recordedby the pediatricianhimself or by a trainedmedical assistant. The meanfor bodyweight, length and head cir- cumferencealong with theirrespectivestandard Following parameterswere recorded as de- de- viationsal observedfrom birth to six months scribedbelow at birth andevery 15days thereafter: of age arepresented in Tablel. a. Body weight(in gm) : An Avery leverbalance The meanbirth weight was 2930 gm and this with measuringintervals of 50 gm anda maximum increasedby anaverage of 721.5gm everymonth to capacity of 10 kg was used. The machinewas a meanof 72ffi gm at six monthsof age.However, checkeddaily with known weightsto ensureaccu- as can be seenfrom Table 1, the increasein body racy. Infants were weightedwith only one light weightwas not uniform over the observedperid. garmentfor the torsoand as far aspossible, weigh- The maximumincrease was of 1090gm in the first ing immediatelyafter a feedwas avoided. monthof life, theminimum being an increase of 330 b. hngth (in cm) : Thecrown to heellength was gm in the sixth month. Birth weight doubledby measuredusing a woodeninfantometer with a slid- approximatelythee monthsof age. ing crosspiece. The meanlength at birth was5 1.2cm and over c. Headcircumference (in cm) : A flexible steel thesix monthsof observation,this increased by 15.6 [apewas used.Anteriorly the tapewas passed just cmto 66.8cm atsix monthsof age.The average gain a6ovethe superciliaryridges and posteriorlyover in lengthper monthwas therefore 2.6 cm.As seen the occipital protuberanceto record the head cir- with the weightpattem, body lengthalso showed a cumference. rapidincrease in the first threemonths of life at an Measurementsthus obtainedwere tabulatedand averageof > 3.0 cm per month.From the fourth the meanand standard deviation for eachparameter monthonwards, this sloweddown to an increaseof at eachobservation period calculated.The numbers only 1.2cm in thesixth month. studiedwere not consideredlarge enough to justify At birth, the meanhead circumference was 34.4 separatetabulation of data for malesand females. cm andover the next six months,this increasedby Basedon thesevalues, separate growth curvesfor 9.4 cm at an averageof 1.6cm per month.Except body weight,length and headcircumference were for thefirst monthwhen the increase was 2.4 cm. the

TABLE I Mean growth parameters from birth to six monihs

Age Number Mean Standard Mean Standard Mean head Standard (Months) of weight deviation length deviation circumference deviation subjects (gm) (gm) (cm) (cm) (cm) (cm)

Birth 208 2930 395 51.2 2.03 34.4 l.l 0.5 95 3540 489 52.3 2.23 35.6 1.3 1.0 107 4020 531 54.6 2.29 36.8 t.2 1.5 87 4450 567 56.1 2.t7 37.6 1.3 2.O 9l 5020 616 57.8 2.ll 38.5 l.l t5 56 5310 708 ffi.2 2.46 39.0 t.4 3.0 70 5740 @8 6r.6 2.36 39.9 1.3 3.5 4l 6050 806 62.5 2.31 40.5 1.0 4.0 69 &20 815 63.7 2.25 40.9 t.2 4.5 44 6710 930 &.8 2.W 41.9 1.3 5.0 50 6930 857 65.6 2.41 42.4 t.4 5.5 37 7100 901 66.1 2.41 43.1 1.6 6.0 50 72ffi 757 66.8 2.34 43.8 1.2

Jour.Marine Medical Society, July-Dec 1999, Vol. 1, No.2 I I5 gowth in head circumferencewas more or less TABLE 3 uniform.At six months.the meanhead circumfer- Mean length (cm) + 2 SD values encewas 43.8 cm. Age Minus Minus Mean Plus Plus (months) The calculatedmeans and values for two stand- 2 SD I SD Weight I SD 2SD arddeviations on eitherside ofthe respectivemeans Birth 47.t4 49.17 5r.2 53.23 55.53 for bodyweight for eachobservations are presented 0.5 47.U 50.07 52.3 54.53 56.76 in Table2. 1.0 50.02 52.3r 54.6 56.89 59.18 1.5 5t.76 53.93 56.1 58.27 fi.M TABLE 2 2.0 53.58 55.69 57.8 59.91 62.02 Mean weight Gm) + 2 SD values 2.5 55.28 57.74 @.2 62.6 65.t2 3.0 56.88 59.24 61.6 63.96 6.32 Age Minus Minus Mean Plus Plus 3.5 57.88 60.19 62.5 64.81 67.t2 (months) 2 SD l SD Weight rsD 2SD 4.0 59.2 61.45 63.7 65.95 68.2 Birth 2t40 2535 2930 3325 3720 4.5 ffi.62 62.1r 9.8 66.89 68.98 0.5 2562 3051 3540 4029 4518 5.0 60.78 63.r9 65.6 68.01 70.42 1.0 2958 3489 40'20 4551 s082 5.5 6t.28 63.69 66.1 68.51 70.92 1.5 3316 3883 4450 5017 5584 6.0 62.r2 u.46 66.8 69.14 7r.48 2.O 3788 4'lM 5020 5636 62s2 2.5 3894 4&2 5310 6018 6726 't036 TABLE 4 3.0 4444 5092 5740 6388 Mean herd circumference (cm) + 2 SD values 3.5 4438 5244 6050 6856 762 4.0 4790 5605 6/.20 7235 8050 Age Minus Minus Mean Plus Plus 4.5 4850 5780 6710 7ffi 8570 (months) 2 SD I SD Weight I SD 2SD 5.0 52t6 ffi73 6930 7787 8&4 Birth 32.2 33.3 34.4 35.5 36.6 5.5 5298 6t99 7100 8001 8902 0.5 33.0 34.3 35.6 36.9 38.2 6.0 5746 6s03 72ffi 8017 8774 1.0 34.4 35.6 36.8 38.0 39.2 1.5 35.0 36.3 37.6 38.9 40.2 The calculatedmeans and values for two stand- 2.0 36.3 37.4 38.5 39.6 N.7 2.5 36.2 37.6 39.0 40.4 41.8 arddeviations on eitherside ofthe respectivemeans 3.0 37.3 38.6 39.9 4t.2 42.5 for length for each observationare presentedin 3.5 38.5 39.5 ,10.5 41.5 42.5 Table3. 4.0 38.5 39.7 40.9 42.t 43.3 The calculatedmeans and valuesfor two stand- 4.5 39.3 40.6 4r.9 43.2 M5 arddeviations on eitherside ofthe respectivemeans 5.0 39.6 41.0 42.4 43.8 45.2 5.5 39.9 41.5 43.1 44.7 46.3 for head circumferencefor each observationare 6.0 4t.4 42.6 43.8 45.0 46.2 presentedin Table4.

DISCUSSION of life was started.As can be seenfrom Table l, In 1944,though there were 993 centersin exist- subjectsdid not reportfor all the Well Baby Clinic ence in British India to promotethe health and visitsand the numbers kept decreasing with increas- welfare of children, no anthropometricdata on the ing infantage. Thus this studybecame semilongitu- Indianinfant and child wasavailable [3]. At thetum dinaland was restricted to thefirst six monthsof life. of thecentury, despite numerous efforts, we still do The meanbirth weightof 2930 gm recordedin not havea suitable'Indian' growthcurve In the [2]. this studyis 340gm shortof theNCHS standard [4] ArmedForces, we havea truly mixedpopulation as and is lower than that of most Indian studiesas well aspre-existing infrastructure and ongoing Well shownin Table5. Evenway back in 1944,an indian BabyClinics. In spiteof theseadvantages, we have studyrecorded a meanbirth weightof 3000gm [3]. beenunable to collateenough data to definegowth Whetherthis lower birth weightreflects the effect parametersfor our infants. of maternalundemutrition in the lasttrimester or is Givqp this background,a longitudinalstudy to due to someother factors merits further investiga- monitoithe growth pattern of infantsin thefirst year tion.

It6 Jour.Marine Medical Society, July-Dec 1999, Vol. 1, No.2 TABLE 5 Comparison of mean weights (gm) of difierent studlcs

First author Ghosh Rao Uklanskaya SwaminathanKhandija Mukharjee Khurana Ghai Agrawal NCHS Narayan year 1944 1953 1960 1964 1967 t970 t97t t992 t979 t997 type of study l,ong* S/L+ Long S/L Long S/L Long CYS" s/L

Birth 3m0 3010 3000 2800 270/J 2898 2980 3140 2930 0.5 3540 1.0 3600 34ffi 3826 3990 3400 3645 3920 4320 1.5 4450 2.0 4130 4713 4500 47t0 4m 4350 4650 5020 ,s 5310 3.0 4908 5302 5770 5000 5560 5630 5650 5740 3.5 6050 4.0 5446 5905 5600 6220 5500 5450 6r'.20 4.5 6710 5.0 6050 596'1 &30 6730 5900 6550 6930 5.5 7100 6.0 65r7 6830 7230 6300 7l& 7350 72ffi o * Long- Longitudinalstudy; + S/L - Semilangitudinatstudy; CIS- CaseStudy

Weight gain was rapid in the first two months reasonfor this slowingdown could be dueto faulty with birth weightbeing doubled between three and weaningpractices and this needsfurther investiga- '/z 3 monthsof age.This is in sharpcontrast to the tion.Another reason could be that the heavier infants accepteddictum that birth weightdoubles between wereperceived to be 'healthy'by their parentsand five and six months of age [3,5-9]. It has been thuswere not brought for furtherweighing, resulting obsenredthat lighter the infant at birth, more the in a decreasein theaverage weight. This is borneout chancesof doubling birth weight by five montils by the fact thatthe numberof infantsweighed kept [3,6].Apart from the lowerbirth weight,faster dou- decreasingmarkedly from threemonths of age(fa- bling of birth weightseen in this studyis probablya ble l). The only methodof eliminatingthis flaw is reflection of the better socio'economicstatus and to conducta full-fledged longitudinalstudy that thefree access to healthcare that the subjects ofthis allowsunintemrpted data to be analysed. studyenjoyed. Iarger studiesare needed to confirm Thecrown to heellength of subjectsin this study as to whether this trend reflects the true growth arehigher than that of any of the comparedIndian potential of our infants. studiesthrough out (Iable 6). In fact,length at birth The maximumweight gain in this studyof 1090 in this study is 51.2 cm which is higher than the gm in the first month is marginallymore thanthe NCHSaverage of 50.5cm [4]. At thee monthsage gain of 1020 gm in the correspondingperiod of too, infantsin this studywere 61.6 cm comparedto NCHS figures [41. Growth was not uniform - a the 6l.l cm of the correspondingperiod of NCHS characteristicof Indian studies[2]. Exceptat birth figures. However, at six months age, the NCHS and at six monthsage, infants in this studywere averagewas higher at 67.8cm comparedto the66.8 heavierthat thosein any previousIndian study re- cm is this study. ferredto 5). Cfable Swaminathanand co-worken in 1964,found val- Weightgain per monthshowed a decreasefrom uesfor all measurementsmuch below the reported the ageof three onwardsin this study.This pattem figures for American and British children [2]. hasalso been reported by Khandujaand co-workers However,most Indian studies have found the length who were studying nutritionally optimisedinfants of Indian infans in no way inferior to that of infants [8]. OtherIndian workers have reported a decelera- from developedcountries [3,5,7,8,13]. This study tion of weight gain from five monthsage in com- hasbrought.out a uniqueaspect that hasnot been parisonwith infantsfrom othercountries [6,7]. One notedin any of the quotedprevious Indian studies

Jour.Marine Medical Society, July-Dec 19919, Vol. I, No.2 1t7 TABLE6 Comparisonof meanhetgbts (cm) of dlfierentstudles

Firstauthor Ghosh Rao UklanskayaSwaminathan Khanduja Mukharjee Khurana Ghai Agrawal NCHS Narayan Year 1944 1953 1960 r9il t967 1970 l97l 1992 ln9 1997 typeofstudy Long s/L Long S/L Long S/L Long gs s/L

Birth 48.9 49.5 49.0 48.1 48.7 49.24 47.95 50.38 50.5 5t.2 0.5 52.3 1.0 52.3 51.25 53.8 54.5 51.4 50.43 53.85 54.6 54.6 1.5 56.1 2.0 57.58 56.6 56.0 57.7 54.7 54.34 56.75 57.8 2.5 fi.2 3.0 61.0 s8.8 58.7 59.9 58.38 59.9 6l.l 61.6 3.5 62.s 4.0 62.83 61.0 60.5 63.5 59.9 6.6 63.7 4.5 64.8 5.0 9.53 62.5 64.0 62.0 @.76 65.6 5.5 65.1 6.0 65.6 &.2 . 65.3 65.12 65.r 67.E 66.E

TABLET Comparison of mean head clrcumference (cm) of dlfiercnt studies

Firstauthor Uklanskaya Swaminathan Khanduja Khurana Ghai NCHS Narayan year 1960 tgu t967 l97l 1979 t997 typeofstudy Long s/L tong I.ong (yS s/L

Birth 33.2s 33.8 33.74 34.1 34.8 34.4 0.5 35.6 1.0 36.6 36.7 34.77 36.9 37.2 36.8 1.5 37.6 2.0 38.0 37.8 38.0 36.92 38.6 38.5 2.5 39.0 3.0 39.5 39.l 37.6 ,!0.6 39.9 3.5 .10.5 4.0 .0.9 39.7 0.3 38.57 &.9 4.5 4t.9 5.0 4t.6 4t.4 Q.7r 42.4 5.5 43.1 6.0 42.1 43.8 in that the meanlength at any given agebelow six the headcircumference of infants in this study was monthsis more thanthat of eventhe NCHS figures. 43.8 cm, the same as the NCHS figure for the This can be taken to representthe true growth po- correspondingage [4]. Unlike body weight and tential of our infants.Why this leadover the Ameri- length,head circumference increased in moreuni- caninfants is lost by six monthsof ageand how best form mannerover the entire period of this snldy. it canbe preventedmerits further detailed investiga- There are axeasdelineated by this study which tion. needinvestigation and the implementationof reme- Like thelength, theheadcircumference of infants dial measures.Specific questionsthat need to be in this study comparedwell with most of the other answeredare : Indian studiesas well as with the NCHS standards a. Is the lower birth weight seenin this studydue as shown in Table 7. [n fact, at six monthsof age, to matemalundemutrition in the third trimes-

II8 Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 ' ter? 4l : l-19. b. Is the slowing down of weight gain from the 4. NelsonWE, BehrmanMD, Kliegman RM, Arvin AM, Edi- third monthonwards a resultof faulty weaning tors.Textbook ofpediatrics. l5th ed. (Indian)Bangalore : practicesor is it dueto thehigh drop-out rate of WB Saunders1996;63-5. subjectsin this study from threemonths age 5. RaoMN, BhattacharyaB. Physiological'norms' in Indians onwards? - Growthcurves of childrenin the first year.IJP 1953:82: c. What arethe adversefactors due to which the 249-@. initial advantagein length(that infants in this 6. Uklonskaya,Buri B, ChoudhuriN, Lathura,Dang, Kumari study have over counterparts)is lost by six R. Physicaldevelopment ofinfants in New Delhi in thefirst monthsof age? yearof life.IJP 196o;lO :2ll-7. Sross rible d. In thelight of the fact thatlength of our infants 7. MukherjeeDK, SethnaNJ, MadhavanR. Height, weight, s57o, is more than that of the NCHS standard,there heightvelocity and weight velocity of BengaliHindu chil- remia is a needto documentthe growthdata of our dren from birrh to I 8 months.IJ P l97O; 31 : 429-37. b and infantsand this may tum out to be betterthan bro- the NCHS standards. 8. KhandujaPC, Agarwal KN, TanejaPN. Growth study in first thout yearof life on optimal nutritional conditiots. Indian pediat- rcrior Furtherinvestigations into the aboveaspects as rics 1967;4 :203-7. lwith well as multicentric standardizeddata gathering from all servicehospitals will help us to generate 9. JohnsonCP, BlascoPA. Infant growth and development. Pediatricsin review.As publishedin pediatrics(Indian ed) true growth patternfor the infantsof our servicemen 1997;9:14663. whoform a truly mixedpopulation, coming from all partsof our country.This in turn, will enableus to 10. AgarwalKN. Figuresas quoted in : Ghai OP. Editor. Essen- generatea NationalGrowth Curve. tial pediatrics3rd edition. New Delhi : Interprint, 1993;G7. perm REFERENCF^S I l. Ghai OP.Editor. Ess€ntialpediatrics 3rd edition. New Delhi ntfor : Interprint, 1993;G7. l. ParkJE. Park K. Preventivemedicine in Obstetric.Paediat- rics and Geriatrics.In : Textbook of preventiveand social 12. SwaminathanMC, Jyothi KK, Singh R, MadhavanS, ,histi- medicine.l2th ed.JabalpurBanarsidas Bhanot; 1990; 302-7. GopalanC. A semi longitudinal study of growth of Indian s and 2. MukherjeeDK. Growth study andIndian norms.In : Gupte children and the related factors.Indian Pediatics 19il: L esby S. Editor. Recentadvances in pediatricsVolume - 3. New (7\:255-63. ssin- Delhi.Jaypee Brothers, 1993; 251-81. 13. KhuranaV, Agarwal KN, Manwani AH, SrivastavaG. dean 3. GhoshL, SenM, ChandrasekarC. A studyof thedevelop- Physicalgrowth in first five yearc.Indian Pediatrics l97I; of in- mentoflndian infantsin a communitvin Calcuna./JP 1944: 8 (7) :3314.

eived ysed. itered were ;ated, from edas ected / was t any geof iolaba.

, No.2 Jour. Marine Medical Society,July-Dec 1999,Vol. I, No.2 1t9 SERUMPOTASSIUM LEVELS IN BETA -2 AGONIST NEBULISATION OF ASTHMATIC CHILDREN

SurgLCdr S DAS*,Surg Capt KS BAWA+, P AGARWAIT#,Surg Cdr S MATHAI*{', . SurgCdr G GIJPTA*'I

ABSTRACT InhaLationtherapy has revolutionised the treahent of bronchirl asthma and nebulisation with respiratory beta-2 agonist solutions has come as a boon for asthmatic childrcn. Even though dose of beta-2 agonlsts through nebulisation results In negligible clroilating plasma concentrations,still hypokalaemia and associatedcardiac disturbances may be potentially serious unwanted effects. rlzn Fifty one childrcn ln the age group of I ll years with mild (Grp. I), moderate (Grp. II) and severeasthma (Grp. III) receivednebulisation with salbutamol (0.f - 0.f5 m'g/kg,n-27), Terbutaline (0.1 - 0.15 mg/hg n-24) were studied. In all three groups the fall of serum potassium was maximun at 90 minutes and mean maximum falls in Gr?. I, Grp.II and Grp.III were0.45 meq/litre (P0.fi)l),0.50meq/litre (P0.ffi1) and 0.7Emeq/libe (P0.1X)1)respectively. There was no statistically sipificant difrerencr in hypokataemtc effect of salbutamol and tcrbutaline. Beta-2 nebulisation in all groups causedrise in heart rate signilicantty (P 0.(X)1).The electrocardiograms were nornaL It was observedthat fall of serum potassiumafter beta-2nebulisation was dose related. Higher doseof nubulisation showedsiqnificantly higher fall in senrm potassirrrnlevels. Beta-2 agonist nebulisadon in acrrte asthma in therapeudc range ln noncardiovascular compromised patients is quite safe.But whenevercontinuous or repeatednebulisation is warTanted for control, the serum potassiumlevels should be estimated to avoid serious hypokalaemia and its compllcations. KEYWORDS:

INTRODUCTION 12,31. hesuccess in findingdrugs with beta-2selec- SubsequentlySwedisJr scientists invented TER- tive agonistsin late 1960'sand early 1970's BULATINE and scientistin Germanysynthesized wasa significantmilestone in historyof an- FENOTEROL.It is interestingto notethat the bron- tiasthmadrug therapy []. chodilator cardiac selectivity of the sym- In the United Kingdom researchersin 1968at pathomimeticdrugs were noted before generalac- Allen and Hanburyshad replaced3 position hy- ceptanceofthe Br andBz receptorsubtype hypothe- droxyl gpup in isoprenalinewith bulkier hy- sis[l]. droxymethylgroup. As they predictedthis produced In 1967l.ands et al proposedthat "Beta"recep a beta agonistbronchodilator with longer duration tors shouldbe dividedinto two differenttypes, 81 of action.The compoundwas active orally as well andBz. I-aterthey classified beta responses on heart, as by inhalation.By furtherincreasing the bulk of adiposetissue and small intestinewith beta-l and the N substitutedalkyl group what a 't' butyl group bronchioles, vasculatures,diaphragm and uterus they obtained a compound with increasedbron- with beta-2receptors []. chodilatorpotency but fewer cardiacside effects. Thiscompound was laternamed "SALBUIAMOL' All theclinically usedBz agonists were available

*PostGraduate Trainee (Paed.); +Sr Adviser (Paed-);#PG Trainee; **Classified Specialist(Paed.), INHS ASVIM, Colabq Mumbai 5

120 Jour. Marine Medical Society,July-Dec 1999,Vol. 1, No.2 -)br inhalationas well as for oral use.The inhaled tamoland terbutaline. routeallowed a smallbut effectivedose of drug to 5. Cardiacanhythmia and hypokalemic effect of be delivereddirectly to the airwaysand this pro- B2 agonistnebulisation. duceda fairly prompt bronchodilator.response.In 6. Safety agonistnebulisation additionit providedan indirectmeans of reducing of82 in acutebron- chial asthma. theside effects of thedrugs, because the dose of the drug wassmall, the amountof drug absorbedfrom METHODS lungs and gastrointestinaltract (as upto 9OVoof The study was conductedat Naval Hospital, inhaleddose is swallowed)resulted in a negligible INHSAsvini from 0l Jan.1996 to 30Jan. 1997. The circulatingplasma concentration, hence less drug studygroup consisted ofadmitted children and those wasavailable to causeextrapulmonary side effects whoreported to emergencydepartment for manage- Inhalationtherapy revolutionised the treatment ybeta-2 [1]. mentof acuteattack of bronchialasthma. Parental of bronchinalasthma for its quick effect reduced hrough informedconsents were obtained in all cases.Chil- untowardside effects. cardiac drenof unwilling parentswere not includedin the Nebulisationwith respiratorysolutions came as studygroup. asthma a boonfor infants,children and patients with co-or- 4) were dinationdifficulties for inhalerdevices. Nebulisen Inclusioncriteria, exclusioncriteria and evalu- arewidely usedin acuteasthma since they provide ation Grp. I, rapid and selectiveadministration of drugsto the Children who had clinical evidenceof bron- rtively. ainvays[4]. Nebuliseralso permits delivery of high chospasmwere considered for the study. Beta-2 drugdoses and is easyto use. Exclusioncriteria : romal. Hypokalemiais potentiallyserious unwanted ef- a) Childrenon prior medicationwith steroidsxan- rlisation fect of Bz agonisttherapy because it hasbeen asso- thenederivative and oral Bz agonists, ciatedwith cardiacarrhythmias [5]. The contribu- b) Childrenrequiring more than two oral nebuli- tientsis tion of hypokalemiato causecardiac arrhythmia and mlevels death in asthmais difficult to establishfor two sationsin first two hours. reasons: (i) Asthma by causinganxiety, tachy- c) Childrenrequiring IV fluids, aminophyllineor cardia,tachypnoea and acid basedisturbances may steroids. also adverselyaffect heart, (ii) Along with Bz d) Anaemicchildren, cardiac murmur or anyCVS agonistother theurapeuticagents used in asthma compromise. also have direct action on heart.However due to e) Childrenwith five or morestools. d TER- existinghaemodynamic instability and cardiac dis- All the childrenwere either admitted to paediat- hesized turbancesin asthma,hypokalemia induced by 82 ric wardor attendedemergency dept of paediatrics rebron- agonisttherapy even though less amount of drugis with complaintsof breathlessnesswere evaluated sym- systemicallyabsorbed by nebulisation,may play a anddetailed history was taken which includedpre- :ralac- contributingfactor for cardiacarrhthymia in patients prolonged vioushistory of similar attack.Any historyof car- /pothe- receivinghigh dose nebulisationwith Bz agonist[5]. diovasculardisease was noted.Physical examina- tion includedheight and weight records, pulse rate, recep- AIMS OFPRESENTSTI.]DY andrhythm, respiratory rate, blood pressure, hydra- rs, Bt l. Changesin serumpotassium level in patients tion status,chest retractions, grunt, nasalflaring, r heart, nebulisedwith 82 agonistin normaltherapeutic cyanosis,air entry,breath sounds and adventitious -l and dose. soundin form of ralesand rhonchiand other sys- uterus 2. The time of peakfall in serumpotassium after temicexaminations. Those children who could gen- nebulisationwith Bz agonist. eratePEFR, their PEFR were recorded. The diagno- sisof bronchialasthma was established on thebasis dlable 3. 82.agonistand hypokalemiadose relationship of historyand clinical findings. Those children who in severeasthmatics. were found to have other respiratoryconditions -bar 5 4. Differencein the hypokalemiceffect of salbu- causingbreathlessness or those suffering from other

l, No.2 Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 t2l systemicdiseases were excluded from the study. 15 minutes.Further revaluation was doneafter 1-5' The severity of the attack was assessedon the minutes.Those who did not improverequiring fur- basisof clinical asthmascore (Table 1) [6,7].Chil- thernebulisation were excluded from study. drenwith clinicalasthma score 5-8 wereconsidered Moderate: Nebulisationwith salbutamoVterbu- mild, 8-10moderate and more than 10 severe. While taline 0.15 mg diluted with two ml normal saline gradingseverity of asthmainto mild, moderateand overperiod of 5 minutes.Continuous oxygen inha- severethe criteria laid downby NationalHeart Lung lationwas started. The child wasre-evaluated after and Blood Institute's,National Asthma Education 15minutes, if the responsewas incomplete (persis- hogramme expert panel reports were taken into tanceof symptomatologyand PEFR improvement consideration(Table 2) [8]. 20Vo)second nebulisation with same dose was given.Again they werere-evaluated after 15 min- TABLE1 utes. Those still showing incompletedresponse Clinical asthma score were given subcutaneousadrenaline and intrave- Score RR Wheeze Accessorymuscle use Dyspnea noussteroids and were excluded from study. 030 Nil Nir Nil Severe: Nebulisationwith salbutamoUterbu- I 3l-45 Mitd Mild Mild 2 46-ffi Moderate Moderate Moderate taline0.15 mg/kg diluted with two ml normalsaline 360 Severe Severe Severe over period of five minutes.Continuous oxygen inhalation was given (8 lit/min) through nebu- liser/mask/trood. Patientswere re-evaluatedafter All the childrenwere given nebulisation with Bz 15 minutes.If PEFR40Vo of baseline/normal or agonist(salbutamoVterbutaline). The cases of salbu- children who could not generatePEFR but their tamol andterbutaline were selected randomly using clinicalasthma score less than 8, a repeatnebulisa- randomnumbers. The protocol for the acuteman- tion with samedose was given. They wererevealed agementof bronchialasthma was as follows : after 15 minutes.Those who werepoor responders Mild : Nebulisationwith salbutamoUterbutalineafter2nd nebulisation(PEFR 507o, clinical asthma 0.1 mg/kg diluted with 2 ml normal salineover score6) they wereconsidered for furthernebulisa- periodof five minutes.Re-evaluated after 15 min- tion, intravenoussteroid, subcutaneous adrenaline utes,if symptomatologypenisted and PEFR 507o of and were excludedfrom the study.Children who normaUbaseline or improvementin PEFR 207o, werepoor respondersafter lst nebulisationPEFR secondnebulisation with samedose was given after 407oof baseline / normaland clinical asthma score

TABLE 2 Estimation of severity of acute asthma

Sign/Symp Moderate

Respiratoryrate Normal to I SD increase Normal to 2 SD increasefor age 2 SD incrcase for age Dyspnea Absentor mild Moderate,speaks in phrascsor Severc,speaks only singleword speakscomplete s€ntences partial sentences or shortphrases Pulsusparadoxus l0mmHg lG20 mmHg 20-40mm Hg Accessorymuscle No intercostalto mild Moderateinlercostal reEaction Severeintercostal and tracheosternal usage retractions with tracheosternalretractions. retractionwith nasalflaring. useof sternocleidomastoid muscles Colour Gocd Pale Possiblycyanotic Auscultation End expiratorywheeze only Wheezeduring entirc cxpiration Breathsounds becoming inaudible and inspiration Oxygensaturation 95% w95% %% PEFR 7(}90% prcdictedor 50.70%predicted or penonal best 50% predictedor personelbest. personalbest. t22 Jour. Martne Medical Society,July-Dec 1999,Vol. I, No.2 -8 they were consideredfor intravenoussteroid and S/T singlenebulisation (ii) Terbutaline(n=9) sub cutaneousadrenaline after lst nebulisationand Group 2 Childrcn with Modsevere (i) Salbutamol(n=10) attack wereexcluded from study. (nz=16) Nebulisedwith 0.15mg/kg/ (ii) Terbutaline(n=6) Thosewho did not havea baseline PEFR,their doseS/T singlenebulisation baseline was taken from PEFR normogramchart Group 3 Childrenwith Mod/severc (i) Salbutamol(n=9) attack tel. (m=lE) Nebulisedwith 0.15mg/kg/ (ii) Terbutaline(n=9) All thosewho fulfilled the criteria,2 ml venous doseS/T nebulisedtwice blood wascollected in a 5 ml graduatedlest tubeby disposableneedle and syringewith all asepticpre- Seventeenchildren had mild attackand werein cautions.Repeat samples were collected at 30 min- groupI.Eight out of themwere administered salbu- utes,90 minutes,120 minutes after nebulisation. An tamol(0.1 mg/kg) and nine administered terbutaline ECG recordingwas'taken at 90 minutesafter nebu- (0.1mg/kg). The resultsare as depicted in Table3. lisation.Test tubes were marked as sample I (before Meanpotassium before nebulisation (salbutamol nebulisation),sample 2 (after30 minutes),sample 3 0.1 mg/kg) was 4.2 meq/lit, at 30 minutesafter (after90 minutes),sample 4 (after120 minutes). The nebulisationwas 4.01 meq/lit (mean fall0.2 meq/lit serumwas subjected to estimationof potassiumand (SD-0.65) (P0.001) at 90 minutes afternebulisation sodiumby flamephotometry. was3.9 meq/lit(mean fall0.36 meq/lit(SD -0.075) (P = 0.001)and at 120 minutesafter nebulisation Data analysis was4.1 meq/lit(mean fall0.l meq/lit(SD - 0.075) Fifty onechildren with acuteasthma fulfilled the (P=0.01).The maximumfall had beenrecorded at inclusion criteria and constitutedthe study group. 90 minutesand the mean is 0.36meq/lit (SD - 0.075) l2Vo cases(6 children) had their lst anack (not (P = 0.001). known caseof bronchial asthmanor had any past Meanserum K* beforenebulisation (Terbutaline historyof breathlessnesswith wheezing).The chil- '/2 0.1 mg/kgbody wt) was4.18 meq/lit after30 min- dren werein the agegroup of I yearsto I I years. utesof nebulisationwas 3.97 meq/lit (mean fall0.2l The male : femaleratio was 15 : 36. 15% of the meq/lit) (SD - 0.1), (P = 0.001) at 90 min after childreneither had associated upper respiratory tract nebulisationwas 3.7 meq/lit (Mean fall0.27 meq/lit) infectionand or fever.All thecases were divided in (SD- 0.07)(P= 0.001).The maximum fall hasbeen three broad gxoups.Each group was further subdi- recordedat 90 minutesand the mean is 0.45meq/lit. videdinto two groupsas follows (n=51). (SD- 0.11)(P = 0.001).

Group I Children with mild attack (i) Salbutamol(n=8) Themean serum K* beforenebulisation in group (nr=17) Nebulisedwith 0.1 mgAg/dose I i.e. both salbutamoland terbutalinewas 4.19

TABLE 3 Scnrm potassium (S.K) in padents ncbullsed with 0.1 mg/kg of salbutamol (s) and terbutaline (I) in Meq/Lit

S. K. before S. K. aftcr S. K. after S. K. after Maximum fall nebulisation 30 minutcs 90 minutes 120minutes s-r --T s-- S-r s------T 4.9 4.2 4.7 3.8 4.5 3.6 4.8 3.0 0.4 0.6 4.2 4.1 4.0 4.0 3.8 3.7 4.0 4.0 0.4 0.4 4.3 4.0 4.0 3.9 4.0 3.6 4.2 3.7 0.3 0.4 3.8 4.2 3.6 3.9 3.4 3.6 3.7 4.0 0.4 0.6 4.0 4.2 3.9 4.0 3.E 3.9 4.0 4.0 0.2 0.3 4.0 4.0 3.9 3.8 3.6 3.6 4.1 0.4 0.4 4.2 4.1 4.0 4.0 3.8 3.6 4.0 3.8 0.4 0.5 4.2 4.2 4.0 4.0 3.8 3.8 4.0 3.9 0.4 0.4 - 4.6 - 4.4 - 4.1 _ 4.3 - 0.5

Jour. Marine Medical Society,July-Dec 1999,Vol. I, No.2 123 TABLE4 Senrmpotassium (S.K.) in patientnebulised with 0.15mg/kg salbutamol (s) and terbutaline (T) in Meq/Lit

S. K. beforc S. K. after S. K. after S. K. after Maximumfall nebulisation 30 minutes 90 minutes 120minuets serumK ST ----T ------T s------T s------4.3 4.6 4.1 4.2 4.8 3.9 - 4.0 0.3 0.7 4.2 4.6 4.0 4.4 3.8 4.0 4.0 4.2 0.4 0.6 4.2 4.4 4.0 4.r 3.8 3.8 4.0 4.2 o.4 0.6 4.2 4.2 3.9 4.0 3.7 3.6 4.0 3.8 0.5 0.6 4.0 4.1 3.8 3.9 3.6 3.6 3.9 3.9 0.4 0.5 4.3 4.2 4.2 3.8 3.8 3.6 4.0 4.0 0.5 0.6 4.3 4.2 3.8 4.0 0.5 4.4 4.0 3.8 3.9 0.6 4.2 4.0 3.8 3.8 0.4 4.2 3.9 3.6 4.0 0.6 meq/litafter 30 minuteswas 3.99 meqnit (mean fall (meanfall 0.46meq/lit) (SD - 0.05)(P = 0.001 ), after is 0.2 meq/li$ (SD - 0.082) (P = 0.001)after 90 120 minute was 3.95 meq/lit (Mean fall 0.28 minuteswas 3.75 meqnit. (Mean fall is 0.4 meqni$ meq/lit)(SD - 0.12)(P = 0.001).The maximum fall (SD 0.103)(P = 0.001),after 120 min was 4.01 wasrecorded at 90 minuetswith meanfall of 0.46 meqnit(mean 0.18, SD 11,p 0.001. meq/lit(SD = g.g5;(P = 0.001). The maximumfall was recordedat 90 minutes Meanserum potassium before nebulisation (ter- andthe mean was 0.4 meq/lit (SD - 0.10) (P = 0.00I ). butaline0.15 mg/kg body wt) was4.35 meq/lit, after In comparingthe hypokalemiceffect of salbutamol 30 minutesit was 4.06 meq/lit (Mean fall 0.29 versusterbutaline there is no significantsdifference. meq/lit)(SD - 0.09)(P = 0.001),after 90 minutesit (SE(d) = 0.45)(unpaired t test). was3.75 meq/lit (Mean fall0.6 meq/lit)(SD - 0.64) (P = 0.001),after 120 minuets it was4.01 meq/lit An ECGwas recorded in all casesat 90 minutes. (Meanfall0.34 meq/lit) (SD - 0.16)(P = 0.01).The Noneshowed any evidence of arhythmiaor hypoka- maximumfall was recordedat 90 min meanfall lemicchanges. There was a significantrise in heart being0.6 meq/lit(SD - 0.06,+)(P = 0.001). ratebetween baseline (i.e. beforenebulisation) and at 90 min (calculatedfrom (ECG).In salbutamolsub Themean serum K+ beforenebulisation of group - groupthe meanrise was 3llmin (SD - 9.3) (P = 2 (thatis bothsalbutamol and terbutaline)was4.21 0.001)and in terbutalinesub group mean rise was meq/lit;at 30 minuteswas 4.03 meqAit(Mean fall - 30.5/min(SD - 0.ll) (P = 0.001).There was no was 0.24 meqflit) (SD 0.096)(P = 0.001)at 90 significantdifference between salbutamol and ter- minuteswas 3.98 meq/lit (Meanfall 0.29 meq/lit) - butalinein increasingheart rate (SE (d) = 4.9) (P = (SD 0.196)(P = 0.001).The maximumfall was 0.1). recordedat 90 minutesand the mean being 0.5 meq/lit(SD - 0.1l) (P = 0.001).The hypokalemic Thirty four childrenpresented with moderateand effectof salbutamolvs terbutalinewas statistically severeattack of asthma.16 childrenout of them significant(Terbutaline being higher) (SE (d) = respondedto singlenebulisation with eithersalbu- 0.03)(P = 0.001)(unpaired t test). tamolor terbutaline0.15 mg/kg and constituted the An ECGwas recorded in all casesat 90 minuets Group 2. In group two, l0 children were given and none showedany evidenceof arrhythmiaor salbutamoland six terbutaline.The resultsare de- hypokalemicchanges. There was a significantrise pictedin Table4. in heartrate from baseline (i.e.before nebulisation) Meanserum potassium before nebulisation (Sal- andat 90 minute(calculated from ECG).In salbu- butamol0.15mg/kg body wt) was4.23 meq/lit, after tamol sub groupthe meanrise was 3?min (SD - 30 min was4.01 (mean fall was0.22 meq/lit) (SD - 13.5)(P = 0.001)and in terbutalinesub group the 0.009)(P= 0.001)after90 minutes was3.77 meq/lit meanrise was 4llmin (SD- 2.8)(P = 0.001).There

124 Jour. Marine Medical Society,July-Dec 1999,VoL I, No.2 -l.lnln s Serum K+ in patients nebuliscd with satbutamol (s) 0.15 mg/hg (2 dmages)and terbutaline (T) 0.15 mg/kg (2 docage)in meqAit

S. K. before S. K. after S. K. after S. K. after Maximum fall nebulisation 30 minutes 90 minutes 120 minutes serum K

ST STST ST ST 4.2 5.2 3.8 4.8 3.6 4.4 3.5 5.0 0.7 0.8 4.2 4.6 3.8 4.2 3.6 3.8 4.1 4.0 0.6 0.8 4.6 5.2 4.2 4.6 3.8 4.4 4.2 4.4 0.8 0.8 , 4.6 4.1 4.t 3.6 3.6 3.2 3.9 3.4 1.0 0.9 4.4 4.2 4.0 3.6 3.6 3.4 3.8 3.5 0.8 0.8 4.2 3.8 3.8 3.6 3.6 3.2 3.6 3.4 0.6 0.6 4.2 4.4 4.0 4.0 3.6 3.6 3.4 3.8 0.8 0.8 ' 4.4 4.2 4.2 4.2 3.6 3.8 3.4 3.4 0.6 0.8 4.6 4.4 4.3 3.8 3.7 3.5 3.9 3.6 0.9 0.9

was no statisticallysignificant difference between (P = 0.001),at 90 minuteswas 3.65 meq/lit (Mean salbutamoland terbutaline (SE (d) = 4.5) (P = 0.05) fall was0.77 meqflit) (SD - 0.12)(P = 0.001),at 120 in increasingheart rate. minuteswas 3.844 meq/lit (Mean fall was 0.58 Eighteenchildren who had mod/severeasthma meq/lit)(SD - 0.0I I ) (P= 0.00I ). Themaximum fall requireda secondnebulisation l5-20 min afterthe wasrecorded most of thetime at 90 minutesand the I stnebulisation, constituted group III. Ninechildren meanmaximum fall was0.78 meq/lit (SD - 0.108) wereadministered salbutamol and nine terbutaline. (P = 0.001).The hypokalemiceffect of salbutamol Theresults as depicted in Tablti5. VS terbutaline(Fig. 7 & 8) was statisticallynot significant(SE (d) = 0.052)(p = 0.1). Mean serum K' before nebulisationof 0.15 mg/kg body wt of salbutamolrepeated after 15-20 An ECG wasrecorded in all casesafter 90 min- min was 4.37 meq(it, after 30 minute was 4.02 utes,none showedany evidenceof arrythimaor meq/lit(Mean fall was0.35 meq/lit) (SD - 0.095)(P hypokalemicchanges except in one casewhich = 0.001),after 90 minutewas 3.65 meq/lit (Mean showedQTC of 0.45 sec.,ST depressionand U fall was0.72meqAit) (SD - 0.15)(P - 0.001),after waveappearance in leadII.The serum K'at thetime 120minutes was 3.8 meq/lit(Mean fall was0.57 of recording(at 90 min) was3.2 meq/lit.There was meq/lit)(SD - 0.21)(P = 0.001).Most cases maxi- significantrise in heartrate from the baseline (i.e. mum fall hadbeen recorded at 90 minutesand the beforenebulisation) and at 90 minutes(calculated meanmaximum fall was0.77 meq/lit (SD - 0.14)(P from (ECG).In salbutamolsub group the meanrise = 0.001). was47 (SD- 15.3)(P = 0.001)and in terbutaline - Meanserum potassium before nebulisation with subgroupthe meanrise was 38.5 (SD 10.2)(P = 2 dosageof terbutaline(0.15 mg/kg body wt) was 0.001).There was no statisticallysufficient differ- 4.47 meq[it, after 30 minuetsit was 3.97 meq/lit encebetween salbutamol VS terbutalinein increas- = =0.1). (Meanfall was0.5 meq/lit) (SD - 0.15)(P = 0.001), ing heartrate (SE (d) 6.1)(P after90 minutesit was3.66 meq/lit (Mean fall was The meanmaximum fall of potassiumwith sal- - 0.62 meq/lit)(SD 0.19)(P = 0.001)being 0.81 butamol in group I (0.1 mg&g/dose)was 0.36 - meq/lit(SD 0.0871)(P = 0.001).The maximum meq/lit (SD - 0.075) and in group II (0.15 fall wasrecorded at 90 minutes,mean fall being0.81 mg/kg/dose)as 0.46 meq/lit (SD - 0.05).The hy- meq/lit.(SD 0-0.087) (P = 0.001). pokalemiceffect was significantly higher (P = 0.01) The meanserum K+ beforenebulisation in group with higherdoses (unpaired t test).The meanmaxi- III that is nebulisationwith salbutamoland terbu- mumfall of potassiumin groupIII (0.15mglkg/dose taline2 dosageswas4.42 meq/lit at 30 minuteswas repeatedafter 15 min) was 0.77 meqAit (SD - 0.14). 3.94meq/lit (Mean fall was0.4 meq/li$ (SD - 0.135) Thehypokalemic effect was higher in groupIII than

Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 125 TABLE5 Comparadvetable between various studies rnd prescntstudy

Nameof the studyDrugs and dosage Maximum fall of Comments Remark and rcfererrce K* in meq/lit

Burgess Salbutamol 0.26meq/lit 9 adult asthmatics Comparableto presentstud et al [L0l (s mg) at 60 min I I children with end stage Significantly highcr McClure Salbutamol 0.75meqnit chronicrcnal failure with than the presentstudy. et al Ull (2.5mg, 25 kg at 90 min initial high potassium 5 mg, 25 kg wt) lnatlza Salbutamol l.l2 meq/lit 15 adult patienton chronic Significantly higher present et al ll2l (20 mg) at 90 min haemodialysiswith initid study (Nebulisedwith high dose) high serumK+ Burgess Salbutamol 0.33mcq/lit Healthy Comparableto presentstudy et al [3] (5 mg) (60-90min) voluntecrs Comparableto prcsentstudy Terbutaline 0.7meq/lit Healthy (Significant difference (s mg) (90.120min) voluntccrs betweensalbutamol vs Terbutalineis comparablcto group II of prcsentstudy) Dickens Salbutamol 0.8 meqnit l0 adult Fall in serumK' significantly et al[l4l (2.5mg) (75-120min) asthmatics higher than present. Lior Salbutamol 0.85meq/lit 15adult Fall in serumK* et alUSl (10mg) at 90 min patientsCRF significantly higher Allon Salbutamol 0.53 meq/tit 15adult end Comparableto prcsentstudy et al 116l (10mg) at 60 min stagerenal failure Bodenharner Salbutamol(2.5 mg) 0.55 meq/lit at 90 min 20 adult asthmatics Comparableto presentstudy et al ll7'l Repeatedevery 30 min and0.65 Meq at 180min Present Salbutamol 0.36mcq/lit 5l children The resuttsare comparableto study (0.1 mg/kgldose) 90 min with acuteasthma studiesreviewed Terbutaline 0.45 meq/lit (0.1mg/kg/dose) 90 min Salbutamol 0.46 meqnit (0.15mg/kg/dose) 90 min Terbutalinc 0.6 meq/lit (0.15mg/kg/dose) 90 min Salbutamol 0.77meq/lit (0.15meAg/dose) 90 min rcpeatedafter 15 min) Terbutaline 0.81meqAit (0.15mgAg/dose) 90 min. repeatedafter 15 min)

$oup II (P = 0.001)(unpaired t test). meqnit(sD - 0.87). The meanmaximum fall of potassiumwith ter- Thehypokalemic effect was significantly higher butaline in group I (0.1 mg/kg/dose)was 0.45 in groupIII than goup II (P = 0.001)(unpaired t meqnit (SD - 0.11) and in group II (0.15 test).This showsincrease hypokalemic effect on mg/kg/dose)as 0.6 meq/lit (SD - 0.64).The hypoka- higherdose. lemiceffect was significantly higher (P = 0.01)with Serumsodium was estimatedin all casesalong higherdose (unpaired t test).The meanmaximum with serumpotassium. Serum sodium did not show fall in potassiumin group III (0.15 mg/kg/dose anychange with B2 agonistnebulisation. repeatedafter 15 min) with terbutalinewas 0.81 r26 Jour.Marine Medical Society, JuIy-Dec 1999, Vol. I, No.2 CONCLUSIONS of Diseasesof Children 1984;138 : 574-6. It canbe concludedfrom the observationsin the 8. Guidelinesfor diagnosisand managementof asthma.Na- presentstudy that thereis a significantdecrease in tionalheart lungs and blood institute, National asthma edu- serumK' level after nebulisationwith 82 agonist cation programme.Expert panel rcport. Joumal of Allergy namely salbutamoland terbutaline.The time of and Clinical Immunologyl99l; 88 : 425-34. maximumfall of serumK+ is around90 minutes 9. GodfrcyS, KamburoffPL, NairnJR, eral. Spirometry,lung afternebulisation with 82 agonist.The hypokalemic volumesand airway resistancein normalchildren aged5 to effect startsat 30 min andpersists at 120min after l8 years.Bit J DisChest 1970;&: 15-24. nebulisation.It is also concludedthat the fall of 10. BurgessCD, BremmerP, Thomas CD, CraneJ,Silbers RW, serumK' after Bz agonistnebulisation is dosere- BeasleyR. NebulizedBz agonistdo not effectplasma sele- lated, with higher dose the fall is significantly nium, glutathione,peroxidase activity in patient with higher.Repeated dosages further decrease serum K' asthma.Inte mational J ournal of Clinic al Pharmac ol ogyand levels.In thepresent study, it is observedthat there Therapewics 1994;32 (6) : 2W2. wasno statisticallysignificant difference in hypoka- lemiceffect of salbutamoland terbutaline. It is con- ll. McClure RI. PrasadVK. BrocklebankJT. Treatmentof cludedfrom the observationof the study that Bz hypokalemiausing intravenous and nebulisedsalbutamol. (2): agonistsnebulisation in therapeuticdoses cause sig- Arch DisChild 1994;'10 126-8. nificantincrease in heartrate but do not causecar- 12. l*anzaHJ, RivarolaG, GracialaGM, NajunZ CJ,Casadei diac anhythmiain non cardiaccompromised pa- D. Rapidcorrection of acutehyperkalemia with nebulized tiens. ECG may showchanges conelating hypoka- salbutamol.Medirc(B Aires)1992; 52 (2):99-102. lemia. 13. BurgessCD, Flatt A, SiebersR, CraneJ, BeasleyR, Purdie REFERENCES G. A comparisonof extent and duration of hypokalemia following threenebulised beta-2 adreno receptor agonists. 1. Stella,O'Donell R. Developmentof betareceptor agnonist EuropianJoumal of ClinicalPharmacology 1989; 36 (4) : drugs.The role ofbeta receptoragonist therapy in asthma 4t5-7. mortality,edited by R. Beasleyand Neil E Pearce1993. 2. Brittain RT, FarmerJB, Jack DJ. A selectiveB adrenergic 14. DickensGR, McCoyRA, WestR, StapezynSki JS,Clifton stimulant,Nature 1968;219 : 862. GD. Effect of nebulisedalbuterol on serumpotassium and cardiacrythm in patientwith asthmaor chronic obstructive 3. HartleyD, JackD, Lunts LIIT, RitchioAC. New classof pulmonarydisease pharmacotherapy. 1994; 14 (6) :729-33. selectivestimulants of B adrenergicreceptors. Nature 1968: 219:861. 15. Liott HH, ChiangSS, Wu SC, HaungTP, ComposeVM, 4. PedersenS. Choice of inhalationtherapy in paediatrics. SmogorzewskiM, Yang WC. Hypokalemiceffect of intra- Europeanrespiratory review. 1994; 4 : 15-88. venousinfusion or nebulisationofsalbutamol in patientwith ch,ronicrenal failure; comparativestudy. Arnencan Journal 5. MartinJ Kendall,Christine A Haffner.The acute unwanted of Kidneydiseases 1994t 23 (2) : 26G7L. effect of 82 receptorantagonist therapy. The role of beta receptoragonist therapy in asthmamortality, edited by R 16. Allon M, ShanklinN. Effectof bicarbonateadministration Bearleyand Neil E Pearce1993. on plasmapotassium in dialysispatients : Interactionwith 6. PullelaRama Devi, Latakumar,Sunit C Singhi,Rajendra insufin and albuterol.Amen:can Journal of Kidney diseases Prasa(Minusingh. Intravenous magnesium sulfate in acute 1996;28(44):508-14. severeasthma not r€spondingto conventionaltherapy. Indra 17. BodenhamerJ, BergstromiR, BrownD, GabowP, Marx JA, Pediateics 1977:34 : 389-91. LowensteinSR. Frequently nebulized B2 agonists for asthma 7. BeckerAB, NelsonNA, SimonsER. The pulmonary index : : Effects of serumelectrolytes. Ann EmergencyMedicine Assessmentof a clinical scorcfor asthma.Americaa Journal 1992;2l (ll) : 133'l-42.

Jour. Maine Medical Society,July-Dec 1999,Vol. I, No.2 127 Case Reports CONGENITAL MALARIA - A REPORTON TWO CASES

Surg Lt Cdr S NARAYAN*, Surg Lt Cdr V HANDE+, Surg Lt Cdr N NATH#

INTRODUCTION maximum of 7.5 mg/dl on day I of lie and then regressed spontaneously. ll speciesof malarialparasites are known to A the follow-up U" transmiftedtransplacentally from mother At last at six months age, the baby exhibited A normal growth and developmental profile. He has rcmained l- Ito the foetusand this modeof transmission asymptomatic and parasitefree during this period. is morecommon in non-immunemothers []. De- spitethis, congenitalmalaria occurs in fewer than Casc 2 57o newbornswhose mothers are infectedand is A 23 years primigravida lady had recurrent episodes of fever directlyrelated to theparasite density in theplacenta with chills and hepatosplenomegalyin the 5th, ?th and 8th month of her pregnancy. All routine investigations were normal and [2]. Neonatalmalaria, on the otherhand, is less multiple blood smearson each of these occasionswere negative uncommonand may result from mingling of in- for malarial parasite. She was treated with chloroquine for cach fectedmaternal blood with thatof the infantduring of theseepisodes and respondedwell each time. the birth process[3]. We presenttwo casesof ma- She delivered a full term, 32fi) gm male baby by spontaneous laria in early infancy from a region endemicfor vaginal delivery. There was no neonatal complication and the malaria. baby was being exclusively breast fed. At 40 days life, the baby was noticed to have "mild cough and CASEREPORTS cold" by the mother for which she sought medical attention three Case I days later. During this time the baby was feeding well and there was no change in his cry and activity. A 29 years second gravida lady was admitted one week before her EDD with high grade fever and chills of one day duration. At admission, the baby weighted 4200 gm, was markedly She had beentreated with chloroquine for malariatwo yearsback. pale, normothermic and had a splenomegaly of six cm with the There was no abnormality on clinical examination. Blood counts liver being palpable 1.5 cm below the right costal margin. There and urine tests were normal. Repeated blood smears failed to was no evidenceoftachycardia, tachypneaor cardiac failure. The reveal any malarial parasite. However, she respondedwell to a baby's hemoglobin was 3.5 gm/dl and peripheral blood smear standard course of chloroquine. revealed ring forms and trophozoites of P. vivax with evidence of cellular hypoplasia. Nine days after admission, she delivered a full term male by spontaneousvaginal delivery. On day four of life, the neonate The baby was treated with chloroquine suspensionand two became lethargicr cry was week and he was not feeding. Clini- transfusionsof whole blmd (20 mUkg body weight/transfusion). cally, temperature was 101.6T, mild icterus was present,a two The baby improved rapidly with the hemoglobin rising to 10.3 cm hepatomegalyand 1.5 cm splenomegalywas detected.Blood gm/dl and the splenohepatomegalyregressing completely by the counts were normal. Peripheral blood smears demonstratedP. 8th day of admission. The baby was discharged on oral iron and vivax. Serum bilirubin was 4.0 mg/dl-, predominantly unconju- multivitamin supplements. gated. On follow-up, the baby has rcmained asymptomatic; clini- gain The neonate was treated with oral chloroquine and made cally therehas been appropriate weight without any evidence was prompt recovery. By the end of the first day of treatment, he ofpallor, hepatomegalyor splenomegalyand the hemoglobin gn/dl. became normothermic, cry and activity improved and he started at 9.3 The baby continues to be on oral iron and multivi- accepting breastfeeds. By the third day oftreatment, parasitemia tamin supplementsand regular follow-up. had cleared off and subsequentblood smearswere negative at 14 DISCUSSION and 28 days of life. Icterus, which was most probably physiologi- cal, was throughout predominantly unconjugated; reached a Congenitalmalaria has been recognised from as

*Graded Specialist (Pediatrics); +Graded Specialist (Medicine); *lGradedSpecialist (Pathology); INHS Dhanvantari, Oo Navy Office, Port Blair - 744 102.

128 Jour.Marine Medical Society, July-Dec 1999,Vol. I, No.2 earlyas a few hoursafter birth to uptoseven weeks is appropriatein this patientkeeping in mind the after birth []. Vertical transmissionof malariais antenatalmaternal clinical profile, demonstration of diagnosedby demonstratingparasitemia in theneo- parasitemiain the baby and severeanemia in an natewithin sevendays of birth or laterif thereis no otherwisehemodynamically stable infant thus indi- possibilityof postpartummosquito-borne transmis- cating the anemiato be graduallyprogressive in sion [4]. Most evidenceindicates that congenital nature. prevalence malariais extremelyrare despite the high Bothpatients responded very well to chloroquine placental of infection[,5]. andhave been doing well on re-assessmentat fol- In children,the clinical presentationof malaria low-ups. may not be typical and this is more so in areas endemicfor thedisease[6]. Clinical features of con- The aim of this reportis to documentthese rare genital malariainclude non-specificfeatures like casesof congenitalmalaria as well as to highlight fever, irritability, feedingproblems, jaundice and the importanceof early diagnosisand treatment of patients hepatosplenomegaly.Unless parasites are demon- these to avoid life+hreateningcomplica- stratedin theblood, the babymay be misdiagrosed tionsof this treatabledisease. as having Rh/ABO incompatibilityor other con- REFERENCES genitalinfections [4]. Hence,the diagnosisof this conditionrequires a highindex of suspicion[,4]. l. Immunity, immunization and infectious diseases : Report and recommendations of the committee on immunization. Complicationsof malariain this agegroup in- Indian Academy of Pediatrics 1994; 15G7. cludeseizures, hypersplenism, splenic rupture, de- hydrationand obstructivejaundice. It is therefore 2. White NJ, Breman JG. Malaria and Babesiosis. In : Issel- imperativethat congenitalmalaria be promptlydi- bacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci AS, Kasper DL Editors. Harrison's principles of intemal medi- agnosedand treated [,5]. cine. l3th ed. New York : McGraw Hill, 1994: 887-95. In thefirst newborn, the mother had a pasthistory of malariaand in the late last trimestershe again 3. Clyde DF. Malaria. In : Behrman RE, Kliegman RM, Arvin presentedwith clinical featuresof malaria. AM. Editors. Nelson textbook of pediatrics. l5th ed. Banga- lore: WB Saunders,1996;974-8. Though slide negative,she respondedwell to chloroquine.The newbornhad non-specific symp- 4. Bradley D, Newbold CL, Warrel DA. Malaria. In : Weather- tomsand signs and was proved to haveparasitemia all DJ, Ledingham JGG, Wanel DA. Editors. Oxford Text- on fourth day of life itself, thus qualifying for a book of Medicine. 3rd ed. Oxford : Oxford Universitv hess. diagnosisof congenitalmalaria. 1996;848-9. In the secondpatient, the mother was treated 5. Malaria in India. In : Park JE, Park K. Editors. Textbook of successfullyfor malariathrice during her pregnancy preventive and social medicine. l2th ed. Jabalpur : Banarsi- despitebeing MP negativeon slideexamination. At das Bhanot, 1990; 183-6. 43 daysof life, the babywas shown to harbourthe 6. Malaria. In : Ghai OP. Essential pediatrics. 4th ed. New malarialparasite. A diagnosisof congenitalmalaria Delhi : Interprint 1996;144-9.

Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 t29 CONGENTIAL CYST OF THE SPLEEN_ A CASE REPORT

Lt Col G RAVINDRANATH, VSMi, Surg Capt RAMESH KIJMAR*I, Surg Cdr G GIIPTA#, Dr. TANVEER A MAJEED+

KEY WORDS: SimpleCongenital Cyst of the Spleen;Splenic Epideruoid

INTRODUCTION transverseincision, the spleenwas mobiliscd and rcmoved taking careto pack off thc peritoncalcavity to prevcntaccidental spill- flystic conditionsof the spleenare relatively age.Interestingly, a large lymph node was found at the 3plenic I uncommon entities in clinical practice. hilum. \-/When seen,two-thirds are parasitic lesions Examinationrevealed spleen size l4xEx4 cms with a cyst and the remainingone-third are non-parasiticcysts wall on lateral sspectmeasuring 6x5 cms with glistening outer capsulewith trabeculationon inner wall. Cyst cavity was filled [U. Of the latter, a large number (70-8OVo)are with 60 ml of strawcoloured fluid- (Frg. l), pseudo-cysts,following splenic trauma or cysts Microscopyrcvealed cyst wall surroundcdby normal splenic which occur following Malaria, Infectious mono- tissue.Cyst wall wascomposedof flattenedorcuboidal epithelial nucleosis,tuberculosis or syphilis. lining dcnudcdat most places.No evidenceof fibror reaction. Fluid revealedoccasional macrophages with no echinococcal The remaining207oarc congenital splenic cysts, [email protected]). also called Epidermoidcysts, true dermoidsor pri- Lymph noderevealed reactive hyperplasia with subcapsular mary congenitalcysts [2,3]. Congenitalsplenic locationofcalcified adult filaria worm. (Fig. 3). cystsare thus relatively rare. One such case in a l0 DISCUSSION yearold child is reported. Congenitalsplenic cysts originate from in-fold- CASEREPORT ing of peritonealmesothelium during splenic devel- A l0 yearold fcmalechild prescntedwith historyof rccurrent anacksof left upper abdominalpain. Thc pain was of moderate opment.These cysts are lined by flattenedor cuboi- intensity, dull aching in characrcrand occasionallyradiating to dal epitheliumof which lOVoare lined by squamous the left shoulder.Thcre was no aggravatingor relieving factc. epithelium.Their sizemay vary from smallto rela- There was history of two attacksof fever with chills.andrigors. tively largecausing pressure symptoms in the form On examination - Averagely built and nourished No pallor iicterus or lymphadenopathy. ? l,ocal exam of abdomenshowed no relevantfindings. There was no organomcgaly.Other systems- NAD Invcstigationsrevcalcd - Hb - lO.7gm%,TLC - 5,300/cmm, DLC - Pooks Mor EOz, Plateletcount - 2,69,00/cmrl PCV 32.8%,Urine - RE/IvtE- NAD, Plain X-ray aM - NAD USG aMomen revcaledan cchoeicarca in the splcenmeas- uring,Ox5(h33 mm with spottycalcification within thc cyst with layering and medium amplitudcechoes and thickencdcyst wall suggestiveof hydatidcyst. However, indirect haem-agglutination test for hydatid was negative. She wastreated with Tab Albendazolel0 mg/kg/dayfor six weeksfollowing which USG wasrepeated" This showedthat the cysthadrcmainedthe same size inspite of reatmentandasurgical consultationwas sought. Keeping in view, the clinical picture and the sizc ofcys! a curativesplenectomy was planned- Using a left upperaMominal Fig. I : Postsplenectomy specimen shoqirlg a largecyst.

rCtassifiedSpecialist (Surgery andPaed. Surgery); *rscnior AdviserinSurgery; rClassified Specialist (Paediatrics); Trainee (Surgcry), INHS ASVINI, Colaba Mumbai 400 005.

t30 Jour. Marine Medical Society,July-Dec 1999,Vol. I, No.2 Fig. 3 : Inci&ntal finding of an adult filarial worm in r Esectcd lymph nodc. mostwidely usedmethod of diagnosis,othen being CT Scanand Arteriography. Immuno-Histochemis- try demonshatesCEA-CA 19-9 in inner epithelial layerimplying mesothelial origin [4]. Smallerasymptomatic cysts are kept under ob- -Cyst servationwith serial ultrasonography.Larger ones Fig. 2 : wall compoccdof ftatrcncOor Cuboidalepithelial arereated by splenectomyas performed in this case. lining (Haematoxylin Eosin stain lfl) x). ld RETERENCES of aMominal pain or pain referredto left shoulder. l. Maingot Abdomind SurgeryVol tr 9th Edition Chapter8l Pressuresymptorns related to compressionof adja- page1679. cent sEucture of stomach, colon occur less fre- 2. Epi&rmoid Cyst of Splen. Journat of Medical Science quently. l99l;45 (4) : EE-90. Physicalexamination may reveala smoothmass 3. Epidcflnoid Clst of Splcen.Turkish Jounul of Paediatrics in left upperquadrant.Inthis child, the mass was too 1989t3:2337. small to be palpable.Plain X-ray may revealspheri- 4. DtschMed WochenSchr. l99l; l16 (37) :137783 cal masswith calcification. Ultrasonographyis the

Jour. Marhe Medical Society,July-Dec 1999,VoL I, No,2 I3I A CASE OF NATAL TEETH

I Surg Lt (D) SSCHOPRA*, Surg Lt Cdr V HANDE+, Surg Lt Cdr S NARAYAN++

INTRODUCTION are natal teeth in contrastto neonatalteeth which eruptwithin the fint thirty daysof life [4]. -f- Natal teeth are prematureeruption of teeth or tooth like structuresthat are presentat birth. The The aetiologyof this phenomenonis unknown, incidenceis reportedto be 1 in 2000-3500new born althoughin some instancesit follows a familial children[1]. Natalteeth are present at birthwhereas pattern.In experimentalanimals, the secretionof neonatalteeth appear in thefirst mouthof life [2]. A severalendocrine organs (thyroid/adrenals) may al- family historyof natalteeth or prematureeruption ter the eruptionof teethand likewise in humans,in is presentin I5-20Voof affectedchildren [3]. Usu- somecases of adrenogenitalsyndrome developing l-* earlyin life, prematureeruption may sometimesbe ally, one or two teetherupt early, most often the ,:i ,?i ffiFl #*#v f. deciduousand mandibular central incisor. The aeti- seen.Most casesdefy explanation[4]. ology of this phenomenonis unknown,although in A seriesof 18 casesof nataland neonatalteeth someinstances it follows a familial pattem[4]. hasbeen studied by Bermanand Silverstonewho reportedthat thesewere essentiallynormal teeth ,',#'q'l:'"#ii CASEREPORT A 26 year old primigravida delivered a term male neonate by compatiblewith chronologicalage of development t"*'' (LSCS). ;ij lower segment Caesarean Section It was an elective t5t. rl. !t LSCS and the indication for surgery was pregnancy induced ,.r.. ii) Attachment of gingival teeth is limited to the hypertension.The neonateweighted 3.2 kg. --a- gingival margin, with little root formation or bony Examination ofthe neonateshowed the baby to be normal in support. Natal teeth may be associatedwith cleft all respects.Systemic examination did not reveal any abnormality palate, Piene-Robin Syndrome, Ellis von Creveld of cardiovascular or respiratory systems.The baby did not have any obvious congenital anomalies or deformities. Syndromeand other anomalies[2].

Examination of the oral cavity revealed two well-formed Natal teeth may result in pain, refusal to feed and crowns of mandibular incisors. They were mobile and loosely may producematernal discomfort due to abrasionor attachedto the gingival margin. The palate was normal and there biting of the nipple during nursing [2]. Some teeth were no eruption cysts in the oral cavity. There was apparently may be mobile to the extent that there is danger of no family history on the side ofeither parent of similar premature displacement and possible aspiration and in these eruption of teeth. cases removal is indicated [4]. If possible, it is In view of the fact that the teeth were extremely mobile and desirable to leave the tooth in situ as it is likely to there was a definite thrcat of aspiration and the neonate was become stabilised within a short time as the other having difficulty in suckling, a decision was taken to extract the teeth. The teeth were extracted by gentle finger extraction with teeth in the arch erupt [4]. It must be stressedthat topical local anaesthetic(lignocaine hydrochloride gel IP) and decision regarding extraction must be made on an was associatedwith minimal bleeding. The teeth had well formed individual basis and extraction requires careful dis- crowns, root development was incomplete. The child has been sectionto prevent tearing ofthe tissueand excessive - followed up after six months there have been no furthereruption haemonhage [2]. of teeth and an X-ray revealed features consistent with radio- graphic frndings of a normal six month old child. REFERENCF.s

DISCUSSION 1. Johnson Ronald Odontologic diseases. In : Lynch MA, Brightman VJ, Greenberg MS. Editors Burket's Oral medi- Deciduousteeth that haveerupted into the oral cine. 8th ed. Philadelphia : JB Lippincott company. 1984; cavityare occasionally seen in infantsat birth. These 540-41.

+Graded #Graded *Denal Ofhcer; Specialist (Medicine); Specialist (Paediatrics)INHS Dhanvantari (7o Navy Office, Port Blair - 744 r02.

132 Jour.Marine Medical Society, July-Dec 1999, Vol. I, No.2 -l 2. The digestivesystem : Oral cavity. In : BehrmanRE, Klieg- 4. Developmentaldisturbances oforal andpara oral structures. man RM, Nelson WE, VaughanVC. Editors, Nelson rext In: ShaeferWG,Hine MK, Levy BM. Editors.A Textbook book of paediatric l4th ed. philadelphia : WB Saunders. oforal Pathology,4th ed.Bangalorc : Eastempress pvt. Ltd. 1992:923-7A. 1993|&-65. 3. King N, Lee A, Prematurelyerupted teeth in new born 5. BermanDS, SilverstoneLM. Natal andNeonatal teeth. Bn'l infants. pediatr J 1989;I 14 : 907_g. Deil J 1975i139 :361-62.

Jour. Martne Medbal Society,JuIy-Dec 1999,Vot. I, No.2 t33 - BOOK REVIEW f

ATLAS OF GYNAECOLOGIC ENDOSCOPY - SecondEdition Edited by Alan GA Gordon,B Victor Lewis & Alan H.De Cherney Pnblishedby Mosby-Wolfe, 1996,Pages 260 Hardbound,Price Rs. 4800/- ISBN 5637-5579-3

The secondedition of this extremelywell illusrated book is a starkcontrast from the lst one published in 1988when GynaecologicalEndoscopic Surgery was in its stagesof infancy.This edition is revolutionary becauseit reflectsquite well the evolution of endoscopyinto a field which will largely guide the futurc of GynaecologicSurgery. This volume covers in depth, all significant advancesin diagnostic and operative laparoscopyand hysleroscopyof the past decade.It has approx. 600 illustrations,of which 500 are in color, which very graphicallyillusEate the lucid t€xt and simple languageof the authors.The book hasthree main sections, oneeach on laparoscopyand hysteroscopy and third dealingwith generalissues in gynaecologicendoscopy like anaesthesiaand futurc tends. The strengthof this book lies in the profuseaccurale, clearly labelledand detailed color illustrationsthat areextnemely essential in the study andpractice ofendoscopy. It is a book that belongsin every endoscopy centre.The prohibitive cost makesit possibleonly for librariesto afford this book wherc it is a must.

SuTgLCdTAKAPUR Dept of Obst. & Gyn. INHS Asvini Colaba,Mumbai 400 005.

134 Joun Marine Medical Sdciety,July-Dec 199, VoL I, No.2 ') rlr\ JoURNALWATCH fur- rbu- Ernest AG Zinrak JD. Carbon Monoxide Polson- patientsorin theambient airatthe sceneof exposure line ing, N Engl J Med, 1998;339 : 1603-16ff/ can help confirm the diagnosis.hrlse oximetry rha- Carbon monoxide (CO) poisoningcontinues to cannot distinguishcarboxyhemoglobin from oxy- rfter be one of the most commoil causesof morbidity in hemoglobin.Thus, spectnophotometricevaluation rsis- the US, occurringmostly in winter. Major sourceof is mandatory.Neuropsychological screening for 30 nent CO is incomplete combustion of hydrocarbons. minutes provides a baseline for assessingsub- was Sourcesinclude motor vehicleexhaust fumes, paint sequentchanges in mentalstatus. CT scanof brain nin- removers,methyl chloride and poorly functioning is helpful to excludeother conditions.Treatment is )nse heating systems. Irthal corrcenEationscan be by removingthe patientsform the sourceof expo- ave- achievedin 10 minutes.CO is a colourless,odour- sure.High flow oxygenpreferably 100% as nonno- lessand non initant gasabsorbed through the lungs. baric oxygenshould be administeredto the patient It competeswith oxygenfor binding to hemoglobin immediately. In patients who have been rescued rbu- with an affinity of approximately240 times greater from a fire, specialconsideration should be given to iline than oxygen,causing shift of oxygenhemoglobin the respiratorystatus and the airway. |,gen dissociationcurve to the left. Free plasmaconcen- . Hyperbaricoxygen therapy (IIBOT) reducesthe ebu- tration is essentialto produceits pathogeniceffect half life of carboxyhemoglobin significantly, after while only carboxyhemoglobinis unableto produce thercbyreducing morbidity and mortality. Comais ilor this effect. Mechanismsof injury include hypoxi4 an undisputedindication for IIBOT. Other indica- their hyperoxygenationof proteinand lipid peroxidation. tions areunconsciousness, cardiac anhythmias pre- Iisa- CO has a harmful effect on pregnantwomen when existingcardiac illness and thosenot rcspondingto nled fetal concentrationsof this gas exceedthat in the normobaricoxygen therapy. rders mother.Clinical signs and sympto.msare non spe- Prevention includes public lhma cific and include tachypnea,nausea, vomiting, sei- education and in- rlisa- zures, syncope,coma, pulmonary edema,anhyth- crcasingthe awarenessof the dangersof carbon monoxide. prevention aline mias cherry red lips, cyanosisand retinal haemor- Secondary aims at warning pgople potentially who rhages.Necrosis of sweatglands is a characteristic about harmful CO concentration ,EF'R feature. in the environment.Proper maintenanceof appli- ancesand CO detectorsmay help in this endeavor.. scorc Delayed neuropsychiatic syndrome include cognitive and penonality changes,Parkinsonisnl dementiaand psychosis.Advanced age is a risk Contributedby: factor.The regionscommonly involved includethe Surg CdrPS TAMPI globuspallidus and deepwhite matter. ClassifiedSpecialist (Medicine and Pulmonology), Fordiagnosis,a high indexofsuspicion is essen- Deptof Medicine,INHS Asvini, tial. Increasedlevels ofCO in theexhaled air ofthe Colaba,Mumbai 400 005. rd sternal Anderson AIt Almgren T, et al. Survival in objectiveof this sttrdywas to comparcsurvival and treated hypertension : Follow up study after two causespecific mortality in hypertensivemen with decades,BI\[.I 19t; 317 z l6il-171. non hypertensivemen fromthe samerandom popu- Treatrnentofhypertension prolongs life andpre- lation and to study mortality and morbidity from vents or delays congestive heart failure, neph- cardiovasculardiseases in the hypertensivemen in rosclerosisand reducesthe incidenceofstnoke. An- relation to effects on cardiovascularrisk factors tihypertensiveEeatment has, however, been less during 22-23 yearsof follow up. It was a prospec- effective in preventingcoronary heart disease. The tive, populationbased, observation study. Six hun- dredeighty six men aged,47-55at screeningwere

Yo.2 Jour.Marhe MedicalSociety, July-Dec 1999, Vol. I, No.2 135 comparedwith 6810 non hypertensivemen. The of IHD wassignificantly relatedonly to serumcho- hypertensivemen having stoppedheatment with lesterolconcenhation in this study.Mortality was eithero blockers,thiazide diuretics or combination almost similar in treated hypertensive(61/686, featment. Mortality, morbidity and adverseeffects 8.9%) andhypertensive men (73216810, 10.8%). It were regisleredat yearly examinationfrom death was thereby concluded that tneatedhypertensive certificates.It was found that treatedhypertensive menhave impaired survival andincreased mortality men had significantly impairedprobability of total fromcardio vascular disease compared with non-hy- survival as well as survival from coronary heart pertensivemen of similar age. These differences diseaseand stroke. All causemortality as well as were observedduring the seconddecade of follow shoke mortality were very similar in hypertensive up. men and normotensivOmen during the first decade but increasedsteadily thereafter despite continuous blood pressurecontol arhonghypertensives. Smok- Contrtbutedby ing, signs of target organ damageand high serum Surg Cdr PS TAMPI cholesterollevels but not blood pressureat scrcen- ClassifiedSpecialist (Medicine and Pulmonology), ing were significantly related to the incidenceof Deptof Medicine,INHS Asvini, coronaryheart disease during follow up. Incidence Colaba,Mumbai 400 005.

136 Jour. Marhe Medical Society,Iuly-Dec 1999,Vol. I, No.2 ncho- tuloBlrNEs FoRAUTHoRS y was U686, Vo).It I . Journal of Marine Medical Society (JMSS) publish- one copy of the typescript, suithbly modified, will be sent )nsive es original articles, case reports, topical reviews, editori- to the author for revision and resubmission. rtality als, special articles, letters to the Editor, book reviews,and All the material pertaining to an article, which is not rn-hy- other scientific information in all disciplines of medical accepted,will be retumed by ordinary post. sciences. €nces 7. Reprints : 15reprints of eacharticle will be sentfree bllow 2. Contents of the JMSS are covered copy right. Arti- of cost to the author whose name is given on the title page cles are acceptedfor publication with the understanding for that purpose. that their contents,all or in part, have not been published Extra reprints will not be supplied. and will not be published elsewhereexcept in an absFact form of with the consent of the Editor. JMSS does not 8. Author's and OC certificates as per NO 24195 accept the responsibility for statements made by the must accompany the article in duplicate, as per thoro authors. The Editorial Board has the right to introduce forma given below: logy)' such changesas may be considerednecessary. Author's certificate : Certified that I have not used 3. Authorship any information or material from official documents graded,restricted and above or any classified information Only those who have materially participated in the obtained in my official capacity. preparation of the article, should be selectedfor author- ship. The final typescript must be read and approved by I have checkedthe article for grammar and spellings. all the authorsand a statementto that effect signedby each hincipal Author author must accompany the article. If more than four Certificate from OC authors contribute to the article; an accompanying state- ment must specify briefly the work done by each author. Certified that I have no objection to the publication of the article entitled 4. Manuscripts must be neatly typed, in double space written throughout, on one side of the sheetof good quality white by bond paper of the size 28 x 22.cm with 3 cm margin on oc both sides.Words should not be hyphenatedat the end of a line. THE VANCOWERSTYLE Three copies, including the original, of the typescript In keeping with the current trends in Medical Journal- should be submitted along with two sets of illustrations. ism and for the sake ofensuring international uniformity Authors must retain a copy of all the above material, as the "Vancouver Style" of publication is to be followed. the Journal tannot be held responsible for its mutilation Detailed information regarding the pattern to be followed or loss in transit or due to any other reason. for articles is given below. Contributors are earnestly 5. The typescripts should be enclosedin a large enve- requestedto note and strictly follow them. preferably lope, superscribed'Article for Publication', not Classilication and Length of Articles folded and sent under registeredcover to: I. ORIGINALARTICLES Editor, The subject should decide the length of the article. Joumal of Marine Medical Society However, the text should not exceed eight typed pages INHS ASVINI (double space)or about 4,000 words, excluding title page Colaba" Mumbai - 400 005. abstractpage, references, tables and legends.The number 6. Acknowledgement / Decision : Material received oftables, illusrations and referencesshould be kept to the for publication will be acknowledgedimmediately. minimum. Besides being evaluatedfor scientific value and accu- 2. CASEREPORTS racy, the typescript is edited for the contentsand precise- Case reports are accepteddnly if they describe inter- ness as also for the style of expressionand presentation. esting facetsof a particular disease,an unusuaUrareentity Each article must not only highJight a new aspectof the or finding. As a rule, CaseReports are given low priority. subject, but must also make enjoyable reading. The text should not exceed 1500 words. There is no The article may further be reviewed by a referee. need to give a comprehensivereview of literature. The Editorial Board has the right to introduce such 3. REVIEW ARTICLES changesas may be considerednecessary. When necessary, Review articles are acceptedonly by invitation.

, No.2 Jour. Marine Medical Society,Juty-Dec 1999,Vot. I, No.2 t37 4. MISCELLANEOUS ARTICLES theauthor's name.T'hey should be indicated in thetext S Technicalnotes, letters to the Editor,brief notes,etc. arabicnumerals enclosed in squarebrackets (e.g. [2]), on will be acceptedonly on their merit. theline of thetext andno assuperior numbers. The Editorial Board may reducethe numberof tables, Ensure that all the referencescited in the text are referencesand illusrations. includedin thelist andvice versa-Underline the name of booVjournalin the list of references. The Typescript The following exampleswill amplyserve to guidein The typescriptcomprises: a) Title page,b) Absfract presentingthe various kinds of references. and key words, c) Text, d) References,e) Tablesand f) Legends.All thesemust stara on separatepages andinthe Journals aboveorder. StandardJoumal Article (List all authorswhen six or a) Title pagegives the title of thearticle, full namesof less;when seven or more,give only fust threeand add er the author(s),affiliations of authors,place of work, and aD. nameand addressof the author for correspondenceand One-wordnames of Journalsshould be given in full, requestfor reprins.Give respective PIN. e.g.Cancer, Gashoenterology, Surgery. Ideally, the title should be of about 60 characters.It For correctabbreviations ofJournals refer to the latest shouldhave no abbreviations.Give full first namesof the IndexMedicus. authors,middle initials andlast name(s).No degregwill Namesof Journalnot indexedmust be givenin full. be printed.Names of all the authorsmust be typedone belowthe other with properfootnote marks after the name. No full point in abbreviationsof the Journal'sname (e.g.NEnglJMed). Otheritems, viz. affiliations(with conespondingfoot- l. You CY, LeBKY, CheyRY, MenguyR. Electrogas- notemarks at the beginning), name and address ofauthors tographicstudy ofpatients with unexplainednausea, for correspondenceand requestfor reprints, should be bloatingand vomiting. Gastroenterology 1980;79 : typedas footnotes. The following marksare available, and 3l l-14. shouldbe usedin thesame order, *,+,#,**,++,## 2. CorporateAuthor. b) Abstract(p. 2) shouldbe typed on a separatesheet. The Royal MarsdenHospital Bone-Marrow Trans- plantationTeam. Failure of syngenericbone-marrow It is a synopsisof themain article and gives an oppor- graftwithout preconditioning in post-hepatitismar- to inducethe readerto go throughthe tunity to the author row aplasia.lnncet L977;2 : 24244. articlein its originalform. In about200 words,(l(X) for 3. No AuthorGiven casereports), divided into a few sentences,it mustgive briefly thehistory and nature of thedisease / subjects; the Anonymous.Coffee drinking and cancer ofthe pan- methods,results, diagnosis and conclusion,giving facts creas(Editorial). Br MedJ 1981;283 : 628. andnot description. 4. JournalSupplement Speculativesurmises, and references to otherworks on MastriAR. Neuropathyof diabeticneurogenic blad- the subjectshould not figurein theabsract. der.Ann Intem Med 1980;92 (2Pt2\: 316-18. Remember- An absractis mini-article. FruminAM, NussbaumJ, EspositoM. Functional asplenia: demonsfiationof splenicactivity by bone Key words : Not more than five important words marrowscan (Abstract). Blood 1979;54(Suppl l) : whichwill helpthe indexer. 20a. The text 5. JournalPaginated by Issue Thetext should be divided into sections,e.g. infroduc- SeamanWH. Thecase of thepancreatic pseudocyst. tion, materiaVsubject/patientsand methods,results, and HospPract l98l; 16(Sep) : 24-5. discussion.Each should have its individualiWand must Books and other Monograph not be mixedwith others. 6. PersonalAuthor(s) References EisenHN. Immunology: anintroduction to molecu- Responsibilityof accuracyof the referenceslies en- lar andcellular principles of the immuneresponse. tirely with the authors,It mustbe ensuredthat the names 5th ed.,New York: Harperand Row. 1974;406. of theauthors cited arecorrectly typed both in the text and 7. Editor,Complier, Chairman as Author in theReference list. DaussetJ, Colombani J, eds.Histocompatibility test- Referencesshould be listedin theorder in whichthey ing 1971.Copenhagen Munksgaard. 1973; l2-8. arecited in the text, and not in the alphabeticalorder of

138 Jour. Marine Medical Society,July-Dec 1999,Vol. I, No.2 hetext b, ! 8. Chapterin a book Tables (follow references) l. [2j), on WeinsteinL, SwartzMN. Pathogenicproperties of Tablesmay be typedin betweentext matter,preferably invading microorganisms.In L SodemanWA Jr, after on near about the paragraphin which the table ) text are SodemanWA, eds.Paihologic physiology mecha- numberis mentioned.They shouldbe seriallynumbered : nameof nismsof disease.Philadelphia WB Saunders.l9?4; in arabicnumerals (Table I, Table 2) and a short title 457-72. shouldspecify the contents. rguidein 9. Publishedhoceedings Paper Horizontallines in the bodyclr4pyl4t ot" DupontB. Bone m.urow transplantationin severe the table,except between a columnheading and is sub- combined imftunodeficiencywith an unrelated headings,should be avoided.Similarly, the verticallines MLC compatibledonor. In: WhiteHI, SmithR, eds. separatingthe columns should be totallyomitted. ten six or Proceedingsof thethird annualmeeting of theInter- Legends(follow tables) nd add e/ national Society for Experimentalhematology. Houston: InternationalSociety for Experimental legendsshould be brief (rarelyexceeding 40 words), :n in full, Hematology.1974;M-6. but mustexplain the salient features of the illustration. 10. Monographin a Series Illustrations thelatest HunnighakeGW, GadekJE, SzapielSV, et a/. The Illustrationsshould be presentedonly if they depict human alveolarmarcophage. In : Harris CC, ed. somethingnew or unusual.They should be seriallynum- r in full. Culturedhuman cells and tissuesin biomedicalre- beredin the orderof their mentionin the text, irrespective search.New York: AcademicPress. 1980; 54-56. il's name of their nature,viz. photograph,drawing or chart,using (StonerGD, ed. Methodsand perspectivein cell only theword Figureand not diagram,graph, etc. biology;vol l). LecEogas- Figuresshould be numberedto correspondto thecase dnausea, I l. AgencyPublication numbers,e.g. Fig. lA, Fig. lB, Fig.2A, Fig.2B, etc. .980;79: RanofskyAL. Surgicaloperations in shortstayhos- Illusrationsare of thefollowing kinds: pitals:United Stated - 1975.Hyattsville, Maryland : NationalCentre for HealthStatistics, 1978; DHEW 1. Photograph,2. transparency,3. diagramor line publicationno (PHS) 78 1785,(Vital and health drawing,and 4. Chart. rw Trans- statistics:series l3: no.34). l. Photographs:Unmounted glossy prins - notmatfin- e-marTo\\' ish - of excellentclarity shouldbe selected.Their size rtitismar- Other Articles ideallyshould be 13x 18cm (5" x 7"). 12. Dissertationor thesis Do notwrite anything on thephotograph, either on the CairnsRB. Infraredspechoscopic studies of solid backor on thefront. f thepan- oxygen(Dissertation). Berkeley, California: 1965; Do not mountthe photographs. l. 156. Do not usepins, staples or evenpaper clips to put the 13. NewspaperArticle photographstogether. Enclose the photos in thin cards,so enicblad- ShafferRA. Advancesin chemistryare startingto thatthey do not getmutilated. 6-18. unlockmysteries of thebrain: Discoveries could help runctional cure alcoholismand insomnia,explain mental ill- Avoid identifiablephotographs, unless you haveob- tainedthe patient's permission to reproducethem. 1by bone ness.How the messengers work. Wall SueetJournal. Suppll) : Aug.1977; 12: I (vol.l), l0(vol. l). 2. Transparenciesand colouredphotographs are not 14. MagazineArticle accepted. RouecheB. Annals of medicine:the SantaClaus 3. Diagramsshould be drawnon thin, white, smooth eudocyst. culture.The New Yorker l97l; Sep4 : 66-81. or glazedcard in Indianblack ink, and not in any other Pleasenote that colour. L The initialshave no periods; 4. Chartsshould be drawn in thesame way as diagrams. 2. The yearfollows the periodicaVpublisher's name (in Type a labelindicating on the top 0 principalauthor caseofBooks[ name,short title of thearticle and the figure number, and r molecu- 3. Editorial,Abstract, etc. appearin parenthesis; pasteit on theback of theillustration. response. 4. Both beginningand ending pages are given. Units ;406. Ifthe referenceis ofonly onepage, underline the page measurements, g, (not number(see 3 above). Usemetric cm, kg, ml cc). No rilitytest- periods,no pluralform (e.g.30 cm,48 kg, 15ml etc.). 12-8. l. l, No.2 Jour.Marine Medical Society, July-Dec 1999, Vol. l, No.2 139 -\ Use radiograph,radiographic and radiographicalnot Suggestionon writing an article v X-ray, skiagram,roentgenogram, roentgenogruphic and Write your manuscript(first rough version),improve roentgenologic upon it and at this stagedecide on the references,tables Man/womaninstead of male/femalepatient etc. Patient andfigures (second rough version). Keep it asidefor 2-3 insteadof case. weeks. Write on separateshees any improvementsin 'Significant'should be reservedfor usein statistical language,presentation, etc., or removal,replacement ofa sense, paraor two. Write the third versionwhich will now be in a presentableshape, get it readby a colleagueor a special- Spellings ist in anotherfield. Implementtheir suggestionsif you British spellingsarc preferredto Americanspellings. approveof them.And get setfor typing the final version (e.g.colour, tumour and not colour,tumour). for submissionto theEditor. In words with diphthongs(ae, oe) retainonly e and For moredetails, please refer to the following: deleteo, (e.g.etiology (aetiology), hemo.(haemo), cecum l. lntemationalCommittee of Medical JournalEditors. I (caecum);esophagus (oseo-phagus) etc. Uniform requiremensfor manuscriptssubmitted to I biomedicaljoumals. Ann Intern Med 1988; lO8 : Avoid 258-65. patiens, Names,initials, hospital numbers of the and 2. Lrntle Brain C. Informationfor authors.J Can Assoc dates. Radiol 1988:39(June) : 157-59. Small articleson singleindividual aspect of the sub- 3. Anonymous.Information for readen and authors. ject, when one larger article,discussing all the aspects AnnIntem Med 1989;I l0 : 14 - l-7. wouldcarry morc weight. Acknowledgement Unfamiliarabbreviations, medical jargon and passive voice. Theseguidelines for authorshave been adapted from the Medical Journalof Armed Forcesof India. Repetitionof materialin resultVobservationsand dis- cussion,in tablesand text, and in text andlegends.

140 Jour. Marine Medical Society,July-Dec 1999,Vol. I, No.2 d x o \o \o \o

astate-ii-ttre-an

fF t3 i' .t F1 f;3.

_6 Enginrering dcgms in Cor{FrbF, Elcctrical, 8ts. MBA, BBA, BCA degres od lyo diplom in ISO 900O El*trooics, Meheical md lodustrial & ProdBtio! fslties -3 Institute of Management Studies Dehradun Institute of Technology Instituterf M"r";:;;#tr rffi; coqt \ooGFI A-16,Sector 8, Noida. Malsi, MussoorieRoad, Dehradun 21. New Cantt. Road. Dehradun t'D d a

p

.D