NBE Journal Nov December 2008 Final

Contents

EditorialClostridium difficile infection 1P.S. Shankar

CommentariesAssisted reproductive technology and anesthetic considerations - review of literature 6Dr JS Dali, Rakesh Garg

Vision 2020 - The right to sight 15R. Jose, Sandeep Sachdeva

Effective communication-resident’s perspective 20R. Jose, Sandeep Sachdeva

Review articlesBasics of MR spectroscopy 24Namita Singh Saini, Giriraj Singh Gujral, S Khushu , RP Tripathi

Image guidance in radiotherapy- from planar to multidimensional radiotherapy 32M K Semwal

Imaging and interventions in HCC 37Nirad Mehta

Importance of plain abdominal radiograph - A pictorial essay 41Sanjay Jain, Ravi Varma

Plain radiograph in congenital heart disease 50Sanjay Jain, Ravi Varma

Gamut of radiological findings in pulmonary aspergillosis 56Ankur Dev

Health system in India 60R.Rose, Sandeep Sachdeva

CorrespondenceGuidelines on DNB thesis 65Manoj Sharma

Recent advancesSugammadex- a novel neuromuscular blocker binding agent – a review 70

Dr JS Dali, Rakesh Garg

Update on prebiotics and probiotics 77Gautam Ray

Original ArticleCohabitational effect of blood pressure among non-genetically related 80pairs in IndiaSanjeev M. Chaudhary, Sanjay S. Kubde, Sanjay B. Agrawal

1Journal of Postgraduate Medical Education, Training & ResearchVol. III, No. 6, November-December 2008

any infections haveemerged with increasedvirulence in the recent

1EditorialEditorialEditorialEditorialEditorial

Myears. Clostridium difficileinfection causes disease inpresence of exposure toantibiotics either during or aftertreatment. It has become anincreasingly important nosoc-omial infection throughout thewestern world over recent years.It results in antibiotic-associateddiarrhoea, antibiotic-associatedcolitis and pseudo-membranouscolitis. The infection resultsfollowing a disturbance in thenormal intestinal flora followingantibiotic therapy.History-An anaerobic organismisolated and cultured with greatdifficulty in 1935 named Bacillusdifficilis(now renamed Clostri-dium difficile) forms the mostcommon cause of nosocomialdiarrhoea1. Antibiotic-associatedcolitis occurs as an off-shoot ofuse of antibiotics and is notedspecially in surgical patients. Thiswas recognized in 1970s. Aprospective study carried out byTedesco and his colleagues in1974 on 200 consecutive patientsreceiving clindamycin showedoccurrence of diarrhoea in 41patients. 20 (10%) of them whoreceived clindamycin exhibitedpseudo-membranous colitis2.Three years later Bartlett andcolleagues found antibiotic-associated pseudo-membranouscolitis to be due to a toxin-producing clostridium3. Since

Clostridium Difficile InfectionP.S. Shankar

Governing Body Member, National Board of Examinations

then C difficile has been the mostcommonly recognized microbialcause of nosocomial diarrhoea.Aetiology-Clostridium difficile isa rod-shaped, gram-positive,anaerobic, spore-forming andcytotoxin producing, bacteriumand is commonly found inhospital wards. Transmissionoccurs primarily in hospitalswhere the patient has beenexposed to antimicrobial agentsand to an environment contam-inated by C difficile spores. Thespores persist in the environmentfor prolonged periods. It happensto be the only anaerobe posingsuch a threat by producing toxinin the colon. Prolonged stay inhospital forms a major risk factor.It is acquired by the feco-oralroute. It colonizes the humanintestinal tract and multipliesafter the resident flora has beenaltered by antibiotic agents Analteration in the normal colonicbacterial flora and impaired hostimmune response, facilitate theproliferation of the organism.There is an increase in incidenceof C difficile-associated diseasein US, Canada and Europe in therecent years due to emergence ofan epidemic strain with increasedvirulence, antibiotic resistance orboth. The hyper-virulent strainhaving a high concentrations ofboth A and B toxins has emergedto cause epidemics. A nation-wide-Swedish study revealed anincreased mortality after the ageof 60 years in C difficile-

associated diarrhoea4. The riskfactors were age over 65 yearsand receipt of fluroquinolones inthe cases reported from Quebec,Canada 5. There were manydeaths from C difficile-associateddisease in Pittsburgh, US. It wasnoted following fluoroquinoloneuse and it required colectomy inmany cases 6.The increaseappears to be due to emergenceof a new strain of C difficile. In187 C. difficile isolates collectedfrom eight outbreaks at US healthcare facilities occurring between2000 and 2003, a previouslyuncommon strain of C difficilewith variations in toxin genes thathas been more resistant tofluoroquinolones was encou-ntered7. The strain belonged totoxinotype III and was positivefor binary toxin.Loo et al inanother microbial analysis with Cdifficile associated enteritis in1703 patients at 12 hospitals inQuebec, Canada noted in 2004that most strains to be resistantto fluoroquinolones and most ofthem had a binary toxin8. Therewas a very high incidence andmortality associated withincreasing age. These data haveproved that more virulent strainsof C difficile are responsible forepidemics in selected locations.They are responsible for moresevere disease, often associatedwith complications necessitatingcolectomy, and death.Pathogenesis-C difficile isusually hospital-acquired. The

Journal of Postgraduate Medical Education, Training & ResearchVol. III, No. 6, November-December 20082

infection gets established whenantibiotic therapy disrupts thenormal colonic bacterial flora.The condition can develop indebilitated patients who have notreceived antibiotic therapy. Onlyabout 3% of healthy adults andup to 20-40% of elderly personsmay carry C difficile and remainasymptomatic carriers 9. They actas a reservoir for infection. Inhealthy persons the organismremains in a metabolicallyinactive spore form and itscolonization is not ordinarilyharmful. The disturbance in theintestinal flora by the antibioticor surgical interference facilitatesits conversion to vegetative formsthat replicate and produce toxins.Exposure to antibiotics is thechief precipitant of C difficile-associated diseases. Though anyantibiotic with an antibacterialspectrum can result in severeintestinal disorder, the mostcommonly implicated antibioticsare clindamyin, cephalosporinsand fluoroquinolones thatdisrupt the normal colonicbacterial flora3,5. There are manystrains of C difficile withdifferent pathogenic potentials.The virulence of the organismsis due to the two exotoxins (A andB) that are cytotoxic andinflammatory and they areproduced by most pathogenicstrains. These toxins aretranscribed from a pathogenicitylocus that comprises five genes:two toxin gene tcdA (toxin A) andtcdB (toxin B) and threeregulatory genes, one of which(tcdC) encodes a putativenegative regulator of toxintranscription10. These toxins bindto the receptors on the surfaceof the intestinal epithelial cells

and get internalized and disruptthe cells significantly by uridine5’-diphosphate glucose depen-dent glucosylation of rhoproteins11. A binary toxinelaborated by C difficile encodedby two chromosomal genes cdtAand cdtB mediate cell-surfacebinding and disrupt the assemblyof actin-filaments and result incell death12. A hypervirulentstrain having a mutation in tcdCis associated with highconcentration of A and B toxins,and this strain was responsible forepidemics in USA, Canada,Europe and Japan13. TedCprotein appears to inhibit toxintranscription during the early.exponential-growth phase of thebacterial life cycle, however it isintriguing why some personscarry them without any clinicalmanifestations. There are alsotoxin-negative organisms that donot produce any disease. Recentout breaks in US and Europewere due to a highly virulent,quinolone-resistant strain, PCRribotype 027 (B1). It was capableof producing toxin 20 timesmore powerful that produced byA and B strains14.

Pathology-Initially the infectionis associated with focal areas ofinflammation with oedema anderythema in the descendingcolon. It progresses withappearance of creamy-whiteadherent plaques on inflamedintact colonic mucosa withoutulceration (pseudo-membrane).Pseudomembranes comprise ofpolymorphs, inflammatory cells,fibrin and debris, and maycoalesce to obscure mucosa.There is secretory diarrhoea. Thebowel wall gets thickened. There

can be toxic megacolon andperforation.

Clinical features-The infectioncommonly develops in elderly,and frail patients often ailing withother co-morbid diseases in thehospital. These patients exhibitsymptoms in the first week ofreceiving antibiotics. Though allantibiotics have the potential tocause C difficile associateddisease, some antibiotics such asClindmycin, second/thirdgeneration cephalosporins,amoxicillin/clavulanate andquinolones. However thedevelopment of the conditionmay be delayed up to 6 weeksafter completion of therapy. Thetherapy would have been stoppedby the time the manifestationbecome apparent. Apart fromprior antibiotic therapy,prolonged hospital admission,nasogastric feeding, immun-osuppression, age and chronicmedical conditions form otherfactors that are associated with Cdifficile-associated disease(CDAD).The manifestationsbegin insidiously. The patientsexhibit lower abdominal pain,low-grade fever and frequentpassage of profuse, watery stools.Often they complain abdominalcramps. Severe colitis may resultin small bowel ileus, toxicdilatation of colon (megacolon),perforation, and progressivemulti-organ failure. Severe casesare associated with diarrhoeawith 15-20 stools per day. Bloodin the stools is unusual. Systemictoxicity is manifested withabdominal cramps, fever, andtachycardia. Ileus or megacolonmay be heralded by cessation ofdiarrhoea 15.


Diagnosis-Colitis has to besuspected in any patient who isreceiving antibiotic or hasreceived antibiotics recently,when they have presented withdiarrhoea. There is leucocytosis,hypoalbuminaemia, and highserum concentration of C-reactive protein. Leucocytosismay precede signs of colitis16.Radiologic imaging of abdomenmay reveal dilated small intestineand colon without any free air.Sigmoidoscopy reveals erythemaof the rectum and colon, andpresence of raised yellow plaquesor an adherent pseudo-membrane. Presence ofpseudomembrane is pathogno-monic. However its absence doesnot exclude the diagnosis as theyare absent in mild cases and inpatients with concomitantinflammatory bowel disease.Biopsy of the area has to be donefor histopathologic study.SevereCl. dificile infection includespseudomembranous colitis, amarked peripheral leucocytosis,acute renal failure andhypotension. C. difficileorganisms may be isolated byanaerobic stool culture. Thepositivity is higher in thoseexhibiting pseudo-membranouscolitis compared to those havingantibiotic-associated diarrhoea.The test though highly sensitivie,is non-specific due to theexistence of non-toxigenicstrains of C difficile that maycolonize the bowel in hospitalisedpatients. Cell cytotoxicitybioassay helps in isolation oftoxins A and B. Cytotoxicbioassay is performed byinoculating stool with culturedcells. The cytopathic effect isabolished by neutralising

antibodies to C difficile toxin.This test is highly sensitive andspecific. However its utility islimited by expense and the timeneeded to perform the assay (3days)14. Rapid enzymeimmunoassay (RIA) is fast (1hour) and cheaper to detect toxinA or B or both. However the testhas a low sensitivity.Prognosis-The mortality in Cldifficile-associated disease(CDAD) varies from 5 to 10percent. To this number the co-morbid conditions in elderly alsocontribute. Many patients whohave received treatment succes-sfully may exhibit recurrence ofdisease, This is because theadministration either ofmetronidazole or vancomycinimpairs resistance to coloniz-ation, and facilitate recurrentinfection. It is commonly noted4 weeks after completion oftreatment.

Management - The administ-ration of the offending antibioticshould be stopped immediatelyfollowing development ofdiarrhoea. This will facilitate thenormal bowel microflora torestore itself. The treatment maybe changed to agents with a lowerrisk of inducing C difficile.Administration of corticoste-roids, and other immunosup-pressive agents and proton pumpinhibitor (PPI) should bediscontinued. The patient has tobe isolated. The hydration of thepatient has to be maintained byadministration of intravenousfluids.The patients who areseverely ill, and those exhibitingileus, colonic dilatation orpseudo-membranous colitis needantimicrobial therapy. Of which

metronidazole and vancomycinare widely used. The patientsmust receive them orally.Metronidazole is selected forinitial treatment and it has to begiven in a dose of 400 mg forseven to ten days. If the responseis not satisfactory, and in moresevere cases vancomycin 125 mgsix-hourly has to be given forseven to ten days. Higher curerates are seen with vancomycinin those with severe cases.Vancomycin is the first linetreatment in patients with severeCDAD. Vancomycin has to berecommended when patients onmetronidazole fail to showimprovement within 72 hours17.Severe cases of CDAD requireaggressive treatment withVancomycin. It must be notedthat IV vancomycin is notsecreted into the lumen of thebowel. Some patients maybenefit with intravenousmetronidazole or vancomycinenema18. Generally these agentscontrol the manifestations after2-3 days. Recurrence of diseasenecessitates administration ofmetronidazole or vancomycin for10 to 14 days. It must be notedthat substantially higher failurerates are encountered in therecent years for metronidazoletherapy19.In a recent studycomparing vancomycin (125 mgfour times a day) withmetronidazole (250 mg fourtimes a day) for the treatment ofClostridium difficile-associateddiarrhoea stratified by diseaseseverity, Zar and colleaguesfound both agents showingsimilar efficacy in mild infection.However, the response rate withVancomycin (98%) was greaterthan that with metronidazole


(90%). Vancomycin was signific-antly more effective in severeinfection20. Metronidazole isrecommended for mild infectiondue to its lower cost and concernsabout the proliferation ofvancomycin-resistant nosoc-omial bacteria. Vancomycin is tobe used as first-line agent inpatients with severe infectionbecause of more promptsymptom resolution and asignificantly lower risk oftreatment failure21. Oralvancomycin may not be suitablefor some patients with severe orfulminant infection due tocoexistent ileus or toxicmegacolon. In such situationsmetronidazole has to be given ina dose of 500 mg four times aday with supplementation ofvancomcin21.20,000 units ofBacitracin orally 6-hourly and 300mg of Fusidic acid orally every 6hours are other drugs that can beutilized in the management for aweek. Probiotic, Saccharomycesboulardii 500 mg twice daily maybe administered as adjunct toantimicrobials. However it is notrecommended in immu-nosuppressed patients or thosewith central intravenous lines asthere is likelihood of occurrenceof fungaemia18. In a smallnumber of cases who aretherapy-resistant, administrationof a filtrate of stools from ahealthy family member, eitherthrough a nasogastric tube or atcolonoscopy may help inreconstitution of faecal flora18.However this procedure is not

popular due to practical andaesthetic reasons. Fulminantcases are treated with intravenousimmunoglobulin, and some casesmay require urgent colectomy.Prevention-It is necessary tomaintain proper hygiene of theward. Periodic disinfection of thehospital environment, andcleaning with dilute bleach has tobe carried out to eliminate Cdifficile spores. Proper washingof hands with soap and water isstressed. Health care workersshould wear gloves and gownswhen entering the room ofpatient. Judicious use ofantibiotics is an important way toreduce the incidence of Cdifficile infection. The use of theepidemiologically implicatedantibiotics such as clindamycin,second and third generationcephalosporins or fluoroqui-nolones are to be restricted insurgical cases. The patients haveto be isolated and treated. Theadministration of probiotics inhospitalized patients requiringantibiotics significantly bringsdown subsequent incidence ofantibiotic associated diarrhoea22.Strict isolation of patients, barriernursing, good hand washingprocedures with soap and water,and environmental decontami-nation with sodium hypochloritesolution to kill the spores on thesurfaces, help in achievingsecondary prevention oftransmission of C difficile and itsspores.The recent surge inoutbreaks shows that knownpathogens can alter their

behaviour and pose new threatwith increased virulence,antimicrobial resistance or both.Even after seven decades of itsisolation C difficile posingdifficulty in containment of itsgrowth and spread.References

1. Hall IC, O’Toole E. Intestinalflora in new-born infants witha description of a newpathogenic anaerobe, Bacillusdifficilis Am J Fid Child1935: 49; 390-402

2. Tedesco FJ, Berton KW,Alpers DH. Clindamycin-associated colitis: aprospective study. Ann InternMed. 1974; 81: 5-9

3. Barlett JG, Onderdook AB,Cisneros RI, Kasper DL.Cl indamycin-assoc ia tedcolitis due to a toxin-producing species ofClostridium in humans. JInfect Dis. 1977; 1:370-8

4. Karlstrom O, Fryklund B,Tullus K, Burman LG. Aprospective nationwide studyof Clostridium difficile-associated diarrhea inSweden. Clin Infect Dist.1998; 26: 141-5

5. Pepin J, Valiquette I, AlaryME, et al. Clostridiumdifficile-associated diarrhoeain a region of Qubec from1991 to 2003: a changingpattern of disease severity.CMAJ 2004; 171: 466-72

6. Muto CA, Pokrywkz M, ShuttK, et al. A large outbreak ofClostridium difficileassociated disease with anunexpected proportion ofdeaths and colectomies at a


teaching hospital followingincreased fluroquinolone use.Infect Control Hosp Epide-miol. 2005; 26: 273-80

7. McDonald LC, Killgore GE,Thompson A, et al. Anepidemic toxin gene-variantstrain of Clostridium difficile.N Engl J Med. 2006; 353:2433-41

8. Loo VG, Poirier L, MillerMA, et al. A predominantlyclonal multi-institutionaloutbreak of Clostridiumdifficile-associated diarrheawith high morbidity andmortality. N Engl j Med.2006; 353: 2442-9

9. McFarland LV, Mulligan ME,Kwok RY, Stamm WE.Nosocomial acquisition ofClostridium difficile infec-tion. N Engl J Med. 1989;320: 204-10

10. Warny M, pepin J, Fang A, etal. Toxin production by anemerging strain of Clostr-idium difficile assoc-iatedwith outbreaks of severedisease in North America andEurope Lancet 2005: 366;1079-84

11. Pepin J, Saheb N, CoulombeMA, et al. Emergence offluoroquinolones as thepredominant risk factor forClostridium difficile associ-ated diarrhea: a cohort studyduring an epidemic inQuebec. Clin Infect Dis.2005; 41: 1254-60

12. Barth H, Aktories K, PopoffMR, Stiles BG. Binarybacterial toxins: biochemistry,biology and applications ofcommon Clostridium and

Bacillus proteins. MicrobiolMol Biol Rev. 2004; 68: 373-402

13. Matamouros S, England P,Dupuy B, Musher DM.Clostridium difficile toxinexpression is inhibited by thenovel regulator TcdC. MolMicrobiol 2007: 64; 1274-88

14. Blossom DR, McDonald LC.The challenge posed byreemerging Clostridiumdifficile infection. Clin InfectDis 2007: 45; 222-7

15. Clark T, Wiselka M.Clostridium difficile infectionCli Med 2008: 8; 544-7

16. Wanahita A, Goldsmith EA,Marino BJ, Musher DM.Clostridium difficile infectionin patients with unexplainedleukocytosis. Am J Med.2003: 115; 543-46

17. Fernandez A, Anand G,Friedenberg F. Factors associ-ated with failure ofmetronidazole in Clostridiumdifficile-associated disease. JClin Gastroenterol 2004: 38;414-18

18. Kuipers EJ, Surawicz CM.Clostridium difficile infect-ion. Lancet 2008 : 371 ; 1486-88

19. Musher DM, Aslam S. LoganN, et al Relatively pooroutcome after treatment ofClostridium difficile colitiswith metronidazole. ClinInfect Dis 2005: 40; 1586-90

20. Zar FA, Bakkanagari SR,Moorthi KM, Davis MB. Acomparison of vancomycinand metronidazole for thetreatment of Clostridium

difficile-associated diarrhoea,stratified by disease severity.Clin Infect Dis 2007: 45; 302-7

21. Kelly GP, LaMont T.Clostridium difficile-moredifficult than ever N Engl JMed 2008: 358; 1932-40

22. Hickson M,D;Souza AI,Muthu N, et al. Use ofprobiotic Lactobacillus prep-aration to prevent diarrhoea-associated with antibioticrandomised double-blindplacebo controlled trial. B MJ 2007: 335; 80


2CommentarCommentarCommentarCommentarCommentaryyyyy

Assisted Reproductive Technology and Anesthetic considerations -review of literature

Dr JS Dali, Rakesh Garg

Department of Anesthesiology and Intensive Care, Maulana Azad Medical College, All India Institute ofMedical Sciences, New Delhi

he first successful livebirth following in-vitrofertilization (IVF) of aT

human oocyte was performed in1978 by Steptoe and Edwardswith the birth of Lousie Brown,the first test tube baby. AssistedReproductive Technology (ART)has gradually evolved into moresophisticated with advancementand better outcome. Similarly therelated anaesthetic techniques aswell. The anesthesiologist may beinvolved in many aspects of thepatient’s treatment, which may becomplex and needs cautious peri-operative management. IVF is afour stage procedure – ovarianstimulation and monitoring,oocyte retrieval, fertilization andembryo transfer. Egg retrievalcan be accomplished laparosc-opically or ultrasound guidedvaginal retrieval.Need of anesthesiologist-Majority of the patients areyoung and healthy but exhibitstress, anxiety and otherpsychological disorders associ-ated with infertility. It isparticularly important for theanesthesiologist to understandthe patient’s anxieties and takesuitable measures to allay it. Theserum hyperprolactinaemic resp-onse to stress is well established1.50-fold transient increase inserum prolactin levels duringoocyte retrieval for in-vitrofertilization has been reportedunder general anaesthesia which

may influence the outcome ofIVF 2,3,4,5. The need of repeatedattempts of IVF before successis achieved, also mandates takingcare of psychological stress andalleviating it. The IVF proceduresare also associated with pain andhence the need of minimizationof pain is a major consideration6.The cooperation of patient isrequired during IVF procedurelike oocyte retrieval, which sometime mandates the need ofanaesthesia even.Anaesthetic considerations-For ART procedures, the factorsto be taken under considerationsincludes the technique ofanaesthesia, pneumoperitoneum(if laparoscopy required), and theeffects of anaesthetic agents onfertilization and cell cleavage. Thelength of exposure to drugs isalso important. Now a days, theART procedures are beingaccomplished as ‘Day care’ casesand the basic principles of‘Ambulatory anaesthesia’ needsto be followed. Laparoscopicoocyte retrieval has now largelybeen superseded by ultrasound-guided transvaginal oocyteretrieval5.Effect of anaesthetic agentson reproductive techniques-Controversy exists regarding theeffects of anesthetic drugsadministered during transvaginalpuncture procedures for oocyteretrieval on conception rates7.Anesthetics have been detected

in follicular fluid, and studiessuggest that these drugs mayadversely affect oocytefertilization and embryonicdevelopment. It has also beenconfirmed that the use of generalanaesthesia with nitrous oxide foroocyte retrieval has an adverseoutcome on the outcome of IVF;the deleterious effect manifestsitself only after embryo transferand leads to lower pregnancy anddelivery rates8,9. Exposure topneumoperitoneum with carbon-di-oxide adversely affects oocytequality and in combination withexposure to general anaesthesiawith nitrous oxide appear toaffect fertilization and cleavage invitro7. However, Rosen et alfailed to demonstrate an adverseeffect of nitrous oxide onfertilization or pregnancy rateswhen administered during anisoflurane-based generalanesthetic technique10. Anest-hetic drugs have been detected infollicular fluid, and a longerperiod of exposure in the generalanesthesia group may haveenhanced the deleterious effectsof these drugs on the oocyteand/or follicular structures,thereby interfering with thereproductive process 11,12,13,14.Halogenated agents have beenassociated with reducedreproductive success in clinicalpractice and must therefore beused with caution7,15. Opioids,and especially fentanyl and


remifentanil, do not seem toaffect reproductive success.Exposure to high concentrationsof different local anestheticsadversely affects fertilization andembryonic development16.However, given that much lowerconcentrations are achievedclinically and that oocytes arewashed after retrieval, the clinicaleffects of using local anestheticsshould be limited and probablyno adverse effects should occur.Pain in IVF-Oocyte retrieval isa fundamental step but reportedto be the most painfulcomponent of the IVFprocedure17,18,19. Although lessinvasive than the laparoscopicapproach, transvaginal oocyteretrieval still remains a painfulprocedure20,21. The painexperienced during oocyteaspiration is caused by thepassage of the needle through thevaginal wall and by mechanicalstimulation of the ovary6,22. Thepain is often described as similarto intensive menstrual pain andis intermittent rather thancontinuous. Factors that mayinfluence the pain are the numberof follicles, duration of theoocyte retrieval procedure, theposition and mobility of theovaries22. Multiple-follicleaspiration would entail a lengthierprocedure, which could affectpain scores when compared withsingle-follicle aspiration23. A goodanalgesic method for oocyteretrieval has to give satisfactorypain relief with rapid onset, rapidrecovery, ease of administrationand monitoring17,18,19. In addition,the analgesic method must haveno toxic effects on the oocytesand embryos since many agents

have been detected in thefollicular f luid shortly afteradministration24,25,26,27.

For alleviating pain of IVF,opioids and benzodiazepines hasbeen used, however, many ofthese agents have been detectedin the follicular fluid, albeit clearevidence to indicate negativeeffects on oocytes, oocytedifferentiation, implantation orpregnancy rate is sparse. Moreand more patients, however, arerequesting sedation or anaes-thesia for ultrasound-guidedoocyte retrieval. It is alsoimportant to use anaestheticagents that are safe, has no toxiceffects on the oocytes andensures the highest fertilizationand pregnancy rates17,28.IVF Anaesthesia techniques-Transvaginal ultrasound-guidedoocyte retrieval as a part of invitro fertilization is the mostcommon method of oocyteretrieval and is a relatively short(20±30 minutes) outpatientprocedure19,22,28. As such, itrequires an anesthetic techniquethat works quickly and effectivelyduring the procedure but alsoallows for a rapid recovery withminimal side effects. Traditionalanalgesic methods used fortransvaginal oocyte retrievalinclude local injection as aparacervical block, conscioussedation using variouspharmacological agents, epiduralblock, subarachnoid block,general anaesthesia, or in somecases no analgesic at all6,23,21,29,30,31-

36. The principle of a balancedmultimodal approach to analgesiahas been shown to be effectiveat treating pain in other clinicalsettings such as cancer23. The end

point of in vitro fertilizationprocedures is ultimately the rateof successful pregnancies.Viscomi et al found no differencein fertilization and pregnancyrates between intravenoussedation and spinal anesthesia37.Rosenblatt et al noted that theaddition of propofol tointravenous sedation for eggretrieval did not affect pregnancyand implantation rates38. Gonenet al did find that generalanesthesia with a number ofdrugs was associated withdecreased pregnancy rates whencompared with epidural anesth-esia39.In a systemic review byStener-Victorin for methods ofconscious sedation duringassisted reproduction techniques,concluded that no singletechnique may be regarded assuperior to other for pain reliefduring oocyte retrieval6. Similarly,in an another Cochrane review byKwan et al and found, on analysisof studies regarding conscioussedation and other alternatetechniques of pain relief, that nosingle method or delivery systemappeared superior for pregnancyrates and pain relief23. Variousmethods for analgesia reviewedwere sedation with midazolam,ketamine, fentanyl, alfentanyl orelectro acupuncture along withparacervical block, intramuscularpethidine and/or piroxicam andgeneral anaesthesia with intrav-enous fentanyl and propofol. Itwas concluded that there isinsufficient evidence to deter-mine the best method of painrelief for oocyte retrieval.Monitored anesthesia care orintravenous sedation withfentanyl and midazolam was usedfor egg retrieval, but patient


discomfort and motion duringthe procedure led to the use ofother anesthetic techniques28.Spinal anesthesia has been usedbecause it provides excellentsurgical anesthesia with minimaluse of intravenous medication.An alternate technique isintravenous general anesthesiawith fentanyl, midazolam, andpropofol. General anaesthesiawill abolish the issue of painduring oocyte retrieval but islikely to have resourceimplications. In choosingappropriate regimens forsedation/analgesia for oocyteretrieval, a balance may need tobe struck between safety andefficacy. The ideal regimen wouldreduce pain to a tolerable level inall patients without the risk ofadverse respiratory or cardiova-scular events23. Cons-cioussedation allows patient co-operation to be maintained andthe procedure to be convenientlyperformed in the outpatientsetting. This remains the mostcommonly used method ofproviding analgesia andanaesthesia during transvaginaloocyte retrieval and is used in84% of IVF clinics in the UK and95% of IVF centers in the USA.By comparison, 16% of UKclinics and about 50% of clinicsin Germany use generalanaesthesia for IVF procedures23.

General anaesthesia-Wilhelmet al compared the outcome ofassisted reproductive technologyprocedures in 251 women whoundergo monitored anaesthesiacare with remifentanil versusgeneral anesthesia (alfentanyl,propofol, isoflurane, nitrousoxide)7. They concluded that the

ppregnancy rates in womenundergoing transvaginal oocyteretrieval for assisted reproductivetechnologies were significantlyhigher with a remifentanil-basedMAC technique than with abalanced general anesthetictechnique involving nitrousoxide.

Regional / Local anaesthesia-In a study by Zaccabri et alvaginal application of EMLA wascompared with paracervicalblock for Oocyte Retrieval. Painwas evaluated by visual analogscore (VAS) and the outcome wasthat no one protocol satisfied thepatients; authors suggestedimprovement of premedicationstrategies. Intervention such asparacervical block when added tothe opiate conferred furtherbenefit23. Paracervical blockinduces good analgesia, which isenhanced further by intravenoussedation6. In study of theintraoperative pain scoresassociated with intravenousfentanyl plus paracervical blockversus electro-acupuncture plusparacervical block favoredintravenous fentanyl for IVF23.Paracervical block with bupiva-caine was superior to paracervicalblock with saline or no treatmentand oral diazepam, andintravenous alfentanyl incombination with paracervicalblock was superior to electro-acupuncture in combination withparacervical block6,24. Regardingabdominal pain 60–120 min afteroocyte retrieval, electro-acupuncture was superior tointravenous alfentanyl, incombination with both paracer-vical block. Randomized, contr-olled trials suggest that pain relief

is superior when a paracervicalblock is used in addition tosedation, as compared withsedation alone17,2. It has also beenshown that patients who receivedonly paracervical block duringoocyte collection experie-nced2.5 times higher levels of vaginaland abdominal pain than thosewho received both paracervicalblock and conscious sedation17.A new technique, pre-ovarianblock (POB), has beenintroduced by one of the authorsof this study (I.Ek)17. The localanaesthetic is infiltrated underultrasound guidance in thevaginal wall and between thevaginal wall and the peritonealsurface near the ovary. Thefollicle aspiration needle is theninserted in exactly the samelocation as the depositedlidocaine. Cerne et al studied pre-ovarian block versus paracervicalblock for oocyte retrieval inprospective, randomized,multicentre study including183patients17. All participants inboth the groups receivedalfentanyl 0.25 – 0.5 mgintravenously prior to procedure.Rescue analgesia was providedwith bolus alfentanyl 0.25 mg. Allpatients received rectalparacetamol 1 g preoperatively.Anxiolysis was given by oralflunitrazepam 0.5 mg or 2.5 mgof midazolam. They concludedthat both techniques providedcomparable pain relief and bothpre-ovarian and paracervicalblock in combination withintravenous alfentanyl may beconsidered safe methods withrapid onset, recovery and ease ofadministration. A paracervicalblock (PCB), in combination withdifferent sedative pre-


medications with or without fast-acting opiates, has been reportedto give acceptable pain reliefduring oocyte aspiration inseveral studies22. Hung et alconcluded from his prospective,randomized, double blind andplacebo controlled study to assessthe efficacy of paracervical blockin the pain relief during eggcollection in IVF that paracer-vical block with lignocaine shouldbe used in conjunction with ivsedation / analgesia (50 mgpethidine and 25 mg promet-hazine given 1 hour prior and 25mg pethidine and 5 mg diazepamgiven 5-10 minutes prior toprocedure ) during egg collectionperformed through thetransvaginal route underultrasound guidance to reducethe pain of the procedure40.Apossible risk associated withparacervical block is the potentialtoxicity of absorbed lidocaine24,41.In human use, however, there isno evidence of adverse eventsassociated with lidocaine17. Noadverse effects on fertilization,cleavage or pregnancy rates wereshown using paracervical block24.Paracervical block with differentdoses of lidocaine has beenstudied, and no differences werefound in pain levels during oocyteretrieval when 50, 100 or 200 mgwas used35,36. Thus, the lowestdose has been recommended.Lidocaine is a well-documentedlocal anaesthetic often used forparacervical block (PCB) inpregnant women. It thus seemsthat the concentration oflidocaine found in the follicularfluid after PCB with 50 mglidocaine does not negativelyaffect fertilization of the human

oocyte or early cleavage of thehuman embryo24. Intrathecalfentanyl, in combination withlocal anesthetics (lidocaine), canimprove the quality and prolongthe duration of intraoperativeanalgesia28. Epidural anaesthesia,the most popular of the obstetricanaesthetic techniques offers noobvious advantages over the IVsedation or the other methods forOocyte Retrieval nor does itimprove the treatment outcome.Propofol-Propofol has been apromising alternative forThiopental for short surgicalprocedures and has been tried foroocyte retrieval. No significantdifferences exist between the twodrugs as regards the fertilizationrate, cleavage rate, pregnancyrate, implantation and abortionrate27. However propofol shouldbe used with caution, despite itsadvantages. Propofol has beensuspected of damaging oocytes.Concentrations of propofol havebeen shown to increase infollicular fluid with time, duringoocyte retrieval26. A study wasdesigned to assess whetherexposure to increasing concent-rations of propofol has anymeasurable effect on in-vitrofertilization, cleavage and embryodevelopment. There was anincrease in the concentrationfrom the first to the last follicle,but no difference was found inthe ratio of mature to immatureoocytes. Nor were anydifferences found in fertilization,cleavage and embryo cellnumber27. It was concluded thatthe time elapsed betweenretrieval of the first and lastoocyte does not affect oocytequality. However it is advisable

that the IVF procedure should bekept as short as possible in orderto limit the accumulation of theanaesthetic in the follicular fluids.Sedation and monitoredanaesthesia care (MAC)-Concerns regarding thepotentially deleterious effects ofanesthetic drugs have led to theuse of anesthetic techniques thatminimize exposure7. Increasingly,these procedures are performedwith sedative and/or analgesicdrugs as part of a monitoredanesthesia care (MAC) technique.Trout SW strongly advocatesconscious sedation (with opioidsand benzodiazepines) for IVF19.Several other studies demon-strated higher pregnancy rates inwomen who underwent oocyteretrieval under MAC withRemifentanil infusion than withGA. Midazolam/Remifentanilregimen was evaluated to be aseffective and safe as propofol/fentanyl regimen. Several opioids,such as, pethidine, morphine,fentanyl and remifentanil, havebeen used as a part of conscioussedation and monitoredanaesthesia care and have beeneffective at reducing perceptionof pain.Lok HI et al in hisprospective randomized trialcomprising 106 patientscomparing patient controlledsedation using propofol (10 mg/mL) and alfentanyl (50 mcg/mL)(bolus dose of 1 mL and effectivelock out time of 18 sec) andphysician administered sedationusing diazepam (0.1 mg/kg) andpethidine (0.5 mg/kg) (adminis-tered intravenously 5-10 minutesprior to procedure, and additionaldoses of pethidine 0.5 mg/kgwere given when required) during


transvaginal ultrasound guidedoocyte retrieval32. Theyconcluded that though patientcontrolled sedation provided lessanalgesia than physician contr-olled sedation but it is safe,satisfactory and accepted bypatients. The combination ofmidazolam and ketamine wascompared with general anaes-thesia with propofol andisoflurane42. No intraoperativepain was remembered in eithergroup. Hein et al. presented dataon two different MAC techniquesthat suggested that the pregnancyrate was higher when acombination of midazolam,fentanyl, and propofol (vs.fentanyl, ketamine, andmethohexital) was used43.Propofol was also used in a morerecent study at two different doselevels to achieve either generalanesthesia or intravenoussedation; and no difference wasfound in the pregnancy outcomerates7. In a comparison betweenpropofol-based general anest-hesia and paracervical localanesthetic blockade, Christiaenset al found no differencesbetween the fertilization rates orembryo cleavage characteristics44.These investigators also reportedthat the initial implantation rateafter propofol anesthesia (13.4%)was similar to the rate in the localanesthetic group (18.6%)7. Theresults of a retrospective chartreview also found no evidencethat the administration ofpropofol during aspiration ofovarian follicles had a negativeimpact on oocyte cumulativeembryo scores, implantation, orpregnancy rates44. Remifentanil,which is a rapid and ultra-shortacting opioid analgesic, also has

been successfully used forultrasonic- guided oocyteretrieval procedures as part of aMAC technique45,46,47. Thepresent retrospective studycompared pregnancy outcome ofART procedures in womenexposed to either generalanesthesia or MAC withremifentanil7. This retrospectivestudy suggests that in womenundergoing transvaginal ultras-ound-guided oocyte retrievalprocedures, the likelihood of asuccessful pregnancy is higherwith a remifentanil-based MACtechnique than with a “balanced”general anesthetic technique.These findings are supported bya preliminary report by Toon etal suggesting an increasedpregnancy rate in women havingspinal compared with generalanesthesia for oocyte retrieval48.Interestingly, use of electro-acupuncture in combination witha paracervical block for oocyteaspiration was judged a goodalternative to an opioid-basedMAC technique, with an evenhigher pregnancy rate49.Patient controlled analgesia(PCA)-PCA may facilitate anindividualized approach and, byallowing women a degree ofcontrol over their drugadministration, lead to higherlevels of patient satisfaction50.The effect of i.v. PCA wasevaluated in two studies and wasconsidered to be as effective asp h y s i c i a n - c o n t r o l l e dtechniques31,32 . Bhattacharya et alperformed the study to evaluatethe efficacy of patient controlledanalgesia during oocyte recovery.They premedicated their patientswith 4 mg midazolam and 25 mcgof fentanyl. Maintenance bolus

doses were then administered bythe clinician or by the patientherself using patient controlledanalgesia pump (10 mcg fentanylbolus with 1 min lock out). Theyconcluded patient controlledanalgesia fentanyl is an effectivealternative to physician admini-stered techniques in terms ofpatient comfort and satisfaction.Despite high satisfaction rates,many women still feel the needfor more analgesia during theprocedure31.However, sincephysician controlled sedationdemands higher doses ofanalgesics and many drugs havebeen found in the follicular fluidshortly after i.v. injection, it isquestionable whether thismethod is optimal in the presentsituation6. Patients also reportedhigh levels of satisfaction withintravenous opiates administeredby a physician or the patient31,32.Electro-acupuncture (EA)-Recently, electro-acupuncture,activates the endogenous opioidsystem responsible for pain hasbeen reported to decrease painduring oocyte retrieval and havefewer negative side effects18,49,51,52.Acupuncture is a pain-relievingmethod that activates endoge-nous pain-inhibiting systems suchas the spinal/ segmental gatemechanism and the endogenousopioid systems52. Electro-acupressure was compared withalfentanyl infusion and was foundto be a good alternative forconventional anaesthesia.Humaidan et al compared therole of electro-acupuncture as analternative to conventionalanalgesic method in anprospective randomized study in200 women53. Both the groupsreceived paracervical block. The


conventional analgesic methodused was benzodiazepinepremedication, alfentanyl 0.25mg boluses. Rescue analgesia wasprovided with intravenousalfentanyl in both the groups.They found significant differencein intraoperative pain. More painin electro-acupuncture group wasattributed probably to adminis-tration of premedication inconventional analgesic group.The procedure was well toleratedin both the groups. Gejervall etal compared the pain relivingeffect and postoperative wellbeing between electro-acupu-ncture and conventional analgesiain an randomized study in 160females for oocyte retrival22.Paracervical block was given inboth the groups. Conventionalanalgesia was provided withintravenous alfentanyl along with0.5 mg flunitrazapem and 1 gparacetamol premedication.Rescue analgesia was providedwith alfentanyl or notrox. Theyconcluded that electro-acupuncture cannot be generallyrecommended as a pain relivingmethod at oocyte aspiration butmight be an alternative forwomen desiring a non-pharmacological method. Anadvantage of electro-acupunc-ture is less postoperativetiredness and confusion comp-ared with conventional analge-sia.Stener-Victorin et al evaluatedthe efficacy of electro-acupu-ncture as peroperative analgesicmethod during IVF in twodifferent syudies18,49. The electro-acupuncture was comp-ared withalfentanyl. Both groups received

paracervical block as well. Thealfentanyl group received 0.5 mgalfentanyl and 0.25 mg atropineintrave-nously directly before aparacervical block was placed andoocyte aspiration began. Rescueanalgesia was boluses ofalfentanyl. They concluded thatanalgesic effects produced byelectro-acupuncture are as goodas those produced by conven-tional analgesics, and the use ofopiate analgesics with electro-acupuncture is lower than whenconventional analgesics alone areused. But women experience lessabdominal pain, less nausea andless stress at 2 h after oocyteaspiration, and also use less opiateanalgesics than when conven-tional analgesics alone are used.Conclusion-Variety of anaest-hetic techniques and analgesicmethods has been used but nodefinite conclusion has yet beenarrived regarding the techniqueof choice for IVF. No methodcould be considered as superiorto other technique if basicconcepts pertaining to IVF aretaken care. Conscious sedation issuitable for cooperative females.In addition to conscious sedationand analgesia, many methods ofpain relief during oocyterecovery are currently in use. Incase general anaesthesia isrequired, the anaesthetic drugsshould be used cautiously andefforts should be made to reducethe anaesthetic duration. Thepreferred modality of peri-operative care should beinvidualized as per the require-ment of the patient.

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14. Achwal M, Abuzeid M,Bovenschen JL, et al.Remifentanil and fentanylconcentrations in follicularf luid during transvaginaloocyte retrieval [Abstract].Anesthesiology 1999;90:A16.

15. Casati A, Valentini G,Zangrillo A, et al. Anaesthesiafor ultrasound guided oocyteretrieval: midazolam/remi-fentanil versus propofol/fentanyl regimens. Eur JAnaesthesiol 1999;16:773–8.

16. Beilin Y, Bodian CA,Mukherjee T, et al. The useof propofol, nitrous oxide orisoflurane does not affect thereproductive success ratefollowing gamete intrafa-llopian transfer (GIFT): amulticenter pilot trial/survey.Anesthesiology 1999; 90:36–41.

17. Cerne A, Bergh C, Borg K,Ek I, Gejervall AL, HillensjoT, Olofsson JI, Stener-Victorin E, Wood M,Westlander G. Pre-ovarianblock versus paracervicalblock for oocyte retrieval.

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18. Stener-Victorin E,Waldenstrom U, Wiland M,Nilsson L, Hagglund L,Lundberg T. Electro-acupu-ncture as peroperativeanalgesic method and itseffects on implantation rateand neuropeptide Y concent-rations in follicular fluid.Human Reproduction 2003;18:1454-1460.

19. Katzenschlager SMS, wolferMM, Langenecker SAK,Sator K, Sator PG, Li B,Heinze G, Sator MO.Auricular electro-acupun-cture as an additional periop-erative analgesic methoddurinh oocyte aspiration inIVF treatment. Humanreproduction 2006;21:2114-2120.

20. Tanbo T, Henriksen T,Magnus O, Abyholm T.Oocyte retrieval in an IVFprogram. A comparison oflaparoscopic and vaginalultrasound guided follicularpuncture. Acta ObstetGynecol Scand1988;67:243–246.

21. Ng EH, Chui DK, Tang OS,Ho PC. Paracervical blockwith and without conscioussedation: a comparison of thepain levels during eggcollection and the postop-erative side effects. FertilSteril2001; 75:711–717.

22. Gejervall AL, Stener-Victorian E, Moller A, JansonPO, Werner C, Bergh C.Electro-acupuncture versusconventional analgesia: a


comparison of pain levelsduring oocyte aspiration andpatients’ experiences of wellbeing after surgery. HumanReproduction 2005;20:728-735.

23. Kwan I, Bhattacharya S,Knox F, McNeil A.Conscious sedation andanalgesia for oocyte retrievalduring IVF procedures: aCochrane review. HumanReproduction 2006;21:1672-1679.

24. Wikland M, Evers H,Jakobsson AH, Sandqvist U,Sjoblom P. The concentrationof lidocaine in follicular fluidwhen used for paracervicalblock in a human IVF-ETprogramme. Human Reprod-uction 1990;5:920–923.

25. Soussis I, Boyd O, ParaschosT, Duffy S, Bower S,Troughton P, Lowe J etal.Follicular fluid levels ofmidazolam, fentanyl, andalfentanyl during transvaginaloocyte retrieval. Fertil Steril1995;64:1003–1007.

26. Christiaens F, JanssenswillenC, Verborgh C, Moerman I,Devroey P, Steirteghem AV,Camu F. Propofol concentr-ations in follicular f luidduring general anaesthesia fortransvaginal oocyte retrieval.Human Reproduction 1999;14:345-348.

27. Ben-Shlomo I, Moskovich R,Golan J, Eyali V, Tabak A,Shalev E. The effect ofpropofol anaesthesia onoocyte fertilization and earlyembryo quality. HumanReproduction 2000;15:2197–2199.

28. Martin R, Tsen LC, Tzeng G,Hornstein MD, Datta S.Anesthesia for in vitrofertilization: the addition offentanyl to 1.5% lidocaine.Anesth Analg 1999;88:523–526.

29. Gonen O, Shulman A,Gehtler Y, Shapiro A,Judeiken R, Beyth Y, Ben-Nun I. The impact ofdifferent types of anesthesiaon in vitro fertilization-embryo transfer treatmentoutcome. J Assist ReprodGenet 1995;12:678–682.

30. Martin R, Tsen LC, Tzeng G,Hornstein MD, Datta S.Anesthesia for in vitrofertilization: the addition offentanyl to 1.5% lidocaine.Anesth Analg1999;88:523–526.

31. Bhattacharya S, MacLennan,Hamilton MPR, TempletonA. Hoe effective is patient-controlled analgesia? Arandomized comparison oftwo protocols for pain reliefduring oocyte recovery.Human Reproduction 1997;12:1440-1442.

32. Lok IH, Chan MTV, ChanDLW, Cheung LP, Hains CJ,Yuen PM. A prospectiverandomized trial comparingpatient-controlled sedationusing propofol and alfentaniland physician-administeredsedation using diazepam andpethidine during transvaginalultrasound-guided oocyteretrieval. Human Reprodu-ction 2002;17:2101–2106.

33. Godoy H, Erard P, DeMunck L, Camus M, Gepts E,Van Steirteghem AC,

Devroey P (1993) Compar-ison of two local anaestheticsin transvaginal ultrasound-guided oocyte retrieval.Human Reprodu-ction 1993;7:1093–1097.

34. Corson L, Batzer FR, GocialB, Kelly M, Gutmann JN, GoKJ, English ME. Isparacervical block anesthesiafor oocyte retrieval effective?Fertil Steril 1994;62:133–136.

35. Ng EH, Tang OS, Chui DK,Ho PC. Comparison of twodifferent doses of lignocaineused in paracervical blockduring oocyte collection in anIVF programme. HumanReproduction 2000;15:2148-2152.

36. Ng EH, Miao B, Ho PC. Arandomized double-blindstudy to compare theeffectiveness of three differ-ent doses of lignocaine usedin paracervical block duringoocyte retrieval. J AssistReprod Genet 2003;20:8–12.

37. Viscomi CM, Hill K, JohnsonJ, et al. Spinal anesthesiaversus intravenous sedationfor transvaginal oocyteretrieval: reproductive out-come, side effects andrecovery profile. Int J ObstetAnesth 1997;6:49 –51.

38. Rosenblatt M, Bradford C,Bodian C, et al. The effect ofpropofol-based sedationtechnique on cumulativeembryo scores, clinicalpregnancy rates, and implant-ation rates in patientsundergoing embryo transferswith donor oocytes. J ClinAnesth 1997;9:614 –617.


39. Gonen O, Shulman A,Ghetler Y, et al. The impactof different types ofanesthesia on in vitrofertilization-embryo transfertreatment outcome. J AssistReprod Genet 1995;12:678.

40. Ng EHY, Tang OS, ChuiDKC, Ho PC. A prospective,randomized, double-blindand placebo-controlled studyto assess the efficacy ofparacervical block in the painrelief during egg collection inIVF. Human reproduction1999;14:2783-2787.

41. Schnell VL, Sacco AG, Savoy-Moore RT, Ataya KM,Moghissi KS. Effects ofoocyte exposure to localanaesthetics on in vitrofertilization and embryodevelopment in the mouse.Reprod Toxicol 1992; 6:323–327.

42. Ben-Shlomo I, Moskovich R,Katz Y, Shalev E. Midaz-olam/ketamine sedativecombination compa-red withfentanyl/propofol/isofluraneanaesthesia for oocyteretrieval. Human Reprodu-ction 1999;14:1757–1759.

43. Hein HAT, Suit CT, DouningLK, et al. Effect ofintravenous sedation on theoutcome of transvaginaloocyte retrieval: a compar-ative study of propofol- andm e t h o h e x i t a l - b a s e dtechniques. BUMC Proc1997;10:71–73.

44. Christiaens F, JanssenswillenC, Van Steirteghem AC,Devroey P, Verborgh C,Camu F. Comparison ofassisted reproductive techno-

logy performance afteroocyte retrieval under generalanaesthesia (propo-fol)versus paracervical localanaesthetic block: a case-controlled study. HumanReproduction 1998;13:2456–2460.

45. Rosenblatt MA, BradfordCN, Bodian CA, Grunfeld L.The effect of a propofol-based sedation technique oncumulative embryo scores,clinical pregnancy rates, andimplantation rates in patientsundergoing embryo transferswith donor oocytes. J ClinAnesth 1997;9:614–617.

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47. Casati A, Valentini G,Zangrillo A, et al. Anaesthesiafor ultrasound guided oocyteretrieval: midazolam/remife-ntanil versus propofol/fentanyl regimens. Eur JAnaesthesiol 1999;16:773–778.

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3CommentarCommentarCommentarCommentarCommentaryyyyy

he suffering and anguishblindness brings hasbeen documented thro-ughout the history.

TCuring blindness is a not a recentphenomenon however conceptof avoidable blindness came intoforefront in the prevention ofblindness control programmemore recently. Avoidable blin-dness has been defined asblindness that could reasonablebe prevented or cured within thelimits of resources that are likelyto be made available. Approxi-mately 75-85% of all blindnessis considered to be avoidable.Blindness is estimated to cost $25billion annually. Thoughblindness afflicts all nations, it ismost vicious in the developingworld. Blindness in developingcountries is generally associatedwith poverty and ignorance andis most commonly found in ruraloften remote and under-developed areas as well as in theurban slums. ‘Sight’ is afundamental right of all humanbeing to appreciate unlimitedblessings of mother-nature andit needs to prevented fromgetting deteriorated; correctedand/or restored by all means andstrategies.Definition-Blindness is definedin different ways by differentpeople. To a layman, blindnessconjures up images of a personwho is completely blind with noperception of light. However, inophthalmic practices not onlythese cases of ‘absolute

Vision 2020 - The Right to SightR. Jose, Sandeep Sachdeva

Directorate General of Health Services, Nirman Bhawan, New Delhi

blindness’ but also those withsevere impaired VISION are alsolabeled as blind. WHO hasdefined blindness as visual acuityof less than 3/60 or acorresponding visual field loss toless than 10 degrees in the bettereye with best possible correctionor inability to count fingers at adistance of 3 meters.1 NationalProgramme for Control ofBlindness [NPCB] in India hasdefined blindness with visualacuity of less than 6/60 orrestriction of field VISION toless than 10 degree in the bettereye with best possible correction[presenting VISION] or inabilityto count fingers at 6 meters [20feet]. Economic blindness refersto that level of VISION, whichhampers the earning potential ofan individual whereas Socialblindness refers to furtherdeterioration in VISION suchthat an individual is not able toundertake activities for dailysustenance and is unable tointeract properly with others inhis/her own family andcommunity. Classification ofblindness as per WHO andNPCB criteria is shown in Table1.2

The WHO study groupemphasized that each countrymust define blindness in relationto its own social and economicconditions, keeping thecategories of visual impairmentin mind. The blindness definitionin India has been more liberalthan their international partners

so as to provide rehabilitationservices to these individual in thecountry whose VISION did notpermit them to earn a livelihood.However, for all internationalcomparisons, standard casedefinitions should be adhered toi.e. cut off point for internationalcomparison was placed at 3/60[inability to count fingers at adistance of 3 meters]. The termvisual impairment includes caseswith blindness as well as lowVISION.Low VISION presents with allthree of the following characte-ristics:�� Impairment of visual

functioning even aftertreatment and/or standardrefractive correction.3

�� Visual acuity ranging fromlight perception to <6/18 ora visual field smaller than 20degrees in the better eye withbest possible correction.1

�� The person uses, or ispotentially able to use,VISION for the planningand/or execution of a task.4

Global- Every five seconds oneperson in the world goes blind;every minute, one child goesblind.5 The first global analysis ofdata on blindness by WHOindicated that in 1975 there were28 million blind people i.e. visualacuity less than 3/60 in the bettereye with best correction.Estimates in 1990 showed thatthis figure would continue toincrease, from 38 million in 1990


to 45 million in 2000. Projectionsbased on the global populationincrease and ageing, predicted 58million blind in 2010 and 75million by 2020 unless specialefforts are taken to arrest andreverse the trend. Of theestimated 45 million blind peoplein 2000, approximately 60% ofblindness due to cataract andrefractive errors [treatable]; 15%was due to trachoma, vitamin Adeficiency and onchocerciasis(Africa) [preventable]; another15% of blindness was due todiabetic retinopathy andglaucoma [partly preventable,although more difficult]; and theother 10% was attributable toage-related macular degenerationand other diseases [more researchrequired for best treatment].6

According to WHO criteria,there were estimated 6.7 millionblind in India as of 2002.1

South East Asia-The 11-countries [Bangladesh, Bhutan,India, Indonesia, Maldives,Myanmar, Nepal, Srilanka, DPRKorea, Thailand, Timor leste] inthis WHO region constitutes25% of worlds population, 40%of world’s poor, 33% of worldsblind, 50% of world’s childhoodblindness, 60% of world’scataract backlog cases andhighest number of blind personsamong WHO regions. Theprevalence of blindness in theregion is around 0.8% [range varyfrom 0.3% for Thailand to 1.5%for Indonesia].7

India-has a population of morethan one billion and the firstsurvey undertaken by IndianCouncil of Medical Research[ICMR] in 1974 indicated aprevalence of 1.38% of general

population [visual acuity <6/60].In the second survey [1986-89]sponsored by GOI-WHO, theprevalence rate increased to1.49% [VA <6/60]. As peravailable information fromvarious studies, there is anestimated 12 million bilaterallyblind persons in India with VA<6/60 in the better eye of whichnearly 07 million are with visualacuity [VA] <3/60 in the bettereye. Recent survey [1999-2001] in15 districts of the countryindicated that 8.5% of 50+population is blind [VA <6/60].VISION 20208-VISION 2020may have different connotationsin different settings andpersonnel choices. In USA, 20/20 stands for optimum eyesightand at the same time, it alsodenotes the year 2020 fromplanning and developmentalperspective. The objective“VISION 2020” is that no oneshould be needlessly blind anylonger by the year 2020. It is aninitiative with a commonobjective, which will allow peoplecutting across nations to work ina focused and coordinatedmanner to help raise globalawareness about blindness andmobilize additional resources toprevent or treat avoidableblindness. VISION 2020 willfurther develop and strengthenthe primary health/eye careapproach to problem ofavoidable blindness. This will bedone on the basis of theinvaluable international andnational experiences alreadygained through ongoing nationalprograms. Finally, the initiativeswill seek broad regional alliancesand eventually a global

partnership for eye care. Thesepartnerships are indispensable inestablishing worldwide thefundamental right “Right toSight” and thus save futuregenerations from the tragedy ofneedless blindness.Global initiative - Manyorganizations have attempted tocombat the problem of blindnessin the past. However it was feltthat there should be an umbrellaunder which all theseorganizations could be unifiedfor effective output.9 A jointinitiative-eventually namedVISION 2020: the Right to Sightwas conceived by World HealthOrganization [WHO] andInternational Agency forPrevention of Blindness [IAPB]and its constituent members. Itwas enshrined to providetechnical guidance and support tocountries that adopt the agendaof strong partnership amongministry of health, national andinternational organizationsinvolved in eye care, professionalorganizations, and civil societygroups- brought together on acommon platform in a nationalprevention of blindness progra-mme.The mission of VISION 2020is to eliminate the main cause ofavoidable blindness in order togive all people in the world,particularly the millions ofneedlessly blind, the right to sight.The goal of VISION 2020 is toeliminate avoidable blindness bythe year 2020. In long term, theinitiative seeks to ensure bestpossible VISION for all peopleand thereby improve their qualityof life. This goal is to be achievedthrough establishment of


sustainable, comprehensive eye-care system as an integral part ofevery national health system.The objectives of VISION 2020include raising the profile-amongkey audiences-of the causes ofavoidable blindness and of thesolutions that will help eliminatethe problem; identify and securethe necessary resources aroundthe world in order to provide anincrease level of activity inprevention and treatmentprogramme; and facilitateplanning, development andimplementation of the threeelements of the VISION 2020strategic plan by nationalprogramme.Strategy of VISION 2020 isbuilt upon a foundation ofcommunity participation, withthree essential components orelements:�� Cost effective disease control

interventions;�� Human resource developm-

ent [training and motivation]�� Infrastructure development

[facilities, appropriate tech-nology, consumables andfunds].

The guiding principles ofVISION 2020 are:�� Integrated into existing health

care system�� Sustainable in terms of

money and other resources�� Equitable care and services

available to all, not just therich

�� Excellence i.e. high standardof care through out.

National response - TheDirector General of WHOlaunched VISION 2020: the

Right to Sight in Geneva on 18th

Feb 1999 which was followed byseries of advocacy workshops inSouth East Asia [WHO] regionduring September 1999 to Feb2000. This lead to national andsub-national consultativeworkshops and processes during2001-03 with formulation ofNational Plan of Action leadingto reinforcement of commitmentand collaboration of stakeholderswherein a road map foramelioration of blindness in thecountry was detailed. Thisincluded physical targets,strategies for strengtheninghuman resource development,eye care infrastructure, advocacy,management informationsystem, national activities,recommendations of nationalworkshops for reduction ofdisease burden & primary eyecare and other importantmilestones. Target diseases forVISION 2020: India includescataract; childhood blindness;refractive errors and lowVISION; corneal blindness,glaucoma; diabetic retinopathyand trachoma [focal].10, 11 Inspiteof various constraints and withreasonable success in controllingcataract-related blindness, otherblinding conditions areincreasingly and adequately beingaddressed in the XIth five-yearplan period [2007-12] ofNational Programme for Controlof Blindness, Government ofIndia. Financial allocation hasbeen increased tremendously tobring other blinding conditions inthe forefront, ophthalmologist inpublic sector are being trained onthese issues at various public andNGO institutions, DiabeticRetinopathy and Glaucoma

screening & management is beingaddressed in this plan, low-VISION aids will be provided inselected medical colleges andRegional Institute of Ophth-almology [RIO], advocacyworkshops are being held atnational and regional level fororienting health personnel andstakeholders, newer strategies arebeing devised to enhancevoluntary eye donation in thecountry through consultativeprocesses, comprehensive evalu-ation of programme as well asIEC component under NPCBhas been commissioned todetermine the strengths andweakness of existing strategies/c o m p o n e n t s / s c h e m e s /mechanism of disbursement offunds and to revamp informationeducation and communication[IEC] component based on theinput from these evaluation,involvement of other stake-holders like Integrated ChildDevelopment Scheme functio-naries [Anganwadi workers etc]under Women and ChildMinistry, Education departmentunder Ministry of HumanResource Development [HRD],Panchyati Raj Institution [PRI]have been specifically roped intostrengthen and increase thevisibility of programme activitiesat grass-root level etc.

VISION 2020- India is aconglomeration of differentNGOs working in eye care in thecountry and came into existencein May 2004 with its secretariatin New Delhi, India. Themember organizations inVISION 2020 team has grown to65 as of March 2008 and itsfounder member included:12


�� International non-govern-mental organization [INGO]-Christoffel- Blindenmission,Germany; Sight Savers Inter-national, United Kingdom;ORBIS International, USA;Opera-tion Eye SightUniversal, Canada; SevaFoundation, USALion Clubs InternationalFoundation, USA

�� National non-governmentalorganization [NGO]-L.VPrasad Eye Institute, AndhraPradesh; Aravind Eye CareSystem, Tamil Nadu

�� National GovernmentalOrganization [GO] - Dr.Rajendra Prasad Institute forOphthalmic Sciences,AIIMS, New Delhi

The prime role played byVISION 2020: India is�� Supportive and participative

in implementation ofNational plan of action ofGovernment of India [GOI]especially in underservedareas;

�� Advocacy through formu-lation of state level plan ofactions and programme;

organizing events like WorldSight Day [2nd Thursday ofOctober], Eye donationfortnight [23rd Aug to 8th Sep]in collaboration & financialassistance from GOI andbuilding strong network ofnational NGOs;

�� Information collection anddissemination: mapping ofINGO for information ofservices and partnership;facilitating development oftraining modules, manuals,protocols, guidelines, reso-urce material pertaining tostrategic thrust area ofVISION 2020 and making itavailable to eye careinstitutions; regular interface/interactions amongst variousstakeholders and keep themupdated on all issues; holdingnational events and regionalconferences with VISION2020 themes every year.

�� Resource management: mob-ilization of resources frommembers and new sources forcar rying out programmeactivities

�� Research and publication

Table-1, Comparison of WHO and NPCB definitions2

WHO-ICD classification ofvisual impairment andblindness

Low VISION

Category [1]

Category [2]

Blindness

Category [3]

Category [4]

Category [5]

Visual acuity

<6/18-6/60 in better eye



<1/60 in better eye-perceptionof light

No perception of light

NPCB categorization ofvisual impairment andblindness

Low VISION

Economic blindness

Social blindness

References

1. Serge Resnikoff, DonatellaPascolini, Danel Etya Ale,Ivo Kocur, RamachandraPararajasegaram, Gopal PPokharel & Silvio P Mariotti.Global data on visualimpairment in the year 2002.Bulletin of the World HealthOrganization, 2004; 82: 844-51

2. GVS Murthy, Sanjeev KGupta, Damoder Bachani.In: The principles andpractice of communityophthalmology. NationalProgramme for Control ofBlindness, Government ofIndia, New Delhi; 2002.

3. Liz Simon. Low VISIONand rehabilitation for olderpeople integrating servicesin the health care system. JCommunity Eye Health,June 2008; 21 [66]: 28

4. The management of lowVISION in children. Reportof a WHO consultation:


Bangkok, July 1992. WorldHealth Organization, 1993.WHO/PBL/93.27.

5. Rao GN. VISION 2020:The right to sight. Indian JOphthalmol 2000;48:3

6. State of the World’s SightVISION 2020: the Right toSight, 1999-2005. WHO.Geneva; 2005.

7. VISION 2020: The Right toSight. Report of anIntercountry Consultationon development of regionalstrategies. Jakarta, 14-17 Feb2000. WHO, Regional officefor South East Asia, NewDelhi; 2001.

8. R.D. Thulasiraj, R.Muralikrishnan. VISION2020: The Global Initiativefor Right to Sight. Availablefrom: http://laico.org/v 2 0 2 0 r e s o u r c e / f i l e s /V I S I O N 2 0 2 0 _ j u l -sep01.pdf.

[Accessed on 2008 Nove-mber]

9. M Deshpande. VISION2020: Right to Sight-India.MJAFI 2008; 64: 302-03

10. Meeting of the workinggroup on VISION 2020: theRight to Sight, India.Ophthalmology section,Directorate General ofHealth Services, Ministry ofHealth and Family Welfare,New Delhi. Report; 2003.

11. Plan of Action. VISION2020: the Right to Sight.Directorate General ofHealth Services, National

Programme for Control ofBlindness, Ministry ofHealth and Family Welfare,New Delhi.

12. Membership details availablefrom www.VISION2020 ind i a .o rg[accessed on 2008 October]

Nitrous oxideNitrous oxide is a relativelyweak anaesthetic. A concen-tration of at least 50 per cent isrequired to produce worthwhileanalgesia. For this reason,nitrous oxide is always mixedwith oxygen instead of air. Twotypes of apparatus are used.The first mixes the two gases(supplied separately) beforedelivery to the patient. Thisapparatus is usually fixedpermanently to the wall, and theconcentration of nitrous oxidecan be adjusted within the rangeof 0-50 per cent or 0-70 percent (depending on nationalregulations). These upper limitsensure that patients will not loseconsciousness and can neverreceive less oxygen than existsin room air (21 per cent). Thistype of apparatus is popular inAustralasia. Being a wall fixture,it is not portable and so cannotbe used for a home delivery.The other kind of apparatuswhich is commonly used tosupply nitrous oxide is called‘Entonox’. In this case, a 50:50mixture of nitrous oxide andoxygen is contained in a singlecylinder . A special valve at thetop of the cylinder reduces thepressure to safe levels (so thereis absolutely no danger of being‘blown up’!). It is not possibleto alter the concentration of

nitrous oxide when usingEntonox, but in practice, thisdoes not seem to be important.One advantage of Entonox isthat it is portable, and cantherefore be used for homedeliveries (in Britain, but not inAustralia). Entonox is also usedin many countries by param-edical personnel to provide painrelief at accident sites and inambulances.Like all drugs that enter thebloodstream, nitrous oxide isdistributed throughout thebody. It also passes very easilyacross the placenta and isdistributed likewise throughoutthe baby’s body. Unlike opioiddrugs, however, nitrous oxide isexcreted from the body veryquickly - and entirely - by thelungs. It does not have to bebroken down (or metabolised)first by the liver and so there areno ‘by-products’. This rapidelimination of nitrous oxidealso applies in the case of thebaby: within five minutes ofbirth it cannot be detected inthe baby’s breath at all. Becauseof its rapid elimination, itdoesn’t really matter how longnitrous oxide is used; the gasdoes not ‘build up’ oraccumulate to any degreewhether it is used for fiveminutes or five hours.Most large surveys have cometo similar conclusions regardingthe effectiveness of nitrousoxide in labour when it is usedproperly. Rather less than 50 percent of women claim satisf-actory relief: 20 per cent obtainsome relief for some of thetime, and approximately 30 percent find it completelyineffective.


4 Effective Communication-Resident’s Perspective

R. Jose, Sandeep SachdevaDirectorate General of Health Services, Ministry of Health and Family Welfare, Nirman Bhawan, New Delhi

C ommunication is part ofour normal relationshipwith other people. We are

not only communicating with‘others’ but also with ‘ourselves’throughout the day. In ourprofessional setting, we areinvolved in communicating withsuperior, colleagues, juniors,patients and their attendant. Ourability to influence others dependon our communication skills e.g.speaking, writing, listening,reading and reasoning.Theseskills are very important in healtheducation especially whileinteracting with patients and theirattendants. Studies have shownthat at least 50% of patients leavethe doctors’ chamber notknowing what they have beentold; 50% of psychosocial andpsychiatric problems are missedby physicians due to lack ofproper communication1; physi-cian interrupt patients on anaverage of 18 seconds whilepatient is describing his/herpresenting problems2; 54% ofpatients’ problems and 45% ofpatient concerns are neitherelicited by the physician nordisclosed by the patient3; and71% of patients stated poorrelationships as a reason for theirmalpractice claims 4 ; whereas 95% of medico-legal cases occurdue to a communicationbreakdown between the patient/relatives and the doctor.5

Research has consistentlydemonstrated that patients’understanding of their

conditions and treatment ispositively related to adherence6,and that adherence, satisfaction,recall, and understanding are allrelated to the amount and typeof information given7 andpatients who understand thepurpose of the prescription aretwice more likely to comply thanthose who do not understand.8This paper reviews the concepts,types, functions, approaches, &barriers of communication andsuggest some tips for developingskills for effective comm-unication.Definition- Communication isregarded as two way process ofexchanging or shaping ideas,feelings and information andarriving at a commonunderstanding of the message.Communication is more thanmere exchange of information.It is a process necessary to paveway for desired changes in humanbehaviour and involve individualand community participation toachieve predetermined goals. 9

Communication and educationare interwoven. The goal of allcommunication is to bring abouta change in the desired directionof the person who receives thecommunication. This changemay be at the cognitive level interms of increase in knowledge;it may be affective in terms ofchanging existing patterns ofbehavior and attitudes; and it maybe psychomotor in terms ofacquiring new skills. These arereferred to as learning objectives.

Communication process-Communication is the basis ofhuman interaction that involvesa complex process of followingcomponents: Sender [source];receiver [audience]; message[content]; channel [medium];feedback [effect]. If any of thesecomponents are missing,effective communication cannottake place.10

Type of communication 11

�� One-way communication[Didactic method]: The flowof communication is one-way from the speaker to theaudience. The familiarexample is the lecturemethod in classroom. Thedrawbacks of didacticmethods are knowledge isimposed; learning isauthoritative with littleaudience participation; nofeedback and does notinfluence human behaviour;

�� Two-way communication[Socratic method]: In a two-way communication, boththe communicator andaudience take part. Theaudience may raise questionsand add their owninformation, ideas andopinions to the subject. Theprocess of learning is activeand more likely to influencebehaviour.

�� Verbal communication: It isa traditional way ofcommunication by way ofmouth and more persuasive

CommentarCommentarCommentarCommentarCommentaryyyyy


than written and printedmatter.

�� Nonverbal communication:Communication can occureven without words. Itincludes a whole range ofbody movements, postures,gestures, facial expressionse.g. smile, raised eyebrows,staring, gazing, etc. Silence isnon-verbal communication.

�� Formal and informalcommunication: Commun-ication has been grouped intoformal [follows lines ofauthority] and informal[grape vine] communication.Informal networks e.g. gossipcircles exist in all organiz-ation. The informal channelsmay be more active, if theformal channels do not caterto the information needs.

�� Visual communication: Thevisual form of commun-ication comprises charts,graphs, pictograms, tables,maps, posters, informationbooklets, magazines etc.

�� Telecommunication andInternet: Telecommunicationis the process of communi-cating over distance usingelectromagnetic instrumentsdesigned for the purpose.Radio, TV, Internet are masscommunication media.

Functions of health commun-ication12- The term healthcommunication is often usedsynonymously with healtheducation which itself is thefoundation of all health-careprogramme and system includingall specialties. Health communi-cation has to cater to the needs

of individual and/or organiza-tion i.e. to provide scientificknowledge or sensitive inform-ation; education; motivation,persuasion, counseling, raisingmorals, health development,building human relation andorganization.Barriers of communication-Health communication mayoften fail due to ‘barriers’between the sender and thereceiver that may result inproblems and concern of variednature. Better understanding ofthese barriers will prepare us todeal with any situation in a moreprepared way. These barriers ofcommunication may be at variouslevels

�� Physiological: difficulties inhearing, expression

�� Psychological: emotionaldisturbances, neurosis, levelof intelligence, language orcomprehension difficulties

�� Environmental: noise, invi-sibility, congestion

�� Cultural: illiteracy, level ofknowledge and underst-anding, customs, beliefs,religion, attitudes, economicand social class differences,language variati-ons, culturaldifficulties, between foreig-ners and nationals, betweenurban and rural.

Approaches and methods inhealth communication-Thereare various approaches andmethods in health commun-ication and each has its ownadvantages and disadvantages ina given setting for achievementof pre-determined health and

family welfare goals. Theapproaches and methods inhealth communication may bebroadly grouped as:

�� Individual approach: Perso-nal contact e.g. in OPD/IPD,home visits, personal letters

�� Group approach: Lectures,demonstrations, discussionmethods- group discussion,panel discussion, symposium,workshop, conferences, semi-nars, role-plays.

�� Mass approach: Television,radio newspaper, printedmaterial, posters, healthmuseums and exhibitions,folk methods, Internet.

Effective communication-After reviewing the concepts,functions and barriers ofcommunication the need foreffective and meaningfulcommunication has to berealized with some introspectionin our life. As reported in anewscolumn some of the causesof communication gap amongstmedical practitioners could be [a]some doctors are inherentlyreserve and less communicativeand more over these skills are nota part of medical teaching; [b]some doctors are very busy andhave taken many attachmentsand as such unable to devote timeand commitment to the patients;[c] some doctors may be havinglack of knowledge of the subjectas well as may not be updated onrecent advances in medicine. 13

Communication is both a scienceand an art that can be cultivatedand developed with little effortand patience. Some tips foreffective communication are,14


Dos� Always think ahead of what

you are going to say�� Use simple words and

phrases that are easilyunderstood.

�� Increase your knowledge onall aspect of subject you aredealing

�� Make effort to appearenthusiastic while speakingensuring clarity and audibility

�� Check twice with the listenerwhether you have beenunderstood accurately or not.

�� In case of an interruption,always do a little recap ofwhat has already been said

�� Always pay attention to thecontent ignoring speakersappearance or manner inwhich message is delivered

�� While listening, maintainyour concentration on thesubject and documentimportant points.

�� Always ask for clarification,if you have failed to grasp thepoint of view of the speaker

�� Repeat what the speaker hassaid to check whatever hasbeen said and what has beenunderstood is the same ornot.

Don’ts

�� Do not interrupt the speaker,react instantly or muttersomething in anger/anguish

�� Do not use technical jargonswhile interacting withpatients

�� Do not speak too fast or tooslow

�� Do not speak in inaudiblesurroundings. You will not beheard.

�� Do not have a mental state ofego or superiority complexwhile addressing a peer orpatient

�� Do not harbor pre-conceivedideas, biases or prejudice overan issue

�� Do not assume that everybody understands you

�� While listening do not glancehere and there. It may distractthe speaker.

�� Do not overload the patientwith information

�� Do not jump to a hastyconclusion that you haveunderstood every thing

C o n c l u s i o n - E f f e c t i v ecommunication is more thansimply transmitting informationto people in professional or socialsetting. No matter how clear theidea is in the mind of sender/communicator, it may still bemarked by poorly chosen words,omissions, lack of coherence,poor organization of ideas,awkward sentence structure, andfailure to clarify the implicationof the message. Each residentwhile undergoing training inrespective specialty must make aconscious effort to learn theintricate art and science ofeffective communication. Thiswill be helpful to candidate notonly during the examination butalso through out life, as s/hewould have an edge ininfluencing people for behaviourchange and making an impact on

the society. We have heard thestory of Eklavya, who learntarchery all by himself. He had noguru [Facilitator!], but only theintense wish to learn. This alonecan drive the learning process butit will help only those few learnerswho are focused and driven bycertain ideals. Similarly there mayhave been gurus who have madegreat disciple out of ordinarypeople. However, it may bedifficult to get such disciples andgurus in present era.15 Till suchtime we are able to find a rightguru, the onus of learningeffective communication,enrichment, development andgrowth lies on the learner in asystem of teaching & trainingthat is based on principle of adultlearning.References

1. Davenport S, Goldberg D,Millar T. How psychiatricdisorders are missed duringmedical consultations.Lancet. 1987;2:439–441

2. Frankel, R.; Beckman, H.Evaluating the patient’sprimary problem(s). In:Stewart M, Roter D., editors.Communicating WithMedical Patients. NewburyPark, Calif: Sage Publications;1989. pp. 86–98

3. Stewart MA, McWhinney IR,Buck CW. The doctor/patient relationship and itseffect upon outcome. J R CollGen Pract. 1979;29:77–81

4. Levinson W. Physician-patient communication. Akey to malpractice


prevention. JAMA. 1994;272:1619–1620

5. Nancy Singh. A HELPingHand: A spotlight. ExpressHealthcare; 2008 June.Available from: http://www.expresshealthcare.in[cited 2008 July 7]

6. Burgoon JK, Pfau M,Parrott R, Birk T, Coker R,Burgoon M. Relationalc o m m u n - i c a t i o n ,satisfaction, compl-iancegaining strategies andcompliance in commun-ication between physiciansand patients. CommunMonogr. 1987; 54:307–324

7. Hall JA, Roter DL, KatzNR. Meta-analysis ofcorrelates of providerbehavior in medical encou-nters. Med Care. 1988;26:657–675

8. Daltroy LH, Katz JN,Morlino CI, Liang MH.Improving doctor patientcommunication. PsychiatrMed. 1991;2:31–35

9. Communication for HealthEducation. K Park. In:Parks Textbook of Preve-ntive and Social Medicine,16th ed. Jabalpur (India): M/s Banarsidas Bhanot; 2000.pp.600-13

10. Directing and Leading. Col.BM Sakharkar. In: Princi-ples of Hospital Adminis-tration and Planning. NewDelhi: Jaypee Brothers;2003. pp. 138-141

11. Communication. HaroldKoontz and Hein Weihrich.

In: Essentials of Manage-ment, 5th ed. New Delhi:Tata McGraw-Hill; 2000.pp. 365-85

12. Information Educationand Communication (IEC)Programmes. WHO, Gen-eva. Available from: http:// w w w . w h o . i n t /r e p ro d u c t i ve - h e a l t h /p u b l i c a t i o n s /interagency_manual_on_RH_in_refugee_situations/a1.pdf. (cited 2008 June 29)

13. Express healthcare. 2001March Issue 01-15.Available from: www.expresshealthcaremgmt.com/20010228/opinion.htm[cited 2008 July 9]

14. Human Resource Manage-ment. JP Gupta and AKSood, editors. In: Conte-mporary Public Health:Policy, Planning andManagement. New Delhi:Apothe-caries foundation;2005. pp. 5.48-5.51

15. ASHA facilitators guide.Book No.1. Ministry ofHealth and Family Welfare,Government of India,Nirman Bhawan, NewDelhi; 2005. pp. 4-5

Recent advances inintravenousanesthesia

Efforts to develop newhypnotic compounds conti-nue, although several haverecently failed in develo-pment. Propofol has beenreformulated in variouspresentations with and

without preservatives.Pharmacokinetic and phar-macodynamic differencesexist between some of thesepreparations, and it iscurrently unclear whetheranyhave substantial advantagesover the original presentation.The use of target-controlledinfusion (TCI) has beenextendedto include paediatricanaesthesia and sedation.Application of TCI toremifentanil is now licensed.Linking ofelectroencephalogram(EEG)monitoring to TCI for closed-loop anaesthesia remains aresearch tool, althoughcommercial development mayfollow. The availability ofstereoisomer ketamine andimproved understandingof itspharmacology have increasednon-anaesthetic use ofketamine as an adjunctanalgesic. It may be useful insubhypnotic doses forpostsurgical patients with painrefractory to morphineadministration.


5ReviewReviewReviewReviewReviewArArArArArticleticleticleticleticle

Mdetermine the molecular stru-cture of a compound or to detectthe presence of a compound. Itdetects electromagnetic signalsproduced by atomic nuclei withan odd number of protons andneutrons and thus can obtain insitu concentrations of chemicalsin normal and diseased tissueaiding medical diagnosis.MRS issimilar to the spectroscopy usedin chemistry/physics to studycomposition of matter in the pasthalf a century. It has been in uselonger than magnetic resonanceimaging (MRI) and has a greatpotential for impacting patientdiagnosis and treatment. In MRIimages of tissues are generatedusing resonance of protons fromwater molecules, while in MRSwater signals are suppressed andinformation is gathered frommagnetic resonance signals ofchemical compounds other thanwater. This gives the spectralsignature of diseased tissues byevaluating the in vivobiochemistry. The information isprovided as a biochemicalspectrum rather than an imageToobtain MRS information oneneeds to trade off spatialinformation (resolution) forchemical information. MRSprocedures are evolving towardsproducing detailed chemicalspectra for each image voxel [1]Currently, the resolution of thesevoxels is limited by the desiredsignal to noise ratio (SNR), the

R Spectroscopy is a noninvasive technique inwhich MR is used to

Basics of MR SpectroscopyNamita Singh Saini, Giriraj Singh Gujral, S Khushu, RP Tripathi

NMR Research Centre Institute of Nuclear Medicine and Allied Sciences, and Department ofRadiodiagnosis & Imaging,Base Hospital, Delhi

tissue concentration of themetabolites of interestTheconcentration of water in tissuesis of the order of 100M, whichis 10,000 times the millimolarconcentrations of most metab-olites being studied by MRS.Thus images made from nonwater metabolites are severelylimited by signal strength.Magnetic field strength is a majordeterminant of MR signalstrength. As the field strengthincreases the MR signalincreases[2]. Hence to get a goodsignal from compounds atmicromolar concentration, it isdesirable to image them at higherfield strength preferably at 1.5Tor higher. In addition to SNRimprovements with increasingfields, the spectrum is spread outso that overlapping signals fromadjacent peaks do not obscurefine detailsBasic principles-Results in bothspectroscopy and MR Imagingfollow directly from thefundamental relationship thatsignal strength is directly deter-mined by magnetic field strengthNuclei with odd no of protonsand neutrons behave as spinningbar magnets and have a magneticmoment and interact with theexternal magnetic field. MRSrequires that the body should beplaced in a strong static externallyapplied magnetic field. The fieldshould be homogenous andshould not vary with time.Another oscillating magnetic fieldcalled the radio frequency ( rf )field produced by the rf coil

needs to be placed around thebody part being examined. Therf coil produces the oscillatingmagnetic field which interactswith the different types of atomicnuclei . There is an exchange ofenergy with nuclei oscillating atthe same frequency as the rfpulse. The rf pulse is switchedoff.Interaction between themagnetic field of atomic nucleiand the main external magneticfield produces an electromagneticsignal. This signal is detected bythe RF coil to give the MRSpectrum. Gradient coils inconjunction with the RF pulsehelp in spatial localizationTheMR spectrum is a plot (intensityversus the frequency) of thenumber of nuclei in differentmagnetic field environments. Byconvention the signal fieldincreases to the left.

Fig-1, Normal MR Spectrum ofthe Brain showing the intensityof the resonance ie the signalon the Y axis and the frequencyon the X axis. The amplitudeof each peak ref lects thenumber of nuclei at thatparticular chemical shift.


Nearly all hydrogen atoms givean MRS signal. Water and fat arepresent in abundance in thehuman body. Since the protonsignal from water and fat are solarge relative to the othermetabolites technique need to beemployed to suppress thesesignals to enable signals fromchemicals in micro molarconcentration to be picked up.Chemical Shifts

According to the larmourequation w0 = ¡ B0,(Equation-1)where B0 is the strength of theexternally applied magnetic fieldand ¡ the gyromagnetic ration thatis characteristic for each type ofatomic nucleus and w0 is theprecessional frequency. Considerbare protons in a magnetic field.If they all gave the same signalfrequency then very littleinformation would be available.It was soon recognized thatprotons which were part of amolecule had a differentresonance frequency from thebare protons. So the effectivefrequency of protons inmolecules was proportional tothe effective magnetic fieldexperienced by them, B effB eff = B0 + Blocal ,(Equation-2)The Blocal can be either positiveor negative. It is the result of twofactors - the magnetic fields ofelectrons circulating around thenuclei and contributions from themagnetic fields of neighboringnuclei. Hence the measuredsignal wmeas can be expressed aswmeas = ¡ B eff , (Equation-3)wmeas = ¡ (B0 + Blocal )wmeas = ¡ B0 + ¡ Blocal

wmeas = ¡ B0 ( 1+ s), (Equation-4)

Equation-4 thus reflects that thelocal magnetic field Blocal ,produced is generally directlyproportional to the strength ofthe applied magnetic field B0. Theproportionality constant, s , iscalled the chemical shift for thenucleus and is typically expressedin parts per million (ppm) of thefrequency in the applied magneticfield. Thus, s is independent ofthe applied field strength and isfixed for the molecularenvironment (structure) of thenucleus.When an externalmagnetic field is applied, most ofthe protons of the body alignparallel to the main magnetic fieldand thus reinforce the appliedmagnetic field; called parama-gnetic while a few align oppositethe main magnetic field;diamagnetic. When the inducedmagnetic field opposes theexternal magnetic field, theeffective field at the nucleus islessened and the nucleus is saidto be shielded. Conversely whenthe induced magnetic fieldincreases the field at the nucleus,it is said to be deshielded.Aparticular atomic species isdetermined by the number ofelectrons that exist around it.However the actual electrondensity around the nucleidepends on the molecularenvironment (hydrogen, coval-ent, electron bonds) and thenumber of electro negativegroups nearby. Protons of thebody arise from two mainsources: water (H2O) and fat(primarily -CH2- groups). Theelectronegative oxygen atoms ofwater tend to pull electrons awayfrom the protons, so the applied

magnetic field experienced bythem is not shielded as much asthe protons in the fat. Thus theproton signals of water and themethyle protons of fat will be atfrequencies that are separated by3.5ppm, regardless of thestrength of the applied externalmagnetic field1.A basic step in spectroscopy islocalization of the region ofinterest in all three spatialdimensions, yielding the volumeof interest. This can beperformed using two methods:single voxel spectroscopy (SVS)or chemical shift imaging (CSI).In clinical practice SVS is theeasier and faster technique forobtaining metabolic inform-ation3. A homogenous magneticfield is an important prerequisitefor obtaining clinically resolvablespectra. Shimming the field in theregion of interest is oftenrequired to ensure homogeneity.Since the water concentration inliving tissues (100M) is so muchgreater than the tissueconcentrations of most metab-olites of interest (10mM), thewater signal is bound tocompletely dominate therecorded signals unless it issuppressed. The most commonapproach to suppress the watersignal is to use chemical shiftselective (CHESS) rf pulses1.Triglycerides in adipose tissuesalso produce a large signal. Sosignal from fat too needs to besuppressed . Application ofchemical shift selective pulsescentred on lipid peak result intheir suppression. Fortunatelythis is not a problem inneuroimaging, as Brain has no fat.


SVS MR image is first obtained.The region of interest (ROI) islocalized; defined as a rectilinearvoxel. A rectilinear voxel isdefined by placing three selectivepulse along the three orthogonalaxes. MRS signal is acquired onlyfrom this voxel. Signal fromnuclei outside this voxel issupressed using gradient pulsescalled crushers. Many additionalgradient pulses are incorporatedinto the pulse sequences tosuppress unwanted echoes arisingfrom outside the selectedvolume.SVS is easier and fastertechnique for obtainingmetabolic information. The voxel(volume element) 4 being sampledhas a minimum size of 1 cm3

SVS have the advantage ofexcellent localization, fieldhomogeneity, and water supres-sion from a small well definedvolume. One can obtain aspectrum within 3 to 10 minutesdepending upon the chosen TR.It allows reliable quantification ofmetabolites. It is used best whenglobal and not focal effects areof interest. (eg hepaticencephalopathy or brain injuryfrom near drowning).

Fig-2, Single voxel spectroscopyshowing a low grade glioma

MRSI / CSI / MultivoxelSpectroscopy-MRS signals aresimultaneously acquired from agrid containing a large number ofrectilinear voxels that include thetissues of interest. CSI has theadvantage of obtaining multiplespectra in one data acquisition.One can obtain information fromdifferent voxels without runninga spectroscopic scan. Single voxelspectroscopy gives one spectrumwhile CSI gives as many as 16 ormore spectra depending upon thevoxel size and the number ofphase encoding steps used. Asingle voxel study can be repeatedmore easily if patient motion issuspected. Pt motion willcompromise the data in CSIcompletely. There is poorerdefinition of the voxel in CSIthan SVS. CSI provides a meansof observing differences inmetabolite levels throughout anorgan or lesion when doneproperly. CSI can also be usefulwhen multiple areas of interestsuch as radiation necrosis andrecurrent tumor need to bedifferentiated. CSI can also helpselect the appropriate site forbiopsy in cases of brain tumorsby guiding the needle to the voxelwhere active tumor tissue ispresent and avoiding voxelsshowing necrotic tissue. CSI alsohelps gain insight into theheterogeneity of tumor tissue byshowing high Cho/Cr ratios invoxels overlying high gradetumor tissues and low Cho/Crratios in voxels overlying lowergrades of malignancy.

Fig-3, CSI: A grid placed over theregion of interest with spectraobtained from each voxel in thegrid , in a single data acquisition.

Advantages of CSI -to assessdifferent regions of a mass,tostudy the brain parenchymaaround the mass, to assessresponse to therapy,to look fortumor recurrence.The acquisition of MRSspectrum takes very long.Becauseof low biological concentrationsand less sensitive nuclei, signalaveraging is needed to increasethe signal to noise ratio. At least128 signal averages are requiredto obtain interpretable spectrawithin a clinically acceptabletime5. Repeated signal acquis-itions thus increases time ofacquisitions. To obtain spectralresolution, that is to separate theindividual peaks in a spectrum ahomogenous magn-etic field


through the ROI. Despite thehuge number of biomolecules intissues, few are identifiable invivo because only freely mobilecompounds that are present insubstantial concent-rations giveenough signals to be detected6.Spectroscopically visible metab-olites include- 1H, 31P, 13C, 7Li and19F1H MRS is preferred because itgives the strongest and mosteasily detectable signal. It isperformed using the samehardware as conventional MRimaging. Majority of neuror-adiologic studies utilise 1H MRS.Information of the identity ofmetabolites is obtained fromtheir peak positions. Quantifi-cation of the metabolites fromthe area under the peaks.

Observable Proton Metabolites

ppm

0.9 – 1.4

1.3

2.0

2.2 – 2.4

3.0

3.2

3.5

1.2

1.48

3.4 & 3.8

Metabolites

Lipids

Lactate

NAA

Glutamine/GABA

Creatine

Choline

Myoinositol

Ethanol

Alanine

Glucose

Properties

Products of Brain destruction

Product of anerobic glycolysis

Neuronal marker

Neurotransmitters

Energy Metabolism

Cell Membrane marker

Glial cell marker

Triplet

Present in meningiomas

Increased in Diabetics

Typically human MRS protocolsuse a magnetic field of 1.5 Teslaor higher.The metabolites commonlystudied in a standard Brainanalysis include Choline,Creatine, NAA, Lactate, Lipid,

Alanine, Glutamate, Glucose,Glu+Gln, Myo-inositol.The MRsignal detected from a volume isdirectly proportional to theconcentration of nucleiSTEAM- (Stimulated echoacquisition mode) pulse sequenceuses a 900 refocusing pulse tocollect signals like a gradientecho. It allows visualization ofmetabolites with short relaxationtimes. Water suppression is moreeffective with this technique. Itsdisadvantages are a possible lossof signal intensity and highsusceptibility to motion, quantumeffects and diffusionPRESS (Point resolved spectro-scopy) sequence refocuses thespins with a 1800 rf pulse like aspin echo. It uses longer echotimes and therefore allows

visualization of metabolites withlonger relaxation times. They areless susceptible to motion,quantum effects and diffusionand have a better SNR thanstimulated echo mode.Most MRspectra are obtained with echo

times of 135 and 270milliseconds. Using long echotimes the signal from most brainmetabolites is lost. Converselyshort echo times allow foridentification of many othermetabolites.Metabolite significance-Eachpeak of the MR spectrum ischaracterized by its resonancefrequency, height, width and area.Height or area under the peak iscalculated to give the measure ofthe concentration of themetaboliteCreatine (resonates at 3.03ppm)-Creatine-phosphocreatineis an energy-producing compo-und in cellular metabolism-provides a measure of the energystores. Creatine is increased inhypometabolic states anddecreased in hypermetabolicstates. In normal spectra creatineis located immediately to the rightof choline.Choline(resonates at 3.2ppm)-is a constituent of cellmembrane serves as a marker ofcellularity- elevated in tumors andinflammatory processes. Parado-xically Choline levels are low invery high grade tumors becauseof presence of necrosis.Therefore 1H MRS is not anindependent diagnostic tool butrather a complementary modalityto clinical MR imaging and PET.Clinical response to a tumor isseen by reduction in the level ofcholine before significantchanges are evident on MRINAA (resonates at 2ppm)- isthe most prominent resonance inproton MRS of the brain. It is aneuronal marker and decreaseswith any disease affecting


neuronal integrity such asneoplasms, infarcts, epilepsy anddementia.There is a markedincrease in NAA only in canavan’sdisease.NAA is generally accep-ted to be localized to the neuronsand any destructive or infilte-rative lesion might therefore beexpected to result in graduatedreduction in NAA signalintensity. For this reason NAA isless useful in evaluation of braintumorsLactate(resonates at 1.32ppm)- It is a doublet of of twodistinct resonance peaks at1.32ppm. Another peak forlactate occurs at 4.1 ppm.Because this is very close to waterit is generally suppressed.Altering echo time generallyconfirms a peak at 1.32 ppm aslactate. At an echo time of 270milliseconds, lactate projectsabove the base line, but at an echotime of 135 milliseconds it isinverted below the base line. Thisphenomenon is called j coupling.It is a product of anaerobicmetabolism-seen in hypoxia.Lactae can be seen even aftertreatment due to treatmentinduced ischemia in tumor tissue.MR spectroscopy shows elevatedlactate in patients who havereceived 40 Gy or more to thebrain. The lactate peak can beidentified before MRI shows anychanges.Lactate and lipidsincrease in anaerobic metabolismand are present in some tumorssuch as high grade astrocytomasand meningiomas.J Coupling-Splitting of thesignal peak arises from thephenomenon of spin-spincoupling between neighbouringnuclei. In addition to the small

electron magnetic field influen-cing the net magnetism at thenucleus, the small nuclearmagnetic fields from nearbyprotons can also contribute to thenet field strength. The precisefield strength contributing to anuclei depends upon theneighbouring nuclei and thechemical bonds between them. Aresonance peak is often split intoa number of equally spaced peaksreferred to collectively asmultiplets. The extent ofcoupling depends upon theproximity of the spins in spacewith the most interactionoccurring if the two spins arechemically bonded. When aproton interacts with a nearbyproton, they are influenced byeach other’s field. The net effecvtof this interaction depends uponwhether the respective fields areoriented with or against theapplied magnetic field direction.Consider a proton A being at onelocation in a molecule. If there isone neighboring proton, theneighboring magnetic field caneither add (+) or subtract (-) withthe proton A’s field & each caseis equally likely. Herefore oneneighboring proton will splitproton A’s signal into two equaland separate peaks. The couplingconstant J represents the distancein Hertz between the adjacentpeaks and is characteristic of thetype of the chemical bond.Because of the J coupling theCH3 signal of lactate appears asa doublet separated by 7 Hz.Lactate assignment to theposition 1.32 ppm is exploited byphase modulation where at TE135 ms it is inverted and at 270ms it becomes upright.

Myoinositol peak occurs at 3.56ppm. It’s levels are raised inAlzheimer’s Disease and HepaticEncephalopathy. Decreasedmyoinositol levels are seen withprotective action of lithium inmania and the development ofdiabetic neuropathy. It is alsoreduced in hyponatremia. Themyoinositol peaks are alsosignificant in head and neckcancersLipids have very short relaxationtimes and are normally notobserved until short echo timesare used. The protons of lipidsproduce peaks at 0.8, 1.2, 1.5 and6.0 ppm. These metabolites maybe increased in high gradeastrocytomas and lymphomasand may ref lect necroticprocesses. Lactate and mobilelipids are normally not present inthe brain. They are shown toincrease in some tumors such ashigh grade astrocytomas andmeningiomas [5]Glutamate and glutamine peaksare located between 2.1 and 2.5ppmMetabolite Ratios Normal AbnormalNAA/Cr 2.0 < 1.6NAA/Cho 1.6 < 1.2Cho/Cr 1.2 > 1.5

Clinical applications of MRS& MRSI�� Brain Tumours-D/D betw-

een infarction/tumour /infection; Degree/grading ofmalignancy; Differentiationbetween radiation necrosis Vsrecurrence of tumour;Insight into the metabolicheterogeneity of tumours;Monitoring response totherapy


�� Lateralisation of epilepticfocus in cases of intractableseizures

�� Degenerative disorders inchildren and elderly individ-uals.

�� Psychiatric DisordersMRS in Brain Tumors-Asmalignancy increases, NAA &Creatine decrease and Cholinelactate, and lipids increase.Verymalignant tumors have highmetabolic rates. This results indepletion of energy stores. As aresult Creatine decreases.Hypercellular tumors with rapidgrowth result in increase incholine .Lipids are found innecrotic portions of tumors.Lactate appears when tumorsoutgrow their blood supply.Elevated choline in the presenceof lactae correlates with a higherdegree of malignancy. Raisedlactate is commonly observed inGBM. Elevation of lactate mayreflect tumor hypoxia. NAAlevels are low in all tumors butthe lowest in high gradeastrocytomas. Presence of lactategenerally reflects necrosis andtherefore a high degree ofmalignancyMeningiomas-Choline is alsoincreased in some slow growingtumors such as meningiomas.The signal of choline is markedlyincreased (upto 300 times) inrecurrent meningiomas. Lactateand alanine may also be elevatedespecially in the fibrous types ofmeningiomas.

Lymphomas-Spectroscopicappearance of lymphomas is

similar to that of primary highgrade astrocytomas andmetastases. MR spectroscopyshows a marked elevation ofcholine and lipids and asignificant reduction in creatineand NAA. MR spectroscopy issuccessful in assessing theresponse of lymphoma totreatment. Successfully treatedlymphomas show progressivedecrease in choline and lipids.Multivoxel spectroscopy-detects infiltration of maliganantcells beyond enhancing tumormargins;Elevated choline-markerof recurrent tumor; RadiationChange - low NAA, Choline,Creatine; Radiation Necrosis-elevated lactate and lipid as well;Metastasis elevated Cho/Cr fromthe metastatic focus but normalspectra from the brain tissueadjacent to the enhancing edgeof the metastatic focus. Gliomasshow elevated Cho beyond tumormargins unlike mets. Non glialtumors show little or no NAAGrading Brain Tumors-MRIhas a limited accuracy in definingtumor boundaries or differen-tiating mild and moderate tumorinfiltration from normal braintissue. It is also known thatgadolinium enhancement doesnot always correlate with thehighest cellularity and infiltrativetumors may extend far beyondthe contrast enhancing areas.MRS correlation with histologyhas shown that increasing Chocontent correlates directly withincreasing tumor grade.Radiation Necrosis-histolo-gically radiation injury is

characterized by damage to thevascular endothelium that mayresult in ischemia and necrosis.MR spectroscopy shows elevatedlactate in patients who havereceived 40 Gy or more to thebrain. The lactate peak can beidentified before any morphol-ogical changes are picked up byMRI. MRS helps in differe-ntiating radiation necrosis fromrecurrent/residual tumor bydemonstrating severely depres-sed levels of NAA, Cho and Crin radiation necrosis. In additionradiation necrosis shows a broadpeak between 0 to 2 ppmcorresponding to cellular break-down products probablyconsisting of free fatty acidslactate and amino acidsMTS MRS can be used tolocalize seizure focus in temporallobe epilepsy as an alternative toPET and SPECT. NAA isreduced in seizure foci. Thisrepresents a neuronal loss ordamage. The epileptogenichippocampus shows a decreaseNAA/Cho ratios and anincreased or normal Cho/Cr .there may be raised levels oflactate after an episode of acutetemporal lobe epilepsy.Abscesses Metabolites whichcan be seen only by using shortecho times. Metabolites includeacetate, lactate, pyruvate andsuccinate. Amino acid signals at0.9ppm-leucine, isoleucine,valine. There is reversal of lactatepeak in the abscesses aftertreatment.AIDS- Patients demonstratemarked metabolic alterations


even with mild AIDS relateddementia Virus infectedmacrophages cause neuronaldamage resulting in drop in NAAlevels. There is decrease in NAA/Cho and NAA/Cr and increasein Cho/Cr in subcortical greymatter. After therapy there isimprovement of NAA/Cr ratios.HIV positive newborns havenormal brain MRI but abnormalspectra as early as ten days afterbirth!Chronic Infarcts- Reduction ofCho, Cr, NAA compared to thecontralateral side. NAA isreduced to a greater extent thanCho or Cr. Subacute to chronicinfarcts demonstrate persistentlevels of lactate within the infarct.Brain infarcts are associated witha marked decrease in cellulardensity in the region of theinfarct which accounts for thereduced metabolite concent-ration. The finding that Cho/

NAA and Cr/NAA is increasedin regions of infarct is due to thefact that there is greater reductionof NAA compared to thecontralateral side than Cho or Cr.This is due to greater loss ofneurons than glial cells in infarcts7

Limitations of MRS�� Studies8 have found that

glioblastoma multiformeshowed paradoxically lowestaverage normalised cholinevalues. This is most likely dueto presence of extensivenecrosis seen in this tumorand partial volume limita-tions. Similar limitation isseen in PET as well- mostmetabolic tumors outgrowtheir blood supply to producenecrotic centers resulting inreduced metabolic activity.Thus potential to miss highlymalignant lesions with PET/MRS suggests caution inusing either technique alone.

Comparison between MR Imaging and MR Spectroscopy

MRI

Deteciton of water signal 1H

High spatial resolution

mGradients are requiredfor localisation of signal inMRI and MRSMRI uses them during theacquisition period

Temporal resolution isin seconds

In MRI pictures areavailable immediately

MRS

Detection of signal from biocehemicals-1H, 31P, 13C, 7Li and 19F

Low spatial resolution

MRS also needs gradients for signal localisation but they have to beswitched off during the acquisition period to ensure homogenityof the external magnetic field during signal acquisition

Temporal resolution is in minutes due to repeated signals and signalaveraging to improve SNR

MR Spectroscopy requires post processing of the FID data tomaximise the information content

�� MRS cannot be performed inor adjacent to bone, air , largevessels and hemorrhagiclesions.

�� Susceptibility artifacts frommetal and shunts mayobscure the spectra.

�� MRS has low sensitivity fordetecting molecules in tissues

Rule of thumb for 1H MRSsignal detection- at least 1micromole of the molecule ofinterest should be present in thevolume of interest. Thereforeonly few of the most heavilyconcentrated molecules arereadily detected with MRS. Itcannot replace brain biopsy forhistological diagnosis, but may beable to better delineate anddefine tumor boundaries andseparate an infiltrative growingglioma from normal brain tissuethereby helping in presurgicalplanning of brain neoplasms


References1. Sanders J A: Magnetic

Resonance Spectroscopy inFunctional Brain ImagingOrrison WW, Lewine J D,Sanders J A, Hartshorne M F: 419-467

2. Mitchell DG ProtonEnvironments and relaxationin MRI Principles MitchellDG, 1999; 9-17.

3. Castillo M, Kwock L, ScatliffJ, Mukerji SK. Proton MRSpectroscopy in neoplasticand non-neoplastic braindisorders. Magn ResonImaging Clin N Am. 1998;6:1-208

4. Maheshwari S, Mukerji S.Proton MR Spectroscopy:Clinical ApplicationsImagingEconomics; The journal ofImaging Technology Mana-gement; Aug 2002

5. Castillo M, Kwock L, MukerjiSK. Clinical Applications ofproton MR Spectroscopy.AJNR 1996; 17 1-5.

6. Lenkinski RE, Schnall MD.MR Spectroscopy and thebiochemical basis ofneurological disease. In AtlasSW, ed. Magnetic ResonanceImaging of the Brain andSpine. New York Raven;19911099 -1121

7. Duijn JH, Matson GBMaudsley AA et al.: Humanbrain infartion proton MRspectroscopy, Radiology183:711-718

8. MJ Fulham, A Bizzi, MJDietz, HH Shih, R Raman,GS Sobering, JA Frank, AJ

Dwyer, JR Alger, and G DiChiro: Mapping of braintumor metabolites withproton MR spectroscopicimaging: clinical relevanceRadiology1992 185: 675-686

Surgery in ancientIndia

Varanasi on the banks of theGanges is one of the holiestplaces in India. It is both the cityof Buddha and a destination ofpilgrimage for millions ofHindus who come to bathe inthe holy river. It is also the homeof Ayurveda, one of the oldestmedical disciplines. Ayurvedameans ‘science of life’, and itsapproach to the body isphilosophical and holistic.Among the greatest of itsancient writings is the SushrutaSamhita, which describes thetradition of surgery in Indianmedicine. Its author is believedto have been the scholarSushruta, who lived over 3,000years ago. Sushruta is said tohave been given his knowledgeby an incarnation of the godVishnu. However, it is alsosuspected that he was simplyreporting medical wisdom thathad been passed down by wordof mouth for centuries. In thebook’s 184 chapters, 1,120conditions are listed, includinginjuries and illnesses relating toageing and mental illness. Forinstance, there are accounts of76 eye conditions, 51 of whichwere treated surgically. Thebook also describes 101 bluntand 20 sharp surgicalinstruments, many of which are

surprisingly similar toinstruments used today. Othertreatments are also discussed,comprising 700 healing plants,57 preparations derived fromanimal sources and 64preparations from minerals.One of the plants was used toproduce suturing thread thathad immunity-boostingproperties. Others providedpain relief and still others werenatural antiseptics.Sushruta alsorecommended using leeches tokeep wounds free of bloodclots. This has only recentlybeen rediscovered and is nowused, especially in plasticsurgery, to help reducecongestion in tissues, especiallyin wounds and in flaps used forreconstructing body parts.

Sushruta’s general advice tophysicians would certainly applyto doctors anywhere and in anyage-A physician who has set outon this path should havewitnessed operations. He mustbe licensed by the king. Heshould be clean and keep hisnails and hair short. He shouldbe cheerful, well-spoken andhonest.

The compendium goes on todescribe some extraordinarysurgical techniques, including arevolutionary nose reconstr-uction, or rhinoplasty. It wascommon practice in ancientIndia to punish criminals byamputating the nose. As a result,Ayurvedic surgeons had plentyof opportunities to practise this.



Radiological imaging andradiation therapy share acommon past. The

Image Guidance in Radiotherapy- From Planar to MultidimensionalRadiotherapy

M K SemwalDepartment of Radiotherapy, Army Hospital Research and Referral

Delhi Cantonment, New Delhi

discovery of X-rays by W CRoentgen in 1895 and thehistorical radiograph of his ownhand was the beginning ofradiation for diagnosis andtherapeutic purposes (Balter S,1989). Since then, over more than100 years, there have beenrevolutionary changes indiagnostic imaging and therapydelivery technology. At the sametime, there has been significantimprovement in theunderstanding of the cancerbiology and its managementstrategies. The changes broughtabout in radiotherapy by i) thetransition from the usage oflargely anatomical images to thenew types of images that canprovide biological data about thetumour, and ii) from rectangularfields with uniform intensity forradiation delivery to intensitymodulated geometrically shapedbeams will be discussed in thisarticle. Generally, the term Imageguided radiotherapy (IGRT) isused in a very specific context inradiotherapy. It usually meansusing on-board imaging system(planar or 3D) to correct forinter-fraction (set-up /organmotion) errors while deliveringthe radiation dose. However, inthis article it will also include theimaging used for delineation of

the tumour/target and normalstructures.The aim in radiothe-rapy is to deliver certaintumouricidal dose to a targetvolume and at the same timespare the surrounding normaltissues as much as possible tominimize treatment relatedtoxicities. On many occasions, thenormal tissue tolerances areusually the limiting factors for theinability to deliver the desireddose to the tumour. All thetechnological innovations inradiotherapy primarily attempt toescalate the target dose withoutincreasing the toxicities. Imageguidance in radiotherapy is acrucial means to achieve thiswherein through the availableimages, the radiation dose isdelivered to the delineated target.This process of using X-rayimages for radiotherapy deliveryguidance can be said to be as oldas radiotherapy; starting withsimple planar images that couldbarley differentiate between boneand soft tissue to today’s CT, MRIand PET imaging. It was CT andMRI in the last over threedecades that provided arevolutionary improvement inour ability to visualize humananatomy. Advances in NuclearMedicine imaging that includesingle photon emissiontomography (SPECT) andpositron emission tomography(PET) hold enormous

opportunity for improving themanagement of cancer in generaland the radiotherapy practice inparticular. For a long time,external beam radiotherapy wasdelivered with rectangular shapeduniform intensity beams: startingwith superficial ( upto 120 kVp)and orthovoltage X-rays (150-500kVp) followed by telecobaltmachines and linear acceleratorsin the 1950s ( Bentel GC, 1992).Beam shaping to conform thedose to the tumour shape, wasusually carried out by usingshielding blocks. This was coarse,time consuming and always notsatisfactory. Similarly, inbrachytherapy, from thepreloaded radium applicators, itwas extremely difficult and inmost cases impossible to shapethe dose envelope to that oftumour volume. However, thetechnological advances duringthe last few decades havesignificantly removed thesehandicaps of conformality andimproved the therapeuticefficacy. These include the linearaccelerators (linacs), treatmentsimulators, high dose rateafterloaders, computerizedtreatment planning etc. Theincorporation of multileafcollimators (MLC) in the linachead heralded the birth ofpresent day 3D conformalradiotherapy (3DCRT) in theearly 1990s (Mohan R et al 1998).


Most recently, it is the intensitymodulated radiotherapy (IMRT)that has gained popularity forachieving still better conformality(Nutting C et al., 2000). Also,particle radiotherapy usingprotons, carbon and some otherheavy ions, though exorbitantlycostly at the moment, may gainwider acceptability for its betterphysical and biological dosimetryproperties.Target volumes in radiot-herapy - The InternationalCommission of RadiologicalUnits and Measurements (ICRU)in its report number 50 (1993)recommended a method for doseprescription and reporting inradiotherapy. In this report theydescribe the gross tumourvolume (GTV) as the “grosspalpable or visible/demonstrableextent and location of malignantgrowth”. This volume isincorporated in the volumeconsidered at risk, the clinicaltarget volume (CTV), defined as“a tissue volume that contains ademonstrable GTV and/orsubclinical microscopic malig-nant disease, which as to beeliminated”. This volume thushas to be treated adequately inorder to achieve the aim oftherapy, cure or palliation. TheGTV and the CTV areanatomical and biologicalconcepts. In addition the ICRUdefines the planning targetvolume (PTV) as “a geometricalconcept, and it is defined to selectappropriate beam sizes and beamarrangements, taking intoconsideration all the possiblegeometrical variations, in order to

ensure that the prescribed doseis actually absorbed in the CTV”.The PTV includes the CTV plusmargins for patient motion, organmotion, organ shape and sizevariation and uncertainties inbeam placement. A new term i.e.biological target volume BTV hasalso been coined in recentliterature. This may help inescalating the dose in a specificvolume of a target dependingupon it biological property suchas higher tumour burden.Aimingto deliver a known homogeneousdose to the PTV has so far beenthe paradigm in radiotherapy. Butthe emerging biological imagingmay reveal the non-uniformity interms of tumour burden,radiosensitivity within the PTVand hence the need to delivernon-uniform dose throughIMRT may bring about aparadigm shift in the dosedelivery concept. In fact, currenttechnology for deliveringconformally shaped externalbeam radiotherapy (IMRT) mayhave exceeded our ability tolocalize tumours and normaltissues by conventional imagingtechniques. The ability of IMRTto “paint” or “sculpt” the doseleads to the question as to whatneeds to be painted or sculpted.It is believed that non-invasivebiological imaging may providethe pertinent information toguide the painting or sculpting forthe optimal dose distribution.Important for IMRT, the spatialdistribution of radiobiologicalphenotypes will be the basis fordesigning the dose distributionconforming both the physical and

biological attributes of thetumour. The following fewparagraphs describe how thevarious imaging modalities andon-board imaging systems haveimpacted the practice ofradiotherapy.

Target Delineation

CT, MRI and Ultrasound(US)imaging techniques-CT hasplayed a pivotal role in theprocess of defining the extent ofthe tumour target volume. It hasmany advantages such as highspatial integrity, high spatialresolution, excellent bonystructure depiction and the abilityto provide electron densityinformation used for radiationdose calculations. With latest 64or even 128 slice CT machines inthe market, time-resolved or 4DCT has become a reality to takecare of the organ motion duringcardiac or respiratory cycles forintrafraction image guidance inradiotherapy.MRI providessuperior soft tissue discrimin-ation especially for CNSstructures and within theabdomen and pelvis and has beenwidely used in the diagnosis andtumour delineation. Withincreasing use of 3T MR imagesand fast-cine MRI, still betterquality images with temporalprocesses such as breathing canbe imaged. The development ofsome specialized MRI scans suchas diffusion and perfusion MRI,dynamic contrast MRI, MRangiography, MR spectroscopicimaging (MRSI) and functionMRI (fMRI) has attracted muchattention for biological and


functional imaging purposes.Ultrasound (US) is another usefulimaging modality for radiationtherapy particularly for prostateimaging. Transrectal US is theimaging modality of choice forprostate seed implant (brachyt-herapy). Incidentally, one of theearly on-board imaging systemsin EBRT for prostate was basedon US imaging.

Biological Imaging-It isdefined as the in vivo charac-terization and measur-ement ofbiological processes at the cellularand molecular level. It is anemerging multidis-ciplinary fieldresulting from the developmentsof molecular biology anddiagnostic imaging that has thepotential to revolutionize cancerdetection, staging, treatmentdecision making and assessmentof response. Biological imagesbroadly include those in themetabolic, biochemical, physio-logical and functional categories.They should also encompassmolecular genotypic andphenotypic images currentlyunder investigations. Forradiotherapy, images that can giveinformation about factors such ashypoxia that influences radiosen-sitivity and treatment outcomecan be called as radiobiologicalimages (Ling CC et al.,2000).MRSI and PET are twovaluable modalities for radiationplanning. 1H MRSI combines theadvantages of obtaining bioch-emical data by water suppressed1H MR spectroscopy with thespatial localization of the data. Astudy on impact of MRSI on the

target volume (CTV) delineationin high-grade glioma demon-strated that although T2 weightedMRI estimated the risk ofmicroscopic disease as being asmuch as 50% greater than MRSI,metabolically active tumourtissue still extended outside T2region in 88% of patients by asmuch as 28 mm. In addition T1weighted MRI suggested a lesservolume and different location ofactive disease as compared toMRSI (Xing et al., 2006). MRspectroscopy is similarly useful incharacterization of prostatetumours. However, despite thegrowing evidence that in vivoMRSI provides unique inform-ation on metabolism that willaffect treatment planning, thismodality has not gained widespread usage.On the other hand,PET has gained popularity forbeing used in treatment planningprocess. Since PET contains noanatomic information aboutnormal structures, it needs to befused with corresponding CTimages for treatment planning.Hybrid PET/CT systems are aresult of this necessity. The mostcommonly used tracer for PETstudies is fluorine-18 labeleddeoxyglucose (FDG), whichprovides a means to study themetabolic activity of the tumourin vivo. In several studies on theimpact of functional imagingwith FDG-PET on targetvolume, it has been shown thatover 50% radiation planning werechanged with PET-CT fusion ascompared to CT alone in the caseof non small cell lung cancer

(NSCLC). The changes includedalteration in AJCC TNM stagingand modification of CTV. It hasalso been shown that a sizeableproportion of patients withlocally advanced NSCLC becameineligible for curative radiot-herapy because of detection ofeither distant metastatic diseaseor extensive intrathoracic disease.Similar results have beenreported for oesophagus cancer( Xing L et al, 2006). Of coursethere are some pitfalls of theFGD- PET in that the tracer canbe nonspecifically taken up byseveral benign conditions such asinflammatory disease, pneu-monia, brown fat, muscle. Also,slow growing indolent tumoursmay be missed by FDG-PET dueto only mild increase in theirglucose metabolism. The recentdevelopment of fluorothymidine(FLT) provides a new oppor-tunity for improving sensitivityand specificity of PET imagingof cancer. Agents, such asantisense molecules, aptamers,antibodies, and antibody fragm-ents can be aimed at moleculartargets for biological imaging.Tumour receptors and certaincellular physiologic activities,including metabolism, hypoxia,proliferation, apoptosis, andangiogenesis provide suchtargets.Biological Conformal Radiot-herapy (BCRT)-As describedabove biological images mayprovide necessary informationregarding the non-uniformity oftumour cells within a PTV andthen IMRT capability may beused to escalate the dose


selectively within the PTV forachieving better control rate atthe same or lesser toxicity levels.For example, MRI/MRSI imagesof choline/citrate ratio can betaken as surrogate for tumourburden or low pO2 within thetumour can be delineated usingPET or MRI or using iodine-124-iododeoxyuridine ( 124IUdR)tracer in PET, tumour repopul-ation during a course ofradiotherapy can be assessed.This information then can beused to define biological targetvolume (BTV) and deliver higherdoses of radiation to the specificvolume within the PTV. Figure 1illustrates the concept of BTVschematically which can improvethe dose targeting to certainregions of the PTV.On-board Imaging-On-boardimaging means acquiring andanalyzing patient images in thetreatment position. This is aimedat reducing inter-fractionuncertainties resulting fromerrors in patient set-up, organmotions, beam placement etc.The concept of on-boardimaging is few decades oldthough its practice has assumedgreater significance recently withthe advent of 3DCRT and IMRTwherein higher doses of radiationwith tighter margin around CTVis aimed to be delivered.Consequently, misdelivery due toset-up errors or organ motionmay result in unacceptableoutcomes in terms of tumourcontrol or toxicities. Even in aseemingly obvious non-movingorgan like prostate, severalstudies have shown organ

position shift of more than 1.0cm in day-to-day treatment (TenH. et al., 1991).In the initial days,portal films in the treatmentposition were taken with themegavoltage X-ray (treatment)beam. The 2D image quality wasjust sufficient for bone and softtissue contrast and helped indetecting any gross mismatchbetween the planned and treatedarea. Electronic portal imagingdevices (EPID) with a fluore-scent screen, a mirror and a CCDcamera were the next system thatwere more convenient than thefilm, giving instant image andhence on-line correction for anyshift became possible. However,the introduction of a-Si based flatpanel detector system hasrevolutionized not only the fieldof radiology but also the on-linereal-time portal imaging system.They are compact and offer farsuperior image quality even withmegavoltage beam. The flat paneldetectors have given birth tocone-beam CT (CBCT) techno-logy which now offers excellentreal-time 3D images on a linearaccelerator and helps in findingthe off-set between the plannedtarget volume and the volumebeing treated. At present, thereare many variations of the real-time (on-line) image guidance inradiotherapy. Some vendors adda special kV X-ray source forCBCT on the linac gantry, someother use the megavoltagetreatment beam for imaging aswell and still other prefer adiagnostic CT on-rail in thetreatment room wherein thetreatment table moves the patient

first into the CT gantry and afterimage acquisition, into thetreating position. In Tomo-therapy, a compact linac ismounted into a CT gantry andthe imaging and slice by slicetreatment of the patient by a fanbeam of megavoltage radiation isakin to a diagnostic helical CT.Conclusion-The technology ofon-board real-time imageguidance has taken the accuracyand precision in the delivery ofradiotherapy to unprecedentedlevels. In combination withIMRT technology and theupcoming biological imaging, thestage is set for practicingbiologically conformal radio-therapy. At present, it can behowever, said that our ability todeliver physically conformal dosehas probably exceeded our abilityto delineate tumour targetbiologically. Therefore, moreefforts are needed in the area ofimaging to reap the full benefitof IM-IGRT delivery technologyand be in a position to delivermultidimensional conformalradiotherapy (MDCRT) that addsbiological dimension to conform-ality with the existing 4D anato-mical dose conformality.References

1. Balter S. The Technicalhistory of radiology. Radio-graphics. Vol 9 (1989).

2. Bentel GC. Radiation Ther-apy Planning. McGraw-HillInc, NY (1992).

3. International Commission onRadiation Units andMeasurements. Report No.


50. Prescribing, recordingand reporting photon beamtherapy. Bethesda. MD(1993).

4. Ling C C, Humm J, Larsen Set al. Towards Multidim-ensional Radiotherapy (MD-CRT) : Biological Imagingand Biological Conformality.Int. J. Radiat. Oncol. Biol.Phys., 47, pp.551-560 (2000).

5. Mohan R, Leibel SA et al.T h r e e - d i m e n s i o n a lConformal Radiotherapy. In:Treatment Planning inRadiation Oncology (KhanFM, Potish RA. Eds.).Williams and Wilkins,Baltimore, ML (1998).

6. Nutting C, Dearnaley DP,Webb S. Intensity ModulatedRadiation Therapy: A ClinicalReview. The Brit. J. Radiology,73, pp. 459-469 (2000).

7. Ten HRK, Forman JD,Heimburger DK, et al.Treatment planning issuesrelated to prostate movementin response to different fillingof the rectum and bladder.Int. J. Radiat. Oncol. Biol.Phys. 20, pp. 1317-1324(19991).

8. Xing L, Thorndyke B,Schreibmann E et al. Overv-iew of Image-guided Radi-ation Therapy. MedicalDosimetry, Vol 31, No. 2, pp.91-112 (2006).

Fig-1: A schematic illustrating the concept of biological target volume (BTV). The regions of hypoxiamay be derived from PET- 18F-misonidazole study, higher tumour burden from MRI/MRSI data ofcholine/citrate ratio, and high proliferation from PET-124IUDR study (Schematic concept Ling CC et al.,2000).

Linac head emitting treatment beam Flat panel detector

for CBCT

KV X-ray source for CBCT

Patient treatment couch

Fig-2: Linear accelerator withon-board imaging system



H

Imaging and Interventions in HCC

Nirad Mehta, Department of RadiologyP.D. Hinduja Hospital & Research Centre, Mumbai

lasm and fifth commonestmalignancy. Its incidence ishighest in Far East and Asia, andincreasing in the western world,because of increasing incidenceof hepatitis B & C. HCC has apoor prognosis with mediansurvival rate less than a year afterdiagnosis. Men are morecommonly affected (M: F 2-8:1).The average age at presentationis 30-50 years in the asianpopulation and 50-70 years in thewest.Pathophysiology- Vast majorityof patients have underlyingcirrhosis. Hepatitis B, Hepatitis Cand alcoholic liver disease are thecommon etiologies, withTyrosinemia, Hemochromatosis,excessive androgens, á1-antitrypsin deficiency andexposure to aflatoxins, thorotrast,oral contraceptives and vinylchloride also being implicated.Development of HCC is a multistep process based on graduallyincreasing size and cellularity:from a regenerative nodule, lowgrade dysplastic nodule, highgrade dysplastic nodule, to HCC.Along with this process,neoangiogenesis and capillariz-ation leads to a sequentialdecrease in portal blood supplyand an increase in arterial supply.As a result, HCC derives its bloodsupply almost exclusively from

epatocellular carcinomais the commonestprimary hepatic neop-

the hepatic artery – a factor usedin imaging for lesion characteriz-ation. HCC is a ‘capsulated’ lesionwhich can have a veryheterogeneous appearance due topresence of hemorrhage,necrosis, fat and calcification. Itis commonly a solitary lesion butmay also be multi focal or evendiffuse.Lung, bone and adrenalsare common sites of metastases,whereas nodes around porta,celiac axis and para aortic regionare most common sites of nodalspread.Imaging-Imaging plays a centralrole in Screening / Surveillance,Evaluation & Staging, Pretreatment Planning, Treatmentand Post treatment Follow up ofHCC. Various imaging modalitiescan be used, either alone or inconjunction.Ultrasound-Ultrasound iswidely available, inexpensive anddoes not utilize ionizingradiation. It therefore is a goodscreening modality. Acombination of USG and Alpha-fetoprotein levels every sixmonths is recommended asscreening procedure in patientswith cirrhosis. Ultrasoundhowever, has its limitations: it ishighly operator dependent,limited by tissue contrast, ribs andbowel gas and has poor sensitivityand specificity. Detection of alesion on ultrasound therefore isoften a starting point inevaluation for HCC.Appearance

of HCC on sonography dependsupon its contents. It is commonlyhypoechoic, (Fig-1a) due to densecellular elements, necrosis andsinusoidal dilatation. It may alsobe heterogeneously hyperechoic(fig-1b), when it contains fat,hemorrhage or fibrotic elements.It may have a surroundingcapsule, which is commonlyhypoechoic.Color Doppler-imaging can playa role by demonstrating vascularinvasion, hypervascularity andarteriovenous shunting. Ultraso-und is also invaluable in providingguidance for percutaneous biopsyand for treatment delivery likeethanol injection andRadiofrequency ablation.CT-Introduction of MDCT hasmade a quantum difference toimaging by its increased speed,coverage and resolution alongwith the ability to reconstructimages in multiple planes andusing different algorithms likemaximum and minimumintensity projections. This hasenabled multiphase CT of liver,which, by better evaluation of theenhancement pattern results inimproved characterization.However, this also demandsmeticulous technique, partic-ularly in the timing ofscans.Technique: Four phases ofcontrast enhancement in liver arerecognized. The early arterialphase starts at 15 sec, lasts 7 – 12sec and reveals enhancement of


hepatic arteries with noparenchymal enhancement (Fig-2a). Late Arterial phase starts at30 seconds, lasts 12 sec. Arterialenhancement persists, along withearly portal venous andparenchymal enhancement, butno hepatic venous enhancement.Portal Venous Phase starts at 60– 70 sec and represents peak ofparenchymal and portal-venousenhancement with opacificationof hepatic veins. The fourth ordelayed phase, also called theequilibrium phase starts atapproximately 150 seconds. Forevaluation of possible HCC, atleast a three phase study isrecommended, with scansobtained in late arterial phase,portal venous phase and thedelayed phase in addition to theplain scan. Although the earlyarterial phase does notsignificantly add to the detection,it is still useful for evaluation ofthe arterial blood supply andvascularity.Usually, 120 – 150 ccof contrast material containing370mg/ml of iodine is used,injected at a rate of 4-6 ml/sec,followed by a saline flush. Toobtain optimal enhancement invarious phases, fixed timing,bolus triggering or test bolus maybe used.HCC is seen as iso tohypodense lesion on plain scans(Fig-2a). It shows intenseenhancement on arterial phase,appearing hyperdense ascompared to the liverparenchyma, which in this phasedoes not show enhancement. Forsmaller lesions, the enhancementis usually uniform, where aslarger lesions showheterogeneous enhancement dueto various elements within the

tumour. (Fig-2b). A variegatedpattern may also be seen, due toabnormal internal vessels. A rare,but specific finding is a ‘nodulewithin a nodule’ – an enhancingnodule within an iso/hypodensenodule, which represents an HCCwithin a dysplastic nodule. Thecapsule, when present is seen asa hypodense rim.On the portalvenous phase, HCC becomes isoto hypodense (early wash out)against the background ofenhancing liver parenchyma (Fig-2c). Venous invasion can be wellassessed on this phase, as can thenodal spread. However, cautionis recommended in commentingabout the nodal spread, aspatients with cirrhosis may havelocally enlarged nodes withoutHCC. On the delayed phase,HCC appears hypodense inrelation to the rest of the liverparenchyma, even as the ‘capsule’reveals progressive enhancement.– a finding specific for HCC.MRI- MRI has distinctadvantages over CT in notemploying radiation and a safercontrast agent with much lowerrisk of contrast nephropathy(Although recent reports ofGadolinium induced NSF/NFDshould make one cautious). It ismore sensitive and specific thanCT, especially in differentiatingbetween cirrhotic nodules (RN,DN) and HCC.Technique-T1weighted Fast Spoiled GradientEcho, Single Shot Fast Spin Echoand Double Echo T1 – In phase– Out phase sequence forassessment of Fat – watercontent are routinely used,followed by Post GadoliniumDynamic Multiphase T1weighted sequence. This, in

principle is identical tomultiphase CT, using thehypervascularity and arterialenhancement for lesioncharacterization.Appearance ofHCC on T1 WI is variable,depending upon the contents(Fig-3a). Hyperintensity suggestspresence of fat, copper orglycoproteins. It is invariablyhyperintense on T2WI (Fig-3b).Capsule when present, appearshypointense. On dynamic postcontrast images, like in CT, itshows intense enhancement inarterial phase, early wash out inthe portal venous phase and hasan enhancing capsule (Fig-4).Pre treatment Evaluation-Surgery remains the besttreatment option and both CTand MRI are used for pre surgicalevaluation. In addition to the no.,size and distribution of lesions,assessment of tumour vascularity,venous invasion and extrahepaticspread is made. Liver volumetry,vascular anatomy and presenceof any other lesions or findingswhich may influence surgery mayalso be required.Imaging Guided Interventions-DSA, Ultrasound, CT and morerecently, MRI have been used forguidance in Interventionalprocedures.Biopsy-If the imaging featuresare characteristic, biopsy isseldom required and should beavoided in potentially operablelesions, because of the risk oftumour seeding. CT andUltrasound can both be used asguidance modalities. Ultrasoundhas the advantage of being widelyavailable, non ionizing nature andreal time guidance and should be


preferred when lesion isvisualized on sonography.

Chemoembolisation-Drugsand other agents can be deliveredusing super selective microcatheters. It can double lifeexpectancy and can be repeatedaggressively (Fig-5).PercutaneousAblation: Option for patientswith early stage HCC who are notresection or transplantcandidates. Destruction of thetumour tissue is achieved usingeither chemical substances(Ethanol, Acetic Acid) or bymodifying temperature (Radiofr-equency, Laser, cryotherapy)Ethanol injection is simple, lowcost and effective, achievingtumour necrosis in 90 – 100% oflesions less than 2 cm., while RFablation is preferred in lesionsbetween 2- 5 cm. (Fig-6)

New Developments-Interestingdevelopments are taking place inall imaging modalities, which mayinfluence liver imaging in future.Newer contrast agents inultrasound, Perfusion imaging inCT and development of parallelimaging, better sequences andimaging at 3T in MRI are likelyto influence evaluation of liverlesions.

Fig-1a, Hypoechoic HCC

Fig-1b, Heterogeneouslyhyperechoic HCC

Fig-2a,Large HCC on plainCT

Fig-2b Enhancement on earlyarterial phase

Fig-2c,Late arterial Phase

Fig-2d,Wash out in portalvenous phase. Note the en-hancing capsule.

Fig-3a,HCC on T1 WI

Fig-3b,HCC on T2 WI

Fig-4a,Dynamic arterial phase– note the enhancement


Fig-4b,Wash out on portalvenous phase. Note enhanc-ing capsule.

Fig-5a,Pre -embolisation se-lective arteriogram. Note thehypervascular tumour

Fig-5b,Post chemoembolis-ation.

Fig-6a,Rt. Lobe HCC

Fig-6b,RF probe deployed inthe lesion with prongs open

Fig-6c,Follow up CT showslack of enhancement in the le-sion

Surgical in ancientRome

In the ruins of Pompeii, turnedinto a time capsule by a volcaniceruption in AD 79, is a housethat belonged to a Greeksurgeon. It was identified, in1887, by its large stores ofsurgical equipment – more than100 instruments. Since therewas relatively little innovation inthese tools from the time ofHippocrates in the 5th centuryBC, instruments like theseremained typical of surgicalpractice for nearly a millennium.In fact, some of them, such asthe vaginal speculum, did notchange significantly until the20th century.The instrumentsfound at Pompeii represent thenormal range that a surgeon of

the time would have needed.They were mostly bronze, brassor copper, but blades andneedles were almost invariablymade of iron or steel. Most ofthe instruments could be heatedup and used for cautery. Byheating the instruments, thesurgeons were, without realisingit, sterilising them.

Circumcision, scars andbrands-The Romans distrustedmost of the foreigners they hadconquered, and foreigners whowanted to fit in would try tohide telltale differences. Thatwasn’t always easy, especially inthe public baths that everyrespectable Roman visited everyday. The Romans, whocelebrated the nude body in artand sport, viewed any abnormalappearance of the genitals withdistaste, even amusement. TheJews were well known for theirinsistence on male circumc-ision, but they were not theonly circumcised men known tothe Romans. Egyptian priestsalso practised it, as did Arabs,Ethiopians and Phoeni-cians.Certain scars weredespised. The manly thing wasto have battle scars on the front.To have scars on your back wasa mark of shame – it showedthat you had turned your backin battle and run away or, worse,that you had been whipped –only slaves were whipped.Brands were also hated, as they,too, revealed that you had oncebeen (or still were) a slave,someone who could never enjoyrespect.



Despite the emergence ofsuperior imaging mod-alities, the plain abdo-

Importance of Plain Abdominal Radiograph - A Pictorial Essay

Sanjay Jain, Ravi VarmaDepartment of Radiology, Prince Aly Khan Hospital, Mumbai

minal radiograph remains thepreferred method of initialradiological examination inpatients presenting with acuteabdomen. This article discussesthe findings in common adultacute abdominal conditions andreviews the role of plainabdominal radiography in themodern scenario.Radiographic technique-Asupine abdomen and an erectchest are the basic standardradiographs 1(Fig-1). A horizontalray abdominal radiograph, eithererect or left lateral decubitus (Fig-2), is frequently taken todemonstrate fluid levels. Theerect or decubitus radiographicprojections more accuratelydepict bowel wall and valvulaeconniventes thickness.2(Fig-3).The erect chest radiograph issuperior to the erect abdominalradiograph in demonstratingsmall pneumoperitoneum.Plain Abdominal Radiograph:Normal Appearance -Relativelylarge amounts of gas arenormally present in the stomachand colon but only a smallamount is usually seen in thesmall bowel. Air and fluid arenormal contents of the smallbowel, and short fluid levels arenot abnormal on an erectradiograph. The amount of gaspresent in a normal colon is

extremely variable, from almostnone to what may appear to beabnormal gaseous distension(Fig-4). Sufficient gas is usuallypresent for the colonic haustra tobe identified readily. Large bowelcaliber is very variable.1Normalsmall bowel appearances arecharacterized by diameter lessthan 3 cms; wall thickness lessthan 3mm; fold thickness lessthan 3mm and three to five air-fluid levels less than 2.5 cm inlength, particularly in the rightlower quadrant. Normal largebowel appearances arecharacterized by less than 6 cmsfor transverse colon and less than9 cms for caecum.Abnormal Plain Radiographfindings-These include dilat-ation of bowel; abnormal gasdistribution; abnormal bowel wallpattern; inflammatory conditionsand abdominal calcification. Letus examine them one by one.Dilatation of bowel-Gastricdilatation may be due to causeslike mechanical gastric outletobstruction (peptic ulcer,carcinoma), paralytic ileus, gastricvolvulus , intubation and airswallowing. Mechanical gastricoutlet obstruction leads to a hugefluid-filled stomach that occupiesmost of the abdomen and is seenon the radiograph as a soft-tissuemass with little or no bowel gasbeyond. Gastric volvulus resultsfrom twisting of the organaround its long axis (organoaxial)

or around its mesentery(mesentericoaxial)3 (Fig -5A,B).Abnormal intestinal air fluidlevels needs to be consideredwhen more than two fluid levelsare present in dilated small bowel(caliber greater than 2.5cm) (Fig-6). Small and large bowelobstruction may occur as a)Mechanical obstruction: intrinsicluminal obstruction or extrinsiccompression; b) Ileus: severefunctional impairment of transitof intestinal contents because ofdecreased peristaltic activity ofthe GI tract in the absence ofmechanical obstruction and c)Colonic pseudo-obstruction:severe functional impairment oftransit of colonic contents andmassive dilatation of the colon,in the absence of mechanicalobstruction, because ofuncoordinated, nonperistaltic, orattenuated colonic musclecontractions.Mechanical obstruction-Mechanical obstruction can betotal or partial. Differentiationbetween total versus partial obstr-uction or pseudo-obstruction iscritical because the first isgenerally treated surgically,whereas the latter two aregenerally treated medically.4

Mechanical small bowel obstruc-tion causes small-bowel dilatationand a reduction in caliber of largebowel. The amount of gaspresent in the large boweldepends on the duration of


obstruction and whetherobstruction is complete /incomplete. Plain radiographchanges may appear after 3-5hours if there is complete smallbowel obstruction, and areusually marked after 12 hours.With incomplete obstruction,changes on plain radiograph maytake days to appear. Plainradiographs are diagnostic in50% to 70% cases. Radiologicdiagnosis requires a dilated, gas-filled proximal bowel and acollapsed gasless distal bowel. Atransition zone between dilatedand non dilated bowel is a highlyspecific sign of small bowelobstruction4. Unfortunately, thissign is not sensitive. The stringof beads sign, due to a line ofgas bubbles trapped between thevalvulae conniventes, is seen onlywhen very dilated small bowel isalmost completely filled withfluid, and is virtually diagnosticof small bowel obstruction [Fig7A,B].1 If the plain abdominalradiograph is suggestive ofcomplete small bowel obstru-ction, further radiologicalinvestigations are not necessary,although many surgeons find CTevidence of the likely causeuseful. If the plain radiographsuggests partial obstruction andconservative management iscontemplated, then the patientsare serially monitored clinicallyand radiologically. Patients whohave an uncertain diagnosis oftotal versus partial mechanicalobstruction may prove to havepartial obstruction by graduallyimproving clinically withconservative therapy. Contra-riwise, patients initiallymisdiagnosed with partialobstruction or pseudo-obstru-

ction may manifest radiographicsigns of progressive mechanicalobstruction.1

Closed loop obstruction andstrangulation-In closed loopobstruction, a bowel segment isoccluded at two points, for e.g.incarcerated hernia, volvulus andcolonic obstruction withcompetent ileocaecal valve. Aclosed loop obstruction rapidlydilates and is at risk ofperforation. In hernia andvolvulus, the mesenteric vesselsare strangulated leading to bowelischemia rendering it more proneto complications of necrosis andperforation.If the closed loop isfluid-filled, it may be visible on aradiograph as a soft-tissue massor pseudotumour. If the loopcontains gas, it will be readilyvisible as a ‘coffee bean’ shadow.However in many cases,strangulating obstruction may beindistinguishable from simplesmall bowel obstruction on plainabdominal radiograph. It isimportant to diagnose closedloop obstruction and strangu-lation at the earliest because themortality rises with treatmentdelay. Hence there is a rationalefor performing CT in cases whereconservative management isplanned to avoid missingstrangulation, which wouldrequire urgent surgery.1

Small vs large boweldilatation: radiological distin-ction-In small bowel dilationhaustra is absent , the valvulaeconniventes is present. Thenumber of loops is many withtheir distribution of loopscentrally located with dimensionof loops 3-5cms. The presenceof solid feces is the only reliable

sign that the loop is large bowel.The other signs can bemisleading. Be aware of certainpitfalls. Small bowel fluid levelsare by no means specific forobstruction. When severe painis present anywhere in the body,or when respiration is laboured,the amount of air swallowed isincreased, producing gas-filled,slightly dilated loops of bowelwith relatively little fluid. Theterm meteorism is applied to thisappearance1Radiologically it isdifficult to distinguish meteorismfrom intestinal obstruction butthe clinical history andexamination enable the radiol-ogical findings to be interpretedcorrectly. Abdominal radiographcan be normal in patients withcomplete, closed-loop orstrangulated obstruction if thebowel loops are fluid-filled.4

Fluid-filled bowel loops are notreadily appreciated on plainradiographs, but are more easilyseen on USG and CT

Causes of small bowelobstruction-These includeadhesions, hernia, volvulus,ischemic stricture, intussus-ception, gall stone ileus, foreignbody, malrotation and tumor. Ahernia may be identified as a gas-filled viscus below the level of theinguinal ligament. Visualizationof a hernia does not always meanthat it is the cause of theobstruction. If, however a dilatedsmall bowel loop can beidentified that points directly tothe inguinal region and that alsocontains a gas shadow in anunusual position, a diagnosis ofobstruction due to the hernia canbe made


Adynamic ileus-Ileus is anobligatory physiologic responseto abdomen surgery [Fig 8].Duration is related to operativesite. Duration is longest aftercolonic surgery. GI functionreturns after surgery in an orderlyand predictable manner. Smallintestinal motility recovers after0 to 24 hours. Gastric motilityrecovers by 24 to 48 hours.Colonic motility recovers by 48to 72 hours.4Post operative ileusis prolonged by metabolicderangement, intra-abdominalinflammation and severeinfections like pneumonia. Plainabdominal radiograph revealspronounced small boweldilatation with lesser degree ofcolonic dilatation. It is difficult todifferentiate post operative ileusfrom mechanical small bowelobstruction occuring within 30days of abdominal surgery. Plainradiograph cannot distinguishbetween them and additionalimaging studies are required(contrast studies or CT scan)4.

Localised ileus is seen inconditions like pancreatitis,appendicitis (sentinel loops)Large bowel obstruction-LBOis an abdominal emergencyassociated with high morbidityand significant mortality.Themost common cause of LBO iscolorectal carcinoma, followed bycolonic volvulus and diverticulardisease. The clinical presentationvaries with the cause. The plainradiographic findings depend onthe site of obstruction andcompetency of ileocaecal valve.In a minority of patients theileocaecal valve remainscompetent and, in spite ofmarked distension of the

caecum, the small bowel is notdistended. More often, a closedileo-caecal valve also leads tosmall bowel distension. Inpatients with incompetentileocaecal valve, there may bedecompression of the caecumand ascending colon and markedsmall bowel dilatation.In a reviewof 140 cases of suspected largebowel obstruction, the plainabdominal radiograph had 84%sensitivity and 72% specificity indiagnosing large bowelobstruction.4 The plain radiogr-aphic appearances of large bowelobstruction are indistinguishablefrom acute colonic pseudo-obstruction, and any patient withsuspected large bowel obstru-ction therefore requires furtherimaging (contrast enema or CTscan)

Caecal volvulus1 -It can occuronly when the caecum andascending colon are on amesentery. In about 50% ofcases, the caecum twists andinverts so that the upper pole ofcaecum and appendix occupy theleft upper quadrant. In othercases the twist occurs in an axialplane without inversion and thecaecum still occupies the righthalf of the abdomen. One or twohaustral markings are generallyseen, even though there isconsiderable caecal distension(Fig-9). Left side of colon isusually collapsed

Sigmoid volvulus-The radiog-raphic features 3 are ahaustralmargin, apex under left hemidiaphragm/above tenth thoracicvertebra, liver overlap sign, leftflank overlap sign and pelvisoverlap sign (Fig -10 ).

Acute colonic pseudo-obstruction (ACPO)4 -ACPO is a variant of ileus,characterized by massive colonicdilatation. ACPO can be fatal. Itis believed to result fromincreased sympathetic stimu-lation or decreased parasym-pathetic activity. Ogilvie firstdescribed this syndrome in 1948in association with retrope-ritoneal malignancy infiltratingthe celiac plexus. It has been seenin postoperative state, nonop-erative trauma, neurologicdisease, malignancy, cardiop-ulmonary disease, intra-abdominal pathology, obstetricdisorders and retroperitonealpathology. Most of the casesspontaneously resolve withconservative therapy. Howeverdelayed diagnosis and inappro-priate therapy frequently occurs,which results in markedlyincreased morbidity andmortality. Perforation and colonicischemia are important complic-ations.Colonic pseudo-obstru-ction is diagnosed only afterexcluding mechanical large bowelobstruction. Massive colonicdilatation is present [Fig 11]. Anair-filled dilated colon extendingdistally to the rectosigmoidstrongly favors the diagnosis ofACPO rather than large bowelobstruction, but this sign isinsensitive. A colonic cut-offpoint favors the diagnosis oflarge bowel obstruction; however40% of patients with ACPO alsoappear to have a cut-off point.Thus, it is difficult to reliablydistinguish between large bowelobstruction and ACPO on plainradiographs alone, hence contrastenemas, CT scan or colonoscopy


are frequently necessary for thediagnosis.Abnormal Gas Distribution-They are seen as pneumope-ritoneum, gas in bowel wall, gasin retroperitoneum and gas inwall of other organsPneumoper i toneum-T hepresence of free gas in theabdomen in the unoperatedabdomen almost always indicateshollow viscus perforation.According to Rosco Miller, aslittle as one ml of free gas can bedetected on erect chest film orleft lateral decubitus abdominalfilm. It is also important torecognize the signs ofpneumoperitoneum on supineradiographs. These are listedbelow : a) Visualization ofperitoneal surface intra-abdominal organs : bowel –Rigler’s sign (Fig-12) and trianglesign, gall bladder sign, inferiorliver margin sign (Fig-13) , roofof the bladder ; b) Visualizationof surface ligaments as infalciform ligament (Fig-14),football sign, ligamentum teres,gastrocolic ligament, urachus andmedial & lateral umbilicalligament (Fig-5); c) Air inintraperitoneal recesses as inMorrison’s pouch-doge’s capsign, lesser sac, inferior border ofheart and pneumoscrotum; d)Extraluminal gas on liver as indiffusely lucent liver(Fig-16),anterior-superior bubble, ill-defined periduodenal lucencyand fissure of ligamentum teres.Postoperative pneumoperito-neum-Nearly all intraperitonealair is resorbed by 1 week.Presence of large amounts of air4-5 days postoperatively shouldraise suspicion of perforation.

Mimics of pneumoperi-toneum-These includes entitylike Chiladiti’s syndrome,subphrenic abcess, basal atelect-asis, subdiaphragmatic fat andpneumatosis intestinalisGas in bowel wall - If linear gasstreaks are seen in the bowel wall,intestinal infarction should besuspected. Other radiologicalsigns are non specific – slightlydilated loops of small bowel,bowel wall thickening and freegas if perforation has occurred.Pneumatosis cystoids intestinalisis an uncommon conditionconsisting of cyst-like collectionsof gas in the walls of hollowviscera.Its aetiology is unknown.The patients do not present withacute abdomen. This condition ismentioned here becauseoccasionally the cysts mayrupture, producing apneumoperitoneum withoutevidence of peritonitis. Unnece-ssary laparotomy can be avoidedif the characteristic radiographicappearance is recognized.Gas in retroperitoneum-Thecauses includes perforation ofposterior peptic ulcer, perforatedsigmoid diverticular disease,colonoscopy and other iatrogeniccauses. Retroperitoneal gas cantrack superiorly into themediastinum, and inferiorly intothe buttock and thigh.Gas in wall of other organs-Itis due to pneumobilia, portal veingas, emphysematous pyelonep-hritis (Fig-17), emphysematousgastritis (Fig-18), emphysematouscholecystitis, emphysematouscystitis (Fig -19) and necrotizingpancreatitis (Fig-20), pancreaticabscess and gangrenous bowel(Fig-21) .

Abnormal bowel wall pattern

Small bowel ischemia isrepresented by thickening ofsmall bowel wall due to edemaand hemorrhage, Gas in thebowel wall. CT scan is far moresensitive.Large bowel ischemia isfeatured by ‘Thumbprinting’ orfocal thickening of colonic walldue to submucosal hemorrhageand edema creating an extrinsicimpression on the luminal gas(Fig-22).Inflammatory bowel disease-An assessment of the extent ofcolitis, the state of the mucosa,the depth of ulceration and thepresence / absence of toxicmegacolon and perforation canbe made. Disease is likely to beinactive where there are formedfaeces, while a complete absenceof faecal residue suggestsextensive colitis. Mucosalchanges are outlined byintraluminal gas (Fig-23). Whenthe bowel becomes dilated andthe haustra disappear, theulceration has penetrated themuscle layer and the patientmoves in a high-risk group whereurgent surgery must beconsidered. Toxic megacolon isa fulminating form of colitiswhere the inflammationbecomes transmural andulceration extends deep into themuscle with neuromusculardegeneration. Dilatation of >5cm represents an initial stage ofthe process. In established casesthe dilatation may be > 8.5 cm.Haustration is always absent, andtoxic megacolon should not bediagnosed if it is preserved.Changes are observed mainly inthe transverse colon due to thesupine position of the patient.


Acute appendicitis-In acuteappendicitis, abnormalities areseen in less than 50% of cases.The radiological findings on plainabdominal radiograph are statedbelow in their relative order ofimportance. Appendicolith(coprolith, faecolith or appen-diceal calculus) – seen in 10-20%of all cases of appendicitis(Fig-24). An appendicolith is formedby precipitation of calcium andphosphate rich mucus around anidus of inspissated faecesassociated with luminalobstruction. Appendicolith andabdominal pain means a 90%probability of appendicitis. Thepresence of appendicolithindicates a high probability forg a n g r e n e / p e r f o r a t i o n .Approximately 50% of patientswith a demonstrable append-icolith will have a perforatedappendix at the time of surgery.Children are more likely to havevisible calculi. The other findingsinclude sentinel loop – dilatedatonic ileum containing a fluidlevel, dilated caecum, wideningof the properitoneal fat line,blurring of the properitoneal fatline, Right lower quadrant hazedue to fluid and edema, scoliosisconcave to the right, right lowerquadrant mass indenting thecaecum and blurring of the rightpsoas outline. All the abovefindings, with the exception ofappendicolith, are non-specificAcute cholecystitis-This ischaracterized by Gall stones,Right hypochondrial mass,Duodenal/hepatic flexure ileusand Gas within biliary systemAcute pancreatitis-This isfeatured by Sentinel loop, Gasfilled duodenal cap & loop, Small

bowel ileus and Dilated colonparticularly transverse andascendingAbdominal calcification withacute abdomen should alert theradiologist for Gall stones, Limeybile, Appendicolith, Pancreaticcalculim, Renal calculi (Fig-25),Ureteric calculi, Calcifiedaneurysm and Teeth / bone inovarian dermoidConclusion-The plain abdom-inal radiograph will continue tobe the primary radiologicalinvestigation in patients withacute abdomen. In certainconditions, the plain radiographis diagnostic. In some conditions,it provides useful but limitedinformation. Sometimes thefindings are nonspecific andfurther investigations with othermodalities are indicated.References1. Iain Morrison. The plain

abdominal radiograph andassociated anatomy andtechniques. In Grainger &Allison’s Diagnostic Radio-logy. Ed A.Adam, A.K.Dixon. 5th ed. ChurchillLivingstone Elsevier: 2008.p.589-608

2. Robert E. Mindelzun, JamesJ. McCort. Acute Abdomen.In Alimentary TractRadiology, 4th ed. AlexanderR . M a r g u l i s , H . Jo a ch i mBurhenne.The C.V.MosbyCompany:1989.p.291-361

3. Stuart Field. The AcuteAbdomen. In Textbook ofRadiology and MedicalImaging. David Sutton editor.5th ed. Churchill Livings-tone:1993.p.881-882Medical Clinics of NorthAmerica 92 (2008)

Fig-1: Normal abdominal sig-nature

Fig-2 : Left lateral decubitusradiograph taken with hori-zontal beam shows free gasbetween the right border ofliver and body wall

Fig-3 : Normal jejunal loops


Fig-5 A: Organoaxial volvulusof stomach

Fig-5B : Organoaxial volvulus ofstomach

Fig-6: Complete small bowelobstruction - Multiple dilatedsmall bowel loops with air-fluid levels are seen with littlegas in the colon

Fig-7B : String of pearls’ - di-agnostic sign of small bowelobstruction

Fig-8: Postoperative ileus:There is pronounced gastricand small bowel dilatationwith a lesser degree of colonicdilatation

Fig-9 : Caecal volvulus: Con-vergence of the medial wallsof the loop points to the right,a typical finding in caecal vol-vulus


Fig-10 : Sigmoid volvulus: dis-tended ahaustral sigmoid loop(white arrow), inferior conver-gence of the walls of the sig-moid loop to the left of themidline, and approximationof the medial walls of the sig-moid loop as a summation line(black arrow).

Fig-11:Massive colonic dilata-tion in a case of acute colonicpseudo- obstruction. Thesame radiographic appear-ance can also be produced bymechanical colonic obstruc-tion, toxic megacolon andmesenteric ischemia.

Gas-to-fluid ratio < 1:1



Gas-to-fluid ratio >1:4, bestseen on erect film



Gas-to-fluid ratio 1:1, sameon supine and erect

radiographs

Gas-to-fluid ratio 1:1, sameon supine and erect

radiographs

Gas-to-fluid ratio 1:1, sameon supine and erect radio-

graphs

Fig-7A : Varying Gas-to-fluid ratio


Fig-12: Rigler’s sign ofpneumoperitoneum: Bothsides of the bowel wall can beseen

Fig-13: Pneumoperitoneum:In a supine radiograph, freegas collects under the inferiorsurface of liver (‘inferior livermargin’ sign)

Fig-14: The falciform ligamentis outlined by free gas in theabdomen. This sign is seenonly when there is largeamount of pneumoperit-oneum.

Fig-15: Umbilical ligamentsare outlined by pneumoprito-neum

Fig-16: Extraluminal gas isseen over the liver, a sign ofpneumoperitoneum on supineradiograph

Fig-17: Emphysematouspyelonephritis

Fig-18: Emphysematous gas-tritis

Fig-19: Emphysematous cysti-tis

Fig- 20: Necrotising pancre-atitis

Fig-21: Linear collections ofgas are seen in the right co-lonic wall – Gangrenous bowelwas found at surgery


Fig-22: Thumbprinting: focalthickening of colonic wall dueto submucosal hemorrhageand edema creating an extrin-sic impression on the luminalgas.

Fig-23: Ulcerative colitis - Nofaecal residue is seen in thecolon. Diffuse luminalnarrowing is seen due tospasm

Fig-24: Child with acute abdo-men : Appendicolith and ab-dominal pain means a 90%probability of appendicitis

Fig-25: Left renal pelvic calcu-lus

Hippocratescontribution to

medicineTradition knows sevenphysicians named Hippocrates,of whom the second isregarded as the most famous.Of his life we know but little.He was born at Cos in 460 or459 B.C., and died at Larissaabout 379. How great his famewas during his lifetime is shown

by the fact that Plato compareshim with the artists Polycletusand Phidias. Later he was called“the Great” or “the Divine”.The historical kernel is probablyas follows: a famous physicianof this name from Cosflourished in the days ofPericles, and subsequently manythings, which his ancestors orhis descendants or his schoolaccomplished, were attributedto him as the hero of medical

science. The same was true ofhis writings. What is now knownunder the title of “HippocratisOpera” represents the work,not of an individual, but ofseveral persons of differentperiods and of differentschools. It has thus becomecustomary to designate thewritings ascribed to Hippo-crates by the general title of the“Hippocratic Collection”(Corpus Hippocraticum), andto divide them according totheir origin into the works ofthe schools of Cnidus and ofCos, and of the Sophists. Howdifficult it is, however, todetermine their genuineness isshown that even in the thirdcentury before Christ theAlexandrian librarians, who forthe first time collected theanonymous scrolls scatteredthrough Hellas, could not reacha definite conclusion. For thedevelopment of medicalscience it is of littleconsequence who composedthe works of the school of Cosfor they are more or lesspermeated by the spirit of onegreat master. The secret of hisimmortality rests on the factthat he pointed out the meanswhereby medicine became ascience. His first rule was theobservation of individualpatients, individualizing incontradistinction to theschematizing of the school ofCnidus. By the observation ofall the principles were graduallyderived from experience, andthese, uniformly arranged, ledby induction to a knowledge ofthe nature of the disease, itscourse, and its treatment.



W ith the developmentof echocardiography,radiography now plays

Plain Radiograph in Congenital Heart Disease

Sanjay Jain, Ravi VarmaDepartment of Radiology, Prince Aly Khan Hospital, Mumbai

an ancillary role in the evaluationof patients suspected to havecongenital heart disease. Howe-ver, sometimes, the chest filmprovides the first indication ofunsuspected cardiovasculardisease and in patients withknown cardiac disease, radiogr-aphy offers an importantoverview of the heart andpulmonary circulation and isuseful in follow-up.1

Important Caveats-Certaincaveats need to be emphasized1.

Children with relatively mildstructural defects and even somewith severe or complex diseasemay have normal chest films.This is particularly true innewborns. Chest radiograph doesnot usually provide informationabout specific chamber size,hypertrophy, or intracardiacconnections or malformations.Findings such as boot-shaped oregg-shaped heart are nonspecificfor tetralogy of Fallot ortransposition of the greatarteries. On the other hand, plainfilm findings may be specific forsome extracardiac lesions, such assupracardiac total anomalouspulmonary venous return, rightaortic arch, pulmonary stenosisand coarctation of aorta.Systematic evaluation of heartdisease on chest film-Asystematic evaluation is necessary

for successful diagnosis of heartdisease on chest film. Thefollowing approach advocated byLarry Elliott, is a logical anddisciplined method and should beinculcated by all radiologytrainees. There are three majorstages of analysis2 . Stage 1 –Extracardiac analysis; Stage 2 –Analysis of pulmonary vascula-rity ; Stage 3 – Analysis of cardiacanatomyStage-1, Extracardiac Analysis

Age-Certain cardiac disorderscan be given strong or minimalconsideration on age alone. Innewborns and infants, ventricularseptal defect is the mostcommon, either alone or as partof a more complex process. Inolder children and teenagers, thelesions with VSD have eitherbeen operated upon or haveundergone spontaneous closure.Atrial septal defect is thedominant shunt lesion; alongwith obstructive lesions such asaortic valve stenosis, coarctationof aorta and pulmonary valvestenosis.2

Technical Analysis-Alignment– is the patient rotated? It isimportant because rotation canaccentuate normal structures andmake them appear abnormal. Ininfants alignment of medial endof clavicles is not a reliable wayto detect rotation. Infants areusually immobilized by holding /strapping their arms and waist. Assuch the clavicles may be aligned

correctly, but the trunk can be sotwisted as to result in a rotatedthorax. Therefore, the mostaccurate way to determineproper alignment is to measurethe distance between the end ofthe anterior rib and the lateralmargin of the dorsal spine; theright side should equal theleft.2Films of infants are usuallyobtained in the anteroposteriorand supine positions. Because ofthe small size of the chest, thistechnique results in littlemagnification of the heart, whichis a greater issue with largerchildren. Beam angulation mayalso affect the appearance ofheart and great vessels. Withlordotic positioning, the heartmay appear more globular, withan uplifted apex andaccentuation of the pulmonaryoutflow tract. With reverselordosis, much of the heart maybe obscured by the hemidiap-hragm.1Film quality – over orunderexposure will affect ourjudgment of pulmonary vascu-larity. Ideally, the lungs shouldappear gray, and the dorsal spineand its interspaces should barelybe perceptible through thecardiac shadow. An expiratoryradiograph can cause erroneousinterpretations of cardiomegaly,shunts and infiltrates. Withproper degree of inspiration, theheight of the diaphragm shouldbe at the sixth intercostals spaceanteriorly or the eighth interco-stal space posteriorly.


Skeleton-Anomalies of ribs,spine and sternum. For examplepresence of forked ribs in acyanotic child -think of Fallot’stetralogy. Bilateral rib notching –coarctation of aorta. Hyperseg-mented sternum (more than 5segments), eleven pairs of ribssuggest Down’s syndrome, whichin turn implies an AV canal lesion.Post surgical stigmata –such asregenerating ribs, unilateral ribnotching, surgical sutures andvalve / conduit prosthesis.Abdomen-In every patient,regardless of age, the presence ofthe liver and spleen should beestablished.(Fig-1). In asplenia,hepatic symmetry is seen due toenlargement of left lobe of liver.Next, the position of the stomachmust be determined. Forinstance, if the stomach is right-sided in a patient whose thoraciccontents appear in the usualposition; or is left-sided in apatient whose thoracic contentsare in situs inversus, polyspleniasyndrome and interruption ofthe hepatic segment of theinferior vena cava are almostinvariably present.2

Mediastinum-The last compo-nent of stage 1 evaluationconcerns structures that are, inreality, not extracardiac. Incongenital heart disease, thefollowing have great importance: Position of the aortic arch andPresence or absence ofpulmonary trunkArch anomalies2-The size andposition of the trachea is animportant indicator of archabnormalities. A careful searchshould be made on both frontaland lateral films for displacementor narrowing of the trachea.

Right aortic arch can occur as anisolated anomaly or in associationwith other congenital heartdiseases such as tetralogy ofFallot, truncus arteriosus,etc.(Fig-2). Reliable radiographicsigns of a right aortic arch are a)absence of the normal aorticknob in the left superiormediastinum; b) indentation andslight deviation of the tracheaand c) right-sided descendingthoracic aorta. The position andcontour of the descendingthoracic aorta should be carefullyexamined. In coarctation ofaorta, the only sign in youngerchildren may be a leftwardconvexity to the descendingaorta, which is abnormal inchildren.Pulmonary trunk2-Presence ofpulmonary trunk, regardless ofsize, allows the followinganatomical predictions:a) Thegreat arteries are normally relatedand connected to the appropriateventricles; b) There are twoventricles and c) 3. The twoventricles are normally related. Inother words, its presence virtuallyrules out transposition of greatarteries and the spectrum ofsingle ventricle entities. This ispowerful information usuallyunderutilized by radiologists.Stage-2, Assessment ofpulmonary vascularity :‘Physiologic stage of analysis’

Normal radiographic appea-rance of pulmonary vascul-ature-In adults, the mainpulmonary artery forms the floorof the pulmonary bay on thefrontal chest radiograph. Inchildren and young women, aslight convexity is within normallimits. In the lungs the pulmonary

arteries roughly follow thebronchial branching pattern(Fig-3). The arteries branch and tapersmoothly out from the hilum andcan be followed as discreteshadows to the outer third of thelung. The pulmonary veins ofthe upper lobe collect into thesuperior pulmonary vein, thoseof the lower lobe into the inferiorpulmonary vein. The two veinson each side join the four cornersof the left atrium. Thepulmonary arteries and veins canbe distinguished on the plainradiograph by their course andposition. The lower lobe veinsrun horizontally to reach the leftatrium and are usually distingui-shable from the more verticallyrunning branches of thedescending branch of thepulmonary artery. The upper lobeveins, when visible, lie lateral tothe upper lobe arteries, and runvertically to pass through the hilarshadow to reach the left atrium.Assessment of the pulmonarycirculation is probably the mostimportant observation on thechest radiograph. Analysis of thepulmonary vascularity beginswith the central pulmonaryarteries and veins (hilar vessels)followed by the intrapulmonaryvasculature.

Radiologically normal pulmo-nary vascularity-It is present incongenital heart disease if thepatient is not in heart failure, ifno large shunt is present and ifthere is no extreme pulmonarystenosis. The pulmonaryvascularity may look normal onthe chest radiograph even in thepresence of substantial conge-nital heart disease.2


Increased pulmonary perfu-sion (plethora)- It is recognizedby enlarged central andperipheral pulmonary arteriesand veins in all zones. The sizeof the pulmonary vessels isnoticeably larger only when theflow doubles. This means thatsmaller shunts are not detectable.Detecting moderate increases inf low requires considerableexperience(Fig-4). One usefulsign is to compare the end-onpulmonary artery to the adjacentbronchus. An arterial diametergreater than that of the bronchusis usually suggestive of increasedflow. Another key area is the sizeof vessels as projected below thediaphragm. When the vessels canbe seen this far in the peripheryof the lung, it is usually a reliablesign of increased flow.2 Left – to– right shunts show increasedpulmonary vascularity(Fig-5). Incases where the presence ofincreased vascularity is question-able, analysis of the hilar andintrapulmonary vessels in thelateral and oblique views willoften provide the answer. Over aperiod of time, in patients withsignificant shunt vascularity, thepulmonary arterioles undergoprogressive obliterative changes,the pulmonary vascular resistancesteadily increases giving rise toprecapillary hypertension. Thisstage is called Eisenmenger’ssyndrome (Fig-6). When precap-illary hypertension is severe, thefollowing characteristic radiogra-phic appearance is seen. Promin-ent ‘masslike’ hilar vessels withdiminution in the size of thearteries in the middle and distalthird of the lung.2Pulmonary venous hyperte-nsion (PVH)-Although shunt

lesions are a common cause ofprominent hilar and intrapul-monary vessels in children,prominent vascularity secondaryto entities creating pulmonaryvenous hypertension is the mostcommon abnormal vascularpattern encountered; hence abrief discussion is included. Theelevated pressure in thepulmonary venous channel isfreely transmitted to thepulmonary capillary bed and maybe transmitted to the pulmonaryarterial system as well. Thephysiologic and anatomicresponse of the pulmonaryvasculature and lung parenchymato the effects of PVH arereflected in the chest film as fourprogressive stages: 2 a) Redistri-bution of pulmonary blood flow,which involves shunting of bloodinto the upper lobes and decreasein flow to the lower lobes (theearliest change); b) Interstitialedema which manifests asperibronchial cuffing, Kerleylines ; c) Alveolar edema and d)Chronic changes such ashemosiderin deposits andossificationSystemic Collateral Arteries -Uncommonly, the pulmonaryvasculature appears prominentowing to an increase in flowthrough the systemic collateralarteries. The usual cause is severeFallot’s tetralogy. Systemiccollateral arteries serve as asource of blood supply to thepulmonary arteries. They mayoriginate as bronchial arteries butmay take a variety of other formsas well. Their connections withthe pulmonary arteries areextremely variable, occurring inthe hilum or well into theperiphery of the lung. Distinction

between prominent pulmonaryarteries and veins seen in shuntsand systemic collateral arteries isusually not difficult. In the latter,the vessel pattern, althoughprominent, is disorganized andhas a relatively more stringy orreticulated appearance. Theprominence is usually nonunif-orm in the lung or often localizedin the direction of the main stembronchi. This may result in theupper lobe vessels appearingmore prominent than the lower.More important, the hilar arteriesare not large and are usuallyinapparent. A normally formedpulmonary trunk is neverpresent.2

Decreased pulmonary perfu-sion (oligaemia)-Decreasedpulmonary vascularity nearlyalways indicates that there issevere obstruction to the flow ofblood to the lungs fromwhichever ventricle thepulmonary artery arises. This maybe a morphologic right, left orsingle ventricle. The obstructionis usually at the pulmonary valveor just below – in theinfundibulum – or morecommonly at both sites.2 (Fig-7).When there is diminishedpulmonary flow, the hilar andintrapulmonary vessels appearsmall and the hilar vessels are alsoless dense than normal.Recognizing this pattern requiresconsiderable experience. Thelateral view can be ofconsiderable help in evaluatingthe size and density of the hilarvessels.

Stage-3, Cardiovascular Anat-omy Analysis-The next step isto learn to use anatomicalstructures within or outside the


cardiac silhouette to determinethe level of the shunt. Highlysimplified examples are givenbelow. Anomalies that result inpulmonary overcirculation can bedivided into those that producecyanosis and those that don’t.From a strict chest-film point ofview, acyanotic heart lesionsoften cannot be distinguishedfrom cyanotic ones.Acyanotic Congenital HeartDisease-There are fouracyanotic lesions that compriseapproximately 90% of the shuntsencountered – ventricular septaldefect (22% to 25%), patentductus arteriosus (12%), atrialseptal defect (8%) and someform of endocardial cushiondefect (persistent commonatrioventricular canal) (4%)2

Radiologic differentiation-There are no specific x-ray signsfor a VSD or an ASD. The PDAis the only left-to-right shunt thatmay show a specific sign. The ageof presentation is one of themore important indicators of thetype of left-to-right shunt. Whenthere is functional evidence of aleft-to-right shunt, the observermust first attempt to determinethe level of shunt. The size ofthe left atrium is valuable indeciding at which level the defectis located and/or the competencyof the mitral valve. If in a left-to-right shunt it is found that leftatrial enlargement is present, thissuggests that the atrial septum isintact and the defect is either atthe ventricular or great arterylevel, or there is, instead, a shuntat any level, with the additionalcomplication of severe mitral

valve regurgitation.If, on theother hand, the left atrium isnormal in size, this by no meansexcludes a VSD or PDA. In manyinfants and almost all childrenand adults with moderate to largeVSD, left atrial size is normalbecause of closing VSD,development of right ventricularinfundibular stenosis or severepulmonary resistance. In otherwords, when left atrialenlargement occurs in VSD, it isusually confined to infancy.2

Following analysis of the leftatrium, the second step is ananalysis of the aortic arch regionfor evidence of PDA. A PDA isseen as a convex curvilineardensity (‘bucket handle’deformity) just below the aorticarch and above the pulmonarytrunk. Its morphologic basis is afunnel-shaped widening of theaorta around the opening of thePDA, often termed theinfundibulum. In all intracardiacshunts, the aortic arch is often ofnormal size or inapparent. Theright aortic arch has a tendencyto occur almost exclusively inVSD than in other left-to-rightshunt lesions.In the presence ofa left-to-right shunt, absence ofleft atrial enlargement and anormal aortic arch, together withright heart enlargement, favor ashunt at the atrial level. Inchildren and young adults, the leftatrium may enlarge due to mitralincompetence, which, if present,is usually secondary to anincompetent prolapsing mitralvalve. In this case, an ASD cannotbe distinguished from othershunt lesions causing left atrialenlargement. Although there are

no specific x-ray signs for ASD,the diagnosis as well as itsexclusion is facilitated by threestatistical facts2 a) ASD(uncomplicated) is rare ininfancy; b) the vast majority ofshunt lesions in patients olderthan preschool age ASDs and c)ASD occurs more often infemales than other shunt lesions.Cyanotic Congenital HeartDisease-Among patients withcyanotic heart disease, thevascularity is almost alwaysabnormal (either prominent ordiminished).Cyanotic heart disease –overcirculation vascularity-The conditions include Completetransposition (prototype)(Fig-8);Single or univentricular heart;Tricuspid atresia; Double outletright ventricle; Truncus arteri-osus; Common atrium; Aorticatresia and TAPVC abovediaphragm. Statistically, thecombination of overcirculationvascularity and cyanosis indicatescomplete transposition unlessproven otherwise. There are noradiologic features pathognom-onic for complete transposition.2However, certain extracardiacand cardiac findings may indicateanother lesion from the abovelist. For example Skeletalanomalies are commonly seen intruncus arteriosus and commonatrium.Presence of right sidedaortic arch points towardspersistent truncus arteriosusCyanotic heart disease withdecreased vascularity-Thesecases can be subdivided into twomajor groups : a) those associatedwith a large VSD with the right-


to-left shunt occurring from theventricle into the aorta and b)those with right-to-left shuntoccurring at the atrial level.Ventricular Level Shunt-Prototype of this group istetralogy of Fallot. Otherconditions are Single ventricle,Tricuspid Atresia, Double outletright ventricle with severepulmonary Stenosis, Aspleniasyndrome, Corrected transpo-sition with VSD. Roentgenologicfindings indicating a large VSDwith severe pulmonary stenosisare a prominent aorta with a leftaortic arch / (more significantly)right aortic arch; a normal-sizedright atrium; a normal sized heartor only mild cardiomegaly. Theseanatomical findings indicate thatthe right-to-left shunt is at theventricular level. With a largeVSD, when there is severeobstruction to pulmonary flow,no stimulus for moderate ormarked cardiomegaly is present,regardless of the origin of thepulmonary artery, because theventricles can express themselveseasily into the aorta. Moreover,there is usually no tricuspid valveincompetence and thus nostimulus for right atrialenlargement. Extracardiacanalysis can help to differentiatesome of these conditions.Presence of skeletal anomalies isvirtually confined to tetralogy ofFallot. Hepatic symmetryindicates asplenia syndrome.Atrial Level Shunt-Conditionsinclude Isolated pulmonarystenosis or atresia (prototype);Ebstein’s malformation(Fig-9);Tricuspid Atresia; Congenital

tricuspid regurgitation; Perica-rdial effusion and Uhl’s anomaly.The major x-ray findings arevirtually the opposite of thoseabove and consist of aninapparent aorta; a left aortic arch(right aortic arch is rare);moderate to severe cardiomegalysecondary to right atrial and/orright ventricular dilatation causedby massive tricuspid valveincompetence, which is acoexisting lesion in majority ofthe above patients. Analysis ofextarcardiac and cardiac anatomycan further narrow down thedifferential diagnosis.

Conclusion-A systematicapproach is essential in evaluatingchest radiographs in congenitalheart disease. In majority of casesthe above described approachhelps to nar row down to acardiovascular disease categorysuch as left-to-right shunt or left-sided obstructive lesion, which inturn leads to a differentialdiagnosis.

References

1. J.A. Gordon Culham, John B.Mawson. Chest Radiographyin Pediatric CardiovascularDisease In Caffey’s ‘PediatricDiagnostic Imaging’. edThomas L. Slovis. 11th ed.Mosby Elsevier:2008.p.1465-1475

2. Larry P. Elliott. CardiacRadiology In ‘RadiologyD i a g n o s i s - I m a g i n g -Intervention’ ed. JuanM.Taveras, Joseph T.Ferrucci.J.B Lippincott Company:1986, Volume 2

Fig-1 : Extracardiac signs ofcongenital heart disease Plainradiograph reveals dextroga-stria and hepatic symmetry ina neonate suffering fromcomplex cyanotic hear tdisease. Child also hadasplenia and incompleterotation of intestine (Ivemarksyndrome)

Fig-2 : Extracardiac analysis:Right aortic arch is observed.It may occur as an isolatedanomaly or in association withother anomalies like Fallot’stetralogy and persistenttruncus arteriosus


Fig-3 : Normal pulmonaryvascularity: The size of pul-monary artery branches nor-mally do not exceed the sizeof accompanying bronchus

Fig-4: Increased pulmonaryvascularity in patent ductusarteriosus

Fig-5 : Analysis in VSD.Pattern of pulmonary vascul-

arity indicates possibility ofleft-to-right shunt. Child wasacyanotic. This patient couldhave an ASD/VSD/PDA.There are no specific x-raysigns for a VSD or an ASD.The PDA is the only left-to-right shunt that may show aspecific sign. The age ofpresentation is one of themore important indicators ofthe type of left-to-right shunt

Fig-6 : Eisenmenger’s syn-drome in a case of ASD:Prominent ‘masslike’ hilar ves-sels with diminution in the sizeof the arteries in the middleand distal third of the lung.

Fig-7: Decreased pulmonaryvascularity in Tetralogy ofFallot

Fig-8 : Patient was cyanotic.Statistically, the combinationof overcirculation vascular-ity and cyanosis indicatescomplete transposition unlessproven otherwise. There areno radiologic features pathog-nomonic for complete trans-position. In this case, the ad-ditional finding of right sidedaortic arch is highly significantas it strongly suggests persis-tent truncus arteriosus

Fig-9 : Egg on Side sign: Acase of cyanotic heart disease.There is pulmonary oligaemia,severe right atrial dilatationand an inapparent aorta - acase of Ebstein’s malforma-tion



A spergillosis is a mycoticdisease caused by adimorphic fungus

Gamut of Radiological Findings in Pulmonary Aspergillosis

Ankur DevLalendra Upreti, Sunil Puri, Department of Radiology,GB Pant Hospital, New Delhi

belonging to the Aspergillusspecies, usually A fumigatus. Aflavus, A niger, A glaucis and avariety of other genus areoccasionally pathogenic. Aspergi-llus is an intensely antigenic soilfungus; its conidiophores areubiquitous in the atmosphere andhuman exposure inevitable. Inthe airways it is capable ofmultiplying into the hyphal form,under favourable conditions. Thehistologic, clinical, and radiologicmanifestations of pulmonaryaspergillosis represent aspectrum determined by thevirulence of the organisms andthe patient’s immune response1

(Table-1). We discuss theradiological manifestations ofaspergillosis encountered in fourpatients.

Immune status

Hypersensitive

Allergic aspergillosis

Normal

Saprophyticaspergillosis

Mild immunosuppression

Chronic necrotizingaspergillosis

Severeimmunosuppression

Invasive pulmonaryaspergillosis

Discussion

Allergic bronchopulmonaryaspergillosis is caused by acomplex twofold immunologicreaction comprising an acute typeI immediate hypersensitivity

reaction mediated by IgE and adelayed immune complex type IIIreaction mediated by IgG, inresponse to Aspergillus antigens.The fungi proliferate in thetracheo-bronchial tree, constantlyreleasing surface antigens into theairways. With protractedinfection, immunecomplexes andinflammatory cells are depositedin the bronchial mucosa,producing necrosis andeosinophilic infiltrates (type IIIreaction) with bronchial walldamage and bronchiectasis2.Excessive mucus production andabnormal ciliary function lead tomucoid impaction. Many patientscough up thick mucous plugs inwhich hyphal fragments can bedemonstrated at culture orhistologic analysis.In the acutesetting, areas of consolidationmay be seen on the chest

radiograph, ranging indistribution from sub-segmentalto lobar with upper lobepredilection. Tram line shadowsrepresenting edematous bron-chial walls may also be

encountered. Pathologically thealveoli are filled with eosinophils,and the walls of smaller bronchishow eosinophilic infiltrates.Radiologic manifestations in thechronic stage include homogen-eous, tubular, finger-in-gloveareas of increased opacity in abronchial distribution, usuallypredominantly or exclusivelyinvolving the upper lobes3. Theseshadows are related to pluggingof airwaysby hyphal masses withdistal mucoid impaction and canmigrate from one region toanother (Fig-1). CT findings inallergic bronchopulmonaryaspergillosis consist primarily ofmucoid impaction andbronchiectasis involving predo-minantly the segmental andsubsegmental bronchi of theupper lobes (Fig-2). Inapproximately 30% of patients,

the impacted mucus has highattenuation or demonstratesfrank calcification at CT (Fig-3).ABPA is treated with chestphysiotherapy and inhaled orsystemic corticosteroids.


Saprophytic aspergillosis(aspergilloma) is characterised byAspergillus infection withouttissue invasion. It typically leadsto conglomeration of intertwinedfungal hyphae admixed withmucus and cellular debriscolonizing a pre-existent pulmo-nary cavity or ectatic bronchus.Such cavities are usually due totuberculosis, sarcoidosis orhistoplasmosis; rarer causesinclude pulmonary sequestration,bronchogenic cysts andpnematoceles4. Saprophyticaspergillosis manifests on thechest x-ray as a mobile,dependent nodular opacitylocated within a pre-existingcavity (Fig-4). As on theradiograph, the most characte-ristic finding of an aspergillomaon CT consists of an ovoid orround soft tissue attenuation,intra-cavitary mass that usuallymoves when the patientdecubitus is changed (Fig-5,6)5.Aspergillomas are oftenassociated with thickening of thecavity wall and adjacent pleura.Pleural thickening may be theearliest radiographic sign beforeany visible changes are seenwithin the cavity. Reversibility ofthe pleural thickening correspo-nding to the resolution of intra-cavitary fungal material has beendemonstrated at follow-upradiography. Approximately 10%of mycetomas resolve sponta-neously. This reversibilitysuggests that the thickening ofthe cavity wall and pleura aredueto a hypersensitivity reaction6.The imaging differentialdiagnosis of saprophytic aspergi-llosis includes ruptured

echinococcal cyst, Rasmussenaneurysmin a tuberculous cavity,lung abscess, bronchogeniccarcinoma, hematoma, and Pcarinii pneumonia 7.Chronic necrotizing asper-gillosis (semi-invasive asperg-illosis) is characterised atpathologic examination by thepresence of tissue necrosis,granulomatous inflammation andfibrosis resembling post-primarytuberculosis. Many patients haveco-morbid conditions likechronic obstructive airwaydisease, corticosteroid therapy,diabetes mellitus, malnutritionand chronic alcohol intake.Clinically the patients manifestwith chronic productive coughand fever, hemoptysis has beenreported in 15% of affectedpatients8. Radiologic findingsinitially consist of unilateral orbilateral upper lobe consolidationand nodular opacities (Fig-7).Progressive cavitation developsas a result of necrosis of theconsolidated lung parenchyma9.Adjacent pleural thickening iscommonly seen. The radiologicalpicture typically progress slowlyover months or years.

Invasive aspergillosis is aserious pathologic conditioncaused characterised by vascularinvasion, arteriolar thrombosisand ischemic tissue necrosiswhich is invariably seen inimmunocompromised patients.Clinically, patients developcough, pleuritic chest pain, fever,dyspnea, and tachypnea.An earlydiagnosis is essential because adelayed or improperly treatedinfection has a 65%–90%

mortality rate. Clinical findingsmay mimic thromboembolicdisease and microbiologicaldiagnosis may be difficultbecause sputum cultures arepositive in only 10% of patients10.Therefore, more invasivediagnostic approaches, includingbronchoscopy with transbr-onchial biopsy, percutaneousneedle aspiration biopsy, or openlung biopsy, may be required. Theradiographic pattern consists ofperipheral wedge shaped nodulesor single or multiple areas ofconsolidation (Fig-8). Atcomputed tomography (CT) acharacteristic finding in earlyinvasive aspergillosis consists ofa halo of ground glassattenuation surrounding a softtissue nodule. This “halo sign” isrelated to presence of hemor-rhage surrounding the centralnecrotic nodule (Fig-9)10. The CThalo sign is also encountered inother pulmonary infections suchas Candida, Herpes simplex andCytome-galovirus and inmalignant conditions likeKaposi’s sarcoma andhemorrhagic metastases. Thehyphal form of the fungusinvades the pulmonary vascul-ature resulting in pulmo-naryhemorrhage, arterial thrombosis,and eventual infarction. Overtime, with retraction of theinfarcted center and peripheralreabsorptionof necrotic tissue byleukocytes, a central cavity ofdevitalized tissue is formed. Theair crescent sign results when airfills the space between thedevitalized tissue andsurrounding parenchyma. Anopaque rim of hemorrhagic


tissue peripheral to theradiolucency makes visualizationof the air crescent possibleTreatment is with intravenousamphotericin B, the case fatalityis high despite intensive therapy.References

1. Greene R. The pulmonaryaspergillosis: three distinctentities or a spectrum ofdisease. Radiology 1981;140:527-530.

2. McAdams HP, Rosado-de-Christenson ML, TempletonPA, et al. Thoracic mycosesfrom opportunistic fungi:r a d i o l o g i c - p a t h o l o g i ccorrelation. RadioGraphics1995; 15:271-286.

3. Nguyen TE. The glovedfinger sign. Radiology 2003;227:453–454

4. Aquino SL, Lee ST, WarnockML, Gamsu G. Pulmonaryaspergillosis: imagingfindings with pathologiccorrelation. AJR Am JRoentgenol 1994; 163:811-815

5. Franquet T, Müller NL ,Giménez A, Guembe P,Torre J, Bagué S. Spectrumof Pulmonary Aspergillosis:Histologic, Clinical, andRadiologic Findings Radiogra-phics. 2001;21:825-837.

6. Franquet T, Giménez A,Cremades R, Domingo P,Plaza V. Spontaneousreversibility of “pleuralthickening” in a patient withsemi-invasive pulmonaryaspergillosis: radiographicand CT findings. Eur Radiol2000; 10:722-724.

7. Thompson BH, Stanford W,Galvin JR, Kurihara Y. Variedradiologic appearances ofpulmonary aspergillosis.RadioGraphics 1995; 15:1273-1284.

8. Franquet T, Müller NL,Giménez A, Domingo P,Plaza V, Bordes R.Semiinvasive pulmonaryaspergillosis in chronicobstructive pulmonarydisease: radiologic andpathologic findings in ninepatients. AJR Am JRoentgenol 2000; 174:51-56.

9. Gefter WB, Weingrad TR,Epstein DM, Ochs RH,Miller WT. Semi-invasivepulmonary aspergillosis.Radiology 1981; 140:313-321.

10.Blum U, Windfuhr M,Burtrago-Terlez C, SigmundG, Herbst EW, Langer M.Invasive pulmonary asper-gillosis. Chest 1994; 106:1156-1161.

11.Pedro PS. The CT Halo Sign.Radiology 2004; 230: 109.

Fig-1,Chest x-ray shows tubu-lar areas of increased opacityin a bronchial distribution andcystic lucencies with opaquecuffs, representing broncho-celes and bronchiectasis re-spectively.

Fig-2,Spiral chest CT showsmucoid impaction (finger-in-glove sign) of dilated bronchiin the right upper lobe.

Fig-3, HRCT shows ectaticbronchi with thickened wallsfilled with hyperdense mucusin the both upper lobes.

Fig-4, Chest x-ray shows asmooth walled tubercular cav-ity in the right upper zone witha dependent nodular shadow(fungal ball).


Fig-5, Axial CT scan throughthe upper chest shows a thinwalled cavity in the right up-per lobe containing a soft-tis-sue density mass in contactwith the medial wall.

Fig-6,Chest CT with thepatient in the right lateraldecubitus position shows thefungal ball resting along thelateral wall of the cavityindicating mobility.

Fig-7,Chest CT shows an ir-regular airspace opacity in theposterior segment of the rightupper lobe (semi-invasive as-pergillosis confirmed byFNAC).

Fig-8, Spiral CT through theupper chest reveals a pleuralbased wedge shaped infarct inthe anterior segment of theright upper lobe.

Fig-9, HRCT reveals a halo ofground glass haze surround-ing the wedge shaped opacity(infarct)

Medicine in ancientRome

Alexander the Great hadencouraged his physicians toexpand the limits of theirscience, and from the time ofHippocrates, Greek doctorswere recognised as the best inthe world. The Romansadmired them, too, and whenthey conquered the Greeks inabout 100 BC, the physicianswere allowed to continue topractise, now as Romansubjects.However, the firstGreek doctor/surgeon that theRomans encountered wasalmost their last. According tothe naturalist Pliny the Elder,Arcagathus arrived fromGreece in 219 BC. He was madea citizen, and a medical shopwas set up for him at state

expense. Because he was anexpert wound surgeon(uulnerarius), he immediatelybecame popular, but this did notlast. His enthusiastic use of theknife and cautery – that is,cutting and sealing tissue withhigh heat – soon earned him thetitle ‘Executioner’ (Carnifex).More than 100 years elapsedbefore another Greek physician,Asclepiades of Bithynia, tookup residence in Rome.In 46 BC,Julius Caesar granted citizen-ship to all foreigners teaching aliberal art in Rome. Thisincluded the Greek doctors,most of whom were slaves orfreed men. When, in 23 BC,Antonius Musa, once MarkAntony’s slave, cured theemperor Augustus of a seriousillness, he was richly rewardedand won immunity fromtaxation for all doctors. Later,during the reign of Vespasian(AD 69-79), physicians werealso freed from militaryservice.‘It’s not at all surprisingthat the Romans used Greekphysicians,’ says AndrewWallace-Hadrill, director of theBritish School at Rome andprofessor of classics at ReadingUniversity. ‘Greek medicine wasincredibly sophisticated.’Thedemand for Greek physicianscontinued to grow, and manyRoman cities devised taxincentives to get them to stay.But this was strictly privatemedicine, with no set pay scale.Only reputation determinedprosperity. ‘In general, Romansare very superstitious,’ conti-nues Wallace-Hadrill, ‘and tothem the borderline betweenmedicine and magic was veryunclear.



Health System in India

R.Rose, Sandeep SachdevaMinistry of Health & Family Welfare, Nirman Bhawan,New Delhi

Health system is a complexof inter related elementsthat contribute to health

in homes, educational institu-tions, workplace, public placesand communities as well as in thephysical and psychologicalenvironment of an individual andthe health and health-relatedsectors. India is a Union of 35States/Union territories andbeing federal nature ofconstitution of India, States arelargely independent in matterrelating to health delivery. Eachstate, therefore, has developed itsown system of health caredelivery, independent of thecentral government. The centralgovernment responsibilityconsists mainly of policy making,planning, funding, guiding,assisting, evaluating andcoordinating the work of thestate health ministries so thathealth services cover every partof the country and no state lagsbehind for want of these services.The health care serviceorganizations in the countryextend from national to villagelevel.Central level

The Central Council of Healthand Family Welfare wasconstituted by President underConstitution of India andcomprises of Union minister ofHealth and Family Welfare aschairperson, Minister of state anddeputy minister as vice

chairperson, member planningcommission, minister inchargefrom the ministry of health andfamily welfare, Medical educa-tion, & public health from thestates & Union Territories,member of parliament, eminentperson from health and familywelfare sector, and senior officialsfrom the Central Government asits member. The council is theapex advisory body and in thatcapacity considers and recom-mend broad lines of policy inregard to matters concerninghealth and family welfare in allaspects; makes proposal forlegislation in the field of matterrelating to medical, public healthand family welfare; examines thewhole field of inter-statecooperation;recommends tocentral government regardingdistribution of available grant-in-aid for health and family welfarepurpose and reviews periodicallythe work accomplished andestablishes any organizationinvested with appropriatefunctions of promoting andmaintaining cooperation betweenthe central and state health &family welfare administration.The planning commission andministry of planning providesover-arching mechanism forpolicy planning, coordination andimplementation. The otherofficial body of the health systemat the national level consist ofThe ministry of Health and

Family Welfare; The DirectorateGeneral of Health Services.Union Ministry of Health andFamily Welfare-The unionministry of health and familywelfare is headed by a cabinetminister, a minister of state anda deputy health minister. Theseare political appointments.Currently, Union health ministryhas following departmentsDepartment of Health andFamily Welfare; Department ofAYUSH [Ayurveda, Yoga &Naturopathy, Unani, Sidha,Homeopathy]; Department ofHealth Research. Eachdepartment is headed by aSecretary to Government ofIndia as its executive head,assisted by joint secretaries,deputy secretaries and a largecadre of administrative staff. Incommon parlance, it is known asadministrative wing of ministryof health and family welfare. Thefunction of the union healthministry have been set out in theseventh schedule of article 246of the constitution of Indiaunder Union list and theconcurrent listUnion list-The functions givenin the union list are internationalhealth relations and admini-stration of port quarantine;administration of centralinstitutes such All India instituteof Hygiene and public health,Calcutta; National Institute forthe control of Communicable


diseases, Delhi etc.; promotion ofresearch through researchinstitutes and other bodies;regulation and development ofmedical, pharmaceutical, dentaland nursing profession;establishment and maintenanceof drug standards; Collectionand compilation of census andother statistical data; immigr-ation and emigration; Regulationof labour in the working ofmines and oil fields; andcoordination with states andother ministries for promotion ofhealthConcurrent list-The functionlisted under the concurrent list isresponsibility of both the Unionand State governments. Thecentre and the states havesimultaneous powers oflegislation as may be undertakenby the centre. The concurrent listincludes:prevention of extensionof communicable disease fromone unit to another; preventionof adulteration of food stuffs;control of drug and poisons; vitalstatistics;labour welfare;portsother than major; Economic andsocial planning;Populationcontrol and family planning

Directorate General of HealthServices-The Director Generalof Health Services is the principaladviser to the Union governmentin matters relating both tomedical and public health. He isassisted by officers of rank ofadditional director general, ateam of deputies and a largenumber of administrative staff.In common parlance, it is knownas the technical wing of ministryof health and family welfare.Thegeneral functions are surveys,planning, coordination,

programming and appraisal of allhealth matters in the country. Thespecific functions are -Internati-onal health relations andquarantine: All the major ports inthe country and internationalairports are directly controlled byDte. GHS. All matters relating toobtaining assistance andcoordination from internationalagencies are dealt by Dte.GHS;Control of drug standards: Itsprimary function is to lay &enforce standards and control themanufacture & distribution ofdrugs through both central andstate government; Medical storedepot: These depots supply thecivil medical requirements of thecentral and state governments.These depots also handlesupplies from foreign agencies;Post graduate training: Dte.GHSis responsible for administrationof national institutes, which alsoprovide post-graduate training todifferent categories of healthpersonnel; Medical education: Asof date, country has 266 medicalcolleges; Medical Research;Central Government HealthScheme: Health insurancescheme for central governmentand other employees, parliamen-tarians etc; National HealthProgramme; Central HealthEducation Bureau (CHEB):activities includes developmentof education material ofcommunity and health personnelawareness and training on healtheducation to health personnel;Central Bureau of HealthIntelligence (CBHI): collects/collates/compiles, analyze,evaluate and disseminate inform-ation on health statistics; NationalMedical Library [NML] locatedin New Delhi.

State level-By and large, theorganizational structure adoptedby the state is in conformity withthe pattern of the centralgovernment, each headed by aminister and with secretariatunder the charge of Secretary/Commissioner [health and familywelfare] belonging to the cadreof Indian AdministrativeServices [IAS]. However, theorganizational structure in Statedirectorate of health services isnot uniform through out thecountry e.g. in some states, theprogramme officers below therank of Director of healthservices are called as AdditionalDirector health services while inother states they are called Joint/Deputy director health services.In some states, area of medicaleducation is under the charge ofDirector medical education andresearch that is answerabledirectly to the health Secretary/Commissioner of the state. Somestates have created the posts ofDirector [Ayurveda], andDirector [Homeopathy]. Medicalcare facilities under AYUSH inthe country are Ayurveda [2398hospitals & 13914 dispensaries];Unani [268 hospitals & 1010dispensaries]; Siddha [281hospitals & 464 dispensaries];Yoga [08 hospitals & 71dispensaries]; Naturopathy [18hospitals and 56 dispensaries] andhomeopathy [230 hospitals &5836 dispensaries].

District level-In the recent past,states have reorganized theirhealth services structures in orderto bring all health care programsin a district under unified control.This level corresponds to middlelevel management organization


and is a linkage between the stateas well as regional structure onone side and peripheral levelstructures as CHC, PHC and SCon other side. It receivesinformation from the state leveland transmits the same to theperiphery by suitable modific-ation to meet the local needs. Indoing so, it adopts the functionof manager and brings outvarious issues of general,organizational and administrativetypes in relation to themanagement of health services.The district officer with theoverall control is designated asthe Chief Medical and HealthOfficer [CM&HO] or theDistrict Medical and HealthOfficer [DM&HO]. Theseofficers are also known as DMOsor CMOs and are overall inchargeof health and family welfareprogrammes in the district. Theyare responsible for implementingthe programme according topolicies laid down and finalizedat higher level. Deputy CMOsand programme officers assistthese CMOs. Each district usuallyhas a district hospital where mostof the specialty services areprovided and headed by a officerof a rank of Deputy CMO.Community health centres[CHC]/ Sub divisional hospi-tals-Community health centreshave been established for every80,000 to 1,20,000 populationand this centres was proposed toprovide basic specialty services ingeneral medicine, pediatrics,surgery and obstetrics &gynaecology supported by 21paramedical staff and other staff.The CHCs are established byupgrading the sub-district/taluk

hospitals or some of the blocklevel primary health centres orde-novo and are maintained bythe state government. Accordingto available information there are3,910 CHCs in the country.Primary Health Centre andSubcentre-At present there isone primary health centrecovering about 30,000 [20,000 inhilly, desert and difficult terrain’s]or more population. Many ruraldispensaries have been upgradedto create these PHCs. Each PHCshas one medical officer, twohealth assistants-one male andone female, health workers andsupporting staff i.e. in total thereare 14 staff to support medicalofficer. Under National RuralHealth Mission [NRHM], thePHCs have been strengthened byprovision of 3 Staff nurse and anAYUSH practitioner. The mostperipheral health institutionalfacility is the subcentre mannedby one male and one femalemultipurpose health worker.According to norms at mostplaces there is one subcentre forabout 5000 populations [3,000 inhilly, desert areas and in difficultterrain]. Government of Indiabears the salary of ANM andhealth assistant [female]/LadyHealth Visitor [LHV] as per stategovernment pay-scale besidesrent liability and contingencywhereas the salary of male healthworker and health assistant [male]is borne by the state government.As on date there are 23,000 PHCsand 1,44,988 subcentres in thecountry.Other major agencies provi-ding health care in IndiaCentral Government HealthScheme [CGHS]-the scheme

was introduced in Delhi on 1st ofJuly, 1954 with the objective toprovide health care to the centralgovernment employees andmembers of their families and todo away with the cumbersomeand expensive system ofreimbursement of medicalexpenses. The CGHS wasinitially meant for the centralgovernment employees, mem-bers and Ex-members ofParliament, judges of supreme-court and high court, freedomfighters and was later extendedto people working under variousgovernmental organizations,semi-governmental, semi-auto-nomous bodies, accreditedjournalists and ex-governors/ex-vice president of India. As onmarch 2007, there are 247allopathic dispensaries, 85AYUSH dispensaries, 17polyclinic, 70 labs, 19 dental unitsin 24 cities for 9 lakh cardholdersand 33.01 lakh beneficiaries.Employee State InsuranceScheme-ESI Act of 1948 and itssubsequent amendments,provides for welfare services foremployees of industrial,commercial, agricultural andother establishments specified inthe act. The scheme has beenextended to shops, hotel,restaurants, cinemas includingpreview theatre, road motortransport undertaking &newspaper establishment emplo-ying 20 or more persons. Theexisting wage limit for coverageunder act is Rs. 10,000/- permonth [w.e.f. 1.10.2006]. The ESIscheme is being implementedarea-wise by stages in all thestates except few North-EasternStates. The Employees’ State


Insurance Scheme is admini-stered by a Corporate body calledthe Employees’ State InsuranceCorporation (ESIC), which hasmembers representing emplo-yers, employees, the CentralGovernment, State Governm-ents, medical profes-sion and theParliament. The Medical careunder the Scheme is administeredby State Governments, who havethe statutory responsibility in thisregard, except in Delhi State andNoida area of U.P. Besides, theESI Hospital, K.K. Nagar atChennai, ESI Hospital, Thakurp-ukur at Calcutta and ESI Hospitalat Nagda are also being rundirectly by the Corporation. Asper available information [2005],there are 144 ESI hospitals, 42Annexes, and 1427 dispensarieswith 75.70 lakhs registeredemployees and 329.73 lakhsbeneficiaries.Health-care delivery system inRailways-The objectives ofhealth services of IndianRailways include preventive,promotive and curative healthservices for its employees/retired/dependents etc includingindustrial health; to ensureadequate physical standard ofemployees and their periodicalcheck-up; to provide andmaintain accident relief medicalequipment [ARME] includingfirst-aid, to give prompt relief topassengers injured in railwayaccidents; to attend thepassengers taking seriously ill intrains or at railway station;provision of safe food and watersupply; ensuring factory andworkmen compensation act;certification of death occurringin railway premises and

implementation of nationalhealth programme programmeetc. The apex body in railwayshealth directorate is headed byDirector General Railway HealthServices at Railway Board, RailMantralaya, New Delhi. At Zonallevel, there are 16 zonal Railwaysand each Zonal Railway isheaded by one Chief MedicalDirector (CMD) with ChiefHealth Directors in some Zonesand 2 to 3 Dy.CMDs assisted byfew Group ‘B’ officers. Atdivisional level, it is mostlyheaded by Chief MedicalSuperintendents and in someplaces Sr. Medical Superinte-ndents are working as in-chargewith 2461 general duty medicalofficers, 45 dental surgeons and575 visiting specialists. A railwaybeneficiary receives medicaltreatment through availableRailway health facilities or GovtHospital or recognized privateHospital. In extreme emergencysituation when there is no timefor a railway beneficiary to cometo Railway hospital then he/shemay avail treatment in a privatehospital/Government Hospitalin the locality and can claimthrough reimbursement system. There are 121 railway hospitals,661 health units and 133approved private institutions forproviding specialist care notavailable in railway hospitals/health units or nearby othergovernment institution in thecountry.Health-care delivery system inDefence-The Armed ForcesMedical Services (AFMS),consisting of the Army MedicalCorps (AMC), the Army DentalCorps (ADC) and the Military

Nursing Services (MNS) providecomprehensive health care to theserving Armed Forces personnel,their families and dependents,numbering approximately 66lakhs. In addition, Ex-Servicemen and their families arealso entitled to free treatmentfrom Services sources as per rulesand so are the Para MilitaryOrganizations like Assam Rifles,Rashtriya Rifles, Coast Guard aswell as the DRDO and BorderRoad Organization personnel,while posted in the field. ArmedForces Medical Services are alsoactivated in aid to civil authoritiesduring epidemics, naturalcalamities and internal securityduties, especially in inaccessibleand difficult areas. In addition tothis, life saving emergent care isalso provided to all civilians bythe establishments of AFMS.Besides the facilities madeavailable in combat zones, 127hospitals of varying sizes andfacilities, spread over the lengthand breadth of the country, arealso functional. While theperipheral hospitals have basicspecialist facilities, the eightCommand/Army Hospitals havesuper specialist centers with state-of-the-art equipment andfacilities.There is a network ofRegimental Aid Posts manned bydoctors. These are supported by89 Field Ambulances, which aremobile 45 bedded hospitals[forward treatment centre] andcan organize its medical staff intotwo Advance Dressing Stations[ADS] and two Medical AidsPosts [MAP]. There are two FieldAmbulance Units [FMU] in adivision for providing medicalcover. The staff of field


ambulance unit comprises ofCommanding officer [1], secondin command [1], Adjutant [1],surgeon [1], General duty medicalofficers [6], Non technical officer[1], and other supportivestaff.Army medical corps [AMC]provides medical care and othersupport to the defence personneland their families through anetwork of hospitals. AMC alsoprovides for medical manpowerto other wings of the defencesuch as Airforce and the Navy.The post of Director GeneralArmed Forces Medical Serviceswas created in 1949 ascoordinating head of the medicalservices of the Army, Navy andAir Force. The medical units ofAirforce include Air forcehospitals and Institute ofAerospace Medicine, Banglorefor training, aeromedicalevaluation and aerospaceresearch.Private sector and Non-governmental organization-Both formally trained [Allopathyand AYUSH] and informal [quacks]players provide basic healthservices to large proportion ofpopulation in the country with80% share in outpatient and 55%share in inpatient area. Theselargely include corporate houses,private hospitals, nursing homes,polyclinics, trust/voluntary/NGO institutions, privatepractitioners [Trained], andprivate practitioners [untrained orquacks].Challenges, issues andconcern-The main challenges,issues and concerns are toenhance the allocation ofgovernment budget on healthsector with simultaneous increase

in utilization capacity by differentStates/UTs; Improving/Enhan-cing utilization of public healthfacilities by the community;Regulation of private sector;Maintaining equity, quality ofservice and focus on ‘outcome’;Consolidation and strengtheningprimary, secondary and tertiaryhealth care for optimalperformance and building upappropriate referral services withre-emphasis on primary care;Increasing efficiency, effective-ness, responsiveness andaccountability of public healthsystem; Challenge of coordin-ation amongst differentorganization/bodies and stake-holders for planning andimplementation; Communityparticipation.

Ancient medicine inAlexandria

With Alexander the Great’s newempire, the West was connectedto the East and the South forthe first time. The enquiringminds of the Greeks now hadaccess to the rich medicaltraditions of Egypt and India,of the great physician Skar andof Sushruta, India’s firstsurgeon. Precisely whatAlexander’s armies broughtback from India isn’t certain,but all learning, includingsurgical knowledge, advancedrapidly at about this time.Twenty-three centuries ago, onvirgin land on theMediterranean coast of Egypt,Alexander established hisEgyptian capital: Alexandria.After his death in 323 BC, hissuccessor as ruler of Egypt,Ptolemy, was determined tomake the city the most

important in the Greek world.And as part of this, it became agreat centre of science wheremedicine could f lourish.Ptolemy sent agents all over theGreek world to acquire newtexts, and visiting ships wereobliged by law to leave theirmanuscripts to be copied. AsAlexander himself had wished,a great library was built to housethem all. Over half amillennium, it gathered togethersome 700,000 volumes,including the most compreh-ensive body of medical texts inancient history.In addition, thePtolemy family established amuseum – ‘house of the Muses’– a publicly funded researchinstitute. Thanks to this and thegreat library, the developmentand teaching of scientificknowledge flourished as neverbefore. ‘Hippocratic medicine isvery interesting,’ says LawrenceBliquez, professor of classics atthe University of Washington,‘but with the appearance of OnMedicine by the Roman writerCelsus [c. 25 BC-AD 45], wehave much more developedmedicine and much moredeveloped surgery. ‘What’shappened in the meantime?Alexandria has happened. Themuseum has opened, and theruling Ptolemy family is veryliberal in their support of allsorts of research endeavours –medicine, literature, everyth-ing.‘For a good 50-year period,we have people such asHerophilus of Chalcedon andErasistratus of Iulis permittedto perform not only anatomicaloperations on corpses but also,if we’re to believe Galen,vivisection.’


12

Guidelines on DNB thesis

T

Correspondence

the National Board ofExamination for thesis/dissertation that a good largenumber of dissertations arerejected or sent back for themodification. This article is basedon interaction and observationsmade on these dissertations. Thisinitiative has been taken in orderto help the candidates who areselected through a tough AllIndia Entrance Examination andaspire for a better future bypassing through the acid testcalled DNB examination process.This article is also an attempt tocaution the guides andsupervisors of the candidateswho finally sign those theses thatare often rejected or sent formodification. Some one has putvery rightly ‘ one has to find out“if the horse is wrong or the rideris wrong or both” before wereject the thesis and blame eitherthe supervisor or the candidateor the both. “Malice ageist non”-is the dictum while composingthis article, the very idea is to savethe time and energy of thecandidate and the supervisor.This is also intended to bring themedical research, especially theclinical research out of itsambiguous state on unreliabilityto an internationally more

his is a commonobservation with most ofthe assessor selected by

acceptable status. The ease toadmission through differentchannels of inf luences anddifficulty in passing thebenchmarks that has noreservation or capitation feefacility. The r3equest often comesfrom these very quarters to raisethe pass percentage for theseDNB exams! The question oftenasked is as to why the DNBresults are so poor? They shouldhave been better. At the sametime we see good results for thosewho pass out the exams. Hereindeed is the need forintrospection as to what has gonewrong with our under graduateand postgraduate teaching. Whysome candidates from goodinstitutions do well in the theoryand viva voce exams while othersdo not. Is it the defect of theteaching system or the teacherwho are often blamed with notdoing enough in teaching andeducation or the reluctantcandidate who has known themethods of “cake walk” in theexams when the assessors,examiners were internal as wellas the externals are friends of theinternal in the viva-voceexamination. A favorablesituation where more often thannot the theory answer sheets arealso assessed simultaneously. Thisis in stark contrast to the DNBexams where you do not even getyour own city to appear in thepractical viva- voce, what to talk

of the examiner being from yourown institution or the city .Theanswer sheets go to four differentexaminers that are often notconnect with Viva-voce. Viewingthis entirely different scenario,the assessment is bound to behard core and not that of facilityand felicitation in honor of yourown non-performance. TheQuestion I repeat: can the thefuture of Indian health that is inyour hands be left to leniency?Compromising or lowering ofthe subject knowledge of thestudents will further aggravatethe situation as it is today in termsof health care.Selection of the topic on theclinical subject- In clinical workthe selection of topic should bedone after thoroughly studyingthe feasibility as per theinstitutional infrastructure andthe patient influx. This is purelyin order to meet the minimalrequired criteria of numbers thatshall facilitate the statisticalanalysis.Synopsis of the thesis-TheSynopsis of the thesis: to beshown not only to the committeebut also to the assessor to whomthe final thesis has to be sent.This will go a long way inpreventing the rejection of thesis.This should then be substantiatedor supplemented by mid termassessment of the dissertationwork that should also be sent tothe same assessor.


Candidate - They must have aclear vision so as to why they arethere in this course and what aretheir aims and objectives in orderto complete this course: whetherto obtain degree so that one getsa job or to get trained in anacademic life style that will helpthe health of the country as wellas scientific research basedapproach in the field of medicalsciences.The candidate shouldalso know as to how much is hiscontribution to Indian statisticsas original work or enrichment inpooling high quality genuine datathat is inadequate or non-existence on Indian patients.Every project that has to be takenshould be done with the view thatit shall be sent for publication toa peer reviewed ‘indexedjournal”. Thus in such a situationboth the candidate and hissupervisor will be benefited andshall devote more efforts in termsof mind , time and dedicationto the work. The candidate mustrefer to several publicationavailable in scientific researchsuch as “How to Write a Paper”or “Scientific Writing- EasyWhen You know How” byByword Viva Publishers 4262/3Ansari Road, Darya Ganj NewDelhi 110002 ) and get his / herlife style modified in scientificapproach while working for thedissertation. There are suchseveral other publications toguide the dissertation work.Thecut and paste culture: a good largenumber of theses are coming thatare cut and past from the website.I am remained of professor ofpathology who came across onethesis that was totally cut and

paste from websites and therewas no bibliography in that thesis.There are cases where the wholethesis has been copied from somebody else’s M.D. or DNBprobably with a self assurancethat the assessor shall not knowabout it. Yet in another case theidea and subject of the thesis wasgreat but the institution neitherhad infra structure or expertiseto carry it out and hence totalfabrication. In most cases it maynot be possible to detect but thisis not going to help the candidate.There are examples of suchfraudulent work since timeimmemorial when a candidatehad produces a thesis onhyperthermia when theequipment to give the same wasnon-existent in Northern part ofthe country. Or when thecandidate has produced a thesiswhen his department was shutdown by AERB during the tunerof his thesis. Sooner or later thestories leak out and may causeembarrassment to the candidate.Review of literature - In generalthe candidates have habit ofquoting western epidemiologicaldata fresh from Europe ,America and Japan that has littlerelevance in dealing with theIndian population. At least in caseof Oncological Sciences we havenational Cancer Registry ofICMR that is able to provide agreat deal from theirmetropolitan and hospital basedtumor registries. Otherspecializations should be havingsimilar registries to be embarkedupon. If not it is high time that itis created.

Randomization in clinicalsubjects like oncology- Beforestarting the thesis the candidatemust understand the tenets ofscientific research and the trials.The whole project or theprotocol needs to be shown tothe bio statistician of someexperience before the work isstarted. This will give a properdirectives for the selection for thetopic and the minimal desirablenumber of cases that candidatehas to complete during thetraining tenure. It is nice to workon the rarest of the rare diseasebut it should be carried out withadequate number that shallenable it for statistical analysis. Itis here the strict stance that isrequire in the preparation ofdissertation that shall lead toemergence of realistic data onIndian patients. This shall give achance to compare the Indiandata versus oft-repeatedquotations from westernepidemiological data that has norelevance to Indian scenario withregards to the solution,prevention and control of thedisease. There should be properutilization of tools to representthe observation such astabulation, bar diagrammeshistograms etc. It is always betterto follow a standard format ofthesis writing rather than creatingone’s own. Title Page,Certifications, Forwards, Wordsof Gratitude, Index, Abbrevi-ations, Introduction, Aims &Objectives Review of Literature,Material and Methods,Observation, Discussion,Conclusion, Bibliography/refer-


ences, Annexure, Master chartetc.Institutions-The institutionsshould equip themselves to carryout these high profile scientificworks required for the future andcareer of the candidate. Theinstitution should not onlyprovide the proper minimalinfrastructure and staff butshould also provide time to thecandidates for his studies andwork, not using them as cheaplabor for routine work or toappease the employers byenhance the earning from patienttreatment or private practice.Thebio statistician, the dietician, themedical physicist, the physio-therapist etc. the paramedicalfacilities should be provided sothat the work is carried out in aproper manner. Indeed it is ingood favor of the institution ifgood quality research work ispublished in journals ofinternational repute exemplifyingthe genuineness and sinceritybehind the work. This shouldform a national phenomenonfrom every institutionconduction DNB courses.Instead of only few institutionsbeing favored for the acceptanceof publications just because ofthe reasons such as esteemednametag attached to them, highquality contribution from everyinstitution should become theusual happening.Guide-One should not forget thestark reality that the careermaking means good number ofpublications in indexed and peerreviewed journals. One shouldalso not forget the fact that with

the modern informationtechnology tools available thescrutiny and surveillance by thepeer reviewed indexed journals isbecoming stricter, day by day. Insuch a situation the work carriedout should be supervised in sucha manner that it stands the acidtest of the standards observed bythese journals. At any point oftime the DNB dissertation workshould not be taken lightly as itconcerns the candidates futurewho is the future health careprovider of the country as wellas for the patients life or for thatmater the medical sciencesresearch in India. The guideshould have bimonthly review ofthe candidate’s work and just notsign the thesis at the fag end ofthe work , at times without goingthrough the draft even!!. Guideshould also keep in touch withthe NBE in order to appraise theboard about the progress of thecandidate. The NBE shall haveto equip itself for the same.Though to the candidate and tothe NBE this may cost a littleextra in terms of time and moneyand man power but it shallcertainly improve the standardsand solve certain big lookingtrivial problems. The guidehimself has to train himself andapprise himself with the basictenets of medical and clinicalresearch because many a thesethesis have given similar signalsthat the guides lacked scientifictemperament and theythemselves were not beenfounded firmly on fundamentalsof the medical research andtraining work. This is the most

desired change that the guideshave to bring about in themselvesthat the institutions that areapproved for DNB courses neednot remain the commercial healthcomplex but also serve as usefulcenters for serious scientificresearch too. The guides have todevelop a scientific temperamentand the prime aim and objectivefor the DNB candidate should behis research and clinical/academic training and not theeasy, vulnerable manpower toserve and run that institution’sday to day affairs.The Midtermassessment of the thesis workand modification thereby-Thebest way to avoid this malady isto have a mid term assessmentof the dissertation work. Thisshould be done locally by theguide and his departmentalresearch committee and thenshould be sent to the same expertwho is also going to assess thethesis finally.This shall preventthe situation like thesis comingfor the modification when thecandidate has finished his tenurein the institution.What should candidate and hisguide do if the thesis comesfor modification after thetenure is completed?-Firstthing they should remember thatthe medical life is never endinglearning and so is the medicalresearch. The time restraints forthe course in full view thecandidate should not wind up thework, instead continue the worktill the end of the tenure . Thismeans that the candidate isprovide another six months toharvest the cases in order to


fortify his statistical pool;institution and candidate gets anadditional follow up data; thecontinuation of the project mayadd to institutional long termstudy that can be utilized byanother candidate for furtherobservation .They should notforget to send the work report inmid term to the assessorwhosoever he may be throughNBE so that directives ormodification if at all can becommunicated. Candidate shouldcollected sufficient date withprobability of off shoots of thework. Should follow the basictenets of the scientific researchin first place so that the thesisdoes not stand the risk ofrejection or modification.TheGuide should have “on goingprojects” with a wider scope andaims and objectives so that in caseof the diseases that do notprovide sufficient number ofpatients, a better pooling of datais made available to the candidatein form of a retrospective andprospective study.

What should candidate andthe institution do if the guidegoes away!-From the verybeginning the Institutionaladministration should allocate astandby guide who can supervisein case of demise or abstentionof the actual guide of thecandidate. Some kind of co-guideor sub guide. This should bepossible in the institutions wherethere is rapid rate of exit andentry of the consultants as onesees in private five starinstitutions.

Is dissertation just a passportto DNB Degree?-he Issue is notthat the candidate has passed thetheory and practical examinationso he is eligible for the degree. Inthat case there is no need for thedissertation of thesis. Thequestion is that the making of aspecialist should be based on thefirm footing of scientific research, the process of the learning ofmedical science. The purpose ofdissertation is to create a newgeneration of medical scientistwho can contribute genuine –non fraudulent, non copycat datato the pool of Indian scientificdata. The purpose is to shun ordiscourage the fictitious /hijacked or stolen work that is acommon practice in many of theinstitutions. Instead of thecandidate undergoing therigmaroles and grooving for thewhole tenure of the course thatis meant to make him a genuinescientist,the thesis from thepremier institutions or thedepartments that have a nationalor international repute are copiedin-toto and are sent asdissertation and that takes fewdays time in making it . Thepurpose of strict standards in thedissertation is to correct thewrong impression of the peerreviewed index journal and theireditorial board that rejects sucharticles and often accept thearticles blindfoldedly, when itcomes from some handful of socalled premier institutions ofIndia - irrespective of the factthat in that scientific publicationchurning industry many of thepublications there too are farbelow standards , statistics stage

managed like tables ofnumber..... 2, 2za 4 and 4, 4za 16.Referring to the Guides onScientific paper making orresearch procedures-Theliterature available in these booksthat give directives on trials andscientific paper publications willcertainly improve the quality ofIndian medical researchespecially so on the clinical andpara-clinical side and the creditthus has to go to National Boardthat has with its untiring effortshas set a bench mark not only inthe realm of post graduateeducation but also in the realmof medical sciences research. Anarea that needs seriousreformation and image buildingin front of international playersfrom the developed countries. Ina recent experience it was foundthat the candidates havecomplained as to why the resultsin the DNB examination are sopoor from their state- 10 percentonly ! It is apparently the combineor the net result of all the successand failures inclusive ofdissertation, theory paper andpractical viva-voce and one hasto reform oneself at every stepof this tenure and programme.Suggestions to tackling thisproblem - There are audio visualaids provided in form ofCDs,IGNOU programmes onvarious topics through GyanDarshan and Gyan Vaneechannels. And the candidatesmust watch these programmesrelated to their subjects as wellas the associated subjects.Thebroadcast/ telecast schedule isput on the NBE web site and


newsletters.Secondly the CMEsthat are arranged by NBE onvarious topics. The studentshould also attend the CMEsconducted by the scientific bodyof their specialty and for that theInstitutions should give all thepossible help to the candidates toattend these CMEs.The bestsuggestion that has come fromthe crowd of the studentsthemselves is to form a scientificAssociation of DNB candidates.Under the auspices of the sameassociation regular conferencesand seminars to be held onmethods of reforming theeducation and training of thecandidates. There has to be theinteractive sessions with theexperts, the examiners and theadministrators in the NBE so thatthey can put their view point andthe candidates and their guidescan put their view point.Although a stupendous job, thiswill help in a long term mannerthose hundreds of thousands ofaspiring young candidates whowant to become specialists andsuper specialist. The Institutionsthat are already contributing theirmight to conduct DNBsponsored CMEs should take theresponsibility to arrange suchZonal Conferences of Associa-tion of DNB Candidates.

Manoj Sharma

Department of Radiotherapy

Maulana Azad MedicalCollege, New Delhi

History oftreatment ofAneurysm

John Hunter performedperhaps the most famousoperation for an arterialaneurysm

Hunter had observed that theblood supply to the horns ofdeer changed under differentconditions. A rich bloodsupply was present when thecrest was full, but the bloodvessels decreased in numberand size when the horns shed.Hunter inferred that reservevessels, now termed“collaterals”, might develop inhumans if obstructionoccurred in their arteries. InDecember 1785, a beerdelivery man was admitted toSt. George’s Hospital with apulsatile mass in the poplitealfossa, possibly secondary torepetitive trauma against thecoachman’s seat while drivingon rough streets. The patienthad been symptomatic for 3years, he complained of legpain on walking and restedfrequently presumably owingto arterial occlusion distal tothe aneurysm. Standard

treatment at that time entailedabove-knee amputation.Hunter’s previous experi-ments, however, suggestedthat collateral vessels haveformed around the obstru-ction or the leg would havedeveloped gangrene. Thus, heincised above the knee at alocation now known as“Hunter’s canal” and tied fourligatures around the artery.Four sutures were used toavoid sawing through thevessel. After a bout of localinfection, the patient survivedand was discharged fullyambulatory. Later, Hunterperformed four similaroperations and three weresuccessful; the fourth patientdied 26 days postoperatively.In 1804, Antonio Scarpa(1752-1832) wrote a definitivetreatise on the forms anddiagnosis of arterialaneurysms. The first surgicalligation of a femoral arteryaneurysm was performed in1808 by Astley Paston Cooper(1768-1841). Although he isremembered for his contrib-utions to inguinal hernia andfemale breast anatomy, hismost famous operation wasperformed for a leaking iliacartery aneurysm in 1817.Cooper also cautioned thatpatients who present with oneaneurysmal disease should beevaluated for the coexistenceof others, an advice that isequally applicable today.In 1810, Dominique Aneldescribed Anel’s operation“Ligation of an artery immed-iately above and on proximalside of an aneurysm”.


13RecentRecentRecentRecentRecentAdvancesAdvancesAdvancesAdvancesAdvances

S teroidal neuromuscularblocking agents (NMBD),such as rocuronium, are

widely used in clinical anesthesiaand emergency medicine tofacilitate tracheal intubation andartificial ventilation1. Reversal ofneuromuscular blockade isimportant for the acceleration ofpatient recovery and preventionof postoperative residualneuromuscular blockade1,2,3.Currently, the reversal ofneuromuscular blockade isachieved by the administration ofacetylcholinesterase inhibitors(neostigmine, edrophonium, orpyridostigmine)1. Acetylch-olinesterase inhibitors, however,have some problems with theiruse4. Early or “escape” reversalafter a short case or anunexpected cannot intubate,cannot-ventilate scenario usingneostigmine is limited4,5. Theinability of cholinesteraseinhibitors to reverse a profoundnondepolarizing blockade may beone important reason for theunrelenting persistence ofsuccinylcholine in currentanesthetic practice, in particularfor its two principal indications,relaxation for rapid sequenceinduction and ultrashort proce-dures5. In addition, acetylcholin-esterase inhibitors have effectsassociated with stimulation of themuscarinic receptors resulting inbradycardia, arrhythmias, incr-eased secretions and contractionof smooth muscle, though these

Sugammadex- a novel neuromuscular blocker binding agent – aReview

Dr JS Dali, Rakesh GargDepartment of Anesthesiology and Intensive Care, Maulana Azad Medical College

All India Institute of Medical Sciences, New Delhican be counteracted bycoadministration of muscarinicantagonists (atropine orglycopyrrolate)1,4,6,7. However,muscarinic antagonists also haveside effects (blurred vision, drymouth, and tachycardia)1. Fewstudies have attempted to explorethe potential of nonclassicreversal drugs8. In this regard,suramin, a P2-purinoceptorantagonist, can reverse nondepo-larizing neuromuscular blockade, but it has serious side effects thatrender it inapplicable for routineclinical use8.In contrast, purifiedhuman plasma cholinesterase hasbeen shown to be an effective andsafe drug in antagonizingmivacurium-induced neurom-uscular blockade8. Similarly,cysteine has been shown toreverse the neuromuscularblocking effects of gantacurium.Notably, both purified humanplasma cholinesterase andcysteine act independently ofacetylcholinesterase inhibition8.There is thus a clear need for newreversal agents with a rapid onsetof action and an improvedefficacy and safety profile.andhaving the capability to reverseneuromuscular blockadeeffectively, independently of itsdepth.Suggamadex-A novel approachto reversing neuromuscularblockade is sugammadex (Org25969) (Su refers to sugar andgammadex refers to the

structural molecule-gamma-cyclodextrin), a selective relaxantbinding agent (SRBD), made upof a ring of eight sugars, to whichnegatively charged side chainswere added for the purpose ofbinding rocuronium and othersteroid-based neuromuscularblocking agents8,9,10.Mechanism of Action-Sugammadex is inert chemicallyand does not bind to anyreceptor. It acts by rapidlyencapsulating steroidal NMBDsto form a stable complex at a 1:1ratio and thus decreasing the freeconcentration of the drug fromthe plasma1,8,10,11,12,16. This createsa concentration gradient favoringthe movement of the remainingrocuronium molecules from theneuromuscular junction back intothe plasma, where they areencapsulated by freesugammadex molecules. Thelatter molecules also enter thetissues and form a complex withrocuronium. Therefore, theneuromuscular blockade ofrocuronium is terminated rapidlyby the diffusion of rocuroniumaway from the neuromuscularjunction back into the plasma8.Chemical structure-NMBD arequaternary ammonium compo-unds with at least one chargednitrogen atom. Cyclodextrinshave a lipophilic centre but ahydrophilic outer core, attribu-table to negatively charged ionson their surface. These negatively


charged ions on the surface ofsugammadex attract the positivecharges of the quaternaryammonium relaxant, drawing thedrug in to the central core of thecyclodextrin13. The binding ofthe guest molecule into the hostcyclodextrin occurs because ofvan der Waal’s forces,hydrophobic and electrostaticinteractions. The structure of thecyclodextrin is such that all fourhydrophobic rings of thesteroidal relaxant fit tightly withinthe concentric doughnut formingan inclusion complex. This hasbeen confirmed by calorimetryand X-ray crystallography13. Sucha reaction occurs in the plasma—not at the neuromuscularjunction—and the concentrationof free rocuronium in the plasmadecrease rapidly after sugamm-adex administration13.

P h a r m a c o k i n e t i c s - T h eencapsulated complex ofsugammadex and NMBD arefreely filtered by the glomerulusinto the urine. The plasmaclearance of the complex is thesame as the glomerular filtrationrate (120 ml/min)13. Nodissociation of this tightly knitcomplex occurs in the plasma.The main difference in thepharmacokinetic profile ofsugammadex and rocuronium isthat the clearance ofsugammadex is approximatelythree times lower than that ofrocuronium5. In the absence ofsugammadex, rocuronium iseliminated mainly by excretioninto bile and feces. In thepresence of sugammadex,however, urinary excretion of therocu ron ium–sug ammadexcomplex is the major route of

elimination of rocuronium5,7.Interestingly, shortly afteradministration of sugammadex,the total plasma concentration ofrocuronium increases. This canbe explained by redistribution offree rocuronium from theperipheral compartments back toplasma as a result of thedecreased free plasmaconcentration5. Redistributedfree rocuronium is largelyencapsulated by sugammadex,thus increasing the totalrocuronium concentration.Suggamadex and investigationtrials-Sacen et al 6 did their studyon 60 patients undergoingelective surgery with ad e s f l u r a n e – r e m i f e n t a n i l –rocuronium anesthetic techniquewho received either sugamma-dex, 4 mg/kg IV, edrophonium,1 mg/kg IV and atropine, 10 mg/kg IV, or neostigmine, 70 mg/kgIV and glycopyrrolate, 14 mg/kgIV for reversal of neuromuscularblockade at 15 min or longer afterthe last dose of rocuronium usingtrain-of-four (TOF) responses.They found that although theinitial twitch heights (T1) at thetime of reversal were similar inall three groups, the time toachieve TOF ratios of 0.7 and 0.9were significantly shorter withsugammadex (71 ± 25 and 107± 61 s) than edrophonium (202±171 and 331 ± 27 s) orneostigmine (625 ± 341 and 1044±590 s). All patients in thesugammadex group achieved aTOF ratio of 0.9 d”5 min afterreversal administration comparedwith none and 5% in theedrophonium and neostigminegroups, respectively. Theyconcluded that Sugammadex, 4mg/kg IV, more rapidly and

effectively reversed residualneuromuscular blockade whencompared with neostigmine (70mg/kg IV) and edrophonium (1mg/kg IV). In contrast toSorgenfrei et al.7, they found noevidence of a hypotensive effectdue to sugammadex when it wasadministered under steady-stateanesthetic conditions6.In con-trast to propofol, sevofluraneenhances the effects of someNMBDs, including rocuro-nium10. Xue et al14, Kim et al 15

showed that sevoflurane cansignificantly prolong theduration of action ofrocuronium and the time torecovery. These effects are notseen with either propofol orisoflurane. Vanacker et al10

investigated whether sugamm-adex, is equally effective atreversing rocuronium-inducedneuromuscular block in patientsunder propofol or sevofluraneanesthesia. After receivingpropofol for induction, patientswere randomized to propofol (n= 21) or sevoflurane (n = 21).Rocuronium 0.6 mg/kg wasadministered for trachealintubation. At reappearance ofthe second twitch of the TOFratio, sugammadex 2.0 mg/kgwas administered. Meanrecovery time for recovery oftrain-of-four ratio to 0.9 was 1.8min after both propofol andsevoflurane anesthesia. Sugam-madex is reported to be effectiveand well tolerated in healthyvolunteers and surgical patientsat doses up to 16.0 mg/kg11.Additionally, sugammadex atdoses of 2.0–4.0 mg/kg hasbeen shown to safely reversemoderate neuromuscular blockinduced by rocuronium in a


dose-dependent manner. Grou-dine et al11 enrolled 50 patientsinto a Phase II dose-finding studyof the efficacy and safety ofsugammadex. Subjects, anesth-etized with nitrous oxide andpropofol, were randomized toone of two doses of rocuronium(0.6 or 1.2 mg/kg) and to one offive doses of sugammadex (0.5,1.0, 2.0, 4.0 or 8.0 mg/kg).Sugammadex was administeredduring profound block whenneuromuscular monitoringdemonstrated a posttetanic countof one or two. They concludedthat the mean time to recoverydecreased with increasing doses.Sugammadex doses of1.0 mg/kgdid not bind sufficientrocuronium to rapidly reverse aprofound NMB. Doses e”2 mg/kg of sugammadex consistentlyresulted in a TOF ratio e”0.9 in15 min or less. Increasing thedose from this level resulted infaster reversal11.This may indicatethat sugammadexat doses of 0.5–1.0 mg/kg does not reliably bindsufficient rocuronium to producecomplete reversal of theNMBD[17]. A molecule ofsugammadex (molecular weight2178) is approximately 3.6 timesheavier than a molecule ofrocuronium (molecular weight610)11. This would suggest that adose of 1.8 mg/kg ofsugammadex would be requiredbind all the rocuronium in a 0.5mg/kg dose11. Boer et al1

investigated the efficacy andsafety of sugammadex inreversing rocuronium-inducedprofound neuromuscular block-ade at 5 min in 45 patients.Anesthesia was induced andmaintained with propofol and anopioid. Profound neuromuscular

blockade was induced with 1.2mg/kg rocuronium bromide.Sugammadex (2.0, 4.0, 8.0, 12.0,or 16.0 mg/kg) or placebo (0.9%saline) was then administered 5min after the administration ofrocuronium. They concludedthat increasing doses ofsugammadex reduced the meanrecovery time from 122 min(spontaneous recovery) to lessthan 2 min in a dose-dependentmanner. This study showed that,compared with spontaneousrecovery, sugammadex producesrapid and effective reversal ofprofound rocuronium-inducedneuromuscular blockade, withoutsigns of residual or recurrence ofneuromuscular blockade.Increasing the dose of sugamm-adex up to 16 mg/kg reduced themean recovery time to a TOFratio of 0.9 from 122.1 min(spontaneous recovery to lessthan 2 min). A clear dose–response relation between thetime from start of administrationof sugammadex and recovery ofthe TOF ratio to 0.9 was seen1.Suy et al16 explored the dose–response relation of sugamm-adex rocuronium (0.60 mg/kg)and vecuronium (0.1 mg/kg) in80 patients. Compared withplacebo, sugammadex produceddose-dependent decreases inmean time to recovery for alltrain-of-four ratios in therocuronium and vecuroniumgroups. The mean time forrecovery of the TOF ratio to 0.9in the rocuronium group was 31.8min after placebo compared with3.7 and 1.1 min after 0.5 and 4.0mg/kg sugammadex, respec-tively. The mean time forrecovery of the train-of-fourratio to 0.9 in the vecuronium

group was 48.8 min after placebo,compared with 2.5 and 1.4 minafter 1.0 and 8.0 mg/kgsugammadex, respectively. Theyconcluded sugammadex rapidlyreversed rocuronium- orv e c u r o n i u m - i n d u c e dneuromuscular block atreappearance of the secondmuscle twitch. A dose–responserelation was observed withsugammadex for reversal ofboth rocuronium- andv e c u r o n i u m - i n d u c e dneuromuscular block.Sorgenfrei7investigated 27 subjects, rando-mized to receive placebo orsugammadex (0.5, 1.0, 2.0, 3.0, or4.0 mg/kg) for reversal of 0.6mg/kg rocuronium– inducedneuromuscular block. Anesthesiawas induced and maintainedusing intravenous fentanyl andpropofol.. Sugammadex orplacebo was administered atreappearance of T2 of the TOF.Sugammadex decreased medianrecovery time in a dose-dependent manner from 21.0min in the placebo group to 1.1min in the group receiving 4.0mg/kg sugammadex. Doses ofsugammadex of 2.0 mg/kg orgreater reversed rocuroniuminduced neuromuscular blockwithin 3 min. A median of 59–77% of sugammadex wasexcreted unchanged in the urinewithin 16 hr, mostly in the first8hr. Sugammadex increased theproportion of the rocuroniumdose excreted unchanged in theurine (from a median of 19% inthe placebo group to 53% in the4.0-mg/kg group within 16 h).No evidence of recurarizationwas observed in any patient. Theyconcluded that at doses of 2.0mg/kg or greater, sugammadex


safely reversed 0.6 mg/kgr o c u r o n i u m – i n d u c e dneuromuscular block in a dose-dependent manner. Sugammadexenhanced renal excretion ofrocuronium and was excretedunchanged by the kidneys.Whilesugammadex appears to besuperior and an outstandingSRBA, the case report by Eleveldet al.17 reminds us that all drugshave a dose–response type ofpharmacology. They adminis-tered a very small dose ofsugammadex (0.5 mg/kg) for arocuronium neuromuscularblock (0.9 mg/kg). Althoughreversal was initially successful,the neuromuscular block partiallyreappeared18. Cammu et al12

investigated the single i.v. dosesof sugammadex 16, 20, or 32mg/ kg administered simulta-neously with 1.2 mg/kgrocuronium or 0.1 mg/kgvecuronium to 12 anaesthetized(with propofol/remifentanil ) andnon-anaesthetized healthy volun-teers. They found, rocuronium/vecuronium plasma concentr-ations declined faster than thoseof sugammadex. They concludedthat single-dose administrationof sugammadex 16, 20, or 32mg/kg in combination withrocuronium 1.2 mg/kg orvecuronium 0.1 mg/ kg was welltolerated with no clinicalevidence of residual neuromu-scular block, confirming thatthese combinations can safely beadministered simultaneously tonon-anaesthetized subjects.Shields et al4 studied 30anaesthetized patients whoreceived rocuronium 0.6 mg/kgas an initial dose followed byincrements to maintain a deepblock at a level of <10 post-

tetanic counts recorded every 6min. At recovery of T2, followingat least 2 h of neuromuscularblock, patients received theirrandomly assigned dose of 0.5,1.0, 2.0, 4.0 or 6.0 mg/ kg ofsugammadex. The results showeda dose-related decrease in theaverage time taken to attain aTOF ratio of 0.9 from 6:49 minwith the 0.5 mg/ kg dose to 1:22with the 4.0 mg/ kg dose.Theyconcluded that sugammadexeffectively reversed a deep andprolonged neuromuscular blockinduced by rocuronium andrecommended the effectivereversal dose to be 2–4 mg/kg.Sparr et al5 evaluatedsugammadex for reversal ofprofound rocuronium-inducedneuromuscular blockade in 98patients, randomized to receivesugammadex (1, 2, 4, 6, or 8 mg/kg) or placebo at 3, 5, or 15 minafter 0.6 mg/kg rocuronium.They found that the mean timeto recovery of the TOF ratio to0.9 after dosing at 3, 5, and 15min decreased from 52.1, 51.7,and 35.6 min, respectively, afteradministration of placebo to 1.8,1.5, and 1.4 min, respectively,after 8 mg/kg sugammadex. Themedian cumulative excretion ofrocuronium in the urine over 24h was 26% in the placebo groupand increased to 58–74% after 4–8 mg/kg sugammadex. The meanplasma clearances of sugamm-adex and rocuronium were 0.084and 0.26 l/min, respectively. Theyconcluded that sugammadexsafely reversed profoundneuromuscular blockade inducedby 0.6 mg/kg rocuronium in adose-dependent manner. Sugam-madex enhanced the renalexcretion of rocuronium, and its

clearance is approximately onethird that of rocuronium.Hunteret al13 mentioned thataminosteroid agents other thanrocuronium do not interact astightly with sugammadex, butanimal and human studiessuggest that if larger doses of thecyclodextrin (at least 4 mg/kg)are given when T2 hasreappeared, vecuronium can beadequately antagonized. At thisearly stage, it does seem thatsugammadex would need to begiven in even larger doses to beefficacious in reversing pancur-onium13. In contrast, andimportantly, sugammadex doesnot antagonize residual blockinduced by the benzylisoqui-nolinium relaxants such asatracurium and mivacuriumbecause of more bulkyb e n z y l i s o q u i n o l i n i u mstructures13.Dose-The dose-dependency canbe readily explained by the needto bind more rocuronium inplasma as blockade becomesdeeper. Thus, even after theintroduction of sugammadex,neuromuscular monitoring willbe useful, allowing the right doseto be chosen. The alternativewould be to give a largesugammadex dose for all cases, amore expensive course of actionthan monitoring9. The otherquestion that needs to beanswered relates to the possibilityof re-paralysis. If the dose ofsugam-madex given is justenough to capture most of therocuronium in plasma, then therewill be sufficient movement ofrocuronium away from theneuromus-cular junction downthe concentration gradient offree drug into plasma. This may


produce full return of neuromu-scular function. However, withtime, more rocuroniummolecules will be transferredfrom peripheral tissue intoplasma, and there will no longerbe enough free sugammadexmolecules available9. The freerocuronium will then have accessto the neuro-muscular junction,where blockade can ensue.Another issue which needs to betested is to administer sugamm-adex in divided doses: a firstinjection to achieve immediaterecovery, and a second to makesure there is no recurarization9.The tendency to adopt a “onedose fits all” approach for bothrocuronium and sugammadex islikely to become expensive andcontrary to the patient’s bestinterests.Advantages-Sugammadex couldsolve the problems of residualparalysis and failed intuba-tion9.If rocuronium is given atinduction of anesthesia and theairway cannot be secured, promptrestoration of normal neurom-uscular function could beachieved with the appropriatedose of sugammadex9. If largedoses of rocuronium can begiven, the surgeons may bepresented with better surgicalconditions with a more intenseneuromuscular block, andreversal can still be accomplished,because sugammadex appears tobe more reliable thanneostigmine18. When sugamm-adex becomes available, concernsabout reversal of blockade at theend of a case will be diminished.Therefore, anesthesiologists maybe tempted to give larger dosesof rocuronium than they do nowwith a benefit of better intubating

condi-tions, less delay betweeninduction and laryngoscopy, lessdesaturation, less airway trauma,better surgical conditions, fewerrespiratory problems atemergence, less residual paralysis.Moreover, there were minimaleffects on heart rate and arterialpressure following sugammadexadministration4. As the drug doesnot act via the nicotinic receptorsor by influencing the liberationor metabolism of acetylcho-linesterase, there are nomuscarinic side-effects associatedwith its use. Such effects areresponsible for the side-effectsobserved with the use ofanticholinesterase agents requiri-ng the concomitant use ofanticholinergic drugs. Theanticholinergic drugs, inparticular atropine, may produceundesirable tachycardia and/orarrhythmias. The absence ofcardiovascular and othermuscarinic effects during theprocess of reversal will be ofgreat advantage in patients withcardiovascular and respiratorydisease4.Other uses-Sugammadex hasbeen used for rescue agent in apatient of renal failure who hadresidual neuromuscular blockadeafter the use of neostigmine andhad acute respiratory distress19.Concerns-However, there aresome dan-gers. There could be agreater incidence of aware-ness,because total absence ofmovement may mask insufficientanesthesia and analgesia9. Also,the problem of managing theairway after sugammadex hasbeen given, for instance if arepeat procedure needs to beperformed, is not settled9.Perhaps there will be a role for

succinyl-choline after all.Without knowing the depth ofthe rocuronium-induced neur-omuscular blockade, it would bedifficult to know the dose ofsugammadex needed. Perhapsconventional nerve stimulatorswould be sufficient to determinethe presence or absence of thetwitch response, and theappropriate dose of sugam-madex could be administeredaccordingly. Further, the use ofrapid-sequence induction withrocuronium can be facilitated bythe presence of sugammadex.Nevertheless, studies are neededto address the role ofsugammadex as a”rescue”reversal drug in patients withunanticipated difficult airwayswho received rocuronium.Adverse effects-Few adverseeffects were reported that wereconsidered related to sugam-madex. The common werenausea, vomiting10 and QTcprolongation5,8,10,13, hypotension7,increasesd CPK levels18,abnormal values for microa-lbumin, N-acetyl-glucosami-nidase, and/or microglobulin inurine5. The other side effectsreported includes dry mouth,parosmia, a sensation of achanged temperature8.QTc prolongation was attributedto sevof lurane, propofol,morphine used in thesestudies10,12,13 but needs furtherevaluation. The other issueincludes signs characteristic ofinsufficient depth of anesthesia,such as an increase in BispectralIndex, grimacing, moving,sucking on the tube, andcoughing5,7. Theoretically, theanesthetic state might also be


changed due to capture offentanyl and/or propofol bysugammadex. This mechanism,however, is unlikely, because theaffinity of sugammadex fornarcotics and intravenousanesthetics is negligibly small.These effects may also be due tosudden reversal of neurom-uscular block after administrationof sugammadex combined witha surgical stimulus at a time ofinsufficient depth of anest-hesia5,7. The hypotension mayhave been related to adminis-tration of propofol and fentanyl,rather than to sugammadex7.Effect on other drugs-Sugammadex is ineffectiveagainst succinylcholine andb e n z y l i s o q u i n o l i n i u mneuromuscular blockers, such asmivacurium, atracurium, andcisatracurium, because it cannotform inclusion complexes withthese drugs. Therefore, ifneuromuscular blockade must bere-established after usingsugammadex, succinylcholine orone of the benzylisoquinoliniumneuromuscular blockers shouldbe considered. Furthermore,steroidal hormones are alsobound tightly to specific proteincarriers; for example, the sexhormones are bound with veryhigh affinity to globulin. Thepossible effects of thesugammadex-induced improvedsolubility of propofol, midazo-lam, and bupivacaine on thep h a r m a c o d y n a m i c s /pharmacokinetics of thesecompounds have not yet beenstudied.There are concerns thatcyclodextrins could encapsulateother steroidal drugs and indeedendogenous steroids such as

glucocorticoids, sex hormonesand aldosterone13.Status in renal dysfunction-The role of sugammadex in renalcompromised patient has notbeen studied yet. Recovery fromthe effect of an i.v. bolus doseof any drug occurs byredistribution, not elimination.This is thought to be the reasonwhy the effect of this selectiverelaxant binding agent in patientswith renal dysfunction isunaltered13. Much work is stillrequired, however, in thisvulnerable patient group.Pregnancy and drug-No studyfor safety profile in pregnant andlactating females has beenreported till yet.Conclusion-In view of thepotential of sugammadex toreverse even a profound NMB,and its favorable safety profile,this agent may fulfill the criteriaof an ideal reversal agent forrocuronium. Continued safetyand efficacy for this promisingagent will be confirmed in futureclinical studies.References

1. Boer HD, Driessen JJ, MarcusMAE et al. Reversal ofrocuronium induced (1.2mg/kg) profound neuromuscularblock by sugammadex.Anesthesiology 2007;107:239-44.

2. Boer HD, Driessen JJ,Egmond JV, Booij LHDJ.Nonsteriodal neuromuscularblocking agents to reestablishparalysis after reversal ofrocuronium induced neuro-muscular block withsugammadex. Can J anesth2008;55:124-25.

3. Gijsenbergh F, Ramael S,Houwing N, Iersel TV. Firsthuman exposure of Org25969, a novel agent toreverse the action ofrocuronium bromide. Anes-thesiology 2005;103: 695-703.

4. Shields M, Giovanneli M,Mirakhur RK et al. Org25969(sugammadex, a sele-ctive relaxant binding agentfor antagonism of prolongedrocuronium induced neuro-muscular block. BritishJournal of Anaesthesia 2006;96:36-43.

5. Sparr HJ, Vermeyen KM,Beaufort AM et al. Earlyreversal of profound rocuro-nium induced neuromuscularblockade by sugammadex ina randomized multicenterstudy. Anesthesiology 2007;106:935-43.

6. Sacan O, White PF,Tufanogullari B, Klein K.Sugammadex reversal ofrocuronium induced neuro-muscular blockade: a comp-arison with neostigmineglycopyrrolate and edropho-nium atropine. Anesth Analg2007;104:569 –74

7. Sorgenfrei IF, Norrild K,Larsen PB et al. Reversal ofrocuronium induced neuro-muscular block by theselective relaxane bindingagent Sugammadex. Anesth-esiology 2006;106:667-74.

8. Naguib M. Sugammadex:another miestone in neurom-uscular pharma-cology.Anesth Analg 2007;104:575–81.

9. Donati F. Sugammadex: anopportunity for more


thinking or more cook bookmedicine? Can J Anesth 2007;54:689–695.

10. Vanacker BF, Vermeyen KM,Struys MMRF et al.Reversalof Rocuronium-InducedNeuromuscular Block withthe Novel Drug SugammadexIs Equally Effective UnderMaintenance Anesthesia withPropofol or Sevoflurane.Anesth Analg 2007;104:563–8.

11. Scott B. Groudine SB, Soto R,Lien C et al. A Randomized,Dose-Finding, Phase II Studyof the Selective RelaxantBinding Drug, Sugammadex,Capable of Safely ReversingProfound Rocuronium-Induced NeuromuscularBlock. Anesth Analg 2007;104:555–62.

12. Cammu g, Kam PJD,Demeyer I et al. Safety andtolerability of single intrav-enous doses of sugammadexadministered simultaneouslywith rocuronium or vecuro-nium in healthy volunteers.British Journal of Anaes-thesia 2008;100:373-9.

13. Hunter JM, Flockton EA.The doughnut and the hole:a new pharmacologicalconcept for anaesthestists.British Journal of Anaest-hesia 2006;97:123-6.

14. Xue FS, Liao X, Tong SY, etal. Dose-response and time-course of the effect ofrocuronium bromide duringsevof lurane anaesthesia.Anaesthesia 1998;53:25-30.

15. Kim KS, Cheong MA, LeeHJ, Lee JM. Tactileassessment for the reversi-

bility of rocuronium-inducedneuromuscular blockadeduring propofol or sevof-lurane anesthesia. AnesthAnalg 2004;99: 1080-5.

16. Suy K, Morias K, Cammu etal. Effective reversal ofmoderate rocuronium orvecuronium induced neuro-muscular block withsugammadex, a selectiverelaxant binding agent.Anesthesiology 2007;106:283-8.

17. Eleveld DJ, Kuizenga K,Proost JH, Wierda JMKH.Temporary increase in twitchresponse during reversal ofrocuronium induced musclerelaxant with a small dose ofsugammadex. Anesth Analg2007;104:582-4.

18. Miller RD. Sugammadex: anopportunity to change thepractise of Anesthesiolgy?Anesth Analg 2007;104:477-78.

19. Lenz A, Hill G, White PF.Emergency use of sugammadex after failure if standardreversal drugs. Anesth Analg2007;104:585–6.

AneurysmAn aneurysm is the dilatation ofan artery full of spiritous blood.– Fernel (1591). Considerableattention has been giventhroughout ancient and modernhistory to the cause andtreatment of aneurysms. Oneof the earliest texts known, bythe Ebers Papyrus (2000 B.C.),contains a description oftraumatic peripheral arterialaneurysms. GALEN (131-200)defined an aneurysm as a

localized pulsatile swelling thatdisappeared on pressure andwrote, “if an aneurysm bewounded, the blood is spoutedout with so much violence thatit can scarcely be arrested”.Thefirst elective operation fortreatment of an aneurysm wasreported by the most famoussurgeon in Greek antiquity,Antyllus, in the second century.His recommendation foraneurysm repair was namedAntyllus method. “Anoperation for aneurysmwhereby is applied two ligaturesto the artery, cut between themand evacuating its contents”remained the basis of directarterial operations for nextcenturies. He was also first torecognize two forms ofaneurysm – the developmentalcaused by dilatation and thetraumatic following woundingof an artery.In the seventhcentury, details of operativerepair of an arterial aneurysmwere rewritten by Aetius ofAmida in his book DeVosorum Dilatatione (“On theDilation of the Vessels”).Aetius also recognized thedifference between truedegenerative aneurysms andtraumatic false aneurysms.Aetius also believed Galensteachings that no wound healsproperly without the formationof pus, brought about by theapplication of dried herbs(incense).Ambrose Pare (1510-1590), who mainly contributedto the principles of properwound care, also applied hisobservations to aneurysmoperations.


14RecentRecentRecentRecentRecentAdvancesAdvancesAdvancesAdvancesAdvances

S ome facts about humanintestine and intestinalmicroflora

�� Intestines [mainly small gut]is the body’s most importantimmune function relatedorgan, where 60% of body’simmune cells reside. Itcontrols immune response todietary antigens [foodallergies] and microorganismsentering by oral route[rotaand poliovirus, salmonella,listeria, toxoplasma etc.].

�� Total number of cells inhuman body is 1014 of whichonly 10% is mammalian andrest 90% is prokaryotic [oftencalled “MICROFLORAORGAN”]. This implies aclose relation between proand eukaryotes wherebacteria exert a fundamentalcontrol. Intercommunicationrelies on an integratedsignalling system wherecommensal and infectiousbacteria produce a wholerange of molecules [both proand anti-inflammatory] andhomeostasis is maintained bya balance between them. Thisbalance is disrupted byantibiotics, chemotherapy,radiotherapy, infections.

�� Number and type ofbacteria/gm of contents indifferent gut segment is as :oesophagus and stomach - <103, mostly helicobacter and

Update on Prebiotics and ProbioticsGautam Ray

Gastroenterology unit, Department of Medicine, B.R.Singh Hospital, Kolkata

lactobacilli; proximal smallgut – 104 – 106, mostlylactobacilli and Enterococcusfecalis; distal small gut – 107,mostly lactobacilli, coliformsand bacteroides; colon – 1012,mostly coliforms, lactobacilli,enterococci, anaerobes[clostridium, bacteroides,bifidobacterium] and meth-anogenic ones. Humansexcrete about 8 gm bacteriain stool/day equal to ¼ drystool weight.

�� At the level of species andstrains, every individualharbour its own distinctpattern of bacterial comp-osition [with conseq-uenthuge interindividual diversityin this] determined bygenetics, environment [incl-uding in utero environ-mentwith its vertical transmission],diet and disease. In healthyadults, fecal composition isstable over time. The patternis disrupted in the immun-ocompromised, debilitated,elderly people and in ICUsetting.

�� Upper GI tract bacteria haveimportant influences onimmune function [ actingthrough Peyer’s patches insmall gut]. Normal colonicflora maintain integrity ofenterocyte, modulate metab-olic and immunologicprocesses and prevent

colonisation by invasivemicroorganisms.

�� Human colon is unable tonourish itself from blood,nutrition is derived fromluminal contents. Theseinclude short chain fatty acid,polyamines, growth factors,amino acids like glutamine,arginine and cysteine [immu-nonutrients], vitamins andantioxidants which areproduced by commensalprobiotic protective florafrom luminal substrates[called prebiotics]. It isemphasized that 10% calorieand 20% food should becolonic food.

�� Probiotic flora is deficient inindustrialised nations butadequate in vegans, Asia andAfrica.

Definitions

�� Probiotic – Living microo-rganism which upon ingest-ion in adequate numberconfer health benefits beyondgeneral nutrition [preventiveor therapeutic]. The term wascoined in 1965 by Lilley andStillwell.

�� Prebiotic – Non digestiblesubstances that providebeneficial physiological effecton host by selectivelystimulating growth or activityof a limited number [selectgroup] of indigenous favo-urable bacteria [commensals].


These include non starcholigo or polysaccharides[including fibres, oligofr-uctose , inulin, galacto-oligosaccharides, lactulose,breast milk oligosaccharides],complex proteins, shreddedmucosal cells, mucin andother GI secretions, somebacterias and yeasts. Oligof-ructose is naturally found inwheat,onion, banana, honey,garlic, leeks, chicory root.Most prebiotics are used asfood ingredients e.g. inbiscuits, cereals,chocolate,dairy products. An importantcharacteristic of prebiotic isthat no small intestinalenzyme can digest them.

�� Synbiotic – Combination ofpre and probiotic [e.g. babyfood]

Function and mechanism ofaction of probiotics�� Produce essential colonic

food from prebiotics.�� Prevent overgrowth of

pathogenic microorganismsby - competing for food andadhesion with them and theirtoxins; producing bacterio-cins; pH and redox changesby H2O2 production;decreasing their procarcin-ogenic enzyme product-ion.This stabilise thecommensal microflora thusincreasing resistance.

�� Regulation of intestinalfunction by-increasing mucinsecretion, motility and barrierfunction by increasing cellsurvival and their prolifer-ation and differentiation thusdecreasing exposure to food

antigens; bettering nutrientabsorption; scavenging freeradicals; improving splan-chnic blood flow ; loweringammonia production.

�� Improves bioavailability ofnutrients e.g. milk protein,Ca,Mg,Fe along withproduction of vitamins, folicacid and digestive enzymes.

�� Modulates intestinal mucosalimmunity by- strengtheninginnate immunity andmodulation of pathogeninduced inflammation via tolllike receptors which regulatescell signalling pathways likeAKt, MAPK and NFKBeta.This lowers exposure ofimmune cells to toxins andincrease protective immunity;activate local macrophages toincrease IgA secretion andantigen presentation to Blymphocytes and Peyer’spatches, modulate cytokineprofile and inducehyporesponsiveness to foodantigens; eliminating toxinsand unwanted substances e.g.steroid, cholesterol from gutflora.

Effect of antibiotic use on GIfunction-From above discus-sion, it is clear that indiscriminateantibiotic use can alter the GItract microbial ecosystem andnormal bacteria – host intera-ction with disasterous conseq-uences.�� Decreased gut resistance lead

to epithelial break, lowerabsorption and metabolismof nutrients and drugs andincrease bacterial invasion.Examples include malabsor-

ption produced by neomycin,decreased enterohepaticcirculation of estrogens byampicillin and vitamin Kmalabsorption produced byBeta lactam antibiotics.

�� Altered susceptibility toinfection e.g. salmonellacarrier from acute infectionor sepsis in carriers,

�� Colonisation of body byresistant organisms [inascending order of resistancecolon, perineum, urethra,skin, upper respiratory tract]which contaminate theimmediate environmentleading to spread of infectione.g to healthy adults livingwith patient like hospital staffor other patient via hand ofpersonnel.

�� Glossitis, gastritis, pruritusand antibiotic induceddiarrhoea and colitis.

Formulation-Probiotics areused as food or diet supplementand also as pharmaceuticals andnutraceuticals as tablets, capsuleand sachets [freeze dried]. Mostcommon probiotics [functionalfood] are dairy and dairyproducts where lactobacilli byfermentation�� Maintain viability, stability

and preserve key nutrients,vitamins and antioxidants instorage and even duringfreeze drying [e.g. increasedshelf life in yogurt]

�� Produce mild acidity instorage and impart flavourand aroma,

�� Eradicate pathogens. Alsoused in vegetables, animalprotein, legume etc.


Types [genus – species –strain]�� Lactic Acid bacteria [include

lactobacillus and lactococcusspp., streptococcus thermop-hilus] – mostly lactobacilli areused e.g. L.plantarum 299V,acidophilus [LA-5, NCFM],casei [DN114 001,CRL431,F19, Shirota], rhamnosus[LGG, LB21], johnsonii La1,reuteri ATTC55730, saliva-rius UCC118, lactis L1A,bulgaricus.

�� Bifidobacterium – longumBB536, lactis [DR10, Bb12],animalis DN 173010, breveYakult, infantis 35624.

�� E.coli Nissle 1917.�� Saccharomyces cerevesiae

[boulardii] lyo.�� Enterococcus LAB SF 68�� Mixture e.g. Enterogermina

[4 strains of Bacillus clausiilike O/C,NR,SIN,T], VSL#3[1 strain of Strept-ococcusthermophilus, 4 Lactobacillusspp and 3 Bifidobacteriumspp strains]

Clinical application�� Diarrhoea-Treatment of

acute diarrhoea in childrenwhere it reduces severity andduration though mostly inviral ones e.g. L.reuteri,rhamnosus, casei andS.boulardii. Evidence forpreventive effect is onlysuggestive; Treatment ofantibiotic associated diarr-hoea in children and adults[L.rhamnosus GG, S.boula-rdii] and prevention andtreatment of C.difficile colitisin adults [L.casei, S.boular-dii];Treatment of radiation

induced diarrhoea [VSL#3](evidence inadequate).

�� Allergy – atopic dermatitisand eczema, food allergy.(evidence inadequate).

�� Eradication of H.pylori –both by adjuvant effect andincreasing compliance bylowering side effects [entero-germina,lactobacilli spp]

�� Hepatic encephalopathy –Lactulose.

�� Irritable bowel syndrome –alleviates symptoms [L.rham-nosus, B.infantis, VSL#3].

�� Inflammatory bowel disease– maintains remission ofulcerative colitis [E.coli Nissle1917] and prevent initialattack and maintain remissionin pouchitis [VSL#3].

�� Lactose malabsorption –some lactobacillus spp reducesymptoms.

�� Boosting immune response -decrease post operativeinfection in ICU, preventinfluenza in winter (evidenceinadequate).

�� Prevention of -cardiovasculardisease [by lowering choles-terol], - colon cancer[SYNCAN study], NAFLD(evidence inadequate).

�� Necrotising enterocolitis[Bifidobacterium spp] – riskreduced in preterm infants.

Regulation

�� Documentation of healtheffect should be on thespecific strain being sold [ solisting has to be as genus-species-strain on the sample].

�� Results of one strain cannotbe held as evidence for

efficacy of another untestedstrain.

�� Specific dose [i.e. number ofviable cells that will remain tillend of shelf life] at whichbenefit occur has to bementioned, effect at lowerdose cannot be held toproduce beneficial effect e.g.in IBS, dose needed foralleviating symptoms was 100million cfu/day forBifidobacterium but 300 –450 billion cfu tid forVSL#3.

�� The filler or vehicle has to bementioned, another cannotbe used lest it affect shelf lifeand storage conditions.

�� Viability[i.e. shelf life] has tobe mentioned.

�� Must be shown to be effectivein controlled human studies.

�� Safety to be established evenby post marketing survei-llance.

References1. World Gastroenterology

Organisation Practice Guid-elines. Probiotics and Prebio-tics; May 2008

2. American Journal ofGastroenterology 2000 Jan :Vol 95 (Supplement 1).


15OriginalOriginalOriginalOriginalOriginalArArArArArticleticleticleticleticle

P eople who live togethercome to resemble eachother to a greater or lesser

Cohabitational Effect of Blood Pressure Among Non-GeneticallyRelated Pairs In India

Sanjeev M. Chaudhary, Sanjay S. Kubde, Sanjay B. AgrawalDepartment of Preventive and Social Medicine, Indira Gandhi Government Medical College, Nagpur.

degree. This effect is called“cohabitational effect”; theresemblances come through theprocesses of living together.Cohabitation, or the sharing ofthe same or similar householdenvironment, usually implies thesharing of many aspects of lifestyle1. Thus, individuals whocohabit should show concord-ance in cardiovascular risk factorsthat have association with lifestyle, and such concordanceshould increase with duration ofcohabitation. Married couples arepairs who are genetically non-related, but share theenvironment for a considerableperiod of time.Spouse concord-ance is a state where husband andwife are found to have closelysimilar attributes2. Not only dospouses’ analysis assist in teasingout the relative contribution ofgenetic and environmentalfactors, but such studies mightalso provide a rationale both forcase finding and forenvironmental modification.Ascompared to American samples,relatively little is known aboutmarital aggregation of bloodpressure in non-westerncountries in which alternative lifestyles may affect the expressionof traits differently. Another

feature that distinguishes westernsocieties from many Indiangroups is the homogeneityamong family members for manyenvironmental covariates relatingto blood pressure.This study is anattempt to find out proportion ofconcordance of blood pressureamong married couples and tostudy concordance of factors,which affect blood pressureconcordance.Material & methods-this cross-sectional, community based studywas conducted from may 2004 toapril 2005, in jaripatka, which isan urban area under nagpurmunicipal corporation. This areawas selected for feasibility. Theethics committee of indiragandhi government medicalcollege approved the study. Studysubjects were married couples inwhom both husband and wifewere of the age 30 years or more.Couples in whom the wife waspregnant, and those in whomeither or both spouses hadsecondary hypertension wereexcluded.initially a pilot study wasconducted to test the proformaand to have a rough estimate ofthe proportion of concordanceof blood pressure. Theproportion of concordance wasfound to be 64% in the pilotstudy. Expecting 20% non-participation, sample size cameout to be 260 couples. A house-

to-house survey was carried out.It was decided to start with thefirst house and cover all thehouses till the required samplewas reached. Informed writtenconsent was obtained from thehead of the household and thestudy subjects after explainingthem the objectives of thestudy.detailed history regardings o c i o - d e m o g r a p h i ccharacteristics was recorded inpredesigned, pretested proforma.Dietary history was taken by 24hour recall method. Visible fatintake per day was then estimatedas per icmr guidelines3. Level ofsalt consumption was assessed bysimple patient estimation of low(seldom or never) moderate (ifneeded after tasting) or high(routinely before tasting) saltaddition during meals4. Currenthabits regarding physical activity(occupational and leisure-time)were assessed and graded as lightmoderate and heavy5. Stress wasassessed by a self-administeredquestionnaire6, which was to befilled separately by both spouses.Anthropometric indices includ-ing height, weight, waistcircumference and hip circumf-erence were measured accordingto recommended techniques7.Body mass index (bmi) and waist-hip ratio (whr) were calculated.A bmi value of 25 to 30 wasdefined as overweight, and a


value 30 and over, as obese8. Thecriteria for truncal obesity waswhr >0.92 for husbands and whr>0.85 for wives8.fasting bloodsugar estimation was done earlyin the morning after overnightfast, using sure step-plus bloodglucose meter (life scan). Subjectwas considered diabetic if he/shewas a known case of diabetesmellitus or if his/her fastingblood sugar was 120 mg/dl ormore9. Along with blood sugarestimation, blood pressure wasalso measured in the morning;this ensured that there was novigorous physical activity, orconsumption of hot beverageslike tea and coffee, thirty minutesprior to blood pressuremeasurement. Blood pressurewas measured using mercurysphygmomanometer, in the rightarm, with subject in sittingposition. Two readings weretaken over a period of threeminutes; both were recorded andmean value considered foranalysis. The criteria forconsidering a subject as hyperte-nsive was : systolic blood pressure³ 140 mmhg or diastolic bloodpressure ³ 90 mmhg or the useof anti-hypertensive medica-tions10.Criteria for concordance ofvarious factors

�� Blood pressure- Both spouseshypertensive or both normo-tensive

�� Education - Both spouseshaving same level of educa-tion i.e. <12, 12-15, >15

�� Type of die- Both spousesconsuming same diet, eithervegetarian or mixed diet

�� Visible for consumption-Both spouses having similarfat intake i.e. <20 or ³20 gm/day.

�� Salt consumption- Bothspouses having similar levelof salt consumption, either‘low’ or ‘moderate to high’.

�� Physical activity- Bothspouses having same level ofphysical activity i.e. ‘light’ or‘moderate to heavy’ physicalactivity.

�� Body Mass Index- Bothspouses at same BMI leveli.e.<25, 25-30, ³30.

�� Truncal obesity- Presence orabsence of truncal obesity inboth spouses.

�� Stress- Both spouses havingsame number of life timeevents, i.e. <10 or ³ 10.

�� Diabetes Mellitus- Bothspouses diabetic, or bothnon-diabetic.

Percentage, mean and standarddeviation were calculated.Association was tested byapplying Chi-square test.Peasrsons correlation coefficientwas calculated.Results and discussion-a totalof 287 families were visited in thesurvey of which 25 were notwilling to participate, 14 were noteligible and 10 were not available.The required sample size of 260couples were obtained in 238families. All the couples were ofhindu religion. 75% husbandswere businessman, mostly shopowners; 80% wives werehousewife.64.6% couples weremarried for 10-30 years duration.The minimum and maximum

duration of marriage was foundto be 6 months and 57 yearsrespectively. As expected, meanage of husbands was more ascompared to that of wives (tablei). Similar distribution have beenreported by speers ma et al(1989)11 and knuiman mw et al(1996)1.systolic and diastolicblood pressures were lower forwives than for husbands in thelower age groups. This differenceappears to be the general sexdifference rather than onebetween husbands and wives.Systolic blood pressure forhusbands and wives increasedwith age. Diastolic blood pressureincreased with age up to 40 yearsof marriage, after which itlowered both in husbands andwives (table ii). These findings aresimilar to that of speers ma et al(1986)12.149 (57.3%) coupleswere concordant for bloodpressure i.e. Both spouses havingsame level of blood pressure(both normotensive plus bothhypertensive) (table iii). Gearingfr et al (1962)13 found equalnumber of couples who wereconcordant and discordant forblood pressure. High concord-ance was seen upto 20 years ofmarriage and after 30 years ofmarriage. The associationbetween duration of marriageand concordance of bloodpressure was found to besignificant (table iv).concordanceof various factors ranged from43.8% (for bmi) to as high as87.3% (for visible fatconsumption). Concordance fordietary factors was very highamong couples. Concordance ofall these factors (except diabetes


mellitus) did not explainconcordance of blood pressureamong couples (table v). When172 couples in whom bothhusband and wife were of the age30 years or more, and those whowere not under anti-hypertensivemedication were analysed forcorrelation of blood pressure,correlation coefficient for systolicblood pressure was found to be0.03 (non significant) and that fordiastolic blood pressure was 0.07(non significant). Correlationcoefficient in different marriageduration groups was also nonsignificant. (table vi)higherconcordance in the initial periodafter marriage could be due tohigh degree of assortative matingamong couples. Higherconcordance during later yearsafter marriage suggests role ofsome other unknown sharedmarital environmental factorswhich could affect bloodpressure concordance amongcouples. Concordance of bloodpressure could not be explainedby concordance of variousfactors like education, dietaryfactors, physical activity, bodymass index, truncal obesity andlifetime stress, among couples.The observed blood pressureconcordance was influenced bythe concordance of diabetesmellitus among couples. Thuslifestyle interventions thatspecifically target the maritalpartners as a unit may be moreefficacious than individual patienteducation strategies, forprevention and control of co-morbid conditions-hypertensionand diabetes. Further research onconcordance of blood pressure

among couples should be doneto explain new variables, thosethat might illuminate theunidentified shared environm-ental factors that account for theconcordance.References

1. Knuiman MW, Divitini ML,Bartholomew HC, WelbornTA. Spouse correlations incardiovascular risk factorsand the effect of marriageduration. Am J Epidemiol1996 ; 143 (1) : 48 – 53.

2. Haynes SG, Eaker ED,Feinleib M. Spouse behaviourand coronary heart disease inmen : Prospective resultsfrom the Framinghan HeartStudy. Am J Epidemiol 1983; 118 (1) : 1 –22.

3. Gopalan C, Rama Shastri BV,Balasubramaniam SC.Nutritive value of Indianfoods. NIN, ICMR, Hyder-abad, 2000.

4. Little P, Girling G, Hasler A,Trafford A, Craven A. Acontrolled trail of a lowsodium, low fat, high fibrediet in treated hypertensivepatients. The efficacy ofmultiple dietary interven-tions. Post Graduate Med J1990 ; 61 : 616 –621.

5. Retrospective activityquestionnaire. Chapter 15,Habitual physical activity andhealth. WHO 1976 : 150 –153.

6. Singh G, Kaur D, Kaur H.Presumptive stressful lifeevent scale (PSLES) – a newstressful life events scale for

use in India. India J Phychiat1984 ; 26 (2) : 107 –114.

7. Dowse GK, Zimmet P. Amodel protocol for a diabetesand other non-commun-icable diseases field survey.Wld Hlth Statist Quart 1992; 45 : 360 – 372.

8. WHO Technical ReportSeries. Obesity : preventingand managing the globalepidemic, 2002 : No.894.

9. WHO Technical ReportSeries. Prevention of Diab-etes Mellitus, 1994 : 844.

10. WHO Technical ReportSeries. Hypertension control,1996 : 862.

11. Speers MA, Kasl SV, OstfeldAM. Marital correlates ofblood pressure. Am JEpidemiol 1989 ; 129 : 956 –72.

12. Speers MA, Kasl SV,Freeman DH, Ostfeld AM.Blood pressure concordancebetween spouses. Am JEpidemiol 1986 ; 123 : 818 –29.

13. Gearing FR, Clark EG,George P, Schmeitzer MD.Hypertension among relati-ves of hypertensives :Progress report of a familystudy. AJPH 1962 ; 52 (12) :2058 – 65.


Table-I, Mean age of husbands and wives according to duration of marriage

Duration of Marriage

(Years)

< 1010 - 2020 - 3030 - 40

³ 40

Total

No. of Couples(%)

21 (8.1)77 (29.6)91 (35.0)49 (18.8)22 (8.5)

260 (100.0)

Mean age (SD)

Husbands

36.0 (3.7)41.6 (6.1)49.8 (4.8)57.8 (4.4)67.8 (5.2)

49.3 (10.0)

Wives

32.1 (2.7)36.9 (4.3)43.7 (4.3)51.3 (3.8)61.6 (4.5)

43.7 (8.9)

Duration ofmarriage(years)

< 10

10 – 20

20 – 30

30 – 40

³ 40

Table-II, Mean Blood Pressure (Systolic and Diastolic) among husbands and wives accordingto duration of marriage

Total(n=260)

21

77

91

49

22

Systolic Blood Pressure (Mean+ SD)

Diastolic Blood Pressure(Mean + SD)

Husband Wife Husband Wife

127 + 14.7 122.6+10.2 85.4+12.2 80.5 + 8.0

129 + 17.7 124.2+13.6 87.1+10.0 82.0+12.5

133 + 20.3 130.1+16.1 87.8+11.5 85.1 + 9.3

139 + 20.2 142.6 + 17.5 88.0+10.9 90.2 + 9.9

138 + 22.7 153.3 + 20.7 82.2+12.7 87.3+10.1

Table-III,Distribution of couples according to hypertension

Both normotensive 84 (32.3)Both hypertensive 65 (25.0)Only husband hypertensive 70 (27.0)Only wife hypertensive 41 (15.7)

Total 260 (100.0)

No. (%)Hypertension


Table-IV, Duration of marriage and concordance of blood pressure

Concordance of Blood PressureDuration of Marriage (years)

<1010 – 2020 – 3030 – 40

³ 40

Total

Present

16 (76.2)48 (62.3)41 (45.0)28 (57.1)16 (72.7)

149 (57.3)

Absent

5 (23.8)29 (37.7)50 (55.0)21 (42.9)6 (27.3)

111 (42.7)

Total

21 (8.1)77(29.6)91(35.0)49(18.8)22(8.5)

260(100)

*÷2 = 10.07, df = 3, p < 0.05 (Duration of marriage <10, 10-20, 20-30 and e”30 were compared).

Table-V, Concordance of factors associated with Blood Pressure concordance among couples

Factors Concordance(n=260)

Concordance ofBlood Pressure

c2, df, P value

Education 151 (58.0) 87 (57.6) 0.01, 1, >0.05Type of diet 201 (77.3) 112 (55.7) 0.9, 1, >0.05Visible Fat consumption 227 (87.3) 129 (60.4) 0.17, 1, >0.05Salt consumption 211 (81.1) 122 (57.8) 0.12, 1, >0.05Physical Activity 199(76.5) 116(58.3) 0.34, 1, >0.05Body-mass index 114 (43.8) 63 (55.3) 0.35, 1, >0.05Truncal Obesity 140 (53.9) 81 (57.9) 0.04, 1, >0.05Lifetime Stress Events 214 (82.3) 127 (59.3) 2.05, 1, >0.05Diabetes Mellitus 141 (54.7) 96 (68.1) 14.6, 1, <0.01

*Figures in parentheses indicate percentage.

Table-VI,Correlation coefficient of blood pressure among couples

Duration of marriage(years)

< 1010 – 2020 – 30

³ 30

Overall

No. of Couples

20656423

172

Coefficient correlation (r)

Systolic BP

-0.010.04-0.04-0.04

0.03

Diastolic BP

0.070.17-0.04-0.02

0.07P>0.05 for all values of r


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Med. 2002; 347: 284-72. Books and Monograph- Murray RR, Rusenthal KS. Medical Microbiology, 4th ed. St. Lovis: Mosby; 2002.3. Chapter in a book-Meltzen PS, Trent JM. Chromosome alternations in human solid tumors. In :Vogelstein

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