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KUWAIT MEDICAL JOURNAL(like part of the title, year of publication etc.) fromthe references to the citations in the text, unlessvery importent. In the References section, list themin the same sequence as they appeared in the text.Include the names and initials of all authors unlessthere are more than six, in which case, only the firstthree authors shall be mentioned, followed by et al.Do not use automatic numbering, endnotes orfootnotes for references. References to manuscriptseither in preparation or submitted for publication,personal communications, unpublished data, etc. areunacceptable.The author’s name should be followed by thetitle of the article, the title of the journal abbreviatedin the style of the Index Medicus, the year ofpublication, the volume number and the first andlast page numbers. References to books should givethe title of the book, followed by the place ofpublication, the publisher, the year and the relevantpages. Journal titles should be abbreviated accord i n gto the style in Index Medicus. References should belimited to those relating directly to the contents ofthe paper and as shown in the examples below.EXAMPLESArticleB u r rows B, Lebowitz MD. The ß agonistsdilemma (editorial). N Engl J Med 1992; 326:560-561.BookRoberts NK. The cardiac conducting system andHis bundle electrogram. New York, A p p l e t o n -Century-Crofts, 1981; 49-56.Book chapterPhilips SJ, Whisnam JP. Hypertension ands t roke, In: Laragh JH, Bremner BM, editors.Hypertension: pathophysiology, diagnosis, andmanagement. 2nd ed. New York: Raven Press; 1995.p 465-478.WeblinksU.S. positions on selected issues at the thirdnegotiating session of the Framework Conventionon Tobacco Control. Washington, D.C.: Committeeon Government Reform, 2002. (Accessed June 4,2003, at http://www. h o u s e . g o v / re f o r m / m i n /inves.tobacco/index_accord.htm.)AUTHORSHIP AND CONSENT FORMAll authors must give their signed consent forpublication in a letter of submission, which shouldaccompany the manuscript. This letter shouldcontain the statement that “This manuscript (writethe title) is an unpublished work which is not underconsideration elsewhere and the results containedin this paper have not been published previously inwhole or part, except in abstract form. Inconsideration of the KMJ accepting my/oursubmission for publication, the author(s) undersignedhereby assign all copyright ownership to the KMJ.It is expressly certified that I/we, have done/activelyparticipated in this study.” The participation of theauthors must include: conception, design, analysis,interpretation, or drafting the article for criticallyimportant intellectual content. A change inauthorship after initial submission of a manuscriptmust be duly supported with a documentedrequest from the main author, and a removal ofauthorship, duly endorsed by the author deleted.More than six authors are not appreciated for anarticle and if listed, the authors may be asked tojustify the contribution of each individual author.For case reports, not more than three authors areacceptable. Contributions of authors above thislimit and/or any other contributor could be includedin the Acknowledgment section of the article.ACKNOWLEDGMENTA ffiliations with or association of anyorganization with a direct financial interest in thestudy should be clearly disclosed in theAcknowledgment section of the manuscript.Otherwise, it will be considered as having no suchinterests.COPY RIGHTThe publisher reserves copyright on theJournal’s contents. No part may be reproduced,translated or transmitted in any form by anymeans, electronic or mechanical, includingscanning, photocopying, recording or any otherinformation storage and retrieval system withoutprior permission from the publisher. The publishershall not be held responsible for any inaccuracy ofthe information contained therein.SUBMISSION OF MANUSCRIPTSManuscripts should be submitted to:The Editor,Kuwait Medical JournalP.O. Box: 120213013-Safat, KuwaitTelephone (965) 5316023, 5333278; 5317972Fax (965) 5312630; 5333276e-mail : kmj@kma.org.kwWebsite: www.kma.org.kw/KMJiii

June 2007KUWAIT MEDICAL JOURNALEditorialThe Place of Angioplasty and Stenting in the Treatment ofCarotid Artery StenosisProfessor Sir Peter RF BellDepartment of Surgery, University Hospitals of Leicester NHS Trust, Leicester LE2 2DP, UKKuwait Medical Journal 2007, 39 (2): 95-97Varying degrees of stenosis of the internalcarotid artery is a common problem in patients whohave peripheral vascular disease. The corre c ttreatment of this condition has been a matter ofsome debate for years and surgical endarterectomyor grafting, popularized in the 1950s by DeBakeyand Eastcott, remained a controversial operationuntil two large randomized trials proved inpatients who had severe (>70%) symptomaticcarotid stenosis that surgery was very beneficial [1,2] .The results of these large randomized trials weretaken as a signal to do many more caro t i de n d a r t e rectomies, both in patients who weresymptomatic and asymptomatic, even though thetrials related to symptomatic and not asymptomaticpatients.With this increase in activity it was perhapsinevitable that someone would have the idea that ifthe artery was narrowed then it should be treatedby angioplasty and stenting as were many otherarteries in other parts of the body. Since Dotter [3]first described arterial dilatation as a possible wayof treating such lesions interventional radiologistsand more recently cardiologists have consistentlytried to expand the areas in which dilatation can beapplied. The invention of stents took this processeven further because a tool is now available whichwill keep the artery open and prevent collapse to itsprevious state.In the early days of angioplasty the effect ofdilatation and stenting in terms of release of emboliwere not fully appreciated and therefore a numberof interventional radiologists started to insert stentsinto the carotid arteries and published whatappeared to be excellent results [4] . At the outset oneof them realised that emboli may go into the brainand tried to construct a primitive protection devicewhich would avoid this happening, againpublishing excellent re s u l t s [ 5 ] . Because of thenovelty and potential profit from inserting stentscompanies became involved in pushing the processforward and a variety of stents and protectiondevices were invented. A large number of papersemerged from many centres claiming that stentingwas as good as or better than endarterectomy andavoided the serious side effects of a scar andtemporary cranial nerve palsy. None of thesepublications were level 1 evidence, usually theywere single center experiences and as such of littlescientific value. Comparing endarterectomy andstenting was always going to be difficult andremained so, mainly because authors who favouredstenting wished if possible to avoid dealing withthose cases which may cause complications andentering exactly the same patients into the twoarms of such trials is always difficult.The first randomized trial to address thisp roblem was done in Leicester. This trial wasstopped by the monitoring committee because ofthe excessive complications of angioplasty. Thistrial was done on the basis of intention to treatwithout exclusions and remains the only trial ofthat nature where the cases compared wereidentical [6] . Because this trial contained such smallnumbers it was not sufficient to influence patternsof treatment. Other randomized trials then camealong comparing the two treatments, the first beingthe CAVATAS trial [7] . This trial was flawed becausethe protocol changed half way through and thelevel of complications at 10% for endarterectomyand stenting was clearly unacceptable. The nexttrial, the SAPPHIRE trial [ 8 ] , was anotherr andomized trial which suggested th a tendarterectomy and stenting had similar resultsbut stenting had less complications of a myocardialnature. This trial is deeply flawed and has nowlargely been discounted. It was however the trialused by the FDAin America to allow stenting to becarried out in high risk patients. Because of theinvolvement of industry and many other problemsAddress correspondence to:Professor Sir Peter RF Bell, Emeritus Professor of Surgery, University Hospitals of Leicester NHS Trust, 22 Powys Avenue, Oadby, Leicester LE22DP, UK. E-mail: peterrfbell@ntlworld.com

June 2007KUWAIT MEDICAL JOURNAL 97implications for selecting patients for carotid angioplastyand stenting. J Vasc Surg 2004; 39: 958-965.9. Bell P. Limitations to the value of the SAPPHIRE trial. ActaChir Belg 2006; 106:141-143.10. Mas JL, Chatellier G, Bevssen B, et al. Endarterectomyversus stenting in patients with symptomatic severe carotidstenosis. N Engl J Med 2006; 35:1660-1671.11. SPACE collaborative group. Thirty day results from SPACEtrial of stent protected angioplasty versus caro t i dendarterectomy in symptomatic patients randomized noninferiority trial. Lancet 2006; 368:1239-1247.12. Rothwell P, Eliasziw M, Gutnickov S, et al. Analysis ofpooled data from the randomized controlled trials ofendarterectomy for symptomatic carotid stenosis. Lancet2003; 361:107-116.13. CARE investigators. Reduction of stroke incidence aftermyocardial infarction with Pravastat. In: Cholesterol inrecurrent events (CARE Study). Regulation 1999; 99:216-223.14. Halliday A, Lansfeld A, Marro D, et al. MRC-AsymptomaticC a rotid Surgery Trial (ACST) Collaborative Gro u p .Prevention of disabling and fatal strokes by successfulc a rotid endarterectomy in patients without re c e n tn e u rological symptoms: randomized controlled trial.Lancet 2004; 363:1491-1502.15. Biasi GM, Froio A, Dietrich EB, et al. Carotid plaque inecholuscency increases the risk of stroke. In: Caro t i dstenting imaging in carotid angioplasty and risk of stroke(ICAROS) Study. Circulation 2004, 110:756-762.16. Vermer S, Prins N, Den Helier T, Hofman A, Koudstaal P,Breteler M. Silent brain infarcts and the risk of dementiaand cognitive decline. N Engl J Med 2003; 348:1215-1222.

KUWAIT MEDICAL JOURNAL June 2007Review ArticleAdvances in Therapy of Invasive MycosesZia U Khan, Eiman M MokaddasDepartment of Microbiology, Faculty of Medicine, Kuwait University, KuwaitKuwait Medical Journal 2007, 39 (2):98-106ABSTRACTIntroduction: Concurrent with the advances in medicaland transplant technologies, and emergence ofHIV/AIDS as a major public health problem, the numberand type of immunosuppressed individuals hasincreased. This has resulted in an increasing incidence ofopportunistic mycoses. To meet this challenge, the fieldof antifungal therapeutics has made unpre c e d e n t e dprogress in recent years. In this article, we have reviewedsome of the major advances that have taken place in thisarea.Methods: MEDLINE database was searched using thefollowing key words: amphotericin B, lipid formulationsof amphotericin B, triazoles, voriconazole, posaconazole,echinocandins, caspofungin, micafungin, anidulafungin,clinical trials and combination therapy since the year2000.Results: Based on the information retrieved through thesearch, the following inferences could be drawn: (i)voriconazole is as effective as amphotericin B, followedby fluconazole for the treatment of candidemia in nonne u t ropenic patients with fewer side effects, (ii)caspofungin is better tolerated and is as effective asamphotericin B in treating invasive candidiasis and thusmay be preferred in patients with renal impairment, (iii)caspofungin or amphotericin B is still a preferred therapyfor candidemia in neutropenic and critically ill patients,and (iv) voriconazole has replaced amphotericin B insome centers as the drug of choice for treating invasiveaspergillosis including patients with CNS involvement.Conclusions: With the introduction of new antifungalagents, the options for treating invasive mycoses haveconsiderably expanded with improved therapeuticoutcomes. Attention is now being focused to evaluateefficacy of these agents in combination therapy.KEYWORDS: anidulafungin, caspofungin, lipid formulations of amphotericin B, micafungin, posaconazole, voriconazoleINTRODUCTIONInvasive mycoses pose a major diagnostic andtherapeutic challenge. They have emerged asimportant causes of morbidity and mortality amongim m u n o c o m p romised patients, particularly infectingthose who have undergone bone marrow or organtransplantation, or become infected with acquiredimmunodeficiency syndro m e [ 1 , 2 ] . Absence ofspecific signs and symptoms and limitations ofspecificity and sensitivity of the currently availablediagnostic tests make early diagnosis difficult, thusdelaying timely initiation of appropriate antifungalt h e r a p y. Together with the pro g ress made inmedical and transplant technologies, the numberand diversity of immunosuppressed individualshas increased, and so are the types of fungalpathogens infecting them. In fact, some of themould infections that infect the immunosu p p ressed population today were not evendescribed as pathogens 20 or 30 years ago [3,4] . In thiscontext, Professor Howard A. Buechner [5] , as earlyas 1971, wrote that “—-the role of the fungus ise m e rging with frightening rapidity and thephysician who formerly had merely a noddingacquaintance with these disorders will soon findthemselves compelled to take a more active role intheir early detection and proper treatment”. Tomeet these growing complications of modernmedicine, the field of antifungal drug research hasmade considerable pro g ress. Fluconazole anditraconazole, introduced in 1980s, were the firstalternatives to amphotericin B with activity againstC a n d i d a and A s p e rg i l l u s species, re s p e c t i v e l y [6, 7] .Fluconazole continues to be a first line therapyoption for invasive candidiasis in non-neutropenicpatients, besides its well recognized prophylacticuse in selected high-risk patients [7, 8] . While the roleof itraconazole in the treatment of invasivecandidiasis remains to be rationalized, it is beingused as an alternative to amphotericin B forempirical treatment in persistently neutro p e n i ccancer patients (excluding allogeneic transplantrecipients) and in allergic bro n c h o p u l m o n a r ya s p e rgillosis patients to prevent A s p e rg i l l u scolonization [6, 9] .Address correspondence to:Prof. Zia U. Khan, Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait. Tel: 498-6504, Fax: 5332719, E-mail:Ziauddin@hsc.edu.kw

100Advances in Therapy of Invasive Mycoses June 2007Table 1: Efficacy of voriconazole for patients with invasive aspergillosisStudy Study design No. of Primary antifungal Duration Comparator Results CommentssubjectsPerfect Salvage 142 Vori, 6 mg/kg 2 times daily iv on day 1 iv group, 1 -138 None Clinical responseet al [21] (loading dosage), followed by 4 mg/kg days (median rate, 44%2 times daily iv for atleast 3 days, then duration, 18 days);switched to 200 mg 2 times daily po; or for po group, 1 -Vori, 400mg 2 times po (loading dosage), 326 days (medianfollowed by 200 mg 2 times daily po duration, 69 days)Herbrecht Multicenter, Vori, 6, mg/kg 2 times daily iv (loading 2-84 days (mean AmB, 1-1.5 mg/kg Rate of successful Vori group hadet al. [22] randomized 277 dosage), 4 mg/kg 2 times daily duration, 77 days) iv once daily for 1 - outcome, 52.8% for fewer adverse(maintenance dosage) 84 days (median Vori group and events (343 vs.duration, 10 days) 31.6% for AmB 432; p =.02) andgroup (difference, fewer severe21.2%, 95% Cl, adverse events (2610.4% - 32.9%); vs. 45; p=.008); thesurvival rate: 70.8% duration ofvs. 57.9%, respecti- treatment wasvely (95% Cl, 40%- much longer for88%; p = .02) the Vori groupDenning Multicenter, 116 Vori, 6, mg/kg 2 times daily iv 54 - 250 days None Clinical response Vori as effective aset al. [23] open-label, (loading dosage), 3 mg/kg 2 times (median duration, rate, 48% (only 14% AmB followed bynoncomparative daily po (maintenance dosage); and 133 days); iv group, of subjects had Flu; Vori was moresalvage then 200 mg 2 times per day po 1 -40 days; po group, complete response) effective against2 - 219 days Candidatropicalis(32% vs. 6%success rate)(p = .032)Abbreviations: Vori- Voriconazole, AmB- Amphotericin, Flu - Fluconazole, po = per oralare transient visual disturbance (about 30%), rashand hepatitis.Indications: Invasive aspergillosis, esophagealcandidiasis, and refractory infections caused byScedosporium apiospermum and Fusarium species.Dosage: Intravenous route: adults: 6 mg/kg q12h X1 day, then 4 mg/kg q12h; children: 6 mg/kg q12hX 1day, then 4-5 mg/kg q12 h; infants: 8 mg/kgq12h X 1 day, then 6 mg/kg q12h. Oral route: adultand children > 40 kg: 400 mg q12h X 1 day, then200-300 mg q12h; < 40kg: 200 mg q12h X 1 day, then100-150 mg q12h. (Note: more pediatric studies areneeded to determine optimal doses).POSACONAZOLEPosaconazole (Noxafil, Schering-Plough Inc.,NJ) was approved in Europe in October, 2005 fortreating invasive fungal infections in adult patientswho had refractory disease or who were intolerantof certain commonly used antifungal agents. It is anoral second generation triazole with bro a d -s p e c t rum antifungal activity [ 3 0 , 3 1 ] . A p r i m a r yadvantage over voriconazole is its activity againstzygomycetes [31] . It has been shown to retain activityagainst many Candida and Aspergillus isolates thatexhibited resistance to voriconazole, fluconazole,and amphotericin B, although instances of crossresistancein some C a n d i d a isolates have beenreported [32] . Recently, posaconazole has been usedas salvage therapy in 24 patients with activezygomycosis. Eleven out of them had CNSi n v o l v e m e n t [ 33 ] . The success rates were 79% inpatients who were refractory to the standard drug.It has also been found useful as salvage treatmentfor invasive F u s a r i u m infection with successoutcome of 48% [34] . In a well-designed multi-centertrial, Vaquez et al [ 35 ] demonstrated that posaconazolewas as efficacious as fluconazole in the treatment ofo ropharyngeal candidiasis in HIV-infected patients.It was more effective in sustaining clinical successafter treatment was stopped. In September, 2006,FDAhas approved oral suspension of posaconazolefor prophylaxis against invasive Aspergillus andCandida infections in severely immunosuppressedpatients > 12 years of age. This is the first antifungalagent ever approved by FDA for the prevention ofinvasive aspergillosis. The drug appears safe andwell tolerated, even when administered for longperiods. Pharma-cokinetics of posaconazole inchildren are unknown. Posaconazole is extensivelydistributed into tissues and metabolized throughliver. Inhibition of CYP3A4 but not other CYP450enzymes by posaconazole may cause less druginteractions. It might be an appropriate alternative

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102Advances in Therapy of Invasive Mycoses June 2007to amphotericin B for patients with impaired renalfunction. It is not removed by haemodialysis.Although cerebrospinal penetration is poor, reportsof therapeutic efficacy in CNS mycoses haveappeared [36,37] .Indications: Under FDA review for oral treatmentof aspergillosis, zygomycosis and fusariosis inpatients refractory or intolerant to other therapies.It has also been used in Fusarium keratitis. Recentlyhas been approved as prophylactic agent forinvasive A s p e rg i l l u s and C a n d i d a infections ins e v e rely immunosuppressed patients, such ashematopoietic stem cell transplant recipients withgraft-versus-host disease and those with prolongedneutropenia.Dosage: Oral route: adults: 200 mg q6h or 400 mgq12h. It should be administered after meal.Children doses are not yet established.RAVUCONAZOLE AND ALBACONAZOLERavuconazole (Bristol-Myers, Squibb Inc, CT,USA) exhibits potent in v i t ro activity againstCandida spp., Aspergillus spp., C. neoformans, H.capsulatum and C. immitis. Cross-resistance betweenfluconazole and ravuconazole was observed withC. glabrata and is variable among other Candida spp.Ravuconazole is less active than voriconazoleagainst Fusarium, Scedosporium and Tr i c h o s p o ro nspp., and it has no activity against Rhizopus orM u c o r spp. Immunosuppressed animal modelshave confirmed efficacy against C a n d i d a s p p . ,Aspergillus spp., and H. capsulatum [38,39] . Metabolismis primarily hepatic. Ravuconazole is well-toleratedin healthy adults. Drug interactions are uncommon.Ravuconazole and albaconazole are undergoingearly clinical evaluation and their future is uncertain.For all newer triazoles, concerns about emergingd ru g - resistant fungi and the incidence andm a n a g e m e n tof breakthrough infections will dictatetheir role in antifungal prophylaxis and treatment.ECHINOCANDINSThe echinocandins are a novel class of agentsthat irreversibly inhibit [beta]-1, 3-D-glucansynthase, the enzyme complex that forms glucanpolymers in the fungal cell wall, but is absent inmammalian cells. They are active against Candida,A s p e rg i l l u s, but not against C r y p t o c o c c u s,zygomycetes and some other moulds. Interestingly,echinocandins are fungicidal against yeasts andfungistatic against moulds. Their limited toxicityand minimal drug-drug interactions make them anattractive option for treatment of invasive mycoses.C u r re n t l y, these intravenous agents includecaspofungin (Cancidas, Merck Researc hLaboratories, NJ, USA), micafungin (Mycamine,Fujisawa Healthcare Inc. Japan), and anidulafungin(Eraxis, Pfizer Inc.).CASPOFUNGINCaspofungin was the first agent that becameavailable for therapeutic use in the echinocandinclass [40] . It is fungicidal in vitro against Candida spp.including azole-resistant species. Minimalinhibitory concentrations (MIC) are higher forCandida parapsilosis and C a n d i d a g u i l l i e r m o n d i i.Fungistatic activity has been demonstrated againstA s p e rg i l l u s spp. Caspofungin also has activityagainst C. immitis, H. capsulatum and B. dermatitidis.H o w e v e r, Cryptococcus neoformans, zygomycetes,Fusarium spp., Scedosporium spp. and Trichosporonspp. are relatively resistant. Caspofungin has beenapproved by FDAfor adult patients refractory to orintolerant of standard antifungal agents forinvasive aspergillosis and for primary therapy forCandida infections as well as empirical therapy forfever and neutro p e n i a [ 40 , 41 ] . In a randomized,double-blind multinational trial caspofungin wasc o m p a red with liposomal amphotericin B forempirical antifungal therapy in patients withpersistent fever and neutropenia [41] . Caspofunginwas found to be as effective as liposomalamphotericin B for empirical therapy in patientswith persistent fever and neutropenia. It has alsobeen found effective and very well toleratedalternative for salvage treatment of invasivea s p e rg i l l o s i s [ 42 ] . Recently, caspofugin has beenrecommended as a first line treatment option forcandidemia [8] . It was found to be at least as effectiveas amphotericin B for the treatment of candidiasisand candidemia (Table 3) [ 43 ] . In childre n ,caspofungin was effective and well-tolerated forpersistent and pro g ressive candidiasis in 10neonates (9 pre-term). They were treated with adose of 1 mg/kg for the first two days and 2 mg/kgt h e re a f t e r. Nine out of 10 survived, but nopharmacokinetic data were obtained [44] . Walsh eta l [ 45 ] studied pharmacokinetics, safety andtolerability of caspofungin in children withneutropenia using weight-based regimen and bodysurface area regimen. The drug was generally welltolerated and no serious side effects were observed.A dose of 1 mg/kg was found inadequate, anddoses of 50 mg/m 2 /day were necessary to achieveappropriate drug levels. Although caspofungin isneither a substrate for nor an inhibitor of CYP450,some drug-drug interactions have been observedwith cyclosporin, phenytoin, efavirenz, rifampinand other drugs. It appears to have low toxicitywith few adverse effects, such as nausea, fever andflushing.

June 2007KUWAIT MEDICAL JOURNAL 103I n d i c a t i o n s : C a n d i d a infections: intra-abdominalabscesses, peritonitis and pleural space infections,candidemia, esophageal candidiasis; invasiveaspergillosis in patients refractory or intolerant toother antifungal therapies; empiric therapy infebrile neutropenic patients.Dosage: Intravenous: adults: load 70 mg, then 50mg daily; children 50 mg/m2 daily; neonates: 1mg/kg daily X 2 doses then 2 mg/kg daily. (Note:more pediatric studies are required to determineoptimal doses).MICAFUNGINLike caspofungin, micafungin exhibits identicalspectrum of in vitro activity against C. albicans, nonal b i c a n s species and A s p e rg i l l u s species but notagainst zygomycetes and C. neoformans. It has fewerd ru g - d rug interactions and relatively lessexpensive than caspofungin [ 46 ] . It is eff i c a c i o u sagainst invasive candidiasis and asperg i l l o s i s .Although soluble in water, it has poor oralbioavailability. Its pharmacokinetics is similar inadults and children and metabolism is hepatic. Itreceived FDA a p p roval in March 2005 foresophageal candidiasis and for Candida infectionprophylaxis in hematopoietic stem cell transplantrecipients. Two clinical trials have been reported forthe treatment of invasive candidiasis withmicafungin (Table 3) [ 47 , 48 ] . In the first nonrandomized,non-comparative study, micafunginwas found safe and effective in the treatment ofrefractory and new cases of candidemia includingthose caused by C. glabrata with an overall successrate (complete and partial) of 83% [47] . In the secondmulticenter, open-label study, the clinical responsefor candidemia was 100% and for esophagealcandidiasis 71% [ 48 ] . Recently, de Wet et al [ 49 ]conducted a randomized, double blind studycomparing intravenous micafungin (150 mg/d)with intravenous fluconazole (200 mg/d) in thetreatment of esophageal candidiasis. Micafunginwas found to be as efficacious as intravenousfluconazole. In a randomized, double blind trialthat included adults and children with neutropenia,micafungin compared favorably with fluconazolein preventing invasive fungal infections afterhemopoietic stem cell transplantation (80% versus73.5% respectively; p = 0.03) [50] .Indications: Esophageal candidiasis, prophylaxisof Candida infections in patients undergoing stemcell transplantation.Dosage: Intravenous (Mycamine): Adults: Candidainfection prophylaxis in hematopoietic stem celltransplant patients: 50 mg/day over 1 h;esophageal candidiasis: 150 mg/day over 1 h.C h i l d ren: 3 mg/kg (more pediatric studies areneeded to determine optimal dose).ANIDULAFUNGINAnidulafungin (Eraxis) received FDA approvalfor treating candidemia in February 2006. The drugis active in vitro against most Candida spp withfungicidal activity, but like caspofungin, C .parapsilosis and C. guillermondii are more resistant tothis agent [51] . It is fungistatic against Aspergillus spp.and not active against C. neoformans or B .d e r m a t i t i d i s [ 52 ] . Although clinical experience islimited, anidulafungin is comparable tofluconazole in esophageal candidiasis [53] . At the endof randomized, double-blind study of 601 patientswith endoscopically and micro b i o l o g i c a l l ydocumented esophageal candidiasis, rate ofendoscopic success for anidulafungin was 97.2% ascompared to 98.8% in fluconazole group. This wasfound statistically non-inferior to that offluconazole [53] . In a phase 2, randomized, doserangingstudy evaluating the safety and efficacy ofanidulafungin in 123 invasive candidiasis andcandidemia patients, at the end of treatment, thesuccess rates were 84, 90, and 89% in the 50, 75 and100 mg groups, respectively (Table 3) [54] .Indications: Candidemia, esophageal candidiasis,abdominal abscesses, and peritonitis.Dosage: Intravenous: Candidemia: adult: load 200mg day 1, followed by a 100 mg daily dose, tocontinue for at least 14 days after last positiveculture; esophageal candidiasis: load 100 mg day 1,followed by a 50 mg daily dose, continue for at least14 days and for at least seven days followingresolution of symptoms. Doses in children are notyet established.COMBINATION THERAPYWith the availability of voriconazole, lipidformulations of amphotericin B, and echinocandins,the possibilities of using combination antifungalagents have greatly increased. The combination ofamphotericin B and 5-Flucytosine is wellestablished for the treatment of cryptococcalm e n i n g i t i s [ 12 ] . Initial combination studies usingazole antifungals and polyenes in animal modelsyielded synergistic, additive, indifferent or evenantagonistic re s u l t s [ 55 ] . A recently completedrandomized, blinded clinical trial in candidemiapatients suggested a trend towards impro v e doutcomes among non-neutropenic patientsreceiving amphotericin B (0.6-0.7 mg/kg) andfluconazole (800 mg/day) versus fluconazole (800mg/day) alone [ 56 , 57 ] . Results of this study

104Advances in Therapy of Invasive Mycoses June 2007demonstrated a 69% success in favor ofcombination therapy (p = 0.043) over monotherapy(56%). However, success rates utilizing a Kaplan-Meier time -to- failure analysis was notsignificantly different (p = 0.08). The usefulness ofcombination of fluconazole with an echinocandinin Candida infections remains unclear.Currently, invasive aspergillosis is the focus ofcombination therapy in experimental and clinicals t u d i e s [ 58 , 59 ] . In a prospective, multicenter studycomprising patients of proven and pro b a b l einvasive aspergillosis, voriconazole andcaspogungin combination therapy was consideredpreferable to lipid formulation of amphotericin B ina subset of organ transplant recipients, such asthose with renal failure or A. fumigatus infection [60] .Adjunctive immunotherapies and immunereconstitutionwith a view to restoring orenhancing host defenses are other importantstrategies for the successful management of fungalinfection. Reduction of immunosuppression level,w h e re feasible, administration of re c o m b i n a n tcytokines and donor elicited granulocytetransfusion for neutropenic patients have beenused with encouraging results in experimental andclinical studies [61] . Recently, there have been studiesof adjunctive interferon and antibody therapy forcryptococcal meningitis [62] . More recently, Pachl etal [63] reported that an antibody fragment of heatshock protein 90 (Mycograb; manufactured byNeuTec Pharma, Manchester, UK) is effective in thetreatment of human candidiasis. In a double-blind,randomized study involving 117 culture confirmedpatients, a complete overall response was obtainedin 48% patients in the amphotericin B group ascompared to 84% in amphotericin B and Mycograbcombination group, reducing Candida attributablemortality to > four-fold. This molecule has directantifungal activity in vitro against C. albicans and C.neoformans through an unknown mechanism. Thisis a notable advance, giving a new direction to thefield of antimicrobial therapy.CONCLUSIONClinical mycology has entered into an era ofunprecedented therapeutic development. Optionsfor treatment of invasive fungal infections haveincreased with new agents that exhibit improvedtolerability and increased range of activity. Nowattention is being focused on examining the efficacyof these agents in combination with older or neweragents in randomized, controlled clinical studies. Itis hoped that with the availability of newtherapeutic alternatives, it will be possible todevelop effective strategies to prevent and treatthese life-threatening infections in the near future.REFERENCES1. Marr KA, Carter RA, Boeckh M, Martin P, Corey L. Invasiveaspergillosis in allogeneic stem cell transplant recipients:changes in epidemiology and risk factors. Blood 2002;100:4358-4366.2. C h a y a k u l k e e ree M, Ghannoum MA, Perfect JR.Zygomycosis: the re-emerging fungal infection. Eur J ClinMicrobiol Infect Dis 2006; 25:215-219.3. Pfaller MA, Diekema DJ. Rare and emerging opportunisticfungal pathogens: concern for resistance beyond Candidaalbicans and Aspergillus fumigatus. J Clin Microbiol 2004;42:4419-4431.4. Walsh TJ, Groll A, Hiemenz J, Fleming R, Roilides E,Anaissie E. Infections due to emerging and uncommonmedically important fungal pathogens. Clin Micro b i o lInfect 2004; 1:48-66.5. Buechner HA(ed.). Management of Fungus Diseases of theLung. C. Thomas. Springfield, 1971.6. Stevens DA, Kan VL, Judson MA, et al. Practice guidelinesfor diseases caused by Aspergillus. Clin Infect Dis 2000;30:696-709.7. Charlier C, Hart E, Lefort A, et al. Fluconazole for themanagement of invasive candidiasis: where do we standafter 15 years? J Antimicrob Chemother 2006; 57:384-410.8. Pappas PG, Rex JH, Sobel JD, et al. Guidelines for treatmentof candidiasis. Clin Infect Dis 2004a; 38:161-189.9. Maertens J, Boogaerts M. The place for itraconazole intreatment. 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106Advances in Therapy of Invasive Mycoses June 2007Clin Infect Dis 2004; 39:797-802.59. Clemons KV, Stevens DA. Efficacy of micafungin alone or incombination against experimental pulmonary aspergillosis.Med Mycol 2006; 44:69-73.60. Singh N, Limaye AP, Forrest G, et al. Combination ofvoriconazole and caspofungin as primary therapy forinvasive aspergillosis in solid organ transplant recipients: ap rospective, multicenter, observational study.Transplantation 2006; 8:320-326.61. Antachopoulos C, Roilides E. Cytokines and fungalinfections. Br J Haematol 2005; 129:583-596.62. Pappas PG, Bustamante B, Ticona E, et al. Recombinantinterferon- gamma 1b as adjunctive therapy for AIDSrelatedacute cryptococcal meningitis. J Infect Dis 2004;189:2185-2191.63. Pachl J, Svoboda P, Jacobs F, et al. A randomized, blinded,multicenter trial of lipid-associated amphotericin B aloneversus in combination with an antibody-based inhibitor ofheat shock protein 90 in patients with invasive candidiasis.Clin Infect Dis 2006; 42:1404-1413.

June 2007KUWAIT MEDICAL JOURNALReview ArticleGenetics of Type 1 Diabetes MellitusHanan F Al-Mutairi 1 , Ameer M Mohsen 1 , Zaidan M Al-Mazidi 21Department of Pediatrics, Farwaniya Hospital, Kuwait2Department of Pediatrics, Endocrine Unit, Al-Sabah Hospital, KuwaitKuwait Medical Journal 2007, 39 (2):107-115ABSTRACTType 1 diabetes is an autoimmune disease in which thepatient’s immune system destroys the insulin-secretingβ-cells of the pancreas. A majority of cases is thought tooccur as a result of gene-environment interaction. About18 regions of the genome have been linked withinfluencing type 1 diabetes risk. These regions, each ofwhich may contain several genes, have been labeledIDDM1 to IDDM18. The most well-studied is IDDM1,which contains the HLA (Human Leukocyte Antigens)genes that encode immune response proteins. Variationin HLAgenes is an important genetic risk factor, but theyalone do not account for the disease as other genes areinvolved. Other important loci associated with type 1diabetes with much smaller effect than HLA, include theinsulin variable number of tandem repeats, PTPN22(Protein Tyrosine Phosphatase non-receptor type 22), andCTLA-4 (Cytotoxic T-Lymphocyte Antigen-4).This review will focus on genetic factors associated withtype 1 diabetes mellitus.KEYWORDS: cytotoxic T-Lymphocyte antigen-4, insulin gene, protein tyrosine phosphatase non-receptor type 22, type 1 diabetesmellitusINTRODUCTIONType 1 diabetes (T1D) is a multi-factorialautoimmune disease characterized by insulindeficiency, due to the T-cell mediated destruction ofpancreatic β-cells [1,2] . The disease accounts for about10% of all cases of diabetes [3] . There is a markedgeographic variation in incidence, with an annualincidence of more than 40 per 100,000 children inFinland to less than two per 100,000 in Japan [4,5] . Theincidence of T1D in Kuwait was 20.1 per 1000,000children between 0-14 years. The incidence amongboys at 21.1 per 100,000 was slightly higher thanthat among girls at 19.0 per 100, 000 [6] . In addition,there is compelling evidence of a temporal increasein the incidence of T1D, with countries such asFinland experiencing more than a doubling inincidence over the past four decades [7] . The currentglobal increase in incidence of 3% per year is wellreported [3,8] . This rapid rise strongly suggests thatthe action of the environment on susceptibilitygenes contributes to the evolving epidemiology ofT1D [3] . The general population has a 1 in 300 risk ofdeveloping T1D, whereas a first-degree relativewith T1D has a 1 in 2 lifetime risk [9,10] . Prevalence ofT1D in Kuwait was 269.9 per 100,000. There was nosignificant difference in prevalence between maleand female. T1D was more prevalent in the agegroup 10 - 13 years and lowest in the age group 6 -9 years [11] . Monozygotic twins have a concordancerate of 30 to 50%, whereas dizygotic twins have aconcordance rate of 6 to 10% [10] . Eighty-five percentof cases of T1D occur in individuals with no familyhistory of the disease. Diff e rences in risk alsodepend on which parent has diabetes. Children ofmothers who have T1D have only a 2% risk ofdeveloping T1D, where as children of fathers whohave T1D have a 7% risk [10] . In disorders following amendelian pattern of autosomal dominant orrecessive transmission, the pattern of inheritance ofthe disease phenotype is usually obvious. It ismuch more difficult in diabetes to confidentlydefine the reported linkages susceptibility genes,since the mode of inheritance of the genes causingthese complex disorders is unknown [12] .Among the genetic determinants of susceptibility,with more than 18 putative loci identified to date, aregion in chromosome 6p21 (IDDM1) containingthe major histocompatibility complex (MHC) is theonly one consistently associated with T1D ingenome -wide screenings [2] . Candidate gene studiesalso identified the insulin gene (INS) onc h romosome 11 as the second most importantgenetic susceptibility factor, contributing 10% ofgenetic susceptibility to T1D [ 1 3 ] . Over the lastdecade, whole genome screens have indicated thatthere are at least 15 other loci associated with T1D,(This article was presented at the 12 th International Conference of the Kuwait Medical Association, April 1-4, 2007)Address correspondence to:Dr. Hanan F Al-Mutairi, P.O.BOX 49634, Al-Omariya, Kuwait 85157, E-mail: am-mohsn@hotmail.com

108Genetics of Type 1 Diabetes Mellitus June 2007and of those, other two genes intimately associatedwith T-cell activation have been identifiedrecently [3,14-16] . An allele of the gene for a negativeregulator of T-cell activation, cytotxic T- Ly m p h o c y t eantigen 4 (CTLA-4), found on chromosome 2q33, isconsidered to be the third susceptibility locus forT1D and has been associated with increased levelsof CTLA-4 [17] and the frequency of regulatory T-cells [18] . A variant of Protein tyrosine phosphatasenon receptor type 22 (PTPN 22), the gene encodingLY P ( Lymphoid tyrosine phosph-atase), also asuppressor of T-cell activation, has been deemedthe fourth susceptibility factor [3,19, 20] .To date, no single gene is either necessary ors u fficient to predict the development of T1D.Although T1D is likely a polygenic disord e r,epidemiological pattern of T1D, including seasonaland temporal changes in incidence, suggest thate n v i ronmental factors are involved [ 2 1 ] , with theexception of possible role for viruses, infantnutrition, obesity and lack of exercise. Theenvironmental factors that initiate or precipitate theonset of T1D have not been established [21] . Studyingthe genetics of T1D will allow us to better definethis disease, to improve our ability to identifyindividuals at risk, and to predict the risk ofassociated disord e r s [ 9 ] . To the best of ourknowledge, no genetic study was done in Kuwaitto detect the common gene for T1D.PathophysiologyT1D is the most severe type of diabetes,requiring insulin injections on a life long basis [22] .The majority of cases result from pro v e nautoimmune-mediated β cell destruction (Type 1a);approximately 10 to 20% of cases are antibodynegativeand are termed idiopathic (Type 1b) [23] . Adecline in insulin secretion is demonstrated for upto 12 years before the onset of clinical disease.Inflammation of the pancreatic islets (insulitis)involves CD4 + and CD8 + lymphocytes, B-lymphocytes, and macrophages [24,25] .Two mechanisms of onset for T1D are proposed.The first mechanism suggests that environmentalfactors trigger the autoimmune process, most oftenin childhood before 10 years of age [24] . Although thediagnosis of T1D is usually preceded by only a fewweeks of known symptoms, in fact clinical diseasebecomes evident only after a long pro d ro m a lperiod characterized by the gradual destruction ofp a n c reatic beta cells [ 23 ] . The second mechanismsuggests that a superantigen reaction results inrapid destruction of pancreatic beta cells within afew weeks to a month, leading to the onset ofclinical disease [26] .HLA genes in predisposition to T1D:The best evidence for a genetic component in thesusceptibility to T1D comes from studies of theHLA genes in both population and families as wellas from animal models [27] . It has been estimated thatHLA (IDDM1) provides up to 40 - 50% of thefamilial clustering of T1D [28,29] . The HLA region is acluster of genes located within MHC on short armof chromosome 6 (6p21 .3) [21, 27] .The HLA Classes:Within the HLA region, they are grouped intothree classes.Class I genes: (HLA - A, HLA -B and HLA-C)encode class I HLAantigens, located on the surfaceof all nucleated cells [30] .Class II genes: (HLA -DR, HLA-DQ and HLA-DP)p roduce class II HLA antigens that are foundexclusively on B-lymphocytes, macro p h a g e s ,epithelial cells of the islets of Langerhans, andactivated T-lymphocytes. Their expression on othercells may be induced by cytokines such as a-interferon and INF-α [30, 31] .Class III genes: code for complement components(C2, pro p e rdin factor B, C4A and C4B), 21-h y d roxylase and products involved in T- c e l l -mediated inflammation, such as TNF-Aand TNF-B,and acute phase protein [31] .The HLA class II Region:Statistically is the strongest genetic associationwith T1D conferred by HLA class II gene alleles [27] .HLA class II molecule, particularly DR and DQ,account for approximately 40% out of the geneticrisk for T1D development [12, 32] . As the HLA regiondisplays a significant degree for linkagedisequilibrium, it has been very difficult to studythe effect of individual HLA-DQ or DR genesseparately [27] .Spectrum of diabetes risk HLA haplotypes:Several loci within or near HLAcomplex appearto modulate diabetic risk and add furthercomplexicity to the analysis of T1D [33] . Individualwith the highest risk for T1D express bothpredisposing haplotypes: DQA1*0501-DQB1*0201(DQ2), which is almost always inherited withDRB1* 0301 (DR3) and DQA1*0301-DQB1*0302(DQ8), inherited with DRB1*0401 or DRB1*0402(DR4) [34-37] . These individuals have been referred toas DR3/DR4 or DQ2/DQ8 heterozygotes. So, agreat majority of patients carry the HLA -DR3 orDR4 class II antigens and approximately 30% ofpatients are DR3/DR4 hetero z y g o t e s [ 3 3 ] . TheDR3/DR4 genotype confers the highest diabeticrisk with a synergistic mode of action, followed byDR4 and DR3 homozygosity, respectively [38] . Based

June 2007KUWAIT MEDICAL JOURNAL 109on DNAsequencing, the HLA-DQ locus was foundto be the most strongly associated with diabetessusceptibility [33] . The precise mechanism throughwhich HLA-DQ determines disease susceptibility isstill not clear [39] . This locus encodes for severalvariants of the HLA-DQ molecule, a heterodimerconsisting of two glycoprotein chains (α and β)involved in immune recognition and antigenpresentation to CD4 T-cells [33] . In Caucasians, theHLA-DQ heterodimers (the α-chains are labeledDQA1 and the β-chains DQB1) encoded byDQA1*0301, DQB1*0302 and DQA1*0501, DQB1*0201alleles have the strongest association withd i a b e t e s [ 3 1 , 3 3 ] . These alleles are in linkage disequilibriumwith the HLA-DR4 and DR3 alleles [40] .It has also been noted that DQB1*0302 differsfrom DQB1*0301 at position 57, where it lacks anaspartic acid residue [33] . The DQB1*0201 allele alsolacks aspartic acid at position 57, and it has beenproposed that this residue may be involved in themolecular mechanism underlying T1D-encodedsusceptibility [40,41] . In fact, the amino acid residue atposition 57 of the DQ- β chain appears to be criticalfor peptide binding and re c o g n i t i o n [ 4 2 ] . Otherresidues of the DQ- β chain may influence peptidebinding and diabetes susceptibility, and inparticular the combined variation of residues atposition 57 and 70 seem to more strongly correlatewith diabetes risk [ 4 3 , 4 4 ] . An arginine residue atposition 52 of the DQ-α chain also correlates withdiabetes susceptibility [ 4 5 ] . However, some DQB1including DQB1*0302/DQB1*0201 (DR7),DQB1* 0 2 0 1 ( D R 3 ) / D Q B 1 * 0 2 0 1 ( D R 3 ) a n d D Q B 1 * 0 2 0 1 ( D R 3 )/DQB1*0201 (DR7) are low risk [31] .Certain haplotypes of class II HLAgenes exert ap rotective action against the development ofdiabetes. HLA -alleles have also been associatedwith protection from T1D, the haplotypeDQA1*0102/DQB1*0602/DRB1*1501 being knownto confer protection. Evidence suggest that suchp rotection may be mostly encoded by theDQB1*0602 allele and even the first degree relativeswith islet cell antibodies have a low diabetic risk ifthey carry DQB1*0602. However, this protectiveeffect is not absolute [12,34,46,47] .Other loci in the class II region have beenassociated with T1D besides HLA-DQ and DR [27] .HLA-DPB1*0101, DPB1*0301, and DPB1*0202 werereported to be positively and DPB1*0402 negativelyassociated [48-50] .To summarize, some HLA haplotypes areassociated with high, moderate or low risk ofdeveloping T1D whereas some even conferprotection against T1D (Table 1).The HLA class I Region:-A number of observations indicate that class IIgenes cannot explain all of HLA association withTable 1: HLAhaplotypes and type 1 diabetesHigh Risk HaplotypesDR 3 DQA1*0501 DQB1*0201 DRB1*0301DR 4 DQA1*0301 DQB1*0302 DRB1*0401DR 4 DQA1*0301 DQB1*0302 DRB1*0405Predisposing HaplotypesDR2 DQA1*0102 DQB1*0502 DRB1*1601DR4 DQA1*0301 DQB1*0302 DRB1*0402DR4 DQA1*0301 DQB1*0302 DRB1*0404Protective HaplotypesDR2 DQA1*0102 DQB1*0602 DRB1*1501DR6 DQA1*0101 DQB1*0503 DRB1*1401DR7 DQA1*0201 DQB1*0303 DRB1*0701T1D [33] . There is evidence that several alleles at theclass I HLA B and C loci may influencesusceptibility as well as the age of onset [51] and therate of β-cells destruction [52] . In addition, the class Ichain -related MIC-A and MIC-B genes locatedbetween the HLA-B and TNF α genes may alsoeffect T1D susceptibility [33] .The HLA class III Region:The TNF (Tumour Necrosis Factor) gene is astrong candidate from class III, since this genepolymorphisms may affect the production of TNFα,a potent cytokine, thus affecting the immuneresponse potential [33] . It has been reported that TNFα polymorphisms are associated with age of onsetand influence the inflammatory process leading tothe destruction and pancreatic β-cell anddevelopment of T1D [53] .Apart from determining T1D risk, HLA genescan also modulate clinical features of the disease,such as age of onset or outcome of active cellularautoimmunity [54] . Thus, the combination of the DR3and DR4 haplotypes not only predisposes stronglyto T1D but also accelerated disease onset [ 5 4 ] .Conversely, the rare individuals contracting T1Ddespite the presence of the protective DQB1*0602allele generally show a very late onset of disease [55] .In conclusion, the HLA associations with T1Dare complex, with many haplotypes influencingdisease risk [56] .IDDM2: The Insulin Gene:Insulin is composed of two distinct polypeptidechains, chain A and chain B, which are linked bydisulfide bonds. Many proteins that containsubunits, such as hemoglobin, are the products ofseveral genes. However, insulin is the product ofone gene, INS [57] . The research done by Nakayama etal has strongly shown that insulin is a primaryautoantigen in the beginning stages of diabetes.Also, supporting this evidence is the presence ofinsulin antibodies in the blood of prediabetic anddiabetic patients [58] .The insulin gene is the second well establishedsusceptibility locus in T1D on chromosome 11p

110Genetics of Type 1 Diabetes Mellitus June 20071 5 . 5 [ 1 2 , 3 0 ] . It contributes about 10% toward T1Dsusceptibility [59] .The variable number of tandem repeats (VNTRs):The risk area of this locus is localized to a regionflanking the insulin gene that contain a shortsequence of DNA that is repeated many times [16,60] .Because the repeated sequences follow one behindthe other (in tandem) and because the number ofrepeats varies between individuals, this phenomenonis called VNTRs [57] . The VNTRs polymorphism iscategorized into classes I to III.• Class I has alleles that range form 26 to 63repeat units [30] .• Class II has alleles that average around 80repeat units [57] .• Class III has alleles ranging from 141 to 209repeat units [54] .Occurrence rate of VNTR I in the Caucasoidpopulation is approximately 70%, and that of VNTRI I I 30%. VNTR II occurs very rarely [12] .The class of VNTR is associated withsusceptibility to T1D. Short class I alleles areassociated with a higher risk of developing T1D,w h e reas the longer class III alleles areprotective [57,61] . The presence of at least one class IIIallele is associated with a three-fold reduction inthe risk of T1D [57,61] . The mechanism by which theinsulin VNTR polymorphism influence the risk ofT1D is unclear [56] .HLAand insulin regions account for almost 60 -70% of the familial aggregation of T1D. In somepopulation, the combined effects of HLA a n dinsulin contribute less than 50% of familialincreased diabetic risk. Therefore, several genomewidelinkage studies have been conducted toidentify candidate regions that may containunidentified susceptibility genes [12,62] .Cytotoxic T-Lymphocyte Antigen - 4 (CTLA- 4):CTLA- 4 is expressed when the T-cell has beenactivated after antigen presentation. Because it isonly expressed in activated T-cells, and because itdown regulates the function of T-cells, it is likelythat CTLA- 4 has a role in guarding againstautoimmunity [57,63] . Loss of this gene may result inactivated T-cells attacking self antigens. Indeed,genetic variants of CTLA- 4 have been linked withautoimmune disorders [57] . CTLA- 4 gene is localizedon the long arm of chromosome 2 (2q 33) and thisgenetic region, IDDM 12, was previously found tobe associated with predisposition to T1D [17,63] . Someevidence has also been produced to suggest thatCTLA- 4 polymorphisms may influence genee x p ression. Three polymorphisms are curre n t l yknown in CTLA- 4, including a A/G SNPin exon 1,a C/T SNP in the first intron and a microstatelliterepeat in the 3’ untranslated region [54] . CTLA- 4expressed on the cell surface of activated T-cells isresponsible for the attenuation of immune responseby binding to ligands CD80 or CD86 expressed onthe surface of antigen presenting cells [ 1 2 , 6 4 ] . TheCTLA-4-CD80/CD86 interaction decreases synthesisof IL2 or may induce apoptosis in pre v i o u s l yactivated cells [12,64] .Protein tyrosine phosphatase non-receptor type 22(PTPN 22):The fourth established human T1D susceptibilitylocus is PTPN22. It encodes a lymphoid proteintyrosine kinase (LYP) that is important in negativec o n t rol of T-cell activation and in T- c e l ld e v e l o p m e n t [ 1 2 , 2 0 ] . A single nucleotide polymorphismat nucleotide 1858 in PTPN22 was associated withT 1 D [ 1 2 , 2 0 ] . Bottini and co-workers evaluated afunctional polymorphism in LYP gene in two seriesof patients with T1D [33] . This polymorphism is themost potent after IDDM1 and IDDM2. The LYPgene, also termed PTPN22, is a lymphoid tyrosinephosphatase located on chromosome 1 P13 [33] . It isof interest that PTPN22 has an effect similar inmagnitude to the insulin gene polymorphism.Similar to CTLA-4, PTPN22 is a T1D susceptibilitylocus that is shared by several organ specific andsystemic autoimmune diseases [65] .Interleukin (IL):It is well recognized that IL-2 has paradoxicalfunctions in T-cell homeostasis, acting as a potent T-cell growth factor during the initiation of immuneresponses and having a crucial function in thetermination of T-cell responses and maintenance ofself tolerance [ 1 2 ] . The latter function has beenp roposed to be due to a re q u i rement for IL-2signaling for the development and function ofregulatory T-cell, although IL-2 signaling is notrequired for their development in the thymus. Itslevel might affect disease susceptibility via themechanisms that maintain immune homeostasis [66] .It has been proved that although the levels of CD4+CD25+ regulatory T-cells had been normal inpatients with T1D, their ability to suppress T-cellp roliferation was markedly reduced compare dwith control subjects [66] . From this point of view it isa very interesting evidence that the re g i o ncontaining the gene IL-2RA encoding the alphachain of the IL-2 receptor (CD25) on chromosome10p15-p14 could be the fifth susceptibility locus forT1D [67] .IL-6 is a cytokine that has been implicated in anumber of immune mediated diseases [66] . There is apolymorphism at position 174 of the promoterregion of the IL-6 gene that may alter the expression

June 2007KUWAIT MEDICAL JOURNAL 111Table 2: Susceptibility loci for type 1 diabetesLocus Chromosome Candidate GenesIDDM1 6p21.3 HLADR/DQIDDM2 11p15.5 INSULIN (INS) VNTRPTPN22 1p13 PTPN22 (LYP)SUMO4 6q25 (IDDM5) SUM04IDDM3 15q26 -IDDM4 11q13 LRP5, FADDIDDM5 6q25 MnSOD, SUMO4IDDM6 18q12-q21 JK(Kidd), ZNF236, BCL2IDDM7 2q31-33 NEURODIDDM8 6q25-27 -IDDM9 3q21-25 -IDDM10 10p11-q11 GAD2IDDM11 14q24-q31 ENSA, SEL-1LIDDM12 2q33 CTLA-4, CD28IDDM13 2q34IDDM15 6q21IDDM16 14 q 32IDDM17 10q251DDM18 5q31.1 - 33.1 ILI2Bof the gene [68] . IL-6 gene may contribute to thegenetic susceptibility for T1D [68] .IDDM 3 - IDDM 18: (Table 2)IDDM 3 - IDDM 18, with the exception of IDDM17, have all been discovered by linkage studiesusing affected sib-pair families, either in whole orpartial genome scans. For most of these regionspositional candidate genes have been furtheranalyzed [27] .IDDM3 was originally reported to be locatednear the D15 S107 marker on chromosome 15q 26and so far no diabetes susceptibility genes havebeen identified on IDDM3 locus [27] .IDDM4 is a region on chromosome 11q13 andone of its genes which might be involved in T1Dgenetic predisposition that can be coding forFADD, a molecule involved in the apoptosisprocess [69] .The region of chromosme 6q25 that contains theIDDM5 locus includes the Mn-supero x i d edismutase (Mn SOD) genes [33] . MnSOD metabolizesharmful oxygen free radicals and converts theminto less reactive and less harmful molecules [57] .Polymorphism affecting the function of MnSODcould render β-cells more susceptible to fre eoxygen radicals damage [33] . However, this regionmay contain a susceptibility gene that is common tomore autoimmune diseases [70] .Several candidate diabetes susceptibility geneshave been identified in the IDDM6 locus. Theyinclude a gene associated with colorectal cancerthat may be linked to autoimmune disease, a genethat encodes a zinc finger DNA binding domain(ZNF 236) that may be linked with diabetic kidneydisease, and a molecule that opposes apoptosis(bCl-2) [3,57] .Within the IDDM7 locus on chromosme 2q 32are several candidate diabetes risk genes [71] . One isNEUROD 1, a transcription factor regulating thee x p ression of the insulin gene and playing animportant role in the development of pancreatic β-cells [33] .IDDM8 is found on chromosome 6 q 25 - q 27. Atpresent there is no known candidate gene in the 6q25 - q27 re g i o n [ 3 3 ] . IDDM9 has not yet beenapproved [56] .Another susceptibility locus may exist onchromosome 10p11 - q11, and has been termedIDDM10 [72] . The gene GAD2 is closely linked to theregion of chromosome 10. Glutamic aciddecarboxylase (GAD) catalyzes formation of theneurotransmitter GABA. Targeting of this enzymeby autoantibodies has been implicated in thepathogenesis of T1D [57,73,74] . However, several studieshave failed to demonstrate evidence of linkage ofGAD2 to T1D [27] .IDDM11 appears to lie on chromosome 14q 24.3- q31 [33] . Two candidate genes have been recentlymapped to this chromosomal region. The ENSAgene encodes alpha-endosulfine, an endogenousregulator of β-cells K(ATP) channels [ 7 5 ] . Therecombinant alpha-endosulfine has been shown toinhibit sulfonylurea urea binding to β- c e l l smembrane, to reduced K (ATP) channel currentsand to stimulate insulin secretion [75] . The SEL-1Lgene codes for a negative regulator which isrequired for differentiation and maturation of cellsas well as cell-cell interactions during development [ 3 3 ] .S E L - 1 L is abundantly expressed only in thepancreas, and recently shown to be critical for thedevelopment of the pancreas and β-cells [76] .Several IDDM13 candidate genes have yet to beassociated with T1D [27] . IDDM14 has not yet beenapproved [57] . The IDDM 15 locus has been linkedwith T1D and mutations near this region areassociated with a rare form of diabetes calledtransient neonatal diabetes [77] .One of the candidate genes in the IDDM 16locus is the immunoglobulin heavy chain.Immunoglobulins (antibodies) have a central rolein the immune response against foreign antigensand in error can also attack self antigens, resultingin autoimmune disease [57] .IDDM 17 maps to the long arm of chromosome10(10q 25). It was discovered to be linked to T1D,but the candidate gene is not yet known [33] .IDDM 18 was identified and mapped tochromosome 5q 31.1 - q33.1, close to the gene forthe P40 subunit of the IL12 gene, IL 12B [78,79] . IL-12P40 production influence T-cell responses, and maytherefore be important in T1D susceptibility [80] .

112Genetics of Type 1 Diabetes Mellitus June 2007Other Susceptibility Loci:A number of additional chromosomal regionsdemonstrating some evidence of linkage to T1Dhave been identified [27] .The effect of gender and HLA g e n o t y p ecomplicate studies of the contribution of genes onthe X-chromosome to T1D susceptibility [81] .There is also increasing evidence of the key roleof Vitamin D levels in T1D susceptibility [ 82 - 84 ] .Vitamin D has important immunomodulatoryproperties [85] and depletion or relative resistancemay play a part in the aetiology of T1D, possiblythrough effects on insulin secretion [86] .Several studies point to the involvement of TNFin T1D, although the contribution of TNF-α andTNF-β to autoimmune disease in general and todiabetes in particular is not well established [87] .Researchers in Houston (2004) identified a newgene mutation. The gene called SUMO-4contributes a portion of the risk of this form ofdiabetes. SUMO-4 plays a role in regulating theimmune system. When mutated, the gene functionsabnormally, prolonging the inflammatory response.This finding gives scientists a clue about theautoimmune cause of diabetes [88] .At the very end, there is also a report onassociation between CD4 SNP p ro m o t e rpolymorphism and T1D [89] .Environmental Triggers for T1D:Studies in most populations confirm an increasein the incidence of T1D, particularly among youngc h i l d re n [ 3 ] . Some studies however have shownconvincingly that the increases among youngchildren are occurring because of a shift to lowerage at onset rather than an overall increase inincidence in all age groups [3] . These changes are toorapid to be caused by alterations in the geneticb a c k g round and are likely the result ofenvironmental changes [3] . The temporal increase inthe incidence of T1D is almost certainly due toenvironmental factors. Moreover, it was noted thatthe incidence of diabetes has seasonal variationwith an increase in children presenting with T1D inthe fall of autumn and winter suggesting that viralinfections might precipitate the disease [5,12,90] .To date, 14 diff e rent viruses includingpicornaviruses, rotaviruses, herpesvirusis, mumps,rubella and retroviruses, have been reported to beassociated with the development of T1D in humanand animals models [91] . Viruses may be involved inthe pathogenesis of T1D in at least two distinctways: by inducing beta cell -specific autoimmunity,with or without infection of the beta cells (e.g.Kilham rat virus) and by cytolytic infection andd e s t ruction of the beta cells (i . e e n c e p h a l o -m y o c a rditis virus in mice) [ 9 1 ] . Coxsackie viru s e shave been of particular interest because of ahomology between the virus and the target antigenglumatic acid decarboxylase 65 (GAD 65). Bothnegative and positive studies have been re p o r t e d [ 9 2 , 9 3 ] .Nutritional factors were suggested to induceimmunopathological process. Antibodies to milkprotein and T-cells responses to these protein werereported to be increased amongst children withT1D [12] . Gerstein’s extensive meta-analysis demonstrateda weak but statistically significantassociation between T1D and a shortened period ofbreast-feeding [10,94] .Overall, the search for environmental factorscontributing to the development of diabetes hasbeen relatively disappointing. With the exception ofcongenital rubella infection, none have beenconfirmed. Prospective studies will perhaps bringmore light to the problem [12] .CONCLUSIONGenes play an important role in thedevelopment of T1D. The list of known and rarelyoccurring candidate genes associated with T1D isvery long and consistently increasing, pointing tothe extreme genetic heterogeneity of the disease.Theoretically, there are as many potential candidategenes as hormones, receptors, enzymes etc.included in the blood glucose regulation andrelated metabolic processes. To date, more than 250candidate genes have been investigated, and resultshave shown a very high variability in geneassociation with T1D [31] .Researchers have not yet identified all the genemutations that put a person at risk for T1D. Even ifthey did know all of the mutations, researchers findthat people with low risk genes (DR2, DR5, longVNTR) can still develop T1D. So a genetic testmight identify people as negative who eventuallygo on to develop diabetes. Even if a genetic testreveals that a person is at high risk, doctors have nocourse of action for preventing diabetes. Instead,the test may simple add stress to the family.Genetic studies have revealed not only differentcandidate genes for the development of T1D ind i ff e rent population, but also gene variabilitywithin the same population. Thus, the evidence forthe involvement of several genes rather than asingle gene in the genesis of T1D appears to dim theprospects for possible use of gene therapy in thenear future [31] .The combination of susceptibility genes ande n v i ronmental factors may initiate a diseaseprocess that is associated with a formation of anautoimmune response to the insulin-pro d u c i n gcells. This autoimmune reaction is reflected by thepresence of antibodies against prominent antigensin the pancreatic β-cells [22] .

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June 2007KUWAIT MEDICAL JOURNAL 115type 1 diabetes and linkage to chromosome Xp in MHCHLA-DR3 positive patients. Nat Genet 1998; 19:301-302.82. Stene LC, Ulriksen J, Magnus P, et al. Use of cod liver oilduring pregnancy associated with lower risk of type 1diabetes in the offspring. Diabetologia 2000; 43:1093-1098.83. Hypponen E, Laara E, Reunanen A, et al. Intake of vitaminD and risk of type 1 diabetes: a birth-cohort study. Lancet2001; 358:1500-1503.84. Mathieu C, Badenhoop K, Vitamin D and type 1 diabetesmellitus. Trends in Endocrinology and Metabolism 2005;16:261-266.85. Lamire JM, Immunomodulatory role of 1,25 dihydroxyvitaminD3. J Cell Biochem 1992; 49:26-31.86. Hitman GA, Mannan N, McDermott MF, et al. Vitamin Dreceptor gene polymorphisms influence insulin secretion inBangladeshi Asian. Diabetes 1998; 47:688-690.87. Bouqbis L, Akhayat O, Garchon HJ, et al. TNFA-TNFBhaplotypes modify susceptibility to type 1 diabetes mellitusindependently of HLA class II in a Moraccan population.Tissue antigens 2003; 61:72-79.88. Baylor College of Medicine. New gene associated with type1 diabetes. 2004. http://www. s c i e n c e d a i l y. c o m / re l e a s e s/2004/07/040723094436.htm89. Kristiansen OP, Karlsen AE, Larsen ZM, et al. Identificationof a type 1 diabetes-associated CD4 promoter haplotypewith high constitutive activity. Scand J Immunol 2004;59:582-591.90. Yoon JW, Austin M, Onodera T. Isolation of a virus from thepancreas of a child with diabetic ketoacidosis. N Eng J Med1979; 30:1173-1179.91. Hee-Sook J, Ji-Won Y. A New Look at viruses in Type 1Diabetes. Diabetes Metabolism Research and Review 2002;19:8-31.92. Atkinson MA, Bowman MA, Campbell L, et al. Cellularimmunity to a determinant common to glutamate decaboxylaseand coxsackie virus in insulin-dependent diabetes. J ClinInvest 1994; 94:2125-2129.93. Heino L, Lonnrot M, Knip P, et al. No evidence of abnormalregulation of antibody response to coxackie virus B4antigen in prediabetic children. Clin Exp Immunol 2001;126:432-436.94. Gerstein HC. Cow’s milk exposure and type 1 diabetesmellitus: a critical overview of the clinical literature .Diabetes Care 1994; 17:13-19.95. Atkinson MA. Thirty years of investigating theautoimmune basis for type 1 diabetes: Why can’t weprevent or reverse this disease? Diabetes 2005; 54:1253-1263.

KUWAIT MEDICAL JOURNAL June 2007ABSTRACTObjectives: To study the prevalence of hypertensionamongst young and middle aged Kuwaiti citizensattending the primary health care centers and to find itsrelationship with risk factors such as age, gender,smoking, body mass index and exerciseDesign: A cross - sectional study carried out to evaluatenon-labeled hypertensive individuals attending primaryhealth centers for other medical problems.Setting: Two primary health care centers were chosenrandomly from each health region. Data collection sheetwas produced and distributed to primary health carephysicians in the chosen health centers.Original ArticlePrevalence of Hypertension in Young and Middle AgedKuwaiti Citizens in Primary Health CareFotooh Al-Jarky 1 , Najat Al-Awadhi 2 , Hamdyia Al-Fadli 3 , Abdul Salam Tawfic 4 ,Abdul Razzak Al-Sebai 5 , Mahdi Al Mousawi 6Primary Health Care Khaldyia Clinic 1 , Salmiya West Clinic 2 , Ahmadi Clinic 3 ,South Jleeb Al-Shuyokh Clinic 4 , Al Qasser Clinic 5 , Salmiya Clinic 6 , KuwaitKuwait Medical Journal 2005, 37 (2):116-119KEYWORDS: hypertension, prevalence, primary health careSubjects: Eight hundred and sixty patients attending theclinic and twenty practitioners were included in thestudy.R e s u l t s :P revalence of hypertension was found to be 6.4%in males and 6.1% in females. Influence of risk factorssuch as age, body mass index, exercise and smoking wasstatistically significant whereas gender differences werenot significant.Conclusion: Our study emphasizes the importance ofearly detection of hypertension among young andmiddle aged patients and adopting an effective policy onhealth education regarding risk factors at the primaryhealth care center level.INTRODUCTIONHypertension is a common health problem indeveloped countries, and its prevalence is probablyincreasing in nations of the developing world. Alsoknown as the “silent killer”, it may exist forp rolonged periods in the individual withoutsymptoms and may manifest only after causingserious irreversible pathology and complications [ 1 , 2 ] .Hypertension has a proven association with highmortality and morbidity from card i o v a s c u l a r,cerebrovascular and renal disease [3,4] . Its control willsignificantly lower these diseases [5-8] .Hypertension is prevalent in about 20% of adultpopulation in most developed countries [ 9 ] . InKuwait, the most recent data on hypertensionshowed a prevalence rate of 26.3% in 1999 [10] . Allover the world there are few studies about thep revalence of non-labeled hypertension. Manystudies showed a significant relationship betweenhypertension and risk factors such as age, bodymass index, smoking and physical inactivity. Theprimary health centers have the best opportunityfor early detection of hypertension. The aim of thisstudy was to detect the prevalence of undiagnosedhypertension among the younger age group and tofind its relationship with risk factors like age,gender, body mass index, smoking and exercise.SUBJECTS AND METHODSA c ross sectional study was carried out toestimate the prevalence of undiagnosed hypertensionin the five health regions of Kuwait. Two primaryhealth care centers were chosen randomly fromeach health region.A sample of 860 non-labeled individuals wascollected between January 2002 and March 2002. Averbal consent was obtained from the participantswho attended the centers for complaints other thanhypertension. Those who were known hypertensives,had renal impairment, were pregnant or weretaking medication that could cause secondaryhypertension were excluded from the study.Patients with severe or malignant hypertensionwere referred immediately to the medical casualty.Earlier, a pilot study of 50 participants was carriedout and the questionnaire was suitably modifiedfor proper data collection.METHODMeasurements of blood pressure were madeAddress Correspondence to:Dr. Fotooh Al Jarky, RCGP (UK), Primary Health Care, Khaldyia Clinic, Kuwait. Tel: (965) 4834065, Fax: (965) 4817538 E-mail:alalsl@hotmail.com

June 2007KUWAIT MEDICAL JOURNAL 117Table 1: Characteristics of the study sample (n= 860)Factors No. of Patients %SexMale 419 48.7Female 441 51.3Age (Years)21-30 247 28.731-40 307 35.741-50 177 20.651-60 98 11.461-70 31 3.6BMINormal < 25 277 32.2Over Weight (25-30) 315 36.6Obese (31-35) 154 17.9Morbid obese > 35 114 13.3SmokingYes 658 76.5No 202 23.5ExerciseYes 233 27.1No 627 72.9a c c o rding to the recommendations of BritishHypertension Society guidelines for hypertensionmanagement (1999), in order to standardize theexamination of the target subjects [ 11 - 1 3 ] . Measure m e n t sbegan after the subject had rested for five minutesand had avoided smoking and intake of caffeineduring the last half an hour. The patients wereseated in a comfortable chair with their backssupported and arms bared and supported at heartlevel. An appropriate cuff size was used to ensureaccurate measurement. The bladder within the cuffencircled at least 80% of the upper arm. Standardbladder measured 12-13 cm X 35 cm and weinflated the cuff to 30 mmHg above pulse occlusion.The systolic blood pressure was recorded at the firstappearance of a sound and the diastolic bloodpressure was recorded at the disappearance of thesound. Blood pressure was measured twice at twominuteintervals and if the readings differed bymore than 5 mmHg, an additional reading wastaken. We used calibrated mercury sphygmomanometers.Hypertension was diagnosed as per thecriteria laid down by the World Health Organization -International Society for Hypertension (1999). Apatient was labeled hypertensive if an average ofthree readings showed the systolic blood pressureto be 140 mmHg or greater and the diastolic bloodpressure to be 90 mmHg or greater.Data Collection:Data collection sheet included information suchas civil ID, (age, occupation and gender), presenceof life style risk factors like smoking, physicalinactivity or regular exercise (mild physical activityfor 30 minutes at least 3-4 times a week) andTable 2: The prevalence of hypertension and its co-relation withrisk factorsRisk Factors Hypertension p valueYesNon = 60 (7 %) n = 800 (93%)Age21-30 2 0.23 245 28.5 0.00031-40 14 1.62 293 34.241-50 25 2.90 152 17.851-60 13 1.51 85 9.961- 70 6 0.69 25 2.9Total 60 6.95 800 93.1BMI:normal (BMI 35 16 1.96 98 11.4Total 60 6.96 800 93.1ExerciseYes 5 .58 288 26.51 0.001No 55 6.39 572 66.51Total 60 6.97 800 93.02SmokingYes 51 5.93 193 22.44 0.000No 9 1.04 607 70.58Total 60 6.97 800 93.02 0.000measurement of height and weight and calculationof body mass index (BMI). For height and weightm e a s u rement, we used the Detecto-Scale Instru m e n t ,which was calibrated once a day before use.Statistical Analysis:Data was collected and analyzed using thestatistical package for social sciences (SPSS) version11. The chi-square test was used to comparecategorical variables and a p ≤ 0.005 was used as thecut-off level for statistical significance.RESULTSTable 1 shows the characteristics of patients inthe study sample. Male and female patients werealmost equally distributed in the samplepopulation (51.3%, 48.7% respectively). More thanone third of the study sample aged from 31-40 years(35.7%). About two thirds (68.8%) of the studysample had a BMI > 25 (overweight 36.6%, obese17.9% and morbidly obese 13.3%). Almost threequarters of the study sample were smokers and didnot exercise regularly (76.5%, 72.9% respectively).Table 2 shows the percentage of hypertensionwithin the study sample and its correlation withrisk factors. The prevalence of undiagnosedhypertension in the sample was 7%. In the currentstudy, a significant relationship between prevalenceof undiagnosed hypertension and BMI was foundin both sexes (p < 0.001). The prevalence ofhypertension in individuals with high BMI

118Prevalence of Hypertension in Young and Middle Aged Kuwaiti Citizens in Primary ..... June 2007(overweight 2.7%, obese 1.7% and morbid obese1.9%) was more than individuals with normal BMI(0.7%).The study also showed that regular exercise hada significant influence on the prevalence ofhypertension (p < 0.01). Blood pre s s u re was markedlyhigh in individuals who were not exerc i s i n gregularly. Out of 72.9% who were not regularlyexercising, 6.4% were hypertensive. Smoking hadsignificant relationship with the prevalence ofundiagnosed hypertension (p < 0.01).DISCUSSIONThis study showed that the re l a t i o n s h i pbetween age and hypertension was bell shaped,high blood pressure being more prevalent in the 41-50 year age group. Blood pressure consistentlyincreases with age in most populations all over theworld, modified only by genetic and environmentalfactors [14,15] . As more is learned about the naturalhistory of the development of atherosclerosis, it isclear that the process, which results in morbidityand mortality in adults, has its origin in childhoodand adolescence. Traditional risk factors, such ashypertension and dyslipidaemia, are important inthe early stages of the process. This supports therecommendation of screening the young adultpopulation for hypertension [16] . Similar to our study,other studies showed that there is significantrelationship between hypertension and smoking.Smokers should be counseled repeatedly andunambiguously to stop smoking. Patients whocontinue to smoke may not receive full protectionagainst card i o v a s c u l a r, cerberovascular andpulmonary diseases [12,13] . The study also showedthat there is significant relationship between BMIand hypertension. A BMI of ≥ 25 correlates closelywith increased blood pressure [12] . Other studies alsosupport the fact that weight gain is associated withincreased blood pressure and increased incidenceof hypertension [18,19] . In general, being overweight isassociated with a two to six-fold increase in the riskof developing hypertension [20] . Clinical trials haveproved that weight loss is effective in the primaryp revention of hypertension as well as in thereduction of both systolic and diastolic bloodpressure in patients with normal or high bloodpressure [20] . Several epidemiological studies haveshown an association between BMI and bloodp re s s u re in normal and overweight patients.Weight loss has been recommended for the obesehypertensive patient and has been shown to be themost effective non-pharmacological tre a t m e n tapproach [21] . The deposition of excess fat in theupper part of the body (a waist circ u m f e rence of≥ 34 inches in women, or ≥ 39 inches in men) isassociated with the risk of hypertension, dyslipidemia,diabetes and CHD mortality [ 2 2 , 2 3 ] . This, studyshowed that there is a significant re l a t i o n s h i pbetween hypertension and exercise. It has shownthat regularly performed aerobic exercise significantlylowers blood pressure in patients with essentialhypertension [23] . Mild to moderate intensity exercisemay be more effective in lowering blood pressurethan high intensity exerc i s e [ 2 3 ] . Sedentary individualshave a 20 to 50% increased risk of developinghypertension [24] . Regular exercise for 30 minutesfour times per week can result in a 5-10 mmHgreduction in blood pre s s u re in hypertensivepatients and up to 3 mmHg reduction in the bloodpressure of normal people [25] . So the study findingsreveal the necessity for population-wide primaryprevention of hypertension, as well as increasingeffort to detect unfavorable blood pressure levels inteenagers, young adults and others [26-29] .CONCLUSIONIn conclusion, our study showed an incidence of7% for undiagnosed hypertension. There was asignificant influence of risk factors such as higherBMI, lack of exercise and smoking. An educationalp rogram encouraging life style modification ishighly recommended. Also, there is a need toi n c rease the awareness of primary health carephysicians towards the importance of opportunisticscreening, aiming at early detection of undiagnosedhypertensive individuals. Physicians should bemotivated to provide guidance to the populationregarding healthy life style practices that can helpprevent and control hypertension.ACKNOWLEDGEMENTThe authors would like to express their deepappreciation and thanks to Mrs Reem Alsahali forhelping us with the data analysis.REFERENCES1. Abolfotouh MA, Abu-Zeid HA, Abdel Aziz M, et al.Prevalence of hypertension in Saudi Arabia. East MediterrHealth J 1996; 2:211-218.2. Houston MC. Hypertension strategies for therapeuticintervention and prevention of end-organ damage. PrimCare 1991; 18:713-753.3. Misra A. Risk factors for athero s c l e rosis in youngindividuals. J Cardiovasc Risk 2000; 7:215-229.4. 1999 World Health Organization-International Society ofHypertension: Guidelines for the Management ofHypertension. Guidelines Subcommittee. J Hypertens 1999;17:151-183.5. Pocock SJ, McCormack V, Gueyffier F, Boutitie F, FagardRH, Boissel JP. A score for predicting risk of death fromcardiovascular disease in adults with raised blood pressure,based on individual patient data from randomizedcontrolled trials. BMJ 2001; 323:75-81.6. Palatini Pkl, Firgo G, Vriz O, et al. Early signs of cardiacinvolvement in hypertension. Am Heart J 2001; 142:1016-1023.

June 2007KUWAIT MEDICAL JOURNAL 1197. Palmieri V, Watchtell K, Gerdts E, et al. Left ventricularfunction and hemodyamic features of inappropriate leftventricular hypertrophy in patients with systemichypertension: The LIFE Study. Am Heart J 2001; 141:784-791.8. Glasser SP. Hypertension syndrome and cardiovascularevents. High blood pre s s u re is only one risk factor.Postgrad Med 2001; 110:29-36.9. B rown MJ, Hydock S. Pathology, epidemiology anddiagnosis of hypertension, Drug 2000; 2:39-40.10. El-Reshid K, Al-Owaish R, Diab A. Hypertension inKuwait: the past, present and future. Saudi J Kidney DisTransplant 1999; 10:357-364.11. British Hypertension Society Guidelines for HypertensionManagement 1999: summary. BMJ 1999; 4:319-633.12. Carghron RF, Smith EL, McClellan-Holm E. Prevention,detection, evaluation and treatment of high blood pressure.South Med J 2001; 94:1074-1095.13. Caughron KF, Smith EL, et al. The six report of the jointcommittee on prevention, detection, evaluation andtreatment of high blood pressure. Arch Intern 1997; 157:2413-2445.14. Daniels SR. Cardiovascular diseases risk factors anda t h e ro s c l e rosis in children and adolescents. Curre n tAtherosclerosis Reports 2001; 3:479-485.15. Riley CK, Terezhaolmy G T. The patient with hypertension.Quintessence International 2001; 32:671-690.16. Logan AG. Screening for hypertension in young and middleaged adults. Canadian task force on preventive health care2002: 217-220.17. Okubo Y, Miyamoto T, Suwazono Y, Kobayashi E, NogawaK. An association between smoking habit and bloodpressure in normotensive Japanese men. J Hum Hypertens2002; 16:91-96.18. Abdul-Rahim HF, Abu-Rmeilehnu NM, Husseini A ,Holmboe OH, Sen G, Jarvell J, Bjertness E. Obesity andselected co-morbidities in an urban Palestinian population.Int J Obes Relat Metab Disord 2002; 269:58-64.19. Mertens IL. Van Gaal LF. Overweight, obesity, and bloodpressure: the effects of modest weight reduction. ObesityResearch 2000; 8:270-278.20. Dickey RA, Janick JJ. Lifestyle modifications in thep revention and treatment of hypertension. EndocrinePractice 2001; 7:392-399.21. Patel JC. Obesity effective and safe management, Indian JMed Sci 2000; 54:499-507.22. Torgerson JS, Sjostrom L. The Swedish obese subjects. Int JObes Relat Metab Disord 2001; 25:1-4.23. Kokikinos PF, Papademetriou V. Exercise and hypertension.Coron Artery Dis 2000; 29:99-102.24. Holmwood C. Over weight and hypertensive. Aust FamPhysician 2000; 29:559-563.25. Ohkubo T, Hozawa A, Nagatomi R, et al. Effect of exercisetraining on home blood pressure values in older adults. Arandomized controlled trial. J Hypertens 2001; 19:1045-1052.26. Deedwania P. Hypertension. ACC Scientific session 2000;3:33-55.27. He J, Bazzano LA. Effects of lifestyle modification ontreatment and prevention of hypertension. Curr Opin inNephrol & Hypertens 2000; 9:267-271.28. Davis MM, Jones DW. The role of lifestyle management inthe overall treatment plan for prevention and managementof hypertension. Semin in Nephrol 2002; 22:35-43.29. Kaplan NM. Guidelines for the management ofhypertension. Can J Cardiol 2000; 16:1147-1152.

KUWAIT MEDICAL JOURNAL June 2007Original ArticleThe Economic Impact of Smoking on the Health System inKuwaitAsia S Al Hamdan 1 , Sana M Al Ali 1 , Sana M Al Mansour 2 , Adel M Al Terkit 3 , Majed A Radwan 31Primary Care, Al-Saqer Health Clinic, Capital Health Region, Kuwait2Primary Care, Al-Yarmok Health Clinic, Capital Health Region, Kuwait3Primary Care, Preventive Health Department, Capital Health Region, KuwaitABSTRACTObjective: To estimate some of the cost and the economicimpact of smoking on health services in KuwaitDesign: A cross-sectional surveySetting: Al-Saqer and Al-Yarmok Primary Care Centers,KuwaitSubjects: Two thousand two hundred and sixteen (2216)male persons were enrolled in this study.Intervention: Each patient was interviewed by a traineddoctor.Main Outcome measures: The incidence of upper andlower respiratory tract system symptoms with currentKuwait Medical Journal 2007, 39 (2):120-125smokers compared to non-smokers.Results: Our study showed a high prevalence of smokingin Kuwait among adult males aged >18 years (40.6 %). Italso showed a high incidence of both upper and lowerrespiratory tract system symptoms with current smokerscompared to non-smokers (67.5 and 76.9% respectivelycompared to 32.5 and 23.1%).C o n c l u s i o n : Smoking increases health care costs byincreasing the number of clinic visits due to respiratoryillness thereby increasing health services utilization andleading to additional societal burden.KEYWORDS: economic, health care cost, health service utilization, smokingINTRODUCTIONThe smoking epidemic has become a matter ofworld-wide concern. It is generally agreed thattobacco use, particularly smoking, poses anenormous public health problem and is stronglyassociated with an increased morbidity andmortality [1] . It remains the number one cause ofpreventable diseases in many countries and theforemost reason for the four primary causes ofdeath (heart diseases, cancer, emphysema andstroke) [2] .It is widely acknowledged that cigare t t esmoking is strongly associated with incre a s e dmorbidity and mortality due to a number ofdiseases, the most recognized of which is lungc a n c e r [ 3 ] . In addition, the various substancescontained in cigarette smoke are partly responsiblefor malignant tumors of the oral cavity and thepharynx. They are a main risk factor for myocardialinfarction, cerebral thrombosis, arteriosclerosis andchronic obstructive pulmonary diseases such asb ronchitis and emphysema [ 4 ] as compared topersons who have never smoked. The averagedecrease in life expectancy has been estimated to be3 - 8 years depending on smoking habits [5] .On reviewing the literature on smoking, wefound that there was a direct link between smokingand various diseases particularly re s p i r a t o r yillnesses. It increases the incidence and the severityof both upper and lower respiratory tractinfections, including acute bronchitis, asthma andcommunity-acquired pneumonia and more severec h ronic lower respiratory tract diseases. In addition,it is estimated that short-term hospital days areincreased by more than 30 percent for diseaseslinked to smoking. Tobacco is a major contributorto these diseases, which now account for more thanhalf the disease burden on countries. This alarmingincreases threatens to undermine their economicand social development [4] .A c c o rding to World Health Org a n i z a t i o n(WHO), there are about 1.1 billion smokersw o r l d w i d e [ 6 ] . The vast majority - 800 millionsmokers - is in developing countries; 700 million ofthese smokers are men. The use of tobaccocurrently account for three million deaths each yearworldwide [7] . The global health care cost resultingfrom tobacco use exceed $200 billion a year - morethan twice the current health budgets of alldeveloping countries combined [8] . It is predictedthat by the 2020s there will be about 10 millionrelated deaths annually worldwide [9] .Address correspondence to:Dr. Asia S. AL Hamdan, Family Physician, Ministry of Health, Primary Health Care, Al-Saqer Clinic, Kuwait. Tel/Fax: (965) 2519490, E-mail:asiaalhamdan@hotmail.com

June 2007KUWAIT MEDICAL JOURNAL 121Cigarette smoking is the nations’ leading causeof premature mortality, and is responsible for onethirdof all deaths among working - age Americans.Smoking cigarettes is both psychologically andphysiologically addictive. Careless smoking alsocan cause severe burn injuries and death. Many ofthe adverse effects of smoking occur in secondhand(passive) smokers [10] .Twenty-three percent of adults aged 18 years orolder smoke cigarettes. Over 400,000 adults diefrom tobacco-related diseases each year [11] . Smokingaffects not only the tobacco user but also those nearthe smoker, such as family, friends, co-workers andunborn children. A p p roximately 24 billion packagesof cigarettes are purchased annually. In June 2002,the International Agency for Research on Cancerconcluded that involuntary smoking (exposure tosecondhand or “environmental” tobacco smoke)was carcinogenic to humans [12] . National expendituresattributable to cigarette smoking surpass $ 75billion in medical costs plus $80 billion in indirectcosts [13] .The Food and Agricultural Organization of theUnited Nations (FAO) estimated that tobaccoconsumption in developing nations was increasingat a rate of 1.9 percent during 1995 - 2000 [14] . One ofthe reasons which explain this rise is lack ofawareness of health risks associated with tobaccouse, particularly the fact that there is approximatelya 25 - 30 year lag time between the onset ofpersistent tobacco use and the actual deathsattributable to smoking.S m o k i n g - related diseases re p resent an enormouseconomic burden on the health care system. Inaddition to the traditional burden of communicablediseases, developing countries today are faced witha huge increase in non-communicable diseases,mental illness and violence and injuries. Smokingcosts the national health services (NHS) approximately$ 1.5 billion a year for treating diseasescaused by smoking. This includes the cost ofhospital admissions, general practitionerconsultations and prescriptions. In 1997-98, 364,200people were admitted to NHS hospitals to betreated for diseases related to smoking. On anaverage, they occupy 9,500 hospitals bed per yearevery day [15] .In Kuwait, smoking prevalence among adultmales (18 - 60 yrs) was 34.4% in 1998 [16] whilesmoking prevalence among youth (10 -18yrs) wasreported as 23.1% [ 17 ] . Our survey was done toestimate the prevalence of smoking in Kuwait andits economic cost on the health care system.SUBJECTS AND METHODSWe conducted a cross-sectional survey amongpersons seeking medical care at Al-Saqer specializedhealth center (which served Al-Adeiyliyah and Al-Faiha areas) and Al-Yarmok primary health center(which served A l - Yarmok and Qurtoba are a s ) .These were selected as the setting for our study. Wedecided to enroll all male Kuwaiti and non Kuwaitipersons ∆ 18 years coming to these health centers.The survey collected information on socioeconomiccharacteristics (age, marital status, levelof education, employment and nationality),p resence of some chronic diseases such ashypertension, diabetes, cardiovascular diseases,chronic pulmonary diseases, bronchial asthma andsmoking status.Respondents were classified as current smoker,former smoker and never smoker.A current smokerwas defined as anyone who had smoked more than100 cigarettes in his lifetime and continued tosmoke at least one cigarette daily. A former-smokerwas one who had smoked more than 100 cigarettesin his lifetime but no longer smoked. A neversmokerwas one who had never smoked or hadsmoked fewer than 100 cigarettes in his lifetime [18] .Current smokers were asked about onset of regularsmoking, kind of smoking, the number ofcigarettes.All respondents were asked about: reason forhealth center visit, date of last visit to health centeror hospital and the reasons for those visits. We alsocollected data about number of visits to privateclinics as well as pharmacies seeking medical careduring last six months.Data were collected through January - February2003. The number of cases collected during thisperiod was deemed to be enough for analysis(consensus sample). The questionnaire was pilottested on a random sample of one hundred personsand some of the questions were modified before itwas formally used. For the sample, one hundredq u e s t i o n n a i res were distributed and self administere dand a team of trained doctors interviewed Kuwaitiand non-Kuwaiti males age > 18 yrs. The responserate was 100%.In the actual study, two thousand two hundredand sixteen males were interviewed by trainedphysicians and respondents were told that theinformation obtained would be confidential andused only for statistical purposes to minimize nonresponseand under-reporting.Case definition for the illnesses presented bypatients: patients were classified according todiagnosis code of international classification ofdiseases (ICD-10-CM) after confirming the diagnosisfrom the attending physician (Table 1).Data was analyzed using SPSS statisticalp rogram and descriptive statistics includingfrequencies, mean and standard deviation wereused to describe the study findings. The association

122The Economic Impact of Smoking on Health System in Kuwait June 2007Table 1: International classification of diseases andrelated health problems (tenth revision)Cardiovascular System Diseases (I 00-99)I30.9 Acute pericarditisI20.9 Angina PectorisI49.9 ArrhythmiaI70.0 AtherosclerosisI48.0 Atrial fibrilationI42.9 CardiomyopathyI25.9 Chronic ischemic heart disease (IHD)I50.0 Congestive heart failure (CHF)I50.9 Heart FailureI10.0 HypertensionI95.9 HypotensionI50.1 Left ventricular failure (LVF)I34.0 Mitral valve prolapseI21.9 Myocardial Infarction (MI)I73.9 Peripheral Vascular DiseaseI26.9 Pulmonary EmbolismI00.0 Rheumatic FeverI09.9 Rheumatic Heart DiseaseI38.0 Valvular Heart DiseaseUpper /Lower Respiratory (J 00-99)J20.9 Acute bronchitisJ04.0 Acute laryngitisJ35.9 Adenoid EnlargementJ30.4 Allergic RhinitisJ45.9 AsthmaJ47.0 BronchiectasisJ21.9 BronchiolitisJ42.0 Chronic BronchitisJ81.0 Pulmonary oedemaJ00.0 Common ColdJ05.0 CroupJ43.9 EmphysemaJ05.1 EpiglottitisJ33.9 Nasal PolypJ01.0 PneumoniaJ93.8 PneumothoraxJ01.9 SinusitisJ02.9 Sore Throat, PharyngitisJ03.0 TonsillitisJ06.9 Upper Respiratory Tract Infectionsbetween two discrete variables was tested by chisquaretest. A p value of < 0.05 was consideredsignificant. The 95% confidence intervals (CI)around rates were calculated assuming a binomialdistribution.RESULTSA total of 2216 male persons, aged 18 years andabove were enrolled in the survey. 74.5% of themwere Kuwaiti, their mean age was 39 years, 79%were married and 62% were working as officers.R e g a rding educational status, 25.4% hadsecondary school and 24.7% had university leveleducation. 40.6% were current smokers, 13.8% wereex-smokers and 45.6% never smokers. 12% of themhad started smoking at the age of 20 years. Amajority (79.8%) of the respondents smokedTable 2: Smoking status and the incidence of chronicdiseaseChronic diseasesSmoking statusCurrent Non Total p valuen (%) n (%)Diabetes mellitus 61 (51.3) 58 (48.7) 119 p = 0.7 (NS)Hypertension 64 (40.3) 91 (57.2) 155 p = 0.003Cardiovascular disease 9 (40.9) 13 (59.1) 22 p = 0.3 (NS)Chronic pulmonary disease 11 (91.7) 1 (8.3) 12 p < 0.001Bronchial asthma 52 (51) 50 (49) 102 p = 0.88 (NS)Others 147 (47) 166 (53) 313 p = 0.15 (NS)None 518 (45.2) 627 (54.8) 1145 p < 0.001Chi square = 14.39, Degree of Freedom = 6, p value = 0.03Table 3: Smoking status and current symptomCurrent SymptomSmoking statusCurrent Non Totaln (%) n (%)General symptom 158 (36.6) 273 (63.3) 431Upper respiratory 328 (52) 302 (48) 630Lower respiratory 52 (67.5) 25 (32.5) 77Gastro-intestinal 82 (49.7) 83 (50.3) 165Upper & lower respiratory 30 (76.9) 9 (23.1) 39More than one symptom 250 (43.9) 319 (56) 569Chi square = 54.64 Degree of freedom = 5 p value < 0.001 :c i g a rette and 45.8% smoked one packet (20 cigare t t e s )per day.The result of this study was a comparisonbetween current smokers and non-smokers. Exsmokerswere excluded from that comparison.About 6.5% of respondents had diabetesmellitus, 8.6% had hypertension, 1.5% had card i o v a s -cular disease, 0.6% had chronic pulmonary diseaseand 5.5% had bronchial asthma while 57.3% had nochronic illness.The association between smoking status and theoccurrence of chronic diseases was almost similarbetween smokers and non-smokers. An interestingfinding was that smoking expresses the overallassociation with chronic diseases at a p value =0.03. Fisher’s Exact Test was used in case of chronicpulmonary diseases (as the total number was only12 cases) to compare p value association withsmokers and non-smokers. It showed considerablesignificant association (p = 0.001) as shown in Table 2.On reviewing the current symptom (i.e. thereason for visiting the health center on the day ofthe interview) with smoking status, once againthere was high percentage of affliction of both partsof respiratory systems; the percentage of lower andcombined upper and lower respiratory complaintswas 67.5 and 76.9% in current smokers compared to32.5 and 23.1% in non-smokers respectively asshown in Table 3. The difference was statistically

June 2007KUWAIT MEDICAL JOURNAL 123Table 4: Symptoms during the visit to Health Centerwith Smoking StatusSymptom of last visitSmoking statusCurrent Non Totaln (%) n (%)General symptom 139 (35.2) 256 (64.8) 395Upper respiratory 399 (54.7) 330 (45.3) 729Lower respiratory 73 (64.6) 40 (35.4) 113Gastro-intestinal 76 (49.4) 78 (50.6) 154Upper &lower respiratory 16 (80) 4 (20) 20More than one symptom 203 (40.1) 303 (59.9) 506Table 5: Smoking status and the number of visits tohealth center during last six monthsSmoking statusNo. of visits current non Total p value1 - 3 292 521 813 p < 0.0014 - 6 236 202 428 p = 0.0267 - 9 156 52 208 p < 0.00110 - 12 65 21 86 p < 0.001> 12 25 13 38 p = 0.012Chi square = 72.28, Degree of freedom = 5, p value < 0.001Table 6: Smoking status and the number of hospital orprivate clinic visits during last six monthsSmoking statusNo. of visits current non Total p value1 - 2 65 45 110 p = 0.013 - 4 32 14 46 p < 0.0015 - 6 10 6 16 p=0.2(NS)> 7 6 1 7 p = 0.03significant (p < 0.001).Regarding the symptoms at last visit (not theday of the interview) to health center: 64.6% ofcurrent smokers had visited the health center forlower respiratory system symptoms and this wassignificantly higher than the non-smoker group(34.3%, p < 0.001, Table 4). 80% of current smokershad visited the health center for symptoms of bothupper and lower respiratory systems in contrast toonly 20% non-smokers and this was statisticallyhighly significant (p = 0.001).Number of visits to health center during the lastsix months were grouped into intervals (Table 5) , ap value calculated for each group and Normal ZTest used for testing the significance between twoproportions which was highly significant (p

124The Economic Impact of Smoking on Health System in Kuwait June 2007health (2001-2002), the average cost of single visit toGP clinic was equal to 5 KD, while a hospitalcausality visit costs 18 KD. Hospital out-patientvisit costs 40 KD while a hospital admission for oneday costs on an average about 80 KD. Our studyshowed more frequent visits by smokers than nonsmokersto GP clinic and hospitals. 88.9% of currentsmokers had 11 visit per six months to the GP clinicwhich can be considered a burden on health systemservices in a small country like Kuwait with thehigh p revalence of smokers (40.6%). This studyi d e n t i f i e s that burden of smoking on our societywhich consists of these medical costs plusproductivity losses attributable to smoking-relatedmorbidity, disability and premature mortality.In the United States, each year approximately400,000 deaths are attributed to cigarette smokingand costs associated with morbidity attributed tosmoking are substantial [22] . It is estimated that 60%of the direct health care costs in the US go to treattobacco related illnesses [23] .As regards the number of visits to the healthcenter during last six months, we found that thehigher the number of visits higher is the re l a t i o n s h i pto current smokers. This is an indication thatcurrent smokers are using health services moreoften than non-smokers. This may be explained bythe fact that smoking causes chronic healthproblems requiring more visits. Treating tobaccodependence produces a strong return oninvestment by reducing substantially the high costof treating chronic respiratory diseases, myocardialinfarctions and cancers caused by smoking [24] .There was no big difference between smokersand non-smokers when asked about symptomsduring their last visit to the hospital, except forlower respiratory tract symptoms. This was higherin smokers than non-smokers. This is consistentwith many studies that emphasize smoking as acausative agent for respiratory tract illnesses [1,4,21,25] .It was obvious throughout this study thatnumbers of visits to hospitals or private clinics ishigher for current smokers than for non-smokers.We tried to obtain information on all kinds ofhealth seeking behaviour, either at a government orprivate facility, to know the frequency of visits sothat we could estimate the cost of smoking and itsburden either on individual or national level. Wefound a higher number of visits by current smokersthan non-smokers which reflects an additionaleconomic burden .Comparing current smokers with non-smokersas re g a rds the number of visits to a specialpharmacy to seek medications without prescriptionduring last six months, there was insignificantdifference between the two groups.In most countries the re s o u rces devoted tohealth care are increasing and diseases caused bysmoking are a major reason for this increase. Theemphasis of public health policies tends to bestrongly on curative care. Less emphasis is placedon preventive programs which are often viewed asless urgent and less important because they are lessspecific and are focused on groups withinpopulation who may still be healthy. Althoughthese can make a major impact on health educationand economic strategies, these strategies are moreeffective when used in combination [26] .Countries that adopted comprehensive controlson the use of tobacco indoors, high taxes on tobaccoproducts, smoking cessation programs and healtheducation have had considerable success inreducing costs of health care [27] .The smoking-attributable costs described instudies are underestimated for two reasons [28] . First,the cost estimates do not include all direct medicalcosts attributable to cigarette smoking (e.g., burncare resulting from cigarette-smoking-related firesand costs associated with diseases caused bye x p o s u re to environmental tobacco smoke).Second, the indirect costs of morbidity (e.g., due towork loss and bed-disability days) and loss inproductivity resulting from the premature deathsof smokers and former smokers was not includedin these estimates. This suggests that the totaleconomic burden of cigarette smoking is more thantwice as high as the direct medical costs.CONCLUSIONOur survey showed a high prevalence ofsmoking among adult males >18 years old (40.6%).Smokers had more visits to health centers forrespiratory conditions than non smokers leading toan enormous economic burden on the health careservices utilization, thereby increasing health carecost. Smoking cessation programs should bestrengthened to decrease number of smokers in thecommunity and thus decrease illnesses related tosmoking and the overall societal burden.REFERENCES1. Hoffman LH, Strutton DR, Stang PE, Hogue SL. Impact ofSmoking on Respiratory Illness-Related Outpatient VisitsAmong 50-75 Years-Olds in the United States. Clin Ther2002; 24:317-324.2. Thomas LA. Sending unhealthy environments up in smoke.Mich Health Hosp 2002; 38:20-21.3. Doll R, Hill AB. Study of the aetiology of carcinoma of thelung. BMJ 1952; 2:1271-1286.4. Ruff LK, Volmer T, Nowak D, Meyer A. The economicimpact of smoking in Germany. European RespiratoryJournal 2000; 16:385-390.5. West RR. Smoking: its influence on survival and causes ofdeath. J Coll Physicians Lond 1992; 26:357-366.

June 2007KUWAIT MEDICAL JOURNAL 1256. World Health Organization. Tobacco or health: a globalstatus report. WHO, Geneva, 1997, pp 16-19.7. Venkat Narayan KM, Chadha SL, Tandon HR, Shekhawat S,Fernandes RJ, Gopinath N. Prevalence and patterns ofsmoking in Delhi: cross sectional study. BMJ 1996; 312:1576-1579.8. Lopez PR, Boreham AD, Thun JM, Health C. Mortality fromsmoking in developed countries, 1950-2000. Oxford: OxfordUniversity press, 1994.9. Barnum H. The economic burden of the global trade intobacco. Tobacco Control 1994; 3:358-361.10. Nair AK, Brandt EN. Effect of smoking on health care cost.J Okla State Med Assoc 2000; 93:245-250.11. U.S. Department of Health and Human Services. Reducingtobacco use: a report of the surgeon general. Atlanta, GA:Office on Smoking and Health, 2000.12. AIthuis MD, Sexton M, Prybylski D. Cigarette smoking andasthma symptom severity among adult asthmatics. JAsthma1999; 36:257-264.13. Centers for Disease Control and Prevention. Ta rg e t i n gtobacco use: the nations leading cause of death. Availablef rom http://www. c d c . g o v / n c c d p h p / a a g / a a g - o s h . h t m .Accessed 2002.14. US Department of A g r i c u l t u re. Tobacco situation andoutlook report. Washington, DC: US Department ofA g r i c u l t u re, Economic Research Service, CommodityEconomics Division, June 1994; publication no. TBS-227.15. Stapleton J. Cost effectiveness of NHS smoking cessationservices, August 2001. www.ash.org.uk./html/cessation/ashcost.html.16. Memon A. Epidemiology of smoking among Kuwaitiadults: prevalence, characteristics and attitudes. Bulletin ofWHO 2000; 78:1306-1315.17. Al Moumen. Health education department. The epidemiologyof smoking in Kuwait and government interventions, 1999.18. MMWR. Cigarette smoking among adults- United States1992, and changes in definition of smoking. JAMA 1994;272;14-16.19. Brown R, Pinkerton R, Tuttle M. Respiratory infections insmokers. Am Fam Phys 1987; 36:133-140.20. Rennard SI. COPD: Overview of definitions, epidemiology,and factors influencing its development. Chest 1998;113:235-241.21. Feenstra TR, Marianne L, van Genugten L, et al. The impactof Aging and Smoking on the Future Burden of ChronicObstructive Pulmonary Disease: A Model analysis in theNetherland. Am J Respir Crit Care Med 2001; 164:590-596.22. CDC. Cigarette smoking-attributable mortality and years ofpotential life lost - United States, 1990. MMWR 1993; 42:645-649.23. Herdman R, Hewitt M, Laschover M. Smoking-relateddeaths and financial costs: Estimates for 1990: US Congress,Office of Technology Assessment Testimony (OTA), 1993.24. Jarvis MJ, Cintyre D, Bates C, Foulds J. Effectiveness ofsmoking cessation initiatives. Efforts must take into accountsmokers’ disillusionment with smoking and their delusionsabout stopping. BMJ 2002; 324:608-609.25. US Department of Health and Human Services. The HealthConsequences of smoking. Chronic Obstructive airwaysDisease: A Report of the Surgeon General. Rochville, Md.Public Health Service, Office of smoking and health; 1984.US DHHS Publication 84-50205.26. Collins DJ, Lapsely HM. The economic impact of smoking,Pacific Tobacco and Health project, Canberra. AustralianPublishing Service, 1991.27. World Health Organization. World health re p o r t s .Guidelines for controlling and monitoring the tobaccoepidemic (WHO Geneva) 1998.28. Palafox NA, Ou AC, Haberle H, Chen TH. Quantifyingtobacco related health care expenditures in the Republic ofthe Marshall Island. Asian AM Health 2001; 9:74-80.

KUWAIT MEDICAL JOURNAL June 2007ABSTRACTAim: To assess the utility of tissue Doppler imaging(TDI) of mitral valve annulus (MVA) as pre l o a d -independent tool to quantify left ventricular function inlong axisDesign: Cohort study conducted between January 2000and March 2004S e t t i n g : Non-invasive cardiac laboratory, Medicinedepartment, Farwania Hospital, KuwaitPatients and Methods: Ambulatory blood pressure (BP)monitoring, transthoracic echocardiography with Dopplerstudy and treadmill exercise ECG test were done for 150hypertensive patients and 50 normotensive subjects.T h e re were two groups: group I: included 150 hypertensivepatients and group II: included 50 normotensive subjects.Results: There was a significantly decreased ventriculardescent phase and recoil phase of M-mode of MVA (p

June 2007KUWAIT MEDICAL JOURNAL 127We began this study with the hypothesis thatthe TDI of mitral valve annulus (MVA) is a preloadindependenttool and a valid technique to assessleft ventricular (LV) longitudinal fiber function(shortening and lengthening) in hypertensivepatients.The aim of the study was to evaluate the utilityof TDI of the MVA for the assessment of systolicfunction in long axis and diastolic relaxation of theleft ventricle in hypertensive patients.PATIENTS AND METHODSStudy patients:One hundred and fifty hypertensive patientsand 50 normotensive subjects were included in thestudy. All patients were referred by their physiciansto cardiology clinic in Farwania Hospital withblood pressure more than 140/90 mmHg. Sixtypatients complained of chest pain, 40 patientsp resented with shortness of breath (NYHAfunctional classification grade II), and 50 patientswere referred for echocardiographic assessment ofhypertension. All patients were evaluated clinicallyby looking at the history, physical examination, 12-leads ECG and routine laboratory investigations.Exclusion criteria included patients with historyof myocardial infarction, diabetes mellitus,c e re b rovascular disease, valvular disease, calcificationof mitral leaflets or mitral valve annulus,prolonged PR interval, sinus tachycardia, patientswith summation of transmitral flow pattern andpregnant women. Exclusion was based on: medicalhistory, physical examination, fundus examination,urine analysis for proteinuria and 12-leadelectrocardiogram to avoid confounding factors.Blood pressure measurements:M e rcury sphygmomanometer was used tomeasure office systolic and diastolic BP (mmHg).At least two measurements were recorded between8 AM and 11 AM with the patients in a sittingposition with the legs uncrossed and the feet on thefloor. BP was measured after the patient had restedfor 15 minutes. Cuff inflation pressure was thendetermined by palpating the disappearance andappearance of the radial pulse. BP was recordedtwice, with approximately a two-minute interval.Ambulatory blood pressure was recorded with anauscultatory device (Accutracker II). Corre c tposition of the microphone was done by palpatingthe brachial artery. Ambulatory BP was recordedduring the day (6 AM to 10 PM) at one-hourintervals and during the night (10 PM to 6 AM) attwo-hour intervals. Blood Pressure Load is thep e rcentage of all systolic and diastolic BP re c o rd i n g sexceeding the threshold of 140/90 mmHg.Echocardiographic study:Two-dimensional and M-mode echocard i o g r a p h ywas performed for all patients in the study. Theleading edge to leading edge convention was used.Left ventricular dimensions were measured at orimmediately below the tips of mitral leaflets andaveraged over five heart cycles. Left VentricularMass (LVM) and Left Ventricular Mass Index(LVMI) were calculated.Pulsed Doppler echocardiography was obtainedfrom the standard apical four chamber view. Mitralinflow velocity was re c o rded with the samplevolume at mitral annulus level. The transducer wasthen manipulated to obtain the maximal flowvelocity as assessed by the auditory and spectraloutputs. The Doppler measurements were madeduring at least three cardiac cycles using thedarkest part of the spectral recording and were thenaveraged. The following measurements wereobtained: peak velocity of early left ventricularfilling (E), peak velocity of late left ventricularfilling (A) and the ratio between early and late flowvelocity (E/A).Mitral valve annulus motion:This was obtained with the M-mode cursordirected from the apical four chamber view. Thecursor was oriented toward the bright septalmargin of the annulus (fibrous trigone) and thentoward the lateral margin. On each side, the beamwas oriented so that it was perpendicular to thedescent motion of the annular structure. MultipleM-mode re c o rdings of the septal and lateralmargins of the mitral annulus were made. Themotion of the septal and lateral margins wassimilar, and thus, only the motion of the septalm a rgin was re p o r t e d [ 6 ] . Mitral valve annulusdescent is a motion of the mitral annulus towardthe apex and mitral valve annulus recoil is amovement of the mitral annulus toward theatrium [7] .TDI pattern during sinus rhythm:A normal pattern consists of three major signals:a single systolic signal (Sm) and two distinct signalsin early (Em) and late (Am) diastole, timed by theonset of early inflow and atrial contraction,respectively. During isovolumic contraction time(IVCTm) and isovolumic relaxation time (IVRTm),the displayed, smaller biphasic signals arepresumed to be the result of brief geometricalchanges that occur in the LV (induced by differenttiming of long axis and circ u m f e rential axisdynamics and by ventricular interdependence [8] .Treadmill exercise ECG test protocol:All patients in the study underwent the exercise

128Usefulness of Pulsed-Wave Tissue Doppler Imaging of Mitral Valve Annulus for Assessment ... June 2007ECG test using standard or modified Bruce models.Resting ECG was done for all patients to excludepatients with significant ST- segment changes, leftbundle branch block or tachyarrhythmias. Bloodpressure was recorded midway through each stageand at peak exercise. ST- segment level wasmeasured 60 ms after the J point in all 12 leads.E x e rcise induced significant ST- segment depre s s i o nwas defined as horizontal or downsloping STsegmentdepression ≥ 1mm in any lead presentduring exercise test.Stress thallium scintigraphy:Only 62 patients were known to haveundergone stress thallium - 201 scintigraphy in thecourse of their clinical management. The SPECT(single-photon emission computed tomography) inEgypt, India and England. Ischemia by SPECT wasdefined as a stress perfusion defect in an area withnormal perfusion at rest.Statistical analysis:Continuous variables are summarized as amean ± standard deviation (SD). Comparisonbetween two groups was performed with t-test forcontinuous variables and chi-square test forcategorical variables. A p value < 0.05 wasconsidered statistically significant and a p value

June 2007KUWAIT MEDICAL JOURNAL 129Table 1: M-mode of mitral valve annulus and pulsedDoppler mitral valve inflow velocity variables in bothgroups of the studyVariable Group I Group II p-ValueVentricular descent phase (mm) 10.2 ± 1.3 12.8 ± 1.4 < 0.05Ventricular recoil phase (mm) 8.8 ± 0.91 10.3 ± 1.6 < 0.05Atrial phase (mm) 1.92 ± 0.54 2.4 ± 0.73 NSMitral inflow E-velocity (cm/sec) 48.4 ± 3.51 66.1 ± 10.2 < 0.05Mitral inflow A-velocity (cm/sec) 57.2 ± 4.61 34.5 ± 8.4 < 0.05E/Aratio 0.84 ± 0.12 1.94 ± 0.21 < 0.05Table 2: Parameters of TDI of MVA in both groupsVariable Group I Group II p-ValueE-mitral valve annulus (cm/sec) 10.1 ± 2.3 13.6 ± 3.4 < 0.05A-mitral valve annulus (cm/sec) 8.9 ± 1.4 7.2 ± 1.6 NSEm/Am ratio 1.13 ± 0.41 1.89 ± 0.37 < 0.05IVRT (msec) 129.9 ± 12.5 110.2 ± 6.3 < 0.05SCV -mitral valve annulus(cm/sec) 8.2 ± 1.5 10.9 ± 2.1 < 0.05SCT-mitral valve annulus (msec) 236 ± 13.2 208 ± 21.5 NSIVRT = isovolumetric relaxation time, SCT = systolic contraction time, SCV =systolic contraction velocityTable 3: Correlation of tissue Doppler imaging indices ofMVA in hypertensive patients as dependent variables tothe LVMI as an independent variable, where, dependentvariable = Y + LVMI x Slope, (n=70)Dependent variable y Intercept Slope r p-valueE-mitral valve annulus (cm/sec) 18.376 6.792 0.822 < 0.05A-mitral valve annulus (cm/sec) 1.082 2.831 0.839 < 0.05E/Aratio 8.215 0.913 0.782 < 0.05IVRT (sec) 40.241 7.082 0.925 < 0.01SCV -mitral valve annulus(cm/sec) 13.427 0.609 0.517 NSSCT-mitral valve annulus (cm/sec) 290.38 23.615 0.492 NSSCT = systolic contraction time, SCV = systolic contraction velocity, r =regression coefficientdecrease in the systolic contraction velocity (8.2 ±1.5 versus 10.9 ± 2.1 cm/sec, p < 0.05) and asignificant increase in the systolic contraction time(236 ± 13.2 versus 208 ± 21.5 msec, p < 0.05, Table 2).Exercise ECG test:There was an insignificant difference betweenboth groups as regards the peak heart rate duringe x e rcise (165.8 ± 7.66 versus 158.4 ± 9.21beats/minute, respectively, p = NS) but there was asignificant increase in the peak blood pressure anda significant decrease in the duration of the exercisetest in hypertensives with impaired heart raterecovery after exercise than those with normalheart rate recovery (219.6 ± 5.33 versus 197.6 ± 7.42mmHg, p < 0.05 and 6.84 ± 1.92 versus 8.45 ± 2.17minutes, p < 0.05) re s p e c t i v e l y. Forty fivehypertensive patients had a positive test and 105patients had a negative stress ECG test.Stress thallium-201 scintigraphy:Out of 62 patients who had undergone thalliumstress test, only 39 patients had a positive test withcold spot defects. Out of these 39 patients, 38patients had an impaired TDI of the MVA andimpaired M-mode motion of mitral valve ring. Outof 24 patients who had a negative test, eightpatients had an impaired TDI of the MVA andimpaired M-mode motion of MVA.Table 4: Receiver operating characteristic (ROC) curvedata of MVA-TDI in hypertensive patients to predictimpaired LV function in long axis (n=80)Variable Sensitivity False +ve AUC POEE-mitral valve annulus (8 cm/sec) 82% 24% 0.748 38%E/Aratio (120 ms) 73% 46% 0.691 50%SCV -mitral valve annulus(230 msec) 87% 20% 0.872 24%A U C = a rea under curve, IVRT = isovolumetric relaxation time, POE =probability of error with sensitivity 100%, SCT = systolic contraction time,SCV = systolic contraction velocityT h e re was a significant positive corre l a t i o nbetween ventricular descent phase of M-modeMVA (mm) and systolic contraction velocity of TDIof mitral annulus (cm/sec), (y =1.3x+6, r = 0.911, p< 0.05) and the systolic velocity of TDI (9 cm/sec) ofdependent Y-axis corresponded ventricularcontraction phase of M-mode (8mm) ofindependent X axis (Fig. 1). There was a significantnegative correlation between ventricular re c o i lphase of M-mode MVA (mm) and systoliccontraction time of TDI of mitral annulus (cm/sec),(y = 244 - 2.31x, r = 0.962, p < 0.05) and the systolictime of TDI (227 msec) of dependent Y a x i scorresponded with ventricular recoil phase of M-mode (9 mm) of independent X axis (Fig.2).There was a significant correlation between theTDI indices of MVA in the hypertensive patients asdependent variables and the LVMI as anindependent variable but IVRT and SCT-MVA hadan increased correlation coefficient (r) than otherdependent variables (Y-axis) of correlation (r =0.925 & r = -0.936 , p < 0.01 & p < 0.05, respectively,Table 3).Receiver operating characteristic (ROC) curvedata of MVA- TDI in hypertensive patients revealedthat systolic contraction velocity < 8 cm/sec was anindicator for detection of the impaired LVshortening fiber lengthening during systole and thesystolic contraction time > 230 msec was anindicator for detection of the impaired LV

130Usefulness of Pulsed-Wave Tissue Doppler Imaging of Mitral Valve Annulus for Assessment ... June 2007Table 5: Stepwise logistic analysis of hypertensive patientsversus those without impaired TDI of MVA as regards age,gender, smoking, left ventricular hypertrophy, BP load andhypercholesterolemiaIndependent Variable r SE p value 95% CIAge 0.1922 0.0978 < 0.05 1.054 ---- 1.731Gender 0.0258 0.0772 NS 0.923 ---- 1.176Smoking status 0.0632 0.0649 NS 0.976 ---- 1.023LVMI 0.1732 0.0786 < 0.05 0.761 ---- 0.892BPLoad Status 0.1984 0.0641 < 0.05 1.761 ---- 2.892Hpercholesterol 0.0678 0.0378 NS 0.654 ---- 1.531No. of observations =150, BP=blood pressure, CI = confidence interval, LVMI= left ventricular mass index, r = regression coefficient, SE = standard errorTable 6: Stepwise logistic analysis of hypertensivepatients versus those without impaired TDI of MVA asregards antihypertensive drugsIndependent Variable r SE p value 95% CIBeta Blockors 0.1823 0.0871 < 0.05 1.214 ---- 1.936ACE inhibitors 0.0356 0.0789 NS 0.721 ---- 1.270CCB 0.0439 0.0657 NS 0.572 ---- 1.422AR antagonists 0.0241 0.0174 NS 0.621 ---- 1.096Nitrates 0.0973 0.0364 NS 0.751 ---- 1.832No. of observations = 150, ACE = angiotensin converting enzyme, AR =angiotensin receptors, CCB = calcium channel blockers, CI = confidenceinterval, LVMI = left ventricular mass index, r = regression coefficient, SE =standard errorFig. 1: Correlation between ventricular phase of M-mode mitral annulusand systolic contraction velocity of TDI mitral annulusFig. 2: Correlation between ventricular recoil phase of M-mode mitralvalve annulus and systolic contraction time of TDI mitral valve annuluslongitudinal fiber lengthening during diastole(sensitivity = 84% Vs 87%, false +ve = 18% Vs 20%,area under curve=0.837 Vs 0.872 and probability oferror = 20% Vs 24%, respectively, Table 4).Stepwise logistic multivariate analysis revealeda significant relation between the age, bloodpressure load status and LVMI as independentvariables and impaired TDI of MVA (r = 0.1922,0.0984 & 0.1732, 95% CI = 1.054 - 1.731, 1.109 - 2.093& 1.761 - 2.892 respectively, p < 0.05). However,there was no significant relation as regards thegender, smoking status, and hypercholesterolemia(Table 5). As regards the antihypertensive drugst h e re was a significant relation between betablockers and the impaired function of longitudinalfibers of left ventricle but no significant relationbetween AEC inhibitors, calcium channel blockers,angiotensin receptors antagonists and nitrates andthe impaired LV function in long axis (p = NS, Table6).As re g a rds re p ro d u c i b i l i t y, there was nosignificant difference in intra-observer variability(p = NS).DISCUSSIONAlthough longitudinal directed fibers situatedmainly in the subepicardium and subendocardiumregions of the left and right ventricular free wallsand the papillary muscles comprise only a smallp roportion of the total ventricular myocard i a lmass, they play a major role in the maintenance ofnormal ejection fraction and in determiningatrioventricular interactions. So, not surprisingly,loss of longitudinal fiber function leads tocharacteristic disturbances. It has been suggestedthat the movement of the annulus is dependent onthe shortening and lengthening of thelongitudinally oriented myocardial fibers [9] .Longitudinal function is always reduced whenventricular cavity size is increased, in additionejection fraction is reduced. This relation isconsistent enough for long axis amplitude or its

June 2007KUWAIT MEDICAL JOURNAL 131equivalent, the amplitude of atrioventricular ringmotion, to be used as an index of ejection fraction.It applies not only to the left ventricle, where it canbe shown to relate to prognosis but also to the rightventricle, where it provides a simple method ofassessing right ventricular function. When overalllong axis amplitude is low, peak shortening andlengthening rates are reduced. In restrictive leftventricular disease, long axis amplitude is low evenwhen cavity size is normal at end diastole,although the effects of this reduction are apparentin a reduced amplitude of wall thickening and thusof shortening fraction [10] .MVA motion, which is recorded by TDI withhigh feasibility and re p roducibility has beenstudied in the evaluation of the left ventricularfunction [5] . It has long been recognized that the leftventricular diastolic function may be abnormal inpatients with left ventricular hypertrophy at a timewhen systolic function is preserved. This has beendocumented by contrast and nuclear angiographyand by M-mode echocard i o g r a p h y. All thesemethods demonstrate that the velocity of earlydiastolic filling is reduced with or withoutsuperimposed asynchro n y. These findings aremirrored in long axis function when both extentand peak velocity of early diastolic lengthening arereduced and that during atrial systole they areincreased [11] . The overall amplitude of motion ishowever, normal. In left ventricular hypertrophy,therefore, long axis function corresponds closely toconventional views of diastolic function and inthese circumstances it may be appropriate tocalculate the ratio of early to late diastoliclengthening. It is also reasonable to suggest thatpeak diastolic lengthening rate determined by TDImay be an index of early diastolic function [ 12 ] .However, these conclusions are limited to caseswithout asynchrony. In addition, the most commoncause of a reduction of early diastolic lengtheningrate is low overall amplitude of ring motion, whichis characteristic of systolic left ventricular disease.Considering peak velocities of long axis motion inisolation, disre g a rding overall amplitude andtiming is thus likely to lead to misleadingconclusions [13] .Our study revealed that both M-modeechocardiogram and TDI of MVA were markers ofleft ventricular longitudinal fibers shortening andlengthening with subsequent effect on the diastolicfilling of LV and revealed that impaired longitudinalfibers function was due to ischemia independent ofthe presence or absence of left ventricularhypertrophy and this in agreement with previousstudies [5,10] . Haluska et al, [1] from the university ofQueensland, Australia, reported that the longitudinalfunction was the only parameter to be significantlyabnormal at rest in patients without contractilereserve and the failure to increase TDI velocitysignificantly with stress corresponded to the EFresponse.Contrary to the frequent appearance of apicalmovement in the apical views, caused by movementof the heart within the scan plane, the apex isnormally in a fixed position. During systole,contraction of subendocardial and subepicardialfibers, which follow a helical course leads tomovement of the base of the heart toward thea p e x [ 14 ] . The contribution of this longitudinalshortening to overall function probably variesaccording to the circumstances and pathology butits role appears to be substantial. This aspect of LVfunction has received limited attention in the past,perhaps reflecting the difficulties experienced in itsmeasurement. However, recent studies have shownthe TDI measurements of the base-apex function tobe a sensitive marker of ischemia [15] and Haluska etal [1] reported that the results of their study suggest itis a sensitive marker of latent LV dysfunction.Henein and Gibson reported that prolonged leftventricular long shortening and delayed onset oflengthening effectively suppress early diastolictransmitral flow even though the minor axisi n c reases and mitral cusps separate appare n t l ynormally and this grossly asynchronous leftventricular relaxation may interfere with filling bydissipating normal ventricular restoring forces [16] .They suggested that delayed and prolonged longaxis shortening is the primary disturbance, but thismay have been the result of activation disturbance,subendocardial ischemia [17,18] or other causes still tobe identified, either alone or in combination. Thisprolonged shortening interacts with rapid thinningof the posterior left ventricular wall, a process thatwe have already suggested to be autonomous and amajor site of restoring forces [19] and the energynormally coupled to filling is thus dissipated as achange in cavity shape.Methodological considerations:1. M-mode echocardiogram of mitral valve is avalid and useful method to evaluate leftventricular function [20] .2. Pulsed wave TDI of MVA is an advancedmethod to study the systolic and diastolic LVfunction [3,5,6] .Limitations of the study:1. Relatively small number of patients.2. Echocardiogram was done by one observer,so intra-observer variability was evaluatedbut it is difficult to evaluate inter-observervariability.3. Study was not completely blind to theobserver.

132Usefulness of Pulsed-Wave Tissue Doppler Imaging of Mitral Valve Annulus for Assessment ... June 20074. Pulmonary venous flow velocity wasdetected only in 20 patients to estimate leftventricle end-diastolic pre s s u re with TDImitral annulus [14] .5. Only 31 patients were known to haveu n d e rgone cardiac catheterization andcoronary angiography in the course of theirclinical management.6. Isotope cardiac scanning is more accurateand valid method to evaluate diastolicfunction [5] , but it was not easily available .CONCLUSIONMitral valve annular motion velocity measure m e n t susing TDI should be employed routinely during theevaluation of the hypertensive patients.TDI ofmitral valve ring is a clinically useful marker forimpaired LV function in long axis and an indicatorof impaired relaxation of LV in hypertensivepatients independent of the presence or absence ofthe left ventricular hypertrophy.REFERENCES1. Haluska B, Short L, Marwick TH. Relationship ofventricular longitudinal function to contractile reserve inpatients with mitral regurgitation. Am Heart J 2003; 146:183-188.2. Pinicka M, Bartunek J, Wijns W, et al. Tissue Dopplerimaging of left ventricular function after recanalization ofan occluded coronary artery. J Am Coll Cardiol 2004; 43:85-91.3. Stengel SM, Allemann Y, Zimmerli M, et al. Doppler tissueimaging for assessing left ventricular diastolic dysfunctionin heart transplant rejection. Heart 2001; 86:432-437.4. McMahon MY, Nagueh SF, Pignatelli RH, et al.Characterization of left ventricular function by tissueDoppler imaging and clinical status in children withhypertrophic cardiomyopathy. Circulation 2004; 109:1756-1762.5. Wang M, Yip GWK, Wang AYM, et al. Peak early diastolicmitral annulus velocity by tissue Doppler imaging addsindependent and incremental prognostic value. J Am CollCardiol 2003; 41:820-826.6. Sohn DW, Chai IH, Lee DJ, et al. Assessment of mitralannulus velocity by Doppler tissue imaging in theevaluation of left ventricular diastolic function. J Am CollCardiol 1997; 30:474-480.7. Henein MY, Gibson DG. Normal long axis function. Heart1999; 81:111-113.8. Boeck BWL, Cramer MJM, Oh JK, Van der Aa RPLM,Jaarsma W. Spectral pulsed tissue Doppler imaging indiastole: a tool to increase our insight in and assessment ofdiastolic relaxation of the left ventricle. Am Heart J 2003;146:411-419.9. Henein MY, Gibson DG. Long axis function in disease.Heart 1999; 81:229-231.10. Tabata T, Oki T, Yamada H, Abe M, Onose Y, Thomas JD.Subendocardial motion in hypertrophic cardiomyopathy:assessment from long and short axis views by pulsed tissueDoppler imaging. J Am Soc Echocardiogr 2000; 13:108-115.11. Belohlavek M, Bartleson VB, Zobitz ME. Real - time strainrate imaging: validation of peak compression andexpansion rates by a tissue mimicking phantom.Echocardiography 2001; 18:565-571.12. Donovan CL, A r m s t rong WF, Bach DS. QuantitativeDoppler tissue imaging of the left ventricular myocardium:validation in normal subjects. Am Heart J 1995; 130:100-104.13. Jones CJH, Raposo L, Gibson DG. Functional importance ofthe long axis dynamics of the human left ventricle. Br HeartJ 1990; 63:215-220.14. Keren G, Sonnenblick EH, LeJemtel TH. Mitral annulusmotion. Relation to pulmonary venous and transmitralflows in normal subjects and in patients with dilatedcardiomyopathy. Circulation 1988; 78:621-629.15. Derumeaux G, Ovize M, Loufoua J, et al. Doppler tissueimaging quantitates regional wall motion duringmyocardial ischemia and reperfusion. Circulation 1998;97:1970-1977.16. Henein MY, Gibson DG. Suppression of left ventricularearly diastolic filling by long axis asynchrony. Br Heart J1995; 73:151-157.17. Edvarsen T, Skulstad H, Aakhus S, Urheim S, Ihlen H.Regional myocardial systolic function during acutem y o c a rdial ischemia assessed by strain Dopplerechocardiography. J Am Coll Cardiol 2001; 37:726-730.18. Edvardsen T,Urheim S, Skulstad H, et al. Quantification ofleft ventricular systolic function by tissue Dopplere c h o c a rdiography: added value of measuring pre - a n dpostejection velocities in ischemic myocardium. Circulation2002; 105:2071-2077.19. Henein MY, Anagnostopoulos C, Das SK, et al. Leftventricular long axis disturbances as predictors for thalliumperfusion defects in patients with known peripheralvascular disease. Heart 1998; 79:298-300.20. Pai RG, Bodenheimer MM, Pai SM, et al. Usefulness ofsystolic excursion of the mitral annulus as an index of leftventricular systolic function. Am J Cardiol 1990; 67:222-224.21. Hashimoto I, Li X, Bhat AH, Jones M, Zetts AD, Sahn DJ.M y o c a rdial strain rate is superior for evaluation leftventricular subendocardial function compared with tissueDoppler imaging. J Am Coll Cardiol 2003; 42:1574-1583.

June 2007KUWAIT MEDICAL JOURNALOriginal ArticlePerception and Practice of Primary Healthcare Practitionersabout Delivering Preventive Measures and ObstaclesInvolvedFareeda Esmael Moquaddam, Nahil Naser Salmin, Amal Homoud Al-JeheidliPrimary Health Care, Dasma Clinic, KuwaitABSTRACTKuwait Medical Journal 2007, 39 (2):133-137O b j e c t i v e : To assess how adequately practitionersperceive and practice certain preventive measures andwhat are the barriers to providing them in a Kuwaitprimary healthcare centreSetting: Primary Health Care, Dasma Clinic, KuwaitMethods: Cross-sectional survey of general practitionersin 29 primary healthcare centersR e s u l t s : The results of the survey revealed thatpractitioners were familiar with the importance ofclinical preventive medicine. However, lack of time wasc o n s i d e red an important obstacle, for checking BP(49.0%), blood sugar (39.3%), cholesterol level (44.1%),counseling on smoking cessation (81.4%), diet counseling(84.4%) and self breast examination (74.9%). On the otherhand, insufficient training was a barrier to somecounseling pro c e d u res such as smoking cessation(53.0%), diet counseling (52.6%) and self bre a s texamination (36.7%).Conclusion: The study found that insufficient training ofGPs is a major obstacle in delivering preventive care. Thiswas declared by a large number of family and generalpractitioners. This was noticeable when GPs conductedcounseling on smoking cessation, dieting and self-breastexamination. A d d i t i o n a l l y, the study revealed somevaluable recommendations by the GPs.KEYWORDS: Kuwait, obstacles, prevention, primary careINTRODUCTIONThe term “Preventive Medicine” is given to anymedication or procedure that can maintain andpromote health. Moreover, it should contribute tothe reduction of risk factors that result in injury anddisease. In order to achieve these valuableambitions, certain primary, secondary and tertiaryprevention activities must be considered. Primaryp revention activities deter the occurrence of adisease or adverse event for e . g ., smokingcessation [1] . Meanwhile, secondary prevention orscreening like mammography detection of breastcancer [2] will assist in early detection of a disease orcondition in an asymptomatic stage. These result inproviding the right treatment that could delay theo c c u r rence of symptoms. Tertiary pre v e n t i o nmethods like rehabilitation attempts to disallowadverse consequences of existing clinical disease.Preventive activities or services have decreasedmorbidity and mortality from acute or chronicc o n d i t i o n s .H o w e v e , they r were not fully implementedby physicians, patients or the health systems. Thetraditional disease/treatment model should bemodified to incorporate more preventive services [3] .In reality, education alone is not enough toi m p rove prevention. This study supports theappropriate evaluation approach. Such approach isexpected to highlight the most effective ways ofprevention. It also improves our ability to applyobtainable and effective ways of disease preventionand health modalities [4] .Several studies have demonstrated that manypatients did not receive recommended preventivecounseling. At the same time, efforts were made toimprove preventive care but coverage often fell farshort of target level. Simultaneously, primary carephysicians were missing opportunities for healthpromotion and disease prevention in a regularfashion [5-10] .Inspite of previous difficulties, the provision ofprimary and secondary prevention has faced someobstacles. These obstacles involve physicians, patientdeterminants, office system and structural issues [ 11 - 1 4 ] .The intent of this study was to inspect the gapbetween the level of preventive care thatpractitioners perceived as satisfactory and the levelof coverage that has been achieved in primaryh e a l t h c a re settings. Another aim was to knowAddress correspondence to:Dr. Fareeda Esmael MRCGP, Primary Health Care, Dasma Clinic, P. O. Box 43806, Hawalli, Postal Code: 53032, Kuwait. Tel : 2532266 /2532265, Fax: 2549511, E-mail: friend29488@hotmail.com

134Perception and Practice of Primary Healthcare Practitioners about Delivering Preventive Measures... June 2007Table 1: Socio-demographic characteristics of the generalpractitioners*Variables n %Age in yrs< 35 96 48.036 - 45 47 23.5Above 45 57 28.5GenderMale 89 44.5Female 111 55.5EmploymentGeneral practitioner 105 52.5Family practitioner 95 47.5Years of experience in a KuwaitPrimary Healthcare Centre 15 58 29.0*Characteristics of the respondentabout the practitioners’ perception re g a rd i n gobstacles in the delivery of preventive care.SUBJECTS AND METHODSIn Kuwait, there are about 700 practitionersworking in 87 primary healthcare centersdistributed over five governmental health regions.A systematic sampling method was carried out inthis study. As a result, every third clinic was chosenfrom alphabetically ordered tables.The study’s questionnaire incorporated foursections. First, socio-demographic characteristicslike age, gender, job and years of experience inKuwait primary health care centre. Second,practitioners’ satisfaction level on pre v e n t i v emeasures in fields like BP measurement, evaluationof blood sugar and cholesterol level, counseling onsmoking cessation, diet counseling and self breastexamination. Third, in percentages, how many oftheir patients have received preventive measuresguidance during real practice and fourth, what arethe obstacles that may create failure in theirperformance?Prior to the questionnaire, a pilot study wascarried out on 10 practitioners. This was becausethe questionnaire had to be examined and modifiedbased on their feedback. After that, data werecollected through self-administered questionnairesdistributed to general and family medicine practitionersexcluding pediatricians and gynecologists. The collecteddata were processed using Statistical Package forSocial Sciences (SPSS) Window version 11.0.The Pearson chi-square test of independencewas used to test two issues. First, the correlationbetween practitioners’ position and perc e p t i o nabout their performance satisfaction level forp revention measures. Second, it was used toTable 2: Practitioners’ perception about satisfactory levelof performance for prevention measuresPrevention measures Perception %0 - 25 26 - 50 51 - 75 > 75n % n % n % n %BPmeasurement 1 0.5 9 4.5 46 23.0 144 72.0Evaluation of blood sugar 2 1.0 12 6.0 51 25.5 135 67.5Evaluation of chol Level 3 1.5 24 12.0 51 25.5 122 61.0Counseling on smokingcessation 6 3.0 27 13.5 57 28.5 110 55.0Diet counseling 3 1.5 36 18.0 62 31.0 99 49.5Self breast examination 11 5.5 38 19.0 43 21.5 108 54.0Practitioners’ perception about satisfactory level of performance forprevention measuresexamine their position with respect to actualpractice. A value of PT = 0.05 was taken as thesignificance level.RESULTSOut of the 230 questionnaires 200 were returned.Because of crowded clinics, according to their writtencomments, unanswered questionnaires were re t u r n e d .Nevertheless, the response rate was 87%.The study showed that out of the two hundredrespondents 105 (52.5%) were general practitioners,95 (47.5%) were family medicine practitioners, 89(44.5 %) were male while 111 (55.5 %) were female.The majority of them (96, 48 %) were aged < 35years. As regards their years of experience inKuwait primary health center, 30.5% had less thanfive years and 29% had more than fifteen years(Table 1).Doctors were asked about their perception ofperformance satisfaction level on pre v e n t i o nm e a s u res. This questioning was related to BPm e a s u rements, evaluations of blood sugar andcholesterol levels, counseling on smoking cessation,diet and breast self-examination. Almost all of themhave replied it should be > 75% as shown in Table2. However, in actual practice delivery ofpreventive measures was less than 75% (Table 3).Consequently, 72% of practitioners estimatedthat the level of satisfaction for deliveringpreventive measures for BP checking to be > 75%during actual practice. On the contrary, only 29.5%out of the 72% rated it as being > 75%. Now, withrespect to diet counseling 49.5% of them expected itto be > 75%. However, only 9.0% out of the 49.5%rated it as being > 75% in actual practice.L a t e r, doctors were asked about certainobstacles that cause failure in providing preventionmeasures. They pointed out that insufficient timewas the most important obstacle. Percentages forthis obstacle vary from one test to another. Forexample, 48.5% was for BP measurements, 38.5%

June 2007KUWAIT MEDICAL JOURNAL 135Table 3: Preventive measures in actual practicePrevention measures Actual Practice (%)0-25 26-50 51-75 >75BPmeasurement 13 (6.5) 49 (24.5) 79 (39.5) 59 (29.5)Evaluation of blood. sugar 25 (12.5) 54 (27.0) 68 (34.0) 53 (26.5)Evaluation of cholesterol Level 43 (21.5) 60 (30.0) 66 (33.0) 31 (15.5)Counseling on smoking cessation 95 (47.5) 62 (31.0) 29 (14.5) 14 (7.0)Diet counseling 79 (39.5) 70 (35.0) 33 (16.5) 18 (9.0)Self breast examination 127 (63.5) 48 (24.0) 17 (8.5) 8 (4.0)Actual practice of practitioners about prevention measuresfor evaluation of blood sugar and 44.0% forevaluation of cholesterol level, 81.0% for counselingon smoking cessation, 84% for diet counseling and74.5% for self breast examination.Another obstacle was the absence of clearpractice guidelines. This also was different fromone test to another. For instance, it was 13% for BPm e a s u rements testing, 13.0% for evaluation ofblood sugar, 20.5% for evaluation of cholesterollevel, 63.0% for counseling on smoking cessation,62.0% for diet counseling and 55.5% for self breastexamination.As questionnaires progressed, more obstacleswere found. For example, more than 50% of doctorsagreed that lack of training and lack of patient’sinterest (checked by patient motivation) were yetother important obstacles. Lack of evidence forbenefit was the least obstacle for all the preventivemeasures (range was 6%-32%). Furthermore, morethan two third of practitioners agreed thateducating females about self-breast examinationhad caused embarrassment to doctors and patients(Table 4).There was no significant difference between thepractitioners’ position and their perception forperformance satisfaction level with respect toprevention measures. This was the same betweenpractitioners’ position and the actual practice.Respondents perceived other obstacles thatthey have faced: like lack of public awareness forself-help care (45%), lack of systematic organizationof preventive services (30%), no effective system toremind doctors or patients (20%) and no motivationor interest to screen (5%).The last part of the questionnaires dealt with thedoctors’ opinion. They were asked about ways toi m p rove prevention at the level of primaryhealthcare service. They agreed on a number ofrecommendations. First, appointment system hasto be established. Second, training courses must beprovided for doctors and nurses. Third, massiveeducational media coverage through TV, radio,public lectures, brochures and newspaper must bepresented. Fourth, clear protocols or guidelines forall preventive measures have to be created. Fifth,Table 4: Physicians’ opinion about specific obstacles toeach of the six preventive measuresPercentages of physicians agreed on each obstacleObstacles BP Blood Chol. Smoking Diet Selfcheck sugar Level cessation counseling breastexaminationLack of patient interest 21 (10.5) 30 (15.0) 47 (23.5) 159 (79.5) 128 (64.0) 100 (50.0)Lack of time 97 (48.5) 77 (38.5) 86 (43.0) 162 (81.0) 168 (84.0) 149 (74.5)Lack of evidence for benefit 12 (6.0) 12 (6.0) 15 (7.5) 30 (15.0) 32 (16.0) 31 (15.5)Absence of clear practiceguidelines 26 (13.0) 26 (13.0) 41 (20.5) 126 (63.0) 124 (62.0) 111 (55.5)Maneuver causes doctoror patient embarrassment 9 (4.5) 5 (2.5) 8 (4.0) 39 (19.5) 55 (27.5) 143 (71.5)Lack of training 5 (2.5) 6 (3.0) 10 (5.0) 105 (52.5) 103 (51.5) 73 (36.5)Physicians’ opinion about specific obstacles to each of six pre v e n t i v einterventionsthe number of doctors has to be increased in orderto be more time competent. Sixth, trained dieticiansand smoking cessation counselors must beavailable in clinics. Seventh, educational courses ondieting and on smoking counseling have to beimplemented.DISCUSSIONOur study revealed that there was a substantialdifference between the level of preventive care thatpractitioners wanted to provide and the level thatthey were providing in actual practice (Tables 2 and3) indicating that they know the importance ofpreventive health care, and this could motivatethem to seek change and to create a receptiveclimate for new strategies to enhance preventivecare performanceIn Saudi Arabia, primary health care physicianshad their perceptions on periodic health evaluation.About 90% of them recommended periodic healthevaluations. Furthermore, almost all of them (95%)were aware of the benefit and the costs of periodichealth examinations. Nevertheless, they werewilling to carry it out [15] .Then again, lack of time and lack of patient’si n t e rest were the most important obstaclesidentified by practitioners. This was true especiallyif they were involved with counseling rather thansimple diagnostic tests like blood test for sugar orcholesterol [16-18] .The relative importance of specific obstacles wasnot uniform across the preventive interventions aspresented in Table 4. Therefore, if we target theobstacles that are most important, we are mostlikely to succeed. To explain, Table 4 has pointedout that lack of training on counseling was thehighest in importance as compared to otherobstacles. In particular, counseling on smokingcessation, diet and self-breast examination. On thecontrary, lack of training was not an important

136Perception and Practice of Primary Healthcare Practitioners about Delivering Preventive Measures... June 2007obstacle when testing BP, blood sugar orcholesterol. These findings have suggested thatphysicians would benefit from additional trainingparticularly in these three areas [18-21] .Other obstacles to interventions like lack oftime, lack of patient interest and lack of evidencefor benefit were recognized by physicians asimportant. Such preventive services can be easilyd e l i v e red and improved if physicians wereinvolved with educational brief counseling strategies.P revious studies revealed that physiciansconsider practice guidelines as an important sourceof information. However, due to their complexity,length and time required for explanation, theybecame another obstacle in the daily routine [22-26] .Also, absence of an appointment and reminderservice was recognized as another obstacle inp roviding preventive care. Availability of theseitems at primary care level will improve quality ofcare [27-29] . The physicians in this study recommendedthat primary healthcare doctors should applysimple and easy protocols. Also, an eff e c t i v eappointment system must be established.CONCLUSIONTo summarize, this survey demonstrates therelative importance of various obstacles. Theseobstacles had a negative impact on implementingp reventive healthcare service. Practitionersunderstood that obstacles were lack of time, lack oftraining, lack of patient interest and absence ofguidelines, especially for smoking cessation, dietcounseling and self-breast examination.The GPs have come up with a number ofrecommendations. First, an effective appointmentsystem must be established. Second, trainingcourses for doctors and nurses must be provided.T h i rd, there is an urgent need for massiveeducational media coverage through TV, radio,public lectures, brochures and newspaper. Fourth,protocols or guidelines must be clear and easy inorder to implement effective preventive measures.ACKNOWLEDGEMENTSWe are grateful to Professor Mohamed A AMoussa (Head of Research Unit, Kuwait Institutefor Medical Specialization) for his valuable effort,advice and support. We would like to thank thepractitioners who took time to complete the surveyquestionnaire.REFERENCES1. Hensrud DD. Clinical preventive medicine in primary care:background and practice: Rationale and current preventivepractices. Mayo Clin Proc 2000; 75:165-172.2. Hensrud DD. Clinical preventive medicine in primary care:background and practice: Delivering primary preventiveservices. Mayo Clin Proc 2000; 75:255-264.3. Hensrud DD. Clinical preventive medicine in primary care:background and practice: delivering preventive screeningservices. Mayo Clin Proc 2000; 75:381-385. Erratum in:Mayo Clin Proc 2000.4. McAvoy BR, Kaner EF, Lock CA, Heather N, Gilvarry E.Our Healthier Nation: are general practitioners willing andable to deliver? A survey of attitudes to and involvement inhealth promotion and lifestyle counseling. Br J Gen Pract1999; 49:187-190.5. Kushner KF. Barriers to providing nutrition counseling byphysicians: a survey of primary care practitioners. PrevMed 1995; 24:546-552.6. Goodwin MA, Zyzanski SJ, Zronek S, et al.A clinical trial oftailored office systems for preventive service delivery. TheStudy to Enhance Prevention by Understanding Practice(STEP-UP). Am J Prev Med 2001; 21:20-28.7. Smith HE, Herbert GP. Preventive practice among primaryc a re physicians in British Columbia: relation torecommendations of the Canadian Task Force on thePeriodic health Examination. CMAJ 1993; 149:1795-1800.8. Mirand AL, Beehler GP, Kuo CL, Mahoney MC. Explainingthe de-prioritization of primary prevention: physicians’perceptions of their role in the delivery of primary care.BMC Public Health 2003; 3:15.9. Costanza ME, Zapka JG, Harris DR, et al. Impact of aphysician intervention program to increase breast cancerscreening. Cancer Epidemiology Biomarkers Prev 1992;1:581-589.10. Castaldo J, Nester J, Wasser T, et al. Physician attitudesregarding cardiovascular risk reduction: the gaps betweenclinical importance, knowledge, and effectiveness. DisManag 2005; 8:93-105.11. Fontana SA, Baumann LC, Helberg C, Love RR. Delivery ofpreventive services in primary care practices according toc h ronic disease status. Am J Public Health 1997; 87:11 9 0 - 11 9 6 .12. Deedwania PC. Veterans Administrations. Global riskassessment in presymptomatic patient. Am J Cardiol 2001;88:16J-22J.13. Cornuz J, Ghali WA, Di Carlantnio D, Pecoud A, Paccand F.Physicians’ attitude towards prevention: importence ofintervention -specific barriers & physicians’ health habits.Fam Pract 2000; 17: 535-540.14. B rotonse C, Bjorhelund C Bule M, Ciurana R, et al.Prevention and health promotion in clinical practice: Theview of GPs in Europe. Prev Med 2005; 40:595-601.15. al-Rowais N, Khoja T, al-Farra M, al- Nahedh N. Primaryhealth care physicians’ views on periodic health evaluationin Saudi Arabia. East Mediterr Health J 2000; 6:447-456.16. Mellvain HF, Backer EL, Crabtree BF, Lacy N. Physicianattitude and the use of office based tobacco control. FamNed 2004; 79:156-161.17. Nicholas LG, Pond CD, Roberts DC. Dietitian-generalpractitioner interface: a pilot study on what influences theprovision of effective nutrition management. Am J ClinNutr 2003; 77:1039S-1042S.18. Mirand AL, Beehler GP, Kuo CL, Mahoney MC. Physicianperceptions of primary prevention: qualitative base for theconceptual shaping of a practice intervention tool. BMCPublic Health 2002; 2:16.19. Huang J, Yu M, Marin E, Brock S, Carden D, Davis T.Physicians’ weight loss counseling in two public hospitalprimary care clinics. Acad Med 2004; 79:156-161.20. Hudon E, Beaulieu MD, Roberge. Integration of therecommendations of the Canadian Task Force onPreventive Health Care: obstacles perceived by a group offamily physicians. Fam Pract 2004; 21:11-17.21. Nollen NL, Adewale S, Okuyemi KS, Ahluwalia JS,Parakoyi A. Workplace tobacco polices and smoking

June 2007KUWAIT MEDICAL JOURNAL 137cessation practices of physicians. J Natl Med Assoc 2004;96:838-842.22. Helwig A, Bower D, Wolff M, Guse C. Residents findclinical practice guidelines valuable as educational andclinical tools. Fam Med 1998; 30:431-435.23. James PA, Cowan TM, Graham PR, Majeroni BA. Familyphysicians attitudes about and use of clinical practiceguidelines. Am J Fam Pract 1997; 45:341-347.24. Appel LJ, Havas S, Kotchen TA, et al. Primary prevention ofhypertension: Clinical Program. JAMA2002; 288:1882-1888.25. Chasuk RM, Brantley Martin PD. Knowledge and attitudeof family physician about clinical practice guidelines andthe care of patients with type2 diabetes mellitus. LaStsteMed Soc 2001; 153:31-44.26. Stone TT, Kivlahan CH, Cox KR. Evaluation of physicianpreferences for guideline implementation. Am J Med Qual1999; 14:170-177.27. Davis RM, Hwagner E. Managing chronic disease. BMJ1999; 318: 1090 -1091.28. Rosser WW, McDowell I, Newell C. Use of reminder forpreventive procedures in family medicine. Can Med AssocJ 1991; 145:807-814.29. Baskerville NB, Hogg W, Lemelin J. Process evaluation of at a i l o red multifaceted approach to changing familyphysician practice patterns improving preventive care. JFam Pract 2001; 50:W242-249.

KUWAIT MEDICAL JOURNAL June 2007Original ArticleGeneral Practitioners’ Attitudes and Practices towardManaging ObesityAmal Homoud Al-Jeheidli, Farida Ismael Moquddan, Maha Khalid Al-Rumh, Naheel Naser SalminPrimary Health Care, Dasma Clinic, KuwaitABSTRACTO b j e c t i v e : To assess the general practitioners (GPs)attitudes and practices toward obesity management andtheir recommendations for improvements, if anyDesign: Self administered questionnaire having threemain dimensions: socio-demgraphic charactertics of GPs,GPs difficulties in dealing with obese patients andattitudes of GPs toward managing obesityS e t t i n g : Twenty nine primary care centers choosenrandomly out of 87 in KuwaitS u b j e c t s : Data elicited from two hundred generalpractitioners working in 29 primary care centers in KuwaitMain Outcome Measures: To determine reasons fordifficulties facing GPs in managing obese patients inprimary care settings and their solutionsKuwait Medical Journal 2007, 39 (2):138-143Results: The majority of the GPs (85%) reported thatmanagement of obesity must be part of their job.However, one fifth were facing difficulties in dealingwith obese patients all the time. The unavailability ofeither dietitians or nutritionist in clinics was the mostcommon cause for their difficulty in tackling obesity.Most GPs reported that they advise their obese patientsto increase their physical activities. The same GPs rarelyp re f e r red to prescribe medications, or surgery orbehavioral therapy.Conclusion: GPs have proposed some suggestions thatwould improve obesity management at primary carelevel. They include involvement of the media, presenceor easy access to a dietitian and creating separateKEYWORDS: attitudes, barriers, obesity management, practices, primary careINTRODUCTIONObesity is increasing at an alarming ratethroughout the world. Today it is estimated thatthere are more than 300 million obese individualsin the world [1,2] . In white populations living in thewest and north of Europe, Australia, and theUnited States, the prevalence of obesity is similarlyhigh in men and women. Obesity re p resent arapidly growing threat to health [3] .Obesity co-morbidities include coronary heartdisease, hypertension and stroke, certain types ofc a n c e r, non-insulin-dependent diabetes mellitusand other diseases. In addition, the obese sufferfrom social bias; prejudice and discrimination, notonly on the part of the general public but also ofhealth professionals and this may make themreluctant to seek medical assistance [4] . Obesity isdefined as Body Mass Index (BMI) equal to orgreater than 30 kg/m 2 according to WHO in 1998 [3] .The occurrence of obesity is influenced by acomplex interaction of genetic, environmental andbehavioral factors. Therefore, a multidisciplinarytreatment program that enables the physician todraw on the resources of specialists in nutrition,exercise, and behavior modification that workswith the obese patient as an actively involvedmember of the team is needed [ 5 ] . Physician’sinvolvement is necessary for medical assessment,management, counseling and coordination ofmultidisciplinary obesity treatment [6] .The prevalence of obesity seems to be increasingin most parts of the world, even where it used to berare. Obesity represents a major threat to healthand quality of life in the Arabian population [7-10] . InBahrain the prevalence of obesity was significantlyhigher among female subjects (32%) than male(25%) throughout all the age groups [11] . Similart rend was seen in Saudi Arabia where theprevalence of obesity was 24% and 16% re s p e c t i v e l [ y12 ] .In Kuwait the prevalence of overweight andobesity (BMI > 25 and > 30 kg/m 2 ) increased by20.6 and 15.4% and by 13.7 and 8.4% among menand women, respectively, according to the datacollected during two time periods: 1980 - 1981 and1993 - 1994 [ 13 ] . Primary care physicians play acentral role in the systematic assessment andmanagement of obesity [ 14 ] . Guidelines for themanagement of obesity have been developed inAddress correspondence to:Dr. Amal Al Jeheidli, MRCGP, Primary Health Care, Dasma Clinic, P.O. Box 17, Khaldiya, Kuwait. Tel: 2532266 / 2532265, Fax: 2549511,E-mail: Dr_amal67@hotmail.com

June 2007KUWAIT MEDICAL JOURNAL 139Table 1: Socio demographic characteristics of GPs whoparticipated in the surveyVariable n PercentSexFemale 111 55.5Male 89 44.5EmploymentGeneral practitioner 105 52.5Family physician 95 47.5NationalityKuwaiti 104 52.0Non Kuwaiti 96 48.0Age (Years)20 -

140General Practitioners’ Attitudes and Practices toward Managing Obesity June 2007Table 3: Reasons for difficulty in dealing with obesepatientsReasons n To great To some To littleextent extent extentn (%) n (%) n (%) n (%)Lack of confidence 101 (57.7) 3 (1.7) 39 (22.3) 32 (18.3)Lack of training 66 (37.7) 17 (9.7) 44 (25.1) 48 (27.5)Lack of time 10 (5.7) 99 (56.6) 51 (29.1) 15 (18.6)High failure rate 4 (2.3) 82 (45.8) 74 (42.3) 15 (8.6)No guidelines 21 (12.0) 77 (44.0) 47 (26.9) 30 (17.1)No resources, eg. Dietitians 11 (6.3) 110 (62.8) 35 (20.0) 19 (10.9)Table 5: Association between GP’s years of experienceand difficulties faced while counseling obese patientsDifficulties 15 Years p valuen (%) n (%) n (%) n (%)Counseling

June 2007KUWAIT MEDICAL JOURNAL 141encouraging positive behavior and identifyingtreatments .The GPs role includes treating obesityand its emotional and medical consequences [ 24 ] .More than 50% of the physicians were convincedthat obese patients were treated in the asymptomaticpopulation. A study in Te x a s [ 25 ] confirmed thatfamily physicians usually address issues ofnutrition and physical activity in asymptomaticobese adult residents. Then again, this studyshowed that 61% GPs had regular visits by obesepatients and more than 75% of those visits weredifficult to handle. This was confirmed by anotherstudy, where GPs thought that obesity was difficultto be handled in primary care practice [26] .The reasons for the alleged difficulties can beidentified in more depth. Firstly, there was highfailure rate in maintaining ideal weight. Severalstudies showed that success rates in reaching andmaintaining an ideal weight were low [27] . In thesame field, GPs rated that treatments of obesitywere less effective than other chronic diseases [28] .Secondly, there were time constraints. Differentopinion revealed that physicians although theyfaced ‘busy clinical practice settings’ at the primaryc a re clinics nevertheless they succeeded inproviding their patients with a variety of practicestrategies to combat obesity. The key to theirsuccess was based on enlightening each patientwith his or her risk factors. Furthermore, theyrecommended certain diets and encouragedpatients to become active participants in weightloss programs [29] .In reality, the most commonly recommendedtreatments for obesity are the increase of physicalactivities and the reduction in caloric intake. Astudy conducted in the U.S.A. showed that twothirds of physicians provided dietary advice andthree quarters of doctors found that dietary advicewas the responsibility of physicians [30] . In anothers t u d y, 99% of doctors recommended aerobic exerc i s e sand 97% provided dietary counseling [31] . To concur,obesity experts viewed that medications prescribedto obesity patients were less effective and could notreplace diets and exercises [32] . Similarly, this studyshowed that most of GPs preferred not to prescribeanti-obesity medications. Also, this can be due topoor safety profiles of these medications [33] .On the contrary, another study in Korea indicatedthat 68.8% of their physicians prescribed antiobesitymedication without allowing sufficient timefor non-pharmacological therapy to take its effect.This was due to their lack of training on obesitytreatments and management [34] .This study also declared that GPs frequentlyreferred their obese patients to dietitian. This can bedue to lack of time or because patients had beenunder the impression that dietitians provide morehelp than GPs. On the contrary, another studyfinding confirmed that GPs rarely referred obesepatients to health professionals like dieticians forfollow-up or treatment [35] . At the same time, GPs ina different study referred obese individuals whowere in greater need of losing weight or were lessmotivated or were less likely to accept treatmentsbut equally likely to profit from them [36] .As regards to surgical intervention, 94% of theGPs had rarely chosen this as a managementoption. Several studies agreed that surg i c a lp ro c e d u res were underu t i l i z e d [ 37 ] while othersreserved surgical intervention for those with moreserious clinical risks [38] .In Kuwait 86% of doctors did not recommendbehavioral therapy. This could have been due todifferent reasons. First, such therapy option wasnot widely available in Kuwait. Second, there was alack of interest in gaining experience in this field.Third, the therapy was not in agreement withcultural standards. Despite all these reasons, behavioraltherapy has proven positive results. It employedlong term behavior modifications to control impro p e reating habits and behaviors (like eating too rapidlyor eating while watching TV). This study confirmedsuch favorable results and strongly recommendedthis kind of reaction to obesity [39] .Only 33% GPs performed active counseling onobese patients. This low percentage could havebeen due to lack of experience or lack of training inthis field. Also, it could be due to the absence ofclear and specific primary care guidelines. Thoseguidelines were available in certain countries. Theresearchers in those countries suggested expandingthem to counsel obese patients. To elaborate, theguidelines must involve weight loss techniques andthe diff e rent ways of improving patient’s complianceand motivation [40] . Others have agreed that someGPs did not provide enough guidelines on weightmanagement strategies due to inadequate counselingskills and confidence [41] .At any rate, as shown clearly in this study,experience was ranked as the most importantcontributor to knowledge concerning managingobesity [42] .In general, several studies suggested that therewas a need for appropriate approaches andpractices toward obesity. In addition, more informationand training must be available to doctors andhealth professionals. This can be accomplished bykeeping up-to- date with related i n f o r m a t i o n .A d d i t i o n a l l y, seeking skills impro v e m e n tand gettingsocial support are highly recommended to makemanagement programs more effective [43] . Anotherstudy concluded that new strategies must be

142General Practitioners’ Attitudes and Practices toward Managing Obesity June 2007c o n s i d e red and implemented like employingobesity specialists at the primary care clinics [44] .CONCLUSIONIn conclusion, this study demonstrated thatmany GPs believed in their essential role inmanaging obesity although 67% of them have facedsome difficulty from time to time. In order too v e rcome that and promote professional fulfillment,several recommendations were suggested by theGPs. First, the media must be involved to educatepeople about risk factors and unwanted consequencesassociated with obesity. Second, about 28.5% of theGPs think that there is an urgent need for morepractical training for them and their nurses. Third,primary care clinics must have professional dietitiansin order to assist and provide on-job-training.Fourth, some suggest establishing a specializedobesity clinic at the level of primary care centersthus minimizing the number of patients visitingGPs. As a result, GPs will be able to provide moretime and better quality of care to their patients.Finally, there is no doubt that early implementationof proposed recommendations could helpGPs to improve the quality of obesity managementand overcome any unexpected difficulties. Conseque n t l y, GPs will be considered as essential inmanaging obesity and in providing better longterm outcome.REFERENCES1. Seidell JC. Epidemiology of obesity. Semin Vasc Med 2005;5:3-14.2. World Health Organization. Obesity: preventing andmanaging the global epidemic. Report of the WHOConsultation on Obesity WHO; Geneva, 1997.3. Prevention and management of the global epidemic ofobesity. Report of the WHO consultation on obesity. WHO;Geneva, 1998.4. Obesity: preventing and managing the global epidemic.Report of WHO consultation. World Health Organ TechRep Ser 2000; 894:1-253.5. Frank A. A multidisciplinary approach to obesitymanagement: the physician’s role and team carealternatives. J Am Diet Assoc 1998; 98:S44-S48.6. Rippe JM, McInnis KJ, Melanson KJ. Physician involvementin the management of obesity as a primary medicalcondition. Obes Res 2001; 9:S302-311.7. Al-Shammari SA, Khoja TA, Al-Maatouq MA, et al. Highp revalence of clinical obesity among Saudi females: aprospective, cross-sectional study in the Riyadh region. JTrop Med Hyg 1994; 97:183-188.8. Al-Mahroos FJ, Al-Roomi KA. Overweight and obesity inthe Arabian Peninsula: an overview. J R Soc Health 1999;119:251-253.9. El-Mugamer IT, Ali Zayat AS, Hossain MM, Pugh RN.Diabetes, obesity and hypertension in urban and ruralpeople of Bedouin origin in the United Arab Emirates. JTrop Med Hyg 1995; 98:407-415.10. Binhemd T, Larbi EB, Absood G. Obesity in primary healthcare centre: a retrospective study. Ann Saudi Med 1991;11:163-166.11. A l - M a h roos FJ, Al-Roomi KA. Obesity Among A d u l tBahraini Population: Impact of Physical Activity A n dEducational Level. Ann Saudi Med 2001; 21:183-187.12. Al-Nuaim Ar, Al-Rubean K, Al-Mazrou Y, Al-Attas O, Al-Daghari N, Khoja R. High Prevalence Of Overweight AndObesity In Saudi Arabia. Int J Obes Relat Metab Disord1996; 20:547-552.13. Al-Isa AN. Are Kuwaitis getting fatter? Nutr Health 2003;17:185-197.14. Orzano AJ, Scott JG . Diagnosis and treatment of obesity inadults: An applied evidence - based review. Am Board FamPract 2004; 17:359-369.15. Clinical guidelines in the Identification, Evaluation, andTreatment of Overweight and Obesity in Adults. NHLBI,1998.16. Kreuter MW, Chheda SG, Bull FC. How does physicianadvice influence patient behavior? Evidence for a primingeffect. Arch Fam Med 2000; 9:426-43317. Simkin-Silverman LR, Wing RR. Management of obesity inprimary care. Obes Res 1997; 5:603-661.18. Wadden TA, Berkowitz RI, Sarwer DB, Prus-wisniewski R,S t e i n b e rg C. Benefits of life style modification in thepharmacological treatment of obesity: A randomized trial.Arch Intern Med 2001; 161:218-227.19. Heath C, Grant W, Marcheni P, Kamps C. Do family physicianstreat obese patients? Clin Res Meth 1993; 25:401-402.20. Judd H. The management of obesity by general practitioners:report of a questionnaire survey. Royal Australian College ofGeneral Practitioners, 1987 Melbourne. J Fam Pract 1998;4 7 : 3 9 - 4 321. Fogelman Y, Vinker S, Lacher J, Biderman A, Itzhak B, KitariE. Managing obesity: a survey of attitudes and practicesamong Israeli primary care physicians. Int J Obes RelatMetab Disord 2002; 26 :1393-1397.22. Kristeller JL, Hoerr RA. Physician attitudes towardmanaging obesity: differences among six specialty groups.Prev Med 1997; 26:542-549.23. Centre for Reviews and Dissemination. The prevention andtreatment of obesity. Eff Health Care 1997; 3:2.24. Aronne LJ. Classification of Obesity and Assessment ofObesity-Related Health Risks. Obes Res 2002; 10:105S-115S.25. Guo JL, Gottleb NH, Smith MM, Huang PP, Huang CM.Nutrition and physical activity counseling practices offamily practice residents. J Cancer Educ 2002; 17:128-137.26. Brotons C, Ciurana R, Pineiro R, Kloppe P, Godycki-CwirkoM, Sammut MR. EUROPREV. Dietary advice in clinicalpractice: the views of general practitioners in Europe. Am JClin Nutr 2003; 77:1048S-1051S.27. Branlage P, Wittchen HV, Pittrow D, Kirch W. Recognitionand management of over weight and obesity in primarycare in Germany. Int J Obes Relat Metab Disord 2004;28:1299-1308.28. Foster GD , Wadden TA, Makris AP, et al. Primary carephysicians’ attitudes about obesity and its treatment. ObesRes 2003; 11:1168-1177.29. Hensrud DD. Tackling obesity in a 15-minute office visit.Physicians can start patients on an effective weight-lossprogram, despite time constraints. Postgrad Med 2004;115:59-61.30. Loomis GA, Connolly KP, Clinch CR, Djuric DA. Attitudesand practices of military family physicians re g a rd i n gobesity. Mil Med 2001; 166:121-125.31. Kushner RF. Barriers to providing nutrition counseling byphysicians: a survey of primary care practitioners. PrevMed 1995; 24:546-552.32. Bray GA, DeLany J. Opinions of obesity experts on thecauses and treatment of obesity—a new survey. Obes Res1995; 3:419S-423S.

June 2007KUWAIT MEDICAL JOURNAL 14333. Long-term pharmacotherapy in the management of obesity.National Task Force on the Prevention and Treatment ofObesity: Review. (No authors listed). JAMA1996; 276:1907-1915.34. Park HS, Park JY, Cho HJ. Attitudes and reported practicefor obesity management in Korea after introduction of antiobesityagents. J Korean Med Sci 2005; 20:1-6.35. Campbell K, Engel H, Timperio A, Cooper C, Crawford D.Obesity management: Australian general practitioners’attitudes and practices. Obes Res 2000; 8:459-466.36. National Institute for clinical excellence. Surgery to aidweight reduction for people with morbid obesity: Finalappraisal determination. July 2002.37. Binks M, O Neil MP. Referral sources to a weightmanagement program: relation to outcome. J Gen InterMed 2002; 17:596-603.38. Lean ME. Obesity - what are the current treatment option?.Exp Clin Endocrinol Diabetes 1998; 106:22- 26.39. Wadden TA, Sarwer DB, Berkowitz RI. Behaviouraltreatment of the overweight patient. Baillieres’ Best PractRes Clin Endocrinol Metab 1999; 13:93-107.40. Martin PD, Rhode PC, Howe JT, Brantley PJ. Primary careweight management counseling: physician and patientperspectives. J La State Med Soc 2003; 155: 52-56.41. Huang J, Yu H, Marin E, Brock S, Carden D, Davis T.Physicians’ weight loss counseling in two public hospitalprimary care clinics. Acad Med 2004; 79:156-161.42. Cade J, O’Counnell S. Management of weight problems andobesity: knowledge, attitudes and current practice ofgeneral practitioners. Br J Gen Pract 1991; 41:147-150.43. Price JH, Desmond SM, Krol RA, Snyder FF, O’Connell JK.Family practice physicians’ beliefs, attitudes, and practicesregarding obesity. Am J Prev Med 1987; 3:339-345.44. Moore H,Summerbell CD, Greenwood DC, et al. Improvingmanagement of obesity in primary care: cluster randomisedtrial. BMJ 2003; 327:1085-1088.

KUWAIT MEDICAL JOURNAL June 2007Original ArticleOutcome of Non-operative Management of Blunt SplenicTraumaABSTRACTHayan Abdulrahman Bismar, Saleh Mohammed Al-SalamahDepartment of Surgery, College of Medicine, University Unit,King Saud University, Riyadh Medical Complex, Saudi ArabiaObjective: To evaluate the outcome of non-operativemanagement (NOM) and compare it with the operativetreatment in splenic traumaDesign: Aretrospective comparative studySetting: Riyadh Medical Complex, Riyadh, Kingdom ofSaudi ArabiaSubjects: Files of 83 patients managed for blunt splenictrauma over a five year period were reviewed. Patientswere divided in two groups: operative group and nonoperativegroup.Intervention: Thirty five patients were hemodynamicallyunstable and underwent laparotomy with eithers p l e n e c t o m y, splenorrhaphy or partial splenectomy(operative group). Forty eight patients werehemodynamically stable. The diagnosis of splenic injurywas confirmed on CT abdomen. These were initiallymanaged conservatively by serial clinical and laboratorymonitoring in the intensive care unit (ICU) followed byKuwait Medical Journal 2007, 39 (2):144-148bed rest for 5-7 days in the general ward (non-operativegroup).Main outcome measures: Outcome was compared interms of hospital stay, complications, blood transfusionre q u i rements, morbidity and mortality between twogroups.Results: Among 35 patients (42%) with laparotomy, thespleen was removed in 25 patients and preserved in 10patients. Forty eight patients (58%) were hemodynamicallystable and were treated non-operatively. The nonoperativegroup had a more advanced injury grade,required less blood transfusion and had shorter hospitalstay than the operative group. Non-operative managementfailed in four patients and had a success rate 91.7%.C o n c l u s i o n : NOM of blunt splenic trauma inhemodynamically stable patients is safe and effective. Itresults in shorter hospital stay, low morbidity andmortality.KEY WORDS: blunt splenic trauma, non-operative treatment, splenic preservation, splenectomyINTRODUCTIONEver since Reinger reported the first successfulsplenectomy for splenic injury in 1892 [1] , it hadbecome the standard treatment of traumaticrupture of the spleen. Early in the 20th century,many studies revealed the importance of spleen inthe immunity and the asplenic state putting theperson at lifelong risk of susceptibility toinfection [1,2] . This led to a shift in the managementtowards splenic preservation (splenorrhaphy, meshsplenorrhaphy, or partial splenectomy) followingtrauma in the last few decades [3] . The liberal use ofcomputed tomography (CT) in blunt abdominaltrauma has reduced the rate of non-therapeuticceliotomy, as many cases of splenic injuries can bedetected on CT in hemodynamically stable patientswho could be observed and treated non-operatively [ 4 ] .Non-operative management (NOM) for pediatricblunt splenic trauma was first reported byUpadhyaya in 1968 followed by many studies inthe eighties which reported favorable results ofNOM in pediatric patients [5-8] . At the same timemany investigators have applied the NOM toadults splenic trauma and reported encouragingresults [9-11] . NOM is considered the method of choicein treating blunt splenic injuries in hemodynamicallystable patients in most trauma centersthese days. However, few aspects re m a i nc o n t roversial and need to be evaluated. Thiscomparative study was carried out at the RiyadhMedical Complex to evaluate the outcome andexperience of managing blunt splenic traumabetween operative and non-operative groups.PATIENTS AND METHODSThe medical records of 83 patients with splenicinjuries due to blunt abdominal trauma over a fiveyear period from January 2000 to December 2004w e re re t rospectively reviewed for demographicdata, mechanism of injury, hematological andAddress correspondence to:Dr. Saleh M. Al-Salamah, MBBS, FRCS, Associate Professor and Consultant General Surgeon, College of Medicine King Saud University, Dept.of Surgery, University Unit, Riyadh Medical Complex, P.O. Box 261283, Riyadh 11342, Saudi Arabia. Tel: +9661 467 1585, Fax: 01 467 9493,E-mail: smsalamah@hotmail.com

June 2007KUWAIT MEDICAL JOURNAL 145Fig. 1: Algorithmic approch to Blunt Splenic TraumaTable 1: ASST* splenic organ injury scaleCLASS ICLASS IICLASS IIICLASS IVCLASS VHematoma subcapsular < 10% surface area lacerationcapsular tear < 1 cm parenchymal depthHematoma subcapsular 10 - 50% surface areaIntraparenchymal < 5 cm diameterLaceration 1 - 3 cm parenchymal depth not involving aparenchymal vesselHematoma subcapsular > 50% surface area or expandingRuptured subcapsular or parenchymal hematomaIntraparenchymal hematoma > 5 cmLaceration > 3 cm parenchymal depth or involvingtrabecular vesselsLaceration of segmental or hilar vessels producing majordevascularization (> 25% of spleen)Laceration completely shattered spleenHilar laceration injury which devascularized spleen* American Society for the Surgery of Traumaimaging investigations, associated injuries, bloodtransfusion, complications, treatment and surgicalprocedures, morbidity, mortality and hospital stay.The patients were divided into two groups; theoperative management group included patientswho were hemodynamically unstable and requiredexploratory laparotomy. The surgical procedureswere either splenectomy, splenorrhaphy or partials p l e n e c t o m . y The NOM was applied inhemodynamically stable patients on presentationor who were hypotensive and stabilized withminimal intravenous fluids in emergency room.The patients with blunt splenic trauma weremanaged according to the algorithm shown in Fig.1. The diagnosis of intraperitoneal hemorrhage wasconfirmed by diagnostic peritoneal lavage (DPL) orpositive abdominal ultrasonogram (USG) for freeintraperitoneal fluids in hemodynamically unstablepatients. The imaging modalities employed forh e m o d y n a m i c a l l ystable patients were abdominalultrasonogram and CT scan of the abdomen. Thesplenic injuries were classified according to thesplenic injury scale of the American Society for theSurgery of Trauma (ASST) (Table 1). Patients withhigh class injuries were admitted to the IntensiveCare Unit (ICU) for close monitoring for the first 48hours with serial clinical examinations andhemoglobin checkup. Patients with isolated splenicminor injuries were observed in the surgical wardwith close monitoring. Patients were kept on bedrest for 5-7 days. The failure of NOM wasc o n s i d e red when the patient became hemodynamicallyunstable during observation or required more thantwo units of blood transfusion for splenic injury.They underwent exploratory laparo t o m y. Theoutcome of both groups was compared withemphasis on the patients’ age, class of injuries,numbers of blood transfusion, morbidity, mortalityand hospital stay. Statistical analysis was carriedout employing exact Fisher test, Chi-square test,and analysis of variance for comparative analysis ofthe data using IBM-compatible PC and SPSS 10.0for Windows (SPSS Inc., Chicago).RESULTSA total of 83 patients with splenic injuries due toblunt abdominal trauma were treated at the RiyadhMedical Complex over the five year period underreview. There were 72 men and 11 women. Themean age was 23.5 years (range 4-63 years). Themechanisms of injury were as follows: motorvehicle accident in 60 patients, fall from height in 13and sport injuries in 10 patients.Thirty five patients were hemodynamicallyunstable and underwent exploratory laparotomy(operative management group) due to ongoingbleeding from the injured spleen. The remaining 48patients were hemodynamically stable and wereselected for NOM.Thirty five patients underwent exploratoryl a p a rotomy due to ongoing intraperitonealhemorrhage. There were 30 male and 5 femalepatients. The mean age was 24 years (4 - 63 years).Seven patients were less than 13 years of age. Allpatients presented to emergency room withhypovolemic shock. DPL was performed in 30patients and was positive. The other five patientsunderwent USG which showed free intraperitonealfluid. The associated injuries were as follow:thoracic injuries in 18, extremities injuries in 11,head injuries in nine, spinal injuries in two, andpelvic injury in two patients. The associated intraabdominalinjuries were liver in seven,retroperitoneal hematoma in five, mesenteric tearin four, renal injuries in two, duodenum in one,diaphragm in one, and pancreas in one patient. Theclass of splenic injuries were low and moderate in

146Outcome of Non-operative Management of Blunt Splenic Trauma June 2007Table 2: Comparative analysis of operative and NOMgroupsOperative (n = 35, 42%) NOM (n = 48, 57.8%)Age < 13 years: 7 patients Age < 16 years: 13, p < 0.000001Associated injuries ↑ Associated injuries (1 injury /(1.6 injury /patient) patient)Injuries grade:Injuries grade:Severe (IV, V) 40% Severe (IV, V) 23%, p = 0.1519Blood transfusion: all patients Blood transfusion: only 18(100%) patients (37.5%)Received (1 - 10 units)Received (1 - 6 units)Mean: 3.7 units per patient Mean: 0.8 units per patient, p = 0.015Hospital stay (7 - 61) days Hospital stay (3 - 32) daysMean 18.6 days Mean 11.2 days, p = 0.008Complication ↑ Failure: 4 patients (8.33%)Death : 5(severe head injury)Death : No21 patients (I in 3, II in 8 and III in 10) and high in14 patients (class IV in 8, class V in 6).Splenectomy was performed in 25 patients,splenorrhaphy in seven and partial splenectomy int h ree patients. All patients received bloodtransfusion. The average number of blood unitstransfused was 3.7 units /patient (range 1-10 units).Postoperative complications included atelectasis insix patients, pleural effusion in five, urinary tractinfection in five, chest infection in four, hematomain splenic bed in two, wound hematoma in two andwound infection in one patient. One patientsdeveloped complete adhesive bowel obstruction at10th postoperative day and required laparotomyfor adhesiolysis. The mean hospital stay was 18.6days (range 7 - 61 days). Five patients died due tosevere head injuries and multiple trauma and themortality rate in this group was 14 %.Forty eight patients were hemodynamicallystable and were treated conservatively. There were42 male and six female patients with a mean age of21 years (range 5 - 51years). Sixteen patients wereunder 13 years. Ten patients presented with shock.They were resuscitated and stabilized withintravenous fluids (mean 1.75 l / patient, range: 1.5- 2.5 l / patient) and blood transfusion. Eighteenpatients (37.5%) received blood transfusion. Themean number of blood units transfused was 0.8units / patient (range: 1 - 6 units). The remaining 38patients were hemodynamically stable atpresentation. Abdominal USG was performed in 28patients. It was able to detect splenic trauma in 24patients and showed free intraperitoneal fluids inrest of cases with a sensitivity of 85%. A nabdominal CT scan was performed in all patients toconfirm and classify the splenic injuries. The classof injury were as follows: low and moderate in 37patients (class I in 13, class II in 16, class III in 8)and high class in 11 (class IV in 8, class V in 3)a c c o rding to the CT findings. The associatedinjuries were as follows: thoracic injuries in 22,extremities in six, head injury in nine, spinal int h ree and pelvis in two patients. The intraperitonealinjuries were as follows: liver injuries in three (classI in 1, class II in 2), retroperitoneal hematoma intwo, pelvic hematoma in one and renal trauma intwo patients. The mean hospital stay was 11.2 days(range: 3-32 days). The NOM was successful in 44patients (91.7%). Four patients becamehemodynamically unstable after initial period ofconservative treatment. They required exploratorylaparotomy and splenectomy with failure rate ofNOM of 8.3%. All patients with NOM failure wereabove 13 years; two had class IV, one class V andone class III trauma.Comparison of outcome in both operative andNOM groups (Table 2) showed that the operativegroup had a relatively less number of pediatricpatients (20 Vs 33% for NOM patients; p =0.000001). The number of associated injuries washigher in the operative group (1.6 injuries / patientVs 1 injury / patient in NOM group). As regard theseverity of injury, the operative group had a higherclass (V, IV) of injuries than NOM group (40 Vs23%). The incidence of low and moderate classinjury (I, II, III) in the operative group was 60% ascompared to 77% in non-operative group (p =0.1519). All operative group patients received blood(100%) as against only 18 (37.5%) in NOM group.The blood transfusion rate was 3.7 units / patient inoperative group and 0.8 units / patient in NOMgroup (p = 0.015). The hospital stay was longer inoperative group (18.6 days Vs 11.2 days in NOMgroup, p = 0.008). There was no mortality in NOMgroup, while five patients died in the operativegroup. These patients had severe head injuries andpolytrauma (5 injuries / patient).DISCUSSIONThe management of splenic trauma has evolvedwith time, from splenectomy towards splenicpreservation and NOM over the last 25 years. Thesusceptibility to infection and post-splenectomysepsis was well established early in the 20thc e n t u r y [ 1 , 2 ] . Green et al reported major septiccomplications rate of 5.9% (pneumonia, septicemia,meningitis) in post-splenectomy patients [ 1 2 ] . Theoverwhelming post-splenectomy infection (OPSI)can occur in 0.5% cases with a high mortality (>5 0 % ) [ 1 3 - 1 5 ] . This led the surgeons to attemptp reserving the spleen and avoid splenectomywhenever possible. Splenorrh a p h y, mesh splenorrh a p h yand partial splenectomy have been employed asmost common procedures of splenic salvage. In aretrospective review of splenic trauma in 1982,

June 2007KUWAIT MEDICAL JOURNAL 147Hebler et al found that splenorrhaphy and NOMpatients had lower mortality and less infectiouscomplications [9] . Morgestern et al in 1983 treated 17patients nonoperatively without failure. In 1984,Zucker et al noted only one failure (4%) in 14 adultsand 10 children with blunt splenic trauma treatednonoperatively [10,11] . Recently the NOM has replacedthe splenic salvage pro c e d u res in hemodynamicallystable patients in most trauma centers.In this study a total of 83 patients with bluntsplenic trauma were reviewed. We treated 48patients (57.8%) non-operatively. The NOM failedin four patients and had a success rate of 91.6%. Theremaining 35 patients underwent exploratoryl a p a ro t o m y. Splenectomy was performed in 25patients and the spleen was preserved in 10patients. The overall splenic salvage rate was 70%.These results are similar to Pachter et al where 65%of patients with splenic trauma were tre a t e dnonoperatively with success rate of 98% and theoverall splenic salvage rate was 71% [16] . However,others have reported only 40% success rates forNOM and a splenic salvage rate of 50% [17] . Cogbill etal showed that NOM has a higher success rate inchildren (failure rates being 17% in adults and only2% for children) [18] . The largest multicentre studyabout NOM was by Hunt et al, where a total of 2258cases with splenic trauma were reviewed over afive year period [19] . They found that the NOM rateincreased with time from 33.9% to 46%. Pachter et alreported increased frequency of NOM from 13%(from 1978-1989) to 54% (from 1990-1996) [16] .NOM is considered method of choice in themanagement of hemodynamically stable patientswith high success rates and low morbidity [16,17,19] .There are, however, some controversies which needto be addressed. It was argued that NOM willre q u i re more blood transfusion than surg i c a l l ytreated patients. Our study shows that all patients(100%) who were treated surgically received bloodtransfusion at the rate of 3.7 units per patient (range= 1-10 units) while only 18 patients (37%) from theNOM group received blood at the rate of 0.8 units /patient. Similar results were reported by Smith [20] .Another critique for NOM has been that thepatients might have missed intra-abdominal injurywhich could need surgical intervention. Cogbill etal treated 112 patients non-operatively and they hadonly one missed injury (0.91%) [ 1 8 ] . We did notobserve any missed intra-abdominal injuries inNOM patients. The major concern for NOM is thatthis treatment is contraindicated in patients withneurological impairment. Archer et al found nosignificant differences in morbidity, mortality andfailure of treatment or missed visceral injuries inpatients with or without neurological injuries [21] . Wehad five patients with Glasgow Coma Score < 9t reated successfully with NOM. Our studysupports NOM for splenic trauma even in patientswith neurologic impairment provided they haveCT abdomen with oral and intravenous contrastsand are closely monitored with frequent clinicalexamination, preferably in a high dependency orintensive care unit initially. The age of patient hasbeen another concern. Godley et al cautioned intheir study that age > 55 years is a contraindicationfor NOM [22] . The authors reported 10 failures ofNOM out of 11 patients aged > 55 years. HoweverPachter et al found no difference or increased failurerate in patients over 55 years [16] . Our study did nothave any patient more than 50 years in the NOMgroup. Therefore we cannot comment on this aspectwhich remains to be elucidated by further studies.The management of the advanced classs ofsplenic injuries is the most controversial issue inNOM. Cogbill et al concluded that class I and II canbe treated safely and class III can be treated withhigh prediction of failure and recommended thatclass IV and V should be treated surg i c a l l y [ 1 8 ] .Powell et al observed that class III, IV and V splenicinjuries are poor prognostic indicators for NOM [23] .Scalfani et al showed that advanced class of splenicinjuries can be treated non-operatively when theytreated 17 patients with class IV splenic traumawith a success rate of 84% [24] . Our study includednine patients with class III injury with one failure(11%) and 11 patients with class IV and V traumawith three failures (27%). We conclude that advanceclass like III, IV and V can be tre a t e dnonoperatively with high prediction of failure.While one reason for increased bloodtransfusion requirements and higher morbidity andmortality in operated patients could be operativeintervention itself and more severe injury class,hemodynamically stable patients or patients whohad been hemodynamically stabilized with initialvolume replacement, obviously need less bloodtransfusion, have shorter hospital stay and lowermorbidity and mortality rates during NOM.In the present study, 33 patients from NOMgroup had an USG follow up and 15 patients hadCT which showed some degree of improvement inall patients. The follow up CT gives the surgeonfeeling that his patient is in the right way andmakes him feel comfortable by observing theradiological improvement of the injury. Actuallysome recent studies showed that routine follow-upCT for patients managed non-operatively isunnecessary if the patient remained clinicallystable [25,26] . Patients should avoid contact sport foreight weeks at least after having NOM with a CTfollow up [16] .

148Outcome of Non-operative Management of Blunt Splenic Trauma June 2007CONCLUSIONNOM for blunt splenic trauma inhemodynamically stable patients is safe, effective,associated with less blood transfusion, shorterhospital stay, low morbidity and no mortality.However, NOM should be practiced in hospitalswhere the facilities of ICU or HDU are available.REFERENCES1. Pearce RM, Krumbhaar EB, Frazier CH. Experimental &clinical studies. Philadelphia, JB Lippincott, 1918; 3-10.2. O’ Donnell FJ. The value of splenectomy in Banti’s disease.Br Med J 1929; 854.3. Malangoni MA. Splenic salvage; current expectations andresults. In: Mauli KI, Cleveland HC, Strauch GO, WolferthCC, editors. Advances in Trauma. Chicago: Mosby-Year-Book, 1990, p123-141.4. Sorkey AJ, Farnell MB, Williams HJ Jr, Mucha P Jr, IlstrupDM. The complementary roles of diagnostic peritoneallavage and computed tomography in the evaluation ofblunt abdominal trauma. Surgery 1989; 106:794-800.5. Upadhyaya P, Simpson JS. Splenic trauma in children. SurgGynecol Obstet 1968; 126:781-792.6. Wesson DE, Filler RM, Ein SH, Shandling B, Simpson JS,Stephens CA. Ruptured spleen - when to operate? JPediatr Surg 1981; 16: 324-326.7. King DR, Lobe TE, Haase GM, Boles ET Jr. Selectivemanagement of injured spleen. Surgery1981; 90:677-682.8. Kakkasseril JS. Changing treatment of pediatric splenictrauma. Arch Surg1982; 117:758-759.9. Hebeler RF, Ward RE, Miller PW, Ben-Menachem Y. Themanagement of splenic injury. J Trauma 1982; 22:492-495.10. Morgenstern L, Uyeda RY. Non-operative management ofinjuries of the spleen in adults. Surg Gynecol Obstet 1983;157:513-518.11. Zucker K, Browns K, Rossman D, Hemingway D, Saik R.Nonoperative management of splenic trauma.Conservative or radical treatment? Arch Surg 1984; 119:400-404.12. Green JB, Shackford SR, Sise MJ, Fridlund P. Late septiccomplications in adults following splenectomy for trauma:a prospective analysis in 144 patients. J Trauma 1986;26:999-1004.13. Di Cataldo A, Puleo S, Li Destri G, et al. Splenic trauma andoverwhelming postsplenectomy infection. Br J Surg 1987;74:343-345.14. Cullingford GL, Watkins DN, Watts ADJ, Mallon DF. Severelate postsplenectomy infection. Br J Surg 1991; 78:716-721.15. Lynch AM, Kapila R. Overwhelming postsplenectomyinfection. Infect Dis Clin North Am 1996; 10:693-707.16. Pachter HL, Guth AA, Hofstetter SR, Spencer FC. Changingpatterns in the management of splenic trauma: The impactof non-operative management. Ann Surg 1998; 227:708-719.17. Clancy TV, Ramshaw DG, Maxwell JG, et al . Managementoutcomes in splenic injury: a statewide trauma centerreview. Ann Surg 1997; 226:17-24.18. Cogbill TH, Moore EE, Jurkovich GJ, et al. Nonoperativemanagement of blunt splenic trauma: A m u l t i c e n t e rexperience. J Trauma 1989; 29:1312-1317.19. Hunt JP, Lentz CW, Cairns BA, et al. Management andoutcome of splenic injury: the results of a 5-year statewidepopulation based study. Am Surg 1996; 62:911- 917.20. Smith JS Jr, Cooney RN, Mucha P J r. Nonoperativemanagement of the ruptured spleen; a revalidation ofcriteria. Surgery 1996; 120:745-750.21. A rcher LP, Rogers FB, Shackford SR. Selective nonoperativemanagement of liver and spleen injuries inneurologically impaired adult patients. Arch Surg 1996;131:309-315.22. Godley CD, Warren RL, Sheridan RL, McCabe CJ. Nonoperativemanagement of blunt splenic injury in adults: ageover 55 years as powerful indicator of failure. J Am CollSurg 1996; 183:133-139.23. Powell M, Courcoulas A, Gardner M, et al. Management ofblunt splenic trauma: significant differences between adultsand children. Surgery 1997; 122:654-660.24. Sclafani SJ, Shaftan GW, Scalea TM, et al. Nonoperativesalvage of computed tomography - diagnosed splenicinjuries: utilization of angiography for triage andembolization for hemostasis. J Trauma 1995; 39:818-827.25. Allins A, Ho T, Nguyen TH, Cohen M, Waxman K, Hiatt JR.Limited value of routine follow up CT scans in nonoperativemanagement of blunt liver and splenic injuries.Am Surg 1996; 62: 883-886.26. Lawson DE, Jacobson JA, Spizarny DL, Pranikoff T. Splenictrauma: Value of follow up CT. Radiology 1995; 194:97-100.

June 2007KUWAIT MEDICAL JOURNALOriginal ArticleTotal Thyroidectomy for Bilateral Benign Thyroid Disease:Safety Profile and Therapeutic EfficacySalman Yousuf Guraya, Omer Al Faroug EltinayDivision of General Surgery, Department of Surgery, College of Medicine and King Khalid University Hospital,Riyadh, Kingdom of Saudi ArabiaABSTRACTObjective: To analyze the safety and effectiveness of totalthyroidectomy in the surgical management of bilateralmultinodular goiterDesign: RetrospectiveS e t t i n g : King Khalid University Hospital, Riyadh,Kingdom of Saudi ArabiaPatients and Methods: The medical re c o rds of allpatients who underwent total thyroidectomy over a fiveyearperiod (August 2000 through July 2005) at KingKhalid University Hospital, Riyadh, KSA, wereexamined. The data regarding age, sex, indication forsurgery, histological diagnosis, and complications, if anywas extracted from the files.Results: There were a total of 164 patients (113 femaleand 51 male). Their age ranged from 18 - 63 years with amean of 40 ± 11.0 years. Seventy six (46.3%) casesp resented with compressive and 29 (17.6%) withKuwait Medical Journal 2007, 39 (2):149-152thyrotoxic symptoms; 24 (14.6%) for cosmetic reasons, 18(10.9%) for suspected malignancy and 3 (1.8%) withretrosternal extension. Multinodular goiter was the mostf requent histological finding (reported in 88, 51.8%patients) followed by colloid goiter in 22 (13.4%) cases.Incidental thyroid malignancy was recorded in 13 (8%)subjects, (five papillary and six follicular carcinomas, onelymphoma and one follicular variant of papillarycarcinoma). Permanent recurrent laryngeal nerve (RLN)palsy and permanent hypoparathyroidism occurred inone (0.6%) and five (3%) patients respectively. There wasno mortality.Conclusion: Total thyroidectomy is a safe alternative forpatients with bilateral multinodular goiter. Thisprocedure has low complication rate and eliminates theneed for re-operation for recurrent goiter and unexpectedthyroid malignancy.KEYWORDS: hypoparathyroidism, multinodular goiter, recurrent laryngeal nerve palsy, total thyroidectomyINTRODUCTIONMultinodular goiter (MNG) is the mostcommon indication for thyroidectomy in endemiciodine-deficiency re g i o n s [ 1 ] . Although totalthyroidectomy represents almost half of all thyroidoperations carried out [2,3] , its role in the treatment ofbenign thyroid disease remains contro v e r s i a l .There is growing evidence that total thyroidectomyis appropriate for patients with MNG when there issignificant nodular disease involving both lobes [4,5] .Subtotal thyroidectomy has previously beenadvocated for the treatment of bilateral nodulardisease but recurrence rates as high as 45 percenthave been reported [6] . In general, about half of thepatients who develop recurrence of benign goiterrequire surgical re-excision, which carries a greatlyincreased risk of permanent complications [7,8] . Atthe same time, several studies have demonstratedthat total thyroidectomy can be performed with amorbidity rate comparable to that of lesserprocedures [9,10,11] .The central premise of this study was toevaluate the outcome of total thyroidectomy forbenign thyroid affections in a tertiary careinstitution.PATIENTS AND METHODSBetween August 2000 and July 2005, all patientsundergoing total thyroidectomy for bilateral MNGwere enrolled in this retrospective study. Patientswith thyroid cancer, recurrent goiter and thosep resenting with solitary thyroid nodules wereexcluded from the series. Thus the studypopulation represents a select group of patients forwhom the preoperative clinical diagnosis andintention was the surgical treatment of bilateralMNG. Data was extracted regarding patients’ age,sex, indications for surgery, operation performed,final histological diagnosis and complications.Goiter was evaluated by three components: thyroidfunction test by free thyroxine and thyro i dstimulating hormone, fine needle aspirationAddress correspondence to:Dr Salman Yousuf Guraya FRCS, Assistant Professor Surgery and Consultant Surgeon, College of Medicine Taibah University, P.O. Box: 30001Madina Al Munawara, Kingdom of Saudi Arabia, Tel: +966 4 8460008, E- mail: drsyg7@yahoo.com

150Total Thyroidectomy for Bilateral Benign Thyroid Disease: Safety Profile and Therapeutic Efficacy June 2007Table 1: Indications for total thyroidectomy (n = 164)Indication Number %(female, male)Suspected malignancy 18 (10, 8) 10.9Thyrotoxicosis 29 (25, 4) 17.6Cosmetic/patient’s apprehension 24 (19, 5) 14.6Compressive symptoms 76 (49, 27) 46.3Retrosternal extension 03 (2, 1) 1.8Unknown 14 (5, 9) 8.5Table 3: Complications of total thyroidectomy (n = 164)Complication Number %Hemorrhage 2 1.2Seroma 14 8.5Wound abscess 06 3.6Recurrent laryngeal nerve palsyTemporary 11 6.7Permanent 01 0.6HypoparathyroidismTemporary 28 17Permanent 05 03cytology (FNAC) to exclude malignancy andultrasonography to define the extent of disease. CTscan was used selectively in patients with massive,retrosternal or clinically malignant goiter, or in asuspected posterior extension of the nodules. Apreoperative serum calcium concentration (totaland corrected) was checked routinely andlaryngoscopic examination of the vocal cords wasdone, if necessary. Surgeon’s assessment of thepatients’ voice was a reliable method to suspectvocal cord palsy during the postoperative period [12] .Total thyroidectomy was performed by as t a n d a rd technique of capsular dissection.Recurrent laryngeal nerves (RLN) were routinelyidentified on both sides and every attempt wasmade to identify and preserve the parathyroidglands. Those glands with compromised bloodsupply were excised, diced and reimplanted in thesternocleidomastoid muscle. All wounds wereclosed with suction drains and in the absence ofany complication patients were discharged on thethird day.Postoperative serum calcium levels wereestimated twice daily for 48 hours after surgery andthen subsequently as re q u i red. Calcium supplementwas given if serum calcium level dropped below 1.9mmol/l or in case of symptomatic hypocalcemia.Hypoparathyroidism was considered transient ifthe patient could be weaned from calciumsupplement within six months and labeled aspermanent if the patient re q u i red calciumtreatment to maintain normal serum calcium for sixmonths or longer. Laryngoscopy was advisedpostoperatively in patients with hoarseness or lossTable 2: Histological diagnosis of thyroid specimens (n =164)Histopathology Number %Benign 151 92Multinodular goiter 85 51.8Colloid goiter 22 13.4Thyroid hyperplasia 14 8.5Hashimoto’s thyroiditis 17 10.3Grave’s disease 08 4.8Follicular adenoma 05 3.0Malignant 13 8.0Papillary carcinoma 05 3.0Follicular carcinoma 06 3.6Lymphoma 01 0.6Follicular variant of papillarycarcinoma 01 0.6of voice quality and RLN palsy was defined astransient if there was a laryngoscopic evidence ofRLN recovery within six months of operation. Oralthyroxine supplementation was started on the dayof discharge at a dose of 100-200 microgram perday, according to the body weight. Follow up wasplanned two weeks after discharge, every threemonths for the first year and then every six monththereafter with thyroid function test and serumcalcium, if indicated. The data analysis andi n t e r p retation was performed on SPSS 10.0software package (SPSS Inc., Chicago, IL).RESULTSOne hundred and sixty-four patients wereincluded in this study which included 113 womenand 51 men with a mean age of 40 ± 11.0 years(range = 18-63 years). Compressive symptomsobserved in 76 (46.3%) patients were the mostfrequent indication for total thyroidectomy (Table1). FNAC analyses reported 116 colloid goiters, 13t h y roid hyperplasia, 14 thyroiditis, 3 follicularadenoma, and 18 inconclusive aspirates. Thehistological diagnoses of the resected thyroid glandspecimens is detailed in Table 2 and includes 13(8%) patients with thyroid cancer: 5 (3%) papillary,6 (3.6%) follicular carcinoma, 1 (0.6%) lymphoma,and 1 (0.6%) follicular variant of papillarycarcinoma. Thyroid malignancy was not detectedby FNAC in these patients preoperatively. Table 3lists the complications encountered in this study.Major early postoperative complications such ash e m o r rhage, huge seromas or wound infectionrequiring re-operation occurred in 22 (13.4%)patients collectively. Temporary RLN was observedin 11 (6.7%) cases (7 right sided and 4 left sided).One (0.6%) patient sustained permanent right RLNp a l s y. Twenty eight (17%) patients developedtransient and five (3%) permanent hypoparath y roidism. Permanent RLN and hypoparathy-

June 2007KUWAIT MEDICAL JOURNAL 151roidism were seen in the same patient who hadtough adhesions between the gland ands u r rounding tissue (histopathology: papillarycarcinoma). There was no mortality in this study.DISCUSSIONThe outcome of endocrine surgical diseases ism e a s u red by the success of the operation atrelieving the endocrinopathy and the ability of thesurgeon to minimize postoperative morbidity [13] .Currently, opinions differ on both the proper extentof primary resection and the need for re-operationfor nodular benign thyroid disease [ 14 ] . Subtotalthyroidectomy was advocated to be safer than totalthyroidectomy [15] as it was thought that leavingbehind some thyroid tissue would pre v e n tsubsequent thyroxine replacement. However,nodules can also arise from portions of the glandthat were previously normal, and small nodulescan become symptomatic. In addition, recurrencerates as high as 42 to 45 percent have been reportedfollowing subtotal thyro i d e c t o m y [ 16 , 17 ] . The incidenceof recurrence has been directly related to a longpostoperative follow up and to large amounts ofremnant tissue [18,19] Most recurrences develop 10 to20 years after the primary surgery [20] . It has beendocumented that total thyroidectomy can beperformed safely in benign nodular goiter, but reoperationscarry a five-fold risk of surg i c a lcomplications where both sides had been dissectedpreviously [11,20,21,22,23] . Patients with recurrent MNGoften present with severe symptoms, includingdyspnea, dysphagia, and pain which may be due toa small postero-lateral lobule of the thyroid leftbehind during subtotal thyroidectomy. This oftenextends into the retro- esophageal area, causingsignificant pre s s u re symptoms [ 9 ] . Scarring anddisruption of normal tissue planes make furtherthyroid surgery more hazardous.Bron et al [23] concluded in their study on 834patients that total thyroidectomy for benign thyroiddisease prevented disease re c u r rence and minimizedthe morbidity associated with secondary operation.Giles and associates [ 1 ] reported 8.2 perc e n tincidence of thyroid cancer in MNG withoutprevious suspicion of malignancy and that subtotalthyroidectomy resulted in a substantial number ofcompletion thyroidectomies. Our study revealed an8 percent incidence of incidentally diagnosedt h y roid malignancy without the need for re o p e r a t i o n .The only strong argument against totalthyroidectomy is the potentially higher associatedcomplication rate. However, with experience andappropriate surgical technique, the morbidity oftotal thyroidectomy can be minimized [24,25] . Presentstudy demonstrated 0.6 percent incidence ofpermanent RLN palsy and 3 percent incidence ofpermanent hypoparathyroidism while re c e n tstudies of total thyroidectomy for benign diseasehave reported an incidence of 0.3 to 1.7 percent and0.7 to 3 percent re s p e c t i v e l y [ 20 , 26 , 27 ] . This is littledifferent from the complication rates recorded aftersubtotal thyroidectomy; 0.2 percent for permanentRLN palsy and 0.3 percent for permanenth y p o p a r a t h y ro i d i s [ 2 m0 ] . Capsular dissection technique,which reduces damage to parathyroid glands andp rotects RLN, has reduced the morbidity incomparison to the complication rates describedearlier [28] . During re-operation the incidence of RLNpalsy ranges from 15 to 23 percent for temporary[8, 29]and 2.6 to 15.5 percent for permanent palsywhich makes total thyroidectomy the procedure offirst choice by many surgeons, whenever the wholegland shows nodular transformation [7,30] . Publisheddata described 47 to 53 percent incidence formalignancy in prophylactic completion thyro i d e c t o m yspecimens after initial lobectomy for solitaryt h y roid nodule [ 31 , 32 ] . This observation furthersubstantiates the role of total thyroidectomy in caseof unexpected thyroid malignancy, which willallow I 131 scanning to detect and treat metastaticdisease. The reported incidence of 0.9 to 1.6percent [7,30] for permanent hypoparathyroidism isslightly higher than 0.6 percent noted in our study.The current policy to reimplant diced parathyroidglands in muscle is widely accepted as an efficientway to avoid long term hypoparathyroidism [33] .CONCLUSIONWe recommend total thyroidectomy for bilateralmultinodular goiter to prevent disease recurrenceand to obviate the need for completiont h y roidectomy in case of a final diagnosis ofthyroid malignancy.REFERENCES1. Giles Y, Boztepe H, Terzoiglu T, Tezelman S. The advantageof total thyroidectomy to avoid reoperation for incidentalthyroid cancer in multinodular goiter. Arch Surg 2004;139:179-182.2. Gough IR, Wilkinson D. Total thyroidectomy formanagement of thyroid disease. World J Surg 2000; 24:962-963.3. Khadra M, Delbridge M, Reeve TS, Poole AG, Crummer P.Total thyroidectomy: its role in the management of thyroiddisease. Aust N Z J Surg 1992; 62:91-95.4. Rossi RL, Cady B, Silverman ML, Wool MS, Horner TA.Current results of conservative surgery for differentiatedthyroid carcinoma. World J Surg 1986; 10:612-622.5. Liu Q, Dijuricin G, Prinz R. Total thyroidectomy for benignthyroid disease. Surgery 1998; 123:2-7.6. Waldstrom C, Zedenius J, Guinea A, Reeve T, Delbridge L.Multinodular goiter presenting as a clinical single nodule:how effective is hemithyroidectomy? Aust NZ J Surg 1998;69:34-36.7. Mishra A, Agarwal A, Agarwal G, Mishra SK. To t a l

152Total Thyroidectomy for Bilateral Benign Thyroid Disease: Safety Profile and Therapeutic Efficacy June 2007thyroidectomy for benign thyroid disorders in an endemicregion. World J Surg 2001; 25:307-310.8. Reeve TS, Delbridge L, Brady P, Crummer P, Smyth C.Secondary thyroidectomy: a twenty-year experience. WorldJ Surg 1988; 12:449-453.9. Colak T, Akca T, Kanik A, Yapici D, Aydin S. Total versussubtotal thyroidectomy for the management of benignmultinodular goiter in an endemic region. Aust NZ J Surg2004; 74:974-978.10. Koru N, Asci C, Yilmazlar T, et al. Total thyroidectomy orlobectomy in benign nodular disease of the thyro i d :changing trends in surgery. Int Surg 1997; 82:417-419.11. Pappalardo G, Guadalaxara A, Frattaroli FM, Illomei G,Falaschi P. Total compared with subtotal thyroidectomy inbenign nodular disease: personal series and review ofpublished reports. Eur J Surg 1998; 164:501-506.12. Menegaux F, Turpin G, Dahman M, et al. Secondarythyroidectomy in patients with previous surgery for benigndisease: a study of 203 cases. Surgery 1999; 126:479-483.13. Reeve TS, Delbridge L, Cohen A, Crummer P. To t a lt h y roidectomy: the pre f e r red option for multinodulargoiter. Ann Surg 1987; 206:782-786.14. Wilson DB, Staren ED, Prinz RA. Thyroid Reoperations:Indications and risk. Am Surg 1998; 64:674-678.15. Hay ID, Grant CS, Taylor WF, McConahey WM. Ipsilaterallobectomy versus bilateral lobar resection in papillarythyroid cancer: a retrospective analysis of surgical outcomeusing a novel prognostic scoring system. Surgery 1987;102:1088-1095.16. Rojdmark J, Jarhult J. High long term recurrence rate aftersubtotal thryoidectomy for nodular goiter. Eur J Surg 1995;161:725-727.17. Geerdsen JP, Frolund L. Recurrence of non toxic goiter withand without prospective thyroxine medication. ClinEndocrinol 1984; 21:529- 533.18. Piraneo S, Vitri P, Galimberti A, Salvaggio A, Bastalgi A.Ultrasonographic surveillance after surgery for euthyroidgoiter in patients treated or not treated with thyroxine. EurJ Surg 1997; 163:21-26.19. Zelmanovitz T, Zelmanovitz F, Genro S, Gus P, de AzevedoMJ, Gross JL. Analysis of the factors associated with therecurrence of post thyroidectomy goiter. Rev Assoc MedBras 1995; 41:86-90.20. Delbridge L, Guinea AI, Reeve TS. Total thryoidectomy forbilateral benign multinodular goiter: effect of changingpractice. Arch Surg 1999; 134:1389-1393.21. Siragusa G, Lanzara P, Di Pace G. Subtotal thyroidectomyor total thyroidectomy in the treatment of benign thyroiddisease: our experience [in Italian]. Minerva Chir 1998;53:233-238.22. Gough IR, Wilkinson D. Total thyroidectomy for managementof thyroid disease. World J Surg 2000; 24:962-965.23. Bron LP, O’Brien CJ. Total thyroidectomy for clinicallybenign disease of the thyroid gland. Br J Surg 2004; 91:569-574.24. Gough IR. Total thyroidectomy: indications, technique andtraining. Aust NZ J Surg 1992; 62:87-89.25. Bhattacharyya N, Fried MP. Assessment of the morbidityand complications of total thyroidectomy. Arch OtolaryngolHead Neck Surg 2002; 128:389-392.26. Thomusch O, Machens A, Sekulla C, Ukkat J, Lippert H,Gastinger I. Multivariate analysis of risk factors forpostoperative complications in benign goiter surg e r y :prospective multicenter study in Germany. World J Surg2000; 24:1335-1341.27. Liu Q, Dijuricin G, Prinz RA. Total thyroidectomy inmanagement of 909 patients with thyroid disease. Surgery1998; 123:2-7.28. Martensson H, Ternis J. Recurrent laryngeal palsy rate inthyroid gland surgery related to operations and nerves atrisk. Arch Surg 1985; 120:475-477.29. Wheeler MI. Thyroid surgery and the recurrent laryngealnerve. Br J Surg 1999; 86:291-292.30. Muller PE, Kabus S, Robens E, Spelsberg F. Indication, risks,and acceptance of total thyroidectomy for multinodulargoiter. Surg Today 2001; 31:958-962.31. Eroglu A, Berberglu U, Buruk F, Yildirim E. Completionthyroidectomy for differentiated thyroid cancer. J SurgOncol 1995; 59:261-267.32. Pasieka JL, Thompson NW, Mcleod MK, Burney RE. Theincidence of bilateral well differentiated thyroid cancerfound at completion thyroiectomy. World J Surg 1992;16:711-717.33. de Roy van Zuidewijin DBW, Songun I, Kievit J, van deVelde CJH. Complications of thyroid surgery. Ann SurgOncol 1995; 2:56-60.

June 2007KUWAIT MEDICAL JOURNALOriginal ArticleThe Influence of Insufficient Exposure to Sunlight onVitamin D Deficiency and Related Symptoms amongWomen in the State of KuwaitSameer Al-Shammari, Reda Helal, Rashed Al-Hamdan, Osman Mapkar, Koppolu PrasadDepartment of Medicine, Al-Jahra Hospital, KuwaitABSTRACTObjectives: To study Vitamin D deficiency as a cause ofosteomalacia in young women and to assess thetherapeutic effects of high dose vitamin D and sunlightexposureDesign: ProspectiveSetting: Al-Jahra hospital, KuwaitS u b j e c t s : Twenty four consecutive patients withosteomalacia presenting to the endocrinology clinicI n t e r v e n t i o n :High dose vitamine D, calcium supplements,sunlight exposure and increased consumption of dairyproductsMain outcome measure: We confirm that adequatesunlight exposure is an essential factor in the preventionof osteomalacia.Results: All the 24 patients were female and their meanage and standard deviation (SD) was 23.08 ± 9.14 years.The means and SD of initial biochemical parameters andKuwait Medical Journal 2007, 39 (2):153-156during treatment respectively were: serum calcium = 2.12± 0.14, 2.24 ± 0.37 mmol/l (N = 2.2 - 2.6), seru mphosphate = 0.88 ± 0.26, 1.28 ± 0.24 mmol/l (N = 0.8 - 1.6),alkaline phosphatase = 413.1 ± 292.2, 220.7 ± 186.0mmol/l (N = 95 - 200), urinary calcium = 1.26 ± 0.95, 2.16± 1.67 mmol/24 hr (N = 0.33 - 7.5), urine phosphate = 8.10± 6.14, 8.52 ± 8.87 mmol/24 hr (N = 13 - 42), serum PTH= 38.68 ± 23.43, 10.85 ± 4.49 pmol/l (N = 0.7 - 5.6),25(OH)D = 8.10 ± 8.05nmol/l (N = 23 - 113) and bonedensitometry scan = -2.086 ± 0.91.Conclusion: Osteomalacia due to insufficient sunlightexposure and inadequate dairy product consumption isnot uncommon even in a sunny climate. The patientsimproved after treatment with high dose of vitamin D,adequate sunlight exposure and consumption dairyproducts.KEYWORDS: health education, high dose vitamin D, sunny climate, osteomalaciaINTRODUCTIONSince 1920, rickets has almost disappeared inthe western world because of the use of cod liveroil or vitamin D preparations and by adequateexposure to sunshine [1,2] . In 1967 it was recognizedthat osteomalacia was more common thanexpected especially in elderly women [3] . The majorrole of vitamin D is to increase the absorption ofcalcium and phosphate for the mineralization ofthe skeleton. Vitamin D deficiency results in failureof mineralization of a growing or a mature bonecausing rickets in children or osteomalacia inadults respectively. Vitamin D3 or cholecalciferol, issynthesized in the skin from conversion of theprecursor, 7-dehydrocholesterol by the ultraviolet(UV) light of the sun. UV radiation passes throughglass and most plastics but not through heavyclothing and sunscreens [1] .Vitamin D is hydroxylated in the liver into 25-hydroxyvitamin D [25(OH)D], which is the majorcirculating metabolite [4] . Further hydroxylation into1, 25-dihydroxyvitamin D [1,25(OH) 2D] occursprimarily in the kidney. The hydroxylation in thekidney is stimulated by parathyroid hormone(PTH) and suppressed by phosphate. 1,25(OH)2Dis the most active metabolite stimulating theabsorption of calcium and phosphate from the gut,whereas 25(OH)D has limited biological activity.Vitamin D binding protein (DBP) binds vitamin Dand its metabolites and transports them in thebloodstream. Some nutrients also contain vitaminD3, e . g ., fatty fish, eggs and fortified dairyproducts. Vitamin D deficiency causes stimulationof the parathyroid glands, which may lead to highbone turnover, bone loss, and hip fracture s .Vitamin D deficiency was suspected in patientswith symptoms of bone pain and muscle weaknessand was diagnosed by low serum calcium andphosphate levels and elevated alkaline phosphataseactivity. In this study, we reviewed the cause of(This article was presented at the 12 th International Conference of the Kuwait Medical Association, April 1-4, 2007)Address correspondence to:Dr. Sameer Al-Shammari, P.O. Box 528, Jahra Central 01005, Kuwait. E-mail: tafi88@yahoo.com

154The Influence of Insufficient Exposure to Sunlight on Vitamin D Deficiency and Related ... June 2007vitamin D deficiency in patients with osteomalaciathat was complicated with osteoporosis in some ofthem in a place with sunny climate (Kuwait) andassessed the clinical and biochemical effect of highdoses of vitamin D in the treatment of osteomalacia.SUBJECTS AND METHODSFrom July 2002 to June 2003, we recruited 24consecutive patients with osteomalacia. Patientswere referred to the metabolic bone disease clinic inAl-Jahra hospital, Kuwait, from orthopedic ormedical outpatient clinics for evaluation ofosteomalacia. They presented with symptoms ofbone pain, fatigue, proximal muscle weakness,biochemical findings and/or radiological imagessuggestive of osteomalacia. Other causes of ricketsand osteomalacia apart from vitamin D deficiencysuch as inadequate dietary ingestion or insufficientsunlight exposure were excluded by appropriateclinical and laboratory investigations. The clinicalparameters recorded were: age, sex, exposure tosunlight (exposure of the uncovered face and armsor lower legs to sun light at least 10 minutes daily),diet that contain at least 1 g of calcium per day, andsymptoms of generalized weakness, numbness,bone pain, and signs of proximal myopathy. Thebiochemical parameters recorded initially and aftertreatment with high dose vitamin D were: serumcalcium, phosphate, alkaline phosphatase, urinarycalcium and phosphate, PTH and 25(OH)D levels.The bone mineral density of the lumbar andfemoral sites was performed in most patients usinga DEXA scan. Osteopenia is defined according tothe WHO as T- Score = -1 and > -2.5 ando s t e o p o rosis as T- s c o re ≤ -2.5. Complete bloodcount, liver and renal profiles were performed in allpatients. Patients were treated with oral vitamin D(ergocalciferol) 600,000 U per week for two weeks,then every other week for two doses then oncemonthly for three months. They were also givenoral calcium 1.5 g per day in the form of calciumcarbonate or citrate. Symptoms of hypercalcemia ifany, such as lethargy, fatigue, confusion, nausea,vomiting, constipation, polyuria, polydipsia andabdominal pain were noted. Health education inthe value of sunlight exposure for at least 10minutes daily of the uncovered skin such as theface, arms and/or legs and consumption of at least1 g of calcium daily from dairy product, greenvegetables and/or fish consumption was given tothe patients verbally in the clinic. Exclusion criteriaincluded patients with liver, gastrointestinal orkidney disease and those on any medication thati n t e r f e res with vitamin D metabolism such asantiepileptic drugs.RESULTSAll the 24 patients diagnosed with osteomalaciaTable 1a: P re - t reatment biochemical values of patients withosteomalaciaPatient Calcium Phosphate Alkaline Urinary PTH25 (OH)DNo. (mmol/l) (mmol/l) phospha- Calcium phosphate (pmol/l) leveltase(mmol/l) (mmol/24hr) (nmol/l)1 2.24 0.9 738 0.87 9.6 32.4

June 2007KUWAIT MEDICAL JOURNAL 155Table 1b: biochemical values post-treatment with high dose of vitD.Patient Calcium Phosphate Alkaline Urinary PTH25 (OH)DNo. (mmol/l) (mmol/l) phospha- Calcium phosphate (pmol/l) leveltase(mmol/l) (mmol/24hr) (nmol/l)1 2.51 1.32 273 7.1 2.68 4.7 1022 2.29 1.71 126 0.9 4.7 1.2 1203 2.36 1.22 72 3.49 10.1 5.9 784 2.34 1.57 144 6.2 9.4 4.4 1125 2.17 1.01 224 2.33 8.43 10.1 1556 2.18 0.92 119 3.32 12.3 5.5 2227 2.32 1.67 34 1.04 21.4 2.8 808 2.04 1.32 85 4.12 4.5 16.3 969 2.4 1.39 469 3.66 16.3 19.1 10910 2.6 1.22 122 2.46 7.92 17.4 6511 2.26 1.77 272 2.8 9.4 6.1 19412 2.4 1.44 360 2.61 8.8 12.6 9013 2.35 1.34 215 1.99 1.01 4.61 5014 2.4 1.47 68 3.21 5.96 2.33 14115 2.32 1.35 166 1.86 6.73 5.5 —-16 2.31 1.19 93 1.02 8.7 4.93 7817 2.09 1.12 219 1.82 0.27 6.22 8918 2.34 1.35 122 2.0 5.4 3.8 —-19 2.3 1.41 96 0.98 4.2 2.15 3920 2.61 2.44 112 3.21 4.47 5.2 12021 2.4 1.33 147 — — —- 7522 2.2 1.04 401 2.31 6.11 7.01 8123 2.19 1.02 213 1.97 9.01 5.7 6524 2.41 1.23 89 3.12 .95 4.3 91— = data not availablehr (normal = 13-42), serum PTH = 38.68 ± 23.43,10.85 ± 4.49 pmol/l (normal = 0.7-5.6), 25(OH)D =8.10 ± 8.05 nmol/l (normal = 23-113) and skeletal X-ray showed pseudofractures (looser’s zones, whichare nearly pathognomonic features of rickets andosteomalacia) in some of our patient andpathological fracture in one patient. Bonedensitometry scan showed osteopenia andosteoporosis in most patients and the mean T-Scorewas - 2.086 ± 0.91. All symptoms and signsimproved dramatically during treatment with highdose of vitamin D and calcium. Health educationthat helped in greater exposure to sunlight (at least10 minutes daily) and an increase in theconsumption of dairy products to obtain approximately1 g of calcium daily had an important role inthe management. There were no re p o r t e dsymptoms or biochemical finding of hyperc a l c e m i a .DISCUSSIONIn our study, we found that patients in a sunnyclimate like Kuwait may still present withosteomalacia due to vitamin D deficiency as a resultof insufficient sunlight exposure and inadequatedairy product intake. Almost all our patient (96%)consumed less than 1,000 mg of calcium per week,while the daily requirement is about 1,200 mg. Alsosome of our patients were from the lowsocioeconomic status and lived in houses wherelittle if any sunlight was allowed to enter. Theywere also ignorant about the value of vitamin Dand calcium for the process of bone mineralization.They were eating very minimal amounts of calciumcontaining products (because they did not like milkand/or diary products) and they were wearingtraditional or religious clothing that covered all thebody except the eyes (long dress hejab, niquab,abaya, gloves and socks). This resulted ininadequate exposure to sunlight re q u i red forvitamin D synthesis. These overclothing styleamong women as young as eight years old maylead to vitamin D deficiency. This also explains whyall our patients were female since this clothinghabit is exclusive to women. This is in agreementwith a previous study which concluded thatvitamin D deficiency in the Middle East was due toclothing habits [5] . It is also known from previousstudies that UV radiation passes through glass andmost plastics [ 1 ] but not through clothing andsunscreen [6,7] .The prevalence of osteomalacia due to vitaminD deficiency is unknown in Kuwait and anepidemiological study is required.Almost all of our patients presented with typicalnon-specific symptoms of osteomalacia such aslethargy, proximal muscle weakness, and diffusebone pain. We noticed that proximal muscleweakness is so prominent among our patients thatit can be used as a good indicator of improvementfollowed by other symptoms like diffuse bone painand the feeling of lethargy. On presentation onepatient had symptoms of hypocalcemia (numbnessand tingling sensation around the mouth andc o r rected serum calcium found to be low (1.8mmol/l) and another had a pathological fracturedue to severe osteoporosis which is a knowncomplication of severe osteomalacia.The clinical diagnosis of osteomalacia is basedon the findings of low levels of 25(OH)D, serumcalcium, serum phosphate, urinary calcium andphosphate and increased levels of alkalinephosphatase, PTH. These abnormal biochemicalfindings result from vitamin D deficiency whichresults in decreased intestinal absorption of calciumand phosphate that consequently lead to secondaryh y p e r p a r a t h y roidism. The cornerstone in thediagnosis of osteomalacia is the demonstration of areduction in the mineral apposition rate,mineralization surface, and bone formation rate,which can be measured after the administration ofdouble tetracycline labels before the bone biopsy.The diagnosis of osteomalacia in our patients wasobvious from the clinical presentation, biochemicalfinding and radiological images. Therefore, therewas no need for an invasive pro c e d u re liketranscortical bone biopsy to establish the diagnosis.

156The Influence of Insufficient exposure to Sunlight on Vitamin D Deficiency and Related ... June 2007We treated our patients with oral vitamin D(Ergocalciferol) 600,000 U per week for two weeks;then every other week for two doses and then oncemonthly for three months. We closely observedthem for clinical features or biochemical finding ofvitamin D intoxication such as bone resorption,h y p e rcalcemia, hypercalciuria, and/or re n a lfunctional impairment. We did not encounter anycomplication when using such large doses ofvitamin D in healthy young patients. Hyperc a l c e m i adue to high dose of vitamin D has been reported infew previous studies, where hypercalcemia wasobserved in older patients with a dose of 2000IU/day and in one patient receiving a single oraldose of 600,000 IU. We did not have thiscomplication possibly because our patients wereyoung, healthy and without renal impairment andwe treated them for short period of time. Theo c c u r rence of vitamin D intoxication is ratherunpredictable, and it may occur even after years.Although practical, high doses may not be as safeas low doses.We also treated our patient with 1-3 g ofelemental calcium per day. Serum calcium wasnormal in 87.5% of patients and that was due tocompensatory secondary hyperparathyro i d i s m .Calcium deficiency has been suggested as a causeof rickets in children with apparently goodexposure to sunlight in Nigeria and Bangladesh [8,9] .Another study also showed that a very low dietarycalcium intake might cause histologicalosteomalacia [10] .Results of treatment of patient with vitamin Dmay be judged by monitoring the improvement inclinical features, biochemical tests such as increaseof serum 25(OH)D, the decrease of serum PTH,decrease of markers of bone turnover, increase inBMD and decreased incidence of fractures.P revention of vitamin D deficiency bysupplementation with a daily dose of 400-800 IU orconsumption of milk fortified with vitamin D3 (400IU/ quart or 400 IU/ liter) is very effective but maybe impractical [ 11 ] . Higher doses are seldom necessary,but 100,000 to 300,000 IU by mouth or byintramuscular injection have been used once everysix months or once yearly because of the ease ofadministration, obviating the need of checkingcompliance [5-7] . In these studies, hypercalcemia wasnot observed.Health education in the value of sunlighte x p o s u re for at least 10 minutes daily of theu n c o v e red skin e . g ., face, arms and legs andconsumption of at least 1 g of calcium daily fromdairy product, green vegetables and/ or fishconsumption should be widely recommended.CONCLUSIONOsteomalacia due to vitamin D deficiencysecondary to insufficient sunlight exposure andinadequate dairy product consumption is notuncommon in women of Jahra region of Kuwait inspite of the sunny climate. They impro v e dsymptomatically and biochemically, without illeffects, after treatment with high dose of vitamin D,and after health education that helped in greatere x p o s u re to sunlight and an increase in theconsumption of dairy products to obtainapproximately 1 g of calcium daily.REFERENCES1. Holick MF. McCollum award lecture 1994. Vitamin D: newhorizons for the 21 s t c e n t u r y. Am J Clin Nutr 1994; 60:619-630.2. Holick MF. Environmental factors that influence thecutaneous production of vitamin D. Am J Clin Nutr 1995;61:638-645.3. Sedrani SH, Elidrissy AWTH, El Arabi KM. Sunlight andvitamin D status in normal Saudi subjects. Am J Clin Nutr1983; 38:129-132.4. Norman AW, Roth J, Orci L. The vitamin D endocrinesystem: steroid metabolism, hormone receptors, andbiological response (calcium binding proteins). Endocr Rev1982; 3:331-366.5. Sedrani SH, Elidrissy AWTH, El Arabi KM. Sunlight andvitamin D status in normal Saudi subjects. Am J Clin Nutr1983; 38:129-132.6. Matsuoka LY, Wortsman J, MacLaughlin J, Hollis BW, Lu Z,Holick MF. Clothing prevents ultraviolet-B radiationdependentphotosynthesis of vitamin D. J Clin EndocrinolMetab 1992; 75:1099-1103.7. Matsuoka LY, Ide L, Wortsman J, MacLaughlin J, Holick MF.Sunscreens suppress cutaneous vitamin D synthesis. J ClinEndocrinol Metab 1987; 64:1165-1168.8. Fischer PR, Rahman A, Cimma JP, Kyaw-Myint TO, KabirAR, Talukder K. Nutritional rickets without vitamin Ddeficiency in Bangladesh. J Trop Pediatr 1999; 55:291-293.9. Okonofua F, Gill DS, Alabi ZO, Thomas M, Bell JL,Dandona P. Rickets in Nigerian children: a consequence ofcalcium malnutrition. Metabolism 1991; 40:209-213.10. Marie PJ, Pettifor JM, Ross F, Glorieux FH. Histologicalosteomalacia due to dietary calcium deficiency in children.N Engl J Med 1982; 307:584-588.11. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 andcalcium to prevent hip fractures in elderly women. N EnglJ Med 1992; 327:1637-1642.

June 2007KUWAIT MEDICAL JOURNALOriginal ArticleDelivery after Prior Cesarean Section in KuwaitAlexander Omu 1,2 , Majedah Al-Azemi 1,2, Jehad Al-Harmi 1,2, Huda Abdul Azeem 2 , Hanan N Al-Salem 21Department of Obstetrics and Gynecology, Faculty of Medicine and 2 Maternity Hospital, KuwaitABSTRACTIntroduction: There has been a dramatic increase in ratesof cesarean section (CS) worldwide. Vaginal deliveryafter prior CS is one of the strategies to reduce the highCS rate.Objective: To evaluate the mode of delivery after priorCS over a 14 year period from 1992 to 2005Study Design: Retrospective Clinical StudySetting: Maternity Hospital, KuwaitSubjects and Methods: The socio-demographiccharacteristics and the mode of delivery after prior CS of12,725 eligible women were extracted from the annualreports, perinatal and maternal committee re c o rd s ,patient files and the central CS registers for validation.Results: Out of 12,725 women with prior CS, 7655 (60%)achieved vaginal delivery (spontaneous vaginal delivery86% and instrumental vaginal delivery 14%). In 8%INTRODUCTIONThere has been a marked increase in the rate ofcesarean section (CS) worldwide [1,2] . To lessen thishigh rate and decrease the health care costsassociated with CS, deliberate efforts were made tore-examine the practice of elective CS [3-5] . Routineelective CS for a second delivery for women withprior lower segment CS results in an excess ofmaternal morbidity and mortality and a high costto medical re s o u rces and the medical team [ 6 - 8 ] .Complications related to further cesare a ndeliveries include placenta previa, accreta andhysterectomies. There are now many reports ofsignificant reduction of CS rates, while maintainingor even improving perinatal outcome [9] . Vaginalbirth after cesarean delivery has therefore beenadvocated as a safe and practical means ofreducing the overall CS rate. However, thep roportion of women who attempt vaginaldelivery after prior CS has decreased larg e l ybecause of concern about increased maternal andperinatal morbidity [10] . In some centers, only onet h i rd of patients with lower segment CS willrequire the procedure again if allowed a trial oflabor [11] .Kuwait Medical Journal 2007, 39 (2):157-161KEYWORDS: indications, prior CS, vaginal deliverywomen, elective CS was carried out mainly for abnormalp resentation, medical disorders, macrosomia andmultiple pregnancies. There was a downward trend inthe vaginal delivery rate from 65.7% in 1992 to 51.3% in2005. Infertility / IVF and multiple pregnancies increasedt h ree-fold as indications for repeat emergency CSbetween 1992-1995 and 2000-2005 periods. CS rate afterinduction of labor was 52% whereas 48% had vaginaldelivery.C o n c l u s i o n : After a prior CS, vaginal delivery wasachieved in 60% of the women with few complications.With appropriate selection of patients, vaginal delivery issafe. Active management of labor and involvement ofsenior staff in the decision to perform repeat CS isadvocated.Concerns have been raised by many about theoverall risk of uterine rupture for women with aprior cesarean delivery undergoing a subsequenttrial of labor. The risk has been estimated to bebetween 0.2 and 1.0 percent [12,13] . McMahon et al [14]d i rectly addressed the issue of maternal andperinatal morbidity and mortality associated withtrial of labor in 3249 women with previous CS ascompared to 2889 women who chose to have arepeat CS. There were no differences in perinataloutcomes, number of maternal deaths nor mildmaternal morbidity and mortality. The likelihoodof major complications however, was almostdouble in women undergoing trial with a scar.T h e re have also been strong arguments thatelective CS will prevent long term consequences ofpregnancy, labor and delivery such as urinary andanal incontinence and utero-vaginal prolapse as aresult of vaginal birth [6] . A contrary view suggeststhat the etiology of incontinence is multi-factorialwith many risk factors other than vaginald e l i v e r y [ 7 ] . The re p roductive consequences ofmultiple CSs should always be considered whenmaking policy decisions re g a rding risk-benefit(This article was presented at the 12 th International Conference of the Kuwait Medical Association, April 1-4, 2007)Address correspondence to:Dr. Alexander E. Omu, Department of Obstetrics and Gynecology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.Fax: 00965 5338906, E-mail: omu @hsc.edu.kw

158Delivery after Prior Cesarean Section in Kuwait June 2007analysis of vaginal delivery [15] . In Kuwaiti societywhere members prefer large families, the decisionfor a repeat CS after prior CS should be takencarefully so as not to limit the family size of thewoman.The objective of this study was to evaluate themode of delivery after prior CS over a 14 year period(from 1992-2005) at the Maternity hospital, Kuwait.SUBJECTS AND METHODSMaternity Hospital supervises more than 40percent of all deliveries in the State of Kuwait, withabout 14,000 deliveries annually. All women whodelivered in the hospital after one previous lowersegment CS between 1992 and 2005 form thesubjects of this study. All patients includedbelonged to the Maternity Hospital catchment area.Data regarding the study subjects was collectedfrom four related sources:1. The perinatal committee reports: This committeeis made up of obstetricians, neonatologists, nursesand other health workers in the hospital. Thecommittee meets monthly to consider all perinataldeaths and review data on maternal backgroundand characteristics of the pregnancy.2. Annual Reports: These are compiled as annualaudit reports.3. Patient files: The socio-demographic characteristicsof the patients were documented from the files,including the age, parity, intra-partum events anddetails of operative deliveries, gestation at delivery,birth-weight and maternal and perinatal outcome.4. CS registers: Indications for primary CS andthe mode of delivery after prior CS were extractedfrom the central CS registers for validation.Statistical Analysis: Percentages and mean valuesplus standard deviations were calculated forcomparison using Student t test to compare pairedvariables and Mann-Whitney test was used forcontinuous variables. For evaluation of trend overthe years, logistic re g ression analysis was carried outwith adjustment for age, parity and gestation. The levelof significance was accepted as a p value ≤ 0.05.RESULTSDelivery after a prior CS was evaluated in 12,725women as shown in Table 1. Their mean age was 28± 9 years (range = 18 to 45 years) and mean paritywas 3.2 ± 0.9. Elective CS, defined as planned withthe patient admitted a night before the operation,was the mode of delivery in 1023 (8%) or 20.3percent all those that eventually had a repeat CS. Ofthe 11,702 women with prior cesarean that startedlabor, 4047 (34.6%) were delivered by emergencyCS, while 7655 (65.4%) were delivered per vaginum.Table 1: Characteristics of women with prior CSCharacteristics No. of Women with Per centPrevious one CSAge (years)< 20 534 4.221-24 3741 29.425-29 4263 33.530-34 2367 18.635-39 1387 10.9> 40 433 3.4Parity1 3792 29.82 2596 20.43 2291 18.04 2621 20.6> 5 1425 11.2Vaginal delivery after CS:The overall vaginal delivery rate after prior CSwas 60.2 percent between 1992 and 2005. Table 2summarizes the trend in vaginal delivery between1992 and 2005, showing an overall vaginal deliveryrate of 60 percent with a rate of 66 percent in thefirst quarter (1992-1995) and dropping significantlyto 51 percent in the last quarter (2003 - 2005) of thestudy (p < 0.02). Spontaneous vaginal delivery wasthe main mode of delivery in 85.9 percent ofwomen that delivered vaginally, 10.4 percent hadvacuum extraction and 3.4 percent had forcepsd e l i v e r y. Although breech presentation in thepresence of a previous CS was usually an indicationfor elective CS in the hospital, 0.2 percent of allwomen that delivered vaginally, were deliveredeither by spontaneous vaginal breech delivery or byassisted breech delivery probably after late arrivalto the labor room in advanced second stage oflabor.Indications for CS after prior cesarean delivery:Analysis of the indications for elective andemergency CS is shown in Table 3 in order toexplain the reasons for the decrease in the vaginaldelivery rate. There was no significant difference inthe elective CS rate of about 20 percent (18 - 23%)during the study period, nor with known andcommon indications like abnormal presentation,medical disorders, macrosomia and pre v i o u svaginal operations. However, there was significantincrease in CS among women with antepartumhemorrhage (p < 0.05) and a two-fold increase formultiple pregnancy (p < 0.01) between the first andsecond halves of the study. Similarly, there was nosignificant change in the emergency CS rate,especially in such indications as prolonged laborand failure to pro g ress, fetal distress, cephalopelvicdisproportion and failed induction of labor.Two indications for repeat CS revealed almost a

June 2007KUWAIT MEDICAL JOURNAL 159Table 2: Mode of vaginal delivery after prior CSTable 3: Indications of CS after prior CS1980-84 1985-89 1992-95 1996-99 Totaln (%) n (%) n (%) n (%)Previous CS 3996 (68.9) 4302 (65.2) 2151 (60.3)2276 (55.1)* 12725Vaginal delivery* 2625 (65.7) 2633 (61.2) 1229 (54.6) 1168 (51.3) 7655 (60.2)Spontaneous vaginaldelivery 2256 (86.0) 2262 (85.9) 1045 (85.0) 1016 (87) 6579 (85.9)Vacuum extraction 273 (10.4) 276 (10.5) 133 (10.8) 113 (9.7) 795 (10.4)Forceps delivery 87 (3.3) 90 (3.4) 47 (3.9) 39 (3.3) 263 (3.4)Breech delivery 9 (0.3) 5 (0.2) 47 (3.9) - 18 (0.2)* Significant decrease between 1980 and 1999: p < 0.01Table 4: Effects of the indications of prior CS on mode of deliveryduring current pregnancyIndications for Vaginal delivery Emergency CS Elective CS Totalprior CS after prior CS after prior CS after prior CSn (%) n (%) n (%)Failure to progress in labor 2311(74.4) 536 (17.3) 258 (8.3) 3105 (24.4)Cephalo-pelvic Disproportion 616 (20.5) 2087 (69.4) 302 (10.1) 3003 (23.6)Fetal distress 2014 (81.6) 279 (11.3) 176 (7.1) 2469 (19.4)Abnormal presentation 1447 (60.8) 888 (38.4) 158 (7.1) 2379 (18.7)Failed induction 152 (47.8) 148 (46.7) 17 (5.3) 318 (2.5)Others 965 (65.5) 488 (43.3) 98 (8.7) 1451 (11.4)Total 7655 (60.2 ) 4047 (31.8 ) 1023 (8.0 ) 12,725three-fold increase in the second half of the study.These include infertility/IVF-ET (p < 0.001) andmultiple pregnancies (p < 0.001). These two factorscannot fully account for the downward trends invaginal delivery rates.Effects of the indications in patients with priorCS:Analysis of the indications in patients with priorCS is shown in Table 4. The odds ratio of achievingvaginal delivery after prior CS was highest for fetaldistress (OR = 4.8, 95% CI 3.4, 6.2), failure toprogress (OR = 3.8, 95% CI 3.0, 5.6) and abnormalpresentation (OR = 3.2, 95% CI 2.2, 2.6) whereas itwas lowest for cephalo - pelvic disproportion (OR =0.8, 95% CI - 0.4,1.2) and was associated with thelowest vaginal delivery rate of 20.5 percent.Effects of the mode of delivery on perinatal andmaternal outcome:T h e re were significantly more pre t e r mdeliveries by elective CS and emergency CS than byvaginal delivery (15.3% and 12.4% versus 6.5%; p

160Delivery after Prior Cesarean Section in Kuwait June 2007Table 5: Outcome of delivery after prior CS according tothe mode of deliveryVaginal delivery % Emergency CS % Elective CSn = 7655 n = 4047 % n = 1023Gestational age at delivery40 weeks 5.8 14.6 2.8Birthweight< 2.5 Kg 7.2 13.2 15.32.5-4.0 Kg 87.2 75.2 73.1>4.0 kg 5.6 11.6 11.6Perinatal mortality 97 (1.3%) 69 (1.7%) 19 (1.8%)Maternal Morbidity 11(1.4 per 1000) 8 (2.0 per 1000) 4 (3.9 per 1000)Postpartum hemorrhageRuptured uterus 5 (0.7 per 1000) 4 (1.0 per 1000) -Retained placenta 7 - -Placenta accreta 2 (0.3 per 1000) 3 (0.74 per1000) 3 (2.9 per 1000)per 1000 in women delivered by emergency CS.Suspicion or impending rupture of the uterus wasusually an indication for emergency CS. Ruptureduterus had no effect on perinatal mortality (noperinatal death) but in three women, cesare a nhysterectomy was carried out because of severepostpartum hemorrhage from major placentaprevia and placenta accreta.DISCUSSIONThe present study has demonstrated that a trialof labor after prior CS is safe in about 60 percent ofwomen in Kuwait but only 48 percent afterinduction of labor. The crude perinatal mortality inthe present study was 14.5 per 1000. If the extremep reterm births and congenital anomaliesincompatible with life were excluded, the perinatalmortality among women with vaginal deliveryafter prior cesarean section could be comparablewith the general maternity population perinatalmortality rate of 9 -10 per 1000. The outcome of thepresent study is similar to the outcomes of previousstudies in which vaginal delivery occurred in 50 -80 percent cases following a prior CS [5,14,16] . In arecent study in which a trial of labor was carriedout in 17, 613 women with previous CS, the successrate was 73.7% (65.6% after induction of labor) [17] .Like in the present study, there were fewcomplications. The downward trend of vaginaldelivery after prior CS with decline of 22 percent(65% in 1980 - 84 to 51% in 1995 - 99) is of greatconcern. This is due to the three main indications,viz antepartum haemorrhage, successful infertilitymanagement with in-vitro fertilization andconsequent multiple pregnancies. This was theo fficial policy of the Assisted Repro d u c t i v eTechnology team then and the anxiety of thepatients. These factors cannot fully account for thedrop in vaginal delivery rates. The present studyhas also shown that history of previous CS is animportant factor in the outcome in a subsequentpregnancy. This is consistent with a recent report byBujold et al [18] . When the indication for a prior CSwas cephalo-pelvic disproportion, the rate ofvaginal delivery was lower than when theindication was not a recurrent cause. The mainconcern for vaginal delivery after prior CS is that ofuterine ru p t u re [ 19 ] . In the present study, theincidence of uterine rupture was 0.7 per 1000 forvaginal delivery and 1.0 per 1000 for emergency CS.This is much lower than an overall risk of uterinerupture for women with a prior cesarean deliveryu n d e rgoing subsequent trial labor which isreported to be between 0.2 and 1 percent [20] and 0.4to 8.0 percent in patients undergoing oxytocinaugmentation [21,22] . This risk can be further reducedby appropriate selection of patients, method ofinduction and adequate monitoring during labor. Itmust be pointed out however that a symptomaticuterine dehiscence of 0.5 to 2% after vaginaldelivery is associated with minimal morbidity andit is hardly identified.Socol et al [ 3 ] have successfully intro d u c e dguidelines promoting vaginal birth after CSt h rough active management of labor andcirculation of CS rates of attending obstetricians.This has significantly led to reduction of CS rates.Myers and Gleischer [ 5 ] took similar steps, formanagement of fetal distress and bre e c hpresentation, in which it was mandatory to take asecond opinion before performing a nonemergencyCS.As part of the decision making pro c e s s ,information and counseling should aim to estimatespecific risks and probability of successful vaginaldelivery or risk factors for failure of trial of laborafter prior CS [23,24] . Every hospital should thereforeestablish practice guidelines on the management ofpatients with prior CS. For example, after Medlinedatabase analysis of articles published fro mJanuary 1, 1995 to February 28, 2004, on vaginaldelivery after CS, a Canadian group developedguidelines on the management of delivery afterprior CS [ 25 ] . The highlight of these guidelinesincluded the need for informed consent,conducting the delivery in a hospital with resourcesand availability of operating-room staff andcontinuous electronic monitoring.CONCLUSIONIn well selected women, vaginal delivery afterprior CS carries a low risk. There is a need to reviewthe liberal policy of operative delivery followingsuccessful assisted reproductive technology. Thetrend towards fewer vaginal deliveries after priorCS can be halted and reduced through active

June 2007KUWAIT MEDICAL JOURNAL 161management of labor and involvement of seniorstaff in the decision making process of repeat CS inpatients with history of prior CS.ACKNOWLEDGEMENTSWe offer our sincere gratitude to our past andpresent medical colleagues who participated in themanagement of patients who form the subject ofthis study and to all the nurses and support staff.REFERENCES1. Notzon FC, Cnattingius S, Bergsjo P, Cole S Taffel S, Irgen I,Dattveit AK. CS delivery in the 1980’s: Internationalcomparison by indication. Am J Obstet Gynecol 1994;170:495-504.2. Wilkinson C, McIIwaine G, Boulton-Jones C, Cole S. Is arising CS rate inevitable? Brit J Obstet Gynaecol 1998;105:45-52.3. Socol ML, Gancia PM, Paeceman AM, Dooley SL. Reducingcesarean births in a primarily private university hospital.Am J Obstet Gynaecol 1993; 168:1748-1754.4. Cowan RK, Kinch RAH, Ellis B, Anderson R. Trial of laborfollowing CS. Obstet Gynecol 1994; 83:933-936.5. Miller DA, Fidelia GD, Paul RH. Vaginal Birth afterCaesarean Section. N Engl J Med 1996; 335:689-695.6. Wall LL. Cost effectiveness of elective CS after one prior lowtransverse cesarean. Obstet Gynecol 2000; 96:482.7. Grobman WA, Peaceman AM, Socol ML. Cost-effectivenessof elective cesarean delivery after one prior low transversecesarean. Obstet Gynecol 2000; 95:745-751.8. Walker R, Golois E, Turnbull D, Wilkinson C. Why chooseCS. Lancet 2001; 357: 635-636.9. Myers SA, Gleischer N. A successful programe to lower CSrates. N Eng J Med 1998; 319:1511-1516.10. Landon MB, Hauth JC, Leveno KJ, et al. Maternal andperinatal outcomes associated with a trial of labor afterprior cesarean delivery N Engl J Med 2005; 352:1718-1720.11. Lopez-Zeno JA, Peaceman AM, Adashek JA, Socol ML. Acontrolled trial of program for active management of labor.N Engl J Med 1992; 326:450-454.12. Chazotte C, Cohen WR. Catastrophic complications ofprevious CS. Am J Obstet Gynecol 1990; 163:738-742.13. Caughey AB, Shipp T D, Repke JT, Zelop CM, Cohen A,Lierberman E. Rate of uterine rupture during trial of laborin women with one or two prior cesarean deliveries. Am JObstet Gynecol 1999; 181:872-876.14. McMahon MJ, Luther ER, Bowes WA, Olshan A F.Comparison of a trial of labor with an elective second CS. NEngl J Med 1996; 335:689-695.15. Pare E, Quinones JN, Macones GA. Vaginal birth after CSversus elective repeat CS: assessment of maternaldownstream health outcomes. BJOG 2006; 113:75-78.16. Phelan JP. Clark SL, Diaz FP. Am J Obstet Gynecol 1987;157:1510-1515.17. Rageth I.C, Fuz,G Grossenbacher H. For the Swiss workingGroup of Obstetric and Gynecologic Institutions. ObstetGynecol 1999; 93:332-337.18. Bujold E, Gauthier RJ. Should we allow a trial of labor aftera previous Cesarean for dystocia in the second stage oflabor? Obstet Gynecol 2001; 98:652-655.19. Smith GCS, White IR, Pell JP, Dobbie R. Predicting Cesareanand Uterine Rupture among women Attempting VaginalBirth after Prior CS. PLos Med 2: e 25220. Lagrew DC Jr, Morgan MA. Decreasig the caesaereansection rate in a private hospital: Success without mandatedclinical changes. Am J Obstet Gynecol 1996; 174:184-191.21. Davies GAL, Hatin PM, McGrath MJ. Vaginal Birth afterCaesaerean. Physcian’s perception and practice. J ReprodMed 1996; 41:515-520.22. Hibbard JU, Ismail MA, Wang Y, Te C, Karrison T, IsmailMA. Failed vaginal birth after a CS: how risky is it? Am JObstet Gynecol 2001; 184:1365-1371.23. Rozenberg P. The counselling of patient with prior C-section. Gynecol Obstet Fertil 2005; 33:1003-1008.24. Smith GC. Outcome Associated with a trial of Labor afterPrior Cesarean Delivery. N Engl J Med 2005; 352:1718-1720.25. Martel MJ, MacKinnon CJ. Guidelines for vaginal birth afterp revious Cesarean birth. J Obstet Gynaecol Can 2005;27:164-188.

KUWAIT MEDICAL JOURNAL June 2007Original ArticleObesity and Cardiovascular Risk Factors in Kuwaiti AdultsFasial H. Al Orifan 1 , Hanan E. Badr 2 , Mohammed Abdul Sabour Se’adah 1 , Khalid Elias Khadadah 3 , Basel AlKordi 1 , Adel Abass 11Ministry of Health, Kuwait2Department of Community Medicine and Behavioral Sciences, Faculty of Medicine, Kuwait University, Kuwait3Primary Health Care Department, Kuwait Oil Company, KuwaitABSTRACTObjective: To assess the association between obesity[adult Body Mass Index (BMI) ≥ 30] and cardiovascularrisk factors among adult Kuwaiti nationalsDesign: A cross sectional study conducted among adultKuwaiti nationals (20-44 years old)Setting: Qurtoba Police Health Center and Abdulla AlSalem Health Center, KuwaitSubjects: A sample of 296 subjects was selectedIntervention: Routine examination for those who havenever been diagnosed with any chronic health problem.Main Outcome Measure: Prevalence of obesity, levels offasting blood sugar, blood pressure and blood lipidprofile.Results: Obesity was prevalent among 42% of the samplewith male preponderance. Obese individuals were significantlyKuwait Medical Journal 2007, 39 (2): 162-166KEY WORDS: obesity, cardiovascular risk factors, Kuwaitat higher risk of developing cardiovascular risk factorssuch as higher total cholesterol (OR=48, CI:9.8-235.9),LDL (OR=28, CI:9.3-81.3), impaired fasting blood sugar(OR=16, CI:6.2-43.2), prehypertensive systolic bloodp re s s u re (OR=5.4, CI:1.9-15.4) and pre h y p e r t e n s i v ediastolic blood pressure (OR=5.5, CI:1.2-25.9) than nonobesesubjects after adjusting other confounders.Conclusion: Obesity prevalence is an alarming healthproblem in the studied areas in Kuwait. It is associatedwith a wide range of cardiovascular risk factors thatindicate a warning sign of probable future increase in CVdiseases in this population. Further studies coveringrepresentative samples of all Kuwaitis are suggested.Obesity prevention programs related to communityconcerns are recommended.INTRODUCTIONObesity and overweight are both labels forranges of weight that are greater than what isnormally considered healthy for a given height.Adult obesity (BMI ≥ 30) and its co-morbidd i s o rders re p resent a significant public healthconcern and they are considered the leading causesof morbidity and premature mortality around theworld [1,2] . In the United States, about one third ofthe population was overweight and another thirdwas obese [2] . The prevalence of adult overweight(BMI range 25 - 29.9) and obesity is increasingre g a rdless of age, socioeconomic, or ethnicitydifferences [3] .Body weight is the result of a balance betweene n e rgy taken in and energy expended. It is acondition in which natural energy stored in fattissue is expanded far beyond usual levels to thepoint where it impairs health [4] . Obesity is definedas too much body fat with an abnormalaccumulation of fat in proportion to body size [2,4] .Obesity is now recognized as a major risk factorfor coronary heart disease. It also harms more thanjust the heart and blood vessels system; it is a majorcause of gall stones and can worsen degenerativejoint disease [ 4 ] . Obesity is associated with significantmorbidity including hypertension, type-2 diabetesmellitus and hyperlipidemia, as well as hyperuricemiaand some forms of cancer especiallycancer colon [5] .Coronary heart disease (CHD) is an importantand a prime cause of premature death; it remainsthe major killer of both men and women. Obesity isbecoming a major concern worldwide due to itsp roven relation to CHD. Multiple risk factorscontribute to the pro g ression and primarydevelopment of CHD and that the risk of CHD canbe significantly reduced through reduction ofmodifiable risk factors. Obesity is one of the majormodifiable risk factors [6] . Multiple cardiovasculardisease (CVD) risk factors tend to cluster inindividuals, thereby compounding the risk. Obesityand physical inactivity are associated with(This article was presented in the 12 th International Conference of the Kuwait Medical Association, April 1-4, 2007)Address correspondence to:Hanan E. Badr, MD, MPH, Dr. Ph, Department of Community Medicine and Behavioral Sciences, Faculty of Medicine, Kuwait University. Fax:965 533 8948, E-mail: hanan29@yahoo.com, hanan@hsc.edu.kw

June 2007KUWAIT MEDICAL JOURNAL 163increased risk of heart disease, as well as elevatedc h o l e s t e rol levels, blood pre s s u re and triglycerides [ 7 ] .Epidemiologic studies have identified severale n v i ronmental factors that contribute to thecontinued weight gain. The foremost among thesea re increasingly sedentary lifestyle and theavailability of energy-dense (high fat content), lowfiberfoods. Additional societal trends that arethought to have contributed included smoking andeating away from home particularly fast-foodwhich is typically caloric-dense [2] .Obesity is major health problem in Kuwait,more than half of adult females and almost onethird of adult males are obese [8] . The importance ofdetection and management of obesity to reduce therisk of correlated complications especially CVDprompted us to initiate this study to assess theassociation between obesity and card i o v a s c u l a rrisk factors among adult Kuwaiti nationals.SUBJECTS AND METHODSA c ross-sectional study was carried out onindividuals attending the Quortuba and AbdullaAl-Salem Primary Health Care Centers for routineexamination. The inclusion criteria were individualsnot suffering from or ever diagnosed with anyc h ronic disease such as diabetes, hypertension,heart problems or dyslipidemia. All the subjectswere adult Kuwaiti nationals aged between 20 - 44years. Pregnant women were excluded. Ac o n v e n i e n c esample of 296 subjects was chosen for this study.After a verbal consent from each individual tobe included in the study, a relevant history, physicalexamination and laboratory investigations wereperformed as part of routine check up.Data collected included personal data such asage, gender and lifestyle risk factors like currentsmoking status and level of regular aero b i cphysical activity (such as brisk walking at least 30minutes per day, most days of the week accordingto the recommendation of lifestyle modification,Seventh report of the Joint National Committee onPrevention, Detection, Evaluation and Treatment ofHigh blood Pressure) [5] . Blood pressure (BP) wasmeasured and divided to four categories accordingto the same Committee [5] as follows: Category I(normal) was those whose systolic blood pressure(SBP) was < 120 mmHg and diastolic bloodpressure (DBP) was < 80 mmHg. Category II (prehypertensivestage) was subjects with SBP between120-139 mmHg and/or DBP 80-89 mmHg. CategoryIII (stage I hypertension) were those with SBPbetween 140-159 mmHg and/or DBP 90-99 mmHg.Category IV (stage II hypertension) were individualswith SBP > 160 mmHg and/or DBP > 100 mmHg.Subjects’ weight and height were measure dusing the Detecto-Scale. Calibration was doneevery morning before use. BMI was calculated.Subjects with BMI equal or greater than 30.0 kg/m2were classified as obese, and those with BMI lessthan 30.0 kg/m 2 were considered as non-obese [4,9,10] .Blood samples were collected in the laboratoryfollowing the usual pro c e d u res. Fasting bloodsugar (FBS) (after 6-8 hours of fasting) and lipidsprofile (after 12-14 hours of fasting) were measured.FBS was classified according to the WHOcriteria [8] as normal ( 4.1 mmol/l). Also HDL was classified intodesirable (> 1.55 mmol/l), borderline (0.90 - < 1.55mmol/l) and high risk (< 0.90 mmol/l). Finally TGlevels were classified into desirable (< 4.0 mmol/l),borderline (4.0 - < 5.2 mmol/l) and high risk (> 5.2mmol/l).Data were analyzed using the StatisticalPackage for Social Sciences (SPSS), version 13.Student t-test, Chi-square test and binary logisticre g ression test were used to examine theassociation between obesity and diff e re n tcardiovascular risk factors at level of significance ofp < 0.05, and 95% confidence interval (CI).RESULTSThe study was conducted among 296 Kuwaitiadults; most of them were males (60.1%). The meanage of non-obese individuals (29.5 ± 6 years) wassignificantly lower (p < 0.05) than that of obesesubjects (31.2 ± 6.5 years). Obesity was detectedamong 124 subjects (41.9%); male genderdominated both groups of obese (59.7%) and nonobese(60.5%) individuals with no significantsignificant difference. Smoking was almost equallydistributed in both groups (37% for each). Inaddition, about one third of the obese and nonobesesubjects (33.7% and 35.5% respectively) werepracticing exercise on a regular basis with nosignificant difference.Table 1 shows the bi-variate analysis of differentrisk factors associated with obesity. Almost all therisk factors were significantly more pre v a l e n tamong the obese subjects than the non-obese. The

164Obesity and Cardiovascular Risk Factors in Kuwaiti Adults June 2007Table 1: Prevalence and mean (SD) of risk factors associated withobesity in Kuwaiti adultsNon-obese Obese p-valuen = 172 n = 124% %Systolic BP(mmHg)Normal 95.3 71.0 < 0.001*Pre-hypertensive 4.7 29.0Mean (SD) 106.2 (13.5) 115.97 (12.5) < 0.001**Diastolic BP(mmHg)Normal 98.3 87.1 < 0.001*Pre-hypertensive 1.7 12.9Mean (SD) 69.3 (7.4) 74.1 (8.0) < 0.001**Fasting Blood SugarNormal 95.3 67.7 < 0.001*Impaired 4.7 32.3Mean (SD) 5.4 (0.5) 5.7 (0.6) < 0.001**Total CholesterolDesirable 84.9 35.5 < 0.001*Borderline high risk 14.0 42.7High risk 1.2 21.8Mean (SD) 4.5 (0.8) 5. 5 (1.1) < 0.001**LDLCholesterolDesirable 82.6 37.9 < 0.001*Borderline high risk 14.5 30.6High risk 2.9 31.5Mean (SD) 2.8 (0.7) 3.6 (0.97) < 0.001**HDLCholesterolDesirable 13.4 7.3 NS*Borderline high risk 75.0 73.4High risk 11.6 19.4Mean (SD) 1.2 (0.3) 1.1 (0.3) < 0.01**TriglyceridesDesirable 99.4 93.5 < 0.01*Borderline high risk 0.6 3.2High risk 0.0 3.2Mean (SD) 1.01 (0.697) 1.7 (1. 4) < 0.001***Chi-square test, ** Student-t testtable revealed that the mean SBP (115.97 Vs 106.2)and DBP (74.1 Vs 69.3) was significantly higheramong obese individuals than the non-obeserespectively. The same pattern applied to FBS, TC,LDL, and TG where the mean values weresignificantly higher in the obese subjects. None ofthe subjects was detected as diabetic, hypertensivestage I or II.Multivariate binary logistic regression analysiswas performed to eliminate the effect of allpotential confounders. Crude and adjusted oddsratios were estimated for various cardiovascularrisk factors as illustrated in Table 2. Obesity was thedependent variable (0 = non-obese individuals, 1 =obese individuals). The classification matrix overallp rediction accuracy showed that 80.3% of thesubjects were correctly identified by the model.Two models were examined for potentialconfounders and to avoid overlap between relatedvariables (example SBPand DBP) and TC with LDLand HDL. Six risk factors stood for the independentvariables that entered the first model asTable 2: Binary logistic regression of some CV risk factors associatedwith obesityVariables Crude ORs Adjusted ORsp OR CI p OR CIAge< 0.05 1.04 1.01-1.08 NS 0.96 0.91-1.02GenderMale (RG)Female NS 0.97 0.60-1.55 NS 1.78 0.92-3.42FBSNormal (RG)Impaired < 0.0001 9.76 4.37-21.80 < 0.000116.39 6.23-43.16SBPNormal (RG)Pre-hypertensive < 0.0001 8.39 3.74-18.83 < 0.001 5.44 1.93-15.35TCDesirable (RG)Borderline high risk < 0.0001 7.33 4.07-13.20 < 0.0001 10.79 5.24-22.26High risk < 0.0001 44.80 10.25-195.87 < 0.0001 48.06 9.79-235.96TGDesirable (RG)Borderline high risk NS 5.86 0.65-53.116 NS 3.65 0.24-56.11The adjusted variables are: age, gender, FBG, SBP, TC and TG.NS = not significant, RG = reference groupTable 3: Binary logistic regression of other CV risk factors associatedwith obesityVariables Crude ORs Adjusted ORsp OR CI p OR CIAge < 0.05 1.04 1.01-1.08 NS 0.99 0.94-1.04GenderMale (RG)Female NS 0.97 0.60-1.55 < 0.05 2.35 1.19-4.62FBSNormal (RG)Impaired < 0.0001 9.76 4.37-21.80 < 0.0001 13.30 5.33-33.19DBPNormal (RG)Pre-hypertensive < 0.001 8.35 2.38-29.32 < 0.05 5.48 1.16-25.88LDLDesirable (RG)Borderline high risk < 0.0001 4.95 2.51-8.39 < 0.0001 5.42 2.68-10.95High risk < 0.0001 23.57 8.78-63.28 < 0.0001 27.56 9.35-81.28HDLDesirable (RG)Borderline high risk NS 1.80 0.80-4.08 NS 2.49 0.83-7.50High risk < 0.05 3.07 1.16-8.11 < 0.05 5.15 1.28-20.63TGDesirable (RG)Borderline high risk NS 5.86 0.65-53.116 NS 3.95 0.33-46.77The adjusted variables are: age, gender, FBG, DBP, LDL, HDLand TGNS = not significant, RG = reference groupdemonstrated in Table 2. The table revealed thatthree factors (adjusted odds) represented the riskfactors of obesity (TC especially the high risk levelsranked the highest risk factor followed by FBS andSBP).Increased levels of TC showed significant veryhigh risk aspect (OR=45, CI: 10.3 - 195.9) among the

June 2007KUWAIT MEDICAL JOURNAL 165obese adults as an individual factor. Its riskreinforced (OR = 48, CI: 9.8 - 235.9) when adjustedto other factors and towered the odds. The cruderisk of impaired FBS was almost 10 times in obeseindividuals compared to non-obese and its riskboosted to rank the second odds (OR = 16, CI:6.2 -43.2) when adjusted for other risk factors.P re-hypertensive SBP was significantly eighttimes crude odds among the obese individuals andshrank to five odds (CI: 1.9 - 15.4) when adjustedcompared to non-obese subjects. SBP ranked thethird major risk factor among obese persons.The second model included seven independentvariables as shown in Table 3. Although the crudeanalysis demonstrated that the older the age, thehigher risk to be obese, its effect disappeared whenadjusted for confounding. The gender showed areverse picture. It did not show individual odds butits effect came to light when adjusted for other riskfactors. Females significantly showed two odds tobe obese than males.High value of LDL illustrated highly significantcrude odds (OR = 24, CI: 8.8 - 63.3) in the obeseindividuals and its risk was reinforced to rank asthe first risk factor in the second model whenadjusted to other risk factors (OR = 28, CI: 9.3 -81.3). The protective effect of HDL was obvious inboth the crude and the adjusted analysis, while therisk of its high levels increased from three odds (CI:1.2 - 8.1) as an individual factor to five odds afteradjustment (CI: 1.3 - 20.6) in obese subjects morethan the non-obese group.Pre-hypertensive DBP showed significant highcrude odds (OR = 8, CI: 2.4 - 29.3) for the obesesubjects but its risk diluted (OR = 5, CI: 1.2 - 25.9)when other factors were adjusted.DISCUSSIONThis study showed a high prevalence of obesityamong Kuwaiti adults of both sexes. Although theresults cannot be generalized to the wholepopulation as it was a convenience sample ratherthan a random sample, it can reflect an ingredientof the overall picture of obesity problem in thisc o m m u n i t y. Considering that this conveniencesample that attended the clinic for ro u t i n eexamination may exhibit a healthy volunteer effectas documented in the epidemiological literature, aninherited potential bias cannot be neglected. Thep resent results also revealed significant associationsbetween obesity and CVD risk factors. Theassociation between obesity and increased chancefor developing impaired FBS, hypertension, andhypercholesterolemia was supported by the study.Obesity (mainly visceral obesity) increases insulinresistance and lead to development of type IIdiabetes. In turn insulin resistance results inspecific abnormalities of lipid metabolismcharacterized by elevated levels of plasmatriglycerides and low levels of HDL cholesterol [13,14] .Obesity is a modifiable condition that canprevent the occurrence of associated risk factorssuch as adverse lipid, blood pressure, and insulinlevels [15] . The high prevalence of obesity in thepresent study is in concordance of a previous studywhich found that one third of adult Kuwaitis areobese [16] . Moreover, the Kuwait Annual NutritionSurveillance (2005) found that 41.7% and 33.9% ofadult males were overweight and obeserespectively. Among adult females the prevalencewas 32.7% and 41.0% respectively [17] . Arecent studyhas shown an increased prevalence of obesity [18] .This study revealed a high level of TC and LDLin the obese individuals compared to the non-obesegroup. This finding is of crucial importance as itrepresents the first alarming risk for CVDs. Thisdefinitely is the result of unhealthy eating habitsand increased intake of fast foods and other high fatcontent food practiced by the Kuwaiti communityin all age groups. This finding also necessitates theurgent interference of health programmers to planintervention programs that aim at modifying thelifestyle and eating habits.Impaired FBS ranked as the second risk forobese individuals. Studies have shown that modestweight loss significantly reduces the prospectiverisk for diabetes; also weight loss accompanyingintensive lifestyle interventions (e.g. low-fat dietand regular exercise) in patients with known heartdisease has been shown to reduce progression andeven promote improvement of card i o v a s c u l a rdisease [2] . There is an increased risk of developingtype 2 diabetes mellitus (CVD risk equivalent) inthose who have impaired FBS [ 11 ] . This is inaccordance with the finding of the present study.Also, studies showed that among persons with aBMI > 30 who already have an impaired FBS andare at risk for developing type 2 diabetes, adoptinglifestyle changes that decrease weight will reducerisk by over 50 to 60% [19] . This emphasizes thecrucial need for urgent intervention to control andreduce the incidence of this current incre a s i n ghealth problem in Kuwait among all ages.Hypertension in obese patients, together with itsconcomitant metabolic findings appears to bedriven primarily by the obesity itself whereas thehypertension in lean individuals appears to bedriven primarily by heightened reactivity of therennin-angiotensin and sympathetic systems [6] . Thisis in accordance with the prehypertensive stage ofSBP and DBP found in the obese subjects in thecurrent study that may progress to the disease stagewith its subsequent CV risk effect.Data from observational studies involving more

166Obesity and Cardiovascular Risk Factors in Kuwaiti Adults June 2007than one million individuals have indicated thatdeath from both ischemic heart disease (IHD) andstroke increases from levels as low as 115 mmHgS B Pand 75 mmHg DBP u p w a rds. For every 20 mmHgsystolic or 10 mmHg diastolic increase in BPthere isa doubling of mortality from both IHD and stroke [9] .The initial treatment of overweight and obesepatients should include dietary fat restriction andincreased activity, simply to eat less and exercisemore [2] . Nutritional counseling, behavior therapy,drugs and surgery are other available ways forweight reduction. With most forms of treatment,weight can be lost, but most persons return to theirp re t reatment weight within five years [ 2 0 ] . Thisemphasizes the importance of encouraging moreexercise and the importance of its maintenanceamong adults that will help them to avoidindulging in risks leading to CVD. Many ways forweight reduction are known that help in weightloss such as diet and nutritional counselling.Achieving significant weight loss and reachingideal body weight for age and sex has to be amandatory intention among all obese andoverweight individuals. Awareness campaigns andhealth education programs should be at the top ofthe agenda of health authorities and programmers.CONCLUSIONPrevalence of obesity in Kuwaiti adults in thereferred areas of the study is alarming. It has asignificant association with different cardiovascularrisk factors especially high total cholesterol andLDL, impaired FBG and hypertension. Immediateintervention is highly recommended to reduce therisk of coronary heart problems among theseKuwaitis. Further studies on large scale representativeof the whole Kuwaiti population arenecessary to determine the extent of the problem.Early appropriate intervention programs andmanagement regimens are highly recommended.REFERENCES1. Lopez R. Urban sprawl and risk for being overweight orobese. Am J Public Health 2004; 94:1574-1579.2. James PT, Rigby N, Leach R. The obesity epidemic,metabolic syndrome and future prevention strategies. Eur JCardiovasc Prev Rehabil 2004; 11:3-8.3. Moran R. Evaluation and Treatment of Childhood Obesity.Am Fam Physician 1999; 59:871-873.4. Orzano AJ, Scot JG. Diagnosis and Treatment of Obesity inAdults: An Applied Evidence-Based Review. J Am BoardFam Pract 2004; 17:359-369.5. The Seventh Report of the Joint National Committee onPrevention, Detection, Evaluation, and Treatment of HighBlood Pressure. U.S. Department of Health and HumanServices, National Institute of Health. National Heart,Lung, and Blood Institute. National High Blood PressureEducation Program; NH Publication No. 04-5230, August2004.6. Syed MA, Clasen ME, Donnelly JF. Management ofdyslipidemia in Adults. Am Fam Physician 1998; 97:3794.7. A l J a roudi WA, Peterson JL. Obesity, diabetes andassociated risk factors. Curr Treat Options Cardiovasc Med2006; 8:67-78.8. World Health Organization. Department of NoncommunicableDisease surveillance, Geneva. Definition,Diagnosis and Classification of Diabetes Mellitus and itsComplications, Report of a WHO Consultation, Part 1:Diagnosis and Classification of Diabetes Mellitus, 1999.9. h t t p : / / w w w. c d c . g o v / n c c d p h p / d n p a / o b e s i t y / d e f i n i n g .htm, Overweight and obesity. Defining overweight andobesity. Definitions for adults.10. Irons BK, Snella KA, Mccall K, Maclauglin EJ, Villarreal M.Update on The Management of Dyslipidemia. Am J HealthSyst Pharm 2002; 59:1615-1625.11. Centers for Disease Control and Prevention. UpdatePrevalence of Overweight among Children, Adolescents,and Adults - United States, 1988-1994. MMWR Morb MortalWkly Rep 1997; 46:198-202.12. Neutel JM, Smith DG, Graettinger WF. MetabolicCharacteristics of Hypertension: importance of positivefamily history. Am Heart J 1993; 126:924-929.13. Weber MA. Role of Hypertension in Coronary A r t e r yDisease. Am J Nephrol 1996; 16:210-216.14. Weber MA, Neutel JM, Smith DG. Contrasting ClinicalProperties and Exercise Responses in Obese and LeanHypertensive Patients. J Am Coll Cardiol 2001; 37:169-174.15. Weber MA. Hypertension, the metabolic syndrome, and therisk of developing diabetes: is it time to change theguidelines? J Clin Hypertens 2004; 6:425-427.16. Lawlor DA, Leon DA. Association of Body Mass Index andObesity Measured in early Childhood with Risk ofC o ronary Heart Disease and Stroke in Middle A g e .Circulation 2005; 111:1891-1896.17. Kuwait Nutrition Surveillance System, 2005 re p o r t .Administration of Food and Nutrition. Ministry of Health.State of Kuwait.18. AL-Kandari YY. Prevalence of obesity in Kuwait and itsrelation to socio-cultural variables. Obesity Reviews 2006;7:147-154.19. World Health Organization. Global InfoBase Online: QuickCompare Introduction 2005.20. Jackson RT,Al-Mousa Z, Al_Raqua M, Prakash P, MuhannaA. Prevalence of coronary risk factors in healthy adultKuwaitis. Int J Food Sci Nutr 2001; 52:301-311.

June 2007KUWAIT MEDICAL JOURNALCase ReportLaparoscopic Excision of Mesenteric Cyst: Case ReportMohammed B Al-Haifi, Abdulsamad M Abdulsmad, Talib H JumaDepartment of Surgery, Al-Amiri Teaching Hospital, KuwaitKuwait Medical Journal 2007, 39 (2):167-169ABSTRACTMesenteric cysts are one of the rarest abdominal tumors.Optimal surgical treatment requires complete excision ofthe cyst to avoid re c u r rence or possible malignanttransformation. The advent of laparoscopic surgery hasallowed resection of these cysts to be achieved withoutfull laparotomy.We report a case of a mesenteric cyst which was excisedcompletely using the laparoscopic approach.KEYWORDS: abdominal tumor, laparoscopy, mesenteric cystINTRODUCTIONMesenteric cysts (MC) are a rare surg i c a lcondition occurring approximately in 1 / 200,000 -350,000 [1,2] . The aetiology is unknown and the rarityof the tumor has led to confusion about their natureand classification [2] .The majority are asymptomatic and if found ared i s c o v e red incidentally during abdominal explorationor radiological examination.The treatment of MC was surgical excision byl a p a ro t o m y. However, in 1993 Mackenzie [ 3 ] d e s c r i b e dthe first laparoscopic excision of a MC. Since then16 cases have been reported [4] .We report a case of calcified MC which wascompletely excised using the laparoscopic appro a c h .CASE REPORTA 44-year-old lady known to have right renalstones was re f e r red to us from the uro l o g ydepartment with a reported accidental discovery ofa left lumbar mobile non-tender abdominal mass.Plain abdominal X-Ray film showed a calcifiedmass in left lumbar region (Fig. 1).Ultrasound and CT abdomen showed a 4 x 4 x 2cm well defined calcified cystic mass in the leftpara-umbilical region and two small right renalcalcified stones (Fig. 2 & 3).Laparoscopic exploration was done through a10 mm port in the infra-umbilical incision afterinsufflation with a Veres needle. The cyst was seenin the mesentery of the jejunum. Three additionalabdominal ports were inserted; a 10 mm in rightupper quadrant, a 5 mm in left upper quadrant anda 5 mm in the left iliac fossa. The cyst wascompletely excised using cautery scissor and bluntdissection. Then the cyst was retrieved by anendobag through the 10 mm infra-umbilical port.The operation time was 95 minutes. The patientwas discharged home on the second postoperativeday.Pathological examination revealed a 5 cmunilocular cyst. Microscopy showed fibrotic wallwithout a lining, with dystrophic calcification andwith features of fat necrosis.DISCUSSIONMC are uncommon abdominal tumors firstdescribed by Benevieri in 1507 [5] . They are tumors ofthe mesentery from duodenum till the rectum buta re most commonly seen in the small bowelmesentery [6] .They are invariably benign, although 3% arefound to be malignant [7] . MC may occur at any agebut the highest incidence is in the fourth decade oflife as in our case. Although MC are oftenasymptomatic, they can present with abdominalpain, weight loss and as an abdominal mass [8] . Fiftyp e rcent of MC are palpable on physicalexamination and are typically mobile transverselyand not longitudinally [1] as in our case. Accuratediagnosis was seldom made pre o p e r a t i v e l y [ 7 ] .Nowadays with the wide use of ultrasound and CTscan, correct diagnosis and localization of the cystcould be made [9] . Although calcification of the wallis unusual, our case had calcification of the wall onthe plain abdominal X-Ray film.Pathologically, MC vary in size and shape froma few centimeters to a size that can occupy theAddress correspondence to:Dr. Mohammed B. Al- Haifi, FRCSed, P.O. Box 18666, Farwania 81007 Kuwait. Tel: 2464724, E-mail:dr_alhaifi@hotmail.com

168Laparoscopic Excision of Mesenteric Cyst: Case Report June 2007Fig. 2: Ultrasound abdomen showing a 4 x 4 x 2 cm, well defined calcifiedcystic mass in the left para-umbilical regionFig. 1: Plain abdominal X-Ray film showing calcified mass in the leftlumbar regionTable 1: Ross classification of MC. according tohistological characteristics of the cyst wallDiagnosisHistological FeatureLymphangiomaEnteric duplication cystEnteric cystMesothelial cystNon - pancreatic pseudocystEndothelial liningEnteric lining, double muscleline with neural elementEnteric lining, no muscle LayerMesothelial liningNo epithelial lining fibrous wallperitoneal cavity [1] . They can be single or multiple,uni or multiloculated. The color of the cyst contentscan vary from clear or milky or dark bro w ndepending on the location of the cyst and thep resence of hemorrh a g e [ 9 ] . Ross et al [ 10 ] h a v eclassified the MC depending on the histologicalcharacteristics of the cyst wall as shown in Table 1.The treatment of choice is complete surgicalexcision [3] . Occasionally resection of the adjacentgut is necessary due to the involvement of themesenteric vessels [ 11 ] . Other treatment optionsinclude simple drainage or marsupilization that areassociated with high rates of recurrence.In the past, surgical excision re q u i red fulllaparotomy. Nowadays, these cysts can be resectedl a p a ro s c o p i c a l l y, ever since Mackenzie in 1993Fig. 3: CT scan abdomen showing a 4 x 4 x 2 cm, well defined calcifiedcystic mass in the left para-umbilical regionreported the first successful laparoscopic excisionof a mesenteric cyst [ 3 ] . The advantages of thel a p a roscopic approach as compared to opens u rgery are less postoperative pain, earlierrecovery, shorter hospital stay and better cosmesis.CONCLUSIONMC are rare yet well recognized cause of anabdominal mass. The laparoscopic approach allowsdefinitive diagnosis and complete resection of MCwhich ensures fast recovery and better pain control.REFERENCES1. Vanek VW, Philips AK. Retroperitoneal mesenteric andomental cysts. Arch Surg 1984; 119:836-842.2. Al awan MH, Said AS, Al Sharif IM. Retroperitoneal andmesenteric cysts. Singapore Med S 1999; 40:121-124.3. Mackenzie DJ, Shapiro SJ, Gorden LA, Ress R. Laparoscopic

June 2007KUWAIT MEDICAL JOURNAL 169excision of mesenteric cyst. J laparoendosc Surg 1993;3:395-3994. Morrison CP, Wemjss-Holden SA, Maddern GJ. A noveltechnique for the laparoscopic resection of mesenteric cysts.Surg Endosc 2001; 15:556 - 559.5. Bless DP, Coftin CM, Bower RS, Stockmann PJ, Ternberg JL.Mesenteric cyst in children. Surgery 1994; 115:571-577.6. Sardi A, Patrick KJ, Minken SL. Mesenteric cyst. Am J Surg1987, 53: 58-60.7. Kurts RJ, Heimann TM, Holt J, Beck AR. Mesenteric andretro peritoneal cysts. Ann Surg 1986; 203:109-112.8. Mason JE, Soper NS, Burt LM. Laparoscopic excision ofmesenteric cyst, a report of two cases. Surg Laparosc Endosc& Percutan Techn 2001; 11:382-384.9. Hardi WS, Hardly SD. Mesenteric cysts. Am J Surg 1970;119:640-645.10. Ross PP, Olmsted WW, Moser RP, Datchmann HjermstadBH, Sobin LA. Mesenteric and omental cyst classificationwith imaging correlation. Radiology 1987; 164:327-332.11. Leiw SC, Glenn DC, Stoney DW. Mesenteric cyst: Reviewarticle. Aust NZ J Surg 1994; 64:741-744.

KUWAIT MEDICAL JOURNAL June 2007Case ReportSolid and Papillary Epithelial Neoplasm (SPEN) of thePancreas in a Pregnant LadyMargaret Linny Austin 1 , Sameer M Humad 1 , Vinod Kumar Grover 21Departments of *Radiology and 2 Surgery, Al-Jahra Hospital, KuwaitKuwait Medical Journal 2007, 39 (2):170-173ABSTRACTState-of-the-art cross-sectional imaging has led to therealization that the prevalence of cystic neoplasms in thepancreas is much higher than initially estimated. This hasalso permitted the diff e rentiation of most cystic neoplasmsbased on cyst size, shape, wall thickness, internalarchitecture, location and presence of calcifications. Thesolid and papillary epithelial neoplasm (SPEN) of thepancreas is a rare low-grade cystic malignancy, seenmainly in adolescent and young adult females. Wepresent the imaging findings of SPEN of the pancreas ina young pregnant lady that was accurately diagnosedpreoperatively.KEYWORDS: imaging, pancreas, SPENINTRODUCTIONSolid and papillary epithelial neoplasm of thepancreas (SPEN) is a rare low-grade malignancymainly found in adolescent and young women ofAsian and far Eastern origin. Clinically, patients areasymptomatic or may present with non-specificsigns and symptoms including nausea, vomitingand upper abdominal discomfort caused by theusually great size of the tumor. Surgical resection iscurative in most instances [1,2,3] .CASE REPORTA 34-yr-old Arab pregnant lady, a mother of six,presented with complaints of a dragging sensationin the upper abdomen. The gestational age of herfetus was 16 weeks at the time of examination.T h e re was no history of previous biliary tractdisease, pancreatitis, or trauma. She denied rearinganimals at home. There were no complaints ofarthralgia. Her laboratory tests including her bloodand eosinophil count were normal.Ultrasound of 8/2/2003 revealed a 14 x 11 cmwell encapsulated complex, heterogeneous masswith cystic and solid components in the tail of thep a n c reas, displacing the spleen laterally andcompressing the left kidney posteriorly withoutevidence of invasion. The cystic mass showedposterior enhancement (Fig. 1). The other organs,including the liver, spleen, kidneys, gallbladderand biliary tract were normal. Pelvic ultrasoundrevealed a single live fetus (of gestational age 16weeks) in the uterine cavity. The ovaries andadnexae were normal. There was no free fluid.Because of the high radiation dose delivered bycomputed tomography (CT) abdomen to thepatient and in particular to the fetus, it was decidedto proceed to magnetic resonance imaging (MRI) ofthe abdomen rather than CT scan. MRI revealed awell encapsulated predominantly cystic mass (asrevealed by the low signal on T1- Fig. 2 and highsignal on T2- Fig. 3) with peripheral mural orfrond-like areas of intermediate signal intensitydue to the solid component. The fat suppressedimages emphasized the cystic nature of the mass(Fig. 4). Gross hemorrhage was not pre s e n t ,although a minimal hemorrhagic component couldnot be excluded. The fibrous capsule was seen as ahypointense rim on T1 and T2. Administration ofgadolinium would have enhanced the evaluationof this tumor but was refused by the patient, eventhough its use is safe for the mother and the fetus.Because of the clinical presentation and theradiographic findings, the strong possibility of aSPEN of the pancreas was raised.On ultrasound guided aspiration of the cyst, 40ml watery blood stained fluid was withdrawn.Cytology from the solid area of the cyst and fluidshowed few sheets and dispersed small cuboidalepithelial cells without nuclear atypia and withscanty cytoplasm, macrophages, eosinophils andneutrophils. Findings were suggestive of a benignepithelial neoplasm.Address Correspondence to:Dr. Margaret Linny Austin, Dept. of Radiology Al-Jahra Hospital, Kuwait. P O Box 21396 Safat 13074, Kuwait. Tel: +965- 4577198, E-mail:Linny_Austin@Hotmail.Com

June 2007KUWAIT MEDICAL JOURNAL 171Fig. 1: Ultrasound of SPEN, tail of pancreas, showing the large, wellencapsulated,predominantly cystic tumor with a frond of solid tumor inthe right lower cornerFig. 2: Axial T1W MR (500/10) shows the homogenous low signalintensity of the fluid and low-intermediate signal of the wedge-shapedsolid componentFig. 4: Axial Fat Suppressed T2W MR (5181/90) showing the cysticcomponent of the tumor as high signal intensity with the peripheralwedge shaped solid component as intermediate signal intensity.Fig. 3: Coronal T2W MR (4000/110) demonstrates the well-encapsulatedcystic mass in the tail of the pancreas. Don’t miss the in-house guest inthe pelvis.On 12/7/2003, the patient underwent a cesariansection. The incision was extended upwards andthe cyst was inspected. It was nearly 20 cm indiameter and arising from the tail of the pancreas.1500 ml of hemorrhagic fluid was aspirated. Thecyst was then excised in toto. The distal end of thepancreas was closed with TIAstapler and oversewnwith vicryl 00. It was also covered with omentum.Hemovac drain was put in the lesser sac and theabdomen was closed. Miniheparin started pre o p e r a t i v e l ywas continued postoperatively till the patientFig. 5: CT abdomen with oral and I.V. contrast showing a small postoperativecollection in the tail of pancreasbecame fully mobile. Fluid per Hemovac drainshowed raised amylase for three days, and thepatient was discharged on the 11th postoperativeday.Two weeks later, the patient complained ofabdominal pain in the left upper quadrant.Ultrasound followed by CT abdomen showed asmall collection in the region of the tail of thepancreas (Fig. 5) as well as a small infarct in the tipof the spleen (Fig. 6). Both were managed conservatively,

172Solid and Papillary Epithelial Neoplasm (SPEN) of the Pancreas in a Pregnant Lady June 2007Fig. 6: CT abdomen with oral and I.V. contrast showing post-operativeinfarcts in the spleenand the patient has since been well.Pathologically, the gross specimen measured 20x 16 x 11 cm. It weighed 1.450 kg. It had a thinfibrous capsule and a hemorrhagic, partly necroticcenter. Microscopically, the tumor had solid, cystic,pseudo-papillary and trabecular pattern of growth.The solid component showed poorly supportedvessels. Areas of myxoid change with thin bloodfilled channels were noted. The tumor cells hadovoid nuclei and granular eosinophilic cytoplasm.At one focus, invasion of the capsule was noted.Findings confirmed the diagnosis of SPEN.DISCUSSIONCystic neoplasms of the pancreas are relativelyuncommon, representing only 10-15% of pancreaticcysts and 1% of pancreatic cancers [4] . SPENs arerare pancreatic tumors with a reported incidence of0.17% to 2.5% among exocrine pancreatic tumors [5] .Pre-operative diagnosis is important, since surgicalresection is curative. They occur in young femaleswith an average age of 24 years [3] . When found inolder females, these tumors are associated with ahigher grade of malignancy [6] .SPENs are large tumors with an averagediameter of 9 to 18 cm [6] and about 58% arise in thetail of the pancreas [1] . On imaging, these tumors canbe solid [3] , but are usually cystic with a well formedcapsule.It is well characterized on ultrasound by areas ofinternal hemorrhage seen as increased internalechoes, along with cystic degeneration, fluid-debrislevels and posterior enhancement due to the cysticcomponent. Peripheral calcification may be present,but is better detected by CT [4,5] . Mural nodules arealso occasionally seen by ultrasound.On computed tomography, the SPEN has a solidperiphery and central cystic degeneration withhemorrhage. The fluid contents hence show densitygreater than water. Peripheral calcification, whenpresent, is best detected by this modality. A welldefinedhypodense capsule is seen, which showsenhancement with contrast. Tumor vascularity ismoderate [2,4,6] .MR has proved to be a valuable modality in theevaluation of SPEN. Because MR imaging issensitive to fluid, it has great potential in theassessment of cystic neoplasms [6,7] . T1 and T2Wimages demonstrate a heterogeneous welldemarcatedmass with areas of low and high signalintensity respectively. This appearance reflects thecomplex nature of the solid, cystic, hemorrhagicand necrotic components [1] . The cyst fluid improvesthe contrast resolution within the mass, delineatingsubtle irregularities of the cyst wall which aid in thed i ff e rential diagnosis between benign and malignantneoplasms, and pseudocysts [7] . It also increases thespecificity by demonstrating the hemorrh a g i ccomponent on T1 weighting due to theparamagnetic component of methemoglobin [6,8] . Thefibrous capsular rim is hypointense on T1 and T2.The capsule and the solid portion of the tumor mayenhance with gadolinium. This mass can be seen todisplace adjacent stru c t u res, as in this study,without invasion [1, 6] .P a t h o l o g i c a l l y, SPEN is a large wellencapsulatedmass. It has a thick fibrous capsulewith mixed cystic, solid and pseudopapillarypattern. The solid areas consist of sheets ofepithelial cells whereas the papillary areas consistof a fibrovascular core lined with cuboidal orcolumnar epithelial cells. Hemorrhage occurs dueto the rupture of the poorly supported vascularnetwork traversing the tumor [1,2,5] .The differential diagnosis would include thegamut of cystic pancreatic neoplasms including thes e rous or microcystic adenomas, mucinous ormacrocystadenomas, cystic non functioning isletcell tumors and intraductal papillary mucinoustumors [1,2,5] . The age of presentation, the site of thetumor within the pancreas (i.e., head, body or tail)and the cross-sectional imaging characteristics ofsize of the tumor, presence or absence ofcalcification and septae and the presence of acapsule would help in the differentiation of theselesions. The main distinguishing features are asfollows:Serous or microcystic cystadenoma or glycogenrich cystadenoma presents in 60 year old females,usually in the region of the head of the pancreas. Ithas thin septae separating multiple cysts 1 mm to 2cm in size which are distributed in a peripherallocation within the tumor giving it a honeycomb ora lace like appearance. Central stellate scars with asunburst pattern of calcification can be seen. MRimaging shows delayed enhancement of the scar oncontrast enhanced images. These are usually benigntumors [2,8,9] .

June 2007KUWAIT MEDICAL JOURNAL 173Mucinous or macrocystic cystadenoma presentin 40-50 year old females and are malignant orpotentially malignant. These lesions have largercysts (more than 2 cm in diameter) and areunilocular or multilocular. Thick septae, solidmural nodules and peripheral coarse calcificationsare present [2,8,9] .Intraductal papillary mucinous tumors are rare.Two-thirds of the patients are men, with a peak ageof incidence at sixty. Most patients present withpancreatitis. The lesion is characterized by markeddistension of the pancreatic duct with a larg eamount of mucus, leading to cyst formation. CTscan may reveal a cystic mass of the pancreas or adilated pancreatic duct which may be similar tochronic pancreatitis [3] .Cystic non-functioning islet cell tumors aresmall in size ranging from 4 mm to 2 cm and arevery vascular. They also have a different enhancingpattern with intravenous contrast [2] .Pseudocysts, though inflammatory in nature,deserve a mention in the list of diff e re n t i a ldiagnosis. They are the sequel of acute or chronicpancreatitis, trauma or pancreatic cancer. They areusually located within the pancreas but can presentin the retroperitoneum, mediastinum or even theparenchyma of the liver, kidney or spleen. They aresingle, unilocular with internal echoes due to fluidor debris. They lack a solid component and areencapsulated by fibrous tissue [8, 9] .The SPEN presents at a younger age than theabove mentioned tumors. They generally lackinternal septations and multiple loculations. Thel a rge size, the well-defined capsule, theheterogeneous mixed solid and cystic pattern andthe hemorrhagic component seen as high signalintensity on T1 weighted imaging serve todistinguish the SPEN from other cystic pancreaticneoplasms.With the appropriate clinical setting, theimaging findings can be highly suggestive for thediagnosis of SPEN. This tumor should be primarilyconsidered in a young female presenting with alarge, well-defined cystic mass in the pancreas,with heterogeneous pattern. An accurate diagnosisis invaluable, since total surgical resection has anexcellent prognosis.REFERENCES1. Mergo PJ, Helmberger TK, Buetow PC, Helmberger RC,Ros PR. Pancreatic Neoplasms: MR imaging and pathologiccorrelation. Radiographics 1997; 17:281-301.2. Buetow PC, Buck JL, Pantongrag-Brown L, Beck KG, RosPR, Adair CF. Solid and Papillary neoplasm of the pancreas:imaging and pathologic correlation in 56 cases. Radiology1996; 199:707-711.3. Demos TC, Posniak HV, Harmath C, Olson MC, Aranha G.Cystic lesions of the pancreas. AJR 2002; 179:1375-1388.4. Bennet GL, Hann LE. Pancreatic Ultrasonography. SurgClin N Am 2001; 81:259-277.5. Dong PR, Lu DSK, Degregario F, Fell SC, Au A., Kadell BM.Solid and papillary neoplasm of the pancreas: radiologicalpathologicalstudy of five cases and review of literature.Clin Radiol 1996; 51:701-705.6. Hammond N, Miller FH, Sica GT, Gore RM. Imaging ofcystic diseases of the pancreas. Radiol Clin N Am 2002;40:1243-1262.7. Megibow AJ, Lavelle MT, Rofsky NM. MR imaging of thepancreas. Surg Clin N Am 2001; 81:307-320.8. Megibow AJ, Lavelle MT, Rofsky NM. Cystic tumors of thePancreas: The radiologist. Surg Clin N Am 2001; 81:489-495.9. Sarr MG, Kendrick ML, Nagorney DM, Thompson GB,Farley DR, Farnell MB. Cystic Neoplasms of the Pancreas -Benign to Malignant epithelial Neoplasms. Surg Clin N Am2001; 81:497-506.

174KUWAIT MEDICAL JOURNAL June 2007Case ReportSAPHO: an Unusual Cause of Pulmonary NodulesNufoud Al- Shammari 1 , Alexander J Henderson 2 , Cameron TC Kennedy 3 , Simon C Langton Hewer 41Department of Pediatrics, Pulmonary Unit, Mubarak Al-Kabeer Hospital, Kuwait2,3,4Departments of Pediatric Respiratory Medicine and Pediatric Dermatology, Bristol Royal Hospital for Sick Children,Bristol BS2 8BJ, UKABSTRACTSAPHO is a clinical syndrome comprising of synovitis,acne, pustulosis, hyperostosis and osteitis. We report acase of SAPHO presenting in a child re f e r red forinvestigations of persistent radiological abnormalities inKuwait Medical Journal 2007, 39 (2):174-176KEYWORDS : child, pulmonary nodules, lung disease, SAPHOthe chest. Pulmonary involvement in SAPHO has beenreported rare l y, is asymptomatic and may be morecommon than has been described.INTRODUCTIONSAPHO is a clinical syndrome comprising ofsynovitis, acne, pustulosis, hyperostosis and osteitis.Pulmonary involvement has been described rarelybut this cause of multiple nodular lesions on chestradiography should be differentiated from otherpossible diagnoses as it follows a benign course andrequires no specific therapy. Here we present a caseof SAPHO presenting in a child re f e r red forinvestigation of persistent radiological abnormalitiesin the chest.Case presentationA ten-year-old boy was assessed for persistentlung X-ray abnormalities eleven months after aprimary illness with myalgia and an erythematousrash with pustular eruptions on the soles of bothfeet. He made an intial recovery but two monthslater he developed a widespread, papular eruptionwith pustule formation. This was most florid on theexposed areas of the limbs and was associated witharthralgia, abdominal pain and muscle weakness.He was investigated for an infective cause of thisillness but cultures and serology were not positive.During the ensuing six months the rash relapsedand remitted.Four months after his initial symptoms, hedeveloped swelling of the left angle of hismandible. A dental abscess was diagnosed and hehad extraction of a primary molar. Cytologicalexamination of material from the site demonstratednon-specific, chronic inflammatory changes. Onemonth later he developed another swelling over themedial end of his left clavicle. This persisted forone month and resolved spontaneously. Chest X-rays taken six weeks apart showed multiple lesionsin the left lower lobe and costophrenic angle. Hehad no respiratory symptoms at this time but theradiological lesions persisted for six months and hewas referred to us for advice.Examination demonstrated a swelling over theleft sternoclavicular joint (Fig. 1) and scaly papuleswith occasional pustules distributed mainly on histrunk but with peripheral lesions (Fig. 2). Biopsy ofa skin lesion demonstrated mild, superficial,perivascular dermatitis. He had no pulmonarysymptoms or signs and his pulmonary functionwas normal. Computed tomography of the chest(Fig. 3) showed areas of density at both lung basesthat were consistent with areas of radiologicalabnormalities on plain chest X-ray (Fig. 4). Therewas no evidence of interstitial lung disease. Thelesions were judged to be previous areas ofi n f a rction with subsequent residual fibro s i s .Extensive investigations, including autoimmuneprofile, atypical pneumonia screen, Borrelia titers,T and B cell subsets, neutrophil function, antiHiband Tetanus titer and Mantoux test did notdemonstrate any evidence of autoimmune disease,immune deficiency or infection. His lung functiontests were normal and bone scan showed areas inhis right clavicle consistent with osteitis.We believe that the combination of osteitis of theclavicle and plantar pustulosis in our patient isconsistent with SAPHO syndrome.Address correspondence to:Nufoud Al - Shammari, Department of Pediatrics, Pulmonary Unit, Mubarak Al - Kabeer Hospital, P.O Box: 43787, Code: 32052, Hawalli,Kuwait. Tel: 965-5318502, Fax : 965-5311430, E-mail: nufoud_q8@hotmail.com

June 2007KUWAIT MEDICAL JOURNAL 175Fig. 1: Swelling over the left sternoclavicular jointFig. 2: Scaly papules with occasional pustules on the trunkFig. 3: CT chest showing areas of reported residual scarringDISCUSSIONSAPHO was first described in 1987 [1] and ischaracterized by variable bony involvement withor without a concurrent pustular dermatosis.Affected bones include the chest wall, sacroiliacjoints and long bones. Bony changes includehyperostosis, aseptic osteomyelitis, and arthritis.Skin involvement is also variable and includes oneor more of the following: palmoplantar pustulosis,acne conglobata or fulminans, hidradenitissuppurativa, pustular psoriasis and dissectingcellulitis of the scalp.Benhamou and others described four majordiagnostic criteria to establish the diagnosis [2] . Anyone of the following is regarded as sufficient todiagnose SAPHO:• Acne conglobata, acne fulminans, orhidradenitis suppurativa with osteoarticularmanifestationsFig. 4: Bilateral linear densities at lung bases.

176SAPHO: an Unusual Cause of Pulmonary Nodules June 2007• Palmoplantar pustulosis with osteoarticularmanifestations• Axial or appendicular hyperostosis with orwithout a sterile pustular dermatosis• C h ronic re c u r rent multifocal osteomyelitisinvolving the axial or appendicular skeleton withor without a pustular dermatosisSAPHO has been described mainly in childrenbut also young to middle-aged adults. Most of thepublished cases have been reported from Japan orNorthern and Western Europe. Discrepancies in thereported prevalence may relate to under re c o g n i t i o nor under-reporting of the condition although it hasbeen suggested that ethnic immunogenetic variationmay account for some of the geographicalheterogeneity in prevalence [3] . The cause of SAPHOremains unknown. An infectious aetiology has beensuggested and Propiono-bacterium acnes has beenisolated from the lesions [4] . P. acnes is an anaerobic,Gram positive bacillus that has been implicated ins e v e re cases of acne but it is a common skinsaprophyte and its presence does not necessarilyimply causation.The course of SAPHO is usually relapsing andremitting. Bone lesions may persist for many yearsand hyperostosis remains stable on sequentialradiological examinations. Pulmonary involvementin SAPHO has been reported rarely [5-7] although itmay be more common than previously described,as it appears to remain asymptomatic and detectionrelies on fortuitous discovery of the associatedradiological abnormalities. The major implicationof making this diagnosis is to differentiate thepulmonary lesions from other potential causes andavoid the need for unnecessary investigations ortreatment. The presence of pulmonary lesions inSAPHO does not appear to alter the benign, albeitprotracted, nature of the condition. However, theinvolvement of the lungs in this condition is stillpoorly understood and there may be a case forpulmonary assessment of all patients newlydiagnosed with SAPHO.CONCLUSIONSAPHO is an important clinical entity that maybe confused with other less benign conditionsaffecting the skin, bones and lungs of children andyoung adults. The history and pattern of skindisease is often the key to the diagnosis and earlyrecognition of this syndrome can pre v e n tunnecessary and potentially hazardous investigationsand treatment.ACKNOWLEDGEMENTSThe authors wish to thank Dr M Hughes,Consultant Pediatrician, North Devon DistrictHospital, UK for referring this case.REFERENCES1. Chamot AM, Vion B, Gerster JC. Acute Pseudosepticarthritis and palmopustular psoriasis. Clin Rheumatol1986; 5:118-123.2. Benhamou CL, Chamot AM, Khan MF. Synovitis-acne -pustulosis hyperosteomyelitis Syndrome(SAPHO). A newsyndrome among the spondyloarthropathies? Clin ExperRheumatol 1988; 6:109-112.3. Khan MF, Chamot AM : SAPHO Syndrome. Rheum DisClin of N Amer 1992; 18:225-246.4. Gerster JC, Lagier R, Livio JJ. Propionibacterium acnes inspondylitis with palmoplantar pustulosis. Ann Rheum Dis1990; 49:337-339.5. Vaile JH, Langlands DR, Prichard MG. Sapho syndrome: anew pulmonary manifestation ? J Rheumatol 1995; 22:2190-2191.6. Ravelli A, Martin A. Sapho syndrome and pulmonarydisease. J Rheumatol 1996; 23:1482-1483.7. K a rem E, Manson D, Laxer RM, et al. Pulmonary associationin a case of chronic recurrent multifocal osteomyelitis.Pediatr Pulmonol 1989; 7:55-58.

June 2007KUWAIT MEDICAL JOURNALABSTRACTCase ReportRetropharyngeal Candidal Abscess in a Neonate: CaseReport and Review of LiteratureSontenam V S Mallik A Rao, Muneera Al Adwani, Chandramouli BharatiDepartment of Radiology, Al Jahra Hospital, KuwaitKuwait Medical Journal 2007, 39 (2):177-180Retropharyngal abscess (RPA) in a newborn baby is veryr a re. It is usually caused by group B hemolyticstreptococci and other aerobic or anerobic bacteria. Theabscess may cause compression of airway and breathingdifficulties with resultant life - threatening complications.We report here a rare case of RPA caused by Candidaalbicans in a newborn, who presented with cyanosis to theNeonatal Intensive Care Unit (NICU) in Jahra Hospitaland was treated successfully after thorough investigations.To the best of our knowledge this is the first such casereport, considering the causative organism, cyanosis andage of the baby.KEY WORDS: Candida albicans, neonate, retropharyngeal abscessINTRODUCTIONRetropharyngal abscess (RPA) is a potentiallyserious deep space neck infection. RPA can be ofmedical or traumatic origin. Non-traumatic RPA islargely a disease of younger children, as a result ofdevelopmental aspects of the neck lymphaticsystem [1-3] . Among children it is very rare in thenewborn. The abscess occurs either by lymphatic orhematogenous spread from oral or upperrespiratory tract infections. Also transmission ofinfection from maternal circulation or the genitaltract is known. A e robes, anerobes and gramnegative organisms were involved as causativeorganisms, more commonly the Staphylococci andg roup B hemolytic S t re p t o c o c c i [ 2 , 3 ] . Review ofliterature revealed that RPA due to Candida albicansin early neonatal period has not been reported.CASE REPORTA newborn female baby weighing 3.5 kg wasdelivered by normal spontaneous vaginal deliverywith an Apgar score of 8/9. At one hour afterdelivery she developed two cyanotic attacks withstridor (without feeding) and the baby was shiftedto the NICU by the neonatologist with a provisionaldiagnosis of congenital laryngomalacia. In the next48 hours the stridor was controlled and mildhypocalcemia was corrected. At the end of the 1stweek, it was found that the child was developingcyanosis and stridor in supine position and wasbetter and more comfortable in prone positionwithout cyanosis or stridor. Also, extensive oralmucosal candidiasis was noted.While searching for the causes of laryngealobstruction and doubtful swelling in the neck, theENT surgeon had asked for an X-ray of the necklateral view. It showed widened prevertebral spacewith smooth indentation over posterior pharyngealwall (Fig. 1). Ultrasound (US) scanning revealed an o n - c o m p ressible cyst like lesion with possibleentrapped air pockets in the re t ro and leftparapharyngeal region (Fig. 2). No change in size ofthe lesion was observed when the child cried. Sincethe lesion was inconclusive on US, CT scan neckwas suggested. This showed a 37x 28x 20 mm sized( a p p roximate), well marginated lesion withenhancing thick wall and internal air fluid levels inthe re t ropharyngeal and left parapharyngealspaces (Figs. 3 and 4). Pharyngolarynx, carotidsheath and esophagus were compressed anddisplaced. No communication with airway oresophagus could be appreciated. A CT diagnosis ofa RPA was made.As the diagnosis of abscess in the newbornwithout obvious risk factors is unconvincing, theneonatologists insisted on a MRI scan to excludecongenital lesions. The MRI neck also showedsimilar findings as the CT scan i.e., retro and leftparapharyngeal lesion with thick enhancing walland air fluid levels in the lesion causingcompression of the airway (Figs. 5, 6 and 7). Nocommunication with pharyngolarynx or esophagusAddress correspondence to:Dr.Sontenam V.S.Mallik, MD,DNB, FRCR (London), Radiologist, Department of Radiology, Al Jahra Hospital, P.O.Box.1807, Jahra 01020,Kuwait. Tel/Fax: (965) 4577198, E-mail:svsmrao@yahoo.co.in

178Retropharyngeal Candidal Abscess in a Neonate: Case Report and Review of Literature June 2007Fig. 1: Lateral X-ray neck showing widened pre-vertebral space andsmooth posterior indentation over airwayFig. 2: 2D B-mode Ultrasound showing cystic lesion with echogenicdebris and thick wall causing displacement of carotid sheath contentsFig. 3: Plain CT scan neck showing fluid attenuating lesion in retro andleft parapharyngeal space causing elevation and compression of airwaywas noted. Hemogram showed leucocytosis withn e u t rophilia, lymphocytosis, eosinphilia. (WBC16.7 x 10 9 / l, NE 49%, LY 36%, MO 6%, EO 9%) andnormal RBC and platelet count. Diagnostic andtherapeutic US guided percutaneous needleaspiration yielded approximately 15 ml of lightgreenish yellow pus which showed a cell count ofRBC 3840 cells/mm 3 , WBC 181,760 cells/mm 3 with97% neutrophils and 3% lymphocytes. Culture ofthis pus yielded the growth of Candida specieswhich on yeast culture was identified as Candidaalbicans, sensitive to amphotericin B, fluconazoleand 5 - flucytosine. Further blood test detectedcandidal antigen 1:2 by latex agglutination test.Treatment was then started with ambisone, 3 mgonce a day as infusion over two hours andi n c reasing daily by 1 mg for ten days with total dosenot exceeding 50 mg. Also, antibiotics were givenFig. 4: Contrast enhanced CT scan neck showing moderate enhancementof the lesion wall with air-fluid levelss i m u l t a n e o u s l y. With this clinical course andmanagement the baby improved within two weekswith no cyanotic spells or stridor. During thecourse, CT and US scans were repeated to see theradiological improvement. Resolving air fluidlevels with collapsed abscess and opened upairway was noted after ten days (Fig. 8). Furtherfollow up was advised with the pediatric and ENTsurgeon and the child was discharged.DISCUSSIONA deep space neck infection, RPA is a seriousand occasionally life-threatening condition due toits anatomic location and the potential to obstructthe upper airway [3] . The presentation of RPA issometimes subtle, and the constellation of findingsis apparently variable. However, eighty-fivep e rcent of newborns with early-onset infectionpresent within 24 hours [4,6] . Common presenting

June 2007KUWAIT MEDICAL JOURNAL 179Fig. 5: MRI neck T2W axial image showing globular lesion with air-fluidlevels and isointense rim in retro and left parapharyngeal spacesFig. 6: Post Gad T1W axial image showing enhancing thick abscess wallwith compression of the oropharynxFig. 7: Post Gad.T1W sagittal image showing vertical extent of the abscesswith compression and anterior displacement of pharyngolarynxsymptoms in infants include fever (100%), neckswelling (84%) and anorexia (58%). The physicalsigns include cervical adenopathy (69%),re t ropharyngeal bulge (43%; do not palpate inchildren), fever, stridor (23%), torticollis (18%) andrarely, cyanosis [5,6] . Early-onset of sepsis in neonatesis associated with acquisition of m i c ro o rg a n i s m sf rom the mother. The micro o rg a n i s m s m o s tcommonly associated with early-onset infectioninclude group B Streptococcus (GBS), Escherichia coli,Haemophilus influenzae, and Listeria monocytogenes.Late-onset sepsis occurs at 7-90 days of life and isa c q u i red from the care-giving enviro n m e n t .Organisms that have been implicated in causinglate-onset sepsis include Staphylococcus aureus, Ecoli, Klebsiella, Pseudomonas, Enterobacter, Candida,Fig. 8: Follow up CT scan after 10 days showing completely resolvedabscess with opened up airwayGBS, Serratia, Acinetobacter, and anaerobes. Studieshave shown that premature infants and low birthweight babies have an increased incidence ofsepsis [6] . RPA of bacterial origin were reported inlate neonatal period with Staphylococcus as maincausative organism.C a n d i d a, like bacteria may infect fetus byhematogenous dissemination from umbilical

180Retropharyngeal Candidal Abscess in a Neonate: Case Report and Review of Literature June 2007vessels. The original source is usually the mother,as in our case or may be hospital nursing staff,contaminated supplies or caretakers. In others, itmay be a complication of bacterial pharyngitis orrarely, vertebral osteomyelitis or wound infection.The possible cause in our case was transmissionfrom the maternal genital tract. Oral candidiasis orthrush generally peaks at two weeks of life andsubsequently other candidal sepsis like systemicabscesses occur [ 6 , 7 ] . An abscess in the re t ro p h a r y n g e a lspace may cause compression of airway or ruptureinto the pharynx with aspiration of pus or it maydissect into the esophagus or a major blood vesselor into the mediastinum with resultant mortalitydue to mediastinitis being as high as 50%. Thetraditional management of RPA has been surgicaldrainage of the pus collection, with an intra - oralincision. Yet some cases are managed withantibiotics alone [8] . Percutaneous aspiration has alsobeen described as a therapeutic pro c e d u redepending on the individual case such as ours,which proved successful. If the baby exhibits signsof severe upper airway obstruction, endotrachealintubation or tracheostomy may be required asdefinitive treatment. The differential diagnosis inour case should include all congenital cystic lesionsand air containing masses of the neck, likelaryngocele, airway diverticula, bronchial cleftcysts and cystic hygroma.A retrospective chart review at the PrimaryChildren’s Medical Center (PCMC) in Salt LakeCity, Utah, about RPA in children revealed that 64patients were diagnosed to have RPA of nontraumaticorigin in the five year period reviewed.The median age of the patients was 36 months.Overall, 48 (75%) of the 64 patients were youngerthan five years, and 10 (16%) were younger thanone year. Stridor as presenting symptom was foundin one patient only.Arecent 10 year review at KingsCounty Hospital in Brooklyn, NY, revealed that30% of the cases were in pediatric patients aged 16months to eight years [9] . A 35 year review of casesinvolving children who were treated for RPA atChildren’s Hospital in Los Angeles revealed that50% patients were younger than three years and71% were younger than six years. A review inSydney, Australia, found that, in 55% of pediatricRPA cases, the children were younger than oneyear, with 10% diagnosed in the neonatal period [9] .However none of these studies had a baby affectedwith RPA in the early neonatal period or soon afterbirth.CONCLUSIONIn newborn babies, especially those with highrisk of sepsis, who present with airway obstruction,stridor or cyanosis, a thorough analysis andinvestigation into the various etiological factorsshould be done, in addition to routine cardiaccauses, as early recognition and aggressive therapyis mandatory in RPA, to save precious babies fromlife-threatening complications.ACKNOWLEDGEMENTSWe would like to thank all the doctors in NICU,Jahra Hospital for their care and management ofthe baby with good feedback.REFERENCES1. Fleisher GR. Retropharyngeal and lateral pharyngealabscess. In: Fleisher R, Ludwig S, editors. Textbook ofPediatric Emergency Medicine. 4 th ed. Philadelphia, PA:Lippincott Williams & Wilkins; 2000, p 744.2. Hughes J, Martin RJ, Clutterbuck EJ. Retro p h a r y n g e a linfection with Staphylococcus aureus in a hemodialysispatient. Am J Nephrol 1993; 13:435-436.3. Beasley DJ, Amedee RG. Deep neck space infections. J LaState Med Soc 1995; 147:181-184.4. Barratt GE, Koopmann CF Jr, Coulthard SW. Retropharyngealabscess-- a ten-year experience. Laryngoscope 1984;94:455-463.5. Pontell J, Har-El G, Lucente FE. Retropharyngeal abscess:clinical review. Ear Nose Throat J 1995; 74:701-704.6. Klein JO, Marcy SM. Bacterial Sepsis and Meningitis.Infectious Diseases of the Fetus and Newborn Infant. 4thed. 1995; p 835-878.7. Ralph D. Feigin. Pediatric infectious diseases. 3rd ed. 1992;p 805-808, 1907-1916.8. Broughton RA. Non-surgical management of deep neckinfections in children. Pediatr Infect Dis J 1992; 11:14-18.9. Joseph Kahn, Edwards MS. Clinical indicators ofChildhood retropharyngeal abscess. Am J Emerg Med 2004;13:333-336.

KUWAIT MEDICAL JOURNAL June 2007Case ReportTransient Diabetes Mellitus following L- AsparaginaseTherapyABSTRACTAshok Shenoy Kudgi 1 , Mukta Nithyananda Chowta 1 , Rajeev Aravindakshan 21Department of Pharmacology, 2 Department of Community Medicine,Kasturba Medical College, Mangalore, IndiaKuwait Medical Journal 2007, 39 (2):188-189Hyperglycemia may occur as a complication in patientswith leukemia during induction of remission with L-asparaginase and steroids. The reported incidence isabout 10%. The presentation of this complication mayvary from mild glucose intolerance to severe, or evenfatal, diabetic ketoacidosis. We report a case of a 15-yearoldgirl who developed transient diabetes mellitusfollowing L-asparaginase therapy with ketoacidosis asthe mode of presentation.KEYWORDS: hyperglycemia, ketoacidosis, L-asparaginase, leukemia,INTRODUCTIONL-asparaginase is commonly used in combinationwith doxorubicin, vincristine, methotrexate andp rednisolone for the treatment of acutelymphoblastic leukemia (ALL). Leukemic cells arehighly sensitive to chemotherapy. In over 90% ofpatients, a complete remission in 4-6 weeks can beachieved with prednisolone, vincristine, L-asparaginase and doxorubicin combination chemotherapy.We report a case of severe hyperglycemiaand ketoacidosis following administration of L-asparaginase in an adolescent girl.Case ReportA 1 5 - y e a r-old girl diagnosed to have acutelymphatic leukemia (FAB L1 Type) was oninduction chemotherapy with vincristine, L-asparaginase, doxorubicin, intrathecal methotre x a t eand prednisolone as per the NCI-MCP-841p ro t o c o l [ 1 ] . The laboratory evaluation re v e a l e dhemoglobin of 45 g/l (0.70 mmol/l), total leukocytecount of 10 x 10 9 cells/l and a platelet count of 35 x10 9 cells/l. Peripheral smear showed 25% leukemicblast cells. The patient received three units ofpacked cells prior to commencement ofchemotherapy. She was given L-asparaginase at adose of 10,000 units intravenously, vincristine 2 mgweekly, doxorubicin 40 mg weekly, prednisolone 60mg daily and intrathecal methotrexate 12.5 mgweekly as the part of I1 regimen in the protocol. Thesecond dose of L-asparaginase was given on daythree of induction of chemotherapy.On day eight, patient became lethargic andirritable, developed severe abdominal pain, vomitingand deep and rapid inspiration (respiratory rate 30/ minute). Her blood pressure was 110/70 mmHg,serum amylase and electrolytes were normal. Thetotal count was 3.1 x 10 9 cells/l, hemoblobin 111 g/l(1.72 mmol/l). Suspecting septicemia, she wasgiven ceftazidime 1 g q8H and gentamicin 100 mgq 24H. On day 10, patient did not improve andrandom blood sugar at this point of time was 277mg/dl and urine tested positive for ketone bodies.There was no family history of diabetes mellitus.Regular insulin was started in a dose of four unitsq8H, which was escalated to 10 units q8H. Thefasting blood sugar (FBS) values on days 12, 16, 18,22 were 9.05 mmol/l, 6.77 mmol/l, 5.55 mmol/land 3.33 mmol/l respectively. She was put onbovine insulin mixtard (30:70) in a dose of 20 unitsin the morning and 10 units at night on day 21which was then reduced to 16 units morning and 8units at night. Her blood sugar was controlled andFBS values on days 26, 29, 39 and 51 were 3.72mmol/l, 4.61 mmol/l, 5.0 mmol/l and 3.89 mmol/lre s p e c t i v e l y. The dose of insulin was furtherreduced to 8 units morning and 4 units night and itwas stopped on day 55. Her prednisolone dose wasreduced to 40 mg/day and further to 20 mg/dayover a period of five days and it was stopped onday 41. On day 38, clinical remission of ALL wasobtained which was confirmed by bone marrowAddress correspondence to:Dr. Ashok Shenoy K., Associate Professor, Department of Pharmacology, Kasturba Medical College, Light House Hill Road, Mangalore - 575001,Karnataka, India. Fax:+91-824-2425092, E-mail:ashok.shenoy@manipal.edu, dr_ashok_shenoy@rediffmail.com

June 2007KUWAIT MEDICAL JOURNAL 189examination. After remission, patient was taken forRegimen I2 wherein cyclophosphamide 800 mgs t a t, 6-mercaptopurine (6-MP) 75 mg daily forseven days and intrathecal methotrexate 12.5 mgweekly was administered. Cranial irradiation wasgiven. Then the patient was subjected toconsolidation chemotherapy (Regimen I2A) with 6-MP, cyclophosphamide and cytosine arabinoside.The patient was subjected to a re i n d u c t i o nprotocol (RI1) wherein vincristine and doxorubicinwere administered as before and prednisolone at 40mg/day. L-asparaginase was omitted. Fasting andpostprandial blood sugars were monitore dcarefully and no elevation was found. RI1 phasewas completed without any adverse event.Consolidation chemotherapy was completed onday 100. Pre s e n t l y, the patient has achievedremission and is on maintenance treatment withmethotrexate and 6-MP.DISCUSSIONSeveral investigators have demonstrated thee ffect of L-asparaginase on carbohydratemetabolism. L-asparaginase has shown hyperglycemiain rabbits [2] and this has been shown to bepotentiated by prednisolone [3] . Cetin M et al [4] havedocumented hyperglycemia in six out of 136c h i l d ren receiving L-asparaginase wherein twodeveloped ketoacidosis requiring insulin therapy.Gillette et al [ 5 ] reported a case of transientdiabetes mellitus (DM) in a 10-year-old girl whorequired insulin therapy. Pui et al [6] showed thatchildren more than 10 years of age, a positivefamily history of DM and obesity had a higher riskof developing hyperglycemia. The risk and severityof DM increases when L-asparaginase and steroidsare used concomitantly which is generally selflimiting[7] . However, in our case, concurrent use ofsteroids cannot be implicated as the sole causesince the patient did not develop hyperglycemiaduring the reinduction (RI2) protocol where i nprednisolone was used and L-asparaginase wasomitted. In fact, in normal individuals,corticosteroids have been found to protect againstfasting ketosis [8] .The possible mechanism by which L-asparaginase causes hyperglycemia and ketoacidosisis by hypoinsulinemia resulting from an inhibitionof insulin synthesis secondary to extreme depletionof L-asparagine or destruction of preformed insulin [ 9 ] .L-asparaginase can cause pancreatitis [10] . However,the clinical picture and normal serum amylaselevels make pancreatitis unlikely in this patient.We recommend that oncologists watch for thisserious adverse effect even when the drug is usedin low doses. Close monitoring for hyperglycemiaand glycosuria should be continued duringtherapy.REFERENCES1. Chabner BA, Ryan DP, Area LP, Carbonero RG, Calabresi P.Antineoplastics agents. In: Goodman and Gilman’s ThePharmacological Basis of Therapeutics, Hardman JG andLimbird LE, editors. 10th ed. New York: McGraw Hill; 2001,p 1389-1459.2. Trigg ME, Gaynon PS, Uckun FM. Acute LymphoblasticLeukemia in Children. In: Holland JF et al, editors. CancerMedicine. 4th ed. Baltimore :Williams and Wilkins; 1997, p2945-2960.3. Ortega JA. Nesbit ME Jr, Donaldson MH, et al. L-asparaginase, vincristine and prednisone for induction offirst remission and acute lymphoblastic leukemia. CancerRes 1977; 37:535-540.4. Cetin M, Yetgin S, Kara A, et al. Hyperg l y c e m i a ,ketoacidosis and other complications of L-asparaginase inchildren with acute lymphoblastic leukemia. J Med 1994;25:219-229.5. Gillette PC, Hill LL, Starling KA, Fernbach DJ. Transientdiabetes mellitus secondary to L-asparaginase therapy inacute leukemia. J Pediatrics 1972; 81:109-111.6. Pui CH, Burghen GA, Bowman WP, Aur RJA. Risk factorsfor hyperglycemia in children with leukemia receiving L-asparaginase and prednisone. J Pediatrics 1981; 99:46-50.7. Khan A, Adachi M, Hill JM. Diabetogenic effect of L-asparaginase. J Clin Endocrinol Metab 1969; 29:1373-1376.8. Khan A, Adachi M, Hill JM. Potentiation of Diabetogeniceffect of L-asparaginase by prednisolone. Hormone MetabRes 1970; 2:275-2769. Land VJ, Sutow WW, Fernbach DJ, Lane DM, Williams TE.Toxicity of L-asparaginase in children with advancedleukemia. Cancer 1972; 30:339-347.10. Kinsell LW, Margen S, Michaels GD, Reiss R, Frantz R,Carbone J. Studies in fat metabolism. III. The effects ofACTH, of cortisone and of other steroid components uponfasting induced hyperketonemia and ketonuria. J ClinInvest 1951; 30:1491.

June 2007KUWAIT MEDICAL JOURNALCase ReportMale Adolescent with Systemic Lupus ErythematosusMona Hussain Badawi, Enamul Haque, Hesham AbdulazizDepartment of Pediatrics, Al-Adan Hospital, KuwaitABSTRACTKuwait Medical Journal 2007, 39 (2):181-183Systemic lupus erythematosus (SLE) is uncommonin children, especially in male adolescents (10-20years of age). We present the case of an 11 year oldboy in whom the diagnosis was missed in the firstinstance because of vague initial presentation andlack of suspicion. Raised antinuclear antibody(ANA) and anti-double stranded DNA ( a n t i - d sDNA) antibody titers that were checked afterappearance of malar erythematous rash providedthe diagnosis. The patient responded well tocorticosteroid therapy.KEY WORDS: antinuclear antibodies, male adolescent, systemic lupus erythematosusINTRODUCTIONSystemic lupus erythematosus (SLE) is uncommonin male children and young adolescents (10-20years of age). Its reported incidence and prevalenceis shown in Table 1. Although the American Collegeof Rheumatology (ACR) include definitive clinicalfeatures amongst diagnostic criteria for SLE, yet itis known to present with protean, albeit initially,atypical manifestations [1] .We came across a young male adolescent, 11years old, in whom the diagnosis was delayedbecause of the vague initial manifestation and lackof suspicion. It merits presentation here because ofthe paucity of its occurrence in male adolescentsand to promote awareness of this condition inpatients of this age group.CASE REPORTNH, a previously healthy 11 - y e a r-old boy,p resented with two weeks, history of fever,generalized fatigue and ill-health. On physicalexamination he looked sick and was febrile (temp39 0 C). He was normotensive (BP 110/60 mmHg),and his pulse rate was 110/minute. He did not haveany arthrlagias, myalagias or skin rash. Systemicexamination was normal. No obvious focus ofinfection was found. Investigations results (Table 2)were as follows: CBC showed pancytopenia withWBC count of 1.9 x10 9 /l, (neutrophils 0.8x10 9 /l),hemoglobin 89 g/l and platelet count 125x10 9 /l.The erythrocyte sedimentation rate (ESR) wasmarkedly elevated (117 mm/1st hour, Westergren).C R P was normal. Biochemical profile showedraised hepatic enzymes (ALT = 150 IU/l and AST =350 IU/l).In view of persistent fever, deteriorating clinicalcondition and no identifiable focus of infection, thepatient was treated empirically with IV cefotaximeand gentamycin, but without any noticeablebenefit. A week later, the patient developedextensive erythematous rash on the malar area offace, limbs, palms and soles (Fig. 1). He alsodeveloped oral ulcers and bleeding from the buccalmucosa. Though he complained of generalizedbody aches, there were no objective signs of anybone or joint involvement. At this stage thepossibility of SLE was considered and this wasconfirmed with findings of conspicuously raisedANA (2647.6 IU/ml) and raised double strandedDNA antibody (2783.3 IU/ml) titers. Additionally,complement levels were also significantly reduced(C3 0.24g/l, C4 < 0.1 g/l). Serum protein electroph o resis showed polyclonal rise in gammaglobulins.The patient was given pulse therapy with IVmethylprednisolone, 20 mg/kg/day for three days.He also received IV Immunoglobulin, 400 mg/kgfor five days. The response was dramatic. He soonbecame afebrile, and the erythematous rashd i s a p p e a red; he stopped complaining of generalizedaches and looked well. Subsequently the patientwas started on methotrexate and oral glucocorticoidtherapy (prednisolone 20 mg/day). Until thewriting of this report (one year since the diagnosis)the child continues to remain in re m a r k a b l eremission on a daily maintenance dose ofprednisolone 10 mg on alternate days.Address correspondence to:Dr.Mona Hussain Badawi, DCH, MRCP, Department of Pediatrics, Al-Adan Hospital, Kuwait. POB 46969, Haedia- 64020, Kuwait. Fax:3941624, E-mail:monabadawi@hotmail.com,mona_badawi@hotmail.com, hesham38y@hotmail.com

182Male Adolescent with Systemic Lupus Erythematosus June 2007Table 1: Incidence and prevalence of SLE in differentethnic groups [1]Table 2: Results of relevant laboratory investigations atadmission and after four weeks of treatmentEthnic groupIncidence Rate Prevalence Rate(per 100,000) (per 100,000)At admission After 4 weeks Reference valueof treatmentUS adults 2-5 120US children < 15 years 0.5-0.6US white females < 20years 4.4Oriental females < 20 years 31Black females < 20 years 19.8DISCUSSIONSystemic lupus erythematosus is a well knownauto-immune disease that presents with proteanmulti-organ manifestations. The incidence of SLEvaries worldwide. In the United States, incidence ofthis disease among children younger than 15 yearsof age is 0.5-0.6 per 100,000 per year, with aprevalence rate of 14-50 per 100,000; the rates beinghigher in females than in males [1-4] .SLE is uncommon in children and youngadolescents (10-20years of age). Its occurrence isparticularly rare in male subjects. This combinedwith the fact that its clinical presentation, especiallyi n i t i a l l y, can often be varied and vague, thediagnosis of SLE in male children is frequentlymissed in the first instance.SLE can present with a wide variety of clinicalfeatures, reflecting multi-organ involvement. Thisis matched serologically by the presence of a widespectrum of auto-antibodies. The clinical markersinclude malar erythematous rash, arthralgias,myalgias or renal involvement [5] . SLE should also bec o n s i d e red when generalized fatigue occurs incombination with mucocutaneous manifestationswhich evolve over some time.H o w e v e r, elevated levels of A N A and antidsDNA antibodies remain the sheet anchor for itsdiagnosis. The case presented here is an example.In this instance, no suspicion was raised initiallybecause the patient who is a male young adolescentp resented only with fever and was tre a t e dempirically for infection in absence of evidence ofany specific cause of fever. It was when hedeveloped erythematous rash, particularly onmalar area of face that suspicion of SLE was raisedand specific investigations like ANA, anti dsDNAand serum complement levels were undertaken.These led to the diagnosis of SLE. The ACR has laiddown definitive clinical and laboratory criteria forthe diagnosis of SLE. The patient should have atleast four out of the eleven criteria that occur in thecourse of this disease [5-7] .The most useful screening tests that arerecommended for diagnosis of SLE includecomplete blood count, erythrocyte sedimentationrate and testing for antinuclear antibody [ 8 - 10 ] .Hb (g/l) 86 11 115-155WBCS (x10 9 /l) 1.6 7.5 4.5-13.5Neutrophils(x10 9 /l) 0.7 5.4 3-5.8Lymphocyte(x10 9 /l) 0.7 1.6 1.5-3Platelets (x10 9 /l) 125 574 150-400ESR(mm 1st hour) 115 8 0-10CRP(mg/l) 6

June 2007KUWAIT MEDICAL JOURNAL 183erythematosus. In: Textbook of Rheumatology, Vol 2. WBSaunders, 1997; p 1028-1056.7. Hahn BH. Management of systemic lupus erythematosus.In: Textbook of Rheumatology, Vol 2. WB Saunders, 1997; p1040-1056.8. Lehman TJ, Hanson V, Singsen BH, Kornreich MK,Bernstein B, King K. The role of antibodies directed againstdouble-stranded DNA in the manifestations of systemiclupus erythematosus in childhood. J Pediatr 1980; 96:657-661.9. Barron KS, Silverman ED, Gonzales J, Reveille D. Clinical,serologic and immunogenetic studies in childhood-onsetsystemic lupus erythematosus. Arthritis Rheum 1993;36:348-354.10. H o c h b e rg MC. Updating the American College ofRheumatology revised criteria for the classification ofsystemic lupus erythematosus. Arthritis Rheum 1997;40:1725.11. Tucker LB, Menon S, Scheller JG, Isenberg DA, Adult andchildhood-onset systemic lupus erythematosus: Acomparison of onset, clinical features, serology andoutcome. Br J Rheumatol 1995; 34:866-872.

KUWAIT MEDICAL JOURNAL June 2007Case ReportAspergillus Pseudomembranous TracheobronchitisComplicating Treatment of COPD ExacerbationsAlia Al-Alawi 1 , Frank Ryan 21Department of Medicine, Amiri Hospital, Kuwait2Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, CanadaABSTRACTKuwait Medical Journal 2007, 39 (2):184-187Aspergillus pseudomembranous tracheobronchitis is anuncommon form of invasive aspergillosis that affectsimmuno-compromised hosts. We describe the clinicaland radiological features of this form of invasiveaspergillosis occurring in two patients with severe COPDas a complication of treatment with corticosteroids andbroad spectrum antibiotics.KEY WORDS: aspergillosis, COPD, tracheobronchitisINTRODUCTIONA s p e rgillus pseudomembranous tracheobro n c h i t i sis a form of invasive pulmonary aspergillosis that islimited to the tracheobronchial tree. Aspergillushyphae invade the airways and form plugs that canlead to airway obstruction. It occurs most commonlyin neutropenic patients receiving chemotherapybut has also been described following org a ntransplantation, viral infections (particularly influenza),diabetes mellitus, renal and hepatic failure and inpatients with acquired immunodeficiency syndro m e .In addition to these underlying diseases, a historyof treatment with corticosteroids and antibiotics iscommon. Patients usually present with dyspnea,cough and wheezing. They occasionally expectoratemucus plugs or tracheobronchial casts. The diagnosisis confirmed by demonstrating fungal invasion ofthe airways. The condition is associated with a highmortality rate despite treatment. There are threep revious case reports of aspergillus tracheobro n c h i t i soccurring in patients with COPD. We report twofurther cases, describe their clinical and radiologicalfeatures and speculate on the role of corticostero i dt h e r a p y, broad spectrum antibiotics and possiblyantecedent viral respiratory tract infection in theo c c u r rence of this rare, but frequently lethal,complication of COPD exacerbations.Case 1A 6 7 - y e a r-old female cigarette smoker withknown COPD presented to hospital in the fall of1998 with increasing shortness of breath. A chestradiograph showed evidence of hyperinflation ofthe lungs but no infiltrates. She was admitted witha diagnosis of COPD exacerbation and was treatedempirically with bronchodilators, systemicc o r t i c o s t e ro i d s and cefuroxime. Erythro m y c i nwas added later because of failure to improve.S p i rometry showed an FEV1 of 0.65L ( 3 1 %predicted).The patient continued to deteriorate. Shedeveloped herpes labialis and a painful red eye,subsequently confirmed to be herpes simplexkeratitis. She also had oral candidiasis. A follow-upchest radiograph 12 days later showed poorlydefined bilateral nodular opacities (Fig. 1). Highresolution CT of the chest (Fig. 2) demonstratedextensive bilateral centrilobular nodular andbranching linear opacities (tree-in-bud pattern).Also noted were a few randomly distributednodules measuring 5 to 10 mm in diameter andpatchy bilateral ground glass opacities. Bronchialwall thickening was present involving mainly thesegmental and subsegmental bronchi of the upperlobes. Bronchoscopy revealed pharyngeal candidiasisand extensive membranous, slightly hemorrhagicexudates throughout the trachea and pro x i m a lmain-stem bronchi. The membrane was adherentand attempted suction caused slight bleeding. Thewashings showed the psuedomembrane to containA s p e rg i l l u sand cultures grew A s p e rg i l l u sf u m i g a t u s .Tr a n s b ronchial and endobronchial biopsies confirmedthe presence of inflammatory psuedomembraneswithin which were fungal elements morphologicallyAddress Correspondence to:Dr. Alia Al-Alawi, P.O. Box 3876- Mushrif-40190, Kuwait. Tel : 965 245 0005, Fax: 965 244 7584, E-mail: aliamed@yahoo.com

June 2007KUWAIT MEDICAL JOURNAL 185Fig. 2: HRCT of case 1 showing centrilobular nodular opacities (thinarrows) and branching linear opacities (thick arrow) (tree-in-bud pattern)with itraconazole. Despite treatment she developedworsening respiratory failure and died. Permissionfor autopsy was declined.Fig. 1: Chest X-ray of case 1 showing poorly defined bilateral nodularopacitiesconsistent with A s p e rg i l l u s. The mucosa andsubmucosa were inflamed and there was squamousmetaplasia. Serum immunoglobulin level showed apattern consistent with acute phase reaction but noevidence of immunoglobulin deficiency. A d i a g n o s i sof A s p e rg i l l u spsuedomembranous tracheobro n c h i t i swas made. The disease was differentiated fromallergic bronchopulmonary aspergillosis (ABPA) bythe following: (1) the absence of peripheraleosinophilia, (2) the absence of the appearances ofABPA on endobronchial biopsy (e.g. allergic mucinand eosinophils), (3) the presence of inflammatorypsuedomembranes that are not known to occurwith ABPA, and (4) the progression of the diseasedespite high doses of systemic stero i d s .Amphotericin B was commenced and the patientwas transferred to the intensive care unit fori n c reasing shortness of breath and stridor. Shei m p roved significantly on Amphotericin B butwhen switched to oral itraconazole she deterioratedand Amphotericin B was re-started. Two monthsafter admission, she coughed up a large grayishtracheobronchial cast, histology of which revealedorganized inflammatory psuedomembranes. Thepatient improved gradually and was dischargedfrom hospital after a three-month stay. She hadreceived a total dose of 2705 mg of Amphotericin Band was discharged on no antifungal therapy.One year later the patient was readmitted tohospital with increasing shortness of bre a t h .Sputum cultures grew Aspergillus, and a CT chestshowed areas of bronchiectasis and new nodularopacities. She was presumed to have reactivation ofinvasive aspergillosis and was started on treatmentCase 2A 74-year-old male with COPD presented withshortness of breath and cough. A chest radiographshowed hyperinflation but was otherwise unre m a r k a b l e .Peripheral white blood cell count was normal.S p i rometry revealed an FEV1 of 0.58l (23%predicted). He was admitted to hospital with adiagnosis of COPD exacerbation and was treatedwith bronchodilators, cefuroxime, erythro m y c i nand systemic corticosteroids. Cefuroxime was laterswitched to cefotaxime. Despite five days of tre a t m e n t ,the patient’s condition pro g ressed to acuterespiratory failure necessitating transfer to theintensive care unit and endotracheal intubation. Hedeveloped leukocytosis with a neutro p h i l i cpredominance. Arepeat chest X-ray showed diffusereticulonodular infiltrates. A high resolution CTchest revealed extensive bilateral centrilobularnodular and branching linear opacities andb ronchial wall thickening. Sputum culture waspositive for A s p e rg i l l u sf u m i g a t u s. On bro n c h o s c o p i cexamination, copious thick white secretions wereobserved throughout the entire tracheobronchialtree with adherent plaques in the right main-stembronchus and psuedomembranes more distally inthe right lower lobe. Bronchoscopic biopsiesshowed numerous fungal hyphae ( a s p e rg i l l u s )within material consistent with psuedomembranes.B ronchial washings grew A s p e rg i l l u s f u m i g a t u s.Both the bronchoscopy findings and the CTappearances were consistent with psuedomembranoustracheobronchitis, and the patient wasstarted on treatment with nebulized andintravenous liposomal Amphotericin B. Despitetreatment, the patient developed signs of septicshock and died eight days later of respiratory andrenal failure.

186Aspergillus Pseudomembranous Tracheobronchitis Complicating Treatment of COPD Exacerbation June 2007DISCUSSIONAspergillus tracheobronchitis is an uncommonmanifestation of acute a s p e rg i l l u sinfection occurring inless than 7% of cases of pulmonary aspergillosis [1] .Infection is confined to the larger airways, often withthe formation of inflammatory pseudomembranes [ 2 ] .The disease has several morphological forms [3] . Thefirst consists of intraluminal growth of the fungusinvolving more or less the entire circumference ofthe airway wall. Grossly, such disease may take theform of psuedomembranes lining and partiallyo b s t ructing the airway lumen or completelyocclusive mucus / fungus plugs. The infection isoften confined to the mucosa and extension beyondthe bronchial wall is unusual. Depending on theextent and location of airway disease, aff e c t e dpatients may be asymptomatic or complain ofvariable degrees of dyspnea and hemoptysis. Bothpatients in our report had this form of aspergillust r a c h e o b ro-nchitis, probably with an additionalcomponent of aspergillus bronchopneumonia.A second morphological variety of aspergillustracheobronchitis consists of one or more discreteplaques limited to a relatively small area of theairway wall. Such infection can remain localized tothat site and grow within the lumen to form ano b s t ructing mass. More commonly, the fungusinvades the trachea or bronchial wall and extendsinto adjacent tissue. Complications include fistulaformation between the airway and mediastinum,esophagus or pleura, and pulmonary arteryinvasion with pleural hemorrhage.The final form of tracheobronchial aspergillosisis the least common and is seen predominantly inthe smaller bronchi and bronchioles. Histologically,the abnormality is characterized by bronchocentricgranulomatosis.Unlike angioinvasive aspergillosis whichtypically afflicts patients who are pro f o u n d l yimmunocompromised, it has been suggested thatAspergillus tracheobronchitis is more common inmild to moderately immunocompromised patients,which may explain the endobronchial localization [ 4 ] .N e u t ropenia was the underlying factor in 55p e rcent of patients presenting with a s p e rg i l l u stracheobronchitis [1] . It has also been suggested thatT-cell abnormalities, such as those occurringfollowing influenza A infection, may contribute tothis form of aspergillosis [5] . Boots et al reported acase of aspergillus tracheobronchitis in a healthypatient following influenza A i n f e c t i o n [ 5 ] . Thatpatient had a persistent lymphopenia involving Tcells and NK cells associated with cutaneousa n e rg y. The disease has also been reported inpatients with no known risk factors [ 1 ] .Tracheobronchial aspergillosis has been reported inCOPD patients [ 6 - 8 ] . Many of these patients hadreceived corticosteroids or bro a d - s p e c t ru mantibiotics [2] . It was found in a case control studythat invasive aspergillosis, although rare in COPD,was associated with the use of high doses ofc o r t i c o s t e roids and multiple broad spectru mantibiotics [9] . It is possible that an alteration in themicrobial flora in the airways of these patients as aconsequence of broad spectrum antibiotic therapy,coupled with the immunosuppressive effects ofhigh dose corticosteroids, predisposed tocolonization and infection of their airways bya s p e rg i l l u s. Our patients were receiving bothcorticosteroids and broad spectrum antibiotics tot reat their COPD exacerbations. Patient 1 alsoreceived a short course of oral steroids one yearprior to presentation but there is no record of thesecond patient having received corticostero i d sprior to presentation. Viral infections are a commonprecipitant of COPD exacerbations, but we do notknow whether either of our patients had influenzaor another viral respiratory tract infection as theprecipitating cause of their acute illness.Patients with aspergillus tracheobronchitis can beasymptomatic. The most common pre s e n t i n gcomplaints are cough, fever, dyspnea, chest painand hemoptysis [1,2] . They occasionally expectorateintraluminal mucus plugs [2] . These mucus plugs canbe filled with fungal hyphae [2] and are usuallyculture positive for aspergillus. In our report, bothpatients complained of dyspnea and were febrile.Patient No.1 also had a history of coughing up at r a c h e o b ronchial cast that contained A s p e rg i l l u s,many weeks after initial presentation.The diagnosis of aspergillus tracheobronchitis istypically delayed because of the insidious onset,nonspecific signs and symptoms and lack ofradiographic abnormalities. The radiologic picturemay show only slight changes since the infection ismainly limited to the trachea and bronchi. Theradiological findings range from normal to bilateralc o n s o l i d a t i o n [ 10 ] . High resolution CT characteristicallyshows centrilobular nodules and branching linearopacities giving a pattern known as “tre e - i n -bud” [11] . Both of our patients also had bronchial wallthickening.Treatment of A s p e rg i l l u s t r a c h e o b ronchitis issimilar to that of the other forms of invasiveaspergillosis. Amphotericin B is the treatment ofchoice. Itraconazole has also been successfullyused. Nebulized Amphotericin B can also be added.Systemic steroids have no role in the treatment ofAspergillus tracheobronchitis. Rather steroids are arisk factor for the disease [9] . The mortality rate ishigh with 43 percent patients dying despitetreatment and cure achieved in only 21 percent [1] .Our patients died of their disease, with patient No.1improving initially but succumbing later during a

June 2007KUWAIT MEDICAL JOURNAL 187reactivation of her disease. Extrathoracic spread ofdisease can occur despite initiation of antifungaltherapy [1] .The diagnosis of aspergillus tracheobronchitis,although rare, should be considered in a patientwith a COPD exacerbation who deterioratesdespite receiving high dose corticosteroids andbroad spectrum antibiotics. Clues to the diagnosisinclude the development of ill-defined nodules onthe chest radiograph, centrilobular nodules witht ree-in-bud appearance on high resolution CT,coughing up casts or thick mucus plugs and thebronchoscopic appearance of pseudomembranes.The diagnosis is confirmed by histopathologicalevidence of inflammatory psuedomembranescontaining Aspergillus in the proximal or distalairways. Urgent treatment with systemic andpossibly nebulized antifungal therapy is essential,as the mortality is high, even with pro m p ttreatment.REFERENCES1) Kemper CA, Hostetler JS, Follansbee SE, et al. Ulcerativeand plaque- like tracheobronchitis due to infection withaspergillus in patients with AIDS. Clin Infect Dis 1993;17:344-352.2) Al-Alawi A, Ryan CF, Flint JD, Muller NL. Aspergillusrelatedlung disease. Can Respir J 2005; 12:377-387.3) Fraser RS. Pulmonary aspergillosis: Pathologic andPathogenetic features. Pathol Annu 1993; 28:231-277.4) Young RC, Bennett JE, Vogel CL, Carbone PP, DeVita VT.Aspergillosis: the spectrum of the disease of 98 patients.Medicine 1970; 49:147-173.5) Boots RJ, Paterson DL, Allworth AM, Faoagali JL.Successful treatment of post-influenza necro t i z i n gb ronchial aspergillosis with liposomal amphotericin B,gamma interferon and GM-CSF. Thorax 1999; 54:1047-1049.6) Hines DW, Haber MH, Yaremko L, Britton C, MclawhonRW, Harris AA. Psuedomembranous tracheobro n c h i t i scaused by aspergillus. Am Rev Respir Dis 1991; 143:1408-1411.7) Nicholson AG, Sim KM, Keogh BF, Corrin B.Psuedomembranous necrotizing bronchial asperg i l l o s i scomplicating chronic airways limitation. Thorax 1995;50:807-808.8) Thommi G, Bell G, Liu J, Nugent K. Spectrum of invasivepulmonary aspergillosis in immunocompetent patientswith chronic obstructive pulmonary disease. South Med J1991; 84:828-831.9) Muquim A, Dial S, Menzies D. Invasive aspergillosis inpatients with chronic obstructive pulmonary diseases. CanResp J 2005; 12:199-204.10) Logan PM, Muller NL. Thoracic radiology. High resolutioncomputed tomography and pathologic findings inpulmonary aspergillosis: a pictorial essay. Can Assoc RadiolJ 1996; 47:444-452.11) Franquet T, Muller NL, Gimenez A, Guembe P, de la TorreJ, Bague S. Spectrum of pulmonary Aspergillosis: histologic,clinical and radiologic findings. Radiographics 2001;21:825-837.

KUWAIT MEDICAL JOURNAL June 2007ABSTRACTCase ReportSymptomatic Large Coronary Artery Aneurysm Associatedwith Sirolimus - Eluting Stent ImplantationMohammad AlMutairi, Khaled AlMerriDivision of Cardiology, Chest Diseases Hospital, KuwaitKuwait Medical Journal 2007, 39 (2):190-192We report a case of a symptomatic large aneurysm in theleft anterior descending coronary artery in a 55-year-oldfemale one year and five months after implantation of asirolimus-eluting stent. This is a rare complication of adrug-eluting stent.KEYWORDS: aneurysm, angioplasty, drug-eluting stent, sirolimusCASE REPORTA 5 5 - y e a r-old lady presented to Card i o l o g ydepartment in June 2005 with crescendo angina andearly positive excercise stress test. Coro n a r yangiography demonstrated good left ventricularsystolic function and mild diffuse atheroscleroticplaques in the right and left circumflex coronaryarteries. There was a 90% long proximal leftanterior descending coronary artery (LAD) stenosis(Fig. 1A). Planned percutaneous coronary interventionwas performed using a 3.0 mm x 33 mm Sirolimus-eluting stent (Cypher). The end result was goodwith no residual stenosis (Fig. 1B). Aspirin andclopidogrel (300 mg) were started 24 hours beforethe procedure. Glycoprotien IIb IIIa inhibitor wasused during the procedure.During hospital stay, the patient evolved withno precordial pain and no electrocardiographic orenzymatic alternations were observed. Twenty-fourhours after stent implantation, the patient wasdischarged from the hospital with a clopidogrelprescription of 75 mg / day for one year and aspirin81 mg / day indefinitely.The patient presented with a similar precordialpain two months later to a hospital in India duringher vacation. Coronary angiography revealed apatent LAD stent.Over the last year the patient continued tocomplain of the same precordial pain and wasre f e r red for exercise stress test with nuclearimaging. Exercise stress testing was positive withhorizontal 1.5 mm ST segment depression in leadsV2 - V6 in stage 2 of the Bruce protocol. Thalliumimaging demonstrated medium size area ofreversible ischemia involving the antero - l a t e r a lwall. The patient was re f e r red for coro n a r yangiography.C o ronary angiography revealed good leftventricular systolic function. A n g i o g r a p h i cappearance of the left main coronary artery wasnormal. Mild to moderate atherosclerotic plaquesin the right and left circumflex coronary arterieswere observed.There was a large coronary aneurysm in theLAD artery in the intra-stent distal portion (Fig. 2).Intravascular coronary ultrasound (IVUS) imagingwas performed (Fig. 3) and this demonstrated thelarge aneurysm, stent malapposition and a 70% instentre-stenosis proximal to the aneurysm.Considering the character of the aneurysm andthe involvement of a large diagonal branch thepatient was advised to undergo coronary arterybypass grafting (CABG).DISCUSSIONRandomized studies with the use of dru g -eluting stents have demonstrated an inhibition ofneointimal hyperplasia in majority of patients [1,2] .With the increasing use of these stents, informationon their longterm effect is extremely important.The formation of a coronary aneurysm, definedas a dilation of the coronary artery that exceed 1.5times the re f e rence diameter of the adjacentc o ronary segments that are angiographicallyn o r m a l [ 3 ] , has been reported after cor o n a r yangioplasty, direct coronary atherectomy and laserangioplasty at a frequency that varies from 2 to10% [4] . At the STRESS study [3] , the presence of a(This article was presented at the 12 th International Conference of the Kuwait Medical Association, April 1-4, 2007)Address Correspondence to:Mohammad AlMutairi, MD, FRCPC, ABIM, Division of Cardiology, Chest Diseases Hospital, Sabah Area, Kuwait. Fax: (965) 4891941, E-mail:malmut99@hotmail.com

June 2007KUWAIT MEDICAL JOURNAL 191(A)(B)Fig.1: RAO cranial view showing (A) pre- and (B) post-stent implantationFig.2: Coronary angiography showing a large LAD aneurysmcoronary artery aneurysm was observed in 3.9%patients submitted to Palmaz-Schatz stent implant.The mechanism involved in prevention of restenosisby drug eluting stents and the antimitoticeffects of the anticancer drugs were consideredresponsible for the delayed healing eff e c t sfollowing balloon dilation resulting in aneurysmformation.Rab et al [ 5 ] have reported the occurrence ofc o ronary artery aneurysms in 32% patientssubmitted to stent placement, when corticoid drugsand colchicine were administered after the implant.These investigators concluded that the aneurysmformation was probably increased due to theconcomitant use of anti-inflammatory agents.Regarding the present case, another possibleFig.3: IVUS image showing malapposition of the stent and the largeaneurysmexplanation for the aneurysm formation is the lateincomplete apposition of the stent filament. This isdefined as a separation of one or more stentfilaments from the intima with no overlap on thelateral branch and evidence of blood flow behindthe filament. It occurs in 4 to 5% of non-elutingstents and at an unknown frequency in dru g -eluting ones. Many hypotheses have beenformulated to explain its origin, such as positiveregional vascular remodeling, plaque regression,late dissolution of the thrombotic material capturedby the stent filaments, cell necrosis, apoptosis, andallergic reaction to sirolimus [6] .Intravascular ultrasound would be essential inplanning a therapeutic strategy. One could verify

192Symptomatic Large Coronary Artery Aneurysm Associated with Sirolimus - Eluting ... June 2007whether it was a pseudoaneurysm or tru eaneurysm by the presence of the three- layeredappearance typical of the coronary artery [7] . Simplystenting over the origin of the dilated segment willoften cover the entrance of the dilated systemresulting in closure of the aneurysm area. Ap o l y t e t r a f l l u o roethylene (PTFE) covered stentcould be employed to seal off the area. A recentlypresented method by Iakovou et al [8] used a custommodifiedPTFE-covered stent. Our patient, however,was advised to undergo CABG because there wasin-stent re-stenosis as well as involvement of a largediagonal branch.REFERENCES1. Morice MC, Serruys PW, Souza JE et al. A randomizedcomparison of a sirolimus-eluting stent with a standardstent for coronary revascularization. N Engl J Med 2002;346:1773-1780.2. Moses JW, Leon MB, Popma JJ, et al. Sirolimus-elutingstents versus standard stents in patients with stenosis in anative coronary artery. N Engl J Med 2003; 349:315-333.3. Slota PA, Fischman DL, Savage MP, Rake R, Goldberg S.Frequency and outcome of development of coronary arteryaneurysm after intracoronary stent placement andangioplasty. Am J Cardiol 1997; 79:1104-1105.4. Bal ET, Thijs Plokker HW, Van de Berg EM, et al.Predictability and prognosis of PTCA - induced coronaryartery aneurysms. Cathet Cardiovasc Diagn 1991; 22:85-88.5. Rab ST, King SB 3rd, Roubin GS, Carlin S, Hearn JA,Douglas JS Jr. Coronary artery aneurysms after stentplacement: a suggestion of altered vessel wall healing in thepresence of anti-inflammatory agents. J Am Coll Cardiol1991; 18:1524-1528.6. Mintz GS, Shah VM, Weissman NJ. Regional remodeling asthe cause of late malapposition. Circulation 2003; 107:2660-2663.7. Lubell D, Gruberg L, Hermiller JB, Gouschior P. Post-stentvery proximal left anterior descending coronary arteryaneurysm. J Invasive Cardiol 2005; 17:230-232.8. Iakovou I, Stankovic G, Montorfano M, et al. Isoverdilatation of 3.0 mm sirolimus-eluting stent associatedwith a higher restenosis rate? Cathet Cardiovasc Interv2005; 64:129-133.

June 2007KUWAIT MEDICAL JOURNALSelected Abstracts of Articles PublishedElsewhere by Authors in KuwaitKuwait Medical Journal 2007, 39 (2):193-196Risk Factors for Diabetic Retinopathy in Kuwaiti Type 2 DiabeticPatientsAl-Adsani AMPO Box 31098, Sulaibikhat 90801, Kuwait. Fax. +965 4883418. E-mail: amsaladsani@yahoo.comSaudi Med J 2007; 28: 579-583Objective: To determine the risk factors associated with diabetic retinopathy in Kuwaiti subjects withtype 2 diabetes.Methods: Kuwaiti subjects with type 2 diabetes (n=165) attending the Diabetic Clinic at Al-SabahHospital, Kuwait between October 2000 and March 2005 were screened for diabetic retinopathy.Results: Any diabetic retinopathy was found in 40% while 20.6% had sight threatening retinopathy.Mild NPDR was present in 21.2%, moderate to severe non-proliferative diabetic retinopathy (NPDR)in 7.9%, and proliferative diabetic retinopathy (PDR) in 3.0%. Maculopathy was present in 10.3% and7.9% of the patients were photocoagulated. Compared to those without retinopathy, diabetic patientswith any retinopathy were significantly older (51.7 +/- 10.3 versus 47.2 +/- 9.5 years; p

194Selected Abstracts of Articles Published Elsewhere by Authors in Kuwait June 2007of age. Eighty-six (50%) of the patients had aseptic meningitis and 19 (11%) had partially treatedmeningitis. The remaining 67 (39%) were diagnosed with bacterial meningitis. The underlyingorganisms were: Neisseria meningitidis (49%), group B streptococci (18%), Streptococcus pneumoniae(18%), Mycobacterium tuberculosis (6%), Gram-negative organisms (6%), and Haemophilus species(1.5%). Twelve percent required admission to the intensive care unit. At the time of discharge from thehospital, 9% had neurological sequelae, the majority of which were in patients who had S.pneumoniae meningitis. Two patients died during the study period. Conclusions: N. meningitidis isthe leading bacterial agent of bacterial meningitis in Kuwait. S. pneumoniae is responsible for themajority of neurological sequelae of bacterial meningitis in infants and young children. The results ofthis study can be used in future public health planning in the context of the newly available vaccines.Clinical and Microbiological Investigations of Typhoid Fever in anInfectious Disease Hospital in KuwaitDimitrov T, Udo EE, Albaksami O, Al-Shehab S, Kilani A, Shehab M, Al-Nakkas ADepartment of Medical Laboratories, Microbiology Section, Infectious Diseases Hospital,PO Box 4710, Safat 13048, Kuwait. E-mail: dimitrov_varn90@hotmail.comJ Med Microbiol 2007; 56:538-544Aretrospective analysis of 135 typhoid cases was conducted to review the clinical, epidemiologicaland microbiological characteristics of enteric fever cases diagnosed and treated at the InfectiousDiseases Hospital, Kuwait, from 2002 to 2005. Diagnosis of patients was based on clinical features,serology and blood culture. The susceptibility testing of the isolates to ampicillin, chloramphenicol,trimethoprim-sulfamethoxazole, ceftriaxone, ciprofloxacin and nalidixic acid was performed by thedisc diffusion method, and MICs of ceftriaxone and ciprofloxacin were determined by Etest. Of 135typhoid fever patients, 108 (88 %) were treated with ceftriaxone and 27 (20 %) were treated withciprofloxacin. The mean time for fever defervescence with ciprofloxacin therapy was 8 days and 6.3days for those treated with ceftriaxone. Of the 135 Salmonella enterica serotypes Typhi and ParatyphiA isolated from patients, 50 (37 %) were multidrug resistant (MDR) and 94 (69.6 %) isolates of bothserotypes were nalidixic acid resistant (NAR). Between 90 and 100 % of MDR and NAR strains haddecreased susceptibility to ciprofloxacin (0.125-1 microg ml(-1)). Low-level resistance to ciprofloxacin(MIC 0.125-1 microg ml(-1)) was also detected in 13.8 and 33.3 % of nalidixic acid-susceptible isolatesof S. Typhi and S. Paratyphi A, respectively. All isolates were susceptible to ceftriaxone. Two relapsesoccurred in the ciprofloxacin-treated group. MDR strains and strains resistant to ciprofloxacin andceftriaxone are a major threat in the developing world. A situation is fast approaching where theemergence of highly resistant Salmonella isolates is quite likely. Proper steps must be taken to avoida pandemic spread of MDR S. Typhi strains.Cultural Factors and Patients’ Adherence to Lifestyle MeasuresSerour M, Alqhenaei H, Al-Saqabi S, Mustafa AR, Ben-Nakhi AFamily Practice Specialty Training Program (FPSTP), Capital Health Region, Hawalli 32056, KuwaitE-mail: drserour@hotmail.comBr J Gen Pract 2007; 57:291-295B a c k g r o u n d : N o n - a d h e rence to preventive and therapeutic lifestyle recommendations amongpatients at high risk of cardiovascular disease is more prevalent and varied than previously thought.The problem needs to be addressed by those who are involved in the care of these patients. AIM: To

June 2007KUWAIT MEDICAL JOURNAL 195measure adherence and barriers of complying with lifestyle recommendations among patients withhigh cardiovascular risk factors.Design of Study: Prospective study.Setting: Six family-practice health centres in Kuwait.Method: Data are from 334 Kuwaiti adult males and females with hypertension, type 2 diabetes, orboth, who completed a routine clinic visit in one of six family practice centres. Trained staff used astructured questionnaire to obtain a detailed medical history regarding exercise habits and barriers tocompliance with diet and exercise programmes. Clinical criteria assessed were height, weight, and thecontrol of blood pressure and blood sugar.Results: From the study sample, 63.5% of patients reported that they were not adhering to any dietregimen, 64.4% were not participating in regular exercise, and 90.4% were overweight and obese. Themain barriers to adherence to diet were unwillingness (48.6%), difficulty adhering to a diet differentfrom that of the rest of the family (30.2%), and social gatherings (13.7%). The main barriers toadherence to exercise were lack of time (39.0%), coexisting diseases (35.6%), and adverse weatherconditions (27.8%). Factors interfering with adherence to lifestyle measures among the total samplewere traditional Kuwaiti food, which is high in fat and calories (79.9%), stress (70.7%), a highconsumption of fast food (54.5%), high frequency of social gatherings (59.6%), abundance of maids(54.1%), and excessive use of cars (83.8%).Conclusion: The majority of individuals in the sample were overweight, did not engage inrecommended levels of physical activity, and did not follow dietary recommendations. Additionalcultural and demographic variables need to be considered to improve adherence to lifestylemeasures.Outcome and Survival in Different Peritoneal Dialysis ModalitiesAl-Hilali N, Al-Humoud H, Nampoory M, Ninan A, Johny KDivision of Nephrology, Department of Medicine, Mubarak Al-Kabeer Hospital, KuwaitE-mail: dralhilali@yahoo.comTher Apher Dial 2007; 11:101-106Peritoneal dialysis (PD) has been accepted as a treatment option for patients with end-stage renaldisease, yet experience with PD in Arab countries is limited. This study was undertaken to evaluatethe outcome and survival of different PD modalities. All patients managed at the Mubarak Al-KabeerHospital Kuwait between August 1982 and December 2003 using PD for three months or more wereincluded in the study. Demographic features, outcome and survival of the patients were analyzed.Four hundred and fifteen patients with end-stage renal failure were admitted into the PD program.Their mean age was 52.06 +/- 16.43 years. Hospital-based intermittent peritoneal dialysis (IPD),continuous ambulatory peritoneal dialysis (CAPD), nightly intermittent peritoneal dialysis (NIPD)and continuous cycling peritoneal dialysis (CCPD) were preferred by 203 (48.9%), 176 (42.4%), 30(7.2%) and 6 (1.4%) patients respectively. The mean duration of follow up was 12.7 +/- 11.7 months.Fifty-five (13.3%) patients were continuing on PD, 55 (13.3%) had shifted to hemodialysis, 73 (17.6%)underwent renal transplantation, 114 (27.5%) died, 34 (8.2%) returned to their native countries, 79(19%) transferred to other centers and follow up was lost for 5 (1.45%) patients. Patient survival at twoyears was 56%, 72% and 87% in IPD, CAPD and NIPD respectively. Technique survival at two yearswas 60.6%, 75.4% and 100% in IPD, CAPD and NIPD respectively. Peritoneal dialysis modalitiesprovide a feasible modality of renal replacement therapy. The overall outcome and patient andtechnique survival in home PD modalities were better than hospital-based PD.

KUWAIT MEDICAL JOURNAL June 2007Forthcoming Conferences and MeetingsCompiled and edited byBabichan K ChandyKuwait Medical Journal 2007, 39 (2):196-202Applying Heart Failure Guidelines in the RealWorld: A Case Based ApproachJun 01-02, 2007Baltimore, MD, United StatesContact: Blackwell Futura Media Services, OneResearch Drive, Suite 400 A, Westborough, MA,01581Tel: 508-614-1415; Fax: 508-616-5568E-mail: media@blackwellfuturacourses.com2 n d International Congress of Gender Medicine 2007Jun 02-04, 2007Vienna, AustriaContact: Ingrid DobiasTel: 43-69-917-038-916; Fax: 43-180-400-634E-mail: ingrid.dobias@gendercongress.comSociety of Nuclear Medicine (SNM) 2007 AnnualMeetingJun 02-06, 2007Washington, DC, United StatesContact: Erica GoughTel: 703-708-9000; Fax: 703-709-9274E-mail: MeetingInfo@snm.org11 th Congress of the Movement Disorder SocietyJun 03-07, 2007Istanbul, TurkeyContact: The Movement Disorder Society, 611 EastWells Street, Milwaukee, WI 53202 USATel:1-414-276-2145; Fax: 1-414-276-3349E-mail: congress@movementdisorders.orgWorld Congress on Hyperhomocysteinemia - 6 thConference on Homocysteine MetabolismJun 05-09, 2007Saarbruecken, GermanyContact: Mr. KnappTel: 49-68-411-630-708; Fax: 49-68-411-630-703E-mail: contact@homocysteine-conference.orgInternational Pharmceutical Regulatory andCompliance CongressJun 06-07, 2007Brussells, BelgiumContact: Paul TunnecliffTel: 800-864-4549; Fax: 760-418-8084E-mail: registration@hcconferences.comHIV/AIDS 2007Jun 06-11, 2007Kololi, GambiaContact: Anthony F. England, Ph.D.Tel: 31-302-145-715; Fax: 31-302-145-715E-mail: england@mangosee.com3 rd International Workshop on HIV and HepatitisCo-infectionJun 07-09, 2007Paris, FranceContact: Jo-Els van der WoudeTel: 31-302-307-147; Fax: 31-302-307-148E-mail: jo-els.vanderwoude@vironet.comHeart Valve SummitJun 07-09, 2007Washington, DC, United StatesContact: Heart House, 2400 N Street NW,Washington DC, 20037Tel: 202-375-6000; Fax: 202-375-70002 n d International Congress on Neuropathic C o n g ressJun 07-10, 2007Berlin, GermanyContact: Ilana EliavTel: 41-229-080-488; Fax: 41-227-322-850E-mail: neuropathic@kenes.comHeart Failure 2007Jun 09-12, 2007Hamburg, GermanyContact: Heart Failure 2007 Congress SecretariatE-mail: HFsecretariat@escardio.org4 th World Congress of the International Society ofPhysical and Rehabilitation MedicineJun 10-14, 2007Seoul, Korea, Republic of KoreaContact: 4th ISPRM SecretariatTel: 82-2-566-6339; Fax: 82-2-565-2434E-mail: isprm2007@intercom.co.kr2 nd National Medicaid CongressJun 13-15, 2007Washington DC, United StatesContact: Paul TunnecliffTel: 800-684-4549; Fax: 760-418-8084E-mail: registration@hcconferences.com

June 2007KUWAIT MEDICAL JOURNAL 1973 rd International Congress on GastrointestinalOncologyJun 14-16, 2007Hersonissos Crete Island, GreeceContact: Mrs Tina FragkakiTel: 302-109-730-697; Fax: 302-109-767-208E-mail: gi-oncology2007@heliotopos.netWell Aging, Andropause, MenopauseJun 15-16, 2007Luxembourg, LuxembourgContact: Monardo ClaudineTel: 35-226-264-134; Fax: 35-226-264-175E-mail: mail@andropause.luEuropean Meeting on Hypertension 2007Jun 15-19, 2007Milan, ItalyContact: Meeting OrganiserTel: 39-0-392-333-357; Fax: 39-0-39-322-274E-mail: giuseppe.mancia@unimib.itCardiology & Women’s Health CruiseJun 16-30, 2007St. Petersburg, RussiaContact: Sea Courses CruisesTel: 1-888-647-7327; Fax: 1-888-547-7337E-mail: cruises@seacourses.com3 rd International Conference on Birth Diseases andDisabilitiesJun 17-22, 2007Rio de Janeiro, BrazilContact: Monica Cevidanes, PMPTel: 55-212-266-9150; Fax: 55-212-266-9175E-mail: monica@jz.com.brNeurology: Clinical Trials-2007Jun 19-20, 2007Kiev, UkraineContact: Meeting Organiser Tel:00-38-0-632-776-465; Fax: 00-38-0-445-331-270E-mail: markov@nbscience.comMedical Management System 2007Jun 19-20, 2007Kiev, UkraineContact: Meeting OrganiserTel:00-380-632-776-465; Fax: 00-380-445-331-270E-mail: markov@nbscience.comClinical Trials Results of GastroenterologicalProducts, Practical Value from the Point of View ofEvidence MedicineJun 19-20, 2007Kiev, UkraineContact: Dr MarkovTel: 38-0-632-776-465; Fax: 38-0-445-331-270E-mail: markov@nbscience.com5 th Amsterdam Menopause SymposiumJun 19-21, 2007Amsterdam, NetherlandsContact: Irene HehenkampTel: 00-31-334-345-730; Fax: 00-31-334-345-720E-mail: ihehenkamp@marktwo.nlStrengthening Your Palliative Care Program: ALevel II Seminar for Growth & SustainabilityJun 21-23, 2007Orlando, FL, United StatesContact: Hallia BakerTel: 212-201-2680E-mail: capcevents@mssm.ed9 th Congress on Cardiovascular UpdateJun 21-24, 2007Tehran, IranContact: Mohammad HasaniTel: 982-166-903-890; Fax: 982-166-903-890E-mail: irsa@email.com3 rd Annual Heart & Vascular Conference: Lub Dub& Splash 2007Jun 22-23, 2007Boyne Falls, MI, United StatesContact: Cindy HolmanTel: 800-248-6777; Fax: 231-487-7855E-mail: cholman@northernhealth.orgXIX ISHR World CongressJun 22-26, 2007Bologna, ItalyContact: I&C s.r.l. - ISHR 2007, Via A. COSTA 2,40134 BOLOGNA - ITALYTel: 39-0-516-144-004; Fax: 39-0-516-142-772E-mail: info@ishr-italy2007.orgCardiovascular MR & CT: State of the ArtJun 23-26, 2007Washington, DC, United StatesContact: Heart House, 2400 N Street NW,Washington DC, 20037Tel: 202-375-6000; Fax: 202-375-7000Diabetes CampJun 23-30, 2007Seattle, WA, United StatesContact: Sandra BarnhartTel: 1-800-422-0711; Fax: 727-527-3228E-mail: sandra@continuingeducation.net

198Forthcoming Conferences and Meetings June 2007Cardiology Update in Primary Care Medicine: AnEvidence-Based ApproachJun 25-29, 2007Sarasota, FL, United StatesContact: Eva Easterwood / Cristina Colon,American Medical Seminars, Inc, c/o HyattSarasota on Sarasota Bay, 1000 Boulevard of theArts, Sarasota, Florida 34236-4808Tel: 866-267-4263 / 1-941-388-1766; Fax:1-941-365-7073E-mail: mail@ams4cme.comIntegrated Care Pathways 2007Jun 27-28, 2007London, England, United KingdomContact: Clare GallagherTel: 02-0-85-411-399E-mail: clare@healthcare-events.co.ukThe Annual Interventional Cardiology Conference- CARDIOALEXJun 27-29, 2007Bibliotheca Alexandrina, EgyptContact: International Center for Organization &Marketing, Address: El Asdekaa building (1) -Masged El Asdekaa st. Garden city Smouha -Alexandria - EgyptTel: 203-4-204-849; Fax: 203-4-204-849E-mail: icom@dataxprs.com.eg17 th International Epilepsy Symposium: EpilepsySurgeryJun 27-29, 2007Cleveland, OH, United StatesContact: The Cleveland Clinic Center forContinuing Education, 9500 Euclid Ave. KK31,Cleveland, Ohio 44195Tel: 954-659-5490 / 800-762-8173 / 216-444-5696;Fax: 954-659-5491E-mail: cme@ccf.orgCARDIOALEX 2007 PanArab InterventionalCardiology ConferenceJun 27-29, 2007Alexandria, EgyptContact: Professor Samir Morcos RaflaTel: 00-20-101-495-577; Fax: 00-20-34-204-849E-mail: smrafla@yahoo.comCritical Care 2007Jun 27-29, 2007London, England, United KingdomContact: Amy Tranter;Tel: 02-0-75-016-711E-mail: amy.t@markallengroup.com34 th International Congress on ElectrocardiologyJun 27-30, 2007Istanbul, TurkeyContact: PROB_ZTel: 90-2-122-346-505; Fax: 90-2-122-346-520E-mail: ice2007@probiz.com.tr46 th European Society for Pediatric EndocrinologyMeetingJun 27-30, 2007Helsinki, FinlandContact: Pauline Bertrand, ESPE Secretariat,BioScientifica, Euro House, 22 Apex Court.Woodlands, Bristol, BS32 4JT, UKTel: 44-0-01-454-642-208; Fax: 44-0-1-454-642-222Practical Ob-Gyn Ultrasound: Spotlight onChronic Pelvic PainJun 28-30, 2007Orlando, FL, United StatesContact: American College of Obstetricians andGynecologists, 409 12th St., S.W., PO Box 96920,Washington, D.C. 20090-6920Tel: 202-638-5577E-mail: coding@acog.orgClinical Approaches to OB/GYNJun 29-Jul 01, 2007Savannah, GA, United StatesContact: Meeting OrganiserTel: 706-721-3967 / 800-221-6437; Fax: 706-721-4642E-mail: jnorton@mail.mcg.eduEssentials of Women’s Health: An IntegratedApproach to Primary Care and Office GynecologyJul 01-06, 2007Big Island, HI, United StatesContact: UCSF Office of Continuing MedicalEducation, 3333 California Street, Room 450, SanFrancisco, CA 9411Tel: 415-476-4251 / 415-476-5808; Fax: 415-476-0318/ 415-502-1795E-mail: info@ocme.ucsf.eduTreatment Trends in Surgery CruiseJul 01-08, 2007Ketchikan, AK, United StatesContact: Sea Courses CruisesTel: 1-888-647-7327; Fax: 1-888-547-7337E-mail: cruises@seacourses.comWomen’s Health/Infectious Disease/DermatologyJul 01-13, 2007Rome, ItalyContact: Sandra BarnhartTel: 1-800-422-0711E-mail: sandra@continuingeducation.net

June 2007KUWAIT MEDICAL JOURNAL 199International Summer University - Phd in HealthSciences - Course in Advanced Research MethodsJul 02-13, 2007Viareggio, ItalyContact: Barbara MaroniTel: 00-39-0-22-666-880; Fax: 00-39-0-22-361-226E-mail: smm@unambro.itInternational Summer University - Master TeacherCertificate in Person Centered Clinical MethodTeachingJul 02-20, 2007Viareggio, ItalyContact: Barbara MaroniTel: 00-39-0-22-666-880; Fax: 00-39-0-22-361-226E-mail: smm@unambro.it31 st British Congress of Obstetrics andGynaecologyJul 04-06, 2007London, England, United KingdomContact: Conference and Postgraduate MeetingsDepartmentTel: 44-0-2-077-726-200; Fax: 44-0-2-077-230-575E-mail: conference@rcog.org.ukAdvances in the Molecular Pharmacology andTherapeutics of Bone DiseaseJul 10-11, 2007Oxford, England, United KingdomContact: Janet CromptonTel: 44-0-1-453-549-929; Fax: 44-0-1-453-548-919E-mail: janet@janet-crompton.comObstetrics and Gynecology-Core CourseJul 10-14, 2007Philadelphia, PA, United StatesContact: Office of CME, 1020 Locust Street, SuiteM5, Philadelphia, PA 19107-6799 Tel:1-888-JEFF-CME / 215-955-6992; Fax: 215-923-3212E-mail: edservices@lists.jefferson.eduNeurology Review 2007Jul 10-20, 2007Rome, ItalyContact: Sandra BarnhartTel: 1-800-422-0711; Fax: 727-527-3228E-mail: sandra@continuingeducation.net14 th International Meeting on Advanced SpineTechniques (IMAST)Jul 11-14, 2007Paradise Island, BahamasContact: IMAST Meeting Planning Office c/oBroadWaterTel: 630-681-1040; Fax: 630-682-5811E-mail: IMAST@Broad-water.comInternational Symposium on Paget’s DiseaseJul 12-13, 2007Oxford, England, United KingdomContact: Janet CromptonTel: 44-0-1-453-549-929; Fax: 44-0-1-453-548-919E-mail: janet@janet-crompton.comHeart Failure ManagementJul 12-15, 2007Chapel Hill, NC, United StatesContact: Hope Murdock / Gail WilkinsTel: 919-962-2118; Fax: 919-962-1664E-mail: hope_murdock@med.unc.edu /gail_wilkins@med.unc.eduGenomics and Oncology-2007Jul 14-15, 2007Kiev, UkraineContact: Meeting OrganiserTel: 0-38-0-632-776-465; Fax: 00-38-0-445-331-270E-mail: markov@nbscience.comTechniques & Applications of Molecular BiologyJul 16-19, 2007Coventry, England, United KingdomContact: Dr Charlotte MoonanTel: 0-24-76-523-540E-mail: Charlotte.Moonan@warwick.ac.ukInternational Workshop on Adverse DrugReactions and Lipodystrophy in HIVJul 19-21, 2007Sydney, NSW, AustraliaContact: International Medical PressTel: 44-2-073-980-700; Fax: 44-2-073-980-701E-mail: info@intmedpress.comPediatrics, Ob-Gyn, & Urology Coding &Reimbursement ConferenceJul 21-24, 2007Naples, FL, United StatesContact: LacyTel: 1-866-251-30604 th Ias Conference on HIV Pathogenesis,Treatment and PreventionJul 22-25, 2007Sydney, NSW, AustraliaContact: IAS Headquarters, Ch. de l’Avanchet 33,CH - 1216 Cointrin Geneva, SwitzerlandTel: 41-0-22-7-100-800; Fax: 41-0-22-7-100-899E-mail: info@iasociety.orgInternational Conference on DementiaJul 28-29, 2007Kiev, UkraineContact: Meeting OrganiserTel: 00-38-0-632-776-465; Fax: 00-38-0-445-331-270E-mail: markov@nbscience.com

200Forthcoming Conferences and Meetings June 2007Advances and Changing Trends in MedicineAug 06-08, 2007Miami Beach, FL, United StatesContact: RegistrarTel: 800-462-9633; Fax: 904-953-2954E-mail: cme-jax@mayo.eduOffice Gynecology/Women’s Health for PrimaryCareAug 09-12, 2007Anaheim, CA, United StatesContact: Office of Continuing Medical Education,David Geffen School of Medicine at UCLA ,10920Wilshire Blvd., Suite 1060, Los Angeles, CA 90024-6512Tel: 310-794-2620; Fax: 310-794-2624E-mail: eayala@mednet.ucla.eduPhysician Health, and Oncology CruiseAug 12-19, 2007Ketchikan, AK, United StatesContact: Sea Courses CruisesTel: 1-888-647-7327; Fax: 1-888-547-7337E-mail: cruises@seacourses.com13th International Congress of ImmunologyAug 12-17, 2007Rio de Janeiro, BrazilContact: Congress SecretariatE-mail: ici2007@usp.brThe Art of Clinical ObstetricsAug 16-18, 2007San Antonio, TX, United StatesContact: American College of Obstetricians andGynecologists, 409 12th St., S.W., PO Box 96920,Washington, D.C. 20090-6920Tel: 202-638-5577E-mail: coding@acog.orgXI Colombian Congress of RheumatologyAug 16-19, 2007Medellin, ColombiaContact: Jose F. Molina, MDTel: 57-1-635 0840; Fax: 57-1-621 5145E-mail: jfmolina@une.net.coOncology Medicine 2007Aug 18-19, 2007Kiev, UkraineContact: Meeting OrganiserTel: 00-38-0-632-776-465; Fax: 00-38-0-445-331-270E-mail: markov@nbscience.comIMMUNORIO 2007: 13 th International Congress ofImmunologyAug 21-25, 2007Rio de Janeiro, BrazilContact: Mrs. Monica Cevidanes, ExecutiveSecretariat: JZ Congressos, Rua GuilherminaGuinle, 272 - 2⁄ andar, Rio de Janeiro - Brazil -22270-060Tel: 55-21-2266-9150; Fax: 55-21-2266-9174E-mail: immuno2007@jz.com.br12 th Annual Challenges in Critical CareAug 24, 2007Hershey, PA, United StatesContact: Penn State College of Medicine, MCG220, 44 East Granada Avenue, Room 1108, P.O.Box 851, Hershey, PA 17033Tel: 717-531-6483; Fax: 717-531-5604E-mail: ContinuingEd@hmc.psu.eduAndropause, Menopause -2007Aug 25-26, 2007Kiev, UkraineContact: Meeting OrganiserTel: 00-38-0-632-776-465; Fax: 00-38-0-445-331-270E-mail: markov@nbscience.com3 rd Asia Pacific Congress in Maternal FetalMedicineAug 29-31, 2007Nanjing, ChinaContact: 3rd APCMFM SecretariatTel: 852-2632-1535; Fax: 852-2636-0008E-mail: apcmfm@med.cuhk.edu.hkMayo Clinic Gastroenterology & HepatologyBoard ReviewSep 06-09, 2007Chicago, IL, United StatesContact: Mayo Clinic - Mayo School of ContinuingMedical EducationTel: 800-323-2688E-mail: cme@mayo.eduPathology & Laboratory Coding &Reimbursement ConferenceSep 09-11, 2007Orlando, FL, United StatesContact: LacyTel:1-866-251-30608 th World Congress of Perinatal MedicineSep 09-13, 2007Florence, ItalyContact: MCA Events - Roberto CaflischTel: 39-0-234-934-404; Fax: 39-0-234-934-397E-mail: caflisch@mcaevents.org

June 2007On Ovulation Induction 2007Sep 13-15, 2007Rome, ItalyContact: Emanuela RuggeriTel: 00-39-0-51-223-260; Fax: 00-39-0-51-222-101E-mail: info@gynepro.itWomen’s HealthSep 15-22, 2007Honolulu, HI, United StatesContact: Sandra BarnhartTel: 1-800-422-0711; Fax: 727-527-3228E-mail: sandra@continuingeducation.netInterventional Ultrasound in new Millenium-2007Sep 15-16, 2007Kiev, UkraineContact: Meeting OrganiserTel: 00-38-0-632-776-465; Fax: 00-38-0-445-331-270E-mail: markov@nbscience.comAOCOG 2007: The XX Asian and OceanicCongress of Obstetrics and GynecologySep 21-25, 2007Tokyo, JapanContact: Secretariat of AOCOG 2007, c/o ICSConvention Design, lnc. Sumitomo Corp. JinbochoBldg, 3-24, Kanda-Nishikicho, Chiyoda-ku, Tokyo101-8449, JAPANTel: 81-3-3219-3541; Fax: 81-3-3292-1811E-mail: aocog2007@ics-inc.co.jpObesity Treatment-2007Sep 22-23, 2007Kiev, UkraineContact: Meeting OrganiserTel: 00-38-0-632-776-465; Fax: 00-38-0-445-331-270E-mail: markov@nbscience.com3 rd International Clinical Trials SymposiumSep 23-26, 2007Sydney, NSW, AustraliaContact: Sandra IbrahimTel: 61-29-545-000; Fax: 61-292-513-552E-mail: info@clinicaltrials2007.comReproductive Health 2007Sep 26-28, 2007Minneapolis, MN, United StatesContact: Carole BerkeTel: 202-466-3825; Fax: 202-466-3826E-mail: cberke@arhp.orgMammography Update 2007Sep 27-28, 2007Madison, WI, United StatesContact: Terese BaileyTel: 608-240-2141; Fax: 608-240-2151E-mail: tmbailey@wisc.eduKUWAIT MEDICAL JOURNAL 201Emergency Medicine -2007Sep 29-30, 2007Kiev, UkraineContact: Meeting OrganiserTel: 00-38-0-632-776-465; Fax: 00-38-0-445-331-270E-mail: markov@nbscience.comPlastic, Reconstructive and Aesthetic Surgery-2007Oct 06-07, 2007Kiev, UkraineContact: Meeting OrganiserTel: 00-38-0-632-776-465; Fax: 00-38-0-4-453-331-270E-mail: markov@nbscience.com17 th World Congress on Ultrasound in Obstetricsand GynecologyOct 07-11, 2007Florence, ItalyContact: IUSOG SecretariatTel: 44-0-2-074-719-955; Fax: 44-0-2-074-719-959E-mail: congress@isuog.org23 rd IUSTI (International Union against SexuallyTransmitted Infections) Europe Conference onSexually Transmitted Infections and HIV/AIDSOct 11-14, 2007Dubrovnik, CroatiaContact: Prof. Mihael Skerlev, M.D., Ph.D,Conference PresidentTel: 385-1-4862-600E-mail: nina.anzulovic@spektar-holidays.hrThoracic Surgery -2007Oct 13-14, 2007Kiev, UkraineContact: Meeting OrganiserTel: 00-38-0-632-776-465; Fax: 00-38-0-445-331-270E-mail: markov@nbscience.com3 rd NRITLD-ERS Joint International Conference onPulmonary Disease, Intensive Care and TBOct 15-18, 2007Tehran, IranContact: Hamideh RastegariTel: 00-982-120-109-677; Fax: 00-982-120-109-484E-mail: tic@nritld.ac.ir4 th International Congress on Menopause &OsteoporosisOct 17-21, 2007Antalya, TurkeyContact: Erhan SenolTel: 90-2-123-684-795; Fax: 90-2-122-306-425E-mail: erhans@vip.com.tr

202Forthcoming Conferences and Meetings June 2007Pain and Headache -2007Oct 20-21, 2007Kiev, UkraineContact: Meeting OrganiserTel: 00-38-0-632-776-465; Fax: 00-38-0-445-331-270E-mail: markov@nbscience.comFetal EchocardiographyOct 25-26, 2007Philadelphia, PA, United StatesContact: Office of CME, 1020 Locust Street, SuiteM5, Philadelphia, PA 19107-6799 Tel: 1-888-JEFF-CME / 215-955-6992; Fax: 215-923-3212E-mail: edservices@lists.jefferson.eduInternational Vascular Conference-2007Oct 27-28, 2007Kiev, UkraineContact: Meeting OrganiserTel: 00-38-0-632-776-465; Fax: 00-38-0-445-331-270E-mail: markov@nbscience.comPacific ASCLEPIOS Gynaecology ObstetricsPerinatology Paediatrics & MidwivesInternational CongressOct 31-Nov 02, 2007Noumea, New CaledoniaContact: Dr Kamel BARGAOUITel: 33-607-686-118; Fax: 33-143-839-985E-mail: kamel@medicom-international.comLimited OB/GYN UltrasoundNov 01-03, 2007Philadelphia, PA, United StatesContact: Office of CME, 1020 Locust Street, SuiteM5, Philadelphia, PA 19107-6799 Tel: 1-888-JEFF-CME / 215-955-6992; Fax: 215-923-3212E-mail: edservices@lists.jefferson.eduBreast ImagingNov 05-09, 2007Palm Springs, CA, United StatesContact: UCSF Office of Continuing MedicalEducation, 3333 California Street, Room 450, SanFrancisco, CA 9411Tel: 415-476-4251 / 415-476-5808; Fax: 415-476-0318/ 415-502-1795E-mail: info@ocme.ucsf.eduDermatological Care For All: A Basic HumanRightNov 06-09, 2007Addis Ababa, Mekele, EthiopiaContact: Loredana BonazzoliTel: 39-658-543-780; Fax: 39-658-543-686E-mail: s.gallicano-desk@fastwebnet.i2 nd SGI International Summit: ReporductiveMedicineNov 08-10, 2007Valencia, SpainContact: Amparo MartinezTel: 00-34-961-974-670; Fax: 00-34-961-974-598E-mail: catedrasg@cac.esThe 2 nd Asia Pacific Congress on Controversies inObstetrics, Gynecology & Infertility (COGI)Nov 08-11, 2007Shanghai, ChinaContact: Ms. Ruthi YahavTel: 972-3-566-6166; Fax: 972- 3-566-6177E-mail: cogichina@comtecmed.comSelective Sentinel Lymphadenectomy and BreastUltrasoundNov 09-10, 2007San Francisco, CA, United StatesContact: UCSF Office of Continuing MedicalEducation, 3333 California Street, Room 450, SanFrancisco, CA 9411Tel: 415-476-4251 / 415-476-5808; Fax: 415-476-0318/ 415-502-1795E-mail: info@ocme.ucsf.edu7 th International Congress on Obstetrics andGynecologyNov 09-13, 2007Tehran, IranContact: Maryam KashanianTel: 98-21-88-309-564-6; Fax: 98-21-88-309-567E-mail: maryamkashanian@yahoo.com /kashanian@icog7.irHepatocellular Carcinoma: Multi-DisciplinaryManagement 2007Nov 10, 2007Los Angeles, CA, United StatesContact: Office of Continuing Medical Education,David Geffen School of Medicine at UCLA , 10920Wilshire Blvd., Suite 1060, Los Angeles, CA 90024-6512Tel: 310-794-2620; Fax: 310-794-2624E-mail: eayala@mednet.ucla.eduAsthma, Pulmonary Hypertension-2007International ConferenceNov 10-11, 2007Kiev, UkraineContact: Meeting OrganiserTel: 00-38-0-632-776-465; Fax: 00-38-0-445-331-270E-mail: markov@nbscience.com

June 2007KUWAIT MEDICAL JOURNALWHO-Facts Sheet1. New Country Estimates Show Heavy Toll Caused by Indoor Air Pollution2. Road Traffic Crashes are the Leading Cause of Death for 10-24 Year Olds3. WHO Proposes Global Agenda on Transplantation4. Global Tuberculosis Epidemic Levelling Off5. World Moves Closer to Eradicating Ancient Worm Disease6. Guidelines on Cultivating Essential Plant used in Anti-Malaria MedicinesCompiled and edited byBabichan K ChandyKuwait Medical Journal 2007, 39 (2):203-2081. NEW COUNTRY ESTIMATES SHOW HEAVYTOLL CAUSED BY INDOOR AIR POLLUTIONIn the 21 worst-affected countries, close to 5% ofdeath and disease is caused by indoor air pollution,according to new estimates published by the WorldHealth Organization (WHO).The first-ever country-by-country estimates ofthe burden of disease due to indoor air pollutionhighlight the heavy toll solid fuel use takes on thehealth and well-being of people around the world.Among the worst affected 11 countries alone,indoor air pollution is to blame for a total of 1.2million deaths a year. Globally, reliance on solidfuels is one of the ten most important threats topublic health.“The prevention potential is enormous” saidSusanne We b e r-Mosdorf, WHO’s A s s i s t a n tDirector-General for Sustainable Development andHealthy Environments. “Solutions are available,and it is our international responsibility to promotethehealth and well-being of those affected, who aremostly women and children.”Worldwide, more than three billion peopledepend on solid fuels, including biomass (wood,dung and crop residues) and coal, for cooking andheating. Exposure to indoor air pollution from solidfuels has been linked to many diseases, inparticular pneumonia among children and chronicrespiratory diseases among adults.A shift towards cleaner and more eff i c i e n tmodern fuels, such as biogas, liquefied petroleumgas (LPG) and kerosene could largely eliminate thishealth risk and prevent 1.5 million deaths a yearglobally. In the short-term, the promotion of moref u e l - e fficient and cleaner technologies, such asi m p roved cooking stoves, smoke hoods andinsulated retained heat cookers, could substantiallyreduce indoor air pollution and would bring aboutmany other convenience and socioeconom i cbenefits.These burdens of disease estimates will assistnational decision-makers in the health, enviro n m e n t ,energy and finance sectors to set priorities forpreventive action. They can also be used to assessthe performance of policies over time. In thecontext of limited resources, burden of diseaseinformation should be complemented withknowledge on technological options in a givencountry and information on the costs and benefitsof such options.For more information contact: Nada Osseiran,Advocacy & Communications Officer, Public Healthand Environment, WHO, Geneva, Tel. +4122 -7914475, Fax: +4122 791 4127. Email:osseirann@who.int.Country by country information on indoor airpollution and its health impacts, available athttp://www.who.int/indoorair/health_impacts/burden/en/index.html2. ROAD TRAFFIC CRASHES ARE THELEADING CAUSE OF DEATH FOR 10-24 YEAROLDSNew Report marks First United Nations GlobalRoad Safety WeekRoad traffic crashes are the leading cause ofdeath among young people between 10 and 24Address correspondence to:Office of the Spokesperson, WHO, Geneva. Tel.: (+41 22) 791 2599; Fax (+41 22) 791 4858; E-mail: inf@who.int; Web site: http://www.who.int/

204WHO-Facts Sheet June 2007years, according to a new report published by theWorld Health Organization (WHO). The report,Youth and Road Safety, says that nearly 400,000young people under the age of 25 are killed in roadtraffic crashes every year. Millions more are injuredor disabled.The vast majority of these deaths and injuriesoccur in low- and middle-income countries. Thehighest rates are found in Africa and the MiddleEast. Young people from economically disadvantagedbackgrounds are at greatest risk in every country.Young males are at higher risk for road trafficfatalities than females in every age group under 25years.Unless more comprehensive global action istaken, the number of deaths and injuries is likely torise significantly. Road traffic collisions cost anestimated $518 billion globally in material, healthand other costs. For many low- and middle-incomecountries, the cost of road crashes re p re s e n t sbetween 1-1.5% of GNP and in some cases exceedthe total amount they receive in internationaldevelopment aid.Youth and Road Safety stresses that the bulk ofthese crashes are predictable - and preventable.Many involve children playing on the street, youngpedestrians, cyclists, motorcyclists, novice driversand passengers of public transport.The report points out that, children are not justlittle adults. Their height, level of maturity, theirinterests, as well as their need to play and travelsafely to school, mean that they require specialsafety measures. Also, the report says, protectingolder youth requires other measures such as lowerblood alcohol limits for young drivers andgraduated license programmes.Youth and Road Safety highlights examples incountries where improved measures such aslowering speed limits, cracking down on drinkdriving,promoting and enforcing the use of seatbelts,child restraints, and motorcycle helmets, aswell as better road infrastructure and creating safea reas for children to play have significantlyreduced the number of deaths and injuries.“The lack of safety on our roads has become animportant obstacle to health and development,”said Dr Margaret Chan, WHO Director-General.“Our children and young adults are among themost vulnerable. Road traffic crashes are not‘accidents’. We need to challenge the notion thatthey are unavoidable and make room for a proactive,preventive approach. “For more information contact: Laura Sminkey,Technical Officer, WHO, Geneva, Tel: +41 22 791 4547,Mobile: +41 79 249 3520, Email: sminkeyl@who.int.3. WHO PROPOSES GLOBAL AGENDA ONTRANSPLANTATIONNew World Observatory Launched with SpainAt the second Global Consultation onTransplantation held in March 2007, the WorldHealth Organization (WHO) presented countriesand other stakeholders with a blueprint forupdated global guiding principles on cell, tissueand organ donation and transplantation.Those principles aim to address a number ofproblems: the global shortage of human materials -particularly organs - for transplantation; the gro w i n gphenomenon of ‘transplant tourism’ partly causedby that shortage; quality, safety and e fficacy issuesrelated to transplantation pro c e d u re s ; traceabilityand accountability of human materials crossingborders.Stakeholders agreed to the creation of a GlobalForum on Transplantation to be spearheaded byWHO, to assist and support developing countriesinitiating transplantation programmes and to worktowards a unified global coding system for cells,tissues and organs.A central theme of the discussions was WHO’sconcern over increasing cases of commerc i a lexploitation of human materials.“Human organs are not spare parts,” said DrHoward Zucker, WHO Assistant Director-Generalof Health Technology and Pharmaceuticals. “Noone can put a price on an organ which is going tosave someone’s life.”“Non-existent or lax laws on organ donationand transplantation encourage commercialism andtransplant tourism,” said Dr Luc Noel, in charge oftransplantation at WHO. “If all countries agree ona common approach, and stop commercial exploitation,then access will be more equitable and we will havefewer health tragedies.”Transplantation is increasingly seen as the bestsolution to end-stage organ failure . E n d - s t a g ekidney disease, for instance, can only be re p a i re dwitha kidney transplant. Without it, the patient will dieor require dialysis for years, which is an expensivep ro c e d u re and often out of reach of poore rpatients. Transplantation is the only option forsome liver conditions, such as severe cirrhosis orliver cancer, and a number of serious heartconditions.Recent estimates communicated to WHO by 98countries show that the most sought after organ isthe kidney. Sixty-six thousand kidneys weretransplanted in 2005 representing a mere 10% of theestimated need. In the same year, 21000 livers and6000 hearts were transplanted. Both kidney andliver transplants are on the rise but demand is alsoincreasing and remains unmatched.

June 2007KUWAIT MEDICAL JOURNAL 205Reports on ‘transplant tourism’ show that itmakes up an estimated 10% of globaltransplantation practices. The phenomenon hasbeen increasing since the mid-1990’s, coincidingwith greater acceptance of the therapeutic benefitsof transplantation and with progress in the efficacyof the medicines - immuno-suppressants - used top revent the body’s rejection of a transplantedorgan.The principles put forward by WHO underscorethat the person - whether recipient of an organ or adonor - must be the main concern both as patientand as human being; that commercial exploitationof organs denies equitable access and can beharmful to both donors and recipients; that organdonation from live donors poses numerous healthrisks which can be avoided by promoting donationfrom deceased donors; and that quality, safety,efficacy and transparency are essential if society isto reap the benefits transplantation can offer as atherapy.“Live donations are not without risk, whetherthe organ is paid for or not. The donor must receiveproper medical follow-up but this is often lackingwhen he or she is seen as a means to making ap rofit,” added Dr Luc Noel. “Donations from deceasedpersons eliminate the problem of donor safety andcan help reduce organ trafficking.”WHO action on transplantation will be aided bya global observatory set up in Madrid under theauspices of the Government of Spain. T h eobservatory, which is linked to the WHO GlobalKnowledge Base, will provide an interface forhealth authorities and the general public to accessdata on donation and transplantation practices,legal frameworks and obstacles to equitable access.In 2005, 66,000 kidney transplants wereperformed, 60% of which in industrializedcountries. Seventy-five per cent of the more than21,000 liver transplants and 6000 heart transplantswere performed in industrialized and emergingeconomies.For more information contact: Daniela Bagozzi,Media Communications, Health Technology andPharmaceuticals, WHO, Tel. +41 22 791 45 44, Mobile:+41 79 475 54 90, E-mail: bagozzid@who.intAll press releases, fact sheets and other WHO mediamaterial may be found at www.who.int.4. GLOBAL TUBERCULOSIS EPIDEMICLEVELLING OFFXDR-TB, HIV/AIDS and other obstacles stillthwarting progressThe global tuberculosis (TB) epidemic haslevelled off for the first time since the World HealthOrganization (WHO) declared TB a public healthe m e rgency in 1993. The Global Tu b e rc u l o s i sControl Report released in March 2007 by WHOfinds that the percentage of the world’s populationstruck by TB peaked in 2004 and then held steadyin 2005.“We are currently seeing both the fruits of globalaction to control TB and the lethal nature of thedisease’s ongoing burden,” said United NationsSecretary-General Ban Ki-moon. “Almost 60 percent of TB cases worldwide are now detected, andout of those, the vast majority are cured. Over thepast decade, 26 million patients have been placedon effective TB treatment thanks to the efforts ofgovernments and a wide range of partners. But thedisease still kills 4400 people every day.”Although the rate at which people developedTB in 2005 was level or even declined slightlycompared to 2004, the actual number of TB casescontinued to rise slowly. The reason for thisdifference is that world population is expanding.The pace at which new TB cases developed in 2005,however, was slightly lower than global populationgrowth. The number of cases in 2005 was 8,787,000,up from 8,718,000 in 2004. An estimated 1.6 millionpeople died of the disease in 2005, 195,000 of thempeople living with HIV.Despite signs that the epidemic may beslowing, there are major impediments to rapidp ro g ress against TB - prominent among them,uneven access to diagnosis and treatment withincountries. “We need to tackle this problem as partof the larger challenge of increasing access toprimary health care services. All people, no matterwho they are or where they live, should have accessto TB diagnosis and treatment as part of a packageof general health services that bring multiple healthbenefits,” said Dr Margaret Chan, WHO Director-General.Other major barriers to progress include:HIV/TB: TB is a major cause of death among peopleliving with HIV/AIDS, and HIV is the main reasonfor failure to meet TB control targets in high HIVsettings, particularly sub-Saharan Africa, whereHIV/AIDS is dramatically fuelling the TBepidemic. Collaboration between TB and HIVprogrammes is key to reducing the burden of TBamong people living with HIV.HIV among TB patients: The Report finds that HIVtesting for TB patients is increasing rapidly inAfrica, but few people living with HIV are beingscreened for TB. “In the last year, we have seenunprecedented collaboration between the TB andHIV communities, but much more is needed if weare to achieve our goal of universal access to quality

206WHO-Facts Sheet June 2007TB and HIV prevention, diagnostic, treatment andc a re services”, said Dr Peter Piot, ExecutiveDirector of UNAIDS.Extensively drug-resistant TB (XDR-TB): T h espread of XDR-TB poses a serious threat to progressand could even reverse recent gains. “We have aclear plan on how to control XDR-TB, but countriesare moving far too slowly on implementing thisplan. Funding is an issue as well. It will take anadditional US$ 650 million globally to implementcontrol of both XDR-TB and multi-drug-resistantTB (MDR-TB) in 2007 alone,” said Dr MarioRaviglione, Director of the WHO Stop TBDepartment. “Beyond that, because of the threat ofXDR-TB, re s e a rch to identify new diagnostics,drugs and vaccines is more vital than ever.”Overall funding gap: Although funds for TBcontrol have risen substantially since 2002, reachingUS$ 2 billion, an additional US$ 1.1 billion will beneeded to meet the 2007 funding requirements setby the Global Plan to Stop TB (2006-2015). A total ofUS$ 56 billion, half of which should be funded byendemic countries and the other half by donors, isneeded for the 10-year plan, but current fundingcommitments indicate a gap of at least US$ 31billion.Lack of infrastructure and capacity: In mostcountries with a high burden of TB, efforts to fightTB are impeded by inadequate laboratory facilitiesand critical shortages of health staff.Should a sustained downward trend in the TBepidemic develop, it is likely that the MillenniumDevelopment Goal of achieving a decrease in thenumber of tuberculosis cases per year will besatisfied years in advance of the 2015 target. Butmuch more rapid progress is needed for countriesto meet the targets in the Global Plan to Stop TB: tohalve 1990 TB case numbers and deaths from thedisease by 2015.The Report finds that the WHO Regions of theAmericas, South-East Asia and the Western Pacificare now on track to meet their 2015 Global PlanTargets; while the African, Eastern Mediterraneanand European regions are not. WHO’s 2005 targetsof 70% case detection and 85% cure were narrowlymissed globally: case detection was 60% andtreatment success was 84%.Multidrug-resistant TB (MDR-TB) and Extensivelydrug-resistant TB (XDR-TB):TB can usually be treated with a course of fourstandard, or first-line, anti-TB drugs. If these drugsare misused or mismanaged, multidrug-resistantTB (MDR-TB) can develop. MDR-TB takes longer tot reat with second-line drugs, which are moreexpensive and have more side-effects. XDR-TB candevelop when these second-line drugs are alsomisused or mismanaged and therefore also becomeineffective. Because XDR-TB is resistant to first- andsecond-line drugs, treatment options are seriouslylimited and the risk of death is extremely high. BothMDR-TB and XDR-TB can be spread from person toperson.The Global Plan to Stop TB (2006-2015), launchedby the Stop TB Partnership (www.stoptb.org) inJanuary 2006, sets forth a roadmap for treating 50million people for TB and enrolling 3 millionpatients who have both TB and HIV ona n t i re t roviral therapy over the next 10 years,saving about 14 million lives. It aims to halve TBprevalence and deaths compared with 1990 levelsby 2015.For more information contact: Geneva/New York:Glenn Thomas, Communications Officer, WHO StopTB Department, mobile +41 79 509 0677, email:thomasg@who.int5. WORLD MOVES CLOSER TOERADICATING ANCIENT WORM DISEASEA neglected tropical disease that has afflictedpeople since ancient times has moved a step closertowards eradication. In early March, twelve morecountries were declared Guinea Worm Free by theInternational Commission for the Certification ofDracunculiasis (Guinea Worm Disease) Eradication.If progress continues at this rate, in less than 2 yearsGuinea Worm could become the second diseaseafter Smallpox to be pushed into oblivion.In the early 1980s, an estimated 3 million peoplein more than 20 countries were affected byDracunculiasis, more commonly re f e r red to asGuinea Worm Disease. Today, that number hassignificantly dropped to about 25,000 cases in 9countries. “This is the culmination of years of effortby local and international groups to see this diseaseeradicated,” says Dr Lorenzo Savioli, Director ofNeglected Tropical Diseases at the World HealthO rganization. Since its creation in 1995, theCommission has certified 180 countries as free ofGuinea Worm . The Commission is now movingcloser to its 2009 deadline for eradication of thedisease worldwide.WHO Certifies Twelve More Countries as GuineaWorm FreeThe Sixth Meeting of the InternationalCommission for the Certification of Dracunculiasis

June 2007KUWAIT MEDICAL JOURNAL 207Eradication held 5-7 March, 2007 at World HealthO rganization Headquarters in Geneva, bro u g h ttogether re p resentatives from a range oforganizations, including the Austrian government,the Carter Center, the Centers for Diseases Controland Prevention, the International Federation of RedCross and Red Crescent Societies and UNICEF todiscuss and certify 12 more countries.In 1995, WHO created the InternationalCommission for the Certification of DracunculiasisEradication as an independent body consisting ofscientific experts from all over the world. Thegroup meets periodically to assess global progresstowards the eradication of Guinea Worm Disease incountries where it remains endemic and to reviewthe list of countries applying for certification - theWHO stamp of approval that declares them free ofGWD transmission.Debilitating diseaseFor countless generations, people have sufferedfrom Guinea Worm Disease (GWD). The diseasewas found in Egyptian mummies and is thought tobe the “fiery serpent” often referred to in texts frompharaonic Egypt and Assyrian Mesopotamia.GWD is endemic in some villages of sub-Saharan A f r i c a . The worm is spread thro u g hcontaminated water. The effects of the disease arecrippling. Its victims develop large ulcers, usuallyin the lower leg. The ulcers swell, at times to thesize of a tennis ball, and burst - releasing aspaghetti-like parasitic worm ranging in lengthfrom 550-800 millimetres (0.8 meters).Victims experience a pain so excruciating thatthey say it feels as if their leg is on fire. The searingpain compels people to jump into water, often thecommunity’s only source of drinking water, torelieve the pain. When the infected personimmerses their leg in the water, the worm in theirleg releases thousands of larvae.The larvae are theningested by water fleas that live in the water. Thusthe cycle begins again—- when a person drinks thewater, they are in effect drinking in the disease.The socio-economic effects of the disease arenumerous. The disability caused by the disease isseasonal, usually re - e m e rging during harvestseason in the villages, which is why it is often called“the disease of the empty granary.” As a result ofthe pain associated with GWD, farmers are leftincapacitated and unable to harvest their crops,contributing to malnutrition in children since theprimary caregivers, the infected parents, are in suchphysical agony that they cannot properly providefor their young. Children affected by GWD missschool for months at a time, hindering theireducational growth. The disease keeps its victimsimprisoned in a cycle of pain and poverty.Infection PreventionThere are a number of low-cost methods toprevent people from becoming infected:• Providing safe drinking water supplies• Filtering drinking water using fine-mesh cloth• Intensifying case containment (health workercan clean the ulcer, gradually pulling out the worm,disinfecting and bandaging the lesion to preventsecondary bacterial infection)• Preventing infected persons from wading intowater sources to relieve the pain• Intensifying health education and socialmobilization• Treating ponds (water sources) with Abate(which kills the water fleas)Coordinated efforts and renewed optimismEradicating GWD in the countries where it isstill endemic remains the most challenging task.The Commission urged partners to endorse theneed for a more aggressive approach towards theeradication of GWD pushing for a higher profile inWHO. For decades, an army of health workersfrom WHO and various organizations all over theworld dedicated to this cause have been deployedand work round-the-clock to ensure that pre v e n t i o nmethods are carried out and existing cases aremonitored. “This disease can be arrested easily, andwith a more stream-lined approach to transmissioncontrol and the priority that the Director-Generalhas given to neglected tropical diseases, we are onour way to eradicating this disease for good,” saysDr Abdul Rahman Al-Awadi, the Chairman of theInternational Commission.The Commission concluded that eradicationremained an achievable goal.The recent commitmentof the Director-General to address the neglectedt ropical diseases as part of poverty-re d u c t i o nstrategies, giving particular attention to A f r i c a ,provides the window of opportunity desperatelyneeded to achieve this goal.For more information contact: Tiffany Domingo,WHO, Geneva, Tel. +41 22 791 1540, Mobile: +41 79516 3136, Email: domingoc@who.int or consulte theweb site: http://www.who.int/dracunculiasis/en/ .6. GUIDELINES ON CULTIVATINGESSENTIAL PLANT USED IN ANTI-MALARIAMEDICINESIn March 2007, the World Health Organization(WHO) published guidelines for the cultivationand collection of Artemisia annua L, a Chinesetraditional medicinal plant which is the source ofartemisinin, used to produce the most effective

208WHO-Facts Sheet June 2007medicines for malaria. The guidelines willcontribute to improving the quality of Artemisiaannua L to further develop artemisinin-basedmedicines, and help ensure a sustainable supply tomeet market demand.Artemisia annua L, used in Chinese traditionalmedicine for centuries, is today considered part ofthe solution where malaria has become resistant toother medicines. Artemisinin-based combinationtherapies (ACTs) have been recommended byWHO since 2001 in all countries where falciparummalaria - the most resistant form of the disease - isendemic.Since then, the world market for pro d u c t scontaining artemisinin derivatives has gro w nrapidly. However, not all artemisinin meets therequired standards to produce quality medicines,making it all the more urgent to promote bestpractices in the cultivation and collection of the rawmaterial used to make the combination therapy.About 40% of the world’s population is at risk ofcontracting malaria which is resistant to othermedicines. Of the 76 countries needing artemisininbasedtreatment today, 69 have adopted the WHOrecommendation to use this therapy.The availability of these treatments still fallsshort of what is needed. Of an estimated 600million people needing A C Ts worldwide, onlyabout 82 million are receiving the tre a t m e n tthrough public sector distribution systems (whichconstitute 90% of antimalarial distribution indeveloping countries).The “WHO monograph on good agriculturaland collection practices for Artemisia annua L.”provides a detailed description of the cultivationand collection techniques and measures requiredfor a harvest to meet quality requirements. Theinformation is based on research data and thepractical experience of several countries wheresuccessful cultivation practices have led to a highyield of good quality Artemisia annua L.As with most medicinal herbs, artemisinin’scontents and efficacy are subject to climatic,geographical and environmental conditions.Not allArtemisia annua plants necessarily containartemisinin and in some places, depending on thequality of the soil and rainfall, the content may bevery low and without industrial value. T h e s efactors make it necessary to run pilot tests ofcultivation on small areas of land to ensure that theland selected is suitable for growing high-yieldplants before large-scale cultivation begins.Cultivation of Artemisia annua re q u i res aminimum of 6 months and extraction, processingand manufacturing of the final product require atleast 2-5 months depending on the pro d u c tf o r m u l a t i o n . High temperatures during postharvesthandling can damage the quality of theplant. After harvesting or collection, the artemisinincontent of the leaves will gradually decrease. Thevalue of the raw material for extraction can be lostafter six to twelve months’ storage.The authors of the guidelines caution governmentson two fronts. First, they must ensure that farmerswork with manufacturers to determine the actualmarket demand for the plant. Recent experience insome countries has shown that overproduction notonly wastes money and time, it can also have anegative effect on the plant’s future yield. Second,they must ensure the availability of the technicalskills and know-how needed to extract artemisininfrom dried leaves.The WHO monograph also aims to provide amodel for countries and researchers to developfurther monographs on good agricultural andcollection practices for other medicinal plants, andpromote the sustainable use of the plant as part ofthe larger aim of protecting the wild resources ofmedicinal plants.Recent estimates of the global malaria burdenhave shown increasing levels of illness and deathcaused by malaria, reflecting the deterioration ofthe malaria situation in Africa during the 1990s.About 90% of all deaths from malaria occur inAfrica, in the areas south of the Sahara, and thegreat majority of these are in children under the ageof five.Key among the factors contributing toincreasing malaria mortality and morbidity is thewidespread resistance of Plasmodium falciparumto conventional antimalarial drugs, such asc h l o roquine, sulfadoxine-pyrimethamine andamodiaquine. The rising tide of counterfeit andsubstandard malaria medicines in parts of Africaand Asia contributes to the problem of resistance.M u l t i d ru g - resistant Plasmodium falciparum malariais also widely prevalent in south-east Asia andSouth America.The Guidelines can be found at:http://www.who.int/entity/medicines/publications/traditional/ArtemisiaMonograph.pdf

انتشار ارتفاع ضغط الدم في المواطنين الكويتيين صغار ومتوسطي السنفي الرعاية الصحية الأوليةPrevalence of Hypertension in Young and Middle Aged Kuwaiti Citizens in Primary HealthCare:الملخصأهداف البحث:‏ دراسة انتشار ارتفاع ضغط الدم بين المواطنين الكويتيين الصغار ومتوسطي السن من مراجعيمراكز الرعاية الصحية الأولية‎٬‎ وإيجاد علاقته بعوامل الخطر مثل العمر وجنس والتدخين ومؤشر كتلة الجسموالتمرين.‏تصميم البحث:‏ أجرينا دراسة مقطعية لتقييم الأفراد المصابين بارتفاع ضغط الدم غير المشخّص‎٬‎ والذينيراجعون مراكز الرعاية الصحية الأولية لمشاكل طبية أخرى.‏مكان الدراسة:‏ تم اختيار مركزين للرعاية الصحية الأولية بشكل عشوائي من كل منطقة صحية.‏ تم إعداداستمارة لتجميع البيانات وتم توزيعها على أطباء الرعاية الصحية الأولية في المراكز الصحية المختارة.‏المرضى تضمنت الدراسة ثمانمائة وستين مريضا من مراجعي العيادات وعشرين ممارسا .النتائج:‏ وجد أن انتشار ارتفاع ضغط الدم في الذكور و‎6.1‎ % في الإناث.‏ كان تأثير عوامل الخطر مثلالعمر ومؤشر كتلة جسم والتمرين والتدخين معتدا إحصائيا‎٬‎ في حين أن الفروق بين الجنسين لم تكن معتدة.‏الاستنتاج تؤكد دراستنا أهمية الكشف المبكر لارتفاع ضغط الدم بين المرضى صغار ومتوسطي العمر‎٬‎وتبني سياسة فعالة للتوعية الصحية بخصوص عوامل الخطر عند مستوى مراكز الرعاية الصحية الأوليةالكلمات الدليلة:‏ ارتفاع ضغط الدم‎٬‎ انتشار‎٬‎ الرعاية الصحية الأولية.‏.% 6.4:1

التأثير الاقتصادي للتدخين على النظام الصحي في الكويتThe Economic Impact of Smoking on Health System in Kuwait:الملخصهدف البحث:‏ تقدير بعض التكلفة والتأثير الاقتصادي للتدخين على الخدمات الصحية في الكويت.‏تصميم البحث:‏ مسح مقطعي.‏مكان الدراسة:‏ مركزا الصقر واليرموك للرعاية الصحية الأولية‎٬‎ الكويت.‏المرضى سجل في هذه الدراسة ألفين ومئتين وستة عشر شخصا من الذكورالتدخل:‏ تم استجواب كل مريض من قبل طبيب متدرب.‏الإجراءات الرئيسية للبحث:‏ وقوع أعراض الجهاز التنفسي العلوي والسفلي لدى المدخنين الحاليين مقارنة بغيرالمدخنين.‏النتائج:‏ أظهرت دراستنا وجود انتشار عال للتدخين في الكويت بين الذكور البالغين بعمر≥‏أظهرت وقوعا عاليا لأعراض الجهاز التنفسي العلوي والسفلي بين المدخنين الحاليين مقارنة بغيرعلى التواليمقارنة بنسبةالمدخنينالاستنتاج يزيد التدخين من تكلفة الرعاية الصحية بزيادة عدد الزيارات للعيادة بسبب الأمراض التنفسية‎٬‎ وهويزيد بذلك من استخدام الخدمات الصحية ويؤدي إلى تحميل عبء إضافي على المجتمع.‏الكلمات الدليلة:‏ اقتصادي‎٬‎ تكلفة الرعاية الصحية‎٬‎ استخدام الخدمات الصحية‎٬‎ التدخين.‏18 سنة 40.6)..((2216)32.5 و‎%23.1‎%)٬ كما67.5) و‎76.9‎ %:2

فائدةتصوير دوبلر للأنسجةبالموجات النبضية لحلقة الصمام التاجي في تقييم مرضى ارتفاع ضغط الدمUsefulness of Pulsed-Wave Tissue Doppler Imaging of Mitral Valve Annulus for Assessmentof Hypertensive Patientsالملخصهدف الدراسة:‏ تقييم فائدة تصوير دوبلر للأنسجة لحلقة الصمام التاجي ٬ كأداة مستقلة لطليعة التحميل من أجلتقييم وظيفة البطين الأيسر في المحور الطويل.‏تصميم البحث:‏ دراسة أترابية أجريت ما بين شهري ينايرمكان الدراسة:‏ مختبر الدراسات القلبية اللا باضعة‎٬‎ قسم الأمراض الباطنة‎٬‎ مستشفى الفروانية‎٬‎ الكويت.‏المرضى وطرق البحث:‏ أجريت مراقبة ضغط الدم الجوالة‎٬‎ تخطيط صدى القلب عبر الصدر ودراسات الدوبلرواختبار تخطيط كهربية القلب مع المجهود لعدد بارتفاع ضغط دم و‎50‎ شخصا أسوياء ضغط الدمكانت هناك مجموعتان:‏ المجموعة الأولى:‏ تضمنت 150 مريضا بارتفاع ضغط الدم ؛ والمجموعة الثانية:‏وتضمنت 50 شخصا أسوياء ضغط الدمالنتائج:‏ كان هناك انخفاض ملحوظ في طور الهبوط البطيني وطور ارتدادي للنمط بحلقة الصمام التاجي؛ ونقص ملحوظ في وسرعة متزايدة للتدفق التاجي في مرضىارتفاع ضغط الدم من أسوياء ضغط الدم أظهرت بيانات منحنى خصائص التشغيل للمتلقي لمؤشرات تصويردوبلر للأنسجة في مرضى ارتفاع ضغط الدم أن سرعة التقلص الانقباضية البالغة

فهم وممارسة ممارسي الرعاية الصحية الأوليةلإيتاءالإجراءات الوقائية والعقباتالمكتنفةPerception and Practice of Primary Healthcare Practitioners about Delivering Preventive Measures andObstacles Involved.الملخصهدف البحث:‏ تقييم مدى إدراك وممارسة الممارسين لبعض الإجراءات الوقائية‎٬‎ وماهية المعوقات التي تعترضتنفيذها في مراكز الرعاية الصحية الأولية بالكويتمكان الدراسة:‏ مركز الدسمة للرعاية الصحية الأولية‎٬‎ الكويتطرق البحث:‏ مسح مقطعي للممارسين العامين في للرعاية الصحية الأوليةالنتائج:‏ كشفت نتائج المسح عن أن الممارسين كانوا واعين بأهمية الطب الوقائي الإكلينيكي.‏ وعلى أية حال‎٬‎ فقداعتبرت قلة الوقت عقبة مهمة‎٬‎ لقياس ضغط الدم (49.0 %)٬ وسكر الدم ومستوى الكولسترولوتقديم المشورة حول الإقلاع عن التدخين (81.4 %)٬ وتقديم المشورة حول الحميةومن ناحية أخرى‎٬‎ كان التدريب غير الكافي عائقا يحول دون إجراءوالفحصبعض إجراءات المشورة على سبيل المثال‎٬‎ كانت نسبة المشورة حول الإقلاع عن التدخين(‏‎53.0‎والمشورة حول الحمية (52.6 %) والفحص الذاتي للثديالاستنتاج : وجدت الدراسة أن تدريب غير الكافي للممارسين العامين يمثل عقبة رئيسية تعترض إيتاء الرعايةالوقائية.‏ وقد أعلن هذا عدد كبير من ممارسي طب العائلة والممارسين العامين؛ وكان هذا ملحوظا عندما يقدمالممارسون العامون مشورة حول الإقلاع عن التدخين ‎٬‎أو عن الحمية أو الفحص الذاتي للثدي إضافة إلى ذلك‎٬‎أوضحت الدراسة بعض التوصيات القيمة من قبل الممارسين العامينالكلمات الدليلة:‏ الكويت‎٬‎ عقبات‎٬‎ وقاية‎٬‎ الرعاية الصحية الأولية.‏(% 84.4)٬(%..٬(% 39.3).(% 36.7).29 مركزا٬(% 44.1)الذاتي للثدي (74.9 %)..4

مواقف وممارسات الممارسين العامين نحو تدبير السمنةGeneral Practitioners Attitudes and Practices toward Managing Obesity٬الملخصهدف البحث:‏ تقييم مواقف وممارسات الممارسين العامين نحو تدبير السمنة وتوصياتهم بخصوص التحسينات‎٬‎إن وجدت.‏استبيان سيكون عنده ثلاثة أبعاد رئيسية:‏ الخصائص الديموغرافية الاجتماعيتصميم البحث:‏ أدار النفس الممارسين العامين في التعامل مع المرضى البدناء ومواقف الممارسين العامينللممارسين العامين نحو تدبير ال السمنة.‏اختار بشكل عشوائي‎٬‎ خارج 87 في الكويت.‏أولية مكان الدراسة:‏ تسعة وعشرون مركز رعاية أولية في الكويترعاية انتزعت من مئتي ممارس عام يعملون في المرضى إجراءات النتيجة الرئيسية:‏ لتقرير أسباب الصعوبة التي تواجه الممارسين العامين في تدبير المرضى البدناء فيالأولية وطرح حلول لها.‏مجالات الرعاية أن تدبير السمنة يجب أن يمثل جزءا من عملهم‎٬‎ بينماالنتائج:‏ ذكرت أغلبية الممارسين العامين %20 منهم كانوا يواجهون صعوبات في التعامل مع المرضى البدناء دائما.‏ كان عدم توفر أخصائيي الحميةولا أخصائيي التغذية في العيادات هو السبب الأكثر شيوعا لصعوبة معالجة السمنة.‏ ذكر أكثر الممارسينيفضلونالعامين أنهم ينصحون مرضاهم البدناء بزيادة أنشطتهم البدنية.‏ نادرا ما كان نفس الممارسين العامين وصف الأدوية‎٬‎ أو الجراحة أو العلاج السلوكي.‏أبدى الممارسون العامون بعض الاقتراحات التي تحسن تدبير السمنة في مستوى الرعاية الأولية؛الاستنتاج والتي تشمل إشراك أجهزة الإعلام‎٬‎ وجود أو الوصول السهل إلى أخصائيي الحمية وإنشاء عيادات تخصصيةمستقلة للسمنة في مراكز الرعاية الأوليةالكلمات الدليلة:‏ الاتجاهات‎٬‎ المعوقات‎٬‎ تدبير السمنة‎٬‎ ممارسات‎٬‎ الرعاية الأولية.‏29 مركز(% 85).٬ صعوبات: البيانات:5

نتائج التدبير غير الجراحيللرضح الطحالي الكليلOutcome of Non-operative Management of Blunt Splenic Trauma.الملخصهدف البحث:‏ تقييم نتائج التدبير غير الجراحي ومقارنته بالمعالجة الجراحية في الرضح الطحالي.‏تصميم البحث:‏ دراسة مقارنة استعاديةمكان الدراسة:‏ مجمع الرياض الطبي‎٬‎ الرياض‎٬‎ المملكة العربية السعودية.‏المرضى : روجعت ملفات تم تدبيرهم للإصابة برضح طحالية كليل على مدى فترة خمسة سنواتتم تقسيم المرضى إلى مجموعتين:‏ المجموعة الجراحية والمجموعة غير الجراحيةالتدخل:‏ كان خمسة وثلاثون مريضا غير مستقرين من حيث ديناميكيات الدم‎٬‎ وخضعوا لفتح البطن معاستئصال الطحال أو رفو الطحال استئصال الطحال الجزئي ‏(مجموعة الجراحة).‏ كان ثمانية وأربعونمريضا مستقرين من حيث ديناميكيات الدم.‏ تم تأكيد تشخيص الرضح الطحالي بإجراء التصوير المقطعي علىالبطن.‏ تم تدبير هذه الحالات أوليا بشكل محافظ بمراقبة إكلينيكية ومعملية متسلسلة في وحدة الرعاية المركزةتلتها راحة في السرير لمدة أيام في العنبر العام ‏(المجموعة غير الجراحية).‏الإجراءات الرئيسية للبحث:‏ تمت مقارنة النتائج من ناحية مدة الإقامة في المستشفى والمضاعفات ومتطلباتنقل الدم والمراضة والوفيات بين المجموعتين.‏أجري لهم فتح البطن‎٬‎ تم استئصال الطحال في 25 مريضا وأبقي فيالنتائج:‏ بينمرضى.‏ كان ثمانية وأربعون مريضا (%58) مستقرين من حيث ديناميكيات الدم دون جراحة.‏ كانلدى المجموعة غير الجراحية درجة إصابة أكثر تقدما‎٬‎ وتطلبت قدرا أقل من نقل الدم وكانت فترة الإقامة فيالمستشفى لأفرادها أقصر من مثيلتها في المجموعة الجراحية.‏ فشل التدبير غير الجراحي في 4 مرضى وحققنسبة نجاح قدرهاالاستنتاج التدبير غير الجراحي للرضح الطحالي الكليل في المرضى المستقرين من حيث ديناميكيات الدميعد إجراء آمنا وفعالا‎٬‎ مع إقامة أقصر في ومراضة ووفيات منخفضتين.‏الكلمات الدليلة:‏ الرضح الطحالي الكليل المعالجة غير الجراحية استبقاء الطحال‎٬‎ استئصال الطحال.‏.10.٬ وعولجوا٬المستشفى ٬٬٬ أو83 مريضا7­535 مريضا (%42)٬.%91.7: إن6

استئصالالدرقية الكلي لعلاج المرض الدرقي الحميد الثنائي الجانب:‏شاكلة الأمان والكفاءة العلاجيةTotal Thyroidectomy for Bilateral Benign Thyroid Disease: Safety Profile and TherapeuticEfficacy.الملخصهدف البحث:‏ تحليل مأمونية وتأثير استئصال الدرقية الكلي في التدبير الجراحي للدراق المتعدد العقد الثنائيالجانب.‏تصميم البحث:‏ دراسة استعاديةمستشفى الملك خالد الجامعي‎٬‎ الرياض‎٬‎ المملكة العربية السعودية.‏مكان الدراسة:‏ المرضى وطرق البحث:‏ تم فحص السجلات الطبية لجميع المرضى الذين خضعوا لاستئصال الدرقية الكلي علىفي مستشفى الملك خالد الجامعي بالرياض‎٬‎ المملكةإلى يوليو مدى خمس سنوات ‏(أغسطس والتشخيصاستخرجت من الملفات البيانات المتعلقة بالعمر‎٬‎ والجنس‎٬‎ واستطباب الجراحة العربية السعودية ٬ والمضاعفات‎٬‎ إن وجدت .الهستولوجي إناث و‎51‎ ذكور)‏‎٬‎ تراوحت أعمارهم ما بينالنتائج:‏ كان هناك ما مجموعهحالة بأعراض ضاغطة و‎29‎ (17.6 %)قدمتمع عمر متوسط قدرهللشك في وجود ورم خبيثلأسباب جمالية‎٬‎وبأعراض الانسمام الدرقي ؛الهستولوجي الأكثر تواترا ‏(وجد فيبامتداد خلف القص.‏ كان الدراق المتعدد العقد هو التشخيص سجلت الخباثة الدرقيةحالة(‏‎13.4‎ في الدراق الغرواني من المرضى)‏ أي ‏(خمس سرطانات حليمية وست جريبية‎٬‎ لمفومة واحدة ومتفاوت جريبيمريضا العرضية في المستديم في واحدواحد للسرطانة الحليمي).‏ حدث شلل العصب الحنجري الراجع الدائم وقصور الدريقات مرضى على التوالي.‏ لم تكن هناك أية وفيات.‏وخمسة بديلا مأمونا للمرضى بالدراق المتعدد العقد الثنائي الجانب؛ ويتسم هذايمثل استئصال الدرقية الاستنتاج بنسبة مضاعفات منخفضة ٬ كما أنه يلغي الحاجة لإعادة الجراحة لعلاج الدراق المتكرر والخباثةالإجراء الدرقية غير المتوقعة.‏العصب الحنجري الراجع‎٬‎ استئصال الدرقيةالدراق المتعدد العقد الكلمات الدليلة:‏ قصور الدريقات الكلي.‏٬63 ­18 سنة٬. (%(20052000164 مريض 113)46.3) 76 (%11.0 ± 40 سنوات.‏ (% 10.9) 18و‎24‎ 14.6) (%22٬ شلل٬ يليه٬ (% 8)٬(% 3).و‎3‎ 1.8) (%% 51.8 813(% 0.6):7

تأثير التعرض غير الكافي لضوء الشمس على نقصفيتامين Dوالأعراض ذات العلاقة بين النساء في دولةالكويتThe Influence of Insufficient exposure to Sunlight on Vitamin D Deficiency and Related Symptomsamong Women in the State of Kuwaitالملخص:‏أهداف البحث:‏ دراسة نقص كسبب لتليّن العظام في الشابات وتقييم التأثيرات العلاجية لفيتامين Dالعالي الجرعةتصميم البحث:‏ تضمنت الدراسة مريضة متتابعة مصابات بتليّن العظام.‏ تم تسجيل المتثابتات الإكلينيكيةوالكيميائية الحيوية مبدئيا وبعد المعالجة بفيتامين D العالي الجرعة.‏مكان الدراسة:‏ مستشفى الجهراء‎٬‎ الكويت.‏المرضى : مريضات متتابعات بتليّن العظام من مراجعات عيادة طب الغدد الصماء.‏التدخل:‏ لا شيء.‏النتيجة الرئيسية للبحث:‏ نؤكد أن التعرض الكافي لضوء الشمس عامل ضروري في منع تليّن العظامإنالنتائج:‏ كان كل المرضى من الإناث وكان متوسط أعمارهن والانحراف المعياريالمتوسط والانحراف المعياري للمتثابتات الكيميائية الحيوية الأولية وأثناء معالجة كانت على التوالي:‏ كالسيومالمصلملي مول/‏ لترالمصل=‏‎186.0‎مليالفسفاتازملي مول/‏ لترملي مول/‏الكالسيوم البولي=‏مول/‏ لترباراثورمون‎8.87‎ملي مول/‏الفوسفاتبيكو مول/‏ لترالمصلومسح قياس كثافة العظم‎8.05‎نانو مول/‏ لترالاستنتاج تليّن العظام بسبب التعرض غير الكافي لضوء الشمس والاستهلاك المعوز لمنتجات الألبان ليسبالأمر النادر حتى في المناخ المشمس.‏ تحسنت المريضات بعد المعالجة بجرعات عالية من فيتامينوالتعرض الكافي لضوء الشمس واستهلاك كميات كافية من منتجات الألبانالكلمات الدليلة:‏ التوعية الصحية‎٬‎ العالي الجرعة‎٬‎ مناخ مشمس تليّن العظام.‏.9.14 ±23.08 سنة.‏فيتامين Dn) ٬(2.6­2.2= فوسفات = 0.88 ± ٬0.260.37 ±2.24 ٬0.14± 2.12٬(1.6­0.8=n) القلوية = 413.1 ٬292.2± ± 220.70.24 ±1.2824 1.67± 2.16 ٬0.95 ± 1.26 ساعة(‏‎­0.33=n٬(200­95=n)24 ساعة ٬(42­13=n)٬(7.5 البولي = 8.10 ٬6.14± ± 8.52±8.10 = 25(OH)D ٬(5.6­0.7=n)4.49±10.85 ٬23.43± 38.68 =.0.91 ± 2.086 ­ =(113­23=n):٬D.٬فيتامين D24٬.8

الولادةبعد عملية قيصرية سابقةفي الكويتDelivery after Prior Cesarean Section in Kuwaitالملخصالمقدمة:‏ كانت هناك زيادة مثيرة في نسب الولادة القيصرية حول العالم.‏ تمثل الولادة المهبلية بعد ولادة قيصريةسابقة إحدى الاستراتيجيات المتبعة لتخفيض النسبة العالية للولادات القيصريةهدف الدراسة:‏ تقييم نمط الولادة بعد عملية قيصرية سابقة خلال فترة ‎14‎سنة منتصميم البحث:‏ دراسة إكلينيكية استعاديةمكان الدراسة:‏ مستشفى الولادة‎٬‎ الكويت.‏المرضى وطرق البحث:‏ تم استخلاص الخصائص السكانية الاجتماعية ونمط الولادة بعد ولادة قيصرية سابقةلعدد سيدة مؤهلة من التقارير السنوية‎٬‎ وسجلات لجنة طب حوالي الولادةوسجلات ملفات المرضى والسجلات المركزية للولادات القيصرية للتوثيق.‏مهبليا ‏(ولادةالنتائج:‏ من بين سيدة تعرضن لولادة القيصرية سابقة ‎٬‎أمكن توليدمهبلية تلقائية وولادة مهبلية باستخدام الأدوات في من النساء‎٬‎ تم تنفيذ الولادة القيصريةالانتخابية بشكل رئيسي بسبب المجيء الشاذ للجنين‎٬‎ ووجود اضطرابات طبية والعملقة والحمل المتعدد.‏ كانهناك اتجاه نزولي في نسبة الولادات المهبلية من في إلى في ٬2005 كما ازداداعتبار العقم/‏ الإخصاب خارج الرحم والحمل المتعدد بنسبة ثلاثة أضعاف كاستطبابات لتكرار الولادةو‎2005­2000‎‏.‏ كانت نسبة الولادة القيصريةالقيصرية بصورة طارئة خلال الفترات ما بينبعد تحريض الولادة بينما أمكن توليد مهبلياالاستنتاج ولادة قيصرية سابقة أمكن تحقيق الولادة المهبلية في من السيدات‎٬‎ ولم يصاحب ذلكسوى مضاعفات طفيفة.‏ بالاختيار الملائم للمريضات تكون الولادة المهبلية مأمونة النتائج.‏ يُنصح بالتدبيرالنشط للولادة وتدخل الأطباء الكبار في اتخاذ قرار تكرار الولادة القيصرية.‏الكلمات الدليلة:‏ استطبابات‎٬‎ ولادة قيصرية سابقة ولادة مهبلية.‏والأمومة ٬1992 إلى .2005(% 60) 7655.٬% 51.3% 60%81992.(% 14% 65.71995­1992. % 48٬٬.٬٬ وذلك12,725% 86٬ % 5212,725: بعد9

السمنة وعوامل الخطر القلبية الوعائية في البالغين الكويتيينObesity and Cardiovascular Risk Factors in Kuwaiti Adultsالملخص:‏٬ وكذلك عوامل الخطر القلبية الوعائيةهدف البحث:‏ تقييم العلاقة بين السمنة ‏[مؤشر كتلة الجسم البالغ بين المواطنين الكويتيين البالغين.‏تصميم البحث:‏ دراسة مقطعية أجري ت بين المواطنين الكويتيين البالغين ‏(العمر:‏الصحي‎٬‎ الكويت.‏مكان الدراسة:‏ مركز الشرطة الصحي بقرطبة ومركز عبد االله السالم تم اختيار عينة منالمرضى التدخل:‏ الفحص الروتيني لأولئك الذين لم يسبق أن شخصوا بأية مشكلة صحية مزمنة.‏انتشار السمنة‎٬‎ مستويات سكر الدم الصائم‎٬‎ وضغط الدم وبروفيل دهون الدم.‏النتيجة الرئيسية للبحث:‏ في خطر أعلىمن أفراد العينة مع سيادة الذكور.‏ كان الأفراد البدناء النتائج:‏ كانت السمنة سائدة بين بشكل ملحوظ لتطوير عوامل الخطر القلبية الوعائية مثل ارتفاع مستويات الكوليستيرول الكلية(‏‎٬48=ORتعطل سكر الدم الصائم OR)البروتين الشحمي الخفيض الكثافة OR) =٬28وضغط الدمالدم الانقباضي قبل الارتفاعيمن المرضى غير البدناء بعد تعديل أسباب الالتباسالانبساطي قبلالأخرى.‏يمثل انتشار السمنة مشكلة صحية خطيرة في المناطق التي تمت دراستها في الكويت‎٬‎ وهي ترتبطالاستنتاج يعد إشارة تحذيرية من الزيادة المستقبلية المحتملة فيبتشكيلة واسعة من عوامل الخطر القلبية الوعائية الأمراض القلبية الوعائية في هذه المجموعة السكانية.‏ نقترح إجراء دراسات أخرى تغطي عينات ممثلة لجميعالكويتيون ٬ كما يوصى بتطبيق برامج الوقاية من السمنة ذات العلاقة بالاهتمامات المجتمعية .الكلمات الدليلة:‏ السمنة‎٬‎ عوامل الخطر القلبية الوعائية‎٬‎ الكويت.‏:CI44­20 سنة)‏[30≤٬(81.3­9.3 :CI(15.4­1.9 :CI ٬5.4= OR)296 مريضا.‏% 42٬(235.9­9.8٬16= :CI ٬(43.2­6.2 ضغطالارتفاعي OR) ٬5.5= :CI (25.9­1.2٬ مما::10