Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Elective cholecystectomy is associated with increased morbidity and mortality in patients with severe Thalassemia: A retrospective case control study.(Ferrata Storti Foundation, 2015) Premawardhena, A.; Fernando, R.; Kumarage, S.; Nishad, N.; de Silva, I.BACKGROUND: Haemoglobin disorders including thalassemia and sickle cell disease are often complicated with gall stone formation. The co-existence of Gilbert's syndrome together with these diseases further increases the risk of gall bladder disease. Some of these patients develop symptomatic disease which necessitates surgical intervention. At present the timing of cholecystectomy for thalassemia is no different from that of the general population with the exception of removal of the gall bladder at the time of splenectomy. This is no longer the case in sickle cell disease where, laparoscopic cholecystectomy is recommended even in asymptomatic patients. This practice however has not been extended to other types of haemoglobin disorders. AIM(S): 1.To assess the perioperative complications of patients with thalassaemia during cholecytetomy and to compare it with non thalassaemics who undergo the procedure. 2. To see if there is enough evidence to recommend elective cholecystectomy for thalassaemics. METHOD(S): We retrospectively studied case notes of thalassemia patients who had cholecystectomy (cases) in two of the biggest thalassaemia centres in Sri Lanka and also of 62 non-thalassaemics (controls) with gall bladder disease who had been scheduled to have gall bladder surgery in the same hospitals and looked at their peri-operative complications. RESULT(S): 98 out of 540 (18%) thalassaemics in the two centres had gall stones. Mean age of cases was 26.8 (SD 10.9) years and of controls 47.5 (SD 19.7) years. 19 (19%) thalassaemics with gall stones had undergone cholecystectomy. Ten patients had cholecystectomy simultaneously with splenectomy. The majority of non-thalassaemic "controls" had laparoscopic cholecystectomy 53/55 (96.3%) whilst the patients with thalassaemia were mostly operated with laparotomy 13/19 (68%). There was a significant excess complications occurring in both early (42.11 vs. 18.1%) and late (31.5 vs. 12.7%) phases in the thalassaemic patients compared with the controls. Among the early complications, sepsis (10.5% vs. 1.8%) and liver abscess formation (5.2 vs. 0%) was significantly different in the groups, adversely affecting the thalassaemics. Recurrent abdominal pain was more common among the thalassaemics as a late complication (P<0.05). Six thalassaemic patients with gall stone disease died during this study, 5(5%) while awaiting surgery and 1(1%) after surgery. There were no deaths among the controls. Out of the deaths, 3 (50%) were directly attributable to gallstone disease. In all three septicemia precipitated heart failure. We found a significant increase of both early and late post-surgical complications in the thalassemia group and also increased mortality most of which was related to severe sepsis. Higher perioperative mortality and morbidity were seen among symptomatic thalassaemic patients with gall stone disease undergoing cholecystectomy. This seems to suggest a strong case for supporting elective cholecystectomy in thalassemics before they develop symptoms. SUMMARY AND CONCLUSION(S): We suggest that laparoscopic elective cholecystectomy be considered for non-sickle, thalassemia patients too who have asymptomatic gall bladder disease, in an attempt to reduce this morbidity and mortality.Item Idiopathic pancreatitis: is it a consequence of an altering spectrum of bile nucleation time?(BMJ Publishing, 2009) Abeysuriya, V.; Deen, K.I.; Navarathne, N.M.M; Kumarage, S.K.INTRODUCTION: The pathogenesis of idiopathic pancreatitis (IP) remains poorly understood. Our hypothesis is that IP is a sequel of the microcrystallisation of hepatic bile. AIMS AND METHODS: A prospective case–control study compared 55 patients (symptomatic cholelithiasis, 30: 14 men, 16 women, median age 36 years, body mass index (BMI) 25.1 ¡ 0.33 kg/m2 ; gallstone pancreatitis, nine: six women, three men, median age 35 years, BMI 24.86 ¡ 0.23 kg/m2 ; and idiopathic pancreatitis, 16: seven women, nine men, median age 34 years, BMI 23.34 ¡ 0.2 kg/m2 ) with 30 controls (15 men, 15 women, median age 38 years, BMI 24.5 ¡ 0.23 kg/m2 , undergoing laparotomy and who had normal gallbladder and no demonstrable stones on ultrasonography). Ultrafiltered bile from the common hepatic duct in patients and controls was anaerobically incubated and examined by polarised light microscopy, for nucleation time (NT). Ethical approval was obtained. RESULTS: Patients were similar to controls. Mean NT in all groups of patients was significantly shorter than controls (established gallstones cumulative mean NT, 1.73 ¡ 0.2 vs controls, 12.74 ¡ 0.4 days vs, p = 0.001, t test and IP patients mean NT, 3.1 ¡ 0.24 days vs controls, 12.74 ¡ 0.4 days, p = 0.001, t test). However, NT in those with IP was significantly longer compared with those with established gallstones (mean NT in IP, 3.1 ¡ 0.24 SEM days, vs cumulative mean in patients with established symptomatic gallstones, 1.73 ¡ 0.2 days, p = 0.002, t test). CONCLUSION: NT in bile in patients with IP is abnormal and is intermediate in NT of lithogenic and non-lithogenic bile.Item Hyperhomocysteinaemia and stroke: a case-control study(Sri Lanka Medical Assosiation, 2004) Ranawaka, U.K.; Niriella, M.A.; Hewamadduma, C.A.A.; Kanakkahewa, N.; Thilakarathna, N.T.; Wickremasinghe, A.R.; Wijesekera, J.C.OBJECTIVES: We sought to identify the importance of hyperhomocysteinaemia as an independent risk factor for stroke. METHODOLOGY: This was a case control study of patients with stroke (n=48) and pair matched controls (age and sex matched; n=48) at the Institute of Neurology, NHSL. Prior ethical approval was obtained from the Ethical Review Committee of the SLMA. Fasting total plasma homocysteine (tHcy) was compared between the two groups. Logistic regression analysis was performed to determine the contribution of hyperhomocysteinaemia as a risk factor for stroke, after controlling for other risk factors, using the 50th percentile of tHcy among controls (tHcy 50) as cut-off value. All strokes (n=48) and ischaemic strokes (n=43) were analysed separately. RESULTS: Cases (mean age = 55.69 years) and controls (mean age = 54.64 years) were well matched. tHcy among controls (mean=16.5l umol/1) was higher than observed from elsewhere, even after excluding those with vascular risk factors (mean=13.8 umol/1). The mean tHcy levels were significantly higher in cases (23.12 umol/1) than in controls (16.51 umol/1, p<0.001). There was no significant difference in tHcy between ischaemic and haemorrhagic strokes, and lacunar and non-lacunar strokes. Logistic regression analysis showed that tHcy 50 was an independent risk factor for haemorrhagic strokes (OR 2.583, p=0.05), and for ischaemic strokes (OR 2.663, p=0.05). CONCLUSION: tHcy levels may be higher than usual among Sri Lankan populations. Hyperhocysteinaemia is an independent risk factor for stroke.Item Incidence and risk factors for Non-Alcoholic Fatty Liver Disease in an urban, adult Sri Lankan population – a community cohort follow-up study(Sage Publishing, 2015) Niriella, M.; Kasturiratne, A.; de Silva, S.; Perera, R.; Subasinghe, C.; Kodisinghe, K.; Priyantha, C.; Rishikeshavan, V.; Dassanayake, A.; de Silva, A.; Pathmeswaran, A.; Kato, N.; de Silva, H.J.INTRODUCTION: We previously reported a community prevalence of 33% for NAFLD in an urban, adult Sri Lankan population. We also found a significant association between patatin-like phospholipase domain containing 3 (PNPLA3) gene rs738409 polymorphism, and susceptibility to NAFLD in the same population, after testing 10 selected single nucleotide polymorphisms (SNPs) in a case control study. AIMS & METHODS: The aim of this study was to assess the incidence and risk factors for NAFLD in this population after seven years of follow-up. The study population consisted of 42-71-year-old adults, originally selected by age stratified random sampling from electoral lists from Ragama, Sri Lanka. The target population was screened initially in 2007 and subsequently invited back for re-evaluation in 2014. On both occasions they were assessed using a structured interview, clinical and anthropometric measurements, liver ultrasound, and biochemical and serological tests. NAFLD was diagnosed on established ultrasound criteria for fatty liver (two out of three criteria: increased echogenecity of the liver compared to kidney and spleen, obliteration of the vascular architecture of the liver and deep attenuation of the ultrasonic signal), safe alcohol consumption (Asian standards: 514 units/week for men, 57 units/week for females) and absence of hepatitis B and C markers. Non-NAFLD controls were defined as subjects who did not have any of the ultrasound criteria for NAFLD. We also performed an updated case-control study to investigate associations of selected genetic variants with incident NAFLD [SNPs: PNPLA3 (rs738409), LYPLAL1 (rs12137855), GCKR (rs780094), PPP1R3B (rs4240624) and NCAN (rs2228603), APOC3 (rs2854117 and rs2854116), ADIPOR2 (rs767870) and STAT3 (rs6503695 and rs9891119)]. RESULTS: Of the 2985 original study participants, 2155 (72.2%) (1244 women and 911 men; mean age 59.2 years [SD, 7.7]) participated in the follow-up assessment. 1322 [mean age 58.9 years (SD, 7.6), 483 (53.0%) men and 839 (67.4%) women] had NAFLD. Out of 795 [466 (58.6%) women] participants who did not have NAFLD in the original study, 365 [226 (61.9%) women, mean age 58.6 years (SD, 7.9)] had developed NAFLD after 7 years, giving an annual incidence rate 6.6%. On multivariate analysis, increased waist circumference [OR 1.96(1.30 – 2.97), p=0.001], BMI4 23 kg/m2 [OR 2.93(1.99 – 4.30), p50.001] and raised plasma triglycerides (TG) [OR 1.49(1.03 – 2.13), p=0.03] were independently predictive of incident NAFLD in this cohort, while raised BP and reduced HDL, were not. In the updated association study involving 1310 cases and 427 controls, we found borderline association with NAFLD at two of the 10 candidate loci: rs4240624 at PPP1R3B and rs738409 at PNPLA3 (one-tailed P=0.044 and 0.033, respectively). CONCLUSION: In this community cohort follow-up study in an urban, adult population in Sri Lanka, the annual incidence of NAFLD was 6.6%. Incident NAFLD was associated with features of the metabolic syndrome, and showed tendency of association at PNPLA3 and PPP1R3B gene polymorphisms. Disclosure of Interest: None declaredItem Association between road accidents and minimal hepatic encephalopathy in a cohort of Sri Lankan cirrhotic drivers(Wiley Blackwell Scientific Publications, 2014) Subasinghe, S.K.C.E.; Nandamuni, Y.; Ranasinghe, S.; Kodisinghe, K.; Niriella, M.A.; de Silva, A.P.; de Silva, H.J.OBJECTIVE: Minimal hepatic encephalopathy (MHE) has no recognizable clinical symptoms of hepatic encephalopathy (HE) but has mild cognitive and psychomotor deficits which can interfere with executive decision making and psychomotor speed. It affects driving ability and previous studies in Western countries have demonstrated an association between MHE and increased road accidents. Our objective was to investigate this association in a cohort of Sri Lankan cirrhotic drivers. METHODS: A prospective, case controlled study ongoing study has been conducted in the Gastroenterology Clinic, University Medical Unit, North Colombo Teaching Hospital, Ragama, from August 2013. Patients with cirrhosis of any aetiology, without overt HE, who had been driving any vehicle during the past one month were subjected to 5 standard pencil-paper based psychometric tests used to detect MHE. Road accidents were recorded for both cirrhotic drivers with MHE and controls. Accidents were categorized as major when they resulted in hospitalization of the involved person/s, and minor when there were no serious injuries. RESULTS: Among 55 cirrhotic drivers with MHE [males, median age 53 years (range 30-60)], 7 (12.7%) reported any type of accident compared to 6 (10.9%) among 55 controls [males; median age 51 years (range 30-60)]. 2/55 (3.6%) cases and 2/55 (3.6%) controls reported minor accidents. There were no major accidents in either group. CONCLUSION: Preliminary results of this ongoing study do not indicate an increased frequency of road accidents in a cohort of Sri Lankan cirrhotic drivers with MHEItem Delayed psychological morbidity associated with snakebite envenoming(Public Library of Science, 2011) Williams, S.S.; Wijesinghe, C.A.; Jayamanne, S.F.; Buckley, N.A.; Dawson, A.H.; Lalloo, D.G.; de Silva, H.J.INTRODUCTION: The psychological impact of snakebite on its victims, especially possible late effects, has not been systematically studied. OBJECTIVES: To assess delayed somatic symptoms, depressive disorder, post-traumatic stress disorder (PTSD), and impairment in functioning, among snakebite victims. METHODS: The study had qualitative and quantitative arms. In the quantitative arm, 88 persons who had systemic envenoming following snakebite from the North Central Province of Sri Lanka were randomly identified from an established research database and interviewed 12 to 48 months (mean 30) after the incident. Persons with no history of snakebite, matched for age, sex, geograpical location and occupation, acted as controls. A modified version of the Beck Depression Inventory, Post-Traumatic Stress Symptom Scale, Hopkins Somatic Symptoms Checklist, Sheehan Disability Inventory and a structured questionnaire were administered. In the qualitative arm, focus group discussions among snakebite victims explored common somatic symptoms attributed to envenoming. RESULTS: Previous snakebite victims (cases) had more symptoms than controls as measured by the modified Beck Depression Scale (mean 19.1 Vs 14.4; p<0.001) and Hopkins Symptoms Checklist (38.9 vs. 28.2; p<0.001). 48 (54%) cases met criteria for depressive disorder compared to 13 (15%) controls. 19 (21.6%) cases also met criteria for PTSD. 24 (27%) claimed that the snakebite caused a negative change in their employment; nine (10.2%) had stopped working and 15 (17%) claimed residual physical disability. The themes identified in the qualitative arm included blindness, tooth decay, body aches, headaches, tiredness and weakness. CONCLUSIONS: Snakebite causes significant ongoing psychological morbidity, a complication not previously documented. The economic and social impacts of this problem need further investigationItem Factors associated with home deliveries in Thampalakamam, Trincomalee(Sri Lanka Medical Association, 2006) Lukumar, P.; Pathmeswaran, A.INTRODUCTION: In Sri Lanka, more than 95% of women deliver in hospital. There is regional variation in the rate of home deliveries, and in some areas a significant number of mothers deliver at home. OBJECTIVE: The objective of the present study was to identify the factors associated with home deliveries in Thampalakamam, Trincomalee. METHODOLOGY: Ours was a community based, exploratory type of case control study. Cases were home deliveries during the period from Jan 1, 2000 to Dec 31, 2002 in Thampalakamam Divisonal Director of Health Services (DDHS) area. Controls were institutional deliveries among women residing in Thampalakamam DDHS area during the same period. A total of 139 cases and 278 controls were identified for this study. Data was collected at the household level using an interviewer-administered questionnaire. RESULTS: The following factors were found to have strong association with home deliveries: being a Muslim (OR = 33.0, 95% CI 16.8-64.8), low (< grade 5) maternal education (OR = 3.5, 95% CI 1.8-6.6), parity more than 3 (OR = 3.2, 95% CI 1.5-6.6) not being visited by a public health midwife (OR = 2.4, 95% CI 0.8-6.9), not being seen by a medical officer during the antenatal period (OR = 7.0, 95% CI 0.6-83.3). Lack of transport (35.5%) was mentioned as main reason for home deliveries by the women. Of the home deliveries 95% were assisted by a traditional birth attendant. CONCLUSIONS: Poor education of women and deficiencies in the delivery of antenatal care were found to be important risk factors for home deliveries.Item Medial temporal lobe atrophy, apolipoprotein genotype, and plasma homocysteine in Sri Lankan patients with Alzheimer's disease(Routledge, 2005) de Silva, H.A.; Gunatilake, S.B.; Johnston, C.; Warden, D.; Smith, A.D.The authors studied the association of Alzheimer's disease (AD) with total plasma homocysteine (tHcy) and apolipoprotein E (apoE)genotype, and the usefulness of measuring medial temporal lobe thickness (MTL) thickness for the diagnosis of AD in Sri Lankan patients. Using criteria of the NINCDS-ADRDA, 23 AD patients and 21 controls were recruited. All underwent MTL-oriented computed tomographic (CT) scans, measurement of plasma tHcy, and apoE genotyping. Mean plasma tHcy was significantly higher in AD patients than controls (p=.001). This association was independent of age, sex, body mass index (BMI), serum folate and vitamin B12, and serum creatinine. The frequency of apoE4 allele was significantly higher (p=.003) in AD patients, and the adjusted odds ratio of AD for the presence of one or more apoE4 alleles compared with none was 10.39 (95% CI 1.77-61.10; p=.010). The mean minimum MTL thickness was significantly higher in control subjects compared to that of AD patients (p<.001). This first report of apoE4, plasma tHcy, MTL thickness, and AD from Sri Lanka shows that high plasma tHcy, the presence of apoE4 allele, and MTL atrophy are associated with AD.Item Non-specific occupational health conditions among brass workers at Gadaladeniya, Sri Lanka(Sri Lanka Medical Association, 2004) Jayawardana, P. L.OBJECTIVE: To determine the effect of exposure to metal dusts, fumes and high temperature levels among brass workers in comparison to a control group. STUDY DESIGN: Analytical cross-sectional study. METHODOLOGY: One hundred and fifty four brass workers were matched for age with 154 controls selected from the local population. An interviewer-administered questionnaire was used to determine the presence of acute and chronic symptoms and metal fume fever. Haemoglobin and blood zinc and copper levels were measured using the cyanmethaemoglobin technique and atomic absorption spectrophotometry respectively. Thermal environmental measurements were carried out by determining wet bulb and globe temperature (WBGT) levels and air velocity. RESULTS: Among the chronic symptoms anorexia (OR = 3.3), distaste (OR = 8.3), and aches and pains (OR = 4.0) were significantly higher in the study group. Among the acute symptoms at work, cough (OR = 4.2), dry nose (OR = 6.8), tearing (OR = 6.3), and itchy eyes (OR = 6.3) were significantly higher in the study group. Sweating was significantly higher in the control group. Metal fume fever was significantly higher among the study group with an OR of 7.6. Levels of both copper and zinc were significantly higher in the study group, although both median and mean values were lower than the normal reference ranges. The recommended WBGT level of 26.1 degrees C for an air velocity of less than 1.53 m/s for heavy work was exceeded only in two workshops. CONCLUSIONS: Prevalence of non-specific symptoms was higher among brass workers. It is necessary to take preventive measures.Item Thyroglobulin epitope recognition in post iodine supplemented Sri Lanka population(Blackwell Scientific Publications, 2003) Okosime, O.E.; Premawardena, L.D.K.E.; Jayasinghe, A.; de Silva, D.G.H.; Smyth, P.P.A.; Parkes, A.B.; Lejeune, P.J.; Ruf, J.; Lazarus, J.H.OBJECTIVE: We previously reported a high prevalence of raised thyroglobulin autoantibodies (TgAb) in apparently healthy Sri Lankan schoolgirls following salt iodination. To characterize these antibodies further we determined the epitopes on thyroglobulin (Tg) with which they react and compared these with serum obtained from both healthy subjects and established autoimmune thyroid disease (AITD) patients from the UK. To extend our study to a wider population within Sri Lanka, we in addition determined the epitopes recognized by a group of AITD patients selected from a thyroid clinic in Sri Lanka, as well as apparently healthy female Sri Lankan tea workers of distinct ethnicity from the schoolgirls and AITD patients. DESIGN: Sri Lankan schoolgirls (n = 282) and adult female tea estate workers (n = 208) were examined for thyroid autoimmune markers. Sera with high TgAb (> 98 kIU/l) were selected from these two groups (n = 36 and 45, respectively) to study epitope-binding patterns. We also examined the sera from 16 AITD patients attending a thyroid clinic in Colombo, 16 patients with AITD from the thyroid clinic at the University Hospital of Wales and 16 sera from healthy control UK women with no evidence of thyroid disease. To determine the epitopes on Tg recognized by the subjects' TgAb, we employed a panel of Tg mouse monoclonal antibodies labelled with alkaline phosphatase in a competitive enzyme-linked immunosorbent assay reaction with the subjects' serum. RESULTS AND CONCLUSIONS: A majority of the Sri Lankan schoolgirls did not react with the immunodominant epitopes and did not differ significantly from healthy subjects from the UK in their Tg epitope recognition pattern. On the other hand, tea estate workers and Sri Lankan AITD patients recognized typical autoimmune thyroid disease epitopes and, in addition, recognized a separate cluster not previously associated with either the autoimmune state or the healthy state. The significance of this cluster requires further clarification