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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Paraspinal extramcduallry erythropoiesis- a rare cause of spinal cord compression: two case reports(Sri Lanka Medical Association, 2004) Arambepola, M.; Premawardhena, A.P.; de Silva, S.; Olivieri, N.; Weatherall, D.J.INTRODUCTION: Extrameduallry erythropoiesis (EME) is characterized by the appearance of haemopoietic tissue outside the bone marrow. When EME occurs, albeit rarely, outside the liver and spleen problems may occur. We describe two patients with haemoglobin E- [β thalassaemia who had spinal cord compression, due to EME masses which was reversed with treatment with hydroxyurea and hypertransfusion. PATIENT A: Was a 27year old with HbE -(β thalassaemia. His mean pre transfusion haemoglobin level was 5.5 g/dl. He presented with a six-month history of progressive numbness of his legs. On examination he was found to be paraparetic. The magnetic resonance scan (MRI) showed external compression of the spinal cord between the 4th and 8th thoracic vertebrae. Patient was put on a hypertransfusion regimen and hydroxyurea and made a complete recovery within 4 weeks. Patient B: Was a 9 year old boy with a diagnosis of Haemoglobin E [β thalassaemia who presented with paraplegia which had developed over 3 months. His spinal MRI showed two masses one in the upper thoracic vertebrae and the other at the 1st lumbar level. He was commenced on hydroxyurea and hypertransfusiion to maintain pre-transfusion haemoglobin at >9.5g/dl) and his neurological recover was remarkable. Six months later he had no neurological deficit. DISCUSSION: The above cases highlight the potentially dangerous complications of EME when it involves the spinal cord. They also highlight that even lesions which are sufficiently large to cause complete paraplegia are potentially reversible. Hypertransfusion, hydroxyurea, surgery and previously been used with varying success. The problem remains in deciding the optimal method of management.Item Randomised, placebo-controlled trial on topiramate add-on therapy for weight reduction and symptomatology in overweight/obese persons with Schizophrenia(Elsevier Ltd, 2022) Chandradasa, M.; Ruwanpriya, S.; de Silva, S.; Rathnayake, L.; Kuruppuarachchi, K.A.L.A.Introduction: Higher cardiovascular mortality is seen with schizophrenia due to the disorder itself and antipsychotic use. South Asians are more vulnerable to developing metabolic disorders than others. Resource-limited settings in South Asia have only a few mental health professionals, and individualised case management is mostly unavailable. Therefore, there is less monitoring and personalised support for diet and physical exercise programmes. Topiramate is useful for weight reduction and improvement of psychopathology in schizophrenia. However, there has been only one previous randomised controlled trial (RCT) done in South Asia, which possesses a quarter of the world's population. Methods: We conducted a double-blind RCT in an outpatient setting in Sri Lanka. We compared topiramate 100 mg/day with a placebo in overweight/obese adults with schizophrenia who have been on antipsychotics for at least a year. We obtained monthly anthropometric measurements and assessed the symptomatology using the brief psychiatric rating scale (BPRS). Results: Fifty patients each in the topiramate and placebo arms completed the study. Topiramate add-on therapy led to significant weight/Body Mass Index reduction and improved symptomatology as measured by the BPRS compared to the placebo. The topiramate group had significantly more reporting of loss of appetite. Discussion: According to available data, this is the RCT with most participants assessing the use of topiramate in schizophrenia and only the second in South Asia. Topiramate was shown to be useful for weight reduction and symptomatic improvement in persons with schizophrenia in a resource-limited setting in South Asia.Item 20 year follow up and survival analysis in a cohort of patients with Haemoglobin E beta Thalassaemia.(Sri Lanka Medical Association., 2019) Olivieri, N.F.; Premawardhena, A.P.; Amir-Arsalan, S.; Ediriweera, D.; Mettananda, S.; Bandara, W.D.; Arambepola, M.; de Silva, S.; Refai, M.A.C.M.; Allen, A.INTRODUCTION & OBJECTIVES: Haemoglobin E beta thalassaemia (EBT) is the commonest beta thalassaemia syndrome in the world and is extremely phenotypically variable. Unlike for transfusion dependent thalassaemia (TDT) there are no clear guidelines for the management of this disease. We have followed up a cohort of 109 patients with EBT for 20 years. Objective of the study was to study the 20-year survival and factors that affect survival. METHODS: Study was conducted at Kurunegala Thalassaemia centre. Transfusions were stopped in 1997 in all 109 patients. Since then they were assessed every three months by the clinical team for the next 20 years. Relevant haematological, biochemical, radiological assessments were done periodically. RESULTS: 32 (30%) of patients were dead at 20 years. Kaplan Meir survival curve identified the median survival to be 51 years. Splenectomy had been done in 73/109 (67%) patients. Splenectomy allowed 66% to be off transfusions even 9.7± 1.3 years post- surgery. However, 33% had to return to transfusions. The commonest cause of death in the cohort was infections (34.3%). Most (72%) infective deaths happened in those who were splenectomised. Transfusions needed to be restarted in 60%, of whom 33% went back to (>8 per year) regular transfusions at a mean 8.4 ±0.8 years after stopping transfusions. CONCLUSION: In this first ever long term follow up study of EBT, significantly shortened survival is observed. Though splenectomy allows prolonged transfusion free phases in many it increases risk of infective deaths. Overall the disease is far less benign than previously thought with a high prevalence of morbidity and mortality.Item The clinical effects of excessive a globin genes : two family studies(Sri Lanka Medical Association, 2003) Premawardhena, A.P.; Fisher, C.A.; Rugless, M.; de Silva, S.; Perera, A.W.V.S.; Olivien, N.F.; Weatherall, D.J.INTRODUCTION: Globin chain imbalance is the central pathogenic abnormality in the thalassaemias, a condition where globin gene expression is reduced. Conversely, the inheritance of excess globin genes too may affect the phenotype. However such examples are rarely found. OBJECTIVES: To describe two families in whom the co-existence of excess a genes was noted together with p - thalassaemia trait. METHODS: During the routine P - globin gene analysis in patients attending the Thalassaemia Unit of the Kurunegala Hospital, two patients were identified to have thalassaemia intermedia phenotype, but with just one (3 - thalassaemia mutation. The clinical details of these patients and their families were studied in detail as was their h'aematological and genetic data. RESULTS: We describe two families in which the propositus had inherited six and eight a - genes respectively together with a single p - thalassaemia mutation. Both patients had the thalassaemia intermedia phenotype. The family members who did not inherit any thalassaemic mutations too had varying, but often marked hypochromic microcytosis. DISCUSSION: We describe the first ever family study of a patient with the combination of 8 a - genes and p - thalassaemia trait. We also describe another family where a member had 6 a - genes together with p thalassaemia trait. This highlights yet another mechanism for the intermedia phenotype in patients with a solitary (3 - globin gene mutation. It also highlights the need for the study of a globin genes in patients with unexplained hypochromic microcytic anaemia.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 Ventilated patients in the Paediatric medical intensive care unit of Lady Ridgeway hospital: an audit(Sri Lanka Medical Association, 2011) Thadchanamoorthy, V.; de Silva, S.; Sarathchandra, J.; Kumarendran, B.INTRODUCTION AND OBJECTIVES: To analyse the outcomes related to ventilated paediatric patients admitted to paediatric ICU (PICU) in Lady Ridgeway Hospital (LRH). METHODS: This clinical audit recruited consecutive 292 patients admitted to PICU of LRH in 2Q09. The patients who admitted forItem Recent chikungunya outbreak in Sri Lanka 2006-2007(Faculty of Tropical Medicine, Mahidol University, 2007) Abeyewickreme, W.; Bandara, K.B.A.T.; Dayanath, M.Y.D.; Sumanadasa, D.; Hapuarachchi, H.A.C.; Gunawardena, N.K.; Hapugoda, M.D.; Wijesiriwardena, B.; de Silva, S.; Perera, T.BACKGROUND: Chikungunya(CHIK) is a viral disease transmitted by Aedes mosquitoes. Cases with symptoms of CHIK had been reported from several parts of Sri Lanka in 2006-2007. Laboratory testing of samples is a prime requirement for confirmation of transmission. OBJECTIVES: To confirm CHIK infection in suspected patients by rapid Reverse Transcription Polymerase Chain Reaction Assay(RT-PCR), find out manifestations specific for CHIK infection and study the transmission of CHIK virus by vector mosquitoes. METHODOLOGY: Serura. samples and information on clinical manifestations were collected from 189 chikungunya-suspected patients from different geographical areas in Sri Lanka from September 2006 to September 2007. Samples were tested for Chikungunya RNA by RT-PCR. Amplified products were visualized by agarose gel electrophoresis. Adult mosquitoes were also collected from chikungunya case-reported stations. They were tested for Chikungunya RNA through RT-PCR-followed by agarose gel electrophoresis assay. RESULTS: Of the CHIK-suspected patients reported from all parts of the island 86/189 (45.5%) were positive for CHIK virus. Of the PCR positive 06, all had fever with either arthralgia or arthritis or both. Headache (95.3%) and backache (84.6%) were also common among above patients. Eight percent (4/50) of both species of Aedes mosquitoes were RT-PCR positive. DISCUSSION: RT- PCR is important in early diagnosis of the infection and differentiation from dengue fever. The most common clinical symptoms observed were fever with either arthralgia, arthritis or both. Both Aedes aegypti and Aedes. albopictus are important in transmitting the disease.Item Prospective analysis of ventilated patients in the Paediatric Medical Intensive Care Unit of Lady Ridgeway Hospital(Sri Lanka College of Paediatricians, 2012) Thadchanamoorthy, V.; de Silva, S.; Sarathchandra, J.; Kumarendran, B.OBJECTIVE: To determine the characteristics and outcome of ventilated patients in the paediatric medical intensive care unit (PICU) of Lady Ridgeway Hospital for Children (LRH), Colombo. DESIGN: Prospective descriptive study METHOD: The study population consisted of all ventilated paediatric patients admitted to PICU, LRH from 1st March to 31st August, 2009. The factors studied included demographic profile (age, sex, residence, transfer), length of stay on ventilator, indication for ventilation, details of organ dysfunction and the final outcome. RESULTS: There were 152 patients ventilated over the study period of six months. Seventy three were under one year of age. Male to female ratio was 1.17:1. A significant proportion (n=105) were from the Western province. Eighty five patients were transferred from medical wards of LRH. Median duration of ventilation was six days (IRQ 4-10). Indications for ventilation included respiratory problems (85), neurological disorders (13), cardiac causes (5), hepatic problem (1) and miscellaneous diseases (48) including 32 from dengue syndromes. There were 42 deaths among ventilated patients giving an overall mortality rate of 27.6%. Multi-organ dysfunction syndrome (MODS) on admission accounted for 81% of the deaths. Bronchopneumonia (16) and dengue haemorrhagic fever (12) were the main underlying causes of death. Thirty two (21%) had anaemia while in the PICU, 15 of them having anaemia on admission. Nosocomial infection was present in 17 (11%) patients. Children transferred from other provinces had a higher risk of death than those from the Western province (OR=1.5, 95% CI: 0.7 – 3.3). CONCLUSIONS: MODS on admission accounted for 81% of the deaths. Bronchopneumonia and dengue haemorrhagic fever were the main underlying causes of death. Children transferred from other provinces had a higher risk of death compared to those from the Western provinceItem Hemoglobin E-[beta] Thalassemia: Progress Report from the International Study Group(Wiley-Blackwell, 2005) Premawardhena, A.; de Silva, S.; Arambepola, M.; Olivieri, N. F.; Vichinsky, E. P.; Merson, L.; Muraco, G.; Allen, A.; Fisher, C.; Peto, T.; Weatherall, D. J.A long-term observational study of Hb E-beta-thalassemia in Sri Lanka is beginning to define some of the genetic and environmental factors that are responsible for its remarkable phenotypic variability. In this population there is a very small difference between the steady-state hemoglobin levels between the mild and severe phenotypes, and it has been possible to stop transfusion in many of those who have been on long-term treatment of this kind. These preliminary observations, made over the last 7 years, provide directions for future research into this increasingly important disease.Item A Novel molecular basis for beta thalassemia intermedia poses new questions about its pathophysiology(American Society of Hematology, 2005) Premawardhena, A.; Fisher, C.A.; Olivieri, N.F.; de Silva, S.; Sloane-Stanley, J.; Wood, W.G.; Weatherall, D.J.During a study of the molecular basis for severe forms of beta thalassemia in Sri Lanka, 2 patients were found to be heterozygous for beta thalassemia mutations. Further analysis revealed that one of them has a previously unreported molecular basis for severe thalassemia intermedia, homozygosity for quadruplicated alpha globin genes in combination with heterozygous beta thalassemia. The other is homozygous for a triplicated alpha globin gene arrangement and heterozygous for beta thalassemia. Their differences in clinical phenotype are explainable by the interaction of other genetic factors and, in particular, their early management. The clinical course of the 2 propositi underlines the importance of full genotyping and a long period of observation before treatment is instituted, particularly in patients with beta thalassemia intermedia associated with extended alpha globin gene arrangements. The hemoglobin (Hb) F levels in these patients with severe beta thalassemia intermedia, compared with other forms of this condition in the Sri Lankan population and elsewhere, are unusually low, a consistent finding in extended alpha globin gene interactions and in dominant beta thalassemia, raising the possibility that increased levels of HbF production in beta thalassemia may require mutations at both beta globin gene loci