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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Chracterisation of beta giobin mutations in Sri Lankan patients with betathalassaemia intermedia(Sri Lanka Medical Association, 2013) Perera, S.; Silva, D.P.S.I.; Hapugoda, M.; Wickramarathne, M.N.; Wijesirwardhena, I.; Efremove, D.G.; Fisher, C.A.; Weatherall, D.J.; Premawardhena, A.P.INTRODUCTION AND OBJECTIVES: Patients with beta thalassaemia intermedia account for a third of patients attending thalassaemia clinics in Sri Lanka. They show immense phenotypic diversity, the genetic basis for which has not been identified so far. Objective were to characterise beta globin gene mutations in Sri Lankan thalassaemia intermedia patients and to determine how it to influences disease severity. METHODS: We identified 64 thalassaemia intermedia patients from the five main thalassaemia centers; Anuradhapura (n= 6), Kuruncgala (n= 4), Ragama (n= 42), Badulla (n=7) and Chilaw (n=5). Their beta globin DNA sequences were analyzed using ABI PRISM 313lx genetic analyser. RESULTS: Of sixteen patients identified to be homozygous for beta mutations, eleven carried mild beta alleles, IVSI 5 G_C (n= 10) and a rare homozygous promoter mutation - 90 C_T (N=l). Other five were shown to have different types of severe iputations in homozygous state. Nearly half the sample (n=39) was heterozygous for beta mutations. Of them 33 showed mild to severe mutation in one of the alleles IVSI-5 G_C (n=12), IVSI-1 G_A (n= 11) were the commonest. Two patients who were hetcrozygones for beta mutation had a highly unstable Hb variant haemoglobin Mizuho causing severe haemolytic anacma. Hb variants Hb G-Szuhu and Hb G-Coushatta were identified in two patients. CONCLUSIONS: We identified types of beta mutations in some patients with thalassaemia intermedia, which account for the clinical severity.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 Anemia in Sri Lanka: A literature review(Informa Healthcare, 2022) Amarasingha, A.A.D.S.; Silva, H.J.R.L.; Perera, P.S.; Premawardhena, A.P.Anemia is a global health problem. This paper reviews literature on the prevalence of anemia in Sri Lanka. We searched EBSCO (Elton Bryson Stephens Company), Cochrane Library, and Medline for articles on prevalence and molecular basis of anemia in Sri Lanka from January 2000 to May 2021. Forty articles were selected. Most of the studies were on prevalence of anemia among children and pregnant women. All the studies had restricted themselves to assess the contributing factors for anemia in limited age categories. Most articles had attempted to determine the overall prevalence of anemia and the contribution of iron deficiency to it. There were only a few studies on prevalence and molecular basis of hemoglobinopathies and even fewer on the prevalence of anemia of chronic disease. None of the studies had attempted to assess the national prevalence of red cell membranopathies and enzymopathies. The published data on prevalence of anemia in Sri Lanka are incomplete. This review emphasizes the value of a much broader survey on anemia covering all age categories including the elderly and conducting a national survey including anemia of chronic disease and on red cell membranopathies and enzymopathies in Sri Lanka.Item Thalassemia in Sri Lanka(Informa Healthcare,London, 2022) Premawardhena, A.P.; Madushanka, H.D.P.The island nation of Sri Lanka with 22 million people (in 2020) has an estimated 2000 patients with severe thalassemia. The majority have β-thalassemia (β-thal) major (β-TM), and Hb E (HBB: c.79G>A)/β-thal accounts for most of the remainder. Carrier rate for α+-thalassemia (α+-thal) trait is 9.9% and β-thal trait is 2.5%, with very similar rates in the three major ethnic groups (Sinhalese, Tamils and Moors). The distribution of thalassemia type reveals a remarkable variation, even in this small island, mirroring historical distribution of malaria. Even though healthcare is provided free by the state including blood transfusions and chelation, the overall survival of patients of β-TM is still not on a par with that of the Mediterranean countries. A national thalassemia prevention program was set up in 2007, but overall success of the exercise based essentially on dissuasion of marriages is not very promising.Item Retrospective analysis of Pyrexia of Unknown Origin (PUO) among adult patients in a Tertiary Care Hospital in Sri Lanka(Sri Lanka Medical Association, 2021) Premathilaka, L.H.R.A.; Darshana, L.G.T.; Liyanage, I.K.; Nishshanka, N.A.S.; Gamage, M.P.; Gunasena, J.B.; Sajeethan, P.; Mendis, B.M.I.U.; Shashiprabha, W.M.M.; Tilakaratna, P.M.Y.I.; Premawardhena, A.P.Introduction and Objectives Pyrexia of “unknown origin” remains a clinical entity universally despite advances in diagnostic technologies. There are few if any systematic studies on PUO conducted in Sri Lanka. We retrospectively analysed data of patients with PUO from a tertiary care hospital. Methods Records of PUO patients admitted to Colombo North (Teaching) Hospital during the period of January 2015 – January 2020 were extracted from the archives. Details of etiology, diagnosis and usage of medication of each patient was recorded. Results A total of 100 PUO patients were recruited. Majority were males (n=55;54.5%). Median ages of male and female patients were 53.0 and 50.0 years respectively. A final diagnosis had been reached in the majority (n=65;65%). Mean number of days of hospital stay was 15.16 (SD; 7.81). Median of the total number of fever days among PUO patients was 30.5. Out of 65 patients whose etiology were identified, the majority were diagnosed with an infection (n = 47; 72.31%) followed by noninfectious inflammatory conditions (n=13; 20.0%) and malignancies (n=5; 7.7%). Tuberculosis was the commonest infection detected (n=15; 31.9%). Mean number of days taken to reach the final diagnosis was 11.57 (SD: 11.42). Contrast enhanced CT scan (CECT) pelvis/abdomen (n = 15; 23.1%) was the commonest investigation leading to the final diagnosis. Antibiotics had been prescribed for the majority of the PUO patients (n=90; 90%). Conclusion Infections, mainly tuberculous, was the commonest cause for PUO while a third of patients remained undiagnosed despite a prolonged hospital stay.Item Assessing liver fibrosis in patients with transfusion dependent beta thalassaemia - a predictive model(Sri Lanka Medical Association, 2021) Padeniya, A.G.P.M.; Ediriweera, D.; de Silva, A.; Niriella, M.A.; Premawardhena, A.P.Introduction and Objectives Liver fibrosis in β-thalassaemia major is mainly due to transfusion-related iron overload. Transient elastography (TE) is an imaging modality which measures liver stiffness/fibrosis non-invasively. TE is simple, safe and efficient. However, inaccessibility and high-cost hinders its routine use. We designed a predictive model to evaluate liver fibrosis using demographic, anthropometric, biochemical and imaging data. Methods Sixteen patients with transfusion dependent beta thalassaemia were recruited to the study. FBC, LFT, serum ferritin and Transient Elastography (TE) and FerriScan measurements were recorded at the baseline and after two years follow up. Multiple regression model was developed to predict liver fibrosis using demographic, anthropometric, biochemical and imaging data. [age, gender, body mass index (BMI), steatosis score, liver iron content, mean pre-Hb over the last year, no of blood transfusions (lifetime), amount of blood ingested over the last year(ml/kg), amount of elemental iron by transfusions over last year(mg/ kg), serum ferritin, SGOT, SGPT and compliance with iron chelation].Results Of 16, 8 (50%) were females, mean (SD) age, BMI and fibrosis scores were 21(4.3) years, 18.8 (2.8) kgm-2 and 9.7(5.7) kPa respectively. Gender, BMI, SGOT, SGPT, compliance, number of transfusions taken lifetime showed significant association with liver fibrosis. The final model showed a coefficient of determination (R2) of 0.859. According to the model, predicted liver fibrosis is given by;-26.18 - 4.38*male+1.01*BMI - 0.11*SGPT+0.32*SGOT+2.78*compliance (rps)+0.04*no. of transfusions. ConclusionThe suggested model is a reliable tool to predict liver fibrosis in transfusion-dependent β-thalassaemia major patients in resource poor settings.Item Marriage patterns in Sri Lanka and the role of consanguinity in thalassaemia: A cross sectional descriptive analysis(Sri Lanka Medical Association, 2019) Goonatilleke, M.D.D.C.; de Silva, S.T.; Rodrigo, R.; Perera, S.; Goonathilaka, G.W.M.R.G.B.; Ramees, L.; Mettananda, S.; Weatherall, D.L.; Premawardhena, A.P.INTRODUCTION & OBJECTIVES: Consanguineous marriages play an important role in the propagation of thalassaemia. There is a paucity of data on consanguineous marriages in modern Sri Lankan society and its effect on thalassaemia births. We studied sociological aspects of Sri Lankan marriages with emphasis on consanguinity, and the prevalence of consanguinity in the parents of patients with thalassaemia. METHODS: Three marriage registrars from each district were asked to record details about the partners of all marriages they registered for 6 months, from July 2009. Parents of patients with thalassemia were interviewed separately, to identify any consanguinity. RESULTS: A total of 5249 marriages were recorded from 22 districts. Average age at marriage was 27.2 9 years for males and 24.0 8 years for females. 3737/5249 (71.2%) of all marriages were Love Marriages, except in the Moor community where 89.2% were Arranged Marriages. Female literacy and education tier levels were higher than in males. Overall national consanguinity rate was 6.4% (337/5249). It was highest among Tamils (20.4%), but only 3.3% among Sinhalese and 3.1% among Moors. In the parents of 405 patients with thalassaemia, overall consanguinity rate was 11.1% (45/405): it was highest among Tamils (33.3%) and lowest among Sinhalese (9.4%). CONCLUSION: Consanguinity among patients with Thalassaemia was almost double the national average. Though not the dominant cause, more emphasis should be given to consanguinity when conducting thalassaemia prevention campaigns. Since they are older and better educated at marriage, female partners should be better targeted in such health education campaigns.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 Transfusion-transmitted Hepatitis C: A cluster of cases in transfusion-dependent Thalassaemia patients in Sri Lanka(Blackwell Scientific Publications,, 2020) Perera, S.; Bonsall, D.; Niriella, M.A.; Allen, A.; Peries, A.C.; Nelumdeniya, U.B.; Dissanayake, R.; Silva, I.; de Cesare, M.; Klenerman, P.; Weatherall, D.J.; Roberts, D. J.; Premawardhena, A.P.OBJECTIVES: To report the clinical and virologic epidemiology of a recent epidemic of hepatitis C in thalassaemia patients in Sri Lanka. BACKGROUND: Transfusion-dependent thalassaemia patients remain at risk for hepatitis C virus (HCV). Here, we report a cluster of recent HCV infections in Sri Lankan thalassaemia patients and examine the phylogenetic relationship of viral sequences. METHODS: We conducted two prospective cross-sectional surveys of 513 patients in four Sri Lankan thalassaemia centres in 2014/2015 and re-surveyed one centre in 2016. We screened for anti-HCV antibodies using the CTK Biotech enzyme-linked immunosorbent assay (ELISA) kits and confirmed active infection by reverse transcription-polymerase chain reaction (RT-PCR) for HCV-RNA. HCV genomes were sequenced by unbiased target enrichment. RESULTS: Anti-HCV antibodies were found in 116/513 (22.6%) of patients initially tested. Active hepatitis C infection was found in 26 patients with no cases of active hepatitis B infection. Of 26 patients with HCV, two were infected with genotype 1(a), and the rest had 3(a). In a single centre (Ragama), 122 patients (120 new cases and two previously tested, but negative) were retested for anti-HCV antibodies. 32/122 (26.2%) patients were seropositive. Twenty-three (23/122; 18.8%) of these new cases were confirmed by HCV PCR (all genotype 3[a]). CONCLUSIONS: There is a significant cluster of recent HCV cases in multiply transfused thalassaemia patients in several centres in Sri Lanka. Most of the viruses shared a close phylogenetic relationship. The results are consistent with recent continuing transfusion-transmitted HCV infection. Routine surveillance for HCV of chronically transfused patients is required irrespective of screening of blood products.Item Pseudo polycythaemia and its association with cardio-metabolic risk factors: A preliminary descriptive analysis from a tertiary care hospital(Sri Lanka Medical Association, 2018) de Silva, S.T.; Amarasena, P.; Dias, M.A.D.H.; Lakmini, K.M.S.; Premathilaka, L.H.R.A.; Ranatunga, R.J.K.L.D.; Moratuwegama, H.M.D.; Siriwardana, S.R.; Niriella, M.A.; Premawardhena, A.P.INTRODUCTION AND OBJECTIVES: Polycythaemia is the result of either an actual increase in red cell mass (true) or relative reduction in plasma volume (spurious). Spurious or pseudo-polycythaemia (PP) is a poorly-researched entity with unexplained increase in mortality noted in previous studies. We aimed to characterize PP and determine an association between PP and metabolic syndrome (MS) in a Sri Lankan clinic-based population. METHODS: Consecutive, consenting adults > 18 years, with two consecutive haemoglobin levels> l 6.5mg/dL and > 16mg/dL and/or PCV >49% and >48% in men and women respectively, with non-tourniquet samples taken few days apart in a well-hydrated state, were recruited from clinics of University Medical Unit, Colombo North Teaching Hospital and from the private sector. Interviewer-administered questionnaire was used to gather data.RESULTS: 46 participants were recruited: 3 (6.5%) had primary polycythemia, 5 (10.9%) had secondary polycythemia due to identifiable causes. 38 (82.6%) patients had PP [mean age 42.2 (SD=l5.2) years and 36 (94.7%) were males]. Of these 14 (36.8%) had diabetes, 22 (57.9%) had hypertension, 25 (65.8%) had hyperlipidemia and 25 (65.8%) were obese. 19 (50%) had fatty liver, 23 (60.5%) were light smokers, 8 (21.1%) consumed alcohol beyond safe limits, 6 (15.8%) had increased neck circumference, 1 (2.6%) had ischemic heart disease, 2 (5.3%) had chronic kidney disease and 2 (5.3%) had hyperuricaemia. Comparison of PP and secondary polycythemia with regard to prevalent components of MS was not possible due to small numbers.CONCLUSION: Components of MS were prevalent among those with PP. The significance of this finding remains unexplained. This needs to be replicated in a larger sample to establish whether these are independent risk factors for the development of PP.