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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Oxidative status in the β-thalassemia syndromes in Sri Lanka; a cross-sectional survey(Elsevier Science-Pergamon Press, 2021) Allen, A.; Perera, S.; Mettananda, S.; Rodrigo, R.; Perera, L.; Darshana, T.; Moggach, F.; Crawford, A.J.; Heirene, L.; Fisher, C.; Olivieri, N.; Rees, D.; Premawardhena, A.; Allen, S.ABSTRACT: In the β-thalassemias, oxidative stress, resulting from chronic hemolysis, globin chain imbalance, iron overload and depleted antioxidant defences, likely contributes to cell death, organ damage, anemia, hypoxia and inflammation. We assessed variations in these parameters in β-thalassemia syndromes in Sri Lanka. Between November 2017 and June 2018, we assessed children and adults attending two thalassemia centres in Sri Lanka: 59 patients with HbE β-thalassemia, 50 β-thalassemia major, 40 β-thalassemia intermedia and 13 HbS β-thalassemia. Median age was 26.0 years (IQR 15.3-38.8), 101 (62.3%) were female and 152 (93.8%) of Sinhalese ethnicity. Methemoglobin, plasma hemoglobin, heme and ferritin were measured as sources of oxidants; plasma total antioxidant capacity, haptoglobin, hemopexin and vitamins C and E assessed antioxidant status; plasma thiobarbituric acid reactive substances and 8-hydroxy-2'-deoxyguanosine assessed oxidative damage; hemoglobin, plasma erythropoietin and transferrin receptor assessed anemia and hypoxia and plasma interleukin-6 and C-reactive protein assessed inflammation. Fruit and vegetable intake was determined by dietary recall. Physical fitness was investigated using the six-minute walk test and measurement of handgrip strength. Oxidant sources were frequently increased and antioxidants depleted, with consequent oxidative damage, anemia, hypoxia and inflammation. Biomarkers were generally most abnormal in HbE β-thalassemia and least abnormal in β-thalassemia intermedia but also varied markedly between individuals with the same thalassemia syndrome. Oxidative stress and damage were also more severe in splenectomized patients and/or those receiving iron chelation therapy. Less than 15% of patients ate fresh fruits or raw vegetables frequently, and plasma vitamins C and E were deficient in 132/160 (82.5%) and 140/160 (87.5%) patients respectively. Overall, physical fitness was poor in all syndromes and was likely due to anemic hypoxia. Studies of antioxidant supplements to improve outcomes in patients with thalassemia should consider individual patient variation in oxidative status both between and within the thalassemia syndromes. KEYWORDS: antioxidants; oxidative damage; oxidative stress; thalassemia; vitamins C and E.Item A nationwide survey of hospital-based thalassemia patients and standards of care and a preliminary assessment of the national prevention program in Sri Lanka(Public Library of Science, 2019) Premawardhena, A.P.; Mudiyanse, R.; de Silva, S.T.; Jiffry, N.; Nelumdeniya, U.; de Silva, U.; Lamabadusuriya, S.P.; Pushpakumara, K.; Dissanayaka, R.; Jansz, M.; Rifaya, I.; Navarathne, U.; Thirukumaran, V.; Arambepola, M.; Bandara, W.D.; Vaidyanatha, U.; Mendis, D.; Weerasekara, K.; de Silva, N**.; Kumara, D.K.S.; Amarasena, S.D.; Hemantha, K. K.; Refai, M.A.C.M.; Silva, I.; Hameed, N.; Rajiyah, F.; Mettananda, S.; Allen, A.; Weatherall, D. J.; Oliveri, N. F.OBJECTIVES:Our aim was to describe the numbers and distribution of patients with different types of thalassemia and to assess the standards of care in all thalassemia treatment centers throughout Sri Lanka and the success of the ongoing prevention programme.METHODS:This cross-sectional island-wide survey was conducted by two trained medical graduates, who visited each thalassemia center to collect data from every patient, using a standardized form. Data was collected through review of patient registers and clinical records.RESULTS: We collected data on 1774 patients from 23 centers. 1219 patients (68.7%) had homozygous β-thalassemia, 360 patients (20.3%) had hemoglobin E β-thalassemia, and 50 patients (2%) had sickle β-thalassemia. There were unacceptably high serum ferritin levels in almost all centers. The annual number of births of patients with β-thalassaemia varied between 45-55, with little evidence of reduction over 19 years. CONCLUSIONS:Central coordination of the treatment and ultimately prevention of thalassemia is urgently needed in Sri Lanka. Development of expert centers with designated staff with sufficient resources will improve the quality of care and is preferred to managing patients in multiple small units.Item Hepcidin is suppressed by erythropoiesis in hemoglobin E β-thalassemia and β-thalassemia trait(American Society of Hematology, 2015) Jones, E.; Pasricha, S.R.; Allen, A.; Evans, P.; Fisher, C.A.; Wray, K.; Premawardhena, A.; Bandara, D.; Perera, A.; Webster, C.; Sturges, P.; Olivieri, N.F.; St Pierre, T.; Armitage, A.E.; Porter, J.B.; Weatherall, D.J.; Drakesmith, H.Hemoglobin E (HbE) β-thalassemia is the most common severe thalassemia syndrome across Asia, and millions of people are carriers. Clinical heterogeneity in HbE β-thalassemia is incompletely explained by genotype, and the interaction of phenotypic variation with hepcidin is unknown. The effect of thalassemia carriage on hepcidin is also unknown, but it could be relevant for iron supplementation programs aimed at combating anemia. In 62 of 69 Sri Lankan patients with HbE β-thalassemia with moderate or severe phenotype, hepcidin was suppressed, and overallhepcidin inversely correlated with iron accumulation. On segregating by phenotype, there were no differences in hepcidin, erythropoiesis, orhemoglobin between severe or moderate disease, but multiple linear regression showed that erythropoiesis inversely correlated with hepcidin only in severe phenotypes. In moderate disease, no independent predictors of hepcidin were identifiable; nevertheless, the low hepcidin levels indicate a significant risk for iron overload. In a population survey of Sri Lankan schoolchildren, β-thalassemia (but not HbE) trait was associated with increased erythropoiesis and mildly suppressed hepcidin, suggesting an enhanced propensity to accumulate iron. In summary, the influence oferythropoiesis on hepcidin suppression associates with phenotypic disease variation and pathogenesis in HbE β-thalassemia and indicates that the epidemiology of β-thalassemia trait requires consideration when planning public health iron interventions.