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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 stress and antioxidant deficiency in the β-thalassaemia in Sri Lanka(Sri Lanka Medical Association, 2021) Perera, S.; Allen, A.; Mettananda, S.; Rodrigo, R.; Perera, L.; Darshana, T.; Moggach, F.; Jackson-Crawford, A.; Heirene, L.; Fisher, C.; Olivieri, N.; Rees, D.; Allen, S.; Premawardhena, A.Introduction In the β thalassaemias oxidative stress is potentially high and this could be further exacerbated in the absence of robust antioxidant defences, such as nutritional vitamin C and E deficiencies. We undertook a comprehensive assessment of oxidant, antioxidant and inflammatory status in patients with subtypes of β-thalassaemia to study these factors in detail. Methods Consenting patients attending the thalassaemia centre in Ragama, (between November 2017 and June 2018) were assessed for the following: methaemoglobin, plasma haemoglobin, heme and ferritin as sources of oxidants, plasma haptoglobin, hemopexin and vitamins C and E as markers of antioxidants, plasma interleukin-6 and C-reactive protein for inflammation. Fruit and vegetable intake was determined by dietary recall. Results 162 patients were recruited. (59 HbE β-thalassaemia, 50 β-thalassaemia major, 40 β-thalassaemia intermedia, 13 HbS β-thalassaemia. Median age was 26.0 years (IQR 15.3-38.8), 101 (62.3%) were female. Oxidants were frequently increased and antioxidants depleted with high levels of oxidant damage, hypoxia and inflammation. Abnormalities were most severe in HbE-β thalassaemia and least severe in β thalassaemia intermedia. Oxidative stress was also more severe in splenectomised patients. Plasma vitamin C concentration was below the lower level of quantitation in 86/160 (53.8%) patients and vitamin E in 130/160 (81.3%) patients. Less than 15% of patients ate fresh fruits or raw vegetables frequently. Conclusion Markedly increased oxidative stress and antioxidant deficiency were observed in this study group, especially in those with HbE β-thalassaemia. Vitamin C & E supplementation may have a role in the long-term management of thalassaemia syndromes.Item Identifying haemoglobinopathy traits and iron deficiency in Sri Lanka using the dtchlorophenolindophenol (DCIP) and one- tube osmotic fragility (OF) tests and measurement of red cell zinc protoporphyrin (ZPP)(Sri Lanka Medical Association., 2019) Perera, P. S.; Premawardhena, A.; Mettananda, S.; Rodrigo, R.; Perera, L.; Weatherall, D. J.; Allen, S.; Allen, A.INTRODUCTION & OBJECTIVES: Effective, low-cost, point-of-care tests are needed for haemoglobinopathy traits and iron deficiency throughout Southeast Asia. The objective of this study is to evaluate a combination of simple, low cost, easy-to-interpret and rapid tests as a "one-stop" screening procedure for identifying carriers of haemoglobin variants and iron deficiency in Sri Lanka. METHODS: Between November 2017 and May 2018, the KKU-OF and KKU modified DCIP tests (KKU, Thailand) were compared with High Performance Liquid Chromatography (HPLC) in a cross-sectional survey of 1324/1332 (99.4%) children attending secondary schools in Gampaha district, Sri Lanka. Iron deficiency was indicated in children with a raised red cell ZPP (Helena Biosciences), and confirmed by measurement of low serum ferritin and normal C- reactive protein (CRP). RESULTS: Median age was 17 years (IQR 16-18), all were Sinhalese and 814/1324 (61.5%) were female. HPLC identified 26 students with β-thalassaemia trait and 3 with HbE trait. The KKU-OF test correctly identified all 26 students with β-thalassaemia trait (sensitivity=100%) but was also positive in 288 samples with a normal HPLC result (specificity= 1007/1295; 85.5%). The KKU-DCIP test was positive only in the 3 students with HbE (100% sensitive and 100% specific). Iron deficiency was present in 148/1318 (11.2%) students. CONCLUSION: This one-stop approach may be an effective and affordable procedure in screening for haemoglobinopathy traits and identifying iron deficiency. We are investigating the causes of the false positive OF test results and planning large scale studies to assess cost-effectiveness.Item The p.H63D allele of the HFE gene protects against low iron stores in Sri Lanka.(Academic Press, 2019) Allen, A.; Premawardhena, A.; Allen, S.; Rodrigo, R.; Manamperi, A.; Perera, L.; Wray, K.; Armitage, A.; Fisher, C.; Drakesmith, A.; Robson, K.; Weatherall, D.In hereditary hemochromatosis, iron overload is associated with homozygosity for the p.C282Y mutation. A second mutation, p.H63D, occurs at significant frequencies in Europe, North Africa, the Middle East and Asia. Early studies in Sri Lanka indicated that the variant had arisen independently, suggesting that it had been the subject of selective pressure. However, its role in iron absorption is unclear. In a survey of 7526 Sri Lankan secondary school students, we determined hemoglobin genotype and measured red cell indices, serum ferritin, transferrin receptor, iron zinc protoporphyrin and hepcidin. These variables were compared according to the presence or absence of the p.H63D variant in a subset of 1313 students for whom DNA samples were available. Students were classified as having low red cell indices if they had an MCV <80 fl and/or MCH <27 pg. Hetero and/or homozygosity for the p.H63D variant was more common in students with normal than low red cell indices (16.4% and 11.9% respectively; p = 0.019). Iron biomarkers and red cell indices were greater in children with the p.H63D variant than in normal and this was statistically significant for MCV (p = 0.046). Our findings suggest that selective pressure by mild iron deficiency contributes to the high frequencies of the p.H63D variant.Item Haemoglobin variants, iron status and anaemia in Sri Lankan adolescents with low red cell indices: A cross sectional survey(Academic Press, 2018) Rodrigo, R.; Allen, A.; Manamperi, A.; Perera, L.; Fisher, C.A.; Allen, S.; Weatherall, D.J.; Premawardhena, A.Iron deficiency complicates the use of red cell indices to screen for carriers of haemoglobin variants in many populations. In a cross sectional survey of 7526 secondary school students from 25 districts of Sri Lanka, 1963 (26.0%) students had low red cell indices. Iron deficiency, identified by low serum ferritin, was the major identifiable cause occurring in 550/1806 (30.5%) students. Low red cell indices occurred in iron-replete students with alpha-thalassaemia including those with single alpha-globin gene deletions. Anaemia and low red cell indices were also common in beta-thalassaemia trait. An unexpected finding was that low red cell indices occurred in 713 iron-replete students with a normal haemoglobin genotype. It is common practice to prescribe iron supplements to individuals with low red cell indices. Since low red cell indices were a feature of all forms of α thalassaemia and also of iron deficiency, in areas where both conditions are common, such as Sri Lanka, it is imperative to differentiate between the two, to allow targeted administration of iron supplements and avoid the possible deleterious effects of increased iron availability in iron replete individuals with low red cell indices due to other causes such as α thalassaemia.