Journal/Magazine Articles
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This collection contains original research articles, review articles and case reports published in local and international peer reviewed journals by the staff members of the Faculty of Medicine
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Item Hemoglobin E-beta-thalassemia: Progress report from the international study group(Blackwell Publishing, 2005) Premawardhena, A.; de Silver, 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 Adaptation to anemia in hemoglobin E-beta thalassemia(American Society of Hematology, 2010) Allen, A.; Fisher, C.; Premawardhena, A.; Peto, T.; Allen, S.J.; Arambepola, M.; Thayalsuthan, V.; Olivieri, N.; Weatherall, D.Hemoglobin E beta thalassemia is the commonest form of severe thalassemia in many Asian countries. Its remarkably variable clinical phenotype presents a major challenge to determining its most appropriate management. In particular, it is not clear why some patients with this condition can develop and function well at very low hemoglobin levels. Here, we demonstrate that patients with hemoglobin E beta thalassemia have a significant decrease in the oxygen affinity of their hemoglobin, that is an increased P(50) value, in response to anemia. This may in part reflect the lower level of hemoglobin F in this condition compared with other forms of beta thalassemia intermedia. The ability to right-shift the oxygen dissociation curve was retained across the spectrum of mild and severe phenotypes, despite the significantly higher levels of hemoglobin F in the former, suggesting that efforts directed at producing a modest increase in the level of hemoglobin F in symptomatic patients with this disease should be of therapeutic value.Item Is the beta thalassaemia trait of clinical importance?(Wiley-Blackwell, 2008) Premawardhena, A.; Arambepola, M.; Katugaha, N.; Weatherall, D. J.Although the beta thalassaemia trait affects millions of people worldwide, there have been no controlled studies to determine whether it is associated with any clinical disability or abnormal physical signs. To address this question, 402 individuals were studied: 217 with beta thalassaemia trait, of whom 154 were aware of the diagnosis and 63 were unaware until after the completion of the study; 89 normal controls; and 96 controls with mild hypochromic anaemia. There was a significant increase in symptoms ascribable to anaemia and episodes of pyrexia in those with the beta thalassaemia trait that were not influenced by prior knowledge that they had this condition. There was no difference in physical findings, notably splenomegaly, between those with beta thalassaemia trait and either control groupItem Age-related changes in adaptation to severe anemia in childhood in developing countries(National Academy of Sciences, 2007) O Donnell, A.; Premawardhena, A.; Arambepola, M.; Allen, S.J.; Peto, T.E.; Fisher, C.A.; Rees, D.C.; Olivieri, N.F.; Weatherall, D.J.Severe forms of anemia in children in the developing countries may be characterized by different clinical manifestations at particular stages of development. Whether this reflects developmental changes in adaptation to anemia or other mechanisms is not clear. The pattern of adaptation to anemia has been assessed in 110 individuals with hemoglobin (Hb) E beta-thalassemia, one of the commonest forms of inherited anemia in Asia. It has been found that age and Hb levels are independent variables with respect to erythropoietin response and that there is a decline in the latter at a similar degree of anemia during development. To determine whether this finding is applicable to anemia due to other causes, a similar study has been carried out on 279 children with severe anemia due to Plasmodium falciparum malaria; the results were similar to those in the patients with thalassemia. These observations may have important implications both for the better understanding of the pathophysiology of profound anemia in early life and for its more logical and cost-effective management.Item 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 Haemoglobin E beta thalassaemia in Sri Lanka(Lancet Publishing Group, 2005) Premawardhena, A.; Fisher, C.A.; Olivieri, N.F.; de Silva, S.; Arambepola, M.; Perera, W.; O Donnell, A.; Peto, T.E.; Viprakasit, V.; Merson, L.; Muraca, G.; Weatherall, D.J.Haemoglobin E beta thalassaemia is the commonest form of severe thalassaemia in many Asian countries, but little is known about its natural history, the reasons for clinical diversity, or its management. We studied 109 Sri Lankan patients with the disorder over 5 years. 25 patients were not receiving transfusion; transfusion was stopped with no deleterious effect in a further 37. We identified several genetic and environmental factors that might contribute to the phenotypic diversity of the disorder, including modifiers of haemoglobin F production, malaria, and age-related changes in adaptive function. Our findings suggest that haemoglobin E beta thalassaemia can be managed without transfusion in many patients, even with low haemoglobin levels. Age-related changes in the pattern of adaptation to anaemia suggest that different and more cost-effective approaches to management should be explored.Item Thalassemia in Sri Lanka: a progress report(Oxford University Press, 2004) Premawardhena, A.P.; de Silva, S.; Arambepola, M.; Olivieri, N.; Merson, L.; Muraco, J.; Allen, A.; Fisher, C.A.; Peto, T.; Vichinsky, E.; Weatherall, D.J.The thalassemias pose an increasing burden for health-care services in many Asian countries. In order to conserve rare resources, it is essential to determine the reasons for the remarkable phenotypic heterogeneity and natural history of these disorders so that the most cost-effective methods for their control and management can be established. A long-term observational study of patients with different forms of thalassemia in Sri Lanka suggests that in addition to the well-defined primary, secondary and tertiary genetic modifiers, environmental factors, particularly malaria, and variation in the ability to adapt to the profound anaemia which characterizes these conditions, may play a significant role in determining their clinical severity. These findings may have important implications for the control and management of thalassemia in Asian populationsItem The Global distribution of length polymorphisms of the promoters of the gucuronosyltransferase I gene(UGTIAI): hematologic and evolutionary implications(Academic Press, 2003) Premawardhena, A.P.; Fisher, C.A.; Liu, Y.T.; Verma, I.C.; de Silva, S.; Arambepola, M.; Clegg, J.B.; Weatherall, D.J.The promoter region of the UDP glucuronosyltransferase 1 gene (UGT1A1) contains a run of thymine-adenine (TA) repeats, usually six (TA)(6). As well as its relationship to Gilbert's syndrome, homozygosity for the extended sequence, (TA)(7) (TA)(7), has been found to be an important risk factor for hyperbilirubinemia and gallstones in patients with hemoglobin E-beta-thalassemia and other intermediate forms of beta thalassemia. To assess the importance of this polymorphism in these common disorders a wide-scale population study of the relative frequency of the size alleles of the UGT1A1 promoter has been carried out. Homozygosity for the (TA)(7) allele occurs in 10-25% of the populations of Africa and the Indian subcontinent, with a variable frequency in Europe. It occurs at a much lower frequency in Southeast Asia, Melanesia, and the Pacific Islands, ranging from 0 to 5%. African populations show a much greater diversity of length alleles than other populations. These findings define those populations with a high frequency of hemoglobin E-beta-thalassemia and related disorders that are at increased risk for hyperbilirubinemia and gall bladder disease and provide evolutionary insights into how these polymorphisms have arisen and are so unequally distributed among human populations.