Browsing by Author "Peto, T."

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    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.
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    The Evolutionary and clinical implications of the uneven distribution of the frequency of the inherited haemoglobin variants over short geographical distances
    (Wiley-Blackwell, 2017) Premawardhena, A.; Allen, A.; Piel, F.; Fisher, C.; Perera, L.; Rodrigo, R.; Goonathilaka, G.; Ramees, L.; Peto, T.; Olivieri, N.; Weatherall, D.
    Studies of the frequency of heterozygous carriers for common inherited diseases of haemoglobin in over 7500 adolescent children in 25 districts in Sri Lanka have disclosed a highly significant variation over very short geographical distances. A further analysis of these findings, including their relationship to the past frequency and distribution of malaria, climatic variation, altitude, ethnic origin and consanguinity rates, have provided evidence regarding the evolutionary basis for the variable distribution of these conditions over short distances. It is likely that the complex interplay between malaria and the environment, together with related ethnic and social issues, exists in many countries across the tropical belt. Hence, these observations emphasise the importance of micromapping heterozygote distributions in high-frequency countries in order to define their true burden and the facilities required for the prevention and management of the homozygous and compound heterozygous disorders that result from their interaction.
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    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.
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    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.
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    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 populations