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 Nutrition in early life, immune-programming and allergies: the role of epigenetics(Allergy and Immunology Society of Thailand, 2013) Amarasekera, M.; Prescott, S.L.; Palmer, D.J.Early life nutritional exposures are significant determinants of the development and future health of all organ systems. The dramatic rise in infant immune diseases, most notably allergy, indicates the specific vulnerability of the immune system to early environmental changes. The associated parallel rise in metabolic diseases including obesity, childhood type 2-diabetes and non-alcoholic fatty liver disease highlights the interplay between modern dietary patterns and increasing abnormalities of both immune and metabolic health. The low-grade inflammation that characterize these non-communicable diseases (NCDs) suggests a central role of the immune system in the pathogenesis of these conditions. Understanding how environmental influences disrupt the finely balanced development of immune and metabolic programing is of critical importance. Diet-sensitive pathways are likely to be crucial in these processes. While epigenetic mechanism provides a strong explanation of how nutritional exposures can affect the fetal gene expression and subsequent disease risk, other diet-induced tissue compositional changes may also contribute directly to altered immune and metabolic function. Although modern dietary changes are complex and involve changing patterns of many nutrients, there is also interest in the developmental effects of specific nutrients such as folic acid levels, which have clear epigenetic effects on programming. Here we examine the current knowledge of the nutritional-programming of immune health and how research into nutritional-epigenetics in the context of allergic disease as one of the earliest onset NCDs can expand our knowledge to discover the biological processes sensitive to nutritional exposures in early life to prevent later disease risk.Item The Costs and cost-cffectiveness of mass treatment for intestinal nematode worm infections using different treatment thresholds(Public Library of Science, 2009) Hall, A.; Horton, S.; de Silva, N.BACKGROUND: It is estimated that almost a half of all of people living in developing countries today are infected with roundworms, hookworms, or whip worms or combinations of these types of intestinal nematode worms. They can all be treated using safe, effective, and inexpensive single-dose generic drugs costing as little as USD 0.03 per person treated when bought in bulk. The disease caused by intestinal nematodes is strongly related to the number of worms in the gut, and it is typical to find that worms tend to be aggregated or clumped in their distribution so that <20% of people may harbour >80% of all worms. This clumping of worms is greatest when the prevalence is low. When the prevalence rises above 50%, the mean worm burden increases exponentially, worms are less clumped, and more people are likely to have moderate to heavy infections and may be diseased. Children are most at risk. For these reasons, the World Health Organization (WHO) currently recommends mass treatment of children > or =1 year old without prior diagnosis when the prevalence is > or =20% and treatment twice a year when the prevalence is > or =50%. METHODS AND FINDINGS: The risk of moderate to heavy infections with intestinal nematodes was estimated by applying the negative binomial probability distribution, then the drug cost of treating diseased individuals was calculated based on different threshold numbers of worms. Based on this cost analysis, a new three-tier treatment regime is proposed: if the combined prevalence is >40%, treat all children once a year; >60% treat twice a year; and >80% treat three times a year. Using average data on drug and delivery costs of USD 0.15 to treat a school-age child and USD 0.25 to treat a pre-school child (with provisos) the cost of treating children aged 2-14 years was calculated for 105 low- and low-middle-income countries and for constituent regions of India and China based on estimates of the combined prevalence of intestinal nematode worms therein. The annual cost of the three-tier threshold was estimated to be USD 224 million compared with USD 276 million when the current WHO recommendations for mass treatment were applied. CONCLUSION: The three-tier treatment thresholds were less expensive and more effective as they allocated a greater proportion of expenditures to treating infected individuals when compared with the WHO thresholds (73% compared with 61%) and treated a larger proportion of individuals with moderate to heavy worm burdens, arbitrarily defined as more than 10 worms per person (31% compared with 21%).Item A Review and meta-analysis of the impact of intestinal worms on child growth and nutrition(Wiley-Blackwell, 2008) Hall, A.; Hewitt, G.; Tuffrey, V.; de Silva, N.More than a half of the world's population are infected with one or more species of intestinal worms of which the nematodes Ascaris lumbricoides, Trichuris trichiura and the hookworms are the most common and important in terms of child health. This paper: (1) introduces the main species of intestinal worms with particular attention to intestinal nematodes; (2) examines how such worms may affect child growth and nutrition; (3) reviews the biological and epidemiological factors that influence the effects that worms can have on the growth and nutrition of children; (4) considers the many factors that can affect the impact of treatment with anthelmintic drugs; (5) presents the results of a meta-analysis of studies of the effect of treating worm infections on child growth and nutrition; (6) discusses the results in terms of what is reasonable to expect that deworming alone can achieve; (7) describes some important characteristics of an ideal study of the effects of deworming; and (8) comments on the implications for programmes of recommendations concerning mass deworming.Item A Novel molecular basis for beta thalassemia intermedia poses new questions about its pathophysiology(American Society of Hematology, 2005) Premawardhena, A.; Fisher, C.A.; Olivieri, N.F.; de Silva, S.; Sloane-Stanley, J.; Wood, W.G.; Weatherall, D.J.During a study of the molecular basis for severe forms of beta thalassemia in Sri Lanka, 2 patients were found to be heterozygous for beta thalassemia mutations. Further analysis revealed that one of them has a previously unreported molecular basis for severe thalassemia intermedia, homozygosity for quadruplicated alpha globin genes in combination with heterozygous beta thalassemia. The other is homozygous for a triplicated alpha globin gene arrangement and heterozygous for beta thalassemia. Their differences in clinical phenotype are explainable by the interaction of other genetic factors and, in particular, their early management. The clinical course of the 2 propositi underlines the importance of full genotyping and a long period of observation before treatment is instituted, particularly in patients with beta thalassemia intermedia associated with extended alpha globin gene arrangements. The hemoglobin (Hb) F levels in these patients with severe beta thalassemia intermedia, compared with other forms of this condition in the Sri Lankan population and elsewhere, are unusually low, a consistent finding in extended alpha globin gene interactions and in dominant beta thalassemia, raising the possibility that increased levels of HbF production in beta thalassemia may require mutations at both beta globin gene loci