Medicine
Permanent URI for this communityhttp://repository.kln.ac.lk/handle/123456789/12
This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
Browse
27 results
Search Results
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 Chracterisation of beta giobin mutations in Sri Lankan patients with betathalassaemia intermedia(Sri Lanka Medical Association, 2013) Perera, S.; Silva, D.P.S.I.; Hapugoda, M.; Wickramarathne, M.N.; Wijesirwardhena, I.; Efremove, D.G.; Fisher, C.A.; Weatherall, D.J.; Premawardhena, A.P.INTRODUCTION AND OBJECTIVES: Patients with beta thalassaemia intermedia account for a third of patients attending thalassaemia clinics in Sri Lanka. They show immense phenotypic diversity, the genetic basis for which has not been identified so far. Objective were to characterise beta globin gene mutations in Sri Lankan thalassaemia intermedia patients and to determine how it to influences disease severity. METHODS: We identified 64 thalassaemia intermedia patients from the five main thalassaemia centers; Anuradhapura (n= 6), Kuruncgala (n= 4), Ragama (n= 42), Badulla (n=7) and Chilaw (n=5). Their beta globin DNA sequences were analyzed using ABI PRISM 313lx genetic analyser. RESULTS: Of sixteen patients identified to be homozygous for beta mutations, eleven carried mild beta alleles, IVSI 5 G_C (n= 10) and a rare homozygous promoter mutation - 90 C_T (N=l). Other five were shown to have different types of severe iputations in homozygous state. Nearly half the sample (n=39) was heterozygous for beta mutations. Of them 33 showed mild to severe mutation in one of the alleles IVSI-5 G_C (n=12), IVSI-1 G_A (n= 11) were the commonest. Two patients who were hetcrozygones for beta mutation had a highly unstable Hb variant haemoglobin Mizuho causing severe haemolytic anacma. Hb variants Hb G-Szuhu and Hb G-Coushatta were identified in two patients. CONCLUSIONS: We identified types of beta mutations in some patients with thalassaemia intermedia, which account for the clinical severity.Item Paraspinal extramcduallry erythropoiesis- a rare cause of spinal cord compression: two case reports(Sri Lanka Medical Association, 2004) Arambepola, M.; Premawardhena, A.P.; de Silva, S.; Olivieri, N.; Weatherall, D.J.INTRODUCTION: Extrameduallry erythropoiesis (EME) is characterized by the appearance of haemopoietic tissue outside the bone marrow. When EME occurs, albeit rarely, outside the liver and spleen problems may occur. We describe two patients with haemoglobin E- [β thalassaemia who had spinal cord compression, due to EME masses which was reversed with treatment with hydroxyurea and hypertransfusion. PATIENT A: Was a 27year old with HbE -(β thalassaemia. His mean pre transfusion haemoglobin level was 5.5 g/dl. He presented with a six-month history of progressive numbness of his legs. On examination he was found to be paraparetic. The magnetic resonance scan (MRI) showed external compression of the spinal cord between the 4th and 8th thoracic vertebrae. Patient was put on a hypertransfusion regimen and hydroxyurea and made a complete recovery within 4 weeks. Patient B: Was a 9 year old boy with a diagnosis of Haemoglobin E [β thalassaemia who presented with paraplegia which had developed over 3 months. His spinal MRI showed two masses one in the upper thoracic vertebrae and the other at the 1st lumbar level. He was commenced on hydroxyurea and hypertransfusiion to maintain pre-transfusion haemoglobin at >9.5g/dl) and his neurological recover was remarkable. Six months later he had no neurological deficit. DISCUSSION: The above cases highlight the potentially dangerous complications of EME when it involves the spinal cord. They also highlight that even lesions which are sufficiently large to cause complete paraplegia are potentially reversible. Hypertransfusion, hydroxyurea, surgery and previously been used with varying success. The problem remains in deciding the optimal method of management.Item Transfusion-transmitted Hepatitis C: A cluster of cases in transfusion-dependent Thalassaemia patients in Sri Lanka(Blackwell Scientific Publications,, 2020) Perera, S.; Bonsall, D.; Niriella, M.A.; Allen, A.; Peries, A.C.; Nelumdeniya, U.B.; Dissanayake, R.; Silva, I.; de Cesare, M.; Klenerman, P.; Weatherall, D.J.; Roberts, D. J.; Premawardhena, A.P.OBJECTIVES: To report the clinical and virologic epidemiology of a recent epidemic of hepatitis C in thalassaemia patients in Sri Lanka. BACKGROUND: Transfusion-dependent thalassaemia patients remain at risk for hepatitis C virus (HCV). Here, we report a cluster of recent HCV infections in Sri Lankan thalassaemia patients and examine the phylogenetic relationship of viral sequences. METHODS: We conducted two prospective cross-sectional surveys of 513 patients in four Sri Lankan thalassaemia centres in 2014/2015 and re-surveyed one centre in 2016. We screened for anti-HCV antibodies using the CTK Biotech enzyme-linked immunosorbent assay (ELISA) kits and confirmed active infection by reverse transcription-polymerase chain reaction (RT-PCR) for HCV-RNA. HCV genomes were sequenced by unbiased target enrichment. RESULTS: Anti-HCV antibodies were found in 116/513 (22.6%) of patients initially tested. Active hepatitis C infection was found in 26 patients with no cases of active hepatitis B infection. Of 26 patients with HCV, two were infected with genotype 1(a), and the rest had 3(a). In a single centre (Ragama), 122 patients (120 new cases and two previously tested, but negative) were retested for anti-HCV antibodies. 32/122 (26.2%) patients were seropositive. Twenty-three (23/122; 18.8%) of these new cases were confirmed by HCV PCR (all genotype 3[a]). CONCLUSIONS: There is a significant cluster of recent HCV cases in multiply transfused thalassaemia patients in several centres in Sri Lanka. Most of the viruses shared a close phylogenetic relationship. The results are consistent with recent continuing transfusion-transmitted HCV infection. Routine surveillance for HCV of chronically transfused patients is required irrespective of screening of blood products.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.Item An islandwide hospital based epidemiological survey of haemoglobinopathies and an assessment of standards of care in 23 centres(Sri Lanka Medical Association, 2017) Premawardhena, A.P.; Mudiyanse, R.M.; Jifri, M.N.; Nelumdeniya, U.B.P.; Silva, D.P.S.I.; Nizri, A.H.M.; Rajiyah, M.O.F.; de Silva, T.U.N.; Pushpakumara, K.R.C.; Dissanayake, D.M.R.; Jansz, M.; Rifaya, M.I.; Navarathne, N.M.U.S.B.; Arambepola, W.W.M.M.; Thirukumaran, V.; Mendis, D.; Weerasekara, K.P.; de Silva, N.N.; Vaidyanatha, U.S.de.S.; Mettananda, D.S.G.; Oliveri, N.F.; Weatherall, D.J.INTRODUCTION & OBJECTIVES: There is no database for haemoglobinopathy patients in Sri Lanka resulting in imprecise knowledge about the distribution and standards of care among patients managed in different centres in the island. The prevention programme commenced in 2007 is not centrally monitored. METHODS: We carried out centre-wise visitation and data gathering of patients with haemoglobinopathies in 2015. 23 centres were visited by researchers who gathered information from patient records. RESULTS: Data was obtained of 1768 patients. Three centres had over 200 patients each and another three centres had between 50-100 patients. There were 8 centres with less than 10 patients each. Beta thalassaemia major (BTM) accounted for 1207 (68.26%) patients. There were 363 patients (20.53%) with Haemoglobin E-β thalassaemia. Sickle cell-β thalassaemia accounted for 51 patients (2.88%). The mean age of BTM patients was 13 years (range 2-44). Ethnic distribution of the haemoglobinopathies (82.5% Sinhalese, 12% Muslims and 5.2% in Tamils) was discrepant to the national ethnic data. Islandwide mean number of new births of all thalassaemics recorded showed a reduction from 66/year between 2004 - 2009 to 48/year between 2010 to 2015.Clinical record keeping was not systematic in most units thus complication rates were hard to obtain. Death data were available only in two units. CONCLUSION: This study identified significant inconsistencies in haemoglobinopathy care between centres. Existence of small centres needs to be recognized by the Ministry of Health. A reducing trend of new births over the last decade was observed.Item “Silent” white matter changes in brain MRI in patients with haemoglobinopathies and their clinical significance(Sri Lanka Medical Association, 2016) Premawardhena, A.P.; Ranawaka, U.R.; Hapangama, A.; Pathmeswaran, A.; Hettiarachchi, S.; Salvin, K.A.; Pilapitiya, T.; Sanjaya, G.; Oilvieri, N.F.; Weatherall, D.J.INTRODUCTION AND OBJECTIVES: Increasing interest has been directed to the study of white matter changes and lacunar infarcts in patients with haemoglobinopathies which are thought to be clinically silent. Previous studies suggest an association with splenectomy and thrombocytosis. The objective was to assess the association of white matter changes in patients with haemoglobinopathies. METHOD: Older patients with haemoglobinopthies attending the Hemals Thalassaemia Unit were assessed by a specialist neurologist and simultaneously had MRI brain. Relevant clinical, biochemical and hematological data were collected. A non-thalassaemic control group (age and sex matched) too were assessed. RESULTS: There were 82 patients (25 Thalassaemia Major,24 Intermedia and 33 Haemoglobin E b thalassaemia) and 19 controls. Mean age of the study group was 32yrs. 21 patients (26%) had MRI changes (20%,29%,27% in the three groups respectively) (p=0.73). 10% of controls had MRI changes. 12 (60%) of the patients with MRI changes were asplenic whilst 53.2% without changes were asplenic (P=0.138). There was no difference in the two groups with platelet counts. (Mean platelet count 581 Vs. 452 (p= 0.709) 58% of patients and 53% of controls had headache as a symptom. Headache was commoner among those with MRI changes (85% vs 51.6%; p=0.008). CONCLUSIONS: The white matter changes in MRI occurred in all three sub groups of thalassaemic patients studied in high frequency. To our knowledge, this is the first report of the association of MRI changes with neurological symptoms in thalassaemic patients. The higher frequency of headache in those with MRI changes suggest that these changes may not be silent as previously believed.Item The clinical effects of excessive a globin genes : two family studies(Sri Lanka Medical Association, 2003) Premawardhena, A.P.; Fisher, C.A.; Rugless, M.; de Silva, S.; Perera, A.W.V.S.; Olivien, N.F.; Weatherall, D.J.INTRODUCTION: Globin chain imbalance is the central pathogenic abnormality in the thalassaemias, a condition where globin gene expression is reduced. Conversely, the inheritance of excess globin genes too may affect the phenotype. However such examples are rarely found. OBJECTIVES: To describe two families in whom the co-existence of excess a genes was noted together with p - thalassaemia trait. METHODS: During the routine P - globin gene analysis in patients attending the Thalassaemia Unit of the Kurunegala Hospital, two patients were identified to have thalassaemia intermedia phenotype, but with just one (3 - thalassaemia mutation. The clinical details of these patients and their families were studied in detail as was their h'aematological and genetic data. RESULTS: We describe two families in which the propositus had inherited six and eight a - genes respectively together with a single p - thalassaemia mutation. Both patients had the thalassaemia intermedia phenotype. The family members who did not inherit any thalassaemic mutations too had varying, but often marked hypochromic microcytosis. DISCUSSION: We describe the first ever family study of a patient with the combination of 8 a - genes and p - thalassaemia trait. We also describe another family where a member had 6 a - genes together with p thalassaemia trait. This highlights yet another mechanism for the intermedia phenotype in patients with a solitary (3 - globin gene mutation. It also highlights the need for the study of a globin genes in patients with unexplained hypochromic microcytic anaemia.Item The worldwide prevalence of the UGT-1A1 promoter polymorphism as a contributor for phenotypic variability in thalassaemia(Sri Lanka Medical Association, 2003) Premawardhena, A.P.; Lilt, Y.T.; Fisher, C.A.; Clegg, J.B.; Weatherall, D.J.INTRODUCTION: The number of TA repeats in the promoter region of the UGTIA1 gene is involved in fine-tuning of the serum bilirubin level. People who inherit more TA repeats than in the wild type (6), tend to have higher than normal Serum bilirubin levels. When homozygosity for 7 repeats is co-inherited with hereditary anaemias the patients have an elevated serum bilirubin level and an increased incidence of gallstone formation. OBJECTIVES: To investigate the pattern of UGTIAI promoter genotype in several diverse populations across the world. METHODS: A fluorescent labeled PCR method was designed which would amplify the region of interest of the UGTIAI gene. The PCR products were separated using (PAGE) polyacrelymide gel electrophoresis. DNA samples for the study were collected from people from 15 countries, from 5 continents. RESULTS: We found remarkable diversity of the UGTIAI polymorphism amongst people of African origin. The haplotype 7/7 was found in very high frequencies in India. Sri Lanka and Bangladesh, and was extremely rare amongst people of Southeast Asian origin. The Europeans and the Africans had intermediate frequencies. DISCUSSION: These results suggest that in people of Southeast Asian origin, a group that has a high prevalence of thalassaemia and other heamoglobinopathies, the UGTIAI polymorphisms are unlikely to be important genetic modifiers of the phenotype. However, Sri Lankans and other South Asians are very likely to be influenced by this polymorphism. These results also support the theory of African origins of Homo sapiens.Item Response of jaundice to phenobarbitone in thalassaemic patients co-inheriting Gilbert syndrome(Sri Lanka Medical Association, 2004) Premawardhena, A.P.; Arambepola, M.; Fisher, C.A.; Oliveiri, N.F.; Weatherall, D.J.INTRODUCTION: Genetic mutations causing Gilbert's syndrome are found in up to 20% of Sri Lankans. The co-existence of Gilbert's syndrome together with haemolytic anaemias can lead to significantly higher level of serum bilirubin and also an increased risk of gall stone formation. In such patients persistent jaundice can be a distressing symptom. We used the hepatic enzyme inducer, phenobarbitone in a pilot study to treat symptomatic hyperbilirubinaemia in patients with haemoglobin E- p thalassaemia and Gilbert' syndrome. MATERIAL AND METHODS: Seven haemoglobin E (3 thalassaemia patients attending the Thalassaemia Unit of the Teaching Hospital Kurunegala in whom jaundice was a significant symptom and Gilberts syndrome mutations had been previously detected were started on phenobarbitone (15mg tds). No patients with predominant direct hyperbilirubinaemia were included in this study. Bilirubin levels were noted prior to the commencement of the study and were repeated 3 months later. RESULTS: Of the 110 patients with haemoglobin E [3 thalassaemia 26 were positive for the Gilberts syndrome mutation. Seven patients were concerned about the excessive yellow discoloration of their sclerae and skin. Their ages ranged from 15 to 24 years. The mean pre-treatment serum total and indirect bilirubin were 137.8 and 113.8 /xmol/1 and the post treatment mean 68.35 and 52.6 jimol/1 respectively (a mean reduction of 49%). The biochemical result was associated with a remarkable clearance of jaundice. The quality of life of these patients significantly improved as a result. There were no drop outs from the study and no side effects were noted in any of the participants. DISCUSSION: Phenobarbitone used at 15 mg tds seems an effective and safe method for treating the aesthetically unacceptable symptom of jaundice in patients with Gilberts syndrome. The lack of complete normalisation of the bilirubin levels may suggest the effect of the underlying haemolysis, the inadequacy of the dosage of phenobarbitone or the co-existence of mutations causing non-inducible hyperbilirubinaemia.
- «
- 1 (current)
- 2
- 3
- »