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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Hydroxyurea for transfusion dependent β-thalassaemia: A randomized double-blind placebo-controlled clinical trial(Sri Lanka Medical Association, 2021) Yasara, N.; Wickramarathne, N.; Silva, I.; Hameed, N.; Attanayaka, A.M.K.R.; Jayasinghe, V.L.; Gunathilaka, P.A.C.K.; Wickramasinghe, N.; Rodrigo, R.; Perera, L; Perera, P.S.; Mettananda, K.C.D.; Manamperi, A.; Premawardhena, A.; Mettananda, S.Introduction and objectives Hydroxyurea induces fetal haemoglobin in vitro however, its clinical usefulness in β-thalassaemia is unclear. Here, we aim to assess the efficacy and safety of oral hydroxyurea in patients with transfusion dependent β-thalassaemia. Methods A phase 3 randomized double-blind placebo-controlled clinical trial was conducted at Colombo North Teaching Hospital in 2019/20. Sixty patients with transfusion dependent β-thalassaemia were randomized into hydroxyurea (10-20mg/kg/day) or placebo groups. Transfused blood volume, pre-transfusion haemoglobin, fetal haemoglobin and adverse effects were monitored during 6-month treatment and post-treatment periods. The study was approved by the ethics committee of University of Kelaniya and registered in Sri Lanka Clinical Trials Registry (SLCTR/2018/024). Results Fifty-four (hydroxyurea-27; placebo-27) patients completed the trial. Mean pre-transfusion haemoglobin (8.2±0.8g/ dLvs8.0±0.88g/dL, p=0.43) and fetal haemoglobin levels (7.9±11.2%vs4.6±4.3%, p=0.17) were higher in hydroxyurea group compared to placebo. Also, transfused blood volume was lower in the hydroxyurea group (94±29ml/kgvs102±28ml/kg, p=0.34). However, none were statistically significant. Based on elevation of fetal haemoglobin (>1.5% from baseline), we identified 12/27 patients who respond well to hydroxyurea (hydroxyurea-responders). Hydroxyurea-responders required significantly lower blood volume (77±27ml/kg) compared to non-responders (108±24ml/kg, p<0.01) and placebo group (102±28ml/kg, p<0.05). HbE β-thalassaemia sub-type (p<0.01) and Xmn1 polymorphism of γ-globin gene (p<0.05) were significant predictors of response to hydroxyurea. No serious side effects due to hydroxyurea were reported. Conclusion Over 40% of patients with transfusion dependent β-thalassaemia- specifically those with HbE β-thalassaemia and Xmn1 polymorphism of γ-globin gene- responded to hydroxyurea and required 25% less blood compared to controls. No serious adverse effects were reported following hydroxyurea treatment.Item Efficacy and Safety of Oral Hydroxyurea in Patients with Transfusion Dependent β Thalassaemia: a Randomized Double-Blind Placebo-Controlled Clinical Trial(Sri Lanka Medical Association, 2020) Yasara, N.; Wickramarathne, N.; Silva, I.; Hameed, N.; Attanayaka, A.M.K.R.; Jayasinghe, V.L.; Wickramasinghe, N.; Rodrigo, R.; Perera, L.; Mettananda, K.C.D.; Manamperi, A.; Premawardhena, A.; Mettananda, S.INTRODUCTION AND OBJECTIVES: Patients with β- thalassaemia require blood transfusions and iron chelation for life. Hydroxyurea is a licenced medication for sickle cell disease but its usefulness in transfusion dependent β-thalassaemia is unclear. Here, we aim to assess the efficacy and safety of oral hydroxyurea in patients with transfusion dependent β-thalassaemia. METHODS: A phase III randomized double-blind placebo-controlled clinical trial was conducted at Thalassaemia Unit of Colombo North Teaching Hospital in 2019. Forty-one patients with transfusion dependent β-thalassaemia were randomized into hydroxyurea (10-20mg/kg/day) or placebo (pharmaceutically inert capsule identical to hydroxyurea) groups. Transfused blood volume, pre-transfusion haemoglobin, haemoglobin F level and side effects were monitored monthly during 6- month treatment and 6-month follow-up periods. Adverse events were assessed by trained medical officers. The study was approved by ethics committee of University of Kelaniya and registered in Sri Lanka Clinical Trials Registry (SLCTR/ 2018/024). RESULTS: Of the 41 (hydroxyurea-20; placebo-21) patients, three discontinued treatment due to thrombocytopenia (hydroxyurea-2) and rash (placebo-1). Baseline characteristics of two groups were similar. Mean pre-transfusion haemoglobin (8.52+0.57 vs 8.38+0.55, p=0.45) and haemoglobin F levels (4.3+7.1% vs 3.1+1.9%, p=0.48) were higher in hydroxyurea group compared to placebo. Also, transfused blood volume was lower in hydroxyurea group (102+24ml/kg vs 111+27ml/kg, p=0.3). However, none were statistically significant. Based on elevation of haemoglobin F (>1.5% from baseline), we identified 6/18 patients as hydroxyurea responders. Hydroxyurea responders required significantly lower blood volume (87+13ml/kg) compared to non-responders (110+25ml/kg, p=0.05) and placebo group (111+27ml/kg, p<0.05) while maintaining higher pre-transfusion haemoglobin level (8.6+0.5 vs 8.4+0.5 and 8.3+0.5). No serious side effects were reported. CONCLUSIONS: One-third of patients with transfusion dependent β-thalassaemia responded to hydroxyurea treatment requiring 20% less blood compared to controls. No serious side effects were reported following hydroxyurea treatment.Item Community prevalence of childhood asthma and atopy(Sri Lanka Medical Association, 2005) Perera, K.P.J.; Rathnayake, A.; Wickramasinghe, N.; Muthukumarana, S.OBJECTIVES: To estimate prevalence of childhood asthma, allergic rhino conjunctivitis and eczema in the community using an interviewer administered questionnaire. To estimate the extent of prophylaxis usage in asthma. SETTINGS: A cross sectional descriptive study in 2003. METHOD: Sample consists of children between 6 months to 13 years (n=2005) in 4 PHM areas randomly selected from Ragama. Diagnosis was based on presence of symptoms in preceding 12 months. Information gathered using a pre-tested questionnaire. Study was ethically approved. Data analysis - Epi Info version 6. RESULTS: Mean age was 6.7 years and 52% were males. Asthma prevalence was 13%. Prevalence in infancy - 4%, 1-5 years -13%, 5-10 years - 15% and 10- 13 years - 11%. Prevalence in males -14%. In females -11% (p=0.03). Lifetime prevalence - 19%. Current wheezing rate - 1.6%. Prevalence of allergic rhinitis - 5%, allergic conjunctivitis 3% and eczema 0.8%. Of all asthmatics, 70% were mild intermittent, 23% mild persistent and 7% moderate persistent. 49% of those who required prophylaxis were already on prophylaxis. Of them, 92% on steroid inhalers. CONCLUSIONS: Prevalence of asthma and allergic rhinitis and eczema are less than when reported by parents (Parent reported prevalence were 23%, 11% and 3% respectively). The majority of asthma was mild intermittent type. Usage of prophylactic medications was nearly 50%.Item Vulvitis granulomatosa, Melkersson-Rosenthal syndrome, and Crohn's disease: dramatic response to infliximab therapy(Wiley-Blackwell, 2012) Wickramasinghe, N.; Gunasekara, C.N.; Fernando, W.S.; Hewavisenthi, J.; de Silva, H.J.No Abstract AvailableItem Effect of Artocarpus heterophyllus and Asteracanthus longifolia on glucose tolerance in normal human subjects and in maturity-onset diabetic patients(Elsevier, 1991) Fernando, M.R.; Wickramasinghe, N.; Thabrew, M.I.; Ariyananda, P.L.; Karunanayake, E.H.Investigations were carried out to evaluate the effects of hot-water extracts of Artocarpus heterophyllus leaves and Asteracanthus longifolia whole plant material on the glucose tolerance of normal human subjects and maturity-onset diabetic patients. The extracts of both Artocarpus heterophyllus and Asteracanthus longifolia significantly improved glucose tolerance in the normal subjects and the diabetic patients when investigated at oral doses equivalent to 20 g/kg of starting material.Item A Preliminary investigation of the possible hypoglycaemic activity of Asteracanthus longifolia(Elsevier, 1989) Fernando, M.R.; Wickramasinghe, N.; Thabrew, M.I.; Karunanayaka, E.H.Investigations were carried out to confirm or otherwise disprove the view held by many Ayurvedic and other traditional medical practitioners in Sri Lanka, that Asteracanthus longifolia possesses hypoglycaemic properties. The effects of an aqueous extract of the whole plant on fasting blood glucose level and glucose tolerance were investigated using Sprague-Dawley rats. The results indicate that aqueous extracts of A. longifolia can significantly lower the fasting blood glucose level and markedly improve the glucose tolerance of the rats. The hypoglycaemic effect produced by a therapeutic dose (equivalent to 5 g/kg of starting material) was comparable to that produced by a therapeutic dose (15 mg/kg of tolbutamide. The magnitude of the hypoglycaemic effect was found to vary with the dosage administered and the storage time of the prepared extract.