Browsing by Author "Perera, P.S."

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Anemia in Sri Lanka: A literature review
(Informa Healthcare, 2022) Amarasingha, A.A.D.S.; Silva, H.J.R.L.; Perera, P.S.; Premawardhena, A.P.
Anemia is a global health problem. This paper reviews literature on the prevalence of anemia in Sri Lanka. We searched EBSCO (Elton Bryson Stephens Company), Cochrane Library, and Medline for articles on prevalence and molecular basis of anemia in Sri Lanka from January 2000 to May 2021. Forty articles were selected. Most of the studies were on prevalence of anemia among children and pregnant women. All the studies had restricted themselves to assess the contributing factors for anemia in limited age categories. Most articles had attempted to determine the overall prevalence of anemia and the contribution of iron deficiency to it. There were only a few studies on prevalence and molecular basis of hemoglobinopathies and even fewer on the prevalence of anemia of chronic disease. None of the studies had attempted to assess the national prevalence of red cell membranopathies and enzymopathies. The published data on prevalence of anemia in Sri Lanka are incomplete. This review emphasizes the value of a much broader survey on anemia covering all age categories including the elderly and conducting a national survey including anemia of chronic disease and on red cell membranopathies and enzymopathies in Sri Lanka.
Cardiovascular risk profile of the estate population of Sri Lanka
(Sri Lanka Medical Association, 2010) Pinidiyapathirage, M.J.; Chackrewarthy, S.; Perera, P.S.; Wijayasinghe, Y.S.; Williams, S.; Williams, S.S.; Kato, N.; Wickremasinghe, A.R.
OBJECTIVES: To estimate the prevalence of biochemical and anthropometric risk markers of cardiovascular diseases in the estate population of Sri Lanka. METHODS: Using a cross sectional design, consenting adults aged 35-64 years resident in 3 selected estates in the Nuwara-Eliya District were recruited with the support of estate medical assistants and welfare officers. AH participants were subjected to an interview, blood pressure and anthropometric measurements and collection of fasting blood samples. RESULTS: Of the 401 participants recruited, 53% were females and 99% were cither Indian or Sri Lankan Tamils. The mean age of the participants was 50.3 years (SD 8.5). 47 (12%) participants had a BMI >25, 8 (2%) a BMI >30. 29 males (15%) and 29 females (14%) had a waist circumference [WC] >90cm and >80 cm, respectively. 151 (38%) participants had systolic blood pressure (SBP) > 140mmHg , 127 (32%) had diastolic blood pressure (DBF) > 90mmHg and 170 (42%) had either SBF > 140 or DBF > 90. 41(10%) participants had fasting blood glucose (FBG) >126mg/dL. In 197 (49%) participants, some form of dyslipidaemia was present. Males had a significantly higher mean BMI, FBG and triglyceride (TG) level and a significantly lower high density lipoprotein (HDL) level as compared to females. CONCLUSIONS: Obesity, as defined by BMI or WC, was low in this population as compared to other reported studies from different population groups in the country. But prevalence of hypertension and dyslipidaemia (especially high TG and low HDL levels in males) was high.
Clinical and molecular heterogeneity among Beta Thalassaemia Intermedia in Sri Lanka
(Sri lanka Medical Association, 2015) Perera, P.S.; Silva, D.P.S.I.; Hapugoda, M.; Wickramarathne, M.N.; Wijesiriwardena, I.; Efremov, D.G.; Fisher, C.A.; Weatherall, D.J.; Premawardhena, A.
INTRODUCTION AND OBJECTIVES: Patients with beta thalassaemia intermedia (Tl) unrelated to haemoglobin E/beta thalassaemia account for an important minority in thalassaemia clinics in Sri Lanka. We investigated the genotypic/phenotypic diversity of this small group of patients. METHOD: Fifty Tl patients identified from five thalassaemia centers were clinically assessed and divided in to severity groups based on agreed criteria. Genetic analysis was done by PCR based techniques. RESULTS: There were 26 mild, 12 moderate and 12 in the severe groups. Ages ranged from 5-65 years. Mean haemoglobin of the whole group was 7.8g/dl. Age at presentation ranged from 3 months - 57 years (mean 16.8yrs) and varied according to severity; 17.8 years in mild to 4.8 years in severe group. 86% were on intermittent transfusions whilst 14% were never transfused. Mean total transfusion load in the three groups ranged from 6, 28 to 89. Majority (60%) had splenomegaly and 12% were splenectomised. The median spleen size of each severity group was 0, 4.5 and 7.5 cm respectively. Thalassaemicfacial features were not_ demonstrable in the majority (86%). Genetic analysis identified the commonest mechanism for Tl to be coexistence of a single beta mutation with excess alpha genes (56%). None of these patients had severe phenotype. Coexistence of two beta mutations with alpha thalassaemia invariably gave rise to severe phenotype. Other mechanisms gave rise to varying disease severity. CONCLUSION: This study highlights the remarkable phenotypic variations in beta Tl in Sri Lanka and identifies some genetic mechanisms which can explain this variation.
Correlation of genotype with phenotype in beta thalassaemia intermedia in Sri lanka
(Thalassaemia International Federation, 2015) Perera, P.S.; Silva, D.P.S.I.; Hapugoda, M.; Wickramarathne, M.N.; Wijesiriwardena, I.; Efremov, D.G.; Fisher, C.A.; Weatherall, D.J.; Premawardhena, A.
Abstract Available
Further characterization of Hemopressin Peptide fragments in the opioid and cannabinoid systems
(Cleveland, International Anesthesia Research Society, 2015) Szlavicz, E.; Perera, P.S.; Tomboly, C.; Helyes, Z.; Zador, F.; Benyhe, S.; Borsodi, A.; Bojnik, E.
BACKGROUND: Hemopressin, so-called because of its hypotensive effect, belongs to the derivatives of the hemoglobin α-chain. It was isolated from rat brain membrane homogenate by the use of catalytically inactive forms of endopeptidase 24.15 and neurolysin. Hemopressin has antihyperalgesic features that cannot be prevented by the opioid receptor antagonist, naloxone. METHODS: In the present study, we investigated whether hemopressin (PVNFKFLSH) and its C-terminally truncated fragment hemopressin 1-7 (PVNFKFL) have any influence on opioid-dependent signaling. Peptides have been analyzed using G-protein-stimulating functional and receptor bindings in this experimental setup. RESULTS: These 2 compounds efficiently activated the G-proteins, and naloxone slightly blocked this stimulation. At the same time, they were able to displace radiolabeled [H]DAMGO, a selective ligand for μ-opioid system, at micromolar concentrations. Displacement caused by the heptapeptide was more modest compared with hemopressin. Experiments performed on cell lines overexpressing μ-opioid receptors verified the opioid activity of both hemopressins. Moreover, the CB1 cannabinoid receptor antagonist, AM251, significantly decreased their G-protein stimulatory effect. CONCLUSIONS: Here, we further confirm that hemopressins can modulate CB1 receptors and can have a slight modulatory effect on the opioid system.
HCV and HBV infection among a cohort of Sri Lankan thalassaemic patients
(Sri Lanka Medical Association, 2015) Perera, P.S.; Niriella, M.A.; Peries, M.A.C.; Nelumdeniya, U.B.; Dissanayake, D.M.R.; de Silva, D.S.I.; de Silva, H.J.; Premawardhena, A.P.
INTRODUCTION AND OBJECTIVES: Previous studies suggest that prevalence of hepatitis C (HCV) and hepatitis B (HBV) virus infections is low in Sri Lanka. Patients with severe thalassaemia are at risk of developing blood borne infections like HBV and HCV. While HBV can be prevented by vaccination, safe blood donor screening practices is the best preventive strategy for HCV. Nationwide HCV blood donor screening was commenced in Sri Lanka in 2009. We studied tne prevalence of HBV and HCV Infections among a Sri Lankan cohort of thaiassaemic patients. Method: All consenting patients with J^JJJfusion dependent thalassaemia in Anuradhapura, Ragama, Baduila, Chilaw centers were screened for HBV and HCV by HBsAg and Anti-HCV antibodies respectively. Those positive during screening for HBV and HCV were confirmed by HBV-DNA and HCV-RNA PCR respectively. Results: A total of 513 patients were tested (Anuradhapura-210, Ragama-184, Badualla-70, Chilaw-49). There were no cases of HBV infection. Anti-HCV antibodies were positive in 97(45.2%), 14(7.6%), 5(7.1%), 0 in the four centres respectively, HCV was confirmed in 32 {15.2%}, 4 (2.2%), 1 (1.4%), 0 patients in the four centres. 2/4 patients from Ragama and the patient from Badualla had blood transfusions from Anuradhapura prior to changing care to present centre. HCV positive patients age ranged from 5-21 years (mean 12.5). Total transfusions ranged from 49-312. CONCLUSION: This is the first report of high HCV prevalence in a specific group to be reported from Sri Lanka, The high prevalence from a single centre (Anuradhapura} is alarming and reasons for this needs urgent investigation.
Hepatitis B and Hepatitis C virus infections among patients with chronic kidney disease from two presumed high-risk centers
(Sri Lanka Medical Association, 2018) de Silva, S.T.; Perera, P.S.; Anuruddhika, H.W.D.; Dassanayake, R.; Niriella, M.A.
INTRODUCTION AND OBJECTIVES: Community prevalence ofhepatitis-C (HCV) and hepatitis-B (HBV) infection is low in Sri Lanka. Patients with chronic kidney disease (CKD) are at high-risk for HBV and HCV infections. We determined the prevalence and risk factors for HBV and HCV among CKD patients in two Teaching Hospitals. METHODS: This cross-sectional, descriptive study was carried out among CKD patients at Nephrology Units in Polonnaruwa and Ragama Teaching Hospitals. CKD was defined as estimated glomerular filtration rate <60ml/min/1.73m2. Consecutive, consenting adult CKD patients with at least one blood transfusion during the past five years were included. All participants were tested for HBsAg and HCV antibodies by ELISA. Those found to be positive for either underwent confirmatory PCR testing. RESULTS: 232 patients were included [Mean-age: 55.83 years; 156 (59.75%) males]. Diabetes mellitus and/or hypertension were the causes of CKD in 137/232 (59.1%). 82/232 (35.3%) had CKD of uncertain aetiology.153/232 (65.9%) were on hemodialysis and 6/232 (2.6%) had received a kidney transplant. One was an intravenous drug user, 3 had tattoos and 86/232 (37.1%) had practiced unsafe sex previously. 145/232(62.5%) had previously received HBV vaccination and 67/232 (28.9%) had received 3 doses of the vaccine before first blood transfusion, hemodialysis or transplant. Sero-conversion testing was not done in 178/232 (76.7%). Six were previously HBsAg positive. On re-testing 4 were positive for HBsAg While none had HCV antibody positivity. All were negative for HBV-DNA on PCR testing. CONCLUSION: Active HBV,HCV infections were not detected in this cohort of CKD patients. Traditional risk factors were uncommon. Complete HBV vaccination was suboptimal and checking for seroconversion was low.
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.
Molecular characterization of β thalassaemia intermedia in Sri Lanka: Genotypic heterogeneity and phenotypic diversity
(University of Kelaniya, Sri Lanka, 2015) Perera, P.S.
Previous studies on thalassaemia in Sri Lanka revealed that one third of patients attending thalassaemia clinics have intermedia phenotype and has shown to be presented with a wide pheno$pic diversity. The majority of them have Hb E/J3 thalassaemia, but a significant minority has been shown to have co-inheritance of {3 thalassaemia minor with extra a globin genes. In this study, a group of (3 thalassaemia intermedia patients without HbE/p thalassaemia was systematically identified for further investigations. Fifty unrelated thalassaemia intermedia patients were identified from the five main thalassaemia centres in the island with mostly presented to the adult thalassaemia clinic at Ragama, Sri Lanka; Patients were assessed clinically and categorized into mild, moderate and severe phenotypic groups according to the clinical severity. Deoxyribonucleic acid (DNA) analysis was performed by Southern blot analysis, Gap polymerase chain reaction (PCR), multiplex ligation-dependant probe amplifications (MLPA) and DNA sequence analysis of PCR products. There were twenty six patients in mild and twelve patients each in moderate and severe phenotypic group in the p thalassaemia intermedia study. Ages were ranged from 5-65 years. Seventeen (34%) of the total thalassaemia intermedia population were homozygous or compound heterozygous for p mutations. Five of the homozygotes carried two mild p alleles including a rare promoter mutation - 90 C-»T, Hb variant alleles of Hb G-Szuhu and Hb G-Coushatta. Nine of the seventeen had inherited with two severe p alleles with a globin gene deletions either one or two. Of the other three individuals in this group one had Xmn I y +/+ polymorphism. In the other two individuals, phenotypes were unable to explain with the molecular analysis data obtained through this study. Individuals who had inherited with two mild |3 alleles or a severe allele with either Hb G-Szuhu or Hb G-Coushatta invariably had a mild phenotype while those individuals who had inherited two severe p alleles with a globin gene deletions invariably had a severe phenotype. Thirty three (66%) q£ the total thalassaemia intermedia population were heterozygous for P mutations, of which twenty eight carried excess a globin gene and had a mild to moderate phenotype. Five phenotypes in this group were unable to explain with the molecular analysis data obtained through this study. About forty three (86%) of the cases found with p thalassaemia intermedia had mutations on the a and p globin gene clusters that would account for their clinical presentation with co-inheritance of additional cc-globin genes and p thalassaemia minor the most common finding. However, seven (14%) of the study population remains to be explained that will result in an extraordinary diversity of lesions revealed within this island cohort.
Rare hemoglobin variants: Hb G-Szuhu (HBB: c.243C>G), Hb G-Coushatta (HBB: c.68A>C) and Hb Mizuho (HBB:c.206T>C) in Sri Lankan families
(Informa Healthcare, 2015) Perera, P.S.; Silva, I.; Hapugoda, M.; Wickramarathne, M.N.; Wijesiriwardena, I.; Efremov, D.G.; Fisher, C.A.; Weatherall, D.J.; Premawardhena, A.
In this short communication, we describe the clinical presentation of unusual hemoglobin (Hb), variants in three Sri Lankan cases under study for β-thalassemia intermedia (β-TI). We believe this is the first report on their occurrence in Sri Lanka as well as from the Indian subcontinent. During a molecular study performed on β-TI patients, we identified three unusual Hb variants as Hb G-Szuhu (HBB: c.243C>G), Hb G-Coushatta (HBB: c.68A>C) and Hb Mizuho (HBB: c.206T>C) in three unrelated families. Hb G-Szuhu and Hb G-Coushatta were found in combination with the common β-thalassemia (β-thal) mutation, IVS-I-5 (G>C). Both probands had mild anemia with greatly reduced red cell indices and had non palpable livers and spleens, however, by ultrasound, both were observed to be enlarged. The final Hb variant, Hb Mizuho, was identified as a heterozygous mutation found in both proband and his mother. Both family members had severe anemia and were regularly transfused and had increased red cell parameters.
Study and comparison of nutritional value of some Sri Lankan traditional rice varieties
(Sri Lanka Association for the Advancement of Science, 2009) Sajiwanie, J.W.A.; Perera, P.S.