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 GDF15 linked to maternal risk of nausea and vomiting during pregnancy(Nature Pub. Group, 2024) Fejzo, M.; Rocha, N.; Cimino, I.; Lockhart, S.M.; Petry, C.J.; Kay, R.G.; Burling, K.; Barker, P.; George, A.L.; Yasara, N.; Premawardhena, A.; Gong, S.; Cook, E.; Rimmington, D.; Rainbow, K.; Withers, D.J.; Cortessis, V.; Mullin, P.M.; MacGibbon, K.W.; Jin, E.; Kam, A.; Campbell, A.; Polasek, O.; Tzoneva, G.; Gribble, F.M.; Yeo, G.S.H.; Lam, B.Y.H.; Saudek, V.; Hughes, I.A.; Ong, K.K.; Perry, J.R.B.; Sutton, C.A.; Baumgarten, M.; Welsh, P.; Sattar, N.; Smith, G.C.S.; Charnock- Jones, D.S.; Coll, A.P.; Meek, C.L.; Mettananda, S.; Hayward, C.; Mancuso, N.; O'Rahilly, S.GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy (NVP) including its most severe form, Hyperemesis Gravidarum (HG), but a full mechanistic understanding is lacking [1-4]. Here we report that fetal production of GDF15, and maternal sensitivity to it, both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally-labelled GDF15 variant we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with beta-thalassemia, a condition where GDF15 levels are chronically high [5], report very low levels of NVP. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally-derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by pre-pregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.Item Association of GDF15 levels with body mass index and endocrine status in β-Thalassaemia(Blackwell Publishing, 2023) Karusheva, Y.; Petry, C.J.; Yasara, N.; Kottahachchi, D.; Premawardhena, A.; Barker, P.; Burling, K.; Sattar, N.; Welsh, P.; Mettananda, S.; O'Rahilly, S.S.OBJECTIVE: GDF15 has emerged as a stress-induced hormone, acting on the brain to reduce food intake and body weight while affecting neuroendocrine function. Very high GDF15 levels are found in thalassaemia, where growth, energy balance and neuroendocrine function are impaired. We examined the relationships between GDF15 and anthropometric measures and endocrine status in β-thalassaemia. DESIGN: Cross sectional study PATIENTS: All β-thalassaemia patients attending the thalassaemia unit of Colombo North Teaching Hospital for blood transfusions. MEASUREMENTS: Anthropometric data, appetite scores, circulating GDF15, IGF, thyroid and reproductive hormone levels in 103 β-thalassaemia patients were obtained. RESULTS: GDF15 levels were markedly elevated in thalassaemia patients (24.2 fold with β-thalassaemia major compared with healthy controls). Among patients with β-thalassaemia major, the relationship between GDF15 and Body Mass Index (BMI) was curvilinear with all individuals with GDF15 levels above 24,000 pg/ml having a BMI below 20 kg/m2 . After adjustment for BMI, age and Tanner stage, serum IGF1 concentrations correlated negatively with GDF15 in all thalassaemia patients (β=-0.027, p=0.02). We found a significant positive relationship between GDF15 and gonadotropin (in both sexes) and testosterone (in males). CONCLUSIONS: GDF15 levels were markedly elevated in patients with β-thalassaemia and its association with BMI is consistent with the known effect of GDF15 to reduce body weight. The inverse association between GDF15 with IGF1 levels may reflect a neuroendocrine impact of GDF15 or an indirect effect via impaired nutritional state. The positive association with testosterone in males and gonadotropins in both sexes, was surprising and should prompt further GDF15 studies on the hypothalamic pituitary gonadal axis. This article is protected by copyright. All rights reserved.Item Analysis of nutritional status and factors associated with undernutrition in children aged 6-59 months in a rural area of Sri Lanka(Sri Lanka College of Paediatricians, 2019) Samarasekara, G.S.; Mettananda, S.; Punchihewa, P.OBJECTIVE: To describe the prevalence and factors associated with undernutrition in children aged 6-59 months in a rural area of Sri Lanka. METHOD: A community-based, cross-sectional study was carried out among children aged 6-59 months attending well baby clinics in Dehiattakandiya Medical Officer of Health area from November 2016 to January 2017. Data collection was done using an interviewer-administered questionnaire. Weight and height measurements were taken with calibrated instruments. Data analysis was done using logistic regression by SPSS 16.0. RESULTS: Four hundred and sixty four children were recruited having a mean age of 29.3 ±14.6 months; 53% were females. Prevalence of stunting, underweight and wasting was 36.4%, 42.9% and 19.0% respectively. The following independent associations were identified: for stunting- low birth weight, breastfeeding beyond 2 years, lower maternal education and paternal smoking; for underweight- birth order more than 2, low birth weight, breastfeeding beyond 2 years, lower maternal education and paternal smoking and alcohol use; for wasting- male sex, low birth weight and paternal smoking. CONCLUSIONS: Low birth weight, prolonged breastfeeding, lower maternal education level and paternal smoking had a significant association with stunting and underweight whilst male sex, low birth weight, and paternal smoking had a significant association with wasting in children aged 6-59 months.Item Clinical and laboratory evaluation of childhood anaemia(Sri Lanka College of Paediatricians, 2020) Mettananda, S.; Williams, S.No Abstract available.Item Microcytic anemia in children: Parallel screening for iron deficiency and Thalassemia provides a useful opportunity for Thalassemia prevention in low- and middle-income countries(Hemisphere Pub. Corp., 2020) Mettananda, S.; Paranamana, S.; Fernando, R.; Suranjan, M.; Rodrigo, R.; Perera, L.; Vipulaguna, T.; Fernando, P.; Fernando, M.; Dayanath, B.K.T.P.; Costa, Y.; Premawardhena, A.ABSTRACT:Microcytic anemia in children is commonly attributed to iron deficiency without attempting to find the cause. Inadequate investigations to exclude hemoglobinopathies lead to missed opportunities for identification of thalassemia carriers. Here we aim to describe the relative contribution of iron deficiency and thalassemia to microcytic anemia in children. This hospital-based prospective study was conducted at the Colombo North Teaching Hospital, Ragama, Sri Lanka. All newly diagnosed patients with microcytic anemia were recruited and data were collected using an interviewer-administered questionnaire. Full blood count, blood film, serum ferritin, c-reactive protein, quantification of hemoglobin sub-types and α-globin genotype were performed using 4 ml of venous blood. A total of 104 children (Male- 60.5%) were recruited. Iron deficiency was the cause for anemia in 49% whilst 16% and 10% had α- and β-thalassemia trait respectively. Seven (6.7%) children had co-existing iron deficiency and thalassemia trait while two coinherited α- and β-thalassemia trait. Children with β-thalassemia trait had significantly higher red cell count and lower mean corpuscular volume compared to children with iron deficiency. However, none of the red cell parameters were significantly different between children with α-thalassemia trait and iron deficiency. Iron deficiency contributes only to half of children with microcytic anemia; one-fourth had thalassemia trait. Co-existence of iron deficiency and thalassemia trait or co-inheritance of α- and β-thalassemia trait were found in 9%. Parallel investigation of children with microcytic anemia to diagnose iron deficiency and thalassemia provides an opportunity to identify thalassemia carriers which is beneficial for thalassemia prevention.Item Delayed-onset Sinus Node Dysfunction in a child victim of Russell's Viper Bite.(Asia Pub., 2020) Athapathu, A.S.; Arunath, V.; Aruppala, A.A.; Hoole, T. J.; Suntharesan, K.; Mettananda, S.ABSTRACT:Cardiac complications following envenomation by Russell's viper venom are uncommon. We describe a 14-year-old girl who developed delayed-onset sinus node dysfunction. She presented with mucosal bleeding, ptosis, and muscle weakness. Her 20-min whole blood clotting time and international normalized ratio were prolonged. The initial electrocardiogram showed sinus tachycardia. Her systemic manifestations responded to antivenom serum. After 24 h, she developed bradycardia and electrocardiography showed sinus node dysfunction with sinus arrest and an atrial escape rhythm. This case shows that arrhythmias can have a delayed onset even after resolution of other systemic manifestations, and even after treatment with antivenom serum. KEYWORDS: Arrhythmias; adolescent; cardiac; electrocardiography; sinus; snake bites; tachycardia; viperidae.Item Streptococcus bovis - unusual etiology of meningitis in a neonate with Down syndrome: a case report(BioMed Central, 2018) Mettananda, S.; Kamalanathan, P.; Dhananja Namalie, K.BACKGROUND: Common etiological agents of neonatal meningitis include group B Streptococcus, Escherichia coli, and Staphylococcus aureus. Here we report a rare pathogen - Streptococcus bovis - causing meningitis in a premature neonate with Down syndrome. CASE PRESENTATION: A 26-day-old Asian male neonate with Down syndrome presented with a history of high-grade fever, poor sucking, poor cry, and reduced activity. On admission, he was febrile and had features of circulatory collapse. A cerebrospinal fluid examination confirmed bacterial meningitis and blood culture isolated the causative organism: group D Streptococcus, which was verified as Streptococcus bovis biotype 2. An echocardiogram did not show evidence of infective endocarditis. CONCLUSIONS: This is probably the first report of neonatal meningitis due to Streptococcus bovis in a child with Down syndrome. Although our patient did not show features of overt immunodeficiency, subtle abnormalities in his immune system would have predisposed him to infection with this unusual organism. This case highlights the need for considering unusual pathogens when managing serious infections in children with Down syndrome.Item Molecular basis and genetic modifiers of thalassemia(Elsevier Health Science, 2018) Mettananda, S.; Higgs, D.R.Thalassemia is a disorder of hemoglobin characterized by reduced or absent production of one of the globin chains in human red blood cells with relative excess of the other. Impaired synthesis of β-globin results in β-thalassemia, whereas defective synthesis of α-globin leads to α-thalassemia. Despite being a monogenic disorder, thalassemia exhibits remarkable clinical heterogeneity that is directly related to the intracellular imbalance between α- and β-like globin chains. Novel insights into the genetic modifiers have contributed to the understanding of the correlation between genotype and phenotype and are being explored as therapeutic pathways to cure this life-limiting disease.Item Phenotypic and molecular characterization of a serum-free miniature erythroid differentiation system suitable for high-throughput screening and single-cell assays(Elsevier Science Inc., 2018) Mettananda, S.; Clark, K.; Fisher, C.A.; Sloane-Stanley, J.A.; Gibbons, R.J.; Higgs, D.R.In vitro erythroid differentiation systems are used to study the mechanisms underlying normal and abnormal erythropoiesis and to test the effects of various extracellular factors on erythropoiesis. The use of serum or conditioned medium in liquid cultures and the seeding of cultures with heterogeneous peripheral blood mononuclear cells confound the reproducibility of these systems. Newer erythroid differentiation culture systems have overcome some of these limitations by using a fully defined, serum-free medium and initiating cultures using purified CD34+ cells. Although widely used in bulk cultures, these protocols have not been rigorously tested in high-throughput or single-cell assays. Here, we describe a serum-free erythroid differentiation system suitable for small-scale and single-cell experiments. This system generates large numbers of terminally differentiated erythroid cells of very high purity. Here we have adapted this culture system to a 96-well format and have developed a protocol to grow erythroid colonies from single erythroid progenitors in minute culture volumes.Item Multiple subcutaneous folds in oculocerebrorenal syndrome of Lowe(Sri Lanka Medical Association, 2013) Wanigasinghe, J.; Mettananda, S.; de Silva, K.S.H.; Gunethilake, S.No Abstract Available