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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Author: search.filters.author.De Silva, D.C.Has files: Yes

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    Congenital titinopathy: comprehensive characterization of the most severe end of the disease spectrum
    (Wiley-Liss, 2025-01) Coppens, S.; Deconinck, N.; Sullivan, P.; Smolnikov, A.; Clayton, J. S.; Griffin, K. R.; Jones, K. J.; Vilain, C. N.; Kadhim, H.; Bryen, S. J.; Faiz, F.; Waddell, L. B.; Evesson, F. J.; Bakshi, M.; Pinner, J. R.; Charlton, A.; Brammah, S.; Graf, N. S.; Krivanek, M.; Tay, C. G.; Foulds, N.C.; Illingworth, M.A.; Thomas, N.H.; Ellard , S.; Mazanti , I.; Park , S.M.; French, C.E.; Brewster , J.; Belteki , G.; Hoodbhoy, S.; Allinson , K.; Krishnakumar , D.; Baynam , G.; Wood , B.M.; Ward, M.; Vijayakumar , K.; Syed, A.; Murugan , A.; Majumdar , A.; Scurr , I.J.; Splitt , M.P.; Moldovan , C.; De Silva, D.C.; Senanayake, K.; Gardeitchik, T.; Arens, Y.; Cooper, S.T.; Laing, N.G.; Raymond , F.L.; Jungbluth , H.; Kamsteeg , E.J.; Manzur , A.; Corley , S.M.; Ravenscroft , G.; Wilkins , M.R.; Cowley, M.J.; Pinese , M.; Consortium, T.R.; Phadke , R.; Davis, M.R.; Muntoni , F.; Oates, E.C.
    Congenital titinopathy has recently emerged as one of the most common congenital muscle disorders. OBJECTIVE To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.METHODS We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.RESULTS Prenatal features included hypokinesia or akinesia and growth restriction. Six pregnancies were terminated. Nine infants were born at or near term with severe-to-profound weakness and required resuscitation. Seven died following withdrawal of life support. Two surviving children require ongoing respiratory support. Most cohort members had at least 1 disease-causing variant predicted to result in some near-normal-length titin expression. The exceptions, from 2 unrelated families, had homozygous truncating variants predicted to induce complete nonsense mediated decay. However, subsequent analyses suggested that the causative variant in each family had an additional previously unrecognized impact on splicing likely to result in some near-normal-length titin expression. This impact was confirmed by minigene assay for 1 variant.INTERPRETATION This study confirms the clinical variability of congenital titinopathy. Severely affected individuals succumb prenatally/during infancy, whereas others survive into adulthood. It is likely that this variability is because of differences in the amount and/or length of expressed titin. If confirmed, analysis of titin expression could facilitate clinical prediction and increasing expression might be an effective treatment strategy. Our findings also further-support the hypothesis that some near-normal-length titin expression is essential to early prenatal survival. Sometimes expression of normal/near-normal-length titin is due to disease-causing variants having an additional impact on splicing.
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    Exploring the impact of occupational exposure: A study on cardiovascular autonomic functions of male gas station attendants in Sri Lanka
    (Wiley periodicals LLC on behalf of the physiological society and the American physiological society, 2024-10) Warnakulasuriya, T.; Medagoda, K.; Kottahachchi, D.; Luke, D.; Wadasinghe, D.; Rathnayake, P.; Ariyawansa, J.; Dissanayake, T.; Sandeepani, P.; De Silva, D.C.; Devanarayana, N.M.
    Fuel dispensing at fuel stations is performed manually by unprotected male gas station attendants in Sri Lanka, who have long working hours. These workers are exposed to hydrocarbon fuels associated with multiple health effects by modulation of the autonomic nervous system. This study was performed to determine cardiovascular autonomic functions among fuel pump attendants in Sri Lanka. Fuel pump attendants (n = 50) aged between 19 and 65 years were identified for the study from seven fuel stations. They were compared with age- and gender-matched controls (n = 46) without occupational exposure to fuel. A physical examination was performed before the autonomic function and heart rate variability (HRV) assessment. There were no significant differences in weight, height, or BMI between the study and the control populations (p > 0.05). Both the systolic blood pressure (SBP) (Mann Whitney U (MWU) = 743.5, p = 0.003) and diastolic blood pressure (DBP) (MWU = 686.5, p = 0.001) were significantly higher among the gas station attendants compared to controls. Valsalva ratio was significantly higher among the study group (MW U = 874.00, p = 0.043) compared to controls. The HRV analysis showed significantly higher SDNN and SD2 (MWU = 842.00, p = 0.034, and MWU = 843.50, p = 0.035 respectively) among the gas station attendants compared to controls. The changes to the cardiovascular autonomic parameters among those exposed to fuel vapor as a gas station attendant indicate an increase in sympathetic outflow to the vessels. In the occupational setting as fuel pump attendants need periodic monitoring.