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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 A large-scale multi-ancestry genome-wide study accounting for smoking behavior identifies multiple significant loci for blood pressure(University of Chicago Press, 2018) Sung, Y.J.; Winkler, T.W.; de Las Fuentes, L.; Bentley, A.R.; Brown, M.R.; Kraja, A.T.; Schwander, K.; Ntalla, I.; Guo, X.; Franceschini, N.; Lu, Y.; Cheng, C.Y.; Sim, X.; Vojinovic, D.; Marten, J.; Musani, S.K.; Li, C.; Feitosa, M.F.; Kilpelainen, T.O.; Richard, M.A.; Noordam, R.; Aslibekyan, S.; Aschard, H.; Bartz, T.M.; Dorajoo, R.; Liu, Y.; Manning, A.K.; Rankinen, T.; Smith, A.V.; Tajuddin, S.M.; Tayo, B.O.; Warren, H.R.; Zhao, W.; Zhou, Y.; Matoba, N.; Sofer, T.; Alver, M.; Amini, M.; Boissel, M.; Chai, J.F.; Chen, X.; Divers, J.; Gandin, I.; Gao, C.; Giulianini, F.; Goel, A.; Harris, S.E.; Hatwig, F.P.; Horimoto, A.R.V.R.; Hsu, F.C.; Jackson, A.U.; Kahonen, M.; Kasturiratne, A.; Kuhnel, B.; Leander, K.; Lee, W.J.; Lin, K.H.; an Luan, J.; McKenzie, C.A.; Meian, H.; Nelson, C.P.; Rauramaa, R.; Schupf, N.; Scott, R.A.; Sheu, W.H.H.; Stancakova, A.; Takeuchi, F.; van der Most, P.J.; Varga, T.V.; Wang, H.; Wang, Y.; Ware, E.B.; Weiss, S.; Wen, W.; Yanek, L.R.; Zhang, W.; Zhao, J.H.; Afag, S.; Alfred, T.; Amin, N.; Arking, D.; Aung, T.; Barr, R.G.; Bielak, L.F.; Boerwincle, E.; Bottinger, E.P.; Braund, P.S.; Brody, J.A.; Broeckel, U.; Cabrera, C.P.; Cade, B.; Caizheng, Y.; Campbell, A.; Canouil, M.; Chakravarti, A.; CHARGE Neurology Working Group; Chauhan, G.; Christensen, K.; Cocca, M.; COGENT-Kidney Consortium; Collins, F.S.; Connel, J.M.; de Mutsert, R.; de Silva, H.J.; Debette, S.; Dorr, M.; Duan, Q.; Eaton, C.B.; Ehret, G.; Evangelou, E.; FAul, J.D.; Fisher, V.A.; Forouhi, N.G.; Franco, O.H.; Friedlander, Y.; Gao, H.; GIANT Consortium; Gigante, B.; Graff, M.; Gu, C.C.; Gu, D.; Gupta, P.; Hagenaars, S.P.; Harris, T.B.; He, J.; Heikkinen, S.; Heng, C.K.; Hirata, M.; Hofman., A.; Howard, B.V.; Hunt, S.; Irvin, M.R.; Jia, Y.; Joehanes, R.; Justice, A.E.; Katsuya, T.; Kaufman, J,; Kerrison, N.D.; Khor, C.C.; Koh, W.P.; Koistinen, H.A.; Komulainen, P.; Kooperberg, C.; Krieger, J.E.; Kubo, M.; Kuusisto, J.; Lanefeld, C.D.; Langenberg, C.; Launer, L.J.; Lehne, B.; Lewis, C.E.; Li, Y.; Lifelines Cohort Study; Lim, S.H.; Lin, S.; Liu, C.T.; Liu, J.; Liu, J.; Liu, K.; Liu, Y.; Loh, M.; Lohmann, K.K.; Long, J.; Louie, T.; Magi, R.; Mahajan, A.; Meitinger, T.; Metspalu, A.; Milani, L.; Momozawa, Y.; Morris, A.P.; Mosley, T.H.Jr.; Munson, P.; Murray, A.D.; Nalls, M.A.; Nasri, U.; Norris, J.M.; North, K.; Ogunniyi, A.; Padmanabhan, S.; Palmas, W.R.; Palmer, N.D.; Pankow, J.S.; Pedersen, N.L.; Peters, A.; Peyser, P.A.; Polasek, O.; Raitakari, O.T.; Renstrom, F.; Rice, T.K.; Ridker, P.M.; Robino, A.; Robinson, J.G.; Rose, L.M.; Rudan, I.; Salako, B.L.; Sandow, K.; Schmidt, C.O.; Schreiner, P.J.; Scott, W.R.; Seshadri, S.; Sever, P.; Sitlani, C.M.; Smith, J.A.; Snieder, H.; Starr, J.M.; Strauch, K.; Tang, H.; Taylor, K.D.; Teo, Y.Y.; Tham, Y.C.; Uitterlineden, A.G.; Waldenberger, M.; Wang, L.; Wang, Y.X.; Wei, W.B.; Williams, C.; Wilson, G.; Wojczynski, M.K.; Yao, J.; Yuan, J.M.; Zonderman, A.B.; Becker, D.M.; Boehnke, M.; Bowden, D.W.; Chambers, J.C.; Chen, Y.I.; de Faire, U.; Deary, I.J.; Esco, T.; Farrall, M.; Forrester, T.; Franks, P.W.; Freedman, B.I.; Froguel, P.; Gasparini, P.; Gieger, C.; Horta, B.L.; Hung, Y.J.; Jonas, J.B.; Kato, N.; Kooner, J.S.; Laakso, M.; Lehtimaki, T.; Liang, K.W.; Magnusson, P.K.E.; Newman, A.B.; Oldehinkel, A.J.; Pereira, A.C.; Redline, S.; Rettig, R.; Samani, N.J.; Scott, J.; Shu, X.O.; van der Harst, P.; Wagenknecht, L.E.; Wareham, N.J.; Watkins, H.; Weir, D.R.; Wickremasinghe, A.R.; Wu, T.; Zheng, W.; Kamatani, Y.; Laurie, C.C.; Bouchard, C.; Cooper, R.S.; Evans, M.K.; Gudnason, V.; Kardia, S.L.R.; Kritchevsky, S.B.; Levy, D.; O'Connell, J.R.; Psaty, B.M.; van Dam, R.M.; Sims, M.; Arnett, D.K.; Mook-Kanamori, D.O.; Kelly, T.N.; Fox, E.R.; Hayward, C.; Fornage, M.; Rotimi, C.N.; Province, M.A.; van Dujin, C.M.; Tai, E.S.; Wong, T.Y.; Loos, R.J.F.; Reiner, A.P.; Rotter, J.I.; Zhu, X.; Bierut, L.J.; Gauderman, W.J.; Caulfield, M.J.; Elliott, P.; Rice, K.; Munroe, P.B.; Morrison, A.C.; Cupples, L.A.; Rao., D.C.; Chasman, D.I.Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10-8) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 × 10-8). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).Item Blood pressure drop in dengue without fluid leakage(Sri Lanka Medical Association, 2013) Miththinda, J.K.N.D.; Premaratna, R.; Ragupathy, R.; de Silva, H.J.INTRODUCTION AND OBJECTIVES: Plasma leakage is considered the most important reason for reduction in blood pressures (BP) in Dengue shock syndrome (DSS). However other causes such as dehydration, vascular dilatation due metabolic causes such as lactic acidosls or reduced cardiac output due to myocarditis or cardiomyopathy may lead to reduction in BP. We document observations in 7 patients with dengue who had reduced BP with no evidence of fluid leakage. METHODS: We monitored 106 patients with confirmed dengue for fluid leakage with ultrasonography and other clinical, haematological and biochemical parameters. These parameters of the 7 patients (Group A) were compared with an age and sex matched group of patients from the same cohort who did not develop any complications (Group B) in order to investigate the reasons for the BP drop. RESULTS: Comparison between Group A vs Group B; systolic blood pressure drop 21.7mmHg (7.9) vs 5.7mmHg (7.9) p =0.025; diastoiic blood pressure drop 17.1mmHg (7.6) vs 7.1mmHg (7.7) p =0.03; percentage rise in Hb 2.8% (3.9) vs 5.3% (4.4) p =0.3; percentage rise of PCV 3.5% (1.5) vs 6.2% (5) ^=0.06. Five out of 7 in Group A and none in Group B had T wave inversions in the ECG in more than 3 consecutive leads. ECHO and cardiac enzymes were not done. CONCLUSIONS: Except for blood pressure drop and ECG changes, there were no significant differences in clinical, haematological or biochemical parameters between the two groups. Our findings suggest an alternative cause for the drop in blood pressure in dengue patients with no evidence of fluid leakage.