Welcome to Hirsla, Landspítali University Hospital research archive

Hirsla is an open access repository, designed as a place to store, index, preserve and redistribute in digital format scholarly work of Landspitali employees. (A/H1N1)

  • MAP1B mutations cause intellectual disability and extensive white matter deficit.

    Walters, G Bragi; Gustafsson, Omar; Sveinbjornsson, Gardar; Eiriksdottir, Valgerdur K; Agustsdottir, Arna B; Jonsdottir, Gudrun A; Steinberg, Stacy; Gunnarsson, Arni F; Magnusson, Magnus I; Unnsteinsdottir, Unnur; Lee, Amy L; Jonasdottir, Adalbjorg; Sigurdsson, Asgeir; Jonasdottir, Aslaug; Skuladottir, Astros; Jonsson, Lina; Nawaz, Muhammad S; Sulem, Patrick; Frigge, Mike; Ingason, Andres; Love, Askell; Norddhal, Gudmundur L; Zervas, Mark; Gudbjartsson, Daniel F; Ulfarsson, Magnus O; Saemundsen, Evald; Stefansson, Hreinn; Stefansson, Kari; 1 deCODE genetics/Amgen, Reykjavik, 101, Iceland. 2 Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland. 3 Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 405 30, Sweden. 4 Department of Radiology, Landspitali University Hospital, Fossvogur, Reykjavik, 108, Iceland. 5 School of Engineering and Natural Sciences, University of Iceland, Reykjavik, 101, Iceland. 6 Faculty of Electrical and Computer Engineering, University of Iceland, Reykjavik, 101, Iceland. 7 The State Diagnostic and Counselling Centre, Kopavogur, 200, Iceland. 8 deCODE genetics/Amgen, Reykjavik, 101, Iceland. hreinn@decode.is. 9 deCODE genetics/Amgen, Reykjavik, 101, Iceland. kstefans@decode.is. 10 Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland. kstefans@decode.is. (Nature Publishing Group, 2018-08-27)
    Discovery of coding variants in genes that confer risk of neurodevelopmental disorders is an important step towards understanding the pathophysiology of these disorders. Whole-genome sequencing of 31,463 Icelanders uncovers a frameshift variant (E712KfsTer10) in microtubule-associated protein 1B (MAP1B) that associates with ID/low IQ in a large pedigree (genome-wide corrected P = 0.022). Additional stop-gain variants in MAP1B (E1032Ter and R1664Ter) validate the association with ID and IQ. Carriers have 24% less white matter (WM) volume (β = -2.1SD, P = 5.1 × 10
  • Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis.

    Alberts, Rudi; de Vries, Elisabeth M G; Goode, Elizabeth C; Jiang, Xiaojun; Sampaziotis, Fotis; Rombouts, Krista; Böttcher, Katrin; Folseraas, Trine; Weismüller, Tobias J; Mason, Andrew L; Wang, Weiwei; Alexander, Graeme; Alvaro, Domenico; Bergquist, Annika; Björkström, Niklas K; Beuers, Ulrich; Björnsson, Einar; Boberg, Kirsten Muri; Bowlus, Christopher L; Bragazzi, Maria C; Carbone, Marco; Chazouillères, Olivier; Cheung, Angela; Dalekos, Georgios; Eaton, John; Eksteen, Bertus; Ellinghaus, David; Färkkilä, Martti; Festen, Eleonora A M; Floreani, Annarosa; Franceschet, Irene; Gotthardt, Daniel Nils; Hirschfield, Gideon M; Hoek, Bart van; Holm, Kristian; Hohenester, Simon; Hov, Johannes Roksund; Imhann, Floris; Invernizzi, Pietro; Juran, Brian D; Lenzen, Henrike; Lieb, Wolfgang; Liu, Jimmy Z; Marschall, Hanns-Ulrich; Marzioni, Marco; Melum, Espen; Milkiewicz, Piotr; Müller, Tobias; Pares, Albert; Rupp, Christian; Rust, Christian; Sandford, Richard N; Schramm, Christoph; Schreiber, Stefan; Schrumpf, Erik; Silverberg, Mark S; Srivastava, Brijesh; Sterneck, Martina; Teufel, Andreas; Vallier, Ludovic; Verheij, Joanne; Vila, Arnau Vich; Vries, Boudewijn de; Zachou, Kalliopi; Chapman, Roger W; Manns, Michael P; Pinzani, Massimo; Rushbrook, Simon M; Lazaridis, Konstantinos N; Franke, Andre; Anderson, Carl A; Karlsen, Tom H; Ponsioen, Cyriel Y; Weersma, Rinse K; 1 Department of Gastroenterology and Hepatology, University of Groningen and University Medical Centre Groningen, Groningen, The Netherlands. 2 Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. 3 Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK. 4 Academic Department of Medical Genetics, University of Cambridge, Cambridge, UK. 5 Norwegian PSC Research Center, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway. 6 Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway. 7 Department of Surgery, Wellcome Trust-Medical Research Council Stem Cell Institute, Anne McLaren Laboratory, University of Cambridge, Cambridge, UK. 8 Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, UK. 9 Institute for Liver and Digestive Health, University College London, Royal Free Hospital, London, UK. 10 Department of Gastroenterology Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. 11 Integrated Research and Treatment Center-Transplantation (IFB-tx) Hannover Medical School, Hannover, Germany. 12 Division of Gastroenterology and Hepatology, University of Alberta, Edmonton, Alberta, Canada. 13 Department of Medicine, Division of Hepatology, University of Cambridge, Cambridge, UK. 14 Department of Clinical Medicine, Division of Gastroenterology, Sapienza University of Rome, Rome, Italy. 15 Center for Digestive Diseases, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. 16 Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. 17 Department of Internal Medicine, Division of Gastroenterology and Hepatology, Landspitali University Hospital, Reykjavik, Iceland. 18 K G Jebsen Inflammation Research Centre and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 19 Division of Gastroenterology and Hepatology, University of California Davis, Davis, California, USA. 20 Sapienza University of Rome, Medico-Surgical Sciences and Biotechnologies, Rome, Italy. 21 Department of Medicine and Surgery, Program for Autoimmune Liver Diseases, International Center for Digestive Health, University of Milan-Bicocca, Milan, Italy. 22 Department of Hepatology, AP-HP, Hôpital Saint Antoine, Paris, France. 23 General Internal Medicine, University Health Network, Toronto General Hospital, Toronto, Canada. 24 Department of Medicine and Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece. 25 Division of Gastroenterology and Hepatology, Mayo Clinic Minnesota, Rochester, Minnesota, USA. 26 Department of Medicine, Snyder Institute of Chronic Diseases, University of Calgary, Calgary, Canada. 27 Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany. 28 Department of Medicine, Division of Gastroenterology, Helsinki University Hospital, Helsinki, Finland. 29 Department of Surgical Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy. 30 Department of Surgery Oncology and Gastroenterology, University of Padova, Padova, Italy. 31 Department of Medicine, University Hospital of Heidelberg, Heidelberg, Germany. 32 Centre for Liver Research, NIHR Biomedical Research Unit, University of Birmingham, Birmingham, UK. 33 Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands. 34 Department of Medicine II, Liver Center Munich, University of Munich, Munich, Germany. 35 Popgen Biobank, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany. 36 Institute for Epidemiology, Christian-Albrechts University, Kiel, Germany. 37 Wellcome Trust Genome Campus, Wellcome Trust Sanger Institute, Cambridge, UK. 38 Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden. 39 Department of Gastroenterology, Università Politecnica delle Marche, Ospedali Riuniti University Hospital, Ancona, Italy. 40 Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland. 41 Department of Internal Medicine Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany. 42 Liver Unit Hospital Clinic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain. 43 Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany. 44 Department of Medicine I, Krankenhaus Barmherzige Brüder, Munich, Germany. 45 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 46 Department for General Internal Medicine, Christian-Albrechts-University, Kiel, Germany. 47 Section of Gastroenterology, Department of Transplantation Medicine, Division of Cancer, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway. 48 Inflammatory Bowel Disease (IBD) Group Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital Toronto, Ontario, Canada. 49 Department of Hepatobiliary Surgery and Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 50 1st Department of Medicine, University of Mainz, Mainz, Germany. 51 Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands. 52 Department of Internal Medicine, University of Thessaly, Larissa, Greece. 53 Department of Hepatology, John Radcliffe University Hospitals NHS Trust, Cambridge, UK. (BMJ Publishing Group, 2018-01-01)
    Primary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications. We collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients-obtained using the Illumina immunochip-with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes. We identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07×10 We present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene
  • Systems analysis of metabolism in platelet concentrates during storage in platelet additive solution.

    Jóhannsson, Freyr; Guðmundsson, Steinn; Paglia, Giuseppe; Guðmundsson, Sveinn; Palsson, Bernhard; Sigurjónsson, Ólafur E; Rolfsson, Óttar; [ 1 ] Univ Iceland, Ctr Syst Biol, Sturlugata 8, Reykjavik, Iceland Show more [ 2 ] Univ Iceland, Med Dept, Sturlugata 8, Reykjavik, Iceland Show more [ 3 ] European Acad Bolzano Bozen, Ctr Biomed, Via Galvani 31, Bolzano, Italy Show more [ 4 ] Landspitali Univ Hosp, Blood Bank, Snorrabraut 60, Reykjavik, Iceland Show more [ 5 ] Reykjavik Univ, Sch Sci & Engn, Menntavegur 1, Reykjavik, Iceland (Portland Press, 2018-07-17)
    Platelets (PLTs) deteriorate over time when stored within blood banks through a biological process known as PLT storage lesion (PSL). Here, we describe the refinement of the biochemical model of PLT metabolism, iAT-PLT-636, and its application to describe and investigate changes in metabolism during PLT storage. Changes in extracellular acetate and citrate were measured in buffy coat and apheresis PLT units over 10 days of storage in the PLT additive solution T-Sol. Metabolic network analysis of these data was performed alongside our prior metabolomics data to describe the metabolism of fresh (days 1-3), intermediate (days 4-6), and expired (days 7-10) PLTs. Changes in metabolism were studied by comparing metabolic model flux predictions of iAT-PLT-636 between stages and between collection methods. Extracellular acetate and glucose contribute most to central carbon metabolism in PLTs. The anticoagulant citrate is metabolized in apheresis-stored PLTs and is converted into aconitate and, to a lesser degree, malate. The consumption of nutrients changes during storage and reflects altered PLT activation profiles following their collection. Irrespective of the collection method, a slowdown in oxidative phosphorylation takes place, consistent with mitochondrial dysfunction during PSL. Finally, the main contributors to intracellular ammonium and NADPH are highlighted. Future optimization of flux through these pathways provides opportunities to address intracellular pH changes and reactive oxygen species, which are both of importance to PSL. The metabolic models provide descriptions of PLT metabolism at steady state and represent a platform for future PLT metabolic research.
  • Frá bræðralagi til fagmennsku. Siðferðileg viðmið íslenskra lækna í hundrað ár. Vilhjálmur Árnason

    Vilhjálmur Árnason; Prófessor í heimspeki við Háskóla Íslands (Læknafélag Íslands, 2018-09)
    Læknar hafa frá öndverðu haft siðferðileg viðmið í starfi sínu. Elsta og þekktasta dæmið er eiðurinn sem kenndur er við gríska lækninn Hippókrates (460-370 f. Kr.). Segja má að hinn siðferðilegi kjarni eiðsins sé fólginn í þessu ákvæði: „Ég heiti því að beita læknisaðgerðum til líknar sjúkum, eftir því sem ég hef vit á og getu til, en aldrei í því skyni að valda miska eða tjóni.“1 Hér er velferð sjúklingsins í fyrirrúmi og enn er vísað til kröfunnar primum non nocere, umfram allt valdið ekki miska, sem meginsiðareglu læknislistarinnar. Samkvæmt nútímalegri greiningu á siðareglum eru slík ákvæði um að gæta hagsmuni sjúklinga hluti af frumskyldum lækna.2,3 Aðrir meginflokkar siðareglna eru félagslegar skyldur við almenning og samfélag, hæfniskyldur að viðhalda þekkingu og færni og skyldur gagnvart starfssystkinum (stundum nefndar bróðurlegar skyldur).
  • Ormur í auga og endurteknar bólgur á útlimum - Sjúkratilfelli

    Davíð Þór Bragason; María Soffía Gottfreðsdóttir; Birgir Jóhannsson; Magnús Gottfreðsson; 1) 2) Augndeild Landspítala 3) 4) Smitsjúkdómadeild Landspítala (Læknafélag Íslands, 2018-09)
    Lýst er tveimur tilfellum af lóasýki hjá konum búsettum hér á landi, 35 ára konu sem fæddist í Afríku og 31 árs konu sem hafði ferðast um Afríku. Þær leituðu til læknis vegna óþæginda frá auga. Við skoðun sást í báðum tilfellum ormur, um 3 cm á lengd og 0,5 mm á breidd, sem hreyfðist undir slímhúð augans. Báðar konurnar höfðu einnig einkenni frá útlimum: endurteknar lotubundnar bólgur og kláða, og vöðvaverki. Greiningin var í báðum tilfellum lóasýki með Calabar-bólgum á útlimum og meðferð með albendazóli og díetýlcarbamazíni leiddi til lækningar. Aukinnar árvekni er þörf gagnvart sýkingum sem hafa verið sjaldgæfar í okkar heimshluta hingað til.

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