http://hdl.handle.net/2336/11204 Search the Channel search http://www.hirsla.lsh.is/lsh/simple-search http://hdl.handle.net/2336/188429 Titill: The anti-microbial peptide LL-37 modulates immune responses in the palatine tonsils where it is exclusively expressed by neutrophils and a subset of dendritic cells.<br/><br/>Höfundar: Sigurdardottir, Sigrun L; Thorleifsdottir, Ragna H; Guzman, Andrew M; Gudmundsson, Gudmundur H; Valdimarsson, Helgi; Johnston, Andrew<br/><br/>Útdráttur: Antimicrobial peptides are essential elements of epithelial defense against invading micro-organisms. The palatine tonsils are positioned at the entry of the airway and the gut and as such are ideally situated to act as immune sentinels in the pharynx protecting against microbial invasion. Tonsils express a number of antimicrobial peptides including hCAP18/LL-37. Here we clearly define the expression of hCAP18/LL-37 in the tonsils showing unequivocally that hCAP18/LL-37 is mainly expressed by infiltrating neutrophils and follicular CD11c+CD13+HLA-DR+ dendritic cells, rarely by macrophages, and never by the epithelium itself. To explore possible functions for follicle-derived LL-37, we stimulated tonsil mononuclear cells with LL-37 in vitro and observed the secretion of the proinflammatory cytokines CCL5 and CXCL9, expression of IFN-γ and MX-1 and down-regulation of chemokine receptors CCR4 and CCR6 which are involved in tissue-selective T cell trafficking. Taken together, these data illustrate new potential immunoregulatory functions for hCAP18/LL-37 in the tonsils. http://hdl.handle.net/2336/145514 Titill: Increased physical fitness among patients following endurance training during haemodialysis.<br/><br/>Höfundar: Ragnarsdóttir, María; Malmberg, Ebba; Strandberg, Emma; Indridason, Olafur S<br/><br/>Útdráttur: Abstract Objective. The study aimed to investigate the effect of 6 months of endurance training of moderate intensity on physical performance and the risk of falling in haemodialysis patients. Material and methods. This was a prospective interventional study in which 21 of 35 eligible patients accepted to participate. The 6-minute walk test (6MWT), timed up and go (TUG), timed stand test and Romberg's test were used to evaluate physical fitness. The Borg scale was used to control the workload. The patients bicycled for 12-40 min with increasing workload according to their capabilities. Wilcoxon signed ranks and McNemar's tests were used for analysis. Results. Of the 21 participants, 12 completed 3 months of training. Their median (range) age was 69 (37-88) years, duration of dialysis was 2.5 (1-11) years and body mass index was 25.0 (20.0-31.9). Romberg's test was positive in four participants at the beginning but in three after 3 months. Nine participants completed 6 months of training; none had a positive Romberg's test at that time. Walking distance increased significantly after 3 and 6 months of training (p = 0.002 and p = 0.012, respectively), and time for the TUG decreased significantly (p = 0.041 and p = 0.044), as did time for the timed stand test (p = 0.015 and 0.018), compared with baseline values. The TUG test was in excess of 14 s in four patients at baseline but only one at the end of training. Conclusion. Endurance training of moderate intensity during dialysis results in significantly increased physical performance in haemodialysis patients. http://hdl.handle.net/2336/129552 Titill: Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction.<br/><br/>Höfundar: Antoniou, Antonis C; Beesley, Jonathan; McGuffog, Lesley; Sinilnikova, Olga M; Healey, Sue; Neuhausen, Susan L; Ding, Yuan Chun; Rebbeck, Timothy R; Weitzel, Jeffrey N; Lynch, Henry T; Isaacs, Claudine; Ganz, Patricia A; Tomlinson, Gail; Olopade, Olufunmilayo I; Couch, Fergus J; Wang, Xianshu; Lindor, Noralane M; Pankratz, Vernon S; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Barile, Monica; Viel, Alessandra; Allavena, Anna; Dall'Olio, Valentina; Peterlongo, Paolo; Szabo, Csilla I; Zikan, Michal; Claes, Kathleen; Poppe, Bruce; Foretova, Lenka; Mai, Phuong L; Greene, Mark H; Rennert, Gad; Lejbkowicz, Flavio; Glendon, Gord; Ozcelik, Hilmi; Andrulis, Irene L; Thomassen, Mads; Gerdes, Anne-Marie; Sunde, Lone; Cruger, Dorthe; Birk Jensen, Uffe; Caligo, Maria; Friedman, Eitan; Kaufman, Bella; Laitman, Yael; Milgrom, Roni; Dubrovsky, Maya; Cohen, Shimrit; Borg, Ake; Jernström, Helena; Lindblom, Annika; Rantala, Johanna; Stenmark-Askmalm, Marie; Melin, Beatrice; Nathanson, Kate; Domchek, Susan; Jakubowska, Ania; Lubinski, Jan; Huzarski, Tomasz; Osorio, Ana; Lasa, Adriana; Durán, Mercedes; Tejada, Maria-Isabel; Godino, Javier; Benitez, Javier; Hamann, Ute; Kriege, Mieke; Hoogerbrugge, Nicoline; van der Luijt, Rob B; van Asperen, Christi J; Devilee, Peter; Meijers-Heijboer, E J; Blok, Marinus J; Aalfs, Cora M; Hogervorst, Frans; Rookus, Matti; Cook, Margaret; Oliver, Clare; Frost, Debra; Conroy, Don; Evans, D Gareth; Lalloo, Fiona; Pichert, Gabriella; Davidson, Rosemarie; Cole, Trevor; Cook, Jackie; Paterson, Joan; Hodgson, Shirley; Morrison, Patrick J; Porteous, Mary E; Walker, Lisa; Kennedy, M John; Dorkins, Huw; Peock, Susan; Godwin, Andrew K; Stoppa-Lyonnet, Dominique; de Pauw, Antoine; Mazoyer, Sylvie; Bonadona, Valérie; Lasset, Christine; Dreyfus, Hélène; Leroux, Dominique; Hardouin, Agnès; Berthet, Pascaline; Faivre, Laurence; Loustalot, Catherine; Noguchi, Tetsuro; Sobol, Hagay; Rouleau, Etienne; Nogues, Catherine; Frénay, Marc; Vénat-Bouvet, Laurence; Hopper, John L; Daly, Mary B; Terry, Mary B; John, Esther M; Buys, Saundra S; Yassin, Yosuf; Miron, Alexander; Goldgar, David; Singer, Christian F; Dressler, Anne Catharina; Gschwantler-Kaulich, Daphne; Pfeiler, Georg; Hansen, Thomas V O; Jønson, Lars; Agnarsson, Bjarni A; Kirchhoff, Tomas; Offit, Kenneth; Devlin, Vincent; Dutra-Clarke, Ana; Piedmonte, Marion; Rodriguez, Gustavo C; Wakeley, Katie; Boggess, John F; Basil, Jack; Schwartz, Peter E; Blank, Stephanie V; Toland, Amanda Ewart; Montagna, Marco; Casella, Cinzia; Imyanitov, Evgeny; Tihomirova, Laima; Blanco, Ignacio; Lazaro, Conxi; Ramus, Susan J; Sucheston, Lara; Karlan, Beth Y; Gross, Jenny; Schmutzler, Rita; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Lochmann, Magdalena; Arnold, Norbert; Heidemann, Simone; Varon-Mateeva, Raymonda; Niederacher, Dieter; Sutter, Christian; Deissler, Helmut; Gadzicki, Dorothea; Preisler-Adams, Sabine; Kast, Karin; Schönbuchner, Ines; Caldes, Trinidad; de la Hoya, Miguel; Aittomäki, Kristiina; Nevanlinna, Heli; Simard, Jacques; Spurdle, Amanda B; Holland, Helene; Chen, Xiaoqing; Platte, Radka; Chenevix-Trench, Georgia; Easton, Douglas F<br/><br/>Útdráttur: The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10(-11) - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers.<br/><br/>Lýsing: To access publisher full text version of this article. Please click on the hyperlink in Additional Links field http://hdl.handle.net/2336/129497 Titill: Changing epidemiology of methicillin-resistant Staphylococcus aureus in Iceland from 2000 to 2008: a challenge to current guidelines<br/><br/>Höfundar: Holzknecht, Barbara Juliane; Hardardottir, Hjordis; Haraldsson, Gunnsteinn; Westh, Henrik; Valsdottir, Freyja; Boye, Kit; Karlsson, Sigfus; Kristinsson, Karl Gustaf; Gudlaugsson, Olafur<br/><br/>Útdráttur: The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) is continuously changing. Iceland has a low incidence of MRSA. A "search and destroy" policy (screening patients with defined risk factors and attempting eradication in carriers) has been implemented since 1991. Clinical and microbiological data of all MRSA patients from the years 2000 to 2008 were collected prospectively. Isolates were characterized by pulsed-field gel electrophoresis (PFGE), sequencing of the repeat region of the Staphylococcus protein A gene (spa typing), staphylococcal cassette chromosome mec (SCCmec) typing, and screening for the Panton-Valentine leukocidin (PVL) gene. Two hundred twenty-six infected (60%) or colonized (40%) individuals were detected (annual incidence 2.5 to 16/100,000). From 2000 to 2003, two health care-associated outbreaks dominated (spa types t037 and t2802), which were successfully controlled with extensive infection control measures. After 2004, an increasing number of community-associated (CA) cases without relation to the health care system occurred. A great variety of clones (40 PFGE types and 49 spa types) were found, reflecting an influx of MRSA from abroad. The USA300 and Southwest Pacific (SWP) clones were common. SCCmec type IV was most common (72%), and 38% of the isolates were PVL positive. The incidence of MRSA in Iceland has increased since 1999 but remains low and has been stable in the last years. The search and destroy policy was effective to control MRSA in the health care setting. However, MRSA in Iceland is now shifting into the community, challenging the current Icelandic guidelines, which are tailored to the health care system.<br/><br/>Lýsing: To access publisher full text version of this article. Please click on the hyperlink in Additional Links field http://hdl.handle.net/2336/129523 Titill: Confidentiality and physicians' health. A cross-sectional study of University Hospital Physicians in four European cities (the HOUPE-study)<br/><br/>Höfundar: Løvseth, Lise Tevik; Aasland, Olaf Gjerløw; Fridner, Ann; Jonsdottir, Lilja Sigrun; Marini, Massimo; Linaker, Olav Morten<br/><br/>Útdráttur: OBJECTIVE: To investigate how the subjective burden of confidentiality can act as a stressor that affects physicians' psychological health and wellbeing.METHOD: Cross-sectional survey data from a sample of university hospital physicians (N=1,956) in four European countries (Sweden, Norway, Iceland and Italy) who participated in the HOUPE (Health and Organization among University hospital Physicians in Europe) study was analysed.RESULTS: About 25% of the participants reported that confidentiality impedes emotional support to a considerable degree. An index of confidentiality as a barrier to seeking support (ICBS) had a negative effect on physicians' health and wellbeing. The effect of ICBS was confirmed and slightly increased when controlled for variables known to buffer the adverse mental and physical effects of stress. Though the physicians in Iceland and in Norway found confidentiality the most challenging, it was the physicians in Italy and Sweden who showed a significant effect of ICBS on their health and wellbeing.CONCLUSIONS: Whether confidentiality is a stressor in its own right or an amplifier of stressful situations in medical practice should be further investigated to gain a better understanding of the effect of confidentiality on physicians' coping, stress and health. In addition, there is a need to investigate how physicians can balance coping with the inevitable emotional demands of medical practice and maintaining the ethics of confidentiality in a way that protects both patients' privacy rights and physicians' health and wellbeing.<br/><br/>Lýsing: To access publisher full text version of this article. Please click on the hyperlink in Additional Links field http://hdl.handle.net/2336/129511 Titill: Agreement between image grading of conventional (45°) and ultra wide-angle (200°) digital images in the macula in the Reykjavik eye study.<br/><br/>Höfundar: Csutak, A; Lengyel, I; Jonasson, F; Leung, I; Geirsdottir, A; Xing, W; Peto, T<br/><br/>Útdráttur: PURPOSE: To establish the agreement between image grading of conventional (45°) and ultra wide-angle (200°) digital images in the macula.METHODS: In 2008, the 12-year follow-up was conducted on 573 participants of the Reykjavik Eye Study. This study included the use of the Optos P200C AF ultra wide-angle laser scanning ophthalmoscope alongside Zeiss FF 450 conventional digital fundus camera on 121 eyes with or without age-related macular degeneration using the International Classification System. Of these eyes, detailed grading was carried out on five cases each with hard drusen, geographic atrophy and chorioretinal neovascularisation, and six cases of soft drusen. Exact agreement and κ-statistics were calculated.RESULTS: Comparison of the conventional and ultra wide-angle images in the macula showed an overall 96.43% agreement (κ=0.93) with no disagreement at end-stage disease; although in one eye chorioretinal neovascularisation was graded as drusenoid pigment epithelial detachment. Of patients with drusen only, the exact agreement was 96.1%. The detailed grading showed no clinically significant disagreement between the conventional 45° and 200° images.CONCLUSIONS: On the basis of our results, there is a good agreement between grading conventional and ultra wide-angle images in the macula<br/><br/>Lýsing: To access publisher full text version of this article. Please click on the hyperlink in Additional Links field http://hdl.handle.net/2336/129510 Titill: Familial monoclonal gammopathy: hyper-responsive B cells in unaffected family members<br/><br/>Höfundar: Steingrímsdottir, Hlif; Einarsdottir, Helga K; Haraldsdottir, Vilhelmina; Ogmundsdottir, Helga M<br/><br/>Útdráttur: Background:  In Iceland, eight families have been identified with multiple cases of monoclonal gammopathies (MG) and other lymphoproliferative diseases. In one of these families with several cases of monoclonal gammopathy of undetermined significance (MGUS) and Waldenströms macroglobulinemia, in vitro stimulation with poke-weed mitogen revealed hyper-responsive B cells showing increased immunoglobulin production in one-third of disease-free family members. Design and methods:  In this study, the families were further traced and the list of names produced was compared with The Icelandic Cancer Registry (ICR) to find all recent cases of lymphoproliferative diseases. First-degree relatives and descendants older than 20 yrs of age (n = 350) were selected for screening for paraprotein. Selected family members were tested for B-cell hyper-responsiveness and the lymphocyte phenotype was analysed by flow cytometry. Results:  Comparison of the total list of 4370 family members with the ICR revealed 22 new cases and screening for serum paraprotein identified nine new cases of MG, eight being first-degree relatives of known probands. Sixty cases of lymphoproliferative diseases are currently known within the eight families, five of them containing both IgG/A and IgM disorders. Twelve hyper-responders (HR) were identified in four families, eight from one family, of whom four were known already. Stimulated B cells from HR had a significantly higher proportion of CD27(+) memory/plasma cells than controls. Conclusion:  Identification of new affected family members by screening confirms a hereditary predisposition to B-cell proliferative diseases. Contrary to most studies, IgG/A and IgM disorders occurred together in five families. In four families, enhanced B-cell responsiveness was found in healthy subjects clustered around cases.<br/><br/>Lýsing: To access publisher full text version of this article. Please click on the hyperlink in Additional Links field http://hdl.handle.net/2336/129342 Titill: Hand osteoarthritis severity is associated with total knee joint replacements independently of BMI : the Ages-Reykjavik study<br/><br/>Höfundar: Jonsson, Helgi; Helgadottir, Gudrun P; Aspelund, Thor; Eiriksdottir, Gudny; Sigurdsson, Sigurdur; Siggeirsdottir, Kristin; Ingvarsson, Thorvaldur; Harris, Tamara B; Launer, Lenore; Gudnason, Vilmundur<br/><br/>Útdráttur: OBJECTIVE: To identify factors associated with having total knee replacement due to osteoarthritis in the AGES-Reykjavik Study, a large population based study of elderly Icelanders.METHODS: Information about total knee and hip joint replacements (TKR,THR) and hand OA (HOA) severity was available in 2195 males and 2975 females, mean age 76±6 years. The prevalence of TKR was 223 (4.3%) and THR 316 (6.1%). We performed a backwards binary logistic regression analysis of possible OA associated variables including age, gender, abdominal circumference, BMI, hs-CRP, cholesterol, statin use, bone mineral density of the spine, education and smoking history as well as HOA severity and the presence of THR.RESULTS: Only three factors showed significant associations with TKR; BMI (p=3.5x10(-17)), HOA severity (p=2.9x10(-8)) and THR (p=0.0002). The highest quintile of BMI was associated with a fivefold risk of TKR compared with the lowest (8% vs 1.6%), and severe HOA had a 2.4 fold risk compared with those with no HOA (8% vs 3.3%). There was no statistical interaction between BMI and HOA. Thus, individuals with BMI<23.5 with no evidence of HOA had a prevalence of TKR of 1.1%, while those with BMI>30.3 and severe HOA had a prevalence of 13.4%.CONCLUSIONS: Hand and hip osteoarthritis in conjunction with BMI are strongly associated with the prevalence of TKR due to osteoarthritis. Together, BMI and HOA severity seem to contribute to the majority of the total TKR prevalence. While BMI has long been recognized as the major risk factor for TKR, the influence of osteoarthritis at other sites may have been underestimated.<br/><br/>Lýsing: To access publisher full text version of this article. Please click on the hyperlink in Additional Links field http://hdl.handle.net/2336/129300 Titill: Trends in prevalence and characteristics of cerebral palsy among Icelandic children born 1990 to 2003.<br/><br/>Höfundar: Sigurdardottir, Solveig; Thorkelsson, Thordur; Halldorsdottir, Margret; Thorarensen, Olafur; Vik, Torstein<br/><br/>Útdráttur: Aim To describe trends in cerebral palsy (CP) prevalence, severity, and associated impairments among 139 Icelandic children (65 males, 74 females) born from 1990 to 1996 (period one) and 1997 to 2003 (period two). Method A population-based study using systematically collected data on motor functioning and associated impairments of children with CP. Mean age at assessment was 5 years 5 months (SD 7.68 mo) in period one and 5 years 5 months (SD 10.44 mo) in period two. Infants with postneonatal CP were excluded. Results Prevalence of CP per 1000 live births was 2.2 in period one and 2.3 in period two (p=0.862); it decreased from 1.5 to 0.9 for children born at term, was stable for preterm births, but increased from 33.7 to 114.6 for very preterm births (p=0.002). Concurrently, neonatal and infant mortality rates decreased in Iceland. The proportion of children born preterm increased over time (p=0.002), whereas improvements in gross motor function assessed with the Gross Motor Function Classification System were confined to term births (p=0.009). The proportion of children with diplegia increased, accompanied by a decrease in the proportion with quadriplegia (p=0.047). Furthermore, among term births there was a significant reduction over time in the proportion of children with epilepsy (p=0.030) and in the proportion with two or more associated impairments (p=0.030). Interpretation Although CP prevalence remained stable over 14 years, we observed a decrease in prevalence and severity of the disability among term births.<br/><br/>Lýsing: To access publisher full text version of this article. Please click on the hyperlink in Additional Links field http://hdl.handle.net/2336/129293 Titill: Molecular signatures of obstructive sleep apnea in adults: a review and perspective<br/><br/>Höfundar: Arnardottir, Erna S; Mackiewicz, Miroslaw; Gislason, Thorarinn; Teff, Karen L; Pack, Allan I<br/><br/>Útdráttur: The consequences of obstructive sleep apnea (OSA) are largely mediated by chronic intermittent hypoxia and sleep fragmentation. The primary molecular domains affected are sympathetic activity, oxidative stress and inflammation. Other affected domains include adipokines, adhesion molecules and molecules that respond to endoplasmic reticulum stress. Changes in molecular domains affected by OSA, assessed in blood and/or urine, can provide a molecular signature for OSA that could potentially be used diagnostically and to predict who is likely to develop different OSA-related comorbidities. High-throughput discovery strategies such as microarrays, assessing changes in gene expression in circulating blood cells, have the potential to find new candidates and pathways thereby expanding the molecular signatures for OSA. More research is needed to fully understand the pathophysiological significance of these molecular signatures and their relationship with OSA comorbidities. Many OSA subjects are obese, and obesity is an independent risk factor for many comorbidities associated with OSA. Moreover, obesity affects the same molecular pathways as OSA. Thus, a challenge to establishing a molecular signature for OSA is to separate the effects of OSA from obesity. We propose that the optimal strategy is to evaluate the temporal changes in relevant molecular pathways during sleep and, in particular, the alterations from before to after sleep when assessed in blood and/or urine. Such changes will be at least partly a consequence of chronic intermittent hypoxia and sleep fragmentation that occurs during sleep.<br/><br/>Lýsing: To access publisher full text version of this article. Please click on the hyperlink in Additional Links field