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  • 1.
    Ahl Jonsson, Christina
    et al.
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Stenberg, Annette
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Hollman Frisman, Gunilla
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    The lived experience of the early postoperative period after colorectal cancer surgery2011In: European Journal of Cancer Care, ISSN 0961-5423, E-ISSN 1365-2354, Vol. 20, no 2, p. 248-256Article in journal (Refereed)
    Abstract [en]

    Colorectal cancer is one of the most common cancer diagnoses and undergoing colorectal cancer surgery is reported to be associated with physical symptoms and psychological reactions. Social support is described as important during the postoperative period. The purpose of this paper was to describe how patients experience the early postoperative period after colorectal cancer surgery.

    Interviews according a phenomenological approach were performed with 13 adult participants, within 1 week after discharge from hospital. Data were collected from August 2006 to February 2007. Analysis of the interview transcripts was conducted according to Giorgi.

    The essence of the phenomenon was to regain control over ones body in the early postoperative period after colorectal cancer surgery. Lack of control, fear of wound and anastomosis rupture, insecurity according to complications was prominent findings.

    When caring for these patients it is a challenge to be sensitive, encourage and promote patients to express their feelings and needs. One possibility to empower the patients and give support could be a follow up phone call within a week after discharge.

  • 2.
    Aleman, Soo
    et al.
    Departments of Gastroenterology and Hepatology, Karolinska University Hospital/Karolinska Institutet, Stockholm.
    Endalib, Sanam
    Departments of Gastroenterology and Hepatology, Karolinska University Hospital/Karolinska Institutet, Stockholm.
    Stal, Per
    Departments of Gastroenterology and Hepatology, Karolinska University Hospital/Karolinska Institutet, Stockholm.
    Loof, Lars
    Clinincal Research Centre, Västerås.
    Lindgren, Stefan
    Skåne University Hospital, Lund/Malmö.
    Sandberg-Gertzen, Hanna
    Örebro University Hospital, Örebro.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Olsson, Sigvard
    Sahlgrenska University Hospital, Göteborg.
    Danielsson, Ake
    Umeå University Hospital, Umeå.
    Wallerstedt, Sven
    Sahlgrenska University Hospital, Göteborg.
    Hultcrantz, Rolf
    Departments of Gastroenterology and Hepatology, Karolinska University Hospital/Karolinska Institutet, Stockholm.
    Health check-ups and family screening allow detection of hereditary hemochromatosis with less advanced liver fibrosis and survival comparable with the general population2011In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 46, no 9, p. 1118-1126Article in journal (Refereed)
    Abstract [en]

    Objective. The information concerning the morbidity and mortality of hereditary hemochromatosis is based primarily on clinical cohorts of symptomatic patients. The major aim of this study was to analyze the long-term prognosis for Swedish patients with this condition, with respect to both clinical features and survival, in relation to the route by which the disease was detected. Patients and methods. 373 patients with hemochromatosis detected through routine health checkups (n = 153), family screening (n = 44), symptoms of arthralgia (n = 23), investigation of other diseases/symptoms (n = 108) or signs of liver disease (n = 45) were monitored for a mean period of 11.9 +/- 5.8 years. The degree of liver fibrosis and survival were analyzed. Results. Overall survival among these patients was not significantly different from that of a matched normal population. The patients diagnosed through health check-ups and family screening were detected at an earlier age and had the highest rate of survival. Liver biopsy at the time of diagnosis revealed cirrhosis in 9% of those detected through the health check-ups and 5% in the case of family screening, compared with 13% for the group with arthralgia, 17% for other diseases/symptoms and 42% for liver disease. Conclusion. Health check-ups and family screening allow detection of hereditary hemochromatosis at an earlier age and with less advanced liver fibrosis, although a few of these patients have already developed cirrhosis. Our study indicates that iron indices should be included in health check-ups, and if abnormal, should lead to further investigation.

  • 3.
    Bager, P.
    et al.
    Aarhus University Hospital, Denmark .
    Befrits, R.
    Karolinska University Hospital, Sweden .
    Wikman, O.
    Stockholm S Gen Hospital, Sweden .
    Lindgren, S.
    Lund University, Sweden .
    Moum, B.
    Oslo University Hospital, Norway .
    Hjortswang, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Hjollund, N.H.
    Aarhus University Hospital, Denmark Hospital Unit Western Jutland, Denmark .
    Dahlerup, J.F.
    Aarhus University Hospital, Denmark .
    Fatigue in out-patients with inflammatory bowel disease is common and multifactorial2012In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 35, no 1, p. 133-141Article in journal (Refereed)
    Abstract [en]

    Background similar to Patients with inflammatory bowel disease (IBD) often complain of fatigue. Aim similar to To investigate the prevalence and characteristics of fatigue among IBD out-patients in Scandinavia and to provide normative values for fatigue in IBD patients. Methods similar to A cross-sectional study was conducted on 425 IBD patients from six out-patient centres in Denmark, Norway and Sweden. Fatigue was measured using the Multidimensional Fatigue Inventory. The patients were also screened for anaemia and iron deficiency. Each centre included approximately 5% of their IBD cohort. The patients were enrolled consecutively from the out-patient clinics, regardless of disease activity and whether the visit was scheduled. The fatigue analysis was stratified for age and gender. Results similar to Using the 95th percentile of the score of the general population as a cut-off, approximately 44% of the patients were fatigued. When comparing the IBD patients with disease activity to the IBD patients in remission, all dimensions of fatigue were statistically significant (P less than 0.05). Being anaemic or iron deficient was not associated with increased fatigue. Being a male patient with ulcerative colitis treated with corticosteroids was a strong determinant for increased fatigue. The normative ranges for IBD fatigue were calculated. Conclusions similar to Fatigue in IBD is common regardless of anaemia or iron deficiency. Fatigue in IBD is most marked for patients less than60 years of age. Stratifying for gender and age is necessary when analysing fatigue, as fatigue is expressed differently between groups.

  • 4.
    Bager, Palle
    et al.
    Aarhus University Hospital.
    Befrits, Ragnar
    Karolinska University Hospital.
    Wikman, Ola
    Stockholm S General Hospital.
    Lindgren, Stefan
    Lund University.
    Moum, Bjorn
    Oslo University Hospital.
    Hjortswang, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Dahlerup, Jens F
    Aarhus University Hospital.
    The prevalence of anemia and iron deficiency in IBD outpatients in Scandinavia2011In: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, ISSN 0036-5521, Vol. 46, no 3, p. 304-309Article in journal (Refereed)
    Abstract [en]

    Objective. To evaluate the prevalence of anemia and iron deficiency (ID) among patients with inflammatory bowel disease (IBD) in the Scandinavian countries. Material and methods. A cross-sectional study including 429 IBD patients from six centers in Denmark, Norway and Sweden. Patients were screened for anemia and ID. Each center included similar to 5% of their IBD cohort. Patients were consecutively seen in the outpatient clinic, regardless of disease activity and whether the visits were scheduled or not. Results. The overall prevalence of anemia was 19% (95% CI: 16--23%). The prevalence was higher among patients with Crohns disease than among patients with ulcerative colitis (p = 0.01). The etiology of anemia was as follows: iron deficiency anemia (20%), anemia of chronic disease (12%), and both conditions (68%). Less than 5% had folate acid or vitamin B12 deficiency. ID was found in 35% (CI: 31-40%) of the patients. Conclusions. Anemia was present in every fifth IBD patient and ID in every third IBD patient.

  • 5.
    Boström, E A
    et al.
    University of Gothenburg.
    Ekstedt, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Sjöwall, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Bokarewa, M I
    University of Gothenburg.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Resistin is Associated with Breach of Tolerance and Anti-nuclear Antibodies in Patients with Hepatobiliary Inflammation2011In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 74, no 5, p. 463-470Article in journal (Refereed)
    Abstract [en]

    Resistin is a cysteine-rich protein, which is abundantly expressed at the site of inflammation, and acts as a regulator of the NF-kB-dependent cytokine cascade. The aim of this study was to evaluate resistin levels in relation to inflammatory mediators, disease phenotype and autoantibody status in a spectrum of pathological conditions of the gastrointestinal tract. Resistin levels were measured with an ELISA in sera originated from 227 patients and 40 healthy controls (HC). Fifty patients diagnosed with non-alcoholic fatty liver disease (NAFLD), 53 ulcerative colitis (UC), 51 Crohns disease (CD), 46 autoimmune hepatitis (AIH) and 27 primary sclerosing cholangitis (PSC) were included. The sera were analysed with respect to biochemical parameters of systemic inflammation and liver function and to the presence of antibodies to nuclear antigens (ANA), mitochondria (AMA) and smooth muscle (SMA). Compared with HC, resistin levels were raised in AIH (P = 0.017) and PSC (P = 0.03); compared with NAFLD, levels were elevated in CD (P = 0.041), AIH (P andlt; 0.001) and PSC (P andlt; 0.001). Patients with elevated levels of resistin were more often treated with corticosteroids, but no difference was found between active disease and clinical remission. Resistin levels were significantly higher in ANA-positive individuals compared with ANA-negative (P = 0.025). Resistin levels were directly correlated with IL-6 (r = 0.30, P = 0.02) and IL-8 (r = 0.51, P andlt; 0.001). Elevated levels of resistin were prominent in patients with hepatobiliary inflammation and were associated with breach of self-tolerance, i.e. ANA positivity. Thus, we propose that resistin may be an important marker of disease severity in autoantibody-mediated gastrointestinal inflammatory diseases.

  • 6.
    Burisch, Johan
    et al.
    Herlev University Hospital.
    Cukovic-Cavka, Silvija
    University Hospital Rebro.
    Kaimakliotis, Ioannis
    Nicosia private practice, Cyprus.
    Shonova, Olga
    Hospital Ceske Budejovice.
    Andersen, Vibeke
    Viborg Reg Hospital.
    Dahlerup, Jens F.
    Arhus University Hospital.
    Elkjaer, Margarita
    Herlev University Hospital.
    Langholz, Ebbe
    Gentofte University Hospital.
    Pedersen, Natalia
    Herlev University Hospital.
    Salupere, Riina
    Tartu University Hospital.
    Kolho, Kaija-Leena
    University Helsinki.
    Manninen, Pia
    Tampere University Hospital.
    Laszlo Lakatos, Peter
    Semmelweis University Med.
    Shuhaibar, Mary
    Adelaide and Meath Hospital.
    Odes, Selwyn
    Soroka Med Centre.
    Martinato, Matteo
    University Padua.
    Mihu, Ion
    Centre Mother and Child University Hospital.
    Magro, Fernando
    Hospital Sao Joao.
    Belousova, Elena
    Moscow Reg Research Clin Institute.
    Fernandez, Alberto
    Hospital Povisa.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Halfvarson, Jonas
    Orebro University Hospital.
    Hart, Ailsa
    University London Imperial Coll Science Technology and Med.
    Munkholm, Pia
    Herlev University Hospital.
    Construction and validation of a web-based epidemiological database for inflammatory bowel diseases in Europe An EpiCom study2011In: JOURNAL OF CROHNS and COLITIS, ISSN 1873-9946, Vol. 5, no 4, p. 342-349Article in journal (Refereed)
    Abstract [en]

    Background: The EpiCom-study investigates a possible East-West-gradient in Europe in the incidence of IBD and the association with environmental factors. A secured web-based database is used to facilitate and centralize data registration. Aim: To construct and validate a web-based inception cohort database available in both English and Russian language. Method: The EpiCom database has been constructed in collaboration with all 34 participating centers. The database was translated into Russian using forward translation, patient questionnaires were translated by simplified forward-backward translation. Data insertion implies fulfillment of international diagnostic criteria, disease activity, medical therapy, quality of life, work productivity and activity impairment, outcome of pregnancy, surgery, cancer and death. Data is secured by the WinLog3 System, developed in cooperation with the Danish Data Protection Agency. Validation of the database has been performed in two consecutive rounds, each followed by corrections in accordance with comments. Results: The EpiCom database fulfills the requirements of the participating countries local data security agencies by being stored at a single location. The database was found overall to be "good" or "very good" by 81% of the participants after the second validation round and the general applicability of the database was evaluated as "good" or "very good" by 77%. In the inclusion period January 1st -December 31st 2010 1336 IBD patients have been included in the database. Conclusion: A user-friendly, tailor-made and secure web-based inception cohort database has been successfully constructed, facilitating remote data input. The incidence of IBD in 23 European countries can be found at www.epicom-ecco.eu. (C) 2011 European Crohns and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  • 7.
    Bäck, Karolina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Brännmark, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Strålfors, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Differential effects of IGF-I, IGF-II and insulin in human preadipocytes and adipocytes - Role of insulin and IGF-I receptors2011In: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 339, no 02-jan, p. 130-135Article in journal (Refereed)
    Abstract [en]

    We compared insulin and IGF effects in adipocytes expressing IR (insulin receptors), and preadipocytes expressing IR and IGF-IR (IGF-I receptors). Treatment of adipocytes with insulin, IGF-II or IGF-I resulted in phosphorylation of IR. Order of potency was insulin greater thanIGF-IIgreater than IGF-I. In preadipocytes IR, IGF-IR and insulin/IGF-I hybrid receptors (HR) were detected. Treatment of preadipocytes with IGF-I and IGF-II 10(-8) M resulted in activation of IGF-IR and IR whereas insulin was more potent in activating IR, with no effect on IGF-IR. In adipocytes glucose transport was 100-fold more sensitive to insulin than to IGFs and the maximal effect was higher with insulin. In preadipocytes glucose accumulation and DNA synthesis was equally sensitive to insulin and IGFs but the maximal effect was higher with IGF-I. In conclusion, insulin and IGF-I activate their cognate receptors and IGF-I also HR. IGF-II activates IR, IGF-IR and HR. Insulin and IGF-I are partial agonists to each others receptors.

  • 8.
    Bäck, Karolina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Islam, Rakibul
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Johansson, Git
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Chisalita, Ioana Simona
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Health Care.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Insulin and IGF1 receptors in human cardiac microvascular endothelial cells: metabolic, mitogenic and anti-inflammatory effects2012In: Journal of Endocrinology, ISSN 0022-0795, E-ISSN 1479-6805, Vol. 215, no 1, p. 89-96Article in journal (Refereed)
    Abstract [en]

    Diabetes is associated with microcirculatory dysfunction and heart failure and changes in insulin and IGF1 levels. Whether human cardiac microvascular endothelial cells (HMVEC-Cs) are sensitive to insulin and/or IGF1 is not known. We studied the role of insulin receptors (IRs) and IGF1 receptors (IGF1Rs) in metabolic, mitogenic and anti-inflammatory responses to insulin and IGF1 in HMVEC-Cs and human umbilical vein endothelial cells (HUVECs). IR and IGF1R gene expression was studied using real-time RT-PCR. Receptor protein expression and phosphorylation were determined by western blot and ELISA. Metabolic and mitogenic effects were measured as glucose accumulation and thymidine incorporation. An E-selectin ELISA was used to investigate inflammatory responses. According to gene expression and protein in HMVEC-Cs and HUVECs, IGF1R is more abundant than IR. Immunoprecipitation with anti-IGF1R antibody and immunoblotting with anti-IR antibody and vice versa, showed insulin/IGF1 hybrid receptors in HMVEC-Cs. IGF1 at a concentration of 10(-8) mol/l significantly stimulated phosphorylation of both IGF1R and IR in HMVEC-Cs. In HUVECs IGF1 10(-8) mol/l phosphorylated IGF1R. IGF1 stimulated DNA synthesis at 10(-8) mol/l and glucose accumulation at 10(-7) mol/l in HMVEC-Cs. TNF-alpha dramatically increased E-selectin expression, but no inflammatory or anti-inflammatory effects of insulin, IGF1 or high glucose were seen. We conclude that HMVEC-Cs express more IGF1Rs than IRs, and mainly react to IGF1 due to the predominance of IGF1Rs and insulin/IGF1 hybrid receptors. TNF-alpha has a pronounced pro-inflammatory effect in HMVEC-Cs, which is not counteracted by insulin or IGF1.

  • 9.
    Bäck, Karolina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Islam, Rakibul
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Johansson, Git
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Chisalita, Simona
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Health Care.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Role of insulin and IGF-I receptors in human cardiac microvascular endothelial cells; metabolic, mitogenic and anti-inflammatory effectsManuscript (preprint) (Other academic)
    Abstract [en]

    Diabetes is associated with coronary microcirculatory dysfunction and heart failure as well as changes in insulin and IGF-I levels. Our aim was to study the role of insulin receptors and IGF-I receptors in metabolic, mitogenic and anti-inflammatory responses to insulin and IGF-I in human cardiac microvascular endothelial cells (HMVEC-C) and, for comparison, also human umbilical vein endothelial cells (HUVEC). Insulin receptor (IR) and IGF-I receptor (IGF-IR) gene expression was studied with real-time RT-PCR. Receptor protein expression and phosphorylation was determined with Western blot and ELISA. The metabolic and mitogenic effects were measured as glucose accumulation and thymidine incorporation. An E-selectin ELISA was used to investigate the anti-inflammatory responses. IGF-IR was more abundant than IR both regarding gene expression and protein in HMVEC-C and HUVEC. Immunoprecipitation with anti-IGF-IR antibody and immunoblotting with anti-IR antibody and vice versa, showed insulin/IGF-I hybrid receptors in these cells. IGF-I 10-8 M significantly stimulated phosphorylation of both IGF-IR and IR in HMVEC-C. In HUVEC IGF-I 10-8 M phosphorylated IGF-IR. IGF-I also stimulated DNA synthesis at 10-8 M and glucose accumulation at 10-7 M. TNF-α significantly increased E-selectin expression whereas no effects were found by insulin, IGF-I or high glucose.

    We conclude that HMVEC-C express more IGF-I receptors than insulin receptors and at physiological concentrations of insulin and IGF-I mainly reacts to IGF-I probably due to the predominance of IGF-I receptors and insulin/IGF-I hybrid receptors. TNF-α has a pronounced pro-inflammatory effect in HMVEC-C which is not counteracted by insulin or IGF-I.

  • 10.
    Bäck, Karolina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Wahlström, Ola
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Gasslander, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Differential expression of insulin and IGF-I receptors in human tissuesManuscript (preprint) (Other academic)
    Abstract [en]

    Insulin and IGF-I are related peptides with similar structure. They both signal via their cognate receptors, the insulin receptor (IR) and the insulin-like growth factor (IGF)-I receptor (IGF-IR).

    Our aim was to simultaneously measure the amount of insulin and IGF-I receptors in different human tissues and also the IR-A and IR-B isoforms to study tissue specific expression

    Renal artery intima-media, myometrium, skeletal muscle or liver tissue samples were obtained from patients undergoing surgery. IR, IGF-IR, IR-A and IR-B gene expression was investigated with real-time RT-PCR and expression of IR and IGF-IR protein was examined by Western blot and ELISA.

    Renal arteries and myometrium expressed the IGF-IR gene to a higher extent than the IR gene, liver expressed more IR than IGF-IR and skeletal muscle expressed almost equal amounts of both receptors. IR-B was the most abundant isoform in all tissues. With Western blot we could detect IR in skeletal muscle, liver and myometrium. With ELISA we found that, normalized to total protein, the highest levels of IGF-IR were found in renal arteries and myometrium and low levels in skeletal muscle and liver. The highest levels of IR were found in liver.

    In conclusion there is a large variation in the quantity and ratio of insulin receptors and IGF-I receptors expressed in different tissues, the extremes being arterial intima media with predominantly IGF-I receptors and liver with predominantly insulin receptors. This suggests that differential expression of insulin and IGF-I receptors is a key mechanism in regulation of growth and metabolism.

  • 11.
    Chen, Fabian
    et al.
    Merck, Clin, Whitehouse Stn, NJ USA .
    Maccubbin, Darbie
    Merck, Clin, Whitehouse Stn, NJ USA .
    Weimer Anderson, Jennifer
    Merck, Clin, Whitehouse Stn, NJ USA .
    McCrary Sisk, Christine
    Merck, GSMP, Whitehouse Stn, NJ USA.
    Kher, Uma
    Merck, Stat, Whitehouse Stn, NJ USA .
    Olsson, Anders
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Bays, Harold E
    L MARC, Louisville, KY USA .
    Following Stable Therapy with Extended Release Niacin/Laropiprant, Continued Extended Release Niacin/Laropiprant Use Reduced Flushing versus Extended Release Niacin Alone in Dyslipidemic Patients in CIRCULATION, vol 124, issue 21, pp2011In: CIRCULATION, American Heart Association , 2011, Vol. 124, no 21Conference paper (Refereed)
    Abstract [en]

    n/a

  • 12.
    Chisalita, Ioana Simona
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Health Care.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Increased IGF1 levels in relation to heart failure and cardiovascular mortality in an elderly population: impact of ACE inhibitors2011In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 165, no 6, p. 891-898Article in journal (Refereed)
    Abstract [en]

    Objective: There are conflicting results regarding the association of circulating IGF1 with cardiovascular (CV) morbidity and mortality. We assessed the relationship between IGF1 levels and heart failure (HF), ischemic heart disease (IHD), and CV mortality in an elderly population taking into account the possible impact of angiotensin converting enzyme (ACE) inhibitors. Design and methods: A total of 851 persons aged 66-81 years, in a rural Swedish municipality, were subjected to medical history, clinical examination, electrocardiography, echocardiography, and fasting plasma samples. They were then followed for 8 years. Results and conclusion: Patients on ACE inhibitors had higher IGF1 levels compared with those without ACE inhibitors. In patients on ACE inhibitors, higher IGF1 values were found in patients with an ejection fraction (EF) less than40% compared with EF greater than= 40%, in patients with higher proBNP levels in quartile 4 vs 1, and in patients with IHD when compared to those without ACE inhibitors (P less than 0.001). In patients without ACE inhibitors, no relationship was found between IGF1 levels and HF or IHD. In multivariate regression, only ACE inhibitors, ECG changes characteristic for IHD, and gender had a significant impact on IGF1. Patients with higher IGF1 levels in quintiles 4 and 5 compared to quintiles 1 and 2 had a 50% higher risk for CV death (P=0.03). This was significant after adjustment for well-known CV risk factors and ACE inhibitors (P=0.03). Conclusions: Our results show that treatment with ACE inhibitors in an elderly population is associated with increased IGF1 levels, especially in patients with impaired cardiac function or IHD. High IGF1 levels tend to be associated with an increased risk for CV mortality.

  • 13.
    Dahle, Charlotte
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Hagman, A.
    Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Ignatova, Simone
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Antibodies against deamidated gliadin peptides identify adult coeliac disease patients negative for antibodies against endomysium and tissue transglutaminase2010In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 32, no 2, p. 254-260Article in journal (Refereed)
    Abstract [en]

    Background This study was done to evaluate the diagnostic utility of antibodies against deamidated gliadin peptides compared to traditional markers for coeliac disease. Aim To evaluate diagnostic utility of antibodies against deamidated gliadin peptide (DGP). Methods Sera from 176 adults, referred for endoscopy without previous analysis of antibodies against tissue transglutaminase (tTG) or endomysium (EmA), were retrospectively analysed by ELISAs detecting IgA/IgG antibodies against DGP or a mixture of DGP and tTG, and compared with IgA-tTG and EmA. Seventy-nine individuals were diagnosed with coeliac disease. Results Receiver operating characteristic analyses verified the manufacturers cut-off limits except for IgA/IgG-DGP/ tTG. In sera without IgA deficiency, the sensitivity was higher for IgA/IgG-DGP (0.85-0.87) compared with IgA-tTg (0.76) and EmA (0.61). All tests showed high specificity (0.95-1.00). Eighteen coeliac disease-sera were negative regarding IgA-tTG, nine of which were positive for IgA/IgG-DGP. Sera from coeliac disease-patients greater than70 years were more often negative for IgA-tTG (50%) and IgA/IgG-DGP (36%) than younger patients (15% and 8% respectively) (P less than 0.01). Three of the four IgA-deficient patients were positive in the IgA/IgG-DGP assay. Conclusions In this study of patients unselected regarding IgA-tTg/EmA, thus unbiased in this respect, IgA/IgG-DGP identified adult coeliac disease patients negative for antibodies against endomysium and tissue transglutaminase. Serology is often negative in elderly patients with coeliac disease; a small bowel biopsy should therefore be performed generously before coeliac disease is excluded.

  • 14.
    Dahlén, Elsa M
    et al.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Andreasson, Thomas
    Sahlgrenska University Hospital, Göteborg.
    Cinthio, Magnus
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Primary Health Care Centres.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Thoracic and Vascular Surgery in Östergötland.
    Is there an underestimation of intima-media thickness based on M-mode ultrasound technique in the abdominal aorta?2012In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 32, no 1, p. 1-4Article in journal (Refereed)
    Abstract [en]

    Measuring intima-media thickness (IMT) in the common carotid artery (CCA) is a valuable resource for the evaluation of subclinical atherosclerosis. The main objective of this study was to explore whether a B-mode ultrasound technique, Philips ATL, and an M-mode ultrasound technique, Wall Track System (WTS), show interchangeable results when measured in CCA and the abdominal aorta (AA). A total of 24 healthy, young subjects were examined. IMT and lumen diameter (LD) of the AA and the CCA were measured twice by two skilled ultrasonographers with two different ultrasound equipment B-mode: (Philips, ATL and M-mode: WTS).The intra-observer variability of IMT in CCA and AA using B-mode showed a coefficient of variation 8% and 9%, and with M-mode 11% and 15%, respectively. Interobserver variability of IMT in CCA and AA using B-mode was 6% and 12%, and with M-mode 11% and 18%, respectively. CCA IMT was 0·53 ± 0·07 and 0·53 ± 0·09 mm using B-mode and M-mode, respectively. However, in AA, IMT was 0·61 ± 0·5 and 0·54 ± 0·10 mm using B-mode and M-mode, respectively. Thus, AA IMT was 11·5% thicker using B-mode (P<0·01). We received adequate IMT readings from the carotid artery as well as the AA using two commonly used B-mode and M-mode techniques. B-mode technique seems to show less variability, especially in the AA. More importantly, the two techniques measured different IMT thickness in the aorta, emphasizing the importance of using similar technique when comparing the impact of absolute values of IMT on cardiovascular disease.

  • 15.
    Dahlén, Elsa M
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Grodzinsky, Ewa
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Nyström, Fredrik
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland.
    Carotid intima-media thickness and apolipoprotein B/apolipoprotein A-I ratio in middle-aged patients with Type 2 diabetes2009In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 26, no 4, p. 384-390Article in journal (Refereed)
    Abstract [en]

    Aims To explore the association between carotid intima-media thickness (IMT) and the apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) ratio compared with conventional lipids in middle-aged patients with Type 2 diabetes.

    Methods We analysed data from 247 patients with Type 2 diabetes, aged 55–66 years, in the Cardiovascular Risk factors in Patients with Diabetes—a Prospective study in Primary care (CARDIPP-1) study. Primary care nurses measured blood pressure and anthropometric characteristics. Blood samples were taken for laboratory analyses. The carotid IMT was determined by ultrasonography at the University Hospital in Linköping and at the County Hospital Ryhov, Jönköping, Sweden.

    Results The ApoB/apoA-I ratio (r = 0.207, P = 0.001), apoB (r = 0.166, P = 0.009) and non-high-density lipoprotein cholesterol (non-HDL-c) (r = 0.129, P = 0.046) correlated with IMT. Conventional lipids, high-sensitivity C-reactive protein (hsCRP), glycated haemoglobin (HbA1c) and systolic blood pressure were not significantly correlated to IMT. A stepwise logistic regression analysis was conducted with IMT as the dependent variable and the apoB/apoA-I ratio, HbA1c, hsCRP, low-density lipoprotein cholesterol (LDL-c), total cholesterol, non-HDL-c and treatment with statins as independent variables. Following adjustment for age and gender, only the apoB/apoA-I ratio remained significantly associated with IMT (odds ratio 4.3, 95% confidence intervals 1.7–10.8, P = 0.002).

    Conclusions We conclude that there was a significant association between the apoB/apoA-I ratio and IMT in middle-aged patients with Type 2 diabetes. The association was independent of conventional lipids, hsCRP, glycaemic control and use of statins.

  • 16.
    Ekstedt, Mattias
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Franzén, Lennart E
    Aleris Medilab, Täby.
    Mathiesen, Ulrik L
    County Hospital, Oskarshamn.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Cardiology. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL. Linköping University, Faculty of Health Sciences.
    Low clinical relevance of the nonalcoholic fatty liver disease activity score (NAS) in predicting fibrosis progression2012In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 47, no 1, p. 108-115Article in journal (Refereed)
    Abstract [en]

    Background/Aims. The nonalcoholic fatty liver disease (NAFLD) activity score (NAS) is a newly proposed system to grade the necroinflammatory activity in liver biopsies of NAFLD patients. This study evaluates the usefulness of the NAS in predicting clinical deterioration and fibrosis progression in NAFLD. Methods. One hundred and twenty-nine patients with biopsy-proven NAFLD were included in a long-term histological follow-up study. Clinical course and change in fibrosis stage were compared between nonalcoholic steatohepatitis (NASH), “borderline NASH,” and “not NASH” patients. Significant fibrosis progression was defined as progression of more than one fibrosis stage or development of end-stage liver disease during follow-up. Results. Eighty-eight patients accepted reevaluation and 68 underwent repeat liver biopsy. Mean time between biopsies was 13.8 ± 1.2 years (range 10.3–16.3). At baseline, NASH was diagnosed in 2 (1.6%) patients, and at follow-up, in 1 (1.5%) patient. A trend toward higher baseline NAS was seen in patients (n = 7) who developed end-stage liver disease (3.1 ± 0.9 vs. 2.2 ± 1.0; p = 0.050). Baseline NAS was associated with progressive disease in a univariate binary logistic regression analysis (p = 0.024), but no difference was seen in the multivariate analysis including the NAS, portal inflammation, and perisinusoidal fibrosis. Moreover, 18% of patients without NASH progressed significantly in fibrosis stage. Conclusions. The ability of the NAS to predict progression of NAFLD is poor. The clinical usefulness of the score is limited due to the significant overlap in clinical development between NAS score groups. To use the NAS as endpoint in treatment trial is not justified.

  • 17.
    Forsgren, Mikael
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Ekstedt, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Andregård, O.
    Dahlström, Nils
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Kihlberg, Johan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Prospective evaluation of liver steatosis comparing stereological point-counting biopsy analysis and 1H MRS2012Conference paper (Other academic)
  • 18.
    Forsgren, Mikael F
    et al.
    Linköping University. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Norén, Bengt
    Linköping University, Department of Medical and Health Sciences, Radiology. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Faculty of Health Sciences.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Physiology. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Faculty of Health Sciences.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Faculty of Health Sciences.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Department of Medical and Health Sciences, Radiology. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Faculty of Health Sciences.
    On the Evaluation of 31P MRS Human Liver Protocols2010Conference paper (Other academic)
  • 19.
    Franck, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Gummesson, Anders
    Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Jernås, Margareta
    Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Guillot, Gilles
    Department of Mathematical Statistics, Chalmers University of Technology and University of Gothenburg, Gothenburg, Sweden; Applied Mathematics and Computer Sciences Department,National Research Institute for Agronomy, Paris, France; Centre for Ecology and Evolutionary Synthesis, Department of Biology, University of Oslo, Oslo, Norway.
    Glad, Camilla
    Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Svensson, Per-Arne
    Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden;.
    Rudemo, Mats
    Department of Mathematical Statistics, Chalmers University of Technology and University of Gothenburg, Gothenburg, Sweden.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Carlsson, Lena M. S.
    Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Olsson, Bob
    Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Identification of adipocyte genes regulated by caloric intake2011In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 96, no 2, p. E413-E418Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Changes in energy intake have marked and rapid effects on metabolic functions and some of the effects may be due to changes in adipose tissue gene expression that precede alterations in body weight.

    OBJECTIVE: To identify genes in adipose tissue regulated by changes in caloric intake independent of changes in body weight.

    RESEARCH DESIGN AND METHODS: Obese subjects were given a very-low calorie diet (VLCD; 450 kcal/day) for 16 weeks. After the diet, ordinary food was gradually reintroduced during 2 weeks while there were minimal changes in body weight. Adipose tissue gene expression was measured by microarray analysis. First, genes regulated during caloric restriction and in the opposite direction during the weight stable re-feeding phase were identified. To verify opposite regulation to that observed during caloric restriction, identified genes were further analyzed using adipocyte expression profiles from healthy subjects before and after overfeeding. Results were confirmed using real time PCR or immunoassay.

    RESULTS: Using a significance level of p<0.05 for all comparisons, 52 genes were downregulated and 50 were up-regulated by caloric restriction and regulated in the opposite direction by re-feeding and overfeeding. Among these were genes that affect lipogenesis (ACLY, ACACA, FASN, SCD), protein synthesis (4EBP1, 4EBP2), beta-oxidation (CPT1B), liberation of fatty acids (CIDEA) and glyceroneogenesis (PCK2). Interestingly, several of these are under control of the master regulator mTOR.

    CONCLUSIONS: The observed transcriptional changes indicate that mTOR plays a central role in the control of diet-regulated adipocyte genes involved in lipogenesis and protein synthesis.

  • 20.
    Gullstrand, Camilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Wahlberg Topp, Jeanette
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Ilonen, Jorma
    Dept of Microbiology Kuopio, Finland.
    Vaarala, Outi
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Progression to type 1 diabetes and autoantibody positivity in relation to HLA-risk genotypes in children participating in the ABIS study2008In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 9, no 3 PART 1, p. 182-190Article in journal (Refereed)
    Abstract [en]

    Background: Autoantibodies against beta-cell antigens together with human leukocyte antigen (HLA)-risk genotypes are used as predictive markers for type 1 diabetes (T1D). In this study, we have investigated the role of HLA-risk and -protective genotypes for development of beta-cell autoantibodies and progression to T1D in healthy children. Methods: T1D-related HLA genotypes and autoantibodies against glutamic acid decarboxylase [glutamic acid decarboxylase antibodies (GADA)] and islet antigen-2 (IA-2A) were studied at 1, 2.5 and 5 yr of age in unselected healthy children and children with T1D participating in the All Babies In Southeast Sweden (ABIS) study. Results: GADA or IA-2A positivity at 5 yr of age was associated with DR4-DQ8 haplotype and DR3-DQ2/DR4-DQ8 genotype. By the age of 6-7 yr, we identified 32 children with T1D among the 17 055 participants in the ABIS study. Eight of 2329 (0.3%) non-diabetic children had permanent autoantibodies, and 143 of 2329 (6%) children had transient autoantibodies. HLA-risk genotypes associated with T1D, whereas protective genotypes were seldom found in children with T1D. Children with permanent autoantibodies had more often risk-associated DR4-DQ8 haplotype than autoantibody-negative children. No associations with HLA-risk or -protective genotypes were found for transient autoantibodies. Conclusions: The strong relation between HLA-risk alleles and T1D once again confirmed that HLA-risk genotypes play an important role for development of T1D. However, HLA genotypes seem not to explain induction of autoantibodies, especially transient autoantibodies, in the general population, emphasizing the role of environmental factors in the initiation of autoimmunity. It seems that HLA-risk genotypes are responsible for maturation of the permanent autoantibody response. © 2008 The Authors Journal compilation © 2008 Blackwell Munksgaard.

  • 21.
    Gustavsson, A
    et al.
    Örebro University Hospital, Sweden.
    Järnerot, G
    Örebro University Hospital, Sweden.
    Hertervig, E
    Lund University Hospital, Sweden.
    Friis-Liby, I
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Blomquist, L
    Karolinska University Hospital, Sweden.
    Karlén, P
    Södersjukhuset, Stockholm, Sweden.
    Grännö, C
    Ryhov Hospital, Jönköping.
    Vilien, M
    Hilleroed Hospital, Denmark.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Verbaan, H
    Malmö General University Hospital, Sweden.
    Hellström, P M
    Karolinska University Hospital, Sweden.
    Magnuson, A
    Örebro University Hospital, Sweden.
    Halfvarson, J
    Örebro University Hospital, Sweden.
    Tysk, C
    Örebro University Hospital, Sweden.
    Clinical trial: colectomy after rescue therapy in ulcerative colitis-3-year follow-up of the Swedish-Danish controlled infliximab study2010In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 32, no 8, p. 984-989Article in journal (Refereed)
    Abstract [en]

    Background The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described.

    Aim To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis.

    Method In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up.

    Results Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P = 0.02). There was no mortality.

    Conclusion The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy.

  • 22.
    Haglund, Sofie
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Interindividual differences in thiopurine metabolism: studies with focus on inflammatory bowel disease2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The thiopurines, 6-mercaptopurine and its prodrug azathioprine, are used in the treatment of inflammatory bowel disease, ulcerative colitis and Crohn´s disease. The main active metabolites are the phosphorylated thioguanine nucleotides (6-TGNs) and methylated thioinosine monophosphate (meTIMP). Both groups contribute to the immunomodulatory effects. About 30-40% of patients fail to benefit from thiopurine treatment. A well-known cause of adverse reactions is decreased or absent thiopurine S-methyltransferase (TPMT) activity. Low TPMT activity is inherited as an autosomal codominant recessive trait and is present in approximately 10% of the population. Although several clinical issues can be solved from determination of TPMT activity, there are cases where it is not possible. In Sweden approximately 25% of IBD-patients display suboptimal 6-TGN concentrations and unexpectedly high concentrations of meTIMP despite a normal TPMT activity. A high meTIMP/6-TGN concentration ratio has been associated with both unresponsiveness to therapy and emergence of adverse reactions. Inosine 5’-monophosphate dehydrogenase (IMPDH) may constitute a candidate gene to explain this metabolite profile, as it is strategically positioned in the metabolic pathway of thiopurines where it competes with TPMT for their common substrate 6-TIMP.

    In paper I a pyrosequencing method was developed for genotyping of at that time all known genetic variants of TPMT. The concordance between genotype and phenotype in 30 individuals was 93%. The allele frequencies of TPMT*3A, *3B, *3C and *2 in a Swedish background population (n=800) were in agreement with those in other Caucasian or European populations. In Paper II-IV we explored the molecular basis of different metabolite profiles, i.e. low, normal and high meTIMP/6-TGN concentration ratios. The activity of IMPDH was measured in mononuclear cells (MNC). Patients with high metabolite ratios had lower IMPDH activity than patients with normal or low ratios, explained by an inverse correlation to red blood cells concentration of meTIMP. No correlation to 6-TGN was observed. Downregulation of IMPDH activity in HEK293 cells with genetically engineered TPMT activity was associated with an increase in meTIMP, but unexpectedly also of 6-TGN, irrespective of the TPMT status. These results suggest effects of pharmacogenes other than TPMT and IMPDH. A whole genome expression analysis was performed, (1) to identify new candidate genes that could explain differences in metabolite profiles, and (2) to study genes with known associations to the metabolic pathway of (thio)purines. The whole genome expression analysis did not identify any significant group differences. In analysis of the thiopurine related genes, three clusters of co-regulated genes were defined. A co-operation between expression levels of SLC29A1 and NT5E in explaining the meTIMP/6-TGN concentration ratio was observed, and individually SLC29A1 and NT5E correlated to 6-TGN and meTIMP, respectively.

    Pysosequencing is a convenient and flexible method which is now run in parallel to phenotyping in our laboratory. Our results also illustrate the complexity of the thiopurine metabolism and suggest that differences between metabolite profiles are explained either by interactions between several genes, each with a small contribution, or at the post-transcriptional level. Search for more precise tools to explain differences in metabolite profiles is needed. Furthermore, in order to investigate small effects it is necessary to analyse metabolite concentrations and gene expression levels, as well as enzyme activities in the target cells of therapy (MNC).

    List of papers
    1. Pyrosequencing of TPMT Alleles in a General Swedish Population and in Patients with Inflammatory Bowel Disease
    Open this publication in new window or tab >>Pyrosequencing of TPMT Alleles in a General Swedish Population and in Patients with Inflammatory Bowel Disease
    Show others...
    2004 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 50, no 2, p. 288-295Article in journal (Refereed) Published
    Abstract [en]

    Background: Interindividual differences in therapeutic efficacy in patients treated with thiopurines might be explained by the presence of thiopurine S-methyltransferase (TPMT) alleles that encode for reduced TPMT enzymatic activity. It is therefore of value to know an individual's inherent capacity to express TPMT. Method: We developed a pyrosequencing method to detect 10 single-nucleotide polymorphisms (SNPs) in TPMT. A Swedish population (n = 800) was examined for TPMT*3A, TPMT*3B, TPMT*3C, and TPMT*2. Patients with inflammatory bowel disease (n = 24) and healthy volunteers (n = 6), selected on the basis of TPMT enzymatic activity, were investigated for all 10 SNPs to determine the relationship between TPMT genotype and phenotype. Results: In the general population we identified the following genotypes with nonfunctional alleles: TPMT*1/*3A (*3A allelic frequency, 3.75%), TPMT*1/*3C (*3C allelic frequency, 0.44%), TPMT*1/*3B (*3B allelic frequency, 0.13%), and TPMT*1/*2 (*2 allelic frequency, 0.06%). All nine individuals with normal enzymatic activity were wild-type TPMT*1/*1. Thirteen individuals with intermediate activity were either TPMT*1/*3A (n = 12) or TPMT*1/*2 (n = 1). Eight individuals with low enzymatic activity were TPMT*3A/*3A (n = 4), TPMT*3A/*3C (n = 2), or TPMT*1/*3A (n = 2). Conclusion: Next to wild type, the most frequent alleles in Sweden are TPMT*3A and TPMT*3C. A previously established phenotypic cutoff for distinguishing normal from intermediate metabolizers was confirmed. To identify the majority of cases (90%) with low or intermediate TPMT activity, it was sufficient to analyze individuals for only 3 of the 10 SNPs investigated. Nevertheless, this investigation indicates that other mutations might be of relevance for decreased enzymatic activity. © 2004 American Association for Clinical Chemistry.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-45829 (URN)10.1373/clinchem.2003.023846 (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
    2. IMPDH activity in thiopurine-treated patients with inflammatory bowel disease - Relation to TPMT activity and metabolite concentrations
    Open this publication in new window or tab >>IMPDH activity in thiopurine-treated patients with inflammatory bowel disease - Relation to TPMT activity and metabolite concentrations
    2008 (English)In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 65, no 1, p. 69-77Article in journal (Refereed) Published
    Abstract [en]

    AIMS: Azathioprine and 6-mercaptopurine are steroid-sparing drugs used in inflammatory bowel disease (IBD). The polymorphic enzyme thiopurine S-methyltransferase (TPMT) is of importance for thiopurine metabolism and occurrence of adverse events. The role of other thiopurine-metabolizing enzymes is less well known. This study investigated the role of inosine-5′- monophosphate dehydrogenase (IMPDH), which is a key enzyme in the de novo synthesis of guanine nucleotides and also strategically positioned in the metabolic pathway of thiopurines. METHODS: IMPDH was measured in 100 healthy blood donors. IMPDH, TPMT and metabolite concentrations were studied in 50 patients with IBD on stable thiopurine therapy. IMPDH activity was measured in peripheral blood mononuclear cells. TPMT activity, 6-methylthioinosine 5′-monophosphate (meTIMP) and 6-thioguanine nucleotide (6-TGN) concentrations were measured in red blod cells, which is the current practice in clinical monitoring of thiopurines. Enzyme activities were related to metabolite concentrations and clinical characteristics. RESULTS: A wide range of IMPDH activity was observed both in healthy blood donors (median 13.1, range 4.7-24.2 nmol mg-1 protein h-1) and IBD patients (median 14.0, range 7.0-21.7). There was a negative correlation between IMPDH activity and dose-normalized meTIMP concentrations (rs = -0.31, P = 0.03), but no evident correlation to 6-TGN concentration or the meTIMP/6-TGN ratio. There were no significant correlations between TPMT activity and metabolite concentrations. CONCLUSION: Even though the meTIMP concentrations correlated inversely to the IMPDH activity, the role of IMPDH in balancing the formation of methylated and phosphorylated metabolites was not evident. Taken together, the results give cause to question established opinions about thiopurine metabolism. © 2007 The Authors.

    Keywords
    6-Mercaptopurine/*pharmacology Adult Aged Aged, 80 and over Azathioprine/*pharmacology Biological Markers Female Humans IMP Dehydrogenase/genetics/*metabolism Immunosuppressive Agents/*pharmacology Inflammatory Bowel Diseases/*drug therapy Male Methyltran
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-43268 (URN)10.1111/j.1365-2125.2007.02985.x (DOI)73262 (Local ID)73262 (Archive number)73262 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13Bibliographically approved
    3. The Role of Inosine-5'-Monophosphate Dehydrogenase in Thiopurine Metabolism in Patients With Inflammatory Bowel Disease
    Open this publication in new window or tab >>The Role of Inosine-5'-Monophosphate Dehydrogenase in Thiopurine Metabolism in Patients With Inflammatory Bowel Disease
    Show others...
    2011 (English)In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 33, no 2, p. 200-208Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:: There is a large interindividual variability in thiopurine metabolism. High concentrations of methylthioinosine-5'-monophosphate (meTIMP) and low concentrations of 6-thioguanine nucleotides (6-TGNs) have been associated with a lower response rate and an increased risk of adverse events. In this study, the role of inosine-5'-monophosphate dehydrogenase (IMPDH) for differences in metabolite patterns of thiopurines was investigated.

    METHODS:: IMPDH activity and thiopurine metabolite concentrations were determined in patients with inflammatory bowel disease and a normal thiopurine methyltransferase (TPMT) phenotype and meTIMP/6-TGN concentration ratio > 20 (n = 26), in patients with a metabolite ratio ≤20 (n = 21), in a subgroup with a metabolite ratio <4 (n = 6), and in 10 patients with reduced TPMT activity. In vitro studies were conducted on human embryonic kidney cells (HEK293) with genetically engineered IMPDH and TPMT activities.

    RESULTS:: Patients with metabolite ratios >20 had lower IMPDH activity than those with ratios ≤20 (P < 0.001). Metabolic ratios >20 were only observed in patients with normal TPMT activity. Downregulation of IMPDH activity in HEK293 cells was associated with an increase in the concentration of meTIMP (fold change: 17 up to 93, P < 0.001) but, unexpectedly, also of 6-thioguanosine monophosphate (fold change: 2.6 up to 5.0, P < 0.001).

    CONCLUSIONS:: These data question the general view of IMPDH as the rate-limiting enzyme in the phosphorylation of thiopurines. Investigations of other mechanisms are needed to more fully explain the various metabolite patterns and outcomes in patients under treatment.

    Place, publisher, year, edition, pages
    Lippincott Williams & Wilkins, 2011
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-66431 (URN)10.1097/FTD.0b013e31820b42bb (DOI)000288498100010 ()21311411 (PubMedID)
    Available from: 2011-03-15 Created: 2011-03-15 Last updated: 2017-12-11Bibliographically approved
    4. Pharmacotranscriptomics in thiopurine treated IBD patients with different metabolite profiles
    Open this publication in new window or tab >>Pharmacotranscriptomics in thiopurine treated IBD patients with different metabolite profiles
    2008 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Thiopurine drugs are used to induce and maintain remission in inflammatory bowel disease. The methyl thioinosine monophosphate (meTIMP)/6-thioguanine nucleotide (6-TGN) concentration ratio has been related to drug response and adverse reactions. Here we investigated for differences in gene expression levels between patients with different metabolite profiles.

    Methods: Transcriptional profiles in blood samples from an exploratory patient cohort (n=21) comprising three groups; patients with normal thiopurine S-methyltransferase phenotype and meTIMP/6-TGN concentration ratio >20, ratio 10.0-14.0 and ratio ≤4, respectively, were assessed by hybridization to microarrays. Results were further evaluated with reverse transcription qPCR [exploratory and a validation cohort of patients (n=33)]. Additionally, known genes of the thiopurine metabolic pathway were analysed separately.

    Results: The whole genome expression analysis did not identify any significant differences between metabolite profiles. Analysis of thiopurine related genes revealed a large interindividual variation in gene expression, but only small differences between metabolite profiles. Three clusters of co-regulated genes were defined based on correlations between gene expression levels. The concentration of meTIMP correlated to the expression of NT5E (rs = 0.33, P = 0.02) and TPMT (rs = - 0.37, P = 0.007). The concentration of 6-TGN correlated to the expression of HPRT1 (rs = - 0.31, P = 0.03) and SLC29A1 (rs = 0.33, P = 0.02). With the exception of SLC29A1, these genes belonged to the same cluster of genes.

    Conclusions: Our results illustrates the complexity of the thiopurine metabolism and suggest that differences between metabolite profiles are explained either by interactions between several genes, each with a small contribution, or at the post-transcriptional level. Search for more precise tools in order to explain differences in metabolite profiles is needed.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-66432 (URN)
    Available from: 2011-03-15 Created: 2011-03-15 Last updated: 2011-03-15Bibliographically approved
  • 23.
    Haglund, Sofie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Söderman, Jan
    Division of Medical Diagnostics, Laboratory Medicine, Ryhov Hospital, Jönköping;.
    Hindorf, Ulf
    Department of Gastroenterology, Lund University Hospital, Lund.
    Grännö, Christer
    Department of Medicine, Ryhov Hospital, Jönköping.
    Danelius, Margareta
    Department of Internal Medicine, Ersta Hospital, Stockholm, Sweden.
    Coulthard, Sally
    Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    The Role of Inosine-5'-Monophosphate Dehydrogenase in Thiopurine Metabolism in Patients With Inflammatory Bowel Disease2011In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 33, no 2, p. 200-208Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:: There is a large interindividual variability in thiopurine metabolism. High concentrations of methylthioinosine-5'-monophosphate (meTIMP) and low concentrations of 6-thioguanine nucleotides (6-TGNs) have been associated with a lower response rate and an increased risk of adverse events. In this study, the role of inosine-5'-monophosphate dehydrogenase (IMPDH) for differences in metabolite patterns of thiopurines was investigated.

    METHODS:: IMPDH activity and thiopurine metabolite concentrations were determined in patients with inflammatory bowel disease and a normal thiopurine methyltransferase (TPMT) phenotype and meTIMP/6-TGN concentration ratio > 20 (n = 26), in patients with a metabolite ratio ≤20 (n = 21), in a subgroup with a metabolite ratio <4 (n = 6), and in 10 patients with reduced TPMT activity. In vitro studies were conducted on human embryonic kidney cells (HEK293) with genetically engineered IMPDH and TPMT activities.

    RESULTS:: Patients with metabolite ratios >20 had lower IMPDH activity than those with ratios ≤20 (P < 0.001). Metabolic ratios >20 were only observed in patients with normal TPMT activity. Downregulation of IMPDH activity in HEK293 cells was associated with an increase in the concentration of meTIMP (fold change: 17 up to 93, P < 0.001) but, unexpectedly, also of 6-thioguanosine monophosphate (fold change: 2.6 up to 5.0, P < 0.001).

    CONCLUSIONS:: These data question the general view of IMPDH as the rate-limiting enzyme in the phosphorylation of thiopurines. Investigations of other mechanisms are needed to more fully explain the various metabolite patterns and outcomes in patients under treatment.

  • 24.
    Hallberg, I
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Toss, G
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Ek, A-C
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Hjortswang, H
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Bachrach-Lindström, M
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Health-related Quality of Life after Vertebral or Hip Fracture in Women - Short Health Scale Useful for Clinical Practice?2010Conference paper (Other academic)
  • 25.
    Hallberg, Inger
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Bachrach-Lindström, Margareta
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Toss, Göran
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Ek, Anna-Christina
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Health Care.
    Health-Related Quality of Life 7 Years After Hip or Vertebral fractures2007Conference paper (Other academic)
  • 26.
    Hambre, David
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Vergara, Marta
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Lood, Yvonne
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Sweden.
    Bachrach-Lindström, Margareta
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    A randomized trial of protein supplementation compared with extra fast food on the effects of resistance training to increase metabolism2012In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 6, p. 471-478Article in journal (Refereed)
    Abstract [en]

    Objective. To prospectively evaluate the effects of resistance training combined with increased energy intake or protein-supplementation on lean body-mass, resting metabolic-rate (RMR) and cardiovascular risk factors. Methods. Twenty-four healthy males (aged 19-32 years) performed resistance exercise for 12 weeks aiming for at least 1 hour training-sessions 3 times a week. The participants were randomized to consume extra protein (33 g whey protein/day) or a meal of fast-food/day (1350 kcal, 41 g protein). Body-composition was measured with Dual-Energy X-ray Absorptiometry (DEXA) and RMR by indirect calorimetry. Fasting blood samples were drawn before and after the 3-month training period and after 12 months. Results. The body weight increased from 75.1 +/- 6.9 kg to 78.7 +/- 7.2 kg (p andlt; 0.0001), without differences between the groups. RMR increased from 1787 +/- 143 kcal/24 h to 1954 +/- 187 kcal/24 h (p andlt; 0.0001, N = 24), which was more than expected from the increase in lean body-mass (increase from 59.7 +/- 4.3 kg to 61.8 +/- 4.1 kg p = 0.004). Fasting serum-insulin levels increased in the fast-food group compared with the extra-protein group (p = 0.03). ApoB increased from 0.691 +/- 0.14 g/L to 0.768 +/- 0.17 g/L, p = 0.004, in the fast-food group only. Long-term follow up after 12 months showed that RMR, body weight, total fat and lean body-masses did not differ from baseline (n = 19). Conclusions. Resistance training for 12 weeks increased RMR and lean body-mass similarly when based on either an increased energy-intake or protein supplement. However, the increase in RMR was higher than expected from the increase in lean body-mass. Thus resistance training could potentially decrease the risk of obesity by induction of increased RMR.

  • 27.
    Hjortswang, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Tysk, Curt
    Orebro Univ Hosp, Dept Med, Div Gastroenterol, Orebro, Sweden.
    Bohr, Johan
    Orebro Univ Hosp, Dept Med, Div Gastroenterol, Orebro, Sweden.
    Benoni, Cecilia
    MAS Univ Hosp, Dept Med, Div Gastroenterol, Malmo, Sweden.
    Kilander, Anders
    Sahlgrenska Univ Hospital, Div Gastroenterol, Dept Med, Gothenburg, Sweden.
    Larsson, Lasse
    Sahlgrenska Univ Hospital, Div Gastroenterol, Dept Med, Gothenburg, Sweden.
    Vigren, Lira
    MAS Univ Hosp, Dept Med, Div Gastroenterol, Malmo, Sweden.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Defining Clinical Criteria for Clinical Remission and Disease Activity in Collagenous Colitis2009In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 15, no 12, p. 1875-1881Article in journal (Refereed)
    Abstract [en]

    Background: Collagenous colitis is a chronic inflammatory bowel disease accompanied mainly by nonbloody diarrhea. The objectives of treatment are to alleviate the symptoms and minimize the deleterious effects on health-related quality of life (HRQOL). There is still no generally accepted clinical definition of remission or relapse. The purpose of this study was to analyze the impact of bowel symptoms on HRQOL and accordingly suggest criteria for remission and disease activity based on impact of patient symptoms on HRQOL. Methods: The design was a cross-sectional postal survey of 116 patients with collagenous colitis. The main outcome measures were 4 HRQOL questionnaires: the Short Health Scale, the Inflammatory Bowel Disease Questionnaire, the Rating Form of IBD Patient Concerns, and the Psychological General Well-Being Index, and a 1-week symptom diary recording number of stools/day and number of watery stools/day. Results: Severity of bowel symptoms had a deleterious impact on patients HRQOL. Patients with a mean of greater than= 3 stools/day or a mean of greater than= 1 watery stool/day had a significantly impaired HRQOL compared to those with less than3 stools/day and less than 1 watery stool/day. Conclusions: We propose that clinical remission in collagenous colitis is defined as a mean of less than3 stools/day and a mean of less than 1 watery stool per clay and disease activity to be a daily mean of greater than= 3 stools or a mean of greater than= 1 watery stool.

  • 28.
    Hjortswang, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Tysk, Curt
    University of Orebro.
    Bohr, Johan
    University of Orebro.
    Benoni, Cecilia
    MAS University Hospital.
    Vigren, Lina
    MAS University Hospital.
    Kilander, Anders
    Sahlgrens University Hospital.
    Larsson, Lasse
    Sahlgrens University Hospital.
    Taha, Yesuf
    Karolinska Institute.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Health-related quality of life is impaired in active collagenous colitis2011In: DIGESTIVE AND LIVER DISEASE, ISSN 1590-8658, Vol. 43, no 2, p. 102-109Article in journal (Refereed)
    Abstract [en]

    Objectives: The characteristic clinical symptoms of collagenous colitis are non-bloody diarrhoea, urgency and abdominal pain. Treatment is aimed at reducing the symptom burden and the disease impact on patients health-related quality of life. The objective of this study was to analyse health-related quality of life in patients with collagenous colitis. Methods: In a cross-sectional, postal HRQL survey, 116 patients with collagenous colitis at four Swedish hospitals completed four health-related quality of life questionnaires, two disease-specific (Inflammatory Bowel Disease Questionnaire and Rating Form of IBD Patient Concerns), and two generic (Short Form 36, SF-36, and Psychological General Well-Being, PGWB), and a one-week symptom diary. Demographic and disease-related data were collected. Results for the collagenous colitis population were compared with a background population controlled for age and gender (n = 8931). Results: Compared with a Swedish background population, patients with collagenous colitis scored significantly worse in all Short Form 36 dimensions (p andlt; 0.01), except physical function. Patients with active disease scored worse health-related quality of life than patients in remission. Co-existing disease had an impact on health-related quality of life measured with the generic measures. Lower education level and shorter disease duration were associated with decreased well-being. Conclusion: Health-related quality of life was impaired in patients with collagenous colitis compared with a background population. Disease activity is the most important factor associated with impairment of health-related quality of life. Patients in remission have a health-related quality of life similar to a background population.

  • 29.
    Holdaas, H.
    et al.
    Rikshospitalet, Oslo, Norway.
    Fellstrom, B.
    Fellström, B., University Hospital, Uppsala, Sweden.
    Cole, E.
    University Health Network, Toronto, Canada.
    Nyberg, G.
    Sahlgrenska Academy, Göteborg, Sweden.
    Olsson, Anders G.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Pedersen, T.R.
    Ulleval University Hospital, Oslo, Norway.
    Madsen, S.
    Skejby Hospital, Aarhus, Denmark.
    Gronhagen-Riska, C.
    Grönhagen-Riska, C., Helsinki University Central Hospital, Helsinki, Finland.
    Neumayer, H.-H.
    Charité, Universitätsmedizin, Berlin, Germany.
    Maes, B.
    University Hospital, Leuven, Belgium.
    Ambuhl, P.
    Ambühl, P., University Hospital, Zürich, Switzerland.
    Hartmann, A.
    Rikshospitalet, Oslo, Norway.
    Staffler, B.
    Novartis Pharma AG, Basel, Switzerland.
    Jardine, A.G.
    University of Glasgow, Glasgow, United Kingdom.
    Long-term cardiac outcomes in renal transplant recipients receiving fluvastatin: The ALERT extension study2005In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 5, no 12, p. 2929-2936Article in journal (Refereed)
    Abstract [en]

    Renal transplant recipients (RTR) have an increased risk of premature cardiovascular disease. The ALERT study is the first trial to evaluate the effect of statin therapy on cardiac outcomes following renal transplantation. Patients initially randomized to fluvastatin or placebo in the 5-6 year ALERT study were offered open-label fluvastatin XL 80 mg/day in a 2-year extension to the original study. The primary endpoint was time to first major adverse cardiac event (MACE). Of 1787 patients who completed ALERT, 1652 (92%) were followed in the extension. Mean total follow-up was 6.7 years. Mean LDL-cholesterol was 98 mg/dL (2.5 mmol/L) at last follow-up compared to a pre-study level of 159 mg/dL (4.1 mmol/L). Patients randomized to fluvastatin had a reduced risk of MACE (hazards ratio [HR] 0.79, 95% CI 0.63-0.99, p = 0.036), and a 29% reduction in cardiac death or definite non-fatal MI (HR 0.71, 95% CI 0.55-0.93, p = 0.014). Total mortality and graft loss did not differ significantly between groups. Fluvastatin produces a safe and effective reduction in LDL-cholesterol associated with reduced risk of MACE in RTR. The lipid-lowering and cardiovascular benefits of fluvastatin are comparable to those of statins in other patient groups, and support use of fluvastatin in RTR. Copyright © Blackwell Munksgaard 2005.

  • 30.
    Hollman Frisman, Gunilla
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Jacobsson, Catrine
    PrioriteringsCentrum.
    Hela teamets kompetens: sjuksköterskors, sjukgymnasters och arbetsterapeuters erfarenheter av att delta i prioriteringsarbete2011Report (Other academic)
    Abstract [en]

     

    When health services cannot meet all care needs we must set priorities. This has always been done, but seldom in a systematic way. In Sweden, the Health Services Act places the responsibility for healthcare priority setting on local governing bodies (mainly the county councils and regions). The task of priority setting is grounded in the ethical platform and must apply across all health services.

    In 2003, the Östergötland County Council initially decided that specific limitations must be established regarding the supply of health services. However, follow-up of the county-council-wide effort to set priorities reveals that this work has not reached far enough down into the organisation.

    Earlier reports from the National Centre for Priority Setting in Health Care describe the initial political decision-making process, the extent to which the policy decisions have been implemented in health care, and the progress of the county council’s prioritisation initiative from 2003 to 2006. With this report we aim to increase knowledge regarding how staff groups other than management- level physicians participated in establishing vertical ranking lists during this period and how these lists were used in Östergötland County Council.

  • 31.
    Holme, I.
    et al.
    Center of Preventive Medicine, Ullevål University Hospital, Oslo, Norway, Department of Biostatistics, Centre for Preventive Medicine, Ullevål University Hospital, Kirkeveien 166, N-0407 Oslo, Norway.
    Cater, N.B.
    Pfizer, Pfizer Inc., New York, NY, United States.
    Faergeman, O.
    Department of Medicine-Cardiology A, Århus University Hospital, Århus, Denmark.
    Kastelein, J.J.P.
    Department of Vascular Medicine, Academic Hospital Amsterdam, Amsterdam, Netherlands.
    Olsson, Anders G.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Tikkanen, M.J.
    Department of Medicine, Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland.
    Lytken, Larsen M.
    Lytken Larsen, M., Department of Medicine-Cardiology A, Århus University Hospital, Århus, Denmark.
    Lindahl, C.
    Pfizer Sweden, Sollentuna, Sweden.
    Pedersen, T.R.
    Center of Preventive Medicine, Ullevål University Hospital, Oslo, Norway.
    Lipoprotein predictors of cardiovascular events in statin-treated patients with coronary heart disease. Insights from the Incremental Decrease in End-points through Aggressive Lipid-lowering Trial (IDEAL)2008In: Annals of Medicine, ISSN 0785-3890, E-ISSN 1365-2060, Vol. 40, no 6, p. 456-464Article in journal (Refereed)
    Abstract [en]

    Background. Few studies have looked into the ability of measurements of apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1) or apoB/apoA-1 to predict new coronary heart disease (CHD) events in patients with CHD on statin treatment. Aims. In the IDEAL trial, to compare lipoprotein components to predict CHD events and to what degree differences in those parameters could explain the observed outcome. Methods. We compared the ability of treatment with atorvastatin 80 mg/day to that of simvastatin 20-40 mg/day to prevent CHD events in patients with CHD and used Cox regression models to study the relationships between on-treatment levels of lipoprotein components to subsequent major coronary events (MCE). Findings. Variables related to low-density lipoprotein cholesterol (LDL-C) carried more predictive information than those related to high-density lipoprotein cholesterol (HDL-C), but LDL-C was less predictive than both non-HDL-C and apoB. The ratio of apoB to apoA-1 was most strongly related to MCE. However, for estimating differences in relative risk reduction between the treatment groups, apoB and non-HDL-C were the strongest predictors. Interpretation. The on-treatment level of apoB/apoA-1 was the strongest predictor of MCE in the pooled patient population, whereas apoB and non-HDL-C were best able to explain the difference in outcome between treatment groups. Measurements of apoB and apoA-1 should be more widely available for routine clinical assessments. © 2008 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS).

  • 32.
    Holmer, Helene
    et al.
    Lund University Hospital.
    Popovic, Vera
    University Clin Centre, Belgrade.
    Ekman, Bertil
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL. Linköping University, Department of Medical and Health Sciences, Endocrinology.
    Follin, Cecilia
    Lund University Hospital.
    Siversson, Ann Britt
    Lund University Hospital.
    Erfurth, Eva Marie
    Lund University Hospital.
    Hypothalamic involvement and insufficient sex steroid supplementation are associated with low bone mineral density in women with childhood onset craniopharyngioma2011In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 165, no 1, p. 25-31Article in journal (Refereed)
    Abstract [en]

    Context: Data on bone mineral density (BMD) are lacking in adults with childhood onset (CO)-craniopharyngioma (CP) with hypothalamic damage from the tumor. In patients with CO GH deficiency, BMD increases during GH treatment. Objective: The aims were to evaluate BMD in adults with CO-CPs on complete hormone replacement, including long-term GH and to evaluate the impact of hypothalamic damage on these measures. Design and participants: BMD (dual-energy X-ray absorptiometry), markers of bone turn over, physical activity and calcium intake were assessed in 39 CO-CP adults (20 women), with a median age of 28 (17-57) years, in comparison with matched population controls. Results: Late puberty induction was recorded in both genders, but reduced androgen levels in females only. Only CP women had lower BMD (PZ0.03) at L2-L4, and reduced Z-scores at femoral neck (P=0.004) and L2-L4 (P=0.004). Both genders had increased serum leptin levels (P=0.001), which significantly correlated negatively with BMD at L2-L4 (P=0.003; r=-0.5) and 45% of CP women had Z-score levels less than= -2.0 S.D. Furthermore, 75% of those with a Z-score less than= -2.0 S.D. had hypothalamic involvement by the tumor. Calcium intake (P=0.008) and physical activity (P=0.007) levels were reduced in CP men only. Levels of ostecalcin and crossLaps were increased in CP men only. Conclusions: Despite continuous GH therapy, low BMD was recorded in CO-CP females. Insufficient estrogen and androgen supplementation during adolescence was the main cause, but hypothalamic involvement with consequent leptin resistance was also strongly associated with low BMD in both genders.

  • 33.
    Jennersjö, Pär E.
    et al.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
    Wijkman, Magnus
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Wiréhn, Ann-Britt
    Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
    Circadian blood pressure variation in patients with type 2 diabetes - relationship to macro- and microvascular subclinical organ damage2011In: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 5, no 3, p. 167-173Article in journal (Refereed)
    Abstract [en]

    Aims

    To explore the association between nocturnal blood pressure (BP) dipper status and macro- and microvascular organ damage in type 2 diabetes.

    Methods

    Cross-sectional data from 663 patients with type 2 diabetes, aged 55–66 years, were analysed. Nurses measured office BP and ambulatory BP during 24 h. Individuals with ≥10% difference in nocturnal systolic blood pressure (SBP) relative to daytime values were defined as dippers. Non-dippers were defined as <10% nocturnal decrease in SBP. Estimated glomerular filtration rate (GFR) was calculated and microalbuminuria was measured by albumin:creatinine ratio (ACR). Aortic pulse wave velocity (PWV) was measured with applanation tonometry over the carotid and femoral arteries.

    Results

    We identified 433 dippers and 230 subjects with a nocturnal non-dipping pattern. Nocturnal SBP dipping was independently of office SBP associated with decreased PWV (p = 0.008), lower ACR (p = 0.001) and NT-proBNP (p = 0.001) and increased GFR (p < 0.001).

    Conclusions

    We conclude that diurnal BP variation provides further information about early macro- and microvascular subclinical organ damage that goes beyond standardized office BP measurements in patients with type 2 diabetes.

  • 34.
    Johannsson, G
    et al.
    Sahlgrens University Hospital.
    Nilsson, A G
    Sahlgrens University Hospital.
    Bergthorsdottir, R
    Sahlgrens University Hospital.
    Burman, P A
    Malmo University Hospital.
    Eden Engstrom, B
    Uppsala University Hospital.
    Ekman, Bertil
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Dahlqvist, P
    Umea University Hospital.
    Ryberg, M
    Umea University Hospital.
    Ragnarsson, O
    Sahlgrens University Hospital.
    Wahlberg Topp, Jeanette
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Lennernas, H
    Uppsala University.
    Skrtic, S
    Sahlgrens University Hospital.
    Improved Quality of Life in Patients with Primary Adrenal Insufficiency by Using a Novel Once-Daily Dual Release Hydrocortisone Tablet: A Randomised Controlled, Cross-Over Trial. in ENDOCRINE REVIEWS, vol 31, issue 3, pp2010In: ENDOCRINE REVIEWS, Endocrine Society , 2010, Vol. 31, no 3Conference paper (Refereed)
    Abstract [en]

    n/a

  • 35.
    Johansson, E
    et al.
    Östergötlands Läns Landsting.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Ingemansson, A
    Östergötlands Läns Landsting.
    Ryn, A-K
    Hallbook, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL.
    Randomized trial of biofeedback or medical treatment for fecal incontinence in NEUROGASTROENTEROLOGY AND MOTILITY, vol 24, issue , pp 183-1832012In: NEUROGASTROENTEROLOGY AND MOTILITY, Blackwell Publishing , 2012, Vol. 24, p. 183-183Conference paper (Refereed)
    Abstract [en]

    n/a

  • 36.
    Kechagias, Stergios
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Broman, Jonas
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Compartmentation of glutamate and glutamine in the lateral cervical nucleus: Further evidence for glutamate as a spinocervical tract neurotransmitter1994In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 340, no 4, p. 531-540Article in journal (Refereed)
    Abstract [en]

    Previous observations indicate that spinocervical tract terminals contain relatively high levels of glutamate. To examine whether these high glutamate levels are likely to represent a neurotransmitter pool or an elevated metabolic pool, the distributions of glutamate- and glutamine-like immunoreactivities were examined in adjacent immunogold-labeled sections of the lateral cervical nucleus. Spinocervical tract terminals were identified by anterograde transport of horseradish peroxidase and wheat germ agglutinin-horseradish peroxidase conjugate from the spinal cord.

    Spinocervical tract terminals were found to contain significantly higher levels of glutamate-like immunoreactivity than other examined tissue compartments (large neuronal cell bodies, terminals with pleomorphic vesicles, astrocytes, and average tissue level). In contrast, the highest levels of glutamine-like immunoreactivity were detected in astrocytes. The different analyzed tissue elements formed three groups with respect to glutamate: glutamine ratios: one high ratio group including spinocervical tract terminals, a second group with intermediate ratios consisting of neuronal cell bodies and terminals containing pleomorphic synaptic vesicles, and a third low ratio group including astrocytes.

    Our findings indicate the presence of a compartmentation of glutamate and glutamine in the lateral cervical nucleus, similar to that postulated in biochemical studies of the central nervous system. The results also show that spinocervical tract terminals have high glutamate: glutamine ratios, similar to those previously observed in putative glutamatergic terminals in the cerebellar cortex. Thus, spinocervical tract terminals display biochemical characteristics that would be expected of glutamatergic terminals and the present findings therefore provide further evidence for glutamate as a spinocervical tract neurotransmitter.

  • 37.
    Kechagias, Stergios
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Lofti, Kourosh
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Läkemedelsorsakad leverskada av kosttillskottet Fortodol: Manipulerat preparat försenade diagnos2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 4, p. 186-188Article in journal (Refereed)
    Abstract [en]

    Summary:

    Pharmaceutical preparations are serious contributors to liver disease. The diagnostic approach of drug-induced liver injury is difficult and requires a high degree of suspicion and the exclusion of alternative causes of liver damage. Adulteration of food supplements is a potential cause of serious hepatotoxicity. A case of severe jaundice after consumption of Fortodol, which according to the manufacturer contained the active substances turmeric and phenylalanine, is reported. Several months later more patients experiencing hepatotoxicity from Fortodol was reported and it was discovered that the toxicity was related to adulteration by nimesulide.

  • 38.
    Kechagias, Stergios
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Zanjani, Sepehr
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Gjellan, Solveig
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization, CMIV.
    Kihlberg, Johan
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization, CMIV. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Radiology in Linköping.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Radiology in Linköping.
    Johansson, Lars
    Uppsala University.
    Kullberg, Joel
    Uppsala University.
    Ahlstrom, Hakan
    Uppsala University.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Effects of moderate red wine consumption on liver fat and blood lipids: a prospective randomized study2011In: Annals of Medicine, ISSN 0785-3890, E-ISSN 1365-2060, Vol. 43, no 7, p. 545-554Article in journal (Refereed)
    Abstract [en]

    Background : There have been no human prospective randomized studies of the amount of alcohol that can induce hepatic steatosis. less thanbrgreater than less thanbrgreater thanMethods : Thirty-two healthy women and twelve healthy men (34 +/- 9 years of age) were randomized to consume 150 ml of red wine/day for women (16 g ethanol/day) or double that amount for men (33 g ethanol/day), or to alcohol abstention for 90 days. Participants underwent proton-nuclear magnetic-resonance spectroscopy for measurement of hepatic triglyceride content (HTGC). Blood samples for assessment of cardiovascular risk were drawn before and after the intervention. less thanbrgreater than less thanbrgreater thanResults: After exclusion of three subjects with steatosis at baseline a trend towards increased HTGC was apparent for red wine (before median: 1.1%, range 0.2-3.9%, after median: 1.1%, range 0.5-5.2%, P = 0.059) a difference that was statistically significant compared with abstainers (p = 0.02). However, no subject developed hepatic steatosis. Low-density lipoprotein (LDL)-cholesterol was lowered by red wine (-0.3 mmol/l, SE-0.1, 95% CI-0.6 to -0.04). less thanbrgreater than less thanbrgreater thanConclusions: Moderate consumption of red wine during three months increased HTGC in subjects without steatosis at baseline. However, since not a single participant developed steatosis we suggest that the threshold of alcohol consumption to define nonalcoholic fatty liver disease should not be lower than the amount in our study.

  • 39.
    Kee Ryu, Sung
    et al.
    Eulji University.
    Mallat, Ziad
    University of Cambridge.
    Benessiano, Joelle
    Paris Descartes University.
    Tedgui, Alain
    Paris Descartes University.
    Olsson, Anders
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Bao, Weihang
    Pfizer Inc.
    Schwartz, Gregory G
    University of Colorado.
    Tsimikas, Sotirios
    University of Calif San Diego.
    Phospholipase A(2) Enzymes, High-Dose Atorvastatin, and Prediction of Ischemic Events After Acute Coronary Syndromes2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 125, no 6, p. 757-U71Article in journal (Refereed)
    Abstract [en]

    Background-Secretory phospholipase A2 (sPLA(2)) and lipoprotein-associated phospholipase A2 (Lp-PLA(2)) are enzyme biomarkers of increased cardiovascular risk and targets of emerging therapeutic agents. Their relationship to cardiovascular events in the setting of high-dose statin therapy compared with placebo in patients with acute coronary syndrome is not known. less thanbrgreater than less thanbrgreater thanMethods and Results-sPLA(2) and Lp-PLA(2) mass and activity were measured in 2587 patients in the Myocardial Ischemia Reduction With Acute Cholesterol Lowering (MIRACL) trial at baseline and after 16 weeks of treatment with atorvastatin 80 mg/d or placebo. Baseline levels of sPLA(2) and Lp-PLA(2) mass and activity were not associated with the primary efficacy measure of the trial of death, myocardial infarction, or unstable angina. However, in the overall cohort, baseline sPLA(2) mass predicted risk of death after multivariable adjustment (hazard ratio for 2-fold increase, 1.30; 95% confidence interval, 1.09 -1.56; P = 0.004). This association remained significant when examined separately in the placebo group but not in the atorvastatin group. Compared with placebo, atorvastatin reduced median sPLA(2) mass (-32.1% versus -23.1%), sPLA(2) activity (-29.5% versus -19.2%), Lp-PLA(2) mass (-35.8% versus -6.2%), and Lp-PLA(2) activity (-24.3% versus 5.4%; P andlt; 0.001 for all). Atorvastatin reduced the hazard of death associated with elevated sPLA(2) mass and activity by approximate to 50%. less thanbrgreater than less thanbrgreater thanConclusions-sPLA(2) mass independently predicts death during a 16-week period after acute coronary syndrome. High-dose atorvastatin significantly reduces sPLA(2) and Lp-PLA(2) mass and activity after acute coronary syndrome and mitigates the risk of death associated with sPLA(2) mass. Atorvastatin may exert antiinflammatory effects on phospholipases that contribute to its therapeutic benefit after acute coronary syndrome.

  • 40.
    Kinlay, S.
    et al.
    Cardiovascular Division, Veterans Affairs Boston Healthcare System, West Roxbury, MA, United States, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, United States.
    Schwartz, G.G.
    Cardiology Division, Veterans Affairs Medical Center, University of Colorado Health Sciences Center, Denver, CO, United States.
    Olsson, Anders G.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Rifai, N.
    Children's Hospital Boston, Harvard Medical School, Boston, MA, United States.
    Szarek, M.
    Pfizer Pharmaceuticals Group, New York, NY, United States.
    Waters, D.D.
    Cardiology Division, San Francisco General Hospital, University of California, San Francisco, CA, United States.
    Libby, P.
    Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
    Ganz, P.
    Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
    Inflammation, statin therapy, and risk of stroke after an acute coronary syndrome in the MIRACL study2008In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 28, no 1, p. 142-147Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - Patients with acute coronary syndromes have an increased risk of stroke. We measured markers of inflammation in the MIRACL study, a randomized trial of atorvastatin versus placebo in acute coronary syndromes, to assess the relationship of inflammation to stroke. METHODS AND RESULTS - Baseline C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) were collected in 2926 (95%) subjects. Baseline markers were related to stroke risk over the 16 weeks of the study. Subjects who subsequently experienced a stroke had higher CRP (27.5 versus 10.2 mg/L, P=0.0032), SAA (30.5 versus 16.0 mg/L, P=0.031), IL-6 (11 231 versus 6841 pg/L, P=0.004), and troponin (6.03 versus 3.19 ng/mL P=0.0032). The risk of stroke was related to greater CRP, SAA, and IL-6 in the placebo group only. Similarly, there was a graded increase in risk of stroke across quartiles of inflammatory markers in the placebo patients only. CONCLUSIONS - In acute coronary syndromes, the early risk of stroke relates to both heightened inflammation and size of myocardial necrosis. Treatment with atorvastatin abrogated the risk associated with elevated markers of inflammation in this study, a finding that provides a novel rationale for the use of statins in acute coronary syndromes. © 2008 American Heart Association, Inc.

  • 41.
    Kronstrand, Robert
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linkoping, Sweden.
    Brinkhagen, Linda
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linkoping, Sweden.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Ethyl glucuronide in human hair after daily consumption of 16 or 32 g of ethanol for 3 months2012In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 215, no 1-3, p. 51-55Article in journal (Refereed)
    Abstract [en]

    The overall objectives of the study were to develop a sensitive method for ethyl glucuronide (EtG) determination in hair and then investigate if a low or moderate intake of ethanol could be differentiated from total abstinence. Forty-four subjects were included in the study, 12 males (7 drinkers and 5 abstinent) and 32 females (14 drinkers and 18 abstinent). The study lasted 3 months and the female drinkers consumed one glass (16 g of ethanol) and the males consumed two glasses (32 g of ethanol) of wine (13.5-14%) daily. Hair samples were collected as close as possible above the skin and the proximal 2 cm were analyzed for EtG. Hair was cut into pieces of about 0.5 cm length and washed before incubation overnight in water and then extracted on Clean Screen EtG Carbon columns. The LC/MS/MS system consisted of a Waters ACQUITY UPLC connected to an API 4000 triple quadrupole instrument. Two transitions for EtG and one for the internal standard EtG-D-5 were measured. The method was linear from 60 to 10,000 pg/sample. Imprecision studies were performed at three levels as well as with an authentic sample. Total imprecision was 16% at 200 pg/sample, 8% at 1000 pg/sample, 6% at 8000 pg/sample and 13% at 29 pg/mg in the authentic sample. Of those who drank two glasses of wine every day, four had measurable amounts of EtG in their hair (5-11 pg/mg), and in only one of the females drinking one glass of wine EtG was quantified (3 pg/mg). Among the 23 abstinent subjects two had traces of EtG in the hair. We conclude that persons who ingested 16 or 32 g of ethanol daily for 3 months presented with low concentrations of EtG in hair, well below the proposed threshold for overconsumption set at 30 pg/mg. In addition, none of those who ingested 16 g/day had concentrations over the proposed abstinence threshold of 7 pg/mg.

  • 42.
    Landberg, Eva
    et al.
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Wahlberg Topp, Jeanette
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Rydén, Ingvar
    Division of Clinical Chemistry, Kalmar County Hospital, Kalmar, Sweden.
    Arvidsson, Britt-Marie
    Division of Clinical Chemistry, Kalmar County Hospital, Kalmar, Sweden.
    Ekman, Bertil
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Detection of molecular variants of prolactin in human serum, evaluation of a method based on ultrafiltration2007In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 376, no 1-2, p. 220-225Article in journal (Refereed)
    Abstract [en]

    Background

    In human blood, there are several molecular variants of prolactin with different biological effects. There is a need for new methods to detect and quantify these variants in order to fully understand the pathophysiological role of prolactin.

    Methods

    A method based on ultrafiltration was optimized, validated and compared to PEG precipitation. Serum samples from 84 patients were analyzed before and after pre treatment on two immunoassays, Elecsys (Roche) and Access (Beckman). Protein G precipitation was used to confirm presence of macroprolactin.

    Results

    The recovery of prolactin after ultrafiltration was lower than after PEG precipitation. A limit of 40% recovery after PEG precipitation corresponded to 27% recovery after ultrafiltration. Using these limits there were total agreement regarding detection of macroprolactin (rs = 0.96). In contrast, recovery of prolactin in samples without macroprolactin showed a considerable disagreement between ultrafiltration and PEG precipitation (rs = 0.48). Within-run CV was 4% for the ultrafiltration method. The correlation coefficient (r) between the immunoassays was 0.96 after ultrafiltration.

    Conclusions

    Ultrafiltration can be used to compare different prolactin immunoassays and to detect macroprolactin in assays with interference from PEG. For samples without macroprolactin ultrafiltration may give additional information reflecting individual variations of other molecular variants of prolactin.

  • 43. Larsson, M. B. O.
    et al.
    Tillisch, K.
    Mayer, E. A.
    Jarcho, J.
    Lalbus, J.
    Naliboff, B.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Brain response during expectation and delivery of visceral stimulation differs between IBS patients and healthy controls: an fMRI study2010Conference paper (Other academic)
  • 44. Larsson, M.
    et al.
    Sjöberg, M.
    Craig, A. D.
    Engström, Maria
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Labus, J.
    University of California, Los Angeles.
    Mayer, E. A.
    University of California, Los Angeles.
    Naliboff, B.
    University of California, Los Angeles.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Tillisch, K.
    University of California, Los Angeles.
    Walter, Susanna A.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Brain Response to Expectation and Delivery of Rectal Distensions Before and After Hypnotherapy and Education Intervention in Irritable Bowel Syndrome (IBS): an fMRI Study2011Conference paper (Refereed)
    Abstract [en]

    Aim & MethodsWe aimed to determine the effect of standardized hypnosis treatment (HYP) on symptom outcomes and brain activity compared to an education intervention (EDU). Twenty-seven women with IBS were evaluated before and after treatment with hypnotherapy (n=17) or educational intervention (n=10). Behavioural treatment outcomes were determined by Severity Scoring System (IBS-SSS). A decrease of 50 points in SSS score was considered clinically significant treatment response. Blood oxygenated level dependent (BOLD) signal were acquired by using a 1.5 T magnetic resonance scanner during expectation and delivery of large rectal distension (45 mmHg). Group comparisons of treatment effects were performed within the general linear model in SPM8. Region of interest analyses were performed with significance threshold of p<0.05, family-wise error corrected.

    ResultsThere were no group differences in baseline SSS scores. Clinically significant change in SSS was observed in HYP (82%, n=14) and EDU (60%, n=6). Mean improvement in SSS was 108 (range -277 to 29) in HYP and 62 (range -250 to 79) in EDU (ns). During cued expectation of rectal distension, HYP was associated with significantly decreased activation in the left dorsal and ventral anterior insula, left mid insula, left ventrolateral prefrontal cortex (vlPFC) and left dorsolateral prefrontal cortex (dlPFC). Respectively, the EDU group showed less BOLD activity in the left ventral anterior insula after treatment. No significant treatment effect on brain response to the 45 mmHg distension was observed.

    ConclusionWhile both treatments improve IBS symptoms, the standardized hypnosis treatment has a more widespread central effect compared to education. The brain effects are seen during the expectation of rectal discomfort, but not during the experience of aversive rectal distensions. These findings are consistent with a HYP-induced reduction in pain expectation, rather than pain perception

  • 45.
    Larsson, M
    et al.
    Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Gastroenterology.
    Tillisch, K
    University of Calif Los Angeles, USA .
    Mayer, E
    Oppenheimer Family Centre Neurobiol Stress, USA .
    Naliboff, B
    Oppenheimer Family Centre Neurobiol Stress, USA .
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization, CMIV.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Do IBS patients without rectal hypersensitivity adapt to repeated aversive rectal distensions? in NEUROGASTROENTEROLOGY AND MOTILITY, vol 24, issue , pp 109-1102012In: NEUROGASTROENTEROLOGY AND MOTILITY, Blackwell Publishing , 2012, Vol. 24, p. 109-110Conference paper (Refereed)
    Abstract [en]

    n/a

  • 46.
    Larsson, Mats
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Tillisch, Kirsten
    UCLA, Los Angeles, USA.
    Craig, Bud
    Barrow Neurological Institute, Phoenix, Arizona.
    Engström, Maria
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Labus, Jennifer
    UCLA, Los Angeles, USA.
    Naliboff, Bruce
    UCLA, Los Angeles, USA.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Ström, Magnus
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Mayer, Emeran
    UCLA, Los Angeles, USA.
    Walter, Susanna
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Brain Responses to Visceral Stimuli Reflect Visceral Sensitivity Thresholds in Patients With Irritable Bowel Syndrome2012In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 142, no 3, p. 463-472Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS:

    Only a fraction of patients with irritable bowel syndrome (IBS) have increased perceptual sensitivity to rectal distension, indicating differences in processing and/or modulation of visceral afferent signals. We investigated the brain mechanisms of these perceptual differences.

    METHODS:

    We analyzed data from 44 women with IBS and 20 female healthy subjects (controls). IBS symptom severity was determined by a severity scoring system. Anxiety and depression symptoms were assessed using the hospital anxiety and depression score. Blood oxygen level-dependent signals were measured by functional magnetic resonance imaging during expectation and delivery of high (45 mmHg) and low (15 mmHg) intensity rectal distensions. Perception thresholds to rectal distension were determined in the scanner. Brain imaging data were compared among 18 normosensitive and 15 hypersensitive patients with IBS and 18 controls. Results were reported significant if peak P-values were ≤.05, with family-wise error correction in regions of interest.

    RESULTS:

    The subgroups of patients with IBS were similar in age, symptom duration, psychological symptoms, and IBS symptom severity. Although brain responses to distension were similar between normosensitive patients and controls, hypersensitive patients with IBS had greater activation of insula and reduced deactivation in pregenual anterior cingulate cortex during noxious rectal distensions, compared to controls and normosensitive patients with IBS. During expectation of rectal distension, normosensitive patients with IBS had more activation in right hippocampus than controls.

    CONCLUSIONS:

    Despite similarities in symptoms, hyper- and normosensitive patients with IBS differ in cerebral responses to standardized rectal distensions and their expectation, consistent with differences in ascending visceral afferent input.

  • 47.
    Lindström, Torbjörn
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Carlsson, Martin
    County Hospital of Kalmar.
    Nystrom, Fredrik H.
    Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL. Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Transient increase in HDL cholesterol during weight gain by hyper-alimentation in healthy subjects2011In: Obesity, ISSN 1930-7381, Vol. 19, no 4, p. 812-817Article in journal (Refereed)
    Abstract [en]

    Determination of lipid levels is fundamental in cardiovascular risk assessment. We studied the short-term effects of fast food–based hyperalimentation on lipid levels in healthy subjects. Twelve healthy men and six healthy women with a mean age of 26 ± 6.6 years and an aged-matched control group were recruited for this prospective interventional study. Subjects in the intervention group aimed for a body weight increase of 5–15% by doubling the baseline caloric intake by eating at least two fast food–based meals a day in combination with adoption of a sedentary lifestyle for 4 weeks. This protocol induced a weight gain from 67.6 ± 9.1 kg to 74.0 ± 11 kg (P < 0.001). A numerical increase in the levels of high-density lipoprotein (HDL)-cholesterol occurred in all subjects during the study and this was apparent already at the first week in 16/18 subjects (mean increase at week 1: +22.0 ± 16%, range from –7 to +50%), whereas the highest level of HDL during the study as compared with baseline values varied from +6% to +58% (mean +31.6 ± 15%). The intake of saturated fat in the early phase of the trial related positively with the HDL-cholesterol-increase in the second week (r = 0.53, P = 0.028). Although the levels of insulin doubled at week 2, the increase in low-density lipoprotein (LDL)-cholesterol was only +12 ± 17%, and there was no statistically significant changes in fasting serum triglycerides. We conclude that hyperalimentation can induce a fast but transient increase in HDL-cholesterol that is of clinical interest when estimating cardiovascular risk based on serum lipid levels.

  • 48.
    Maccubbin, Darbie L
    et al.
    Merck Sharp and Dohme Corp, NJ USA .
    Chen, Fabian
    Merck Sharp and Dohme Corp, NJ USA .
    Weimer Anderson, Jennifer
    Merck Sharp and Dohme Corp, NJ USA .
    Sirah, Waheeda
    Merck Sharp and Dohme Corp, NJ USA .
    McCrary Sisk, Christine
    Merck Sharp and Dohme Corp, NJ USA .
    Kher, Uma
    Merck Sharp and Dohme Corp, NJ USA .
    Olsson, Anders
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Bays, Harold E
    Louisville Metab and Atherosclerosis Research Centre, KY USA .
    Mitchel, Yale B
    Merck Sharp and Dohme Corp, NJ USA .
    Effectiveness and Safety of Laropiprant on Niacin-Induced Flushing2012In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 110, no 6, p. 817-822Article in journal (Refereed)
    Abstract [en]

    Extended-release niacin (ERN) improves multiple lipid parameters but is underused owing to niacin-induced flushing (NIF). Laropiprant (LRPT) reduces NIF; however, its effects on chronic flushing (andgt;6 months) have not been studied. We examined whether after 20 weeks of treatment with ERN/LRPT, patients who continued ERN/LRPT would experience less NIF than patients who stopped LRPT and continued ERN alone. A total of 1,152 dyslipidemic patients were randomized 2:2:1 to group 1, ERN/LRPT 1 g/20 mg/day from 0 to 4 weeks and then ERN/LRPT 2 g/40 mg/day from 5 to 32 weeks; group 2, ERN/LRPT 1 g/20 mg/day from 0 to 4 weeks, ERN/LRPT 2 g/40 mg/day from 5 to 20 weeks, and then ERN 2 g/day without LRPT from 21 to 32 weeks; or group 3, placebo for the entire study. The end points included the number of days each week with a moderate or greater Global Flushing Severity Score (GFSS) andgt;= 4 (primary end point) and the percentage of patients with a maximum GFSS of andgt;= 4 (secondary end point) during the postwithdrawal period (weeks 21 to 32). ERN/LRPT produced significantly less NIF than ERN alone during the postwithdrawal period, as measured by the number of days each week with a GFSS of andgt;= 4 (p andlt; 0.001) and the percentage of patients with a maximum GFSS of andgt;= 4 (p andlt; 0.001; ERN/LRPT 19.6%; ERN 48.9%; placebo 9.2%). Compared with ERN alone, ERN/LRPT produced fewer drug-related adverse experiences during the postwithdrawal period. After 20 weeks of stable maintenance therapy, dyslipidemic patients treated continuously with ERN/LRPT experienced less NIF than did patients who had had LRPT withdrawn and had continued with ERN alone. In conclusion, the results of our study support the long-term efficacy of ERN/LRPT in reducing NIF symptoms.

  • 49.
    Momozawa, Yukihide
    et al.
    Grp Interdisciplinaire Genoprote Appliquee GIGA R.
    Mni, Myriam
    Grp Interdisciplinaire Genoprote Appliquee GIGA R.
    Nakamura, Kayo
    Grp Interdisciplinaire Genoprote Appliquee GIGA R.
    Coppieters, Wouter
    Grp Interdisciplinaire Genoprote Appliquee GIGA R.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Amininejad, Leila
    University Libre Bruxelles.
    Cleynen, Isabelle
    Catholic University Louvain.
    Colombel, Jean-Frederic
    Hop Calmette, Registre MICI Nord Quest France.
    de Rijk, Peter
    University Antwerp VIB.
    Dewit, Olivier
    Catholic University Louvain.
    Finkel, Yigael
    Karolinska Childrens Hospital.
    A Gassull, Miquel
    Hospital Badalona Germans Trias and Pujol.
    Goossens, Dirk
    University Antwerp VIB.
    Laukens, Debby
    University Ghent.
    Lemann, Marc
    University Paris 07.
    Libioulle, Cecile
    Grp Interdisciplinaire Genoprote Appliquee GIGA R.
    OMorain, Colm
    Adelaide and Meath Hospital.
    Reenaers, Catherine
    GIGA R.
    Rutgeerts, Paul
    Catholic University Louvain.
    Tysk, Curt
    Orebro Med Centre Hospital.
    Zelenika, Diana
    Centre Natl Genotypage, Evry.
    Lathrop, Mark
    Centre Natl Genotypage, Evry, France .
    Del-Favero, Jurgen
    University Antwerp VIB.
    Hugot, Jean-Pierre
    Hop Robert Debre.
    de Vos, Martine
    University Ghent.
    Franchimont, Denis
    University Libre Bruxelles.
    Vermeire, Severine
    Catholic University Louvain.
    Louis, Edouard
    GIGA R.
    Georges, Michel
    Grp Interdisciplinaire Genoprote Appliquee GIGA R.
    Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease2011In: NATURE GENETICS, ISSN 1061-4036, Vol. 43, no 1, p. 43-U58Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohns disease(1,2). However, common disease-associated SNPs explain at most similar to 20% of the genetic variance for Crohns disease. Several factors may account for this unexplained heritability(3-5), including rare risk variants not adequately tagged thus far in GWAS(6-8). That rare susceptibility variants indeed contribute to variation in multifactorial phenotypes has been demonstrated for colorectal cancer(9), plasma high-density lipoprotein cholesterol levels(10), blood pressure(11), type 1 diabetes(12), hypertriglyceridemia(13) and, in the case of Crohns disease, for NOD2 (refs. 14,15). Here we describe the use of high-throughput resequencing of DNA pools to search for rare coding variants influencing susceptibility to Crohns disease in 63 GWAS-identified positional candidate genes. We identify low frequency coding variants conferring protection against inflammatory bowel disease in IL23R, but we conclude that rare coding variants in positional candidates do not make a large contribution to inherited predisposition to Crohns disease.

  • 50.
    Munch, Andreas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Ost, A
    Medilab, Taby, Sweden .
    Carlsson, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Magnusson, Karl-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Low levels of bile acids increase bacterial uptake in colonic biopsies from patients with collagenous colitis in remission2011In: ALIMENTARY PHARMACOLOGY and THERAPEUTICS, ISSN 0269-2813, Vol. 33, no 8, p. 954-960Article in journal (Refereed)
    Abstract [en]

    Pandgt;Background Patients with collagenous colitis have an impaired mucosal barrier. Moreover, collagenous colitis is associated with bile acid malabsorption. Bile acids can increase bacterial mucosal uptake in humans. Mucosal barrier function was investigated by exposing colonic biopsies to chenodeoxycholic acid (CDCA) or deoxycholic acid (DCA) in Ussing chamber experiments. Aim To find if low levels of bile acids increase bacterial uptake in colonic biopsies from collagenous colitis patients. Methods The study comprised 33 individuals; 25 with collagenous colitis (14 in clinical remission without treatment, 11 with active disease and 10 examined in clinical remission resulting from treatment with 6 mg budesonide); eight healthy individuals undergoing screening colonoscopy served as controls. Endoscopic biopsies from the sigmoid colon were mounted in modified Ussing chambers and assessed for short-circuit current (Isc), potential difference, trans-epithelial resistance and transmucosal passage of Escherichia coli K12 after adding 100 mu mol/L CDCA or DCA. Results When adding 100 mu mol/L CDCA or DCA, bacterial uptake increased fourfold in biopsies of patients in remission; CDCA 6.5 units [2.5-9.8] and DCA 6.2 units [2.1-22] (median [IQR]), compared with uptake in biopsies without added bile acids 1.6 units [1.1-3] (P = 0.004 and P = 0.01 respectively). In active disease and in patients in remission due to budesonide treatment, bile acids did not affect bacterial uptake. Confocal microscopy revealed trans-epithelial passage of E. coli K12 within 30 min. Conclusions Low concentrations of dihydroxy-bile acids exacerbate mucosal barrier dysfunction in colonic biopsies of patients with collagenous colitis in remission. This allows a substantially increased bacterial uptake, which may contribute to recurrence of inflammation.

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