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  • 1.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences.
    Ekermo, Bengt
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Transfusion Medicine and Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Månsson, A-S.
    Department of Clinical Virology, University Hospital of Malmö, Sweden.
    Svensson, Samuel
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences.
    Widell, A.
    Department of Clinical Virology, University Hospital of Malmö, Sweden.
    Detection and prevention of hepatitis C in dialysis patients and renal transplant recipients: A long-term follow up (1989–January 1997)2002In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 251, no 2, p. 119-128Article in journal (Refereed)
    Abstract [en]

    Background. Hepatitis C is frequent problem in dialysis wards.

    Design.  A long time (1989–97) follow up of hepatitis C virus (HCV) infection in a Swedish nephrology unit was performed with anti-HCV screening, confirmatory antibody tests, viral RNA detection and molecular characterization. Case histories were reviewed with focus, onset of infection, liver morbidity and mortality.

    Results.  In October 1991, 10% (19 of 184) of the patients in the unit (haemodialysis-, peritoneal dialysis and transplanted patients) were verified or suspected HCV carriers, whilst the number at the end of 1996 was 8% (13 of 157). Most patients were infected before 1991 but only in one case from a known HCV-infected blood donor. No new HCV infections associated with haemodialysis occurred during the study period. A total of 13 of 24 viremic patients had HCV genotype 2b, a pattern suggesting nosocomial transmission. This was further supported by phylogenetic analysis of HCV viral isolates in seven. HCV viremia was also common in patients with an incomplete anti-HCV antibody pattern as 8 of the 12 indeterminant sera were HCV-RNA positive.

    Conclusions.  Awareness, prevention, identification of infected patients and donor testing limited transmission. Indeterminant recombinant immunoblot assays (RIBA)-results should be regarded with caution as a result of the relative immunodeficiency in uremic patients. Our data indicate nosocomial transmission in several patients.

  • 2.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Nephrology.
    Eneström, S.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Hed, J.
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Transfusion Medicine and Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Samuelsson, I.
    Section of Nephrology, Department of Internal Medicine. Örebro Medical Centre, Örebro, Sweden.
    Sjöström, P.
    Section of Nephrology, Department of Internal Medicine. Örebro Medical Centre, Örebro, Sweden.
    Autoantibodies to leucocyte antigens in hydralazine-associated nephritis1992In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 231, no 1, p. 37-42Article in journal (Refereed)
    Abstract [en]

    Clinical and laboratory findings and drug history were studied in 17 patients with suspected hydralazine-associated nephritis, five of whom only had renal disease, while twelve also had extrarenal manifestations. Renal biopsies revealed extracapillary proliferative or focal segmental proliferative glomerulonephritis in 10 patients, and tubulo-interstitial nephritis in five patients. Antinuclear antibody (ANA) was found in 16 patients, but none of the 14 patients tested had antibodies to DNA. Tests for antibodies to myeloperoxidase (anti-MPO) and antibodies to neutrophil cytoplasm antigen (ANCA) were performed by ELISA. Twelve of the 14 patients tested had anti-MPO; five of these 14 patients had ANCA, while one had borderline levels. These findings suggest that hydralazine facilitates the induction of a systemic disease with multiple autoantibody production.

  • 3.
    Almroth, Gabriel
    et al.
    Section of Nephrology, Department of Internal Medicine, Medical Centre Hospital, Örebro.
    Sjöström, P.
    Section of Nephrology, Department of Internal Medicine, Medical Centre Hospital, Örebro.
    Svalander, C.
    Department of Pathology, Sahlgren's Hospital, University of Göteborg, Sweden.
    Danielsson, D.
    Department of Microbiology and Immunology, Medical Centre Hospital, Örebro.
    Serum immunoglobulins and IgG subclasses in patients with glomerulonephritis1989In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 225, no 1, p. 3-7Article in journal (Refereed)
    Abstract [en]

    The serum concentrations of IgG, IgA, IgM and of the four subclasses of IgG were determined by radial immunodiffusion in 103 patients, mean age 42 (range 16–72), with various types of glomerulonephritis. Forty-nine healthy blood donors, mean age 41 years (range 19–65), served as controls. Kidney biopsies were obtained from all the patients for examination by histopathology and by immunofluorescence. The glomerulopathies were classified according to WHO criteria.

    The serum immunoglobulin patterns were different for the various clinical groups of patients. Patients with Wegener's granulomatosis, rapidly progressive glomerulonephritis and SLE had a significant increase in total IgG and of IgG4 (P < 0.05–0.001). Patients with minimal change disease had low concentrations of IgG (P < 0.001) with a significant decrease in IgG1 and IgG2 (P < 0.001 and 0.01. respectively). Highly significant increases in IgA were noted for patients with IgA nephritis (P < 0.001) but high levels were also seen in patients with chronic glomerulonephritis. The findings might have diagnostic implications.

  • 4.
    Angelin, Bo
    et al.
    Karolinska University, Sweden; Karolinska University, Sweden.
    Kristensen, Jens D.
    Karo Bio AB, Sweden.
    Eriksson, Mats
    Karolinska University, Sweden; Karolinska University, Sweden.
    Carlsson, Bo
    Karo Bio AB, Sweden.
    Klein, Irwin
    NYU, NY USA.
    Olsson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Stockholm Heart Centre, Sweden.
    Chester Ridgway, E.
    University of Colorado, CO USA.
    Ladenson, Paul W.
    Johns Hopkins University, MD 21205 USA.
    Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein(a) in hypercholesterolaemic patients treated with the liver-selective thyroid hormone receptor agonist eprotirome2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, no 3, p. 331-342Article in journal (Refereed)
    Abstract [en]

    BackgroundLiver-selective thyromimetic agents could provide a new approach for treating dyslipidaemia. MethodsWe performed a multicentre, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of eprotirome, a liver-selective thyroid hormone receptor agonist, in 98 patients with primary hypercholesterolaemia. After previous drug wash-out and dietary run-in, patients received 100 or 200gday(-1) eprotirome or placebo for 12weeks. The primary end-point was change in serum LDL cholesterol; secondary end-points included changes in other lipid parameters and safety measures. ResultsEprotirome treatment at 100 and 200g daily reduced serum LDL cholesterol levels by 235% and 31 +/- 4%, respectively, compared with 2 +/- 6% for placebo (Pless than0.0001). Similar reductions were seen in non-HDL cholesterol and apolipoprotein (apo) B, whereas serum levels of HDL cholesterol and apo A-I were unchanged. There were also considerable reductions in serum triglycerides and lipoprotein(a), in particular in patients with elevated levels at baseline. There was no evidence of adverse effects on heart or bone and no changes in serum thyrotropin or triiodothyronine, although the thyroxine level decreased. Low-grade increases in liver enzymes were evident in most patients. ConclusionIn hypercholesterolaemic patients, the liver-selective thyromimetic eprotirome decreased serum levels of atherogenic lipoproteins without signs of extra-hepatic side effects. Selective stimulation of hepatic thyroid hormone receptors may be an attractive way to modulate lipid metabolism in hyperlipidaemia.

  • 5.
    Bengtsson, Torbjörn
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Gunnarsson, Patrik
    Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Skoglund, Caroline
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Elison, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    The periodontal pathogen Porphyromonas gingivalis cleaves apoB-100 and increases the expression of apoM in LDL in whole blood leading to cell proliferation2008In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 263, no 5, p. 558-571Article in journal (Refereed)
    Abstract [en]

    Objective: Several studies support an association between periodontal disease and atherosclerosis with a crucial role for the pathogen Porphyromonas gingivalis. This study aims to investigate the proteolytic and oxidative activity of P. gingivalis on LDL in a whole blood system by using a proteomic approach and analyze the effects of P. gingivalis-modifed LDL on cell proliferation.

    Methods: The cellular effects of P. gingivalis in human whole blood were assessed using lumi-aggregometry analyzing reactive oxygen species (ROS) production and aggregation. Blood was incubated for 30 min with P. gingivalis, whereafter LDL was isolated and a proteomic approach was applied to examine protein expression. LDL-oxidation was determined by analyzing the formation of protein carbonyls. The effects of P. gingivalis-modifed LDL on fibroblast proliferation were studied using the MTS-assay.

    Results: Incubation of whole blood with P. gingivalis caused an extensive aggregation and ROS-production, indicating platelet and leukocyte activation. LDL prepared from the bacteria-exposed blood showed an increased protein oxidation, elevated levels of apoM and formation of two apoB-100 N-terminal fragments. P. gingivalis-modified LDL markedly increased the growth of fibroblasts. Inhibition of gingipain R suppressed the modification of LDL by P. gingivalis.

    Conclusions: The ability of P. gingivalis to change the protein expression and the proliferative capacity of LDL may represent a crucial event in periodontitis-associated atherosclerosis.

  • 6.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Clinical implications of omics and systems medicine: focus on predictive and individualized treatment2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, no 3, p. 229-240Article, review/survey (Refereed)
    Abstract [en]

    Many patients with common diseases do not respond to treatment. This is a key challenge to modern health care, which causes both suffering and enormous costs. One important reason for the lack of treatment response is that common diseases are associated with altered interactions between thousands of genes, in combinations that differ between subgroups of patients who do or do not respond to a given treatment. Such subgroups, or even distinct disease entities, have been described recently in asthma, diabetes, autoimmune diseases and cancer. High-throughput techniques (omics) allow identification and characterization of such subgroups or entities. This may have important clinical implications, such as identification of diagnostic markers for individualized medicine, as well as new therapeutic targets for patients who do not respond to existing drugs. For example, whole-genome sequencing may be applied to more accurately guide treatment of neurodevelopmental diseases, or to identify drugs specifically targeting mutated genes in cancer. A study published in 2015 showed that 28% of hepatocellular carcinomas contained mutated genes that potentially could be targeted by drugs already approved by the US Food and Drug Administration. A translational study, which is described in detail, showed how combined omics, computational, functional and clinical studies could identify and validate a novel diagnostic and therapeutic candidate gene in allergy. Another important clinical implication is the identification of potential diagnostic markers and therapeutic targets for predictive and preventative medicine. By combining computational and experimental methods, early disease regulators may be identified and potentially used to predict and treat disease before it becomes symptomatic. Systems medicine is an emerging discipline, which may contribute to such developments through combining omics with computational, functional and clinical studies. The aims of this review are to provide a brief introduction to systems medicine and discuss how it may contribute to the clinical implementation of individualized treatment, using clinically relevant examples.

  • 7.
    Bergström, G
    et al.
    University of Gothenburg / Sahlgrenska University Hospital.
    Berglund, G
    Lund University.
    Blomberg, A
    Umeå University.
    Brandberg, J
    Sahlgrenska University Hospital / University of Gothenburg.
    Engström, G
    Lund University.
    Engvall, Jan
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Eriksson, M
    Karolinska University Hospital, Stockholm.
    de Faire, U
    Karolinska Institutet, Stockholm / Karolinska University Hospital, Stockholm.
    Flinck, A
    Sahlgrenska University Hospital, Stockholm / University of Gothenburg.
    Hansson, M G
    Uppsala University.
    Hedblad, B
    Lund University.
    Hjelmgren, O
    University of Gothenburg / Sahlgrenska University Hospital, Gothenburg.
    Janson, C
    Uppsala University.
    Jernberg, T
    Karolinska University Hospital, Stockholm / Karolinska Institutet, Stockholm.
    Johnsson, Å
    Sahlgrenska University Hospital, Gothenburg / University of Gothenburg.
    Johansson, L
    Unit of Radiology.
    Lind, L
    Uppsala University.
    Löfdahl, C-G
    Lund University / Lund University Hospital.
    Melander, O
    Lund University / Skåne University Hospital, Malmö.
    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, Primary Health Care in Motala.
    Persson, Anders
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Persson, M
    Lund University / Skåne University Hospital, Malmö.
    Sandström, A
    Umeå University.
    Schmidt, C
    University of Gothenburg.
    Söderberg, S
    Umeå University.
    Sundström, J
    Uppsala University / Uppsala Clinical Resarch Centre.
    Toren, K
    University of Gothenburg.
    Waldenström, A
    Umeå University Hospital.
    Wedel, H
    Nordic School of Public Health, Gothenburg.
    Vikgren, J
    Sahlgrenska University Hospital, Gothenburg / University of Gothenburg.
    Fagerberg, B
    University of Gothenburg.
    Rosengren, A
    University of Gothenburg.
    The Swedish CArdioPulmonary BioImage Study: objectives and design2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 278, no 6, p. 645-659Article in journal (Refereed)
    Abstract [en]

    Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.

  • 8.
    Björck, Hanna
    et al.
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
    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.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Persson, Karin
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Rundkvist, Louise
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Hamsten, A
    Karolinska Institute.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Eriksson, P
    Karolinska Institute, Stockholm.
    Association of genetic variation on chromosome 9p21.3 and arterial stiffness2009In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 265, no 3, p. 373-381Article in journal (Refereed)
    Abstract [en]

    Genome wide association studies have consistently reported associations between a region on chromosome 9p21.3 and a broad range of vascular diseases, such as coronary artery disease (CAD), aortic and intracranial aneurysms and type-2 diabetes (T2D). However, clear associations with intermediate phenotypes have not been described so far. To shed light on a possible influence of this chromosomal region on arterial wall integrity, we analysed associations between single nucleotide polymorphisms (SNPs) and degree of stiffness of the abdominal aorta in elderly individuals.

    A total of 400 subjects, 212 men and 188 women, aged 70-88 years were included. Arterial stiffness was examined at the midpoint between the renal arteries and the aortic bifurcation. Two CAD- and aneurysm-associated SNPs (rs10757274 and rs2891168) and one T2D-associated SNP (rs1081161) within the 9p21.3 region were genotyped. Aortic compliance and distensibility coefficients were higher in carriers of the rs10757274G and rs2891168G alleles in men reflecting a decrease in aortic stiffness. Adjustment for age and mean arterial pressure had no effect on these associations. The two SNPs were not associated with intima-media thickness or lumen diameter of the abdominal aorta. There were no associations between the rs10811661 SNP and any measure of aortic stiffness.

    Impaired mechanical properties of the arterial wall may explain the association between chromosome 9p21.3 polymorphisms and vascular disease.

  • 9.
    Eriksson, D.
    et al.
    Karolinska Institute, Sweden; Metab and Diabet Karolinska University Hospital, Sweden.
    Bianchi, M.
    Uppsala University, Sweden.
    Landegren, N.
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Nordin, J.
    Uppsala University, Sweden.
    Dalin, F.
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Mathioudaki, A.
    Uppsala University, Sweden.
    Eriksson, G. N.
    Karolinska Institute, Sweden.
    Hultin-Rosenberg, L.
    Uppsala University, Sweden.
    Dahlqvist, J.
    Uppsala University, Sweden.
    Zetterqvist, H.
    Uppsala University, Sweden; Uppsala University, Sweden.
    Karlsson, A.
    Uppsala University, Sweden.
    Hallgren, A.
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Farias, F. H. G.
    Uppsala University, Sweden.
    Muren, E.
    Uppsala University, Sweden.
    Ahlgren, K. M.
    Uppsala University, Sweden.
    Lobell, A.
    Uppsala University, Sweden.
    Andersson, G.
    Swedish University of Agriculture Science, Sweden.
    Tandre, K.
    Uppsala University, Sweden.
    Dahlqvist, S. R.
    Umeå University, Sweden.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Rönnblom, L.
    Uppsala University, Sweden.
    Hulting, A. -L.
    Karolinska Institute, Sweden.
    Wahlberg Topp, Jeanette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Ekwall, O.
    University of Gothenburg, Sweden.
    Dahlqvist, P.
    Umeå University, Sweden.
    Meadows, J. R. S.
    Uppsala University, Sweden.
    Bensing, S.
    Metab and Diabet Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Lindblad-Toh, K.
    Uppsala University, Sweden; Broad Institute MIT and Harvard, MA USA.
    Kampe, O.
    Karolinska Institute, Sweden; Metab and Diabet Karolinska University Hospital, Sweden; Uppsala University, Sweden.
    Pielberg, G. R.
    Uppsala University, Sweden.
    Extended exome sequencing identifies BACH2 as a novel major risk locus for Addisons disease2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 286, no 6, p. 595-608Article in journal (Refereed)
    Abstract [en]

    BackgroundAutoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addisons disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. MethodsTo understand the genetic background of Addisons disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addisons disease and 1394 controls. ResultsWe identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 x 10(-15), MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addisons disease development. We also confirmed the previously known associations with the HLA complex. ConclusionWhilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addisons disease, we have identified BACH2 as a major risk locus in Addisons disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.

  • 10.
    Eriksson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology.
    Nine patients with anti-neutrophil cytoplasmic antibody-positive vasculitis successfully treated with rituximab2005In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 257, no 6, p. 540-548Article in journal (Refereed)
    Abstract [en]

    Objectives. Rituximab (RIT) is a monoclonal anti-CD20 antibody, which depletes B-lymphocytes but not plasma cells. RIT is used for treatment of B-cell lymphomas, but has also shown beneficial effects in autoimmune diseases. In this case series RIT was used in anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis. Design. Case series with a structured follow-up of treated patients. Setting. Departments of Nephrology and Rheumatology of a university hospital. Subjects. Two women with myeloperoxidase-ANCA-positive microscopic polyangiitis and seven patients (five men and two women) with proteinase 3-ANCA-positive Wegener's granulomatosis. All patients were resistant to conventional therapy or had relapsed repeatedly after cessation of cyclophosphamide (Cyc). Interventions. The cases were treated with intravenous infusions of RIT once a week two times (three cases) or four times (six cases). To prevent formation of antibodies to RIT, mycophenolate mofetil (five patients), azathioprine (one patient), or a short course of Cyc (two patients) were added or allowed to continue. Mainoutcome measures. Remission at 6 months assessed with Birmingham vasculitis activity score. The cases were followed 6-24 months and relapse rate was also noted. Results. Eight of nine patients responded completely and one case responded partially. Pulmonary X-ray improved (four cases), progress of lower extremity gangrene stopped (one case), remission of neuropathy was stable (one patient), renal vasculitis went into remission (two cases), and severe musculoskeletal pain improved (one case). Minor relapse in the nose occurred in two cases. No adverse events or major infections were noted. Conclusion. RIT seems promising and safe in ANCA-positive vasculitis, and controlled studies should be conducted. © 2005 Blackwell Publishing Ltd.

  • 11.
    Fändrich, M.
    et al.
    Ulm Univ, Germany.
    Nyström, Sofie
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Bockmann, A.
    Univ Lyon, France.
    LeVine, H. III
    Univ Kentucky, KY 40536 USA; Univ Kentucky, KY USA.
    Hammarström, Per
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Amyloid fibril polymorphism: a challenge for molecular imaging and therapy2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 3, p. 218-237Article in journal (Refereed)
    Abstract [en]

    The accumulation of misfolded proteins (MPs), both unique and common, for different diseases is central for many chronic degenerative diseases. In certain patients, MP accumulation is systemic (e.g. TTR amyloid), and in others, this is localized to a specific cell type (e.g. Alzheimers disease). In neurodegenerative diseases, NDs, it is noticeable that the accumulation of MP progressively spreads throughout the nervous system. Our main hypothesis of this article is that MPs are not only markers but also active carriers of pathogenicity. Here, we discuss studies from comprehensive molecular approaches aimed at understanding MP conformational variations (polymorphism) and their bearing on spreading of MPs, MP toxicity, as well as MP targeting in imaging and therapy. Neurodegenerative disease (ND) represents a major and growing societal challenge, with millions of people worldwide suffering from Alzheimers or Parkinsons diseases alone. For all NDs, current treatment is palliative without addressing the primary cause and is not curative. Over recent years, particularly the shape-shifting properties of misfolded proteins and their spreading pathways have been intensively researched. The difficulty in addressing ND has prompted most major pharma companies to severely downsize their nervous system disorder research. Increased academic research is pivotal for filling this void and to translate basic research into tools for medical professionals. Recent discoveries of targeting drug design against MPs and improved model systems to study structure, pathology spreading and toxicity strongly encourage future studies along these lines to provide an opportunity for selective imaging, prognostic diagnosis and therapy.

  • 12.
    Griffith, May
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Maisonneuve Rosemont Hospital, Canada.
    Alarcon, E. I.
    University of Ottawa, Canada.
    Brunette, I.
    Maisonneuve Rosemont Hospital, Canada; University of Montreal, Canada.
    Regenerative approaches for the cornea2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 280, no 3, p. 276-286Article, review/survey (Refereed)
    Abstract [en]

    The cornea is the transparent front part of the eye that transmits light to the back of the eye to generate vision. Loss of corneal transparency, if irreversible, leads to severe vision loss or blindness. For decades, corneal transplantation using human donor corneas has been the only option for treating corneal blindness. Despite recent improvement in surgical techniques, donor cornea transplantation remains plagued by risks of suboptimal optical results and visual acuity, immune rejection and eventually graft failure. Furthermore, the demand for suitable donor corneas is increasing faster than the number of donors, leaving thousands of curable patients untreated worldwide. Here, we critically review the state of the art of biomaterials for corneal regeneration. However, the lessons learned from the use of the cornea as a disease model will allow for extension of the biomaterials and techniques for regeneration of more complex organs such as the heart.

  • 13.
    Hasib, Lekbira
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Lundberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Functional and homeostatic defects of regulatory T cells in patients with coronary artery disease2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, no 1, p. 63-77Article in journal (Refereed)
    Abstract [en]

    ObjectiveRegulatory T cells (Tregs) are considered atheroprotective, and low levels have been associated with the acute coronary syndrome (ACS), particularly non-ST elevation (NSTE)-ACS. However, the functional properties as well as homeostasis of Tregs are mainly unknown in coronary artery disease (CAD). Here, we investigated the composition and functional properties of naive (n) and memory (m)Tregs in patients with NSTE-ACS and in patients 6-12months post-ACS. MethodsBased on the expression of CD25, FOXP3, CD127, CD45RA, CD39 and CTLA-4, Tregsubsets were defined by flow cytometry in whole blood or isolated CD4(+) T cells. The functional properties of nTregs and mTregs were examined in terms of proliferative capacity and modulation of cytokine secretion. To understand the potential consequences of Treg defects, we also investigated correlations with lipopolysaccharide (LPS)-induced cytokine secretion and ultrasound-defined carotid atherosclerosis. ResultsBoth NSTE-ACS and post-ACS patients exhibited reduced levels of nTregs (P&lt;0.001) compared with healthy control subjects, but without compensatory increases in mTregs. Both nTregs and mTregs from patients showed significantly lower replicative rates and impaired capacity to modulate T-cell proliferation and secretion of interferon-gamma and IL-10. The Treg defect was also associated with LPS-induced cytokine secretion and increased burden of carotid atherosclerosis. ConclusionOur results demonstrate a functional and homeostatic Treg defect in patients with NSTE-ACS and also in stabilized patients 6-12months after ACS. Moreover, this defect was associated with a subclinical proinflammatory and atherogenic state. We believe that the failure to preserve Treg function and homeostasis reflects a need for immune-restoring strategies in CAD.

  • 14.
    Hofmann, R.
    et al.
    Soder Sjukhuset, Sweden.
    Tornvall, P.
    Soder Sjukhuset, Sweden.
    Witt, N.
    Soder Sjukhuset, Sweden.
    Alfredsson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Svensson, L.
    Soder Sjukhuset, Sweden; Soder Sjukhuset, Sweden.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Supplemental oxygen therapy does not affect the systemic inflammatory response to acute myocardial infarction2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 4, p. 334-345Article in journal (Refereed)
    Abstract [en]

    Background. Oxygen therapy has been used routinely in normoxemic patients with suspected acute myocardial infarction (AMI) despite limited evidence supporting a beneficial effect. AMI is associated with a systemic inflammation. Here, we hypothesized that the inflammatory response to AMI is potentiated by oxygen therapy. Methods. The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) multicentre trial randomized patients with suspected AMI to receive oxygen at 6 L min(-1) for 6-12 h or ambient air. For this prespecified subgroup analysis, we recruited patients with confirmed AMI from two sites for evaluation of inflammatory biomarkers at randomization and 5-7 h later. Ninety-two inflammatory biomarkers were analysed using proximity extension assay technology, to evaluate the effect of oxygen on the systemic inflammatory response to AMI. Results. Plasma from 144 AMI patients was analysed whereof 76 (53%) were randomized to oxygen and 68 (47%) to air. Eight biomarkers showed a significant increase, whereas 13 were decreased 5-7 h after randomization. The inflammatory response did not differ between the two treatment groups neither did plasma troponin T levels. After adjustment for increase in troponin T over time, age and sex, the release of inflammation-related biomarkers was still similar in the groups. Conclusions. In a randomized controlled setting of normoxemic patients with AMI, the use of supplemental oxygen did not have any significant impact on the early release of systemic inflammatory markers.

  • 15.
    Hollman, Gunilla
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine.
    Ek, Anna-Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nursing Science.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Only one of four patients with familial hypercholesterolaemia reach cholesterol treatment goals in primary prevention2004In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 256, no 2, p. 176-177Article in journal (Other academic)
  • 16.
    Hollman, Gunilla
    et al.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Gullberg, Mats
    Linköping University, Department of Medicine and Care, Nursing Science. Linköping University, Faculty of Health Sciences.
    Ek, Anna-Christina
    Linköping University, Department of Medicine and Care, Nursing Science. Linköping University, Faculty of Health Sciences.
    Eriksson, Mats
    Centre for Metabolism Endocrinology, Huddinge University Hospital, Stockholm, Sweden.
    Olsson, Anders G.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Quality of life in patients with familial hypercholesterolaemia2002In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 251, no 4, p. 331-337Article in journal (Refereed)
    Abstract [en]

    Objectives.  The primary aim of this study was to analyse quality of life in adult patients with familial hypercholesterolaemia (FH), a genetic disorder with increased risk of coronary heart disease (CHD). Secondary aims were to find explanatory factors for quality of life and anxiety.

    Design. A descriptive cross-sectional design was used.

    Setting.  Outpatients from lipid clinics at two university hospitals in Sweden were included. Patients with heterozygous FH and a randomly selected control group participated by filling out questionnaires.

    Subjects.  Two hundred and eighty patients with heterozygous FH above 18 years of age were asked, and 212 of whom 185 were free of overt CHD, participated. Of a control group of 2980 persons 1485 were included for comparison.

    Methods. We used Likert-type questionnaires: the Quality of Life Index (QLI) consisting of four subscales, the Hospital Anxiety and Depression Scale (HAD), the Mastery Scale measuring coping and a questionnaire on health and lipids constructed for FH patients.

    Results.  Patients with FH were significantly more satisfied with overall quality of life 21.8 ± 0.3 (SEM) vs. controls 21.1 ± 0.1 and this was also the case in three of four subscales, all differences P < 0.05. Anxiety about getting CHD was expressed amongst 86% of the patients with FH.

    Conclusions. Quality of life amongst patients with FH was at least as good as in controls but they were worried about getting CHD.

  • 17.
    Jansson, Kjell
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Karlberg, B E
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine.
    Karlsson, E
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Nylander, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Nyqvist, O
    Karlberg, K-E
    The circulating renin-angiotensin system during treatment with mteprlol or captopril in patients with heart failure due to non-ischaemic dilated cardiomyopathy.1999In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 245, p. 435-443Article in journal (Refereed)
  • 18.
    Jarvinen, T. L. N.
    et al.
    University of Helsinki, Finland; University of Helsinki, Finland.
    Michaelsson, K.
    Uppsala University, Sweden.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Sievanen, H.
    UKK Institute Health Promot Research, Finland.
    Osteoporosis: the emperor has no clothes2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, no 6, p. 662-673Article in journal (Refereed)
    Abstract [en]

    Current prevention strategies for low-trauma fractures amongst older persons depend on the notions that fractures are mainly caused by osteoporosis (pathophysiology), that patients at high risk can be identified (screening) and that the risk is amenable to bone-targeted pharmacotherapy (treatment). However, all these three notions can be disputed. PathophysiologyMost fracture patients have fallen, but actually do not have osteoporosis. A high likelihood of falling, in turn, is attributable to an ageing-related decline in physical functioning and general frailty. ScreeningCurrently available fracture risk prediction strategies including bone densitometry and multifactorial prediction tools are unable to identify a large proportion of patients who will sustain a fracture, whereas many of those with a high fracture risk score will not sustain a fracture. TreatmentThe evidence for the viability of bone-targeted pharmacotherapy in preventing hip fracture and other clinical fragility fractures is mainly limited to women aged 65-80years with osteoporosis, whereas the proof of hip fracture-preventing efficacy in women over 80years of age and in men at all ages is meagre or absent. Further, the antihip fracture efficacy shown in clinical trials is absent in real-life studies. Many drugs for the treatment of osteoporosis have also been associated with increased risks of serious adverse events. There are also considerable uncertainties related to the efficacy of drug therapy in preventing clinical vertebral fractures, whereas the efficacy for preventing other fractures (relative risk reductions of 20-25%) remains moderate, particularly in terms of the low absolute risk reduction in fractures with this treatment.

  • 19.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. World University of Network, Australia.
    The mother-offspring dyad: microbial transmission, immune interactions and allergy development2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 282, no 6, p. 484-495Article, review/survey (Refereed)
    Abstract [en]

    The increasing prevalence of allergy in affluent countries may be caused by reduced intensity and diversity of microbial stimulation, resulting in abnormal postnatal immune maturation. Most studies investigating the underlying immunomodulatory mechanisms have focused on postnatal microbial exposure, for example demonstrating that the gut microbiota differs in composition and diversity during the first months of life in children who later do or do not develop allergic disease. However, it is also becoming increasingly evident that the maternal microbial environment during pregnancy is important in childhood immune programming, and the first microbial encounters may occur already in utero. During pregnancy, there is a close immunological interaction between the mother and her offspring, which provides important opportunities for the maternal microbial environment to influence the immune development of the child. In support of this theory, combined pre- and postnatal supplementations seem to be crucial for the preventive effect of probiotics on infant eczema. Here, the influence of microbial and immune interactions within the mother-offspring dyad on childhood allergy development will be discussed. In addition, how perinatal transmission of microbes and immunomodulatory factors from mother to offspring may shape appropriate immune maturation during infancy and beyond, potentially via epigenetic mechanisms, will be examined. Deeper understanding of these interactions between the maternal and offspring microbiome and immunity is needed to identify efficacious preventive measures to combat the allergy epidemic.

  • 20.
    Jerlock, M.
    et al.
    The Sahlgrenska Academy, Göteborg University, Sweden.
    Kjellgren, Karin
    The Sahlgrenska Academy, Göteborg University, Sweden.
    Gaston-Johansson, F.
    Johns Hopkins University, School of Nursing, Baltimore, MD, USA.
    Lissner, L.
    The Sahlgrenska Academy, Göteborg University, Sweden.
    Manhem, K.
    Sahlgrenska University Hospital/Östra, Gothenburg; Sweden.
    Rosengren, A.
    Sahlgrenska University Hospital/Östra, Gothenburg; Sweden.
    Welin, C.
    The Sahlgrenska Academy, Göteborg University, Sweden.
    Psychosocial profile in men and women with unexplained chest pain2008In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 264, no 3, p. 265-274Article in journal (Refereed)
    Abstract [en]

    Objective.  The aim of this study was to compare men and women with unexplained chest pain (UCP) to a randomly selected population sample free of clinical heart disease with regard to sleep problems, mental strain at work, stress at home, negative life events and health-related quality of life (HRQOL).

    Design and subjects.  The study was conducted at a university hospital in Sweden including 231 patients aged 25–69 without any organic cause for chest pain. As a reference group, 1069 participants, were recruited from the INTERGENE population-based study.

    Results.  Patients with UCP had more sleep problems (OR = 1.8, P < 0.0001), were almost three times more worried about stress at work (OR = 2.9, P < 0.0001), or had more stress at home (OR = 2.8, P < 0.0001), and were twice as likely to have negative life events (OR = 2.1, P < 0.0001). Women, but not men, with UCP, had a higher prevalence of cardiovascular risk factors (obesity, smoking, diabetes and hypertension) compared with references. With regard to HRQOL, UCP patients scored significantly lower than references in all dimensions of the SF-36.

    Conclusions.  In comparison with a healthy reference group, patients with UCP reported more sleep problems, mental strain at work, stress at home and negative life events and had lower health-related quality of life. Aside from immigration the strongest independent psychosocial factors were mental strain at work and negative life events last year in men and stress at home in women.

  • 21.
    Jonasson, Lena
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Tompa, A.
    Department of Microbiology, Ryhov Hospital, Jönköping, Sweden.
    Wikby, A.
    Dept. of Nat. Sci. and Biomedicine, School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Expansion of peripheral CD8+ T cells in patients with coronary artery disease: Relation to cytomegalovirus infection2003In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 254, no 5, p. 472-478Article in journal (Refereed)
    Abstract [en]

    Objectives. The nature of the immune response in coronary artery disease (CAD) is not fully defined. One pathogen that has been linked to atherogenesis, cytomegalovirus (CMV). is known to exert strong and long-lasting effects on peripheral T cells. In the present study, we investigated the effect of prior CMV infection on the immune system in CAD patients. Subjects. Patients with stable angina and angiographically verified CAD (n = 43) and clinically healthy controls (n = 69) were included. Methods. The expression of CD57 and CD28 on peripheral CD4+ and CD8+ T cells was evaluated with three-colour flow cytometry. The findings were related to serological markers of inflammation, T-cell activation and CMV seropositivity. Results. An expansion of CD8+ T cells expressing CD57 but lacking CD28 was seen in the patient group. The numbers of CD8+CD57+ and CD8+ CD28- T-cell subsets were independently related to CMV seropositivity (P < 0.001) but also to CAD per se (P < 0.05). Serum concentrations of C-reactive protein (CRP) and soluble interleukin-2 receptor (sIL-2R) were elevated in the patients but not related to CMV or CD8 + T-cell subsets. Conclusion. A pronounced shift in peripheral T-cell homeostasis was observed in CAD patients. Primarily CMV infection but also CAD per se contributed to the expansion of CD8+ T-cell subsets. The T-cell changes were not related to a systemic inflammatory response but should rather be considered as markers of a chronic antigen exposure and/or immunosenescence in CAD.

  • 22.
    Järemo, Petter
    et al.
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Lindahl, Tomas
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Fransson, Sven Göran
    Linköping University, Department of Medicine and Care, Radiology. Linköping University, Faculty of Health Sciences.
    Richter, Arina
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Individual variations of platelet inhibition after loading doses of clopidogrel2002In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 252, no 3, p. 233-238Article in journal (Refereed)
    Abstract [en]

    Objective.  To investigate individual variations of platelet inhibition after clopidogrel-loading doses.

    Setting.  Department of Cardiology, Linköping University Hospital, Linköping, Sweden.

    Subjects.  Individuals with stable angina pectoris (n = 18) subject to percutaneous coronary interventions (PCI) and subsequent stenting were investigated.

    Methods and experimental protocol.  A 300-mg clopidogrel loading dose was administrated immediately after stenting (day 1) followed by an additional 75 mg clopidogrel after 24 h (day 2). The ADP-evoked platelet fibrinogen binding was analysed to estimate platelet reactivity immediately before angiography and on day 2. A flow cytometry technique was used with two ADP solutions (final concentrations 0.6 and 1.7 μmol L−1) employed as platelet activating agents. Soluble P-selectin was used as a marker of platelet activity.

    Results.  When using 1.7 μmol L−1 ADP to activate platelets four individuals had a strong inhibition (i.e. platelet reactivity <10% of the day 1-value day 2). In contrast, five patients demonstrated a weak inhibition (i.e. platelet reactivity >60% of the day 1-value day 2). Similar results were obtained when using 0.6 μmol L−1 ADP as a platelet-activating agent. Clopidogrel, however, fails to suppress platelet activity as estimated from soluble P-selectin.

    Conclusions.  Clopidogrel evoked platelet inhibition exhibits a considerable individual heterogeneity. Some individuals only had weak responses whereas others displayed strong platelet inhibition. The present flow cytometry technique appears suitable for identifying patients with abnormal reactions after clopidogrel exposure.

  • 23.
    Järemo, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Milovanovic, Micha
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Nilsson, Staffan
    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 East of Östergötland, East County Primary Health Care.
    Buller, Caroline
    Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Post, Claes
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Winblad, Bengt
    Department of Neurobiology, Care Sciences and Society (NVS), KI-Alzheimer’s Disease Research Center, Karolinska Institute, Huddinge; Sweden.
    Alzheimer's disease is characterized by more low-density erythrocytes with increased volume and enhanced β-amyloid x-40 content2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 5, p. 489-492Article in journal (Other academic)
  • 24.
    Kjellgren, Karin
    et al.
    Hälsouniveristetet LInköping.
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Dahlöf, Björn
    Sahlgrenska sjukhuset Göteborg.
    Gill, Hans
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Perceived symptoms amongst hypertensive patients in routine clinical practice - a population-based study1998In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 244, p. 325-332Article in journal (Refereed)
  • 25.
    Lerm, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Netea, M. G.
    Radboud University of Nijmegen, Netherlands.
    Trained immunity: a new avenue for tuberculosis vaccine development2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, no 4, p. 337-346Article, review/survey (Refereed)
    Abstract [en]

    Adaptive immunity towards tuberculosis (TB) has been extensively studied for many years. In addition, in recent years the profound contribution of innate immunity to host defence against this disease has become evident. The discovery of pattern recognition receptors, which allow innate immunity to tailor its response to different infectious agents, has challenged the view that this arm of immunity is nonspecific. Evidence is now accumulating that innate immunity can remember a previous exposure to a microorganism and respond differently during a second exposure. Although the specificity and memory of innate immunity cannot compete with the highly sophisticated adaptive immune response, its contribution to host defence against infection and to vaccine-induced immunity should not be underestimated and needs to be explored. Here, we present the concept of trained immunity and discuss how this may contribute to new avenues for control of TB.

  • 26. Lind, S
    et al.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Eriksson, M
    Rudling, M
    Eggertsen, G
    Angelin, B
    Autosomal recessive hypercholesterolaemia: Normalization of plasma LDL cholesterol by ezetimibe in combination with statin treatment2004In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 256, no 5, p. 406-412Article in journal (Refereed)
    Abstract [en]

    Background. Severe hereditary hypercholesterolaemia is most frequently due to familial hypercholesterolaemia (FH), caused by mutations in the LDL receptor (LDLR) gene. However, a phenotype very similar to FH may also be caused by defects in other genes like the genes for apolipoprotein (apo) B-100 or autosomal recessive hypercholesterolaemia (ARH). Subject. An 8-year-old male of Lebanese origin was diagnosed with severe hypercholesterolaemia and extensive cutaneous and tendon xanthomas. Plasma LDL cholesterol before treatment was 17 mmol L-1, whilst parents and both siblings had normal levels. Diagnosis. Degradation of 125I-labelled LDL in blood lymphocytes was reduced, but not abolished. Sequencing analysis of the LDLR and apoB-100 genes were negative, whilst a splice acceptor mutation in intron 1 (IVS 1 - 1G>C) was detected in the ARH gene. The patient was homozygous for the mutation, whilst the parents were heterozygous. These findings were in agreement with a diagnosis of ARH. Treatment and clinical course. Monthly LDL apheresis and atorvastatin 120 mg daily reduced LDL cholesterol preapheresis level to 4.8 mmol L-1. When ezetimibe was given 10 mg day-1 in combination with rosuvastatin 80 mg day-1, LDL cholesterol was further lowered to 1.6 mmol L-1, which made apheresis unnecessary. Cutaneous and tendon xanthomas disappeared completely and the intima-media thickness of the common carotid arteries decreased. At age 23 he developed a small myocardial infarction. Conclusion. ARH should be considered in cases of severe hypercholesterolaemia with a pattern of recessive inheritance. Combination therapy with high-dose statin and ezetimibe seems to be the treatment of choice in ARH and may reduce or eliminate the need for LDL apheresis treatment.

  • 27.
    Lindenberger, Marcus
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology.
    Kjellberg, Margareta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Karlsson, Erling
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Wranne, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Pericardiocentesis guided by 2-D echocardiography: The method of choice for treatment of pericardial effusion2003In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 253, no 4, p. 411-417Article in journal (Refereed)
    Abstract [en]

    Background. Percutaneous pericardiocentesis guided by 2-D echocardiography has been used at Link÷ping Heart Centre since 1983. Aim. To evaluate our experience of this method including a follow-up and also to determine the aetiology of pericardial effusion. Methods. A retrospective study including 120 of 252 consecutive patients punctured. Results. The two most common aetiologies were cardiac surgery (77% valve surgery), followed by malignant disease. The postsurgical effusions became clinically important a median of 12 days after surgery (range 0-56 days). The median survival in the group with malignant disease was 89 days (30-day survival 87%, 1-year survival 10%). Indwelling catheter was used in 93% of the patients. There was no mortality but one patient needed a second pericardiocentesis after an accidental puncture of the right ventricle. Nine patients had rhythm aberrations. Recurring effusion that needed puncture was seen in 8%. Conclusion. Pericardiocentesis guided by 2-D echocardiography is a safe and efficient method to treat pericardial effusion and also valuable as palliative treatment for patients with malignant aetiology of the effusion.

  • 28. Littorin, B
    et al.
    Nyström, L
    Gullberg, B
    Råstam, L
    Östman, J
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-endo.
    Björk, E
    Blohmé, G
    Bolinder, J
    Eriksson, JW
    Scherstén, B
    Sundkvist, G
    Increasing body mass index at diagnosis of diabetes in young adult people during 1983-1999 in the Diabetes Incidence Study in Sweden (DISS)2003In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 254, no 3, p. 251-256Article in journal (Refereed)
    Abstract [en]

    Objective. To study trends in body mass index (BMI) at diagnosis of diabetes in all young Swedish adults in the age range of 15-34 years registered in a nation-based registry. Design. The BMI was assessed at diagnosis in diabetic patients 15-34 years of age at diagnosis, for a period of 17 years (1983-1999). Islet cell antibodies (ICA) were measured during three periods (1987-1988, 1992-1993 and 1998-1999). Setting. A nationwide study (Diabetes Incidence Study in Sweden). Subjects. A total of 4727 type 1 and 1083 type 2 diabetic patients. Main outcome measures. Incidence-year specific BMI adjusted for age, gender and time of diagnosis (month). Results. Body mass index at diagnosis increased significantly both in type 1 (21.4 ▒ 3.6 to 22.5 ▒ 4.0: P < 0.0001) and in type 2 (27.4 ▒ 6.8 to 32.0 ▒ 6.0, P < 0.0001) diabetic patients, also when adjusted for age, gender and month of diagnosis. A similar significant increase in BMI was found in type 1 diabetic patients and in type 2 diabetic patients in the periods 1987-1988, 1992-1993 and 1998-1999, years when ICA were assessed and considered in the classification of diabetes. Despite this increase in BMI, there was no increase in the incidence of diabetes in young-adult people in Sweden. Conclusion. Body mass index at diagnosis of diabetes in subjects 15-34 years of age has substantially increased during 1983-1999 in Sweden when adjusted for age, gender and month of diagnosis.

  • 29.
    Loffler, S.
    et al.
    Karolinska Institute, Sweden.
    Melican, K.
    Karolinska Institute, Sweden.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Richter-Dahlfors, A.
    Karolinska Institute, Sweden.
    Organic bioelectronics in medicine2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 282, no 1, p. 24-36Article in journal (Refereed)
    Abstract [en]

    A major challenge in the growing field of bioelectronic medicine is the development of tissue interface technologies promoting device integration with biological tissues. Materials based on organic bioelectronics show great promise due to a unique combination of electronic and ionic conductivity properties. In this review, we outline exciting developments in the field of organic bioelectronics and demonstrate the medical importance of these active, electronically controllable materials. Importantly, organic bioelectronics offer a means to control cell-surface attachment as required for many device-tissue applications. Experiments have shown that cells readily attach and proliferate on reduced but not oxidized organic bioelectronic materials. In another application, the active properties of organic bioelectronics were used to develop electronically triggered systems for drug release. After incorporating drugs by advanced loading strategies, small compound drugs were released upon electrochemical trigger, independent of charge. Another type of delivery device was used to achieve well-controlled, spatiotemporal delivery of cationic drugs. Via electrophoretic transport within a polymer, cations were delivered with single-cell precision. Finally, organic bioelectronic materials are commonly used as electrode coatings improving the electrical properties of recording and stimulation electrodes. Because such coatings drastically reduce the electrode impedance, smaller electrodes with improved signal-to-noise ratio can be fabricated. Thus, rapid technological advancement combined with the creation of tiny electronic devices reacting to changes in the tissue environment helps to promote the transition from standard pharmaceutical therapy to treatment based on electroceuticals. Moreover, the widening repertoire of organic bioelectronics will expand the options for true biological interfaces, providing the basis for personalized bioelectronic medicine.

  • 30. Löfgren, U B
    et al.
    Rosenqvist, U
    Lindström, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hallert, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Welfare and Care (IVV), Self-Care and Learning.
    Nyström, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Diabetes control in Swedish community dwelling elderly: More often tight than poor2004In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 255, no 1, p. 96-101Article in journal (Refereed)
    Abstract [en]

    Objective. To determine glycaemic control in elderly patients with diabetes living in community dwelling. Design. Descriptive, cross-sectional and open. Prospective with regard to blood glucose. Setting. Community-dwelling in-patients. Subjects. From a total number of 351 patients in seven Swedish centres of community dwelling we identified and recruited all 45 patients with diabetes receiving treatment with insulin, and/or oral medication. Main outcome measures. Blood glucose was measured fasting, 2 h after breakfast, in the evening and at night, for three consecutive days. Results. Mean HbA1c was 5.9 ± 1.1% (range 3.6-8.6%). The patients were split in three HbA1c-groups for analysis: lower- (3.6-5.3%), middle-(5.4-6.3%) and higher-tertile (6.4-8.6%). The groups where similar with regard to age, time in community dwelling, ability to eat and move around independently, but body mass index was lower in the lower tertile (P < 0.003 and P < 0.04, compared with middle- and higher-tertiles). We recorded 14 episodes with blood glucose ≤4.0 mmol L-1 in eight patients. Blood glucose ≤4.0 mmol L-1 was mostly recorded during night (n = 8) or in the morning (n = 3). Conclusions. Swedish patients with diabetes in community dwelling are over- rather than undertreated and have low HbA1c levels. Despite very regular eating habits and near total compliance with medication, hypoglycaemias are frequent and possibly linked to malnutrition.

  • 31.
    Machens, A.
    et al.
    Martin-Luther-University Halle-Wittenberg, Halle, Saale, Germany.
    Ukkat, J.
    Martin-Luther-University Halle-Wittenberg, Halle, Saale, Germany.
    Brauckhoff, M.
    Martin-Luther-University Halle-Wittenberg, Halle, Saale, Germany.
    Gimm, Oliver
    Martin-Luther-University Halle-Wittenberg, Halle, Saale, Germany.
    Dralle, H.
    Martin-Luther-University Halle-Wittenberg, Halle, Saale, Germany.
    Advances in the management of hereditary medullary thyroid cancer2005In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 257, no 1, p. 50-59Article in journal (Refereed)
    Abstract [en]

    This work draws on recent advances during the era of codon-oriented prophylactic surgery for hereditary medullary thyroid cancer (MTC). Milestones included identification of RET (REarranged during Transfection) as the susceptibility gene, introduction of prophylactic surgery on evidence of a RET germline mutation, revelation of genotype-phenotype correlations within the MEN 2 spectrum and demonstration of age-related progression of MTC. Novel surgical techniques, notably systemic microdissection and compartment-oriented surgery, have greatly enhanced surgical cure. Uncovering molecular pathways from RET genotype to MEN 2 phenotype should provide treatment options for RET mutation carriers whose MTC currently is too advanced for cure.

  • 32.
    Malmqvist, Karin
    et al.
    Internmedicin Danderyd Stockholm.
    Öhman, P
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine.
    Lind, L
    Nyström, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, EMK-endokrin.
    Kahan, T
    Relationships between left ventricular mass and the renin-angiotensin system, catecholamines, insulin and leptin.2002In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 252, p. 430-439Article in journal (Refereed)
  • 33. Milakovic, M
    et al.
    Berg, G
    Eggertsen, R
    Nyström, E
    Olsson, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Radiation Physics.
    Larsson, A
    Hansson, M
    Determination of intrathyroidal iodine by X-ray fluorescence analysis in 60- to 65-year olds living in an iodine-sufficient area2006In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 260, no 1, p. 69-75Article in journal (Refereed)
    Abstract [en]

    Objectives. X-ray fluorescence (XRF) is a non-invasive method for determining the iodine content of the thyroid gland in vivo. In spite of the obvious clinical value of such a method in situations of iodine deficiency or iodine overload, the method has not so far been widely used. The objective was to investigate the applicability of the XRF method in a larger number of subjects. Design and subjects. The study comprised 37 individuals, aged 60-65 years, who had spent their entire life with iodine supplementation through iodinated table salt. Individuals with (previous) thyroid disease were excluded. The individual thyroid function had previously been evaluated by measurements of thyroid-related hormones, thyroid volume and 131-Iodine (131I) uptake which indicated a sufficient iodine intake of the population in the area. Iodine in the right thyroid lobe in each subject was examined using XRF. Results. The mean thyroid iodine concentration was 0.4 mg mL-1, corresponding to a mean total iodine content of 5.2 mg (range 0.9-20.2). There was a pronounced difference between individuals. No correlation was found between iodine concentration and 131I uptake or thyroid volume. Neither was iodine content and 131I uptake correlated. Conclusions. In a population living under iodine-sufficient conditions, a large variation of iodine stored in the thyroid is compatible with euthyroidism. Determination of the iodine pool by XRF investigation is feasible in a clinical setting and the method offers a unique possibility to study the intrathyroidal iodine pool in subjects with thyroid disease. The low radiation dose enables the use of the method in pregnant women and also in young individuals. © 2006 Blackwell Publishing Ltd.

  • 34.
    Mollazadegan, K
    et al.
    Karolinska Institute, Sweden .
    Sanders, D S.
    Royal Hallamshire Hospital, England .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Ludvigsson, J F.
    Karolinska Institute, Sweden .
    Long-term coeliac disease influences risk of death in patients with type 1 diabetes2013In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 274, no 3, p. 273-280Article in journal (Refereed)
    Abstract [en]

    Aim. The aim of this study was to examine mortality in patients with both type 1 diabetes (T1D) and coeliac disease (CD). less thanbrgreater than less thanbrgreater thanMethods. Between 1969 and 2008, we identified individuals with CD through biopsy reports from all pathology departments (n = 28) in Sweden. T1D was defined as a diagnosis of diabetes recorded in the Swedish National Patient Register between 1964 and 2009 in individuals aged andlt;= 30 years. During follow-up, we identified 960 patients with both T1D and CD. For each individual with T1D and CD, we selected up to five subjects with T1D alone (i.e. no CD), matched for sex, age and calendar period of diagnosis, as the reference group (n = 4608). Using a stratified Cox regression analysis with CD as a time-dependent covariate, we estimated the risk of death in patients with both T1D and CD compared with those with T1D alone. less thanbrgreater than less thanbrgreater thanResults. Stratifying for time since CD diagnosis, CD was not a risk factor for death in patients with T1D during the first 5 years after CD diagnosis [hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.43-1.73], but thereafter the HR for mortality increased as a function of follow-up time (5 to andlt;10 years, HR 1.44, 95% CI 0.74-2.79; 10 to andlt;15 years, HR 1.88, 95% CI 0.81-4.36). Having a CD diagnosis for andgt;= 15 years was associated with a 2.80-fold increased risk of death in individuals with T1D (95% CI 1.28-6.12). less thanbrgreater than less thanbrgreater thanConclusion. A diagnosis of CD for andgt;= 15 years increases the risk of death in patients with T1D.

  • 35.
    Mälarstig, A.
    et al.
    Karolinska University Hospital, Stockholm, Sweden.
    Silveira, A.
    Karolinska University Hospital, Stockholm, Sweden.
    Wågsäter, Dick
    Karolinska University Hospital, Stockholm, Sweden.
    Öhrvik, J.
    Karolinska University Hospital, Stockholm, Sweden.
    Bäcklund, A.
    Karolinska University Hospital, Stockholm, Sweden.
    Samnegård, A.
    Karolinska University Hospital, Stockholm, Sweden.
    Khademi, M.
    Karolinska University Hospital, Stockholm, Sweden.
    Hellenius, M.-L.
    Karolinska University Hospital, Stockholm, Sweden.
    Leander, K.
    Karolinska Institute, Stockholm, Sweden.
    Olsson, T.
    Karolinska University Hospital, Stockholm, Sweden.
    Uhlén, M.
    KTH-Royal Institute of Technology, Stockholm, Sweden.
    de Faire, U.
    Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
    Eriksson, P.
    Karolinska University Hospital, Stockholm, Sweden.
    Hamsten, A.
    Karolinska University Hospital, Stockholm, Sweden.
    Plasma CD93 concentration is a potential novel biomarker for coronary artery disease2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 3, p. 229-236Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    A common nonsynonymous single nucleotide polymorphism (SNP) in the CD93 gene (rs3746731, Pro541Ser) has been associated with risk of coronary artery disease (CAD). CD93 is a transmembrane glycoprotein, which is detectable in soluble form in human plasma. We investigated whether the concentration of soluble CD93 in plasma is related to risk of myocardial infarction (MI) and CAD, using a case-control study of premature MI (n = 764) and a nested case-control analysis of a longitudinal cohort study of 60-year-old subjects (analysis comprising 844 of 4232 subjects enrolled at baseline). In addition, SNPs in the CD93 gene were studied in relation to plasma CD93 concentration and CD93 mRNA expression.

    METHODS AND RESULTS:

    A sensitive and specific enzyme-linked immunosorbent assay was established for determination of the plasma CD93 concentration. Subjects were divided into three groups according to tertiles of the distribution of CD93 concentration. Lower odds ratios for risk of MI and incidence of CAD were observed in the middle CD93 tertile (142-173 μg L(-1) ): odds ratio (95% confidence interval), 0.69 (0.49-0.97) and 0.61 (0.40-0.94), respectively. These associations were independent of traditional CAD risk factors. The minor allele of a SNP in the 3' untranslated region of CD93 (rs2749812) was associated with increased plasma CD93 concentrations (P = 0.03) and increased CD93 mRNA expression levels (P = 0.02).

    CONCLUSION:

    The results of the present study suggest that the concentration of soluble CD93 in plasma is a potential novel biomarker for CAD, including MI.

     

  • 36.
    Nielsen, Niels Erik
    et al.
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Olsson, Anders
    Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Gastroenterology. Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences.
    Swahn, Eva
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Plasma lipoprotein particle concentrations in postmenopausal women with unstable coronary artery disease: Analysis of diagnostic accuracy using receiver operating characteristics2000In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 247, no 1, p. 43-52Article in journal (Refereed)
    Abstract [en]

    Background.The contribution of plasma lipids to cardiovascular risk is usually evaluated by measuring plasma concentrations of total cholesterol, triglycerides and HDL cholesterol, and calculating LDL cholesterol concentration. We investigated plasma concentrations of apolipoproteins and lipoprotein particles in women with unstable coronary artery disease (CAD) to evaluate whether these, better than the routine lipid status, could differentiate women with and without coronary atherosclerosis.

    Methods. Blood samples for lipid analyses were collected from 119 angiographically examined postmenopausal 49–79-year-old women with unstable CAD, and from 101 age-matched controls. Mean plasma concentrations were compared and the discriminatory ability of the different variables were tested using receiver operating characteristics (ROC).

    Results. At coronary angiography 19% had normal vessels and 81% had coronary atherosclerosis. A disturbed triglyceride metabolism was the most pronounced lipid abnormality in women with unstable CAD and coronary atherosclerosis. ROC showed that none of the evaluated variables had a particularly high discriminatory power regarding unstable CAD or coronary atherosclerosis. The ratio cholesterol/HDL cholesterol was best with an ROC area of 0.79. Furthermore, the newer lipid variables, i.e. lipoprotein particles and apolipoproteins, were no better than the traditional variables.

    Conclusion. Lipoprotein changes reflecting a disturbed triglyceride metabolism are most pronounced in women with unstable CAD and coronary atherosclerosis. Lipoprotein particles and apolipoproteins alone were no better than lipids and lipoproteins in separating women with from those without coronary atherosclerosis. Our study does not support the measurement of apolipoproteins and lipoprotein particles on the basis of diagnostic accuracy alone.

  • 37.
    Nielsen, Niels Erik
    et al.
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Siegbahn, Agneta
    Department of Clinical Chemistry, University Hospital, Uppsala, Sweden.
    Swahn, Eva
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Markers of hypercoagulation and von Willebrand factor in postmenopausal women with unstable coronary artery disease. Discriminatory ability regarding unstable coronary artery disease and coronary atherosclerosis using receiver operating characteristics2000In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 248, no 2, p. 151-158Article in journal (Refereed)
    Abstract [en]

    Objectives. Many women with typical anginal chest pain have normal coronary angiograms. The pathogenetic mechanisms behind the chest pain in these patients are unknown but may be due to increased thrombogenicity. We evaluated markers of hypercoagulation and thrombosis in women with clinical signs of unstable coronary artery disease (CAD).

    Methods and results. A total of 158 patients with unstable CAD and 101 controls were examined: 16% of the patients had normal vessels and 84% had coronary atherosclerosis at coronary angiography. Mean plasma concentrations of von Willebrand factor antigen, soluble fibrin (SF), thrombin–antithrombin complex and d-dimer were significantly higher, whereas there was no difference regarding prothrombin fragment 1+2 between patients and controls. Patients with coronary atherosclerosis had higher mean plasma levels for most variables compared with those with normal coronary vessels, although only significantly higher for SF. d-Dimer was significantly higher in patients with normal coronary vessels compared with the control group. Although multivariate analyses showed strong significant correlations of the haemostatic variables to the diagnosis of unstable CAD, receiver operating characteristics (ROC) revealed that none of the variables represented high diagnostic accuracy in separating patients with unstable CAD. Likewise, none of the variables was particularly good at identifying coronary atherosclerosis.

    Conclusion. Our results are in favour of a hypercoagulable state in postmenopausal women with unstable CAD and coronary atherosclerosis, whereas this does not seem to be the case in patients with normal vessels. ROC revealed no variable to be particularly clinically useful in separating patients from controls or patients from those without coronary atherosclerosis.

  • 38.
    Nijm, Johnny
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Kristenson, Margareta
    Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Olsson, Anders G.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Impaired cortisol response to acute stressors in patients with coronary disease: Implications for inflammatory activity2007In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 262, no 3, p. 375-384Article in journal (Refereed)
    Abstract [en]

    Objectives: Inflammation is assumed to play a major role in the progress of atherosclerotic disease. We hypothesized that an altered hypothalamic-pituitary adrenal (HPA) axis activity was linked to a disinhibited inflammatory activity in patients with coronary artery disease (CAD).

    Methods: Thirty CAD patients were assessed 12-14 weeks after a first-time acute coronary syndrome. Serum samples were assayed for C-reactive protein (CRP) and interleukin-6. Free cortisol was measured in a 24-h urine sample and in repeated saliva samples 30 min after awakening and at bedtime. The levels of inflammatory markers and cortisol were also determined before and after standardized physical and psychological stress tests.

    Results: The CAD patients had a higher 24-h cortisol secretion and a flattened diurnal slope, resulting from significantly higher cortisol levels at bedtime, compared to clinically healthy controls. The levels of evening cortisol were strongly related to inflammatory markers in serum. When exposed to acute physical and psychological stressors, the CAD patients showed a significantly blunted cortisol response compared to controls. In addition, a stress-induced increase in CRP was only observed in the patient group.

    Conclusions: Patients with CAD exhibited a cortisol pattern that markedly differed from controls. The data indicate that a dysfunctional HPA axis response involves a failure to contain inflammatory activity in CAD patients, thus providing a possible link between stress and inflammation in disease.

  • 39.
    Nilsson, E.
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Orwelius, Lotti
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Kristenson, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Patient-reported outcomes in the Swedish National Quality Registers2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, no 2, p. 141-153Article, review/survey (Refereed)
    Abstract [en]

    Patient-reported outcomes (PROs) are important in the healthcare system to gain understanding of patients views on the effects of a treatment. There is an abundance of available patient-reported outcome measures (PROMs), both disease specific and generic. In the Swedish healthcare system, the national quality registers are obliged to incorporate PROs for certification at a high level. A review of the latest annual applications for funding (n = 108) shows that at present, 93 national quality registers include some form of PROM or patient-reported experience measure (PREM). Half of the registers include some type of generic measure, more than half include disease/symptom-specific measures, and around 40% include PREMs. Several different measures and combinations of measures are used, the most common of which are the EQ-5D, followed by the SF-36/RAND-36. About one-fifth of the registers report examples of how patient-reported data are used for local quality improvement. These examples include enhancing shared decision-making in clinical encounters (most common), as a basis for care plans, clinical decision aids and treatment guidelines, to improve the precision of indications for surgery (patient and healthcare professional assessments may differ), to monitor complications after the patient has left hospital and to improve patient information. In addition, funding applications reveal that most registers plan to extend their array of PROMs and PREMs in future, and to increase their use of patient-reported data as a basis for quality improvement.

  • 40. Nilsson, Tage
    et al.
    Måre, Klas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology UHL.
    Carlsson, A
    Value of structured clinical and scintigraphic protocols in acute pulmonary embolism2001In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 250, no 3, p. 213-218Article in journal (Refereed)
    Abstract [en]

    Purpose. To study the use of a combination of a clinical and scintigraphic protocol in relation to the final outcome diagnosis in patients with clinical suspicion of acute pulmonary embolism (PE). Material and methods. A total of 170 patients with clinical suspicion of acute PE were all examined with ECG, blood chemistry, chest X-ray, pulmonary scintigraphy and selective pulmonary arteriography. The scintigraphic and clinical probabilities of PE were estimated on visual analogue scales (VASs) by different readers unaware of each others' results. The follow-up time was 6 months. In order to establish the final diagnosis a final outcome committee was created. They analysed in retrospect all the clinical and laboratory data and established whether the patient had had PE or not. Results. The final outcome committee concluded that 53 patients had PE. When the scintigraphic and clinical probability judgements were congruent, a combined probability of 1-25% (i.e low probability) had a negative predictive value of 98%. When the combined probability was 26-75% (i.e. intermediate) half of the cases had PE. With a combined probability of 76-100% (i.e. high) the positive predictive value was 100%. Conclusion. By applying a model of combined clinical and scintigraphic probabilities for PE, the diagnosis is ruled in when the combined probability is high, and ruled out when the combined probability is low. However, nearly half of the patients will still have an uncertain diagnosis for which further diagnostic procedures may be allocated.

  • 41.
    Nyström, Fredrik
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Malmqvist, K
    KI, Stockholm.
    Lind, L
    Universitetssjukhuset i Uppsala.
    Kahan, T
    KI, Stockholm.
    Nurse-recorded clinic and ambulatory blood pressures correlate equally well with left ventricular mass and carotid intima-media thickness2005In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 257, no 6, p. 514-522Article in journal (Refereed)
    Abstract [en]

    Objective. To assess relationships between noninvasive ambulatory blood pressure (BP), clinic BP (mean value of three readings in the seated position measured by nurses), structural cardiac indices, intima-media thickness of the common carotid artery and several hormones. Design. Cross-sectional study of 75 subjects with hypertension and left ventricular hypertrophy (HTH) according to echocardiography, 35 subjects with hypertension and normal left ventricular dimensions (HT) and 23 normotensive subjects (NT). Results. We found an excellent correlation between mean 24-h ambulatory BP and clinic BP, the r-value for systolic BP being 0.82 and for diastolic levels 0.78 (both P < 0.0001). Clinic and ambulatory BP correlated equally well with left ventricular (LV) mass index (r-values between 0.55 and 0.64, all P < 0.0001) and to intima-media thickness of the carotid artery (r = 0.18-0.34, P < 0.01). The systolic white-coat effect (clinic BP - day-time BP) was higher in the HTH and HT compared with NT and was weakly correlated to LV mass index (r = 0.18, P = 0.04). Nondippers (mean arterial night/day BP ratio of >0.9) had higher brain (6.1 ± 7.5 pmol L-1 vs. 3.7 ± 3.2 pmol L-1, P = 0.01) and atrial (14 ± 3.4 pmol L-1 vs. 9.3 ± 5.4 pmol L-1, P = 0.04) natriuretic peptide levels, and also exhibited a lower ejection fraction (49 ± 8% vs. 57 ± 9%, P = 0.006), than dippers. Conclusion. Clinic BP recordings performed by nurses as three measurements 1 min apart provide excellent relationship to target organ damage. Nondippers exhibited signs of a more advanced hypertensive organ damage than dippers which corresponds well with the poor prognosis linked to this condition. © 2005 Blackwell Publishing Ltd.

  • 42.
    Olsson, Anders
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Angelin, B.
    Karolinska Institute, Sweden; Karolinska University Hospital Huddinge, Sweden.
    Assmann, G.
    University of Munster, Germany.
    Binder, C. J.
    Medical University of Vienna, Austria; Austrian Academic Science, Austria.
    Bjoerkhem, I.
    Karolinska University Hospital Huddinge, Sweden; Karolinska Institute, Sweden.
    Cedazo-Minguez, A.
    Karolinska Institute Huddinge, Sweden.
    Cohen, J.
    UTSouthwesternMedical Centre, TX USA.
    von Eckardstein, A.
    University of Zurich, Switzerland.
    Farinaro, E.
    University of Naples Federico II, Italy.
    Mueller-Wieland, D.
    University of Cologne, Germany.
    Parhofer, K. G.
    Ludwig Maximilians University of Munchen, Germany.
    Parini, P.
    Karolinska University Hospital Huddinge, Sweden; Karolinska Institute, Sweden.
    Rosenson, R. S.
    Mt Sinai Hospital, NY 10029 USA.
    Starup-Linde, J.
    University of Aarhus, Denmark.
    Tikkanen, M. J.
    University of Helsinki, Finland.
    Yvan-Charvet, L.
    University of Nice Sophia Antipolis, France.
    Can LDL cholesterol be too low? Possible risks of extremely low levels2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, no 6, p. 534-553Article, review/survey (Refereed)
    Abstract [en]

    Following the continuous accumulation of evidence supporting the beneficial role of reducing low-density lipoprotein cholesterol (LDL-C) levels in the treatment and prevention of atherosclerotic cardiovascular disease and its complications, therapeutic possibilities now exist to lower LDL-C to very low levels, similar to or even lower than those seen in newborns and nonhuman species. In addition to the important task of evaluating potential side effects of such treatments, the question arises whether extremely low LDL-C levels per se may provoke adverse effects in humans. In this review, we summarize information from studies of human cellular and organ physiology, phenotypic characterization of rare genetic diseases of lipid metabolism, and experience from clinical trials. Specifically, we emphasize the importance of the robustness of the regulatory systems that maintain balanced fluxes and levels of cholesterol at both cellular and organismal levels. Even at extremely low LDL-C levels, critical capacities of steroid hormone and bile acid production are preserved, and the presence of a cholesterol blood-brain barrier protects cells in the central nervous system. Apparent relationships sometimes reported between less pronounced low LDL-C levels and disease states such as cancer, depression, infectious disease and others can generally be explained as secondary phenomena. Drug-related side effects including an increased propensity for development of type 2 diabetes occur during statin treatment, whilst further evaluation of more potent LDL-lowering treatments such as PCSK9 inhibitors is needed. Experience from the recently reported and ongoing large event-driven trials are of great interest, and further evaluation including careful analysis of cognitive functions will be important. This is an article from the symposium: Risks and benefits of Extremely Low LDL Cholesterol.

  • 43. Orre-Pettersson, A-C
    et al.
    Lindström, T
    Bergmark, V
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    The snack is critical for the blood glucose profile during treatment with regular insulin preprandially.1999In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 245, p. 41-45Article in journal (Refereed)
  • 44.
    Pettersson, Camilla
    et al.
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Ståhlman, Marcus
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Larsson, Thomas
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Fagerberg, Björn
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Wiklund, Olov
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Borén, Jan
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Fogelstrand, Linda
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    LDL-associated apolipoprotein J and lysozyme are associated with atherogenic properties of LDL found in type 2 diabetes and the metabolic syndrome2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 269, no 3, p. 306-321Article in journal (Refereed)
    Abstract [en]

    Objectives  Exchangeable low-density lipoprotein (LDL)-associated proteins can affect the atherogenic properties of LDL. Our aim was to analyze the protein composition of LDL from individuals with or without type 2 diabetes and the metabolic syndrome (T2DM) in relation to other LDL-particle characteristics, to assess whether certain proteins associate more with certain subclasses of LDL typical for T2DM, such as small, apoCIII-rich LDL. Design  LDL from two cohorts of 61-year-old men (n = 19 and 64) with or without T2DM was isolated using size-exclusion chromatography or deuterium oxide-based ultracentrifugation. LDL-associated proteins were identified using mass spectrometry and quantified using two-dimensional gel electrophoresis or enzyme-linked immunosorbent assay. Differently expressed LDL-associated proteins apolipoprotein (apo)J and lysozyme were also measured in serum from a third cohort of women (n = 71) with or without T2DM. Lysozyme binding to advanced glycation end product (AGE)-LDL was examined in vitro. Results  ApoJ and lysozyme were increased in LDL particles with increased apoCIII content and decreased cholesterol content. When isolated with SEC, LDL from individuals with T2DM contained more apoJ and lysozyme and less apoA1 than LDL from control individuals. LDL content of apoJ correlated with a smaller LDL-particle size. Serum levels of lysozyme, but not apoJ, were increased in individuals with T2DM. In vitro, lysozyme associated more with AGE-LDL than with unmodified LDL. Conclusions  Our results indicate that apoJ and lysozyme are increased in LDL with characteristics of small dense LDL in T2DM. Small dense LDL is easily glycated, and the increased affinity of lysozyme for AGE-LDL provides a possible partial explanation for an increase of lysozyme from those with type 2 diabetes.

  • 45.
    Ragnarsson, G
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, GE: gastromed.
    Bodemar, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, GE: gastromed.
    Treatment of irritable bowel syndrome with loperamide oxide. An open study to determine optimal dosage [1]2000In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 248, no 2, p. 165-166Article in journal (Refereed)
  • 46.
    Rydén, Mireille
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Garvin, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Kristenson, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Jonasson, Lena
    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.
    Provitamin A carotenoids are independently associated with matrix metalloproteinase-9 in plasma samples from a general population2012In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 272, no 4, p. 371-384Article in journal (Refereed)
    Abstract [en]

    Background and aim:  Carotenoids in plasma are inversely associated with cardiovascular risk. Low levels can be explained by low dietary intake but also by a number of other factors including inflammatory activity. Given that matrix metalloproteinase (MMP)-9 has an important role in inflammation and cardiovascular disease, we hypothesized that circulating MMP-9 levels would be inversely related to total or single carotenoids in a general population cohort. Methods:  A well-characterized population-based cohort of 285 Swedish men and women (45-69 years) was used for the present study. The intake of carotenoid-rich fruits and vegetables was estimated from a food frequency questionnaire. Levels of MMP-9, C-reactive protein (CRP), interleukin (IL)-6 and six major carotenoids [β-cryptoxanthine, α-carotene, β-carotene, lutein (+ zeaxanthin) and lycopene] were determined in plasma. Results:  Lower plasma levels of total and single carotenoids were associated with lower dietary intake of carotenoids, older age, male sex, lower physical activity, higher alcohol consumption, higher body mass index (BMI), higher systolic and diastolic blood pressures, lower levels of total cholesterol and HDL cholesterol and higher levels of CRP, IL-6 and MMP-9. After multivariate adjustments, plasma levels of total carotenoids and provitamin A carotenoids (β-cryptoxanthine, α-carotene and β-carotene) remained independently associated with sex, dietary intake of carotenoids, BMI, HDL cholesterol and MMP-9, while associations with CRP and IL-6 were not maintained. Neither dietary intake of carotenoid-rich fruits and vegetables, nor vitamin supplement use was associated with MMP-9, CRP or IL-6 levels. Conclusion:  Plasma carotenoids were associated with a variety of factors including age, sex, dietary intake and metabolic variables. A new finding was the independent relationship in plasma between low provitamin A carotenoids and high MMP-9, suggesting a link between these carotenoids, matrix turnover and arterial remodelling. © 2012 The Association for the Publication of the Journal of Internal Medicine.

  • 47.
    Saevik, A. B.
    et al.
    Univ Bergen, Norway.
    Akerman, A. -K.
    Orebro Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Gronning, K.
    Akershus Univ Hosp, Norway.
    Nermoen, I.
    Akershus Univ Hosp, Norway; Univ Oslo, Norway.
    Valland, S. F.
    Innlandet Hosp Trust, Norway.
    Finnes, T. E.
    Innlandet Hosp Trust, Norway.
    Isaksson, M.
    Uppsala Univ, Sweden.
    Dahlqvist, P.
    Umea Univ, Sweden.
    Bergthorsdottir, R.
    Sahlgrens Univ Hosp, Sweden; Sahlgrens Acad, Sweden.
    Ekwall, O.
    Inst Clin Sci, Sweden; Univ Gothenburg, Sweden.
    Skov, J.
    Karolinska Inst, Sweden; Karlstad City Hosp, Sweden.
    Nedrebo, B. G.
    Haugesund Hosp, Norway.
    Hulting, A. -L.
    Karolinska Inst, Sweden.
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Svartberg, J.
    Univ Hosp North Norway, Norway; Arctic Univ Norway, Norway.
    Hoybye, C.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Bleskestad, I. H.
    Stavanger Univ Hosp, Norway.
    Jorgensen, A. P.
    Oslo Univ Hosp, Norway.
    Kampe, O.
    Karolinska Univ Hosp, Sweden; Solna Karolinska Inst, Sweden; Univ Bergen, Norway.
    Oksnes, M.
    Karolinska Univ Hosp, Sweden; Solna Karolinska Inst, Sweden; Haukeland Hosp, Norway.
    Bensing, S.
    Karolinska Inst, Sweden.
    Husebye, E. S.
    Univ Bergen, Norway; Solna Karolinska Inst, Sweden; Univ Bergen, Norway; Haukeland Hosp, Norway.
    Clues for early detection of autoimmune Addisons disease - myths and realities2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 2, p. 190-199Article in journal (Refereed)
    Abstract [en]

    BackgroundEarly detection of autoimmune Addisons disease (AAD) is important as delay in diagnosis may result in a life-threatening adrenal crisis and death. The classical clinical picture of untreated AAD is well-described, but methodical investigations are scarce. ObjectivePerform a retrospective audit of patient records with the aim of identifying biochemical markers for early diagnosis of AAD. Material and MethodsA multicentre retrospective study including 272 patients diagnosed with AAD at hospitals in Norway and Sweden during 1978-2016. Scrutiny of medical records provided patient data and laboratory values. ResultsLow sodium occurred in 207 of 247 (84%), but only one-third had elevated potassium. Other common nonendocrine tests were largely normal. TSH was elevated in 79 of 153 patients, and hypoglycaemia was found in 10%. Thirty-three per cent were diagnosed subsequent to adrenal crisis, in whom electrolyte disturbances were significantly more pronounced (P amp;lt; 0.001). Serum cortisol was consistently decreased (median 62 nmol L-1 [1-668]) and significantly lower in individuals with adrenal crisis (38 nmol L-1 [2-442]) than in those without (81 nmol L-1 [1-668], P amp;lt; 0.001). ConclusionThe most consistent biochemical finding of untreated AAD was low sodium independent of the degree of glucocorticoid deficiency. Half of the patients had elevated TSH levels. Only a minority presented with marked hyperkalaemia or other nonhormonal abnormalities. Thus, unexplained low sodium and/or elevated TSH should prompt consideration of an undiagnosed AAD, and on clinical suspicion bring about assay of cortisol and ACTH. Presence of 21-hydroxylase autoantibodies confirms autoimmune aetiology. Anticipating additional abnormalities in routine blood tests may delay diagnosis.

  • 48.
    Schon, T
    et al.
    Kalmar County Hospital, Sweden .
    Lerm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Stendahl, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Shortening the short-course therapy-insights into host immunity may contribute to new treatment strategies for tuberculosis2013In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 273, no 4, p. 368-382Article, review/survey (Refereed)
    Abstract [en]

    Schon T, Lerm M, Stendahl O (Kalmar County Hospital, Kalmar; and Linkoping University, Linkoping; Sweden). Shortening the short-course therapy: insights into host immunity may contribute to newtreatment strategies for tuberculosis (Review). J Intern Med 2013; 273: 368-382. Achieving global control of tuberculosis (TB) is a great challenge considering the current increase in multidrug resistance and mortality rate. Considerable efforts are therefore being made to develop new effective vaccines, more effective and rapid diagnostic tools as well as new drugs. Shortening the duration of TB treatment with revised regimens and modes of delivery of existing drugs, as well as development of new antimicrobial agents and optimization of the host response with adjuvant immunotherapy could have a profound impact on TB cure rates. Recent data show that chronic worm infection and deficiencies in micronutrients such as vitamin D and arginine are potential areas of intervention to optimize host immunity. Nutritional supplementation to enhance nitric oxide production and vitamin D-mediated effector functions as well as the treatment of worm infection to reduce immunosuppressive effects of regulatory T (Treg) lymphocytes may be more suitable and accessible strategies for highly endemic areas than adjuvant cytokine therapy. In this review, we focus mainly on immune control of human TB, and discuss how current treatment strategies, including immunotherapy and nutritional supplementation, could be optimized to enhance the host response leading to more effective treatment.

  • 49. Schölin, A
    et al.
    Björklund, L
    Borg, H
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Björk, E
    Blohmé, G
    Bolinder, J
    Eriksson, JW
    Gudbjörnsdottir, S
    Nyström, L
    Östman, J
    Karlsson, AF
    Sundkvist, G
    Islet antibodies and remaining β-cell function 8 years after diagnosis of diabetes in young adults: A prospective follow-up of the nationwide Diabetes Incidence Study in Sweden2004In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 255, no 3, p. 384-391Article in journal (Refereed)
    Abstract [en]

    Objectives. To establish the prevalence of remaining β-cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later. Design. Population-based cohort study. Setting. Nationwide from all Departments of Medicine and Endocrinology in Sweden. Subjects. A total of 312 young (15-34 years old) adults diagnosed with diabetes during 1987-88. Main outcome measure. Plasma connecting peptide (C-peptide) 8 years after diagnosis. Preserved β-cell function was defined as measurable C-peptide levels. Three islet antibodies - cytoplasmic islet cell antibodies (ICA), glutamic acid decarboxylase antibodies and tyrosine phosphatase antibodies -were measured. Results. Amongst 269 islet antibody positives (ab+) at diagnosis, preserved β-cell function was found in 16% (42/269) 8 years later and these patients had a higher body mass index (median 22.7 and 20.5 kg m-2,respectively, P = 0.0003), an increased frequency of one islet antibody (50 and 24%, respectively, P = 0.001), and a lower prevalence of ICA (55 and 6%, respectively, P = 0.007) at diagnosis compared with ab+ without remaining β-cell function. Amongst the 241 patients without detectable β-cell function at follow-up, 14 lacked islet antibodies, both at diagnosis and at follow-up. Conclusions. Sixteen per cent of patients with autoimmune type 1 diabetes had remaining β-cell function 8 years after diagnosis whereas 5.8% with β-cell failure lacked islet autoimmunity, both at diagnosis and at follow-up.

  • 50.
    Sjöberg, Folke
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Surgery.
    Singer, M
    Bloomsbury Institute of Intensive Care Medicine, University College of London, London, UK.
    The medical use of oxygen: a time for critical reappraisal2013In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 274, no 6, p. 505-528Article, review/survey (Refereed)
    Abstract [en]

    Oxygen treatment has been a cornerstone of acute medical care for numerous pathological states. Initially, this was supported by the assumed need to avoid hypoxaemia and tissue hypoxia. Most acute treatment algorithms, therefore, recommended the liberal use of a high fraction of inspired oxygen, often without first confirming the presence of a hypoxic insult. However, recent physiological research has underlined the vasoconstrictor effects of hyperoxia on normal vasculature and, consequently, the risk of significant blood flow reduction to the at-risk tissue. Positive effects may be claimed simply by relief of an assumed local tissue hypoxia, such as in acute cardiovascular disease, brain ischaemia due to, for example, stroke or shock or carbon monoxide intoxication. However, in most situations, a generalized hypoxia is not the problem and a risk of negative hyperoxaemia-induced local vasoconstriction effects may instead be the reality. In preclinical studies, many important positive anti-inflammatory effects of both normobaric and hyperbaric oxygen have been repeatedly shown, often as surrogate end-points such as increases in gluthatione levels, reduced lipid peroxidation and neutrophil activation thus modifying ischaemia-reperfusion injury and also causing anti-apoptotic effects. However, in parallel, toxic effects of oxygen are also well known, including induced mucosal inflammation, pneumonitis and retrolental fibroplasia. Examining the available strong clinical evidence, such as usually claimed for randomized controlled trials, few positive studies stand up to scrutiny and a number of trials have shown no effect or even been terminated early due to worse outcomes in the oxygen treatment arm. Recently, this has led to less aggressive approaches, even to not providing any supplemental oxygen, in several acute care settings, such as resuscitation of asphyxiated newborns, during acute myocardial infarction or after stroke or cardiac arrest. The safety of more advanced attempts to deliver increased oxygen levels to hypoxic or ischaemic tissues, such as with hyperbaric oxygen therapy, is therefore also being questioned. Here, we provide an overview of the present knowledge of the physiological effects of oxygen in relation to its therapeutic potential for different medical conditions, as well as considering the potential for harm. We conclude that the medical use of oxygen needs to be further examined in search of solid evidence of benefit in many of the current clinical settings in which it is routinely used.

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