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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.

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  • 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.

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  • 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.

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  • 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.

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  • 9.
    Brighenti, S.
    et al.
    Karolinska Inst, Sweden.
    Lerm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Toward the understanding of human tuberculosis2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 284, no 2, p. 113-115Article in journal (Other academic)
    Abstract [en]

    n/a

  • 10.
    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.

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  • 11.
    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.

  • 12.
    Erlandsson, Helen
    et al.
    Karolinska Inst, Sweden.
    Qureshi, Abdul Rashid
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Ripsweden, Jonaz
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Löfman, Ida Haugen
    Karolinska Inst, Sweden.
    Söderberg, Magnus
    AstraZeneca, Sweden.
    Wennberg, Lars
    Karolinska Inst, Sweden.
    Lundgren, Torbjörn
    Karolinska Inst, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Inst, Sweden.
    Brismar, Torkel B.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Stenvinkel, Peter
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Scoring of medial arterial calcification predicts cardiovascular events and mortality after kidney transplantation2022In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 291, no 6, p. 813-823Article in journal (Refereed)
    Abstract [en]

    Background Progression of vascular calcification causes cardiovascular disease, which is the most common cause of death in chronic kidney failure and after kidney transplantation (KT). The prognostic impact of the extent of medial vascular calcification at KT is unknown. Methods In this prospective cohort study, we investigated the impact of medial calcification compared to a mix of intimal and medial calcification represented by coronary artery calcification (CAC score) and aortic valve calcification in 342 patients starting on kidney failure replacement therapy. The primary outcomes were cardiovascular events (CVE) and death. The median follow-up time was 6.4 years (interquartile range 3.7-9.6 years). Exposure was CAC score and arteria epigastrica medial calcification scored as none, mild, moderate, or severe by a pathologist at time of KT (n = 200). We divided the patients according to kidney failure replacement therapy during follow-up, that is, living donor KT, deceased donor KT, or dialysis. Results Moderate to severe medial calcification in the arteria epigastrica was associated with higher mortality (p = 0.001), and the hazard ratio for CVE was 3.1 (95% confidence interval [CI] 1.12-9.02, p &lt; 0.05) compared to no or mild medial calcification. The hazard ratio for 10-year mortality in the dialysis group was 33.6 (95% CI, 10.0-113.0, p &lt; 0.001) compared to living donor recipients, independent of Framingham risk score and prevalent CAC. Conclusion Scoring of medial calcification in the arteria epigastrica identified living donor recipients as having 3.1 times higher risk of CVE, independent of traditional risk factors. The medial calcification score could be a reliable method to identify patients with high and low risk of CVE and mortality following KT.

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  • 13.
    Fedorowski, Artur
    et al.
    Lund Univ, Sweden; Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Olsen, Monika Fagevik
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Nikesjö, Frida
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Janson, Christer
    Uppsala Univ, Sweden.
    Bruchfeld, Judith
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Lerm, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Hedman, Kristofer
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Cardiorespiratory dysautonomia in post-COVID-19 condition: Manifestations, mechanisms and management2023In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 294, no 5, p. 548-562Article, review/survey (Refereed)
    Abstract [en]

    A significant proportion of COVID-19 patients experience debilitating symptoms for months after the acute infection. According to recent estimates, approximately 1 out of 10 COVID-19 convalescents reports persistent health issues more than 3 months after initial recovery. This post-COVID-19 condition may include a large variety of symptoms from almost all domains and organs, and for some patients it may mean prolonged sick-leave, homestay and strongly limited activities of daily life. In this narrative review, we focus on the symptoms and signs of post-COVID-19 condition in adults - particularly those associated with cardiovascular and respiratory systems, such as postural orthostatic tachycardia syndrome or airway disorders - and explore the evidence for chronic autonomic dysfunction as a potential underlying mechanism. The most plausible hypotheses regarding cellular and molecular mechanisms behind the wide spectrum of observed symptoms - such as lingering viruses, persistent inflammation, impairment in oxygen sensing systems and circulating antibodies directed to blood pressure regulatory components - are discussed. In addition, an overview of currently available pharmacological and non-pharmacological treatment options is presented.

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  • 14.
    Franks, P. W.
    et al.
    Lund Univ, Sweden; Harvard Sch Publ Hlth, MA USA.
    Melén, E.
    Karolinska Inst, Sweden.
    Friedman, M.
    Karolinska Inst, Sweden.
    Sundström, J.
    Akad Sjukhuset, Sweden; George Inst Global Hlth, Australia; Uppsala Univ, Sweden.
    Kockum, I
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Klareskog, L.
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Almqvist, C.
    Karolinska Inst, Sweden.
    Bergen, S. E.
    Karolinska Inst, Sweden.
    Czene, K.
    Karolinska Inst, Sweden.
    Hägg, S.
    Karolinska Inst, Sweden.
    Hall, P.
    Karolinska Inst, Sweden; Soder Sjukhuset, Sweden.
    Johnell, K.
    Karolinska Inst, Sweden.
    Malarstig, A.
    Karolinska Inst, Sweden; Pfizer, Sweden.
    Catrina, A.
    Karolinska Inst, Sweden.
    Hagström, H.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Benson, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Karolinska Inst, Sweden.
    Smith, J. Gustav
    Lund Univ, Sweden; Lund Univ, Sweden; Skane Univ Hosp, Sweden; Gothenburg Univ, Sweden; Sahlgrens Univ Hosp, Sweden.
    Gomez, M. F.
    Lund Univ, Sweden.
    Orho-Melander, M.
    Lund Univ, Sweden.
    Jacobsson, B.
    Norwegian Inst Publ Hlth Genet & Bioinformat, Norway; Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Halfvarson, J.
    Orebro Univ, Sweden.
    Repsilber, D.
    Orebro Univ, Sweden.
    Oresic, M.
    Orebro Univ, Sweden; Univ Turku, Finland; Abo Akad Univ, Finland.
    Jern, C.
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Melin, B.
    Umea Univ, Sweden.
    Ohlsson, C.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Fall, T.
    Uppsala Univ, Sweden.
    Rönnblom, L.
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Wadelius, M.
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Nordmark, G.
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Johansson, Å.
    Uppsala Univ, Sweden.
    Rosenquist, R.
    Karolinska Inst, Sweden.
    Sullivan, P. F.
    Karolinska Inst, Sweden; Univ N Carolina, NC 27515 USA; Univ N Carolina, NC 27515 USA.
    Technological readiness and implementation of genomic-driven precision medicine for complex diseases2021In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 290, no 3, p. 602-620Article, review/survey (Refereed)
    Abstract [en]

    The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.

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  • 15.
    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.

  • 16.
    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.

  • 17.
    Hagström, Hannes
    et al.
    Karolinska Univ Hosp, Sweden; Karolinska Institutet, Solna, Sweden; Karolinska Institutet, Huddinge, Sweden.
    Kechagias, Stergios
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Ekstedt, Mattias
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Risk for hepatic and extra-hepatic outcomes in nonalcoholic fatty liver disease2022In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 292, no 2, p. 177-189Article, review/survey (Refereed)
    Abstract [en]

    Nonalcoholic fatty liver disease (NAFLD) is defined by presence of steatosis in more than 5% of liver cells. The gold standard for diagnosis is liver biopsy, but this is seldom achieved due to costs and risk for side effects, and that is why the diagnosis is mostly made based on a combination of radiology and exclusion of other liver diseases. Disease severity staging can be noninvasively achieved with radiological exams such as elastography or blood-based markers that usually have lower sensitivity and specificity. NAFLD is today the most common chronic liver disease globally with a prevalence estimated to be 25%. Fortunately, for many persons NAFLD is an incidental finding with a good prognosis. Whilst a major focus has been on liver-related outcomes in NAFLD, there has recently been an increased interest in extrahepatic consequences of NAFLD. The most commonly studied outcomes include cardiovascular disease and cancer. The risk of adverse outcomes generally differs according to the baseline fibrosis stage. There is a five-time higher risk of liver-related events in NAFLD patients with fibrosis stage 3 as compared to those with no or little fibrosis. Meanwhile, the presence of nonalcoholic steatohepatitis (NASH) does not seem to influence prognosis in addition to fibrosis stage. Patients with NAFLD clearly have a higher risk for cardiovascular outcomes compared to the general population, with a recent meta-analysis indicating a 37% increased hazard for cardiovascular events as opposed to individuals without NAFLD. The risk of liver cancer is increased, which is mostly driven by presence of cirrhosis, but the increased risk is present also in patients without cirrhosis, and to a greater extent than for other chronic liver disease. Around one-third of patients with NAFLD and liver cancer do not have cirrhosis. Additionally, the risk of extrahepatic malignancies is thought to be moderately increased, with most evidence for a link between NAFLD and colorectal cancer where the risk is approximately 50% higher compared to patients without NAFLD. A particularly salient point is if NAFLD can be considered an independent risk factor for outcomes. Many studies have not been able to adjust for key confounders, or suffer from different forms of bias. The clinical problem is nevertheless to identify persons with an increased risk for adverse hepatic and extrahepatic outcomes. We here discuss the evidence linking NAFLD to severe hepatic and extrahepatic outcomes.

  • 18.
    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.

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  • 19.
    Hedin, C. R. H.
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Sonkoly, E.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Eberhardson, Michael
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken. Karolinska Inst, Sweden.
    Stahle, M.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Inflammatory bowel disease and psoriasis: modernizing the multidisciplinary approach2021In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 290, no 2, p. 257-278Article, review/survey (Refereed)
    Abstract [en]

    Psoriasis and inflammatory bowel disease (IBD) are immune-mediated diseases occurring in barrier organs whose main task is to protect the organism from attack. These disorders are highly prevalent especially in northern Europe where psoriasis has a prevalence of around 3-4% and IBD around 0.3%. The prevalence of IBD in North America has been estimated at around 0.4%. The total incidence rates in northern Europe have been estimated at around 6 for Crohns disease and 11 for ulcerative colitis per 100 000 person-years, compared with an incidence rate of around 280 per 100 000 person-years for psoriasis. Both diseases are less common in countries with a lower index of development. The rise in IBD appears to occur as populations adopt a westernized lifestyle, whereas psoriasis seems more stable and prevalence differences may derive more from variation in genetic susceptibility. The gut microbiota is clearly an important driver of IBD pathogenesis; in psoriasis, changes in gut and skin microbiota have been reported, but it is less clear whether and how these changes contribute to the pathogenesis. Large studies show that most identified genes are involved in the immune system. However, psoriasis and IBD are highly heterogeneous diseases and there is a need for more precise and deeper phenotyping to identify specific subgroups and their genetic, epigenetic and molecular signatures. Epigenetic modifications of DNA such as histone modifications, noncoding RNA effects on transcription and translation and DNA methylation are increasingly recognized as the mechanism underpinning much of the gene-environment interaction in the pathogenesis of both IBD and psoriasis. Our understanding of underlying pathogenetic mechanisms has deepened fundamentally over the past decades developing hand in hand with novel therapies targeting pathways and proinflammatory cytokines incriminated in disease. There is not only substantial overlap between psoriasis and IBD, but also there are differences with implication for therapy. In psoriasis, drugs targeting interleukin-23 and interleukin-17 have shown superior efficacy compared with anti-TNFs, whilst in IBD, drugs targeting interleukin-17 may be less beneficial. The therapeutic toolbox for psoriasis is impressive and is enlarging also for IBD. Still, there are unmet needs reflecting the heterogeneity of both diseases and there is a need for closer molecular diagnostics to allow for the development of precise therapeutics.

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  • 20.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Stress-related neuropeptide systems as targets for treatment of alcohol addiction: A clinical perspective2023In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 293, no 5, p. 559-573Article, review/survey (Refereed)
    Abstract [en]

    Alcohol use is a major cause of disability and death globally. These negative consequences disproportionately affect people who develop alcohol addiction, a chronic relapsing condition characterized by increased motivation to use alcohol, choice of alcohol over healthy, natural rewards, and continued use despite negative consequences. Available pharmacotherapies for alcohol addiction are few, have effect sizes in need of improvement, and remain infrequently prescribed. Research aimed at developing novel therapeutics has in large part focused on attenuating pleasurable or "rewarding" properties of alcohol, but this targets processes that primarily play a role as initiation factors. As clinical alcohol addiction develops, long-term changes in brain function result in a shift of affective homeostasis, and rewarding alcohol effects become progressively reduced. Instead, increased stress sensitivity and negative affective states emerge in the absence of alcohol and create powerful incentives for relapse and continued use through negative reinforcement, or "relief." Based on research in animal models, several neuropeptide systems have been proposed to play an important role in this shift, suggesting that these systems could be targeted by novel medications. Two mechanisms in this category, antagonism at corticotropin-releasing factor type 1, and neurokinin 1/substance P receptors, have been subject to initial evaluation in humans. A third, kappa-opioid receptor antagonism, has been evaluated in nicotine addiction and could soon be tested for alcohol. This paper discusses findings with these mechanisms to date, and their prospects as future targets for novel medications.

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  • 21.
    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.

  • 22.
    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)
  • 23.
    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.

  • 24.
    Holm Nielsen, S.
    et al.
    Nordic Biosci, Denmark; Tech Univ Denmark, Denmark.
    Jonasson, Lena
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Cardiology in Linköping.
    Kalogeropoulos, K.
    Tech Univ Denmark, Denmark.
    Karsdal, M. A.
    Nordic Biosci, Denmark.
    Reese-Petersen, A. L.
    Nordic Biosci, Denmark.
    Keller, U. Auf Dem
    Tech Univ Denmark, Denmark.
    Genovese, F.
    Nordic Biosci, Denmark.
    Nilsson, J.
    Lund Univ, Sweden.
    Goncalves, I
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Exploring the role of extracellular matrix proteins to develop biomarkers of plaque vulnerability and outcome2020In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 287, no 5, p. 493-513Article, review/survey (Refereed)
    Abstract [en]

    Cardiovascular disease (CVD) is the most common cause of death in industrialized countries. One underlying cause is atherosclerosis, which is a systemic disease characterized by plaques of retained lipids, inflammatory cells, apoptotic cells, calcium and extracellular matrix (ECM) proteins in the arterial wall. The biologic composition of an atherosclerotic plaque determines whether the plaque is more or less vulnerable, that is prone to rupture or erosion. Here, the ECM and tissue repair play an important role in plaque stability, vulnerability and progression. This review will focus on ECM remodelling in atherosclerotic plaques, with focus on how ECM biomarkers might predict plaque vulnerability and outcome.

  • 25.
    Hultcrantz, M.
    et al.
    Karolinska Inst, Sweden; Mem Sloan Kettering Canc Ctr, NY 10021 USA.
    Landtblom, A. Ravn
    Stockholm South Hosp, Sweden; Karolinska Inst, Sweden.
    Andreasson, B.
    NU Hosp Grp, Sweden.
    Samuelsson, Jan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Dickman, P. W.
    Karolinska Inst, Sweden.
    Kristinsson, S. Y.
    Univ Iceland, Iceland; Landspitali Natl Univ Hosp, Iceland.
    Bjorkholm, M.
    Karolinska Inst, Sweden.
    Andersson, T. M-L
    Karolinska Inst, Sweden.
    Incidence of myeloproliferative neoplasms - trends by subgroup and age in a population-based study in Sweden2020In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 287, no 4, p. 448-454Article in journal (Refereed)
    Abstract [en]

    Background The reported incidence of Philadelphia-negative myeloproliferative neoplasms (MPNs) differs substantially between previous reports, likely due to true regional differences in incidence and/or variations in the quality and coverage of the cancer registers. Objective We therefore assessed MPN incidence in Sweden during recent years using prospectively collected information captured in Swedish health registers. Methods Patients with MPNs were identified through the Swedish Cancer Register and Swedish Blood Cancer Register between 2000 and 2014. Information on the Swedish population was obtained from the Human Mortality Database. Crude and age-standardized incidence rates of MPNs with 95% confidence intervals (CIs) were calculated. Results A total of 6281 MPN cases were reported to the Swedish Cancer Register and Swedish Blood Cancer Register during 2000-2014. The age-standardized, to the Swedish population in 2000, incidence for all MPNs was 4.45 (95% confidence interval [CI] 4.34-4.56)/100 000 person-years. The age-standardized incidence for polycythemia vera was 1.48 (1.42-1.54), for essential thrombocythemia 1.60 (1.53-1.66) and for primary myelofibrosis 0.52 (0.48-0.56)/100 000 person-years, respectively. The incidence rate of MPNs was substantially higher in the older compared to the younger age groups. The incidence increased during the study period, likely to do better reporting and increasing age of the general population. Conclusion The reported MPN incidences in our study, which were in the higher interval of previously published studies, are likely more accurate compared to previous reports due to the population-based setting and high level of coverage in the Swedish Cancer and Blood Cancer Registers.

  • 26.
    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)
  • 27.
    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.

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  • 28.
    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.

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  • 29.
    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.

  • 30.
    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.

  • 31.
    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.

  • 32.
    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)
  • 33.
    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)
  • 34.
    Lange, C.
    et al.
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany; Univ Lubeck, Germany; Karolinska Inst, Sweden.
    Alghamdi, W. A.
    Univ Florida, FL USA.
    Al-Shaer, M. H.
    Univ Florida, FL USA.
    Brighenti, S.
    Karolinska Univ Hosp Huddinge, Sweden.
    Diacon, A. H.
    Task Appl Sci, South Africa; Stellenbosch Univ, South Africa.
    DiNardo, A. R.
    Baylor Coll Med, TX 77030 USA.
    Grobbel, H. P.
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany; Univ Lubeck, Germany.
    Groschel, M. I.
    Univ Groningen, Netherlands; Natl Reference Ctr Mycobacteria, Germany.
    von Groote-Bidlingmaier, F.
    Task Appl Sci, South Africa.
    Hauptmann, M.
    German Ctr Infect Res DZIF, Germany; Res Ctr Borstel, Germany.
    Heyckendorf, J.
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany; Univ Lubeck, Germany.
    Kohler, N.
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany; Univ Lubeck, Germany.
    Kohl, T. A.
    Natl Reference Ctr Mycobacteria, Germany.
    Merker, M.
    Natl Reference Ctr Mycobacteria, Germany.
    Niemann, S.
    German Ctr Infect Res DZIF, Germany; Natl Reference Ctr Mycobacteria, Germany.
    Peloquin, C. A.
    Univ Florida, FL USA.
    Reimann, M.
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany; Univ Lubeck, Germany.
    Schaible, U. E.
    German Ctr Infect Res DZIF, Germany; Res Ctr Borstel, Germany; Univ Lubeck, Germany; LRA INFECTIONS 21, Germany.
    Schaub, D.
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany; Univ Lubeck, Germany.
    Schleusener, V.
    Natl Reference Ctr Mycobacteria, Germany.
    Thye, T.
    Bernhard Nocht Inst Trop Med, Germany.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Clinical Microbiology and Infectious Diseases, Kalmar County Hospital.
    Perspectives for personalized therapy for patients with multidrug-resistant tuberculosis2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 284, no 2, p. 163-188Article, review/survey (Refereed)
    Abstract [en]

    According to the World Health Organization (WHO), tuberculosis is the leading cause of death attributed to a single microbial pathogen worldwide. In addition to the large number of patients affected by tuberculosis, the emergence of Mycobacterium tuberculosis drug-resistance is complicating tuberculosis control in many high-burden countries. During the past 5years, the global number of patients identified with multidrug-resistant tuberculosis (MDR-TB), defined as bacillary resistance at least against rifampicin and isoniazid, the two most active drugs in a treatment regimen, has increased by more than 20% annually. Today we experience a historical peak in the number of patients affected by MDR-TB. The management of MDR-TB is characterized by delayed diagnosis, uncertainty of the extent of bacillary drug-resistance, imprecise standardized drug regimens and dosages, very long duration of therapy and high frequency of adverse events which all translate into a poor prognosis for many of the affected patients. Major scientific and technological advances in recent years provide new perspectives through treatment regimens tailor-made to individual needs. Where available, such personalized treatment has major implications on the treatment outcomes of patients with MDR-TB. The challenge now is to bring these adances to those patients that need them most.

  • 35.
    Lerm, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    On the relationship between BCG coverage and national COVID-19 outcome: could heterologous herd immunity explain why some countries are better off?2020In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 288, no 6, p. 682-688Article, review/survey (Refereed)
    Abstract [en]

    The COVID-19 pandemic has affected most parts of the global society since its emergence, and the scientific community has been challenged with questions urgently demanding answers. One of the early hypotheses on COVID-19 outcome was that some protection could be offered by the tuberculosis vaccine (BCG), and several clinical studies were initiated along with the emergence of numerous observational studies on the relationship between BCG and COVID-19 severity. In the present work, I demonstrate a strong correlation between the number of years that countries implemented BCG vaccination plans and age-standardized mortality rates during the first months of the pandemic in Europe. Further analyses of age groups in two European countries with comparably few confounding factors and easily identifiable groups of BCG-vaccinated and non-vaccinated subgroups suggest a population-level effect of BCG on national outcomes of COVID-19. This phenomenon of heterologous herd immunity deserves further investigation, both in epidemiological and experimental studies.

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  • 36.
    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.
    Dockrell, H. M.
    London Sch Hyg and Trop Med, England.
    Addressing diversity in tuberculosis using multidimensional approaches2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 284, no 2, p. 116-124Article, review/survey (Refereed)
    Abstract [en]

    Tuberculosis is a complex disease, which can affect many organs other than the lungs. Initial infection may be cleared without inducing immunological memory, or progress directly to primary disease. Alternatively, the infection may be controlled as latent TB infection, that may progress to active tuberculosis at a later stage. There is now a greater understanding that these infection states are part of a continuum, and studies using PET/CT imaging have shown that individual lung granulomas may respond to infection independently, in an un-synchronized manner. In addition, the Mycobacterium tuberculosis organisms themselves can exist in different states: as nonculturable forms, as persisters, as rapidly growing bacteria and a biofilm-forming cording phenotype. The omics approaches of transcriptomics, metabolomics and proteomics can help reveal the mechanisms underlying these different infection states in the host, and identify biosignatures with diagnostic potential, that can predict the development of disease, in progressors as early as 12-18 months before it can be detected clinically, or that can monitor the success of anti-TB therapy. Further insights can be obtained from studies of BCG vaccination and new TB vaccines. For example, epigenetic changes associated with trained immunity and a stronger immune responses following BCG vaccination can be identified. These omics approaches may be particularly valuable when linked to studies of mycobacterial growth inhibition, as a direct read-out of the ability to control mycobacterial growth. The second generation of omics studies is identifying much smaller signatures based on as few as 3 or 4 genes. Thus, narrowing down omics-derived biosignatures to a manageable set of markers now opens the way to field-friendly point of care assays.

  • 37.
    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.

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  • 38. 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.

  • 39.
    Lindahl, B.
    et al.
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Ljung, L.
    Karolinska Inst, Sweden.
    Herlitz, J.
    Univ Boras, Sweden.
    Alfredsson, Joakim
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Region Östergötland, Heart Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Erlinge, D.
    Lund Univ, Sweden.
    Kellerth, T.
    Orebro Univ, Sweden.
    Omerovic, E.
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Ravn-Fischer, A.
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Sparv, D.
    Lund Univ, Sweden.
    Yndigegn, T.
    Lund Univ, Sweden.
    Svensson, P.
    Karolinska Inst, Sweden.
    Ostlund, O.
    Uppsala Univ, Sweden.
    Jernberg, T.
    Karolinska Inst, Sweden.
    James, S. K.
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Hofmann, R.
    Karolinska Inst, Sweden.
    Poor long-term prognosis in patients admitted with strong suspicion of acute myocardial infarction but discharged with another diagnosis2021In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 290, no 2, p. 359-372Article in journal (Refereed)
    Abstract [en]

    Background Characteristics and prognosis of patients admitted with strong suspicion of myocardial infarction (MI) but discharged without an MI diagnosis are not well-described. Objectives To compare background characteristics and cardiovascular outcomes in patients discharged with or without MI diagnosis. Methods The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial compared 6629 patients with strong suspicion of MI randomized to oxygen or ambient air. The main composite end-point of this subgroup analysis was the incidence of all-cause death, rehospitalization with MI, heart failure (HF) or stroke during a follow-up of 2.1 years (median; range: 1-3.7 years) irrespective of randomized treatment. Results 1619 (24%) received a non-MI discharge diagnosis, and 5010 patients (76%) were diagnosed with MI. Groups were similar in age, but non-MI patients were more commonly female and had more comorbidities. At thirty days, the incidence of the composite end-point was 2.8% (45 of 1619) in non-MI patients, compared to 5.0% (250 of 5010) in MI patients with lower incidences in all individual end-points. However, for the long-term follow-up, the incidence of the composite end-point increased in the non-MI patients to 17.7% (286 of 1619) as compared to 16.0% (804 of 5010) in MI patients, mainly driven by a higher incidence of all-cause death, stroke and HF. Conclusions Patients admitted with a strong suspicion of MI but discharged with another diagnosis had more favourable outcomes in the short-term perspective, but from one year onwards, cardiovascular outcomes and death deteriorated to a worse long-term prognosis.

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  • 40.
    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.

  • 41. 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.

  • 42.
    Locht, C.
    et al.
    Univ Lille, France.
    Lerm, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Good old BCG - what a century-old vaccine can contribute to modern medicine2020In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 288, no 6, p. 611-613Article in journal (Other academic)
    Abstract [en]

    n/a

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  • 43.
    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.

  • 44. 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.

  • 45.
    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.

  • 46.
    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)
  • 47. 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.

  • 48.
    Mofors, J.
    et al.
    Karolinska Univ Hosp, Sweden.
    Arkema, E. V.
    Karolinska Univ Hosp, Sweden.
    Bjork, A.
    Karolinska Univ Hosp, Sweden.
    Westermark, L.
    Uppsala Univ, Sweden.
    Kvarnstrom, M.
    Karolinska Univ Hosp, Sweden.
    Forsblad-dElia, H.
    Umea Univ, Sweden.
    Bucher, S. Magnusson
    Orebro Univ, Sweden.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Mandl, T.
    Lund Univ, Sweden.
    Nordmark, G.
    Uppsala Univ, Sweden.
    Wahren-Herlenius, M.
    Karolinska Univ Hosp, Sweden.
    Infections increase the risk of developing Sjogrens syndrome2019In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 285, no 6, p. 670-680Article in journal (Refereed)
    Abstract [en]

    Objective Environmental factors have been suggested in the pathogenesis of rheumatic diseases. We here investigated whether infections increase the risk of developing primary Sjogrens syndrome (pSS). Methods Patients with pSS in Sweden (n = 945) and matched controls from the general population (n = 9048) were included, and data extracted from the National Patient Register to identify infections occurring before pSS diagnosis during a mean observational time of 16.0 years. Data were analysed using conditional logistic regression models. Sensitivity analyses were performed by varying exposure definition and adjusting for previous health care consumption. Results A history of infection associated with an increased risk of pSS (OR 1.9, 95% CI 1.6-2.3). Infections were more prominently associated with the development of SSA/SSB autoantibody-positive pSS (OR 2.7, 95% CI 2.0-3.5). When stratifying the analysis by organ system infected, respiratory infections increased the risk of developing pSS, both in patients with (OR 2.9, 95% CI 1.8-4.7) and without autoantibodies (OR 2.1, 95% CI 1.1-3.8), whilst skin and urogenital infections only significantly associated with the development of autoantibody-positive pSS (OR 3.2, 95% CI 1.8-5.5 and OR 2.7, 95% CI 1.7-4.2). Furthermore, a dose-response relationship was observed for infections and a risk to develop pSS with Ro/SSA and La/SSB antibodies. Gastrointestinal infections were not significantly associated with a risk of pSS. Conclusions Infections increase the risk of developing pSS, most prominently SSA/SSB autoantibody-positive disease, suggesting that microbial triggers of immunity may partake in the pathogenetic process of pSS.

  • 49.
    Mofors, J.
    et al.
    Karolinska Univ Hosp, Sweden.
    Holmqvist, M.
    Karolinska Inst, Sweden.
    Westermark, L.
    Uppsala Univ, Sweden.
    Bjork, A.
    Karolinska Univ Hosp, Sweden.
    Kvarnstrom, M.
    Karolinska Univ Hosp, Sweden.
    Forsblad-dElia, H.
    Umea Univ, Sweden.
    Bucher, S. Magnusson
    Orebro Univ, Sweden.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Theander, E.
    Lund Univ, Sweden.
    Mandl, T.
    Lund Univ, Sweden.
    Wahren-Herlenius, M.
    Karolinska Univ Hosp, Sweden.
    Nordmark, G.
    Uppsala Univ, Sweden.
    Concomitant Ro/SSA and La/SSB antibodies are biomarkers for the risk of venous thromboembolism and cerebral infarction in primary Sjogrens syndrome2019In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 286, no 4, p. 458-468Article in journal (Refereed)
    Abstract [en]

    Background To assess the risk of incident cardiovascular disease in patients with primary Sjogrens syndrome, overall and stratified by Ro/SSA and La/SSB autoantibody status. Methods A cohort of patients with primary Sjogrens syndrome in Sweden (n = 960) and matched controls from the general population (n = 9035) were included, and data extracted from the National Patient Register to identify events of myocardial infarction, cerebral infarction and venous thromboembolism. Hazard ratios were estimated using cox proportional hazard regressions. Results During a median follow-up of 9.5 years, the overall hazard ratio (HR) was 1.6 (95% CI 1.2-2.1) for myocardial infarction, 1.2 (95% CI 0.9-1.7) for cerebral infarction and 2.1 (95% CI 1.6-2.9) for venous thromboembolism. Patients positive for both Ro/SSA and La/SSB autoantibodies had a substantially higher risk of cerebral infarction (HR 1.7, 95% CI 1.0-2.9) and venous thromboembolism (HR 3.1, 95% CI 1.9-4.8) than the general population. These risks were not significantly increased in Ro/SSA- and La/SSB-negative patients. Among autoantibody-positive patients, the highest HR of cerebral infarction was seen after amp;gt;= 10 years disease duration (HR 2.8, 95% CI 1.4-5.4), while the HR for venous thromboembolism was highest 0-5 years after disease diagnosis (HR 4.7, 95% CI 2.3-9.3) and remained high throughout disease duration. Conclusions Primary Sjogrens syndrome is associated with a markedly increased risk of cardiovascular disease and the presence of Ro/SSA and La/SSB autoantibodies identify the subgroup of patients carrying the highest risk. These findings suggest that monitoring and prevention of cardiovascular disease in this patient group should be considered.

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  • 50.
    Mohammad, M. A.
    et al.
    Lund Univ, Sweden.
    Koul, S.
    Lund Univ, Sweden.
    Gale, C. P.
    Univ Leeds, England.
    Alfredsson, Joakim
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Cardiology in Linköping.
    James, S.
    Uppsala Univ, Sweden.
    Frobert, O.
    Orebro Univ, Sweden.
    Omerovic, E.
    Univ Gothenburg, Sweden.
    Erlinge, D.
    Lund Univ, Sweden.
    The association of mode of location activity and mobility with acute coronary syndrome: a nationwide ecological study2021In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 289, no 2, p. 247-254Article in journal (Refereed)
    Abstract [en]

    Background We aimed to study the effect of social containment mandates on ACS presentation during COVID-19 pandemic using location activity and mobility data from mobile phone map services. Methods We conducted a cross-sectional study using data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) including all ACS presentations during the pandemic until 7 May 2020. Using a count regression model, we adjusted for day of the week, daily weather and incidence of COVID-19. Results A 10% increase in activity around areas of residence was associated with 38% lower rates of ACS hospitalizations, whereas increased activity relating to retail and recreation, grocery stores and pharmacies, workplaces and mode of mobility was associated with 10-20% higher rates of ACS hospitalizations. Conclusion Government policy regarding social containment mandates has important public health implications for medical emergencies such as ACS and may explain the decline in ACS presentations observed during COVID-19 pandemic.

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