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  • 1.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences.
    Axelsson, T.
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences.
    Müssener, E.
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences.
    Grodzinsky, Ewa
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Midhagen, Gunnar
    Department of Clinical Microbiology and Immunology, University Hospital of Örebro, Sweden.
    Olcén, Per
    Department of Internal Medicine, Hospital of Lidköping.
    Increased Prevalence of Anti-Gliadin IgA-Antibodies with Aberrant Duodenal Histopathological Findings in Patients with IgA-Nephropathy and Related Disorders2006In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 111, no 3, p. 339-352Article in journal (Refereed)
    Abstract [en]

    Background: Antibodies present in coeliac disease may occur in IgA-nephropathy. This raises the question of food intolerance in the disease. Evidence for a true correlation between the two disorders has however been scarce.

    Design: Sera from 89 patients with IgA-nephropathy and 13 other patients with IgA deposits in the glomeruli of kidney biopsies were analysed for IgA-antibodies to gliadin, endomysium and tissue transglutaminase (92/102 patients).

    Results: Eleven out of 89 (12.4%) of the patients with IgA-nephropathy and five of the 13 others (38%) had elevated titres of IgA-antibodies to gliadin but, in all cases but one, normal IgA-antibodies to endomysium. Patients with IgA-nephropathy and elevated IgA-antibodies to gliadin had elevated total serum IgA more frequently than patients who had not (p<0.01). Two patients with IgA-nephropathy and one with Hennoch Schönlein's purpura had elevated IgA-antibodies to tissue transglutaminase.

    Small bowel biopsy in 7 out of 11 IgA-antibodies to gliadin positive patients with IgA-nephropathy was pathologic in three cases (two with Marsh I). One patient with chronic glomerulnephritis also had Marsh I.

    Conclusions: We found no increased frequency of verified coeliac disease in 89 patients with IgA-nephropathy. Two patients with IgA-nephropathy and one patient with chronic glomerulonephritis with IgA deposits in the kidney biopsy had a Marsh I histopathology. The findings suggest a possible link of celiac disease to IgA-nephropathy and a role for antibodies to food antigens in this disorder.

  • 2.
    Almroth, Gabriel
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nephrology. Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL.
    Lindell, Å
    Åselius, H
    Sörén, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Svensson, L
    Hultman, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Eribe, ERK
    Olsen, I
    Acute glomerulonephritis associated with streptococcus pyogenes with concomitant spread of streptococcus constellatus in four rural families2005In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 110, no 3, p. 217-231Article in journal (Refereed)
    Abstract [en]

    We studied history, renal histopathology and microbiology of an epidemic of acute glomerulonephritis associated with throat infections and uncommon culture results in four neighbour families. A 40-year-old man (index patient) was referred to a university hospital for dialysis and kidney biopsy due to a suspected acute glomerulonephritis. An acute tonsillitis had preceded the condition. Penicillin treatment had been started four days before the discovery of renal failure. Throat swabs were positive for β-hemolytic streptococci, group C (GCS). GCS were also found in throat cultures from his wife and two of their children. The bacteria were typed as Streptococcus constellatus. A third child had S. constellatus expressing Lancefield antigen group G. A neighbour and two of his children fell ill the following week with renal involvement. Throat swabs from both these children were positive for S. constellatus. His third child had erythema multiforme and S. constellatus in the throat while a fourth child had β-hemolytic streptococci group A, Streptococcus pyogenes. Kidney biopsies on the index patient and his neighbour showed an acute diffuse prolipherative glomerulonephritis compatible with acute post-streptococcal nephritis and microbiological analysis of renal tissue revealed in both cases S. pyogenes and S. constellatus. The families had had much contact and had consumed unpasteurized milk from our index patient's farm. In four of seven persons in two additional neighbouring families S. constellatus was found in throat swabs during the same month while two persons carried Streptococcus anginosus expressing the Lancefield C antigen. In conclusion spread of S. constellatus coincided with the occurrence of four cases of acute glomerulonephritis. The two biopsied patients had both S. pyogenes and S. constellatus present in renal tissue. The epidemic either suggested that the outbreak of glomerulonephritis was due to S. pyogenes but coincided with the transmission and colonization of S. constellatus or that the S. constellatus strains were highly pathogenic or nephritogenic and that this organism can be transmitted in such cases.

  • 3.
    Almroth, Gabriel
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nephrology. Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL.
    Uhlin, F
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nephrology. Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL.
    Ekermo, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Isaksson, Barbro
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Kaijser, B
    Andersson, B
    Hahn-Zoric, M
    Sällberg, M
    Perspectives on hepatitis B infections and the efficacy of vaccination (hepatitis B and pneumococci) in dialysis patients2003In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 108, no 1, p. 61-74Article in journal (Refereed)
    Abstract [en]

    Hepatitis B is a well known problem in dialysis units. We therefore examined the historical frequency of hepatitis B carriers in our unit, our vaccination program to hepatitis B virus (HBV), the response to hepatitis B vaccine, the IgG subclass response of anti-HBs and the response and IgG subclass response to pneumococcal vaccination (another vaccine) in dialysis patients. From 1970 and onwards 23 HBV carriers were found, but no new cases of hepatitis B occurred during the study period, i.e. from 1980 and onwards.Only one of the carriers was alive by the end of 2001. In four patients liver disease(in one of them liver cirrhosis) may have been a concomitant cause of death. The antibody response to hepatitis B vaccine was significantly lower in patients than in staff. In four patients a fourth injection was cancelled due to transplantation and bad health, while such data were lacking in 8 cases. In anti-HBs positive patients and controls a significant difference in the response of healthy adults was observed in anti-HBs IgG1 (p<0.001) vs all other IgG subclasses. Dialysis patients had low levels, or negative findings, in all cases, with IgG1 as the highest proportion found (3/11 patients). An antibody response to pneumococcal vaccination was registered in 25 out of 29 dialysis patients (in all 86 %). The IgG-subclass vaccination response to pneumococci in 28 dialysis patients was mainly IgG2 and IgG1 but also occurred in IgG3 and IgG4. Prevaccination antibody levels of the controls were higher in IgG1 and IgG2 (p< 0.01) (n=21) than in dialysis patients (n=28). Hepatitis B is nowadays a rare, but still dangerous disease in nephrology units. Dialysis patients have a reduced response to hepatitis B vaccine and vaccination schedules should be started early as some patients otherwise may not receive a fourth injection. The adequate antibody response to pneumococcal vaccination mainly due to IgG2 and IgG1 antibodies indicates that the antigen involved is important in vaccination responses in dialysis patients.

  • 4.
    Bengtsson, Per
    et al.
    Department of Physiology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden and Department of Surgery and the Research Center, Karolinska Institute, Huddinge University Hospital, Sweden.
    Nilsson, Göran
    Department of Physiology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden and Department of Surgery and the Research Center, Karolinska Institute, Huddinge University Hospital, Sweden.
    Cholecystokinin and Gastrin Inhibit Histamine Stimulated Aminopyrine Uptake in Isolated Rabbit Gastric Glands1989In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 94, no 2, p. 111-122Article in journal (Refereed)
    Abstract [en]

    In the present study we have analyzed if cholecystokinin (CCK) or gastrin (G) can inhibit acid production in isolated rabbit gastric glands as revealed by the aminopyrine technique.

    The results show that G 17 I, CCK 8 NS, CCK 8 S, ceruletide and CCK 39 significantly inhibit histamine induced aminopyrine accumulation. No significant inhibition was noted for G 4, G 34 and NT G 1–13. As a group the CCK peptides were more effective than the gastrin peptides in inhibiting the aminopyrine uptake. CCK 8 S and ceruletide, the most potent inhibitors, reduced histamine induced aminopyrine accumulation with an ED50 of 10−9 and 10−10 M respectively. These potencies are similar to those by which CCK peptides stimulate isolated pancreatic acini to secrete amylase. Inhibition evoked by CCK 8 S was most effective following 20–40 min of incubation time, possibly indicating that the effect is mediated by the release of an intermediate substance.

    The results may therefore indicate a role for cholecystokinin as a physiological inhibitor of acid secretion in the rabbit. The results may also contribute to explain why the potent gastric secretagogue gastrin per se fails to stimulate acid formation in gastric glands isolated from the rabbit.

  • 5.
    Engstrom, Sevek
    et al.
    Uppsala University, Sweden .
    Borgquist, Lars
    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, Research & Development Unit in Local Health Care.
    Berne, Christian
    University of Uppsala Hospital, Sweden .
    Gahnberg, Lars
    University of Gothenburg, Sweden .
    Svardsudd, Kurt
    Uppsala University, Sweden .
    Can costs of screening for hypertension and diabetes in dental care and follow-up in primary health care be predicted?2013In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 4, p. 256-262Article in journal (Refereed)
    Abstract [en]

    Aim. The purpose was to assess the direct costs of screening for high blood pressure and blood glucose in dental care and of follow-up in primary health care and, based on these data, arrive at a prediction function. less thanbrgreater than less thanbrgreater thanStudy population. All subjects coming for routine check-ups at three dental health clinics were invited to have blood pressure or blood glucose measurements; 1,623 agreed to participate. Subjects screening positive were referred to their primary health care centres for follow-up. less thanbrgreater than less thanbrgreater thanMethods. Information on individual screening time was registered during the screening process, and information on accountable time, costs for the screening staff, overhead costs, and analysis costs for the screening was obtained from the participating dental clinics. The corresponding items in primary care, i.e. consultation time, number of follow-up appointments, accountable time, costs for the follow-up staff, overhead costs, and analysis costs during follow-up were obtained from the primary health care centres. less thanbrgreater than less thanbrgreater thanResults. The total screening costs per screened subject ranged from (sic)7.4 to (sic)9.2 depending on subgroups, corresponding to 16.7-42.7 staff minutes. The corresponding follow-up costs were (sic)57-(sic)91. The total resource used for screening and follow-up per diagnosis was 563-3,137 staff minutes. There was a strong relationship between resource use and numbers needed to screen (NNS) to find one diagnosis (P andlt; 0.0001, degree of explanation 99%). less thanbrgreater than less thanbrgreater thanConclusions. Screening and follow-up costs were moderate and appear to be lower for combined screening of blood pressure and blood glucose than for separate screening. There was a strong relationship between resource use and NNS.

  • 6.
    Ferrandis, Maria-José
    et al.
    Department of Clinical Chemistry, Blekinge County Hospital, Sweden.
    Ryden, Ingvar
    Department of Clinical Chemistry, Blekinge County Hospital, Sweden.
    Lindahl, Tomas L.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Larsson, Anders
    Department of Medical Sciences, Section of Clinical Chemistry, Uppsala University, Uppsala, Sweden.
    Ruling out cardiac failure: Cost-benefit analysis of a sequential testing strategy with NT-proBNP before echocardiography2013In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 2, p. 75-79Article in journal (Refereed)
    Abstract [en]

    Objectives. To estimate the possible economic benefit of a sequential testing strategy with NT-proBNP to reduce the number of echocardiographies.

    Methods. Retrospective study in a third-party payer perspective. The costs were calculated from three Swedish counties: Blekinge, Östergötland, and Uppland. Two cut-off levels of NT-proBNP were used: 400 and 300 pg/mL. The cost-effectiveness of the testing strategy was estimated through the short-term cost avoidance and reduction in demand for echocardiographies.

    Results. The estimated costs for NT-proBNP tests and echocardiographies per county were reduced by 33%–36% with the 400 pg/mL cut-off and by 28%–29% with the 300 pg/mL cut-off. This corresponded to a yearly cost reduction of approximately €2–5 million per million inhabitants in these counties.

    Conclusion. The use of NT-proBNP as a screening test could substantially reduce the number of echocardiographies in the diagnostic work-up of patients with suspected cardiac failure, as well as the associated costs.

  • 7.
    Hanberger, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Skoog, Gunilla
    Public Health Agency Sweden, Sweden .
    Ternhag, Anders
    Public Health Agency Sweden, Sweden Karolinska Institute, Sweden .
    Giske, Christian G.
    Karolinska University Hospital, Sweden .
    Antibiotic consumption and antibiotic stewardship in Swedish hospitals2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 2, p. 154-161Article, review/survey (Refereed)
    Abstract [en]

    Background. The aim of this paper was to describe and analyze the effect of antibiotic policy changes on antibiotic consumption in Swedish hospitals and to review antibiotic stewardship in Swedish hospitals. Results. The main findings were: 1) Antibiotic consumption has significantly increased in Swedish hospitals over the last decade. The consumption of cephalosporins has decreased, whereas that of most other drugs including piperacillin-tazobactam, carbapenems, and penicillinase-sensitive and -resistant penicillins has increased and replaced cephalosporins. 2) Invasive infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae have increased, but the proportion of pathogens resistant to third-generation cephalosporins causing invasive infections is still very low in a European and international perspective. Furthermore, the following gaps in knowledge were identified: 1) lack of national, regional, and local data on the incidence of antibiotic resistance among bacteria causing hospital-acquired infections e. g. bloodstream infections and hospital-acquired pneumonia-data on which standard treatment guidelines should be based; 2) lack of data on the incidence of Clostridium difficile infections and the effect of change of antibiotic policies on the incidence of C. difficile infections and infections caused by antibiotic-resistant pathogens; and 3) lack of prospective surveillance programs regarding appropriate antibiotic treatment, including selection of optimal antimicrobial drug regimens, dosage, duration of therapy, and adverse ecological effects such as increases in C. difficile infections and emergence of antibiotic-resistant pathogens. Conclusions. Evidence-based actions to improve antibiotic use and to slow down the problem of antibiotic resistance need to be strengthened. The effect of such actions should be analyzed, and standard treatment guidelines should be continuously updated at national, regional, and local levels.

  • 8.
    Karlsson, Daniel
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Aspvall, Olle
    KI.
    Åhlfeldt, Hans
    Linköping University, Department of Biomedical Engineering.
    Forsum, Urban
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Using the MEDLINE® database to study the concept of urinary tract infections in different domains of medicine2004In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 109, no 2, p. 141-157Article in journal (Refereed)
    Abstract [en]

    As a way of exploring differences between medical domains regarding management of urinary tract infections, we investigated the MEDLINE® database for differences in indexing patterns. Further, our intention was to assess the MEDLINE® database as a source for studying medical domains. We examined the use of main headings, subheadings and the level of main headings in six medical domains that manage urinary tract infections. Many intuitive but also some counterintuitive results were found indicating that the MEDLINE® database is difficult to use for studying medical domains mainly due to unclear semantics both in the headings and the indexing process, which results in variability in indexing. This variability probably hides sig-nificant results. We also conclude that the differences found indicate that in addition to differences between domains, there are also large variations within domains.

  • 9.
    Larsson, Anders
    et al.
    Uppsala Univ, Sweden.
    Hagstrom, Emil
    Uppsala Univ, Sweden; Uppsala Clin Res Ctr, Sweden.
    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.
    Svensson, Maria K.
    Uppsala Univ, Sweden.
    Treatment target re-classification of subjects comparing estimation of low-density lipoprotein cholesterol by the Friedewald equation and direct measurement of LDL-cholesterol2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 2, p. 94-99Article in journal (Refereed)
    Abstract [en]

    Aims: To compare low-density lipoprotein cholesterol (LDL-C) values calculated by the Friedewald equation with direct LDL-C in patient samples and assess the possible impact on re-classification of LDL-C target values for primary prevention or high cardiovascular disease (CVD) risk (amp;lt;2.5 mmol/L) and secondary prevention or very high CVD risk (amp;lt;1.8mmol/L). LDL-C is an important CVD risk factor. Over the last decade, there has been a change in laboratory methodology from indirectly calculated LDL-C with the Friedewald equation to direct LDL-C measurements (dLDL-C). Methods: Reported results for plasma triglycerides, total cholesterol, high-density lipoprotein-cholesterol, and dLDL-C from 34,981 samples analyzed in year 2014 were extracted from the laboratory information system, Uppsala University Hospital, Uppsala, Sweden. Results: dLDL-C was approximately 10% lower than the corresponding LDL-C results calculated by the Friedewald equation in both men and women. In subjects with triglyceride concentrations above 4 mmol/L (n = 1250) the same discordant pattern was seen as for the entire study population. Altogether 5469 out of 18,051 men (30.3%) and 4604 out of 16,928 women (27.2%) were down-classified at least one CVD risk category. A very small number of subject was up-classified, in total 37 out of 18,051 men (0.2%) and 28 out of 16,928 women (0.2%). Conclusions: The two LDL-C methods had a high concordance, but the direct LDL-C measurement consistently gave approx. 10% lower values, and this caused one-third of subjects to be re-classified as having a lower cardiovascular disease risk in relation to recommended LDL-C target values and decision limits.

  • 10.
    Lindahl, Tomas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Arbring, Kerstin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Wallstedt, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Rånby, Mats
    Zafena AB, Borensberg, Sweden.
    A novel prothrombin time method to measure all non-vitamin K-dependent oral anticoagulants (NOACs)2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 3, p. 171-176Article in journal (Refereed)
    Abstract [en]

    Background: There is a clinical need for point-of-care (POC) methods for non-vitamin K-dependent oral anticoagulants (NOACs). We modified a routine POC procedure: Zafena’s Simple Simon™ PT-INR, a room-temperature, wet-chemistry prothrombin time method of the Owren-type.

    Methods: To either increase or decrease NOAC interference, two assay variants were devised by replacing the standard 10 µL end-to-end capillary used to add the citrated plasma sample to 200 µL of prothrombin time (PT) reagent by either a 20 µL or a 5 µL capillary. All assay variants were calibrated to show correct PT results in plasma samples from healthy and warfarin-treated persons.

    Results: For plasmas spiked with dabigatran, apixaban, or rivaroxaban, the 20 µL variant showed markedly higher PT results than the 5 µL. The effects were even more pronounced at room temperature than at +37 °C. In plasmas from patients treated with NOACs (n = 30 for each) there was a strong correlation between the PT results and the concentration of NOACs as determined by the central hospital laboratory. For the 20 µL variant the PT response of linear correlation coefficient averaged 0.90. The PT range was INR 1.1–2.1 for dabigatran and apixaban, and INR 1.1–5.0 for rivaroxaban. Using an INR ratio between the 20 µL and 5 µL variants (PTr20/5) made the NOAC assay more robust and independent of the patient sample INR value in the absence of NOAC. Detection limits were 80 µg/L for apixaban, 60 µg/L for dabigatran, and 20 µg/L for rivaroxaban.

    Conclusions: A wet-chemistry POC PT procedure was modified to measure the concentrations of three NOACs using a single reagent.

  • 11.
    Liss, Per
    et al.
    University of Uppsala Hospital, Sweden.
    Hansell, Peter
    Uppsala University, Sweden.
    Fasching, Angelica
    Uppsala University, Sweden.
    Palm, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Uppsala University, Sweden.
    Iodinated contrast media inhibit oxygen consumption in freshly isolated proximal tubular cells from elderly humans and diabetic rats: Influence of nitric oxide2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 1, p. 12-16Article in journal (Refereed)
    Abstract [en]

    Objectives Mechanisms underlying contrast medium (CM)-induced nephropathy remain elusive, but recent attention has been directed to oxygen availability. The purpose of this study was to evaluate the effect of the low-osmolar CM iopromide and the iso-osmolar CM iodixanol on oxygen consumption (QO(2)) in freshly isolated proximal tubular cells (PTC) from kidneys ablated from elderly humans undergoing nephrectomy for renal carcinomas and from normoglycemic or streptozotocin-diabetic rats. Materials PTC were isolated from human kidneys, or kidneys of normoglycemic or streptozotocin-diabetic rats. QO(2) was measured with Clark-type microelectrodes in a gas-tight chamber with and without each CM (10 mg I/mL medium). L-NAME was used to inhibit nitric oxide (NO) production caused by nitric oxide synthase. Results Both CM reduced QO(2) in human PTC (about -35%) which was prevented by L-NAME. PTC from normoglycemic rats were unaffected by iopromide, whereas iodixanol decreased QO(2) (-34%). Both CM decreased QO(2) in PTC from diabetic rats (-38% and -36%, respectively). L-NAME only prevented the effect of iopromide in the diabetic rat PTC. Conclusions These observations demonstrate that CM can induce NO release from isolated PTC in vitro, which affects QO(2). Our results suggest that the induction of NO release and subsequent effect on the cellular oxygen metabolism are dependent on several factors, including CM type and pre-existing risk factors for the development of CM-induced nephropathy.

  • 12.
    Molinder, Herdis
    et al.
    Karolinska Institute, Sweden.
    Agreus, Lars
    Karolinska Institute, Sweden.
    Kjellström, Lars
    Sabbatsberg Hospital, Sweden.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Faculty of Medicine and Health Sciences.
    Talley, Nicholas J.
    University of Newcastle, Australia.
    Andreasson, Anna
    Karolinska Institute, Sweden; Stress Research Institute, Stockholm University, Stockholm, Sweden.
    Nyhlin, Henry
    Karolinska Institute, Sweden.
    How individuals with the irritable bowel syndrome describe their own symptoms before formal diagnosis2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 4, p. 276-279Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate how individuals fulfilling the Rome II criteria for irritable bowel syndrome (IBS) spontaneously described their symptoms. Method: From a general population, 1,244 randomly sampled adults were asked to describe their gastrointestinal symptoms (if any) verbally, in their own words, at a semi-structured interview. Their own descriptions were sorted into five symptom clusters. The participants independently completed a written questionnaire (the Rome II Modular Questionnaire (RMIIMQ)). Results: A total of 601 participants reported at least one gastrointestinal symptom, and 128 had IBS according to the RMIIMQ. After exclusion of organic causes, previously diagnosed IBS, or additional gastrointestinal diagnosis, 81 participants with IBS according to RMIIMQ remained. Five participants (6%) described symptoms included in the full definition of IBS, but none fulfilled the Rome II criteria completely. Abdominal pain or other IBS-related symptoms were reported by 64 (79%), and 12 (15%) did not report any IBS-like symptom. Conclusion: Previously undiagnosed individuals, who fulfil criteria for Rome II-IBS, often express their complaints in words that do not fit into the current diagnostic criteria.

  • 13.
    Nyberg, Sofia
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Gerring, Edvard
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Gjellan, Solveig
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Vergara Valgañon, Marta
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Effects of exercise with or without blueberries in the diet on cardio-metabolic risk factors: an exploratory pilot study in healthy subjects2013In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 4, p. 247-255Article in journal (Refereed)
    Abstract [en]

    Background. The improvement of insulin sensitivity by exercise has been shown to be inhibited by supplementation of vitamins acting as antioxidants.

    Objective. To examine effects of exercise with or without blueberries, containing natural antioxidants, on cardio-metabolic risk factors.

    Methods. Fifteen healthy men and 17 women, 27.6 ± 6.5 years old, were recruited, and 26 completed a randomized cross-over trial with 4 weeks of exercise by running/jogging 5 km five times/week and 4 weeks of minimal physical activity. Participants were also randomized to consume 150 g of blueberries, or not, on exercise days. Laboratory variables were measured before and after a 5 km running-race at maximal speed at the beginning and end of each period, i.e. there were four maximal running-races and eight samplings in total for each participant.

    Results. Insulin and triglyceride levels were reduced while HDL-cholesterol increased by exercise compared with minimal physical activity. Participants randomized to consume blueberries showed an increase in fasting glucose levels compared with controls, during the exercise period (blueberries: from 5.12 ± 0.49 mmol/l to 5.32 ± 0.29 mmol/l; controls: from 5.24 ± 0.27 mmol/l to 5.17 ± 0.23 mmol/l, P = 0.04 for difference in change). Triglyceride levels fell in the control group (from 1.1 ± 0.49 mmol/l to 0.93 ± 0.31 mmol/l, P = 0.02), while HDL-cholesterol increased in the blueberry group (from 1.51 ± 0.29 mmol/l to 1.64 ± 0.33 mmol/l, P = 0.006).

    Conclusions. Ingestion of blueberries induced differential effects on cardio-metabolic risk factors, including increased levels of both fasting glucose and HDL-cholesterol. However, since it is possible that indirect effects on food intake were induced, other than consumption of blueberries, further studies are needed to confirm the findings.

  • 14.
    Olai, Lena
    et al.
    Uppsala University, Sweden Clin Research Centre, Sweden Dalarna University, Sweden .
    Borgquist, Lars
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    Svardsudd, Kurt
    Uppsala University, Sweden .
    Health problems in elderly patients during the first post-stroke year2012In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 3, p. 318-327Article in journal (Refereed)
    Abstract [en]

    Background. A wide range of health problems has been reported in elderly post-stroke patients. Aim. The aim of this study was to analyse the prevalence and timing of health problems identified by patient interviews and scrutiny of primary health care and municipality elderly health care records during the first post-stroke year. less thanbrgreater than less thanbrgreater thanMethods. A total of 390 consecutive patients, andgt;= 65 years, discharged alive from hospital after a stroke event, were followed for 1 year post-admission. Information on the health care situation during the first post-stroke year was obtained from primary health care and municipal elderly health care records and through interviews with the stroke survivors, at 1 week after discharge, and 3 and 12 months after hospital admission. less thanbrgreater than less thanbrgreater thanResults. More than 90% had some health problem at some time during the year, while based on patient record data only 4-8% had problems during a given week. The prevalence of interview-based health problems was generally higher than record-based prevalence, and the ranking order was moderately different. The most frequently interview-reported problems were associated with perception, activity, and tiredness, while the most common record-based findings indicated pain, bladder and bowel function, and breathing and circulation problems. There was co-occurrence between some problems, such as those relating to cognition, activity, and tiredness. less thanbrgreater than less thanbrgreater thanConclusions. Almost all patients had a health problem during the year, but few occurred in a given week. Cognitive and communication problems were more common in interview data than record data. Co-occurrence may be used to identify subtle health problems.

  • 15.
    Olai, Lena
    et al.
    Uppsala University, Sweden; Clin Research Centre, Sweden; Dalarna University, Sweden.
    Borgquist, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Linköping University, Faculty of Medicine and Health Sciences.
    Svardsudd, Kurt
    Uppsala University, Sweden.
    Life situations and the care burden for stroke patients and their informal caregivers in a prospective cohort study2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 4, p. 290-298Article in journal (Refereed)
    Abstract [en]

    Background. The purpose of this study was to analyse whether the parallel life situation between stroke patients and their informal caregivers (dyads) shown in cross-sectional studies prevails also in a longitudinal perspective.Methods. A total of 377 Swedish stroke patients, aged 65 years, and their 268 informal caregivers were followed from hospital admission and one year on. Analyses were based on patient interviews, functional ability (MMSE) score, Nottingham Health Profile (NHP) score, Hospital Anxiety and Depression (HAD) score, self-rated health score, and the Gothenburg Quality of Life (GQL) activity score. Similar information was obtained by postal questionnaires from informal caregivers, also including information on the nature and amount of assistance provided and on Caregiver Burden (CB) score.Results. Before index admission informal caregivers provided care on average 5 h per week and after discharge 11 h per week (P &lt; 0.0001). Support volume was associated with patient sex (more for men), low patients functional ability, low received municipal social service support, closeness of patient-caregiver relation, and short distance to patients home. Significant positive associations within the dyads were found for HAD anxiety score (P &lt; 0.0001), total NHP score (P &lt; 0.0001), and GQL activity score (P &lt; 0.0001) after adjustment for patients age, sex, functional ability, and patient-caregiver relationship. CB score increased with amount of informal caregiver support, patients age, and with low functional ability and low amount of municipal social service support. All these associations were constant across time.Conclusions. There was an association within the dyads regarding anxiety score, NHP score, and activity score. CB score was generally high.

  • 16.
    Savarese, Gianluigi
    et al.
    Cardiology Unit, Department of Medicine , Karolinska Institutet , Stockholm , Sweden.
    Vasko, Peter
    Department of Medicine , Växjö Hospital , Växjö , Sweden.
    Jonsson, Åsa
    Department of Medicine , Ryhov County Hospital , Jönköping , Sweden.
    Edner, Magnus
    Cardiology Unit, Department of Medicine , Karolinska Institutet , Stockholm , Sweden.
    Dahlström, Ulf
    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.
    Lund, Lars H
    a Cardiology Unit, Department of Medicine , Karolinska Institutet , Stockholm , Sweden.
    The Swedish Heart Failure Registry: a living, ongoing quality assurance and research in heart failure2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 65-69Article, review/survey (Refereed)
    Abstract [en]

    Heart failure (HF) represents a global pandemic. Although in HF with reduced ejection fraction (HFrEF) randomized controlled trials have provided effective treatments, prognosis still remains poor, with signals of undertreatment. HF with mid-range EF (HFmrEF) has no evidence-based therapy, and its characterization is ongoing. Trials in HF with preserved EF (HFpEF) have failed to provide any effective treatment, but there are several concerns about their design. Thus, current challenges in the HF field are: 1) optimizing the use of existing treatments in HFrEF; 2) developing and proving efficacy of new treatments, and of new use of existing treatments in HFpEF and HFmrEF. Here we describe how registry-based research can improve knowledge addressing the unmet needs in HF, and in particular we focus on the contribution of the Swedish Heart Failure Registry to this field.

  • 17.
    Stridh, Sara
    et al.
    Uppsala University, Sweden .
    Palm, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Uppsala University, Sweden .
    Hansell, Peter
    Uppsala University, Sweden .
    Inhibition of hyaluronan synthesis in rats reduces renal ability to excrete fluid and electrolytes during acute hydration2013In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 4, p. 217-221Article in journal (Refereed)
    Abstract [en]

    Background. Hyaluronan (HA) is the dominant glycosaminoglycan in the renomedullary interstitium. Renomedullary HA has been implicated in tubular fluid handling due to its water-attracting properties and the changes occurring in parallel to acute variations in the body hydration status. less thanbrgreater than less thanbrgreater thanMethods. HA production was inhibited by 4-methylumbelliferone (4-MU in drinking water for 5 days, 1.45 +/- 0.07 g/day/kg body weight) in rats prior to hydration. less thanbrgreater than less thanbrgreater thanResults. Following hypotonic hydration for 135 min in control animals, diuresis and osmotic excretion increased while sodium excretion and glomerular filtration rate (GFR) remained unchanged. The medullary and cortical HA contents were 7.85 +/- 1.29 ng/mg protein and 0.08 +/- 0.01 ng/mg protein, respectively. Medullary HA content after 4-MU was 38% of that in controls (2.98 +/- 0.95 ng/g protein, p andlt; 0.05), while the low cortical levels were unaffected. Baseline urine flow was not different from that in controls. The diuretic response to hydration was, however, only 51% of that in controls (157 +/- 36 versus 306 +/- 54 mu l/g kidney weight/135 min, p andlt; 0.05) and the osmolar excretion only 47% of that in controls (174 +/- 47 versus 374 +/- 41 mu Osm/g kidney weight/135 min, p andlt; 0.05). Sodium excretion, GFR, and arterial blood pressure were similar to that in control rats and unaltered during hydration. less thanbrgreater than less thanbrgreater thanConclusions. Reduction of renomedullary interstitial HA using 4-MU reduces the ability of the kidney to respond appropriately upon acute hydration. The results strengthen the concept of renomedullary HA as a modulator of tubular fluid handling by changing the physicochemical properties of the interstitial space.

  • 18.
    Stridh, Sara
    et al.
    Uppsala University, Sweden.
    Palm, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Uppsala University, Sweden.
    Takahashi, Tomoko
    Hoshi University, Japan.
    Ikegami-Kawai, Mayumi
    Hoshi University, Japan.
    Hansell, Peter
    Uppsala University, Sweden.
    Inhibition of mTOR activity in diabetes mellitus reduces proteinuria but not renal accumulation of hyaluronan2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 4, p. 233-240Article in journal (Refereed)
    Abstract [en]

    Objectives. Accumulation of extracellular matrix (ECM) components is an early sign of diabetic nephropathy. Also the glycosaminoglycan hyaluronan (HA) is elevated in the renal interstitium during experimental diabetes. The mammalian target of rapamycin (mTOR) pathway participates in the signaling of hyperglycemia-induced ECM accumulation in the kidney, but this has not yet been investigated for HA. We hypothesized that interstitial HA accumulation during diabetes may involve mTOR activation.Methods. Diabetic rats (6 weeks post-streptozotocin (STZ)) were treated with rapamycin to inhibit mTOR or vehicle for 2 additional weeks. Kidney function (glomerular filtration rate, renal blood flow, urine output) and regional renal HA content were thereafter analyzed. The ability of the animals to respond to desmopressin was also tested.Results. Diabetic animals displayed hyperglycemia, proteinuria, hyperfiltration, renal hypertrophy, increased diuresis with reduced urine osmolality, and reduced weight gain. Cortical and outer medullary HA was elevated in diabetic rats. Urine hyaluronidase activity was almost doubled in diabetic rats compared with controls. The ability to respond to desmopressin was absent in diabetic rats. Renal blood flow and arterial blood pressure were unaffected by the diabetic state. In diabetic rats treated with rapamycin the proteinuria was reduced by 32%, while all other parameters were unaffected.Conclusion. Regional renal accumulation of the ECM component HA is not sensitive to mTOR inhibition by rapamycin, while proteinuria is reduced in established STZ-induced diabetes. Whether the diabetes-induced renal accumulation of HA occurs through different pathways than other ECM components, or is irreversible after being established, remains to be shown.

  • 19.
    Sundstrom, Johan
    et al.
    Uppsala Univ, Sweden; Uppsala Clin Res Ctr UCR, Sweden.
    Bjorkelund, Cecilia
    Univ Gothenburg, Sweden.
    Giedraitis, Vilmantas
    Uppsala Univ, Sweden.
    Hansson, Per-Olof
    Univ Gothenburg, Sweden.
    Högman, Marieann
    Uppsala Univ, Sweden.
    Janson, Christer
    Uppsala Univ, Sweden.
    Koupil, Ilona
    Stockholm Univ, Sweden; Karolinska Inst, Sweden.
    Kristensson, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Trolle Lagerros, Ylva
    Karolinska Inst, Sweden; Karolinska Univ Hosp Huddinge, Sweden.
    Leppert, Jerzy
    Uppsala Univ, Sweden.
    Lind, Lars
    Uppsala Univ, Sweden.
    Lissner, Lauren
    Univ Gothenburg, Sweden.
    Johansson, Ingegerd
    Umea Univ, Sweden.
    Ludvigsso, Jonas F.
    Karolinska Inst, Sweden; Orebro Univ, Sweden.
    Nilsson, Peter M.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Olsson, Hakan
    Lund Univ, Sweden.
    Pedersen, Nancy L.
    Karolinska Inst, Sweden.
    Rosenblad, Andreas
    Uppsala Univ, Sweden.
    Rosengren, Annika
    Univ Gothenburg, Sweden.
    Sandin, Sven
    Karolinska Inst, Sweden; Icahn Sch Med Mt Sinai, NY 10029 USA; Seaver Autism Ctr Res and Treatment Mt Sinai, NY USA.
    Snackerstrom, Tomas
    Uppsala Clin Res Ctr UCR, Sweden.
    Stenbeck, Magnus
    Karolinska Inst, Sweden.
    Soderberg, Stefan
    Umea Univ, Sweden; Umea Univ, Sweden.
    Weiderpass, Elisabete
    Karolinska Inst, Sweden; Inst Populat Based Canc Res, Norway; Univ Helsinki, Finland; Univ Tromso, Norway.
    Wanhainen, Ers
    Uppsala Univ, Sweden.
    Wennberg, Patrik
    Umea Univ, Sweden.
    Fortier, Isabel
    McGill Univ, Canada.
    Heller, Susanne
    Uppsala Clin Res Ctr UCR, Sweden.
    Storgards, Maria
    Uppsala Clin Res Ctr UCR, Sweden.
    Svennblad, Bodil
    Uppsala Clin Res Ctr UCR, Sweden.
    Rationale for a Swedish cohort consortium2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 21-28Article in journal (Refereed)
    Abstract [en]

    We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants data, better return of funders investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.

  • 20.
    Svensson, Erik
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Ertzgaard, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Reconstruction Centre, Department of Rehabilitation Medicine UHL.
    Forsum, Urban
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Bacteriuria in spinal cord injured patients with neurogenic bladder dysfunction2004In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 109, no 1, p. 25-32Article in journal (Refereed)
    Abstract [en]

    The occurrence of bacteriuria in spinal cord injured patients with neurogenic bladder dysfunction who used clean intermittent catheterisation to empty their bladders was studied in order to examine cut-off concentration breakpoints for significant bacteriuria in this group of patients using procedures of the European Urinanalysis Guideline. 344 samples were cultured, yielding 285 isolates. Coagulase-negative staphylococci (27 %), Enterococci (25 %), Klebsiella spp (19 %), and Escherichia coli (12 %) were the most common findings. Bacteria grew at concentrations of 105-108 cfu/L, but only a few at 104 cfu/L. It is concluded that low bacterial concentrations in the urine (105 cfu/L) of patients with neurogenic bladder dysfunction who are on intermittent catheterisation might be as significant for bladder contamination with bacteria as a high bacterial concentration and can possibly be responsible for bladder infections.

  • 21.
    Westermark, Gunilla
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Steiner, Donald
    Gebre-Medhin, Samuel
    Engström, Ulla
    Westermark, Per
    Pro islet amyloid polypeptide (ProIAPP) immunoreactivity in the islets of langerhans2000In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 105, no 2, p. 97-106Article in journal (Refereed)
    Abstract [en]

    Islet amyloid is typically found in type 2 diabetes mellitus and is believed to participate in the beta cell deterioration. The islet amyloid fibril consists of the 37-amino-acid islet amyloid polypeptide (IAPP) but its pathogenesis is only partly understood. We developed several different rabbit antisera against the flanking peptides of the IAPP precursor (proIAPP) and the proIAPP processing sites in order to study the possible occurrence of unprocessed proIAPP or parts thereof in islet amyloid. We applied these antisera in an immunohistochemical study on islet amyloid deposits present in a newly generated mouse strain that over-expresses human IAPP but is devoid of mouse IAPP. Male mice of this strain develop severe islet amyloidosis when given a high fat diet. Generally, the antisera showed no immunoreactivity with the amyloid. However, in scattered single beta cells, where amyloid could be seen intracellularly, immunoreactivity with one or more of the antisera colocalized with the amyloid. Although virtually all amyloid in human islets of Langerhans is found extracellularly, we propose that the initial amyloid formation occurs intracellularly, perhaps by not fully processed or folded (pro)IAPP. This amyloid, which may develop rapidly under certain circumstances, probably leads to cell death. If not degraded these amyloid spots may then act as nidus for further amyloid formation from fully processed IAPP, secreted from surrounding beta cells.

  • 22.
    Westermark, Gunilla T.
    et al.
    Uppsala University, Sweden.
    Krogvold, Lars
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Dahl-Jorgensen, Knut
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, 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, Department of Paediatrics in Linköping.
    Islet amyloid in recent-onset type 1 diabetes-the DiViD study2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 3, p. 201-203Article in journal (Other academic)
    Abstract [en]

    n/a

  • 23.
    Westermark, Gunilla
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Westermark, P
    Nordin, A
    Tornelius, E
    Andersson, A
    Formation of amyloid in human pancreatic islets transplanted to the liver and spleen of nude mice2003In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 108, no 3, p. 193-203Article in journal (Refereed)
    Abstract [en]

    In previous studies we have shown that apparently normal human islets, transplanted under the renal capsule of nude mice, frequently and rapidly develop amyloid deposits derived from the ▀-cell hormone islet amyloid polypeptide (IAPP). In the present study, we show for the first time that human islets, transplanted into the liver or spleen of nude mice, also develop islet amyloid rapidly. Ultrastructural studies of such islets showed that the first aggregation of IAPP takes place within the ▀-cells and that extracellular deposits show up later in the amyloid formation process. We also found that the amount of amyloid formed in human islet grafts placed under the kidney capsule increased with extended (26 weeks) observation time. Moreover, prolonged in vitro culture (14 days) prior to the implantation under the renal capsule seemed to enhance the formation of amyloid in the grafted islets. Since aggregated IAPP has been shown to be toxic to ▀-cells, the finding of amyloid deposits in transplanted islets offers a possible explanation to the frequent loss of function of islets transplanted into diabetic patients.

  • 24. Åkerblom, B
    et al.
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Larsson, A
    ADP activation induces bFGF binding to platelets in vitro2002In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 107, no 3, p. 165-171Article in journal (Refereed)
    Abstract [en]

    Basic fibroblast growth factor (bFGF), is a heparin-binding factor with potent angiogenic properties in vitro and in vivo. bFGF is involved in tumour growth, but it has also been shown to reduce infarct size in experimentally induced acute myocardial infarction. Platelets are also believed to have an important role in both tumour growth and myocardial infarction. We have studied bFGF binding to platelets by flow cytometry. Platelet activation by ADP induces bFGF binding to platelets. bFGF bound to activated platelets will result in a locally high concentration of bFGF in patients with myocardial infarctions and malignant tumours. Addition of recombinant bFGF to platelet rich plasma reduced the percentage of fibrinogen positive platelets. bFGF may thus have an inhibitory effect on platelet aggregation.

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