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  • 1.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Karlberg, Bengt E.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Holm, Ann-Charlotte
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Salivary cortisol: an alternative to serum cortisol determinations in dynamic function tests1998In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 36, no 4, p. 215-222Article in journal (Refereed)
    Abstract [en]

    Salivary cortisol was measured as an alternative to serum cortisol as a marker for adrenocortical function following insulin tolerance test, corticotropin-releasing-hormone stimulation and adreno-corticotrophic hormone stimulation. During insulin tolerance test and corticotropin-releasing-hormone stimulation adreno-corticotrophic hormone was also measured. The tests were performed on healthy control subjects as well as on patients under investigation for various disturbances in the hypothalamic-pituitary-adrenocortical axis (insulin tolerance test: 3 controls on two occasions and 14 patients; corticotropin-releasing-hormone stimulation: 4 controls and 18 patients; adreno-corticotrophic hormone stimulation: 6 controls and 10 patients). Five patients underwent both insulin tolerance test and corticotropin-releasing-hormone stimulation. Using criteria for adequate cortisol response in serum, the patients were classified as good or poor responders. In 42 of the 45 tests performed the same conclusion as to cortisol status was drawn when based on serum and salivary cortisol responses. In healthy subjects and good responders the mean cortisol relative increase was greater in saliva than in serum in all three tests (p < 0.05). Characteristic of the results for the insulin tolerance test was a significant initial mean decrease (p < 0.05), not found in serum, and the highest observed salivary cortisol value was delayed for at least 30 minutes compared to that in serum. Plasma adreno-corticotrophic hormone correlated significantly with the cortisol concentrations determined 15 minutes later in serum (r = 0.54–0.64) and in saliva (r = 0.76–0.85). The more pronounced cortisol response in saliva than in serum and its closer correlation with adreno-corticotrophic hormone offer advantages over serum cortisol, suggesting salivary cortisol measurement may be used as an alternative parameter in dynamic endocrine tets.

  • 2. Anfelter, P
    et al.
    Granerus, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Stenström, Hugo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Medical Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology UHL.
    Eriksson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    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.
    The effect of percutaneous dilatation of renal arterial stenosis on captopril renography in hypertension2005In: Blood Pressure, ISSN 0803-7051, E-ISSN 1651-1999, Vol. 14, no 6, p. 359-365Article in journal (Refereed)
    Abstract [en]

    Background. The clinical effects of percutaneous transluminal renal artery angioplasty (PTRA) in patients with renal vascular stenosis and hypertension is controversial. Methods. We consecutively recruited all 23 patients referred for evaluation of renovascular hypertension that eventually underwent unilateral PTRA, to be investigated with captopril MAG3 renography (CR), both before and after the endovascular procedure. Data were evaluated on an intention-to-treat basis. Results. We found that the relative MAG3 clearance of the stenotic kidney increased (from 29.9 ± 14% to 35.1 ± 14%, p=0.01) and that the creatinine levels fell following the intervention (from 110 ± 19 to 99 ± 17 μmol/l, p=0.0003). Blood pressure levels were also lowered (from 173 ± 32/93 ± 17 to 158 ± 31/86 ± 15 mmHg, p<0.006) while the mean number of anti-hypertensive drugs was unchanged following PTRA (2.9 ± 1.4 before and 2.8 ± 1.3 drugs after the intervention, respectively, p-0.6). Conclusion. This prospective trial showed statistically significant improvements of individual kidney function as measured by CR and blood pressure in subjects with suspected renovascular hypertension treated with PTRA. Although the endovascular procedure was found to be safe, the magniture of the absolute improvements was rather modest. © 2005 Taylor & Francis.

  • 3.
    Assman, Gerd
    et al.
    Tyskland.
    Cullen, Paul
    Tyskland.
    Fruchart, Jean-Charles
    Frankrike.
    Greten, Heiner
    Tyskland.
    Naruszewicz, Marek
    Polen.
    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.
    Paoletti, Rudolfo
    Italien.
    Riesen, Walter
    Schweiz.
    Stoll, Monika
    Tyskland.
    Tikkanen, Matti
    Finland.
    Von Eckardstein, Arnold
    Schweiz.
    Implications of emerging risk factors for therapeutic intervention2005In: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 15, no 5, p. 373-381Article in journal (Refereed)
    Abstract [en]

    Recently, the National Cholesterol Education Panel (NCEP) of the United States of America commented on the implications of new clinical trials for the Adult Treatment Panel III (ATP III) guidelines [Grundy SM, Cleeman JI, Merz CN, Brewer Jr HB, Clark LT, Hunninghake DB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004,110:227-39]. In this commentary, new categories of "moderately high" and "very high" coronary risk were proposed with new "therapeutic options" for low-density lipoprotein (LDL) cholesterol of ≤ 100 mg/dL and ≤70 mg/dL respectively. In ATP III, these "moderately high" risk patients had been classified as moderate risk with an LDL treatment goal of ≤130 mg/dL, while the "very high" risk patients had been classified as high risk with a treatment goal of ≤100 mg/dL. Risk classification in the new NCEP publication is based essentially on the combination of the Framingham risk score plus counting of classical risk factors. In the present document, the International Task Force for Prevention of Coronary Heart Disease responds to this NCEP commentary and supports the suggestion of more intensive LDL cholesterol lowering in particular cases. However, the Task Force feels that a classification based on a combination of a risk score plus a count of emerging risk factors is a more logical way to identify such patients requiring lower LDL cholesterol levels than a scheme in which classical risk factors are taken into account twice, once in a count and once in a risk score. © 2005 Elsevier B.V. All rights reserved.

  • 4. Ballantyne, CM
    et al.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Cook, TJ
    Mercuri, MF
    Pedersen, TR
    Kjekshus, J
    Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S2001In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 104, no 25, p. 3046-3051Article in journal (Refereed)
    Abstract [en]

    Background - Patients with low HDL cholesterol (HDL-C) and elevated triglyceride had an increased risk for coronary heart disease (CHD) events and received the greatest benefit with fibrate therapy in substudy analyses of the Helsinki Heart Study and the Bezafibrate Infarction Prevention Study. Methods and Results - In this post hoc analysis of the Scandinavian Simvastatin Survival Study, which enrolled patients with elevated LDL cholesterol (LDL-C) and CHD, subgroups defined by HDL-C and triglyceride quartiles were compared to examine the influence of HDL-C and triglyceride on CHD events and response to therapy. Patients in the lowest HDL-C (<1.00 mmol/L [39 mg/dL]) and highest triglyceride (>1.80 mmol/L [159 mg/dL]) quartiles (lipid triad, n=458) had increased proportions of other features of the metabolic syndrome (increased body mass index, hypertension, diabetes), men, prior myocardial infarction, prior revascularization, and ▀-blocker use than patients in the highest HDL-C (>1.34 mmol/L [52 mg/dL]) and lowest triglyceride (<1.11 mmol/L [98 mg/dL]) quartiles (isolated LDL-C elevation, n=545). The major coronary event rate was highest in lipid triad patients on placebo (35.9%), and this subgroup had the greatest event reduction (relative risk 0.48, 95% CI 0.33 to 0.69), a significant treatment-by-subgroup interaction (P=0.03) indicated a greater treatment effect in the lipid triad subgroup than the isolated LDL-C elevation subgroup. Conclusions - Patients with elevated LDL-C, low HDL-C, and elevated triglycerides were more likely than patients with isolated LDL-C elevation to have other characteristics of the metabolic syndrome, had increased risk for CHD events on placebo, and received greater benefit with simvastatin therapy.

  • 5.
    Blomberg, Björn
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Helicobacter pylori: Prevalence, heterogeneity, and ulcerogenic properties1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In 117. unselected patients H. pylori infection was found in 49.6% by combining culture and acndme orange stammg of hssue sections. Infection was equally common in the gastric body and antrum. The activity of gastritis was generally higher in the antrum. The overallagreement between acridine orange stain and culture was 0.93.

    Formalin treated H. pylori whole cells were used to immunize rabbits. With the aid of coagglutination and indirect immunofluorescence all H. pylori strains tested were shown to contain cross reactive antigens, but no serum cross-reacted with all strains tested. Multiple, antigenically different, isolates were found in some patients and a provisional serogrouping based on heat-stable antigens was proposed.

    Acid glycine extracts from four H. pylori strains were prepared. Rabbit antisera against these, and ten further, strains showed extensive cross-reactions with all four extracts. An EIA based on H. pylori strain NCTC 11637 had a sensitivity of 90 % and a specificity of 87 %.

    In 197 unselected patient culture, histopathology using acridine orange or Giemsa staining, and serology was evaluated. 33.5 % of patients were infected by H. pylori. The sensitivities for culture/acridine orange stain/Giemsa stain were 0.94/0.86/0.91 respectively. The specificities were 1.0/1.0/0.84. For two commercial serologic tests the negative predictive values were 0.93/0.95 respectively. A strategy of serologic screening to avoidunnecessary endoscopies was suggested, but that positive serology be confirmed by histopathology.

    Sixty-one human gastric isolates of H. pylori were tested for their ability to induce oxidative burst in human neutrophils. A cell bound, heat-labile, property able to induce a strong and rapid oxidative burst in neutrophils in the abscence of opsonins, was found in about one third of strains tested. This property was significantly associated with peptic ulcer disease(p=0.0261, Fisher's exact test).

    Fifty-four clinical isolates of H. pylori were tested for cytotoxin production and their ability to induce oxidative burst in human neutrophils. Nonopsonised, 20 strains showed a rapid and strong oxidative burst, 30 a slow and weak response, and four remaining gave inconclusive results. Cytotoxin production was seen in 10 of 20 rapid and strong inducers, but only in 3 of 30 with a slow and weak response (p=0.0027, Fisher's exact test). 11/15 of the cytotoxin producing strains (p=0.0135) and 13/20 of the rapid and strong inducers (p=0.0209) were from 22 patients with peptic ulcer disease. The ability of some nonopsonised H. pylori to activate neutrophils showed eo-variation with cytotoxin production, but the two properties seem to be independent markers of peptic ulcer disease.

    With theuse of electron microscopy the interactions of human neutrophils with four nonopsonised H. pylori strains, two rapid and strong, two slow and weak inducers of neutrophil oxidative burst were studied in morphologic detail. The rapid inducers were phagocytosed within minutes, whereas the slow inducers showed little reaction even after one hour.

    Conclusions: Histopathology using acridine orange or Giernsa stains correlates well with culture. Serologic screening might be of value to reduce unnecessary endoscopies. A cellbound heat-labile property of some H. pylori strains able to nonopsonised induce a rapid oxidative burst in neutrophils is significantly associated with peptic ulcer disease. This property is also associated with, but independent of, cytotoxin production.

  • 6.
    Blomqvist, Henrik
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Monocyte chemoattractant protein-1 and CC-chemokine receptor-2 in two different conditions related to atherosclerosis2004Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Atherosclerosis is the leading cause of death in the industrialized parts of the world. The pathological process is characterised by increased lipid influx to the arterial wall due to elevated circulating levels of low density lipoprotein (LDL). LDL is oxidatively modified by reactive oxygen species forming oxLDL. OxLDL is highly proinflammatory and is initiating an inflammatory response in the artery by up-regulation of proinflammatory signals e.g. Monocyte chemoattractant protein-1 (MCP-1). MCP-1 is promoting monocyte arrest on the endothelium and subsequent transmigration to the intima. MCP-1 is acting through the CC-chemokine receptor-2 (CCR2) on monocytes. MCP-1 and CCR2 are playing key-roles in atherogenesis through their effect on monocyte recruitment. In this thesis MCP-1 and CCR2 were studied in two clinically different conditions related to atherosclerosis - isolated asymptomatic hypercholesterolaemia and diagnosed coronary artery disease (CAD). We wanted to study the possible differences of proatherogenic patterns in clinical conditions that are at opposite ends in the clinical spectrum of atherosclerosis.

    In paper I, we studied if plasma levels of MCP-1 and the gene expression of CCR-2 were elevated above normal in subjects with asymptomatic, isolated hypercholesterolaemia and if statin treatment could influence plasma levels of MCP-1 and other inflammatory markers. In paper ll we studied the same parameters but in patients with diagnosed CAD as stable angina pectoris and acute coronary syndrome. In neither study we could see any differences regarding MCP-1 or CCR2 between patients and controls. However, in the CAD patients we could see an increased inflammatory activity as elevated levels of CRP. This inflammatory activity was not reflected on any other of the inflammatory markers analysed. In conclusion, the results from this thesis do not support the idea of circulating MCP-1 and CCR2 gene expression on circulating monocytes as clinical markers of atherosclerosis in these patient categories.

    List of papers
    1. Monocyte chemoattractant protein‐1 and CC‐chemokine receptor‐2 in severe hypercholesterolaemia
    Open this publication in new window or tab >>Monocyte chemoattractant protein‐1 and CC‐chemokine receptor‐2 in severe hypercholesterolaemia
    2003 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 63, no 7-8, p. 513-519Article in journal (Refereed) Published
    Abstract [en]

    Objectives: To investigate whether plasma concentrations of monocyte chemoattractant protein‐1 (MCP‐1) and the gene expression of its receptor on the monocyte cell surface CCR‐2 were elevated above normal in subjects with asymptomatic, isolated hypercholesterolaemia and if statin treatment could influence this cytokine.

    Methods: The investigation was designed as a cross sectional study followed by a single, blind, treatment study of patients receiving pravastatin 80 mg/day for 8 weeks. The study included 23 patients with severe hypercholesterolaemia (LDL>5.2 mmol/L) and 39 normocholesterolaemic controls. Blood samples were obtained from patients and controls at baseline and from patients at end of the study and analysed for lipoproteins and inflammatory mediators: MCP‐1, high‐sensitivity C‐reactive protein (HS‐CRP). Isolated peripheral mononuclear cells were analysed for CCR‐2 gene expression.

    Results: Mean plasma LDL‐C was significantly higher in patients than in controls. No difference in plasma MCP‐1 levels or CCR‐2 gene expression was seen between the groups at baseline, nor were there any differences in plasma concentrations of CRP. After treatment with pravastatin, LDL‐C decreased by 31%. Treatment did not significantly affect the levels of MCP‐1 or CCR‐2 gene expression, nor was CRP affected by treatment with pravastatin.

    Conclusions: Our study does not support the view that MCP‐1 plasma levels and CCR‐2 gene expression in circulating monocytes are directly responsible for the monocyte recruitment into the arterial intima in patients with severe asymptomatic hypercholesterolaemia. In addition, the inflammatory response of a high concentration of LDL‐C in isolated asymptomatic hypercholesterolaemia is minute.

    Keywords
    CC‐chemokine receptor‐2, C‐reactive protein, hypercholesterolaemia, inflammation, monocyte chemoattractant protein‐1, pravastatin
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26817 (URN)10.1080/00365510310003274 (DOI)000187774200008 ()11429 (Local ID)11429 (Archive number)11429 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13
    2. Monocyte chemoattractant protein‐1 and CC‐chemokine receptor‐2 in coronary artery disease
    Open this publication in new window or tab >>Monocyte chemoattractant protein‐1 and CC‐chemokine receptor‐2 in coronary artery disease
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Objectives: To investigate the expression of monocyte chemoattractant protein-1 (MCP-1) and CC chemokine receptor-2 (CCR-2) in circulating monocytes in patients with stable (SAP) and acute coronary syndrome (ACS), and relate the findings to circulating levels of MCP-1 and other inflammatory biomarkers.

    Methods: The study included 40 patients each with stable CAD and unstable CAD, and a control group of 50 age- and sex-matched healthy persons. Whole blood was taken and sera were analyzed for MCP-1, IL-6, sVCAM-1, siCAM-1 and P-selectin using ELISA and CRP was analysed by Tina-quant CRP high sensitive assay. Monocytes were isolated from whole blood and were analyzed for CCR-2 and MCP-1 gene expression using realtime RT-PCR.

    Results: No significant differences in gene expression of MCP-1 or CCR-2 were seen between the groups. Neither were any differences in circulating levels of MCP-1-seen. Serum levels of sVCAM-1, siCAM-1 and sP-selectin did not differ between the groups. Mean CRP levels were elevated in the ACS group compared to controls and SAP. Patients with SAP had lower levels compared to controls, probably reflecting the extensive use of statins in this group (96 %). IL-6 was significantly higher in ACS compared to controls and SAP. Positive correlations were seen between MCP-1 vs. sVCAM-1 and sICAM-1.

    Conclusions: Neither patients with SAP nor ACS had different MCP-1 or CCR-2 gene expression compared to controls. The serum levels of MCP-1 did not differ between the groups. In this study, we can not see circulating MCP-1 or CCR-2 gene expression in monocytes as useful clinical tools to decide the severity of CAD in this population.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-97349 (URN)
    Available from: 2013-09-10 Created: 2013-09-10 Last updated: 2013-09-10
  • 7.
    Blomqvist, Henrik
    et al.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Jonasson, L.
    Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
    Olsson, A.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Monocyte chemoattractant protein‐1 and CC‐chemokine receptor‐2 in coronary artery diseaseManuscript (preprint) (Other academic)
    Abstract [en]

    Objectives: To investigate the expression of monocyte chemoattractant protein-1 (MCP-1) and CC chemokine receptor-2 (CCR-2) in circulating monocytes in patients with stable (SAP) and acute coronary syndrome (ACS), and relate the findings to circulating levels of MCP-1 and other inflammatory biomarkers.

    Methods: The study included 40 patients each with stable CAD and unstable CAD, and a control group of 50 age- and sex-matched healthy persons. Whole blood was taken and sera were analyzed for MCP-1, IL-6, sVCAM-1, siCAM-1 and P-selectin using ELISA and CRP was analysed by Tina-quant CRP high sensitive assay. Monocytes were isolated from whole blood and were analyzed for CCR-2 and MCP-1 gene expression using realtime RT-PCR.

    Results: No significant differences in gene expression of MCP-1 or CCR-2 were seen between the groups. Neither were any differences in circulating levels of MCP-1-seen. Serum levels of sVCAM-1, siCAM-1 and sP-selectin did not differ between the groups. Mean CRP levels were elevated in the ACS group compared to controls and SAP. Patients with SAP had lower levels compared to controls, probably reflecting the extensive use of statins in this group (96 %). IL-6 was significantly higher in ACS compared to controls and SAP. Positive correlations were seen between MCP-1 vs. sVCAM-1 and sICAM-1.

    Conclusions: Neither patients with SAP nor ACS had different MCP-1 or CCR-2 gene expression compared to controls. The serum levels of MCP-1 did not differ between the groups. In this study, we can not see circulating MCP-1 or CCR-2 gene expression in monocytes as useful clinical tools to decide the severity of CAD in this population.

  • 8.
    Blomqvist, Henrik
    et al.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Olsson, Anders
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Monocyte chemoattractant protein‐1 and CC‐chemokine receptor‐2 in severe hypercholesterolaemia2003In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 63, no 7-8, p. 513-519Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate whether plasma concentrations of monocyte chemoattractant protein‐1 (MCP‐1) and the gene expression of its receptor on the monocyte cell surface CCR‐2 were elevated above normal in subjects with asymptomatic, isolated hypercholesterolaemia and if statin treatment could influence this cytokine.

    Methods: The investigation was designed as a cross sectional study followed by a single, blind, treatment study of patients receiving pravastatin 80 mg/day for 8 weeks. The study included 23 patients with severe hypercholesterolaemia (LDL>5.2 mmol/L) and 39 normocholesterolaemic controls. Blood samples were obtained from patients and controls at baseline and from patients at end of the study and analysed for lipoproteins and inflammatory mediators: MCP‐1, high‐sensitivity C‐reactive protein (HS‐CRP). Isolated peripheral mononuclear cells were analysed for CCR‐2 gene expression.

    Results: Mean plasma LDL‐C was significantly higher in patients than in controls. No difference in plasma MCP‐1 levels or CCR‐2 gene expression was seen between the groups at baseline, nor were there any differences in plasma concentrations of CRP. After treatment with pravastatin, LDL‐C decreased by 31%. Treatment did not significantly affect the levels of MCP‐1 or CCR‐2 gene expression, nor was CRP affected by treatment with pravastatin.

    Conclusions: Our study does not support the view that MCP‐1 plasma levels and CCR‐2 gene expression in circulating monocytes are directly responsible for the monocyte recruitment into the arterial intima in patients with severe asymptomatic hypercholesterolaemia. In addition, the inflammatory response of a high concentration of LDL‐C in isolated asymptomatic hypercholesterolaemia is minute.

  • 9.
    Bodemar, Göran
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Kechagias, Stergios
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Danielson, BG
    Treatment of anaemia in inflammatory bowel disease with iron sucrose2004In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 39, no 5, p. 454-458Article in journal (Refereed)
    Abstract [en]

    Background: Inflammatory bowel disease (IBD)-associated anaemia usually responds to intravenous iron. If not, additive treatment with erythropoietin has been proposed. The objective of the present retrospective study was to evaluate the effectiveness of treatment with iron sucrose alone. Methods: Sixty-one patients with IBD and anaemia (average haemoglobin 97 g/L) were treated with iron sucrose (iron dose 1.4 ± 0.5 g). The indications for iron sucrose were poor response and/or intolerance to oral iron. Treatment response was defined as an increase in haemoglobin of ≥20 g/L or to normal haemoglobin levels (>120 g/L). Two independent investigators retrospectively assessed laboratory variables, clinical findings, and concomitant medication. Results: Two patients were transferred to other hospitals after treatment and therefore could not be evaluated. Fifty-four of the remaining 59 patients (91%) responded within 12 weeks. Sixty percent of the patients had responded within 8 weeks. Five patients had no or only a partial response to iron sucrose of which three had prolonged gastrointestinal blood losses. Eight patients with normal or elevated levels of ferritin could be considered to have anaemia of chronic disease, and all of them responded to iron sucrose. During a follow-up period of 117 ± 85 (4-291) (mean ± s (standard deviation) (range)) weeks 19 patients (32%) needed at least one second course of iron sucrose because of recurrent disease. Conclusions: Anaemia associated with IBD can be successfully treated with intravenously administered iron sucrose, provided that bowel inflammation is treated adequately and enough iron is given. Treatment with iron sucrose is safe. Follow-up of haemoglobin and iron parameters to avoid further iron deficiency anaemia is recommended.

  • 10. Bojestig, M
    et al.
    Nyström, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Karlberg, Bengt E
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    The renin-angiotensin-aldosterone system is suppressed in adults with Type 1 diabetes2000In: jraas. Journal of the renin-angiotensin-aldosterone system, ISSN 1470-3203, E-ISSN 1752-8976, Vol. 1, no 4, p. 353-356Article in journal (Refereed)
    Abstract [en]

    Poor glycaemic control and high blood pressure are two important risk factors for the development of retinopathy and nephropathy in Type 1 diabetes. The renin-angiotensin-aldosterone system (RAAS) may be involved in this process, since treatment with angiotensin-converting enzyme (ACE) inhibitors postpones the development of these complications. We investigated whether plasma renin activity (PRA), plasma angiotensin II (Ang II) and atrial natriuretic peptide (ANP) differed in Type 1 diabetic patients compared with healthy controls. We recruited 80 patients with Type 1 diabetes of more than 10 years' duration and 75 age-matched controls. We found that PRA and Ang II concentrations were significantly lower in patients than in the controls. The levels of ANP, on the other hand, were higher in patients than in controls. PRA correlated negatively to the mean value of HbA1c during the previous five years. PRA and Ang II were significantly lower in patients with mean HbA1c. >8.4% compared with those with mean HbA1c 7.2%. In summary, we found patients with Type 1 diabetes to have RAAS suppression and increased ANP levels, suggesting a state of fluid retention.

  • 11.
    Bojestig, Mats
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Glycaemic Control and Complications in Type 1 Diabetes1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    There have been substantial changes in the management of diabetes since the 1960' s.We studied all 213 patients in our catchment area in whom Type I diabetes was diagnosed before the age of 15 years between 1961 and 1980, 92% were followed from the onset of diabetes to 1991 or to the time of death

    The cumulative incidence of diabetic nephropathy has decreased substantially in recent decades from 30% to 9% after 25 year's diabetes duration, probably as a result of improved glycaemic control. Neither the cumulative incidence of severe retinopathy nor hypertension (140/90mmHg) changed during the last decades.

    The risk to develop severe retinopathy or nephropathy was higher in patients with Very Poor glycaemic control (HbA1c;::.8.4%) vs. patients with Poor control (HbA1c ~ 7 .2<8.4% )(p<0.001). Patients with Poor control had an increased risk to develop severe retinopathy vs. patients with Good control (HbA1c<7 .2% )(p<0.008) but there was no difference in the risk for nephropathy. No patients with Good control developed nephropathy and only one patient developed severe retinopathy during 25 years of diabetes. Up to a diabetes duration of 25 years both diabetic nephropathy and severe retinopathy can be avoided but the degree of glycaemic control needed for prevention differs.

    The course of microalbuminuria during the 1980's was studied with a 10-year follow up of 109 Type 1 diabetes patients. Only 5 (19%) of the initially micro-albuminuric patients developed macro-albuminuria during the 10 year follow up period and 15 (58%) patients decreased their AER to normal. The initially micro-albuminuric patients, who normalised their AERimproved their glycemic control. In the majority of patients with micro-albuminuria in whom it is possible to obtain a good glycemic control, micro-albuminuria will disappear and the risk of developing nephropathy is markedly reduced.

    PRA and All concentrations were significantly lower in Type 1 diabetic patients (n=80) than in matched healthy controls (n=75). ANP levels were higher in patients than in controls. In the patients PRA correlated negatively to the mean value of HbA1c during the previous five years. Patients with Type 1 diabetes, specially those with very poor glycaemic control, have a suppressed RAS and increased ANP levels.

  • 12.
    Bornfeldt, Karin E.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Actions and interactions of insulin-like growth factor-I and insulin in vascular smooth muscle1991Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Insulin-like growth factor-I (IGF-I) is a polypeptide with structural and biological similarities with insulin, and the receptors for IGF-I and insulin are homologous. The present investigation was devoted to the actions and interactions of IGF-I and insulin in vascular smooth muscle.

    In vascular smooth muscle from intact arteries and in cultured vascular smooth muscle cells there are abundant IGF-I receptors, but very few insulin receptors. IGF-I and insulin stimulated proliferation of cultured vascular smooth muscle cells, and the effects were probably mediated via the IGF-I receptor. However, the maximal growthpromoting effect of IGF-I was twice the maximal effect of insulin. If an acidic amino acid was substituted for the basic amino acid histidine in insulin B-chain (BlO His:::} Asp), like in IGF-I, the maximal growth-promoting activity reached the effect of IGF-1. The amino acid in position 10 in insulin B-chain may thus be important for the growthpromoting activity of insulin.

    Vascular smooth muscle cells express IGF-1 mRNA and produce imm1,1noreactive IGF-1 in vitro. Levels of IGF-1 m RNA were decreased by platelet-derived growth factor (PDGF-BB), basic fibroblast growth factor (bFGF) and serum, whereas IGF-1 and high concentrations of insulin increased IGF-I rnRNA and immunoreactive IGF-I. It is thus possible that IGF-1 is able to increase its own production in an autocrine loop withpositive feedback. The growth-promoting effects of IGF-1 and insulin were weak compared to the effects ofPDGF-BB and bFGF. The results indicate qualitative as well as quantitative differences between IGF-1 and insulin compared to PDGF-BB and bFGF.

    IGF-1 gene expression in aortic tissue was found to be decreased by diabetes and fasting in vivo, and the levels were restored if diabetic rats were treated with insulin.

    Vascular smooth muscle proliferation induced by balloon catheterization was found to be impaired by diabetes and increased by insulin-treatment in vivo, although not to the levels in normal rats. IGF-1 stimulated vascular smooth muscle proliferation in diabetic rats in vivo without affecting the diabetic state, and IGF-I gene expression was increased in proliferating vascular smooth muscle. The results suggest that IGF-I is involved in vascular smooth muscle proliferation in vivo.

    In conclusion, insulin is less potent than IGF-1 in stimulating proliferation of vascular smooth muscle, and the growth-promoting effects of insulin are weaker than the effects ofiGF-1, suggesting that insulin in concentrations found in plasma has little direct effect on vascular smooth muscle proliferation. IGF-1 is probably of importance for vascular smooth muscle proliferation, and the results suggest that IGF-1 can be locally produced and regulated in the vascular wall.

  • 13.
    Bramnert, Margareta
    et al.
    Malmö.
    Ekman, Bertil
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-endo.
    Karlsson, Anders
    Uppsala.
    Olsson, Tommy
    Umeå.
    Rosén, Thord
    Göteborg.
    Valdemarsson, Stig
    Lund.
    Werner, Sigbritt
    Stockholm.
    Riktlinjer för substitutionsbehandling vid hypofyssvikt hos vuxna.2003In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 100, p. 3043-3049Article in journal (Other academic)
  • 14.
    Broqvist, Mats
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Clinical studies in severe heart failure: neurohormonal, electrolyte and metabolic aspects1994Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Congestive heart failure is a common and complex syndrome with a poor prognosis. Although heart disease is usually the primary event, the clinical syndrome is characterised by several extra-cardiac manifestations. Neurohormonal activation seems to play a crucial role for these manifestations and the progression of the disease.

    Twenty-seven consecutive patients with acute left ventricular heart failure were found to have increased plasma concentrations of atrial natriuretic peptide, arginine vasopressin and catecholamines, while the renin-angiotensin system was not activated until diuretic therapy was introduced. To counteract this activation it seems suitable to combine the diuretics with an angiotensin-converting enzyme inhibitor.

    Skeletal muscle biopsies were performed in 22 patients participating in the CONSENSUS trial, which was a randomised, double-blind, placebo-controlled study of the effects of the angiotensin-converting enzyme inhibitor enalapril on mortality in patients with severe congestive heart failure. The biopsies revealed decreased content of magnesium andpotassium while sodium and water were retained in skeletal muscle. Ventricular arrhythmias occurred frequently. The ventricular arrhythmias seemed to be related to lower serum levels of potassium, but no significant correlations were found to muscle electrolyte content. This may indicate that the ratio of electrolytes across the cell membrane is moreimportant for the development of arrhythmias than changes in the absolute amount of electrolytes are. The muscle biopsies also revealed metabolic derangement with decreased content of energy-rich compunds, such as adenosine triphosphate (ATP), phosphocreatine and glycogen,Treatment with enalapril did not seem to influence these peripheral abnormalities, but some beneficial effect was found regarding the prevalence of ventricular arrhythmias.

    In another 22 patients with severe congestive heart failure, similar signs of energy depletion were found in skeletal muscle biopsies. Nutritional assessment, based on anthropometry and serum protein levels, revealed signs of malnutrition in only two patients which is in contrast to a previous reported prevalence of 30-50 % in patients with severe congestive heartfailure. Long-term oral dietary supplementation, given in a randomised, double-blind and placebo-controlled manner, did not change muscle energy content, neither did exercise tolerance improve. Thus, malnutrition did not seem to be a prerequisite for the metabolic changes found in skeletal muscle. Consequently, routine dietary supplementation does not seem to be indicated in patients with congestive heart failure.

  • 15.
    Broström, Anders
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Sleep and health-related quality of life in patients with chronic heart failure and their spouses: a descriptive and interventional study2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The general aim of this thesis was to describe and compare the sleep situation and health-related quality of life in patients with chronic heart failure and their spouses, as well as to evaluate the effects of an intervention with 3-months ofhome based oxygen treatment. Descriptive designs were used to describe how patients with chronic heart failure conceived their sleep situation (I), decisive situations that influenced spouses' support to patients with chronic heart failure in relation to the couple's sleep situation (II), and self-assessed sleep difficulties, daytime sleepiness and their relation to health-related quality oflife in men and women with chronic heart failure, as well as to make a comparison with data from a norm population (III). An interventional design was used to determine the effects of 3-months of home based oxygen treatment regarding both subjective and objective outcomes (IV).

    Daily life, the disease itself and cardiac symptoms influenced the sleep situation and led to ensuing effects, such as fatigue, listlessness, loss of temper, loss of concentration, a need for daytime sleep, seclusion, information and counseling. Patients handled their sleep disturbances by means of support from their psychosocial environment as well as coping mechanisms related to developed patterns of daily life (I). Decisive situations inhibited or stimulated spouses' support to patients with heart failure, in relation to the couples' sleep situation (II). Self-assessed sleep difficulties such as difficulties initiating sleep, difficulties maintaining sleep, and excessive daytime sleepiness were common in patients with chronic heart failure and gave a decreased health-related quality of life compared to chronic heart failure patients without sleeping difficulties (III). Sleep disordered breathing, with a dominance of central sleep apnea was a very common problem, with a high prevalence, but patients suffering from objectively registered sleep disordered breathing did not show decreased health-related quality of life compared to chronic heart failure patients without sleep disordered breathing. A long-term intervention with nocturnal home based oxygen improved functional exercise capacity for both the whole group of patients with chronic heart failure, as well as in patients with chronic heart failure where sleep disordered breathing occurred. The intervention did not give any persistent improvements regarding cardiac function, objective sleep, subjective sleep, sleep disordered breathing, or healthrelated quality of life (IV).

    Sleep disturbances are a complex situation where sleep disordered breathing can be seen as one possible organic trigger, together with psychosocial, as well as environmental factors causing a chain reaction with disturbed sleep, daytime sleepiness and decreased health-related quality of life that leads to physical, social, and mental consequences and needs. Further studies are therefore needed from a holistic perspective on both patients with chronic heart failure and their spouses.

    List of papers
    1. Patients with congestive heart failure and their conceptions of their sleep situation
    Open this publication in new window or tab >>Patients with congestive heart failure and their conceptions of their sleep situation
    2001 (English)In: Journal of Advanced Nursing, ISSN 0309-2402, E-ISSN 1365-2648, Vol. 34, no 4, p. 520-529Article in journal (Refereed) Published
    Abstract [en]

    Aim. To describe, from a nursing perspective, how patients with CHF conceived their sleep situation.

    Background.  Sleep disturbances are very common in patients with congestive heart failure (CHF). Polysomnographic studies have shown that the total duration of sleep is shorter and the sleep structure disturbed, with frequent arousals and sleep stage changes.

    Methods.  A qualitative descriptive design inspired by a phenomenographic approach was employed. Conceptions were collected through interviews with 20 strategically chosen CHF patients.

    Findings.  The findings showed that the patients’ sleep was affected by their daily activities, the disease itself and cardiac symptoms. The sleep disturbances gave effects such as fatigue, listlessness, loss of concentration and loss of temper. These effects led to a need for daytime sleep, seclusion, counselling and information. Patients handled their sleep disturbances through coping mechanisms related to developed patterns of daily life and through support from their psychosocial environment.

    Conclusions. Through an increased awareness of the causes of sleep disturbances in CHF patients, nurses can more effectively meet their caring needs and reduce the psychological stressors that patients develop. Information and education, both to patients and the next of kin, about the disease and the sleep situation, especially good sleeping habits, can help patients to better cope with sleep disturbances.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26827 (URN)10.1046/j.1365-2648.2001.01781.x (DOI)11442 (Local ID)11442 (Archive number)11442 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13
    2. Congestive heart failure, spouses' support and the couple's sleep situation: a critical incident technique analysis
    Open this publication in new window or tab >>Congestive heart failure, spouses' support and the couple's sleep situation: a critical incident technique analysis
    2003 (English)In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 12, no 2, p. 223-233Article in journal (Refereed) Published
    Abstract [en]

    • Sleep related breathing disorders are common as well as a poor prognostic sign associated with higher mortality in patients with congestive heart failure (CHF). These patients often have a shorter total duration of sleep, disturbed sleep structure and increased daytime sleepiness, which can negatively affect all dimensions of the life situation. The spouse has an important role in supporting the patient in relation to sleep disorders, but this role may be adversely affected by the sleep situation of the couple.

    •  The aim of this study was to describe decisive situations that influence spouses' support to patients with CHF in relation to the couple's sleep situation.

    • A qualitative descriptive design using critical incident technique was employed. Incidents were collected by means of interviews with 25 spouses of patients with CHF, strategically selected from two hospital-based specialist clinics in southern Sweden.

    •  Two main areas emerged in the analysis: support stimulating situations and support inhibiting situations. Support stimulating situations described how spouses' support was positively affected by their own adaptation in psychosocial or practical situations, and receiving help from others. Support inhibiting situations described how the spouses' support was negatively affected by sleep disturbances as a result of the patient's symptoms, anxiety in relation to the disease, limitations as a result of the sleeping habits, dissatisfaction with care related to the sleep situation, and being left to cope alone with the problems.

    •  An increased understanding of the stimulating and inhibiting situations influencing spouses' support for patients with CHF can guide health care personnel in deciding if an intervention is needed to improve the sleep situation for patient and spouse.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26829 (URN)10.1046/j.1365-2702.2003.00692.x (DOI)11444 (Local ID)11444 (Archive number)11444 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13
    3. Sleep difficulties, daytime sleepiness, and health-related quality of life in patients with chronic heart failure
    Open this publication in new window or tab >>Sleep difficulties, daytime sleepiness, and health-related quality of life in patients with chronic heart failure
    2004 (English)In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 19, no 4, p. 234-242Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:

    Normal sleep changes with age in duration, fragmentation, and depth. The prevalence of insomnia is high in the elderly general population. In patients with chronic heart failure (HF) objective sleep assessments have shown disturbances such as a shorter total duration of sleep, frequent arousals, and sleep stage changes.

    OBJECTIVE:

    To describe self-assessed sleep difficulties, daytime sleepiness, and their relation to health-related quality of life (HRQOL) in men and women with HF, as well as to make a comparison to data from a norm population.

    METHODS:

    Cross-sectional design including 223 patients with HF, New York Heart Association classification II-IV, assessed using the Uppsala Sleep Inventory-Chronic Heart Failure, the Epworth Sleepiness Scale, Medical Outcomes Study 36-Item Short Form Health Survey, and Minnesota Living With Heart Failure Questionnaire.

    RESULTS:

    The most commonly reported sleep difficulties were initiating and maintaining sleep. The ratio of habitual sleep to the amount of estimated need for sleep was significantly shorter for women (P < .05), and the number of awakenings per night was significantly increased for men (P < .001). A total of 21% suffered from daytime sleepiness. Patients suffering from difficulties maintaining sleep, initiating sleep, and early morning awakenings reported significantly lower HRQOL in almost all dimensions of the SF-36 (P < .05-P < .001) compared to patients without sleeping difficulties, as well as to the normal population. The disease-specific Minnesota Living With Heart Failure Questionnaire showed significantly reduced (P < .05-P < .001) HRQOL as measured by the total and subscale scores for patients suffering from sleeping difficulties compared to patients without sleeping difficulties.

    CONCLUSION:

    Patients with HF have a reduced HRQOL especially if difficulties maintaining sleep, initiating sleep, and early morning awakenings are involved.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24308 (URN)15326979 (PubMedID)3931 (Local ID)3931 (Archive number)3931 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
    4. Effects of long-term nocturnal oxygen treatment in patients with severe heart failure
    Open this publication in new window or tab >>Effects of long-term nocturnal oxygen treatment in patients with severe heart failure
    Show others...
    2005 (English)In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 20, no 6, p. 385-396Article in journal (Refereed) Published
    Abstract [en]

    Sleep-disordered breathing (SDB) is common in patients with heart failure (HF) and leads to disturbed sleep. The objective of this study was to determine the persistent effects of long-term nocturnal oxygen treatment in patients with severe HF regarding (1) objective outcomes, such as sleep, SDB, cardiac function, and functional capacity; (2) subjective outcomes, such as self-assessed sleep difficulties, daytime sleepiness, and health-related quality of life (HRQOL); and (3) the relationship between objective and subjective outcomes. In this open nonrandomized experimental study, 22 patients, median age 71 years, with severe HF were studied before and after 3 months of receiving nocturnal oxygen. The measures used were overnight polysomnography, echocardiography, 6-minute walk test, self-assessed sleep difficulties (Uppsala Sleep Inventory-HF), daytime sleepiness (Epworth Sleepiness Scale), and HRQOL (36-Item Short Form Health Survey and Minnesota Living with Heart Failure Questionnaire). SDB, with a 90% dominance of central sleep apnea, occurred in 41% of the patients with severe HF before intervention. After intervention, functional capacity improved for both the whole group of patients with HF (P < .01) and HF patients with SDB (P < .05). No improvements regarding cardiac function, objective sleep, subjective sleep, or SDB were seen, except for a decrease of > or = 4% desaturations (P < .05). HRQOL did not differ significantly between HF patients with and without SDB before or after intervention with nocturnal oxygen. Long-term nocturnal oxygen treatment improved functional capacity in patients with severe HF, with or without SDB. No improvements were seen regarding sleep, daytime sleepiness, SDB, cardiac function, or HRQOL.

    Keywords
    chronic heart failure, functional capacity, health-related quality of life, oxygen treatment, sleep, sleep-disordered breathing
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-31574 (URN)16485622 (PubMedID)17375 (Local ID)17375 (Archive number)17375 (OAI)
    Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13
  • 16.
    Brändström, H.
    et al.
    Department of Medical Sciences, Uppsala University, Sweden.
    Stiger, F.
    Department of Medical Sciences, Uppsala University, Sweden.
    Kahan, T.
    Division of Internal Medicine, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Melhus, H.
    Department of Medical Sciences, Uppsala University, Sweden.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Öhman, K.P.
    Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences. Departments of Experimental and Clinical Science, Astra Zeneca R&D Mölndal, Sweden.
    Malmqvist, K.
    Division of Internal Medicine, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Lind, L.
    Department of Medical Sciences, Uppsala University, Sweden.
    Kindmark, A.
    Department of Medical Sciences, Uppsala University, Sweden and Departments of Experimental and Clinical Science, Astra Zeneca R&D Mölndal, Sweden.
    A single nucleotide polymorphism in the promoter region of the osteoprotegerin gene is related to intima-media thickness of the carotid artery in hypertensive patients. The Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA)2004In: Blood Pressure, ISSN 0803-7051, E-ISSN 1651-1999, Vol. 13, no 3, p. 152-157Article in journal (Refereed)
    Abstract [en]

    Osteoprotegerin (OPG) is a secreted member of the tumor necrosis factor receptor family, and in previous studies has been shown to regulate osteoclast activity and differentiation. Ablation of the OPG gene in mice results in calcification of the aorta and renal arteries. We have previously reported an association between a single nucleotide polymorphism in the promoter region of OPG and vascular morphology and function in healthy humans. The objective with this study was to confirm our previous results in a larger population, and in addition, to study subjects with hypertension. The OPG genotype was determined by restriction fragment length and the intima-media thickness (IMT) of the common carotid artery was measured by ultrasound in 100 patients with hypertension and left ventricular hypertrophy, and 75 healthy normotensive control subjects. In the hypertensive group subjects with the CC genotype (n = 24) showed a significantly increased IMT compared to those with the TC (n = 52, p = 0.007) and TT (n = 24, p = 0.009) genotype, in the hypertensive group only (mean ± SD for TT = 0.88 ± 0.21 mm, TC = 0.90 ± 0.16 mm, CC = 1.05 ± 0.31 mm). The allele distribution did not differ between hypertensive and control individuals. The present study confirms our previous finding and shows that polymorphism in the promoter region of OPG is associated with vascular morphology in hypertensive subjects. © 2004 Taylor & Francis on licence from Blood Pressure.

  • 17. Cherfan, P
    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.
    Jonasson, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Effects of simvastatin on human t-cells in vivo2005In: European Atherosclerosis Society Congress,2005, 2005Conference paper (Other academic)
  • 18.
    Dahlfors, Gunilla
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans J.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Expression of insulin-like growth factor binding proteins and transforming growth factor-ß1 in human microvascular endothelial and bovine aortic endothelial cells, no effects of high glucoseManuscript (preprint) (Other academic)
    Abstract [en]

    Vascular complications are the major cause of morbidity and mortality in patients with diabetes mellitus. Insnlin-like growth factor-I (IGF-I) and transforming growth factor-ß1 (TGF-ß1) are two growth factors that regnlate vascular smooth muscle cell function in vivo and might be involved in the development of diabetic vascnlar complications. In this study we measnred the expression of IGF-binding proteins (IGFBPs) and TGF-ß1 in human dermal microvessel endothelial cells (HDMEC). We also studied the effect of high glucose levels on the expression of IGFBPs and TGF-ß1 in cnltured HDMEC and bovine aortic endothelial cells (BAEC). Gene expression was measured by an RNase-protection assay and proteins secreted into conditioned medium by ELISA or Western blot. The HDMEC expressed mRNAs for IGF-I and IGFBP-2 through -6 of which IGFBP-4 was the most excessively expressed and IGFBP-2 and -4 were detected in conditioned medium. Culture of HDMEC in high glucose (25 mM) for two passages did not change mRNA expressions for IGFBP-2, -3 or -4 significantly. Neither did low glucose+ mannitol (5.6 mM+ 20 mM) have any effect. In BAEC, high glucose (25 mM) for 48 h or 96 h did not affect IGFBP-3, -4 or -5 mRNA or protein and exposnre of BAEC to high glucose for two passages did also not affect IGFBP mRNA. TGF-ß1 mRNA was expressed by both BAEC and HDMEC. High glucose for two passages did not alter TGF-ß1 gene expression in either BAEC or HDMEC. In conclusion, we show that HDMEC express IGFBPs and TGF-ß1 andthat high glucose does not affect the expression in either HDMEC or BAEC.

  • 19.
    Dahlfors, Gunilla
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Chen, Yun
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Gustafsson, Bertil
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC-2, GE: endomed. Linköping University, Faculty of Health Sciences.
    Inhibitory effect of diabetes on proliferation of vascular smooth muscle after balloon injury in rat aorta2000In: Experimental Diabetes Research, ISSN 1687-5214, E-ISSN 1687-5303, Vol. 1, no 2, p. 101-109Article in journal (Refereed)
    Abstract [en]

    The effect of streptozotocin-induced diabetes on cell proliferation in rat aortic intima-media, as well as on local gene expression of transforming growth factor-β1 (TGF-β1) was studied. TGF-β1 mRNA was measured by solution hybridization and TGF-β1 protein by ELISA. Proliferation was measured by bromodeoxyuridine incorporation into DNA two days after balloon injury. All BrdU-labelled cells observed were smooth muscle cells. After a diabetes duration of 2 and 4 weeks, labelled cells were significantly fewer compared with controls. Circulating levels of total TGF-β1 were lowered in rats with 2 weeks diabetes. Although the balloon injury procedure by itself stimulated the gene expression of TGF-β1, no significant difference in TGF-β1 mRNA content between diabetic and control rats after injury was found. In conclusion: vascular smooth muscle proliferation in vivo is inhibited by the diabetic state in this model of insulin deficient diabetes and this inhibition is not related to an impaired local expression of TGF-β1.

  • 20.
    Dahlfors, Gunilla
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Chen, Yun
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Wasteson, Maria
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans J.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    PDGF-BB-induced DNA synthesis is delayed by angiotensin II in vascular smooth muscle cells1998In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 274, no 5, p. H1742-H1748Article in journal (Refereed)
    Abstract [en]

    The interaction of ANG II with platelet-derived growth factor (PDGF)-BB-induced DNA synthesis was studied in cultured rat aortic smooth muscle cells. PDGF-BB-induced DNA synthesis was delayed (∼6–8 h) by ANG II as shown by a time-course experiment. Losartan, an AT1-receptor antagonist, blocked the transient inhibitory effect of ANG II, whereas the AT2-receptor antagonist PD-123319 had no effect. Autocrine- or paracrine-acting transforming growth factor-β1 (TGF-β1), believed to be a mediator of ANG II-induced inhibitory effects, was not responsible for the delay of PDGF-BB-induced DNA synthesis, because a potent TGF-β1 neutralizing antibody could not reverse this effect of ANG II, nor was the delay of the PDGF-BB effect caused by inhibition of PDGF-β-receptor phosphorylation as shown by Western blot analysis of immunoprecipitated PDGF-β receptor. In conclusion, our results show that ANG II can exert a transient inhibitory effect on PDGF-BB-induced proliferation via the AT1 receptor.

  • 21.
    Dahlfors, Gunilla
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans J.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Effect of nitric oxide on vascular smooth muscle cell proliferation and insulin-like growth factor binding protein expressionManuscript (preprint) (Other academic)
    Abstract [en]

    A possible interaction between nitric oxide (NO) and the insulin-like growth factor (IGF)-system was studied in cultured rat aortic smooth muscle cells. The NO-donor SNAP markedly inhibited basal and sernm-induced DNA synthesis while addition of L-NAME, an inhibitor of endogenous NO production, had no effect. L-NAME did also not significantly affect IGF-I, angiotensin II or TGF-ß1- induced effects on DNA synthesis. IGF-I was shown to stimulate the expression of IGFBP-4 mRNA, as measured by an RNase-protection assay, and angiotensin II inhibited expression of IGFBP-2 mRNA. Addition of L-NAME did not significantly change the effect of IGF-I or angiotensin II on IGFBP mRNA expression, neither did L-NAME or SNAP affect basal expression of IGFBP-2, -4 or -6 mRNA. In conclusion, we found no evidence for interaction of NO with the IGF-system in smooth muscle cells. Nitric oxide did not regulate the expression of IGFBPs and IGF-I-induced smooth muscle cell proliferation was not affected by inhibition of endogenous NO production.

  • 22.
    Ekman, Bertil
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    IGF-I in growth hormone deficiency and in type 1 diabetes2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Both GH-deficiency and type 1 diabetes are associated with low IGF-I levels. The aim with our studies was to develop a dose titration model to obtain physiological IGF-I levels in growth hormone deficiency and to evaluate the relationship between glycaemic control and IGF-I in diabetes. First we established reference values for insulin like growth factor-I (IGF-I) and insulin like growth factor bindingprotein-1 (IGFBP-1) from 101 women and 101 men randomly selected from the population registry. No gender differences in IGF-I levels were fmmd. IGF-1 decreases with advancing age in both sexes, whereas IGFBP-1 increases with age.

    Titrating the GH dose according to population based reference values of IGF-I might be a way to obtain a fairly physiological substitution dose of GH. We hypothesised that a safe and probably effective maintenance dose of GH should increase IGF-I to the mean or slightly below the mean according to age adjusted reference levels. Eighteen adult hypopituitary patients with severe GH deficiency were titrated in steps, according to age adjusted IGF-I levels, to an individual dose of recombinant GH. For comparison 17 untreated healthy control subjects were evaluated. Similar IGF-1 levels armmd the mean for corresponding age were obtained in both sexes, but the maintenance median GH dose was more than twice in the women compared to men. The :individual dose differed markedly and elderly patients needed lower GH doses due to unchanged GH-sensitivity. Six months on the maintenance GH dose induced changes in blood-glucose, lipids, and insulin sensitivity index, indicating increased insulin resistance, which compared with the controls, were a normalisation. No major changes were seen in the variables of the renin-angiotensin-system. A significant increase in atrial natriuretic peptide seems also to be a normalisation if compared with the controls. The patients had less muscle strength and endmance at baseline compared with the controls and increased the muscle strength and endmance about 10 % after GH-substitution, an effect associated with the increase in IGF-I.

    Paradoxically circulating IGF-I is decreased in type 1 diabetes despite increased GH levels. We studied 134 adult patients with type I diabetes (aged 20-60 years), without endogenous insulin secretion, and found that circulating IGF-I were decreased to about 70 % of the values in the reference population. No con·elation between glycaemic control and IGF-I levels was found.

    To conclude the GH dose obtained when normalising circulating IGF-I according to population-based IGF-I levels, depends on GH-sensitivity (gender) and the IGF-1 level aimed for (age). In comparison with matched controls several OR-dependent variables are improved. In type 1 diabetes, our results suggests that the low IGF-I levels are independent of glycaemic control, and can not be corrected with subcutaneous insulin substitution.

    List of papers
    1. Population-based reference values for IGF-I and IGF-binding protein-1: Relations with metabolic and anthropometric variables
    Open this publication in new window or tab >>Population-based reference values for IGF-I and IGF-binding protein-1: Relations with metabolic and anthropometric variables
    Show others...
    1997 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 136, no 2, p. 165-172Article in journal (Refereed) Published
    Abstract [en]

    Population-based reference values for IGF-I and IGF-binding protein-1 (IGFBP-1) have been established. One hundred and one women and the same number of men, 20–70 years old, were randomly selected from the population registry in the community of Linköping. Participation rate was 67%. Venous blood was drawn in the fasting state. Serum IGF-I was measured by RIA after acid-ethanol extraction and IGFBP-1 was determined by ELISA. IGF-I levels did not differ between genders and the decline with age was similar in men and women (men: Y=366–3·28×age (years), r =−0·61, P<0·0001; women: Y=386–3·49×age, r =−0·57, P<0·0001, P=0·4 for difference in slope). There were negative correlations between IGF-I and plasma lipids and blood pressure in both genders, but none was independent of age. Serum angiotensin-converting enzyme activity correlated positively with IGF-I in men independently from age (r =0·21, P=0·01). The distribution of IGFBP-1 was positively skewed and it was higher in women than in men (5·9±4·8 μg/l and 4·0±3·3 μg/l respectively; Mann–Whitney, P=0·002). In men and in the women not taking oestrogen, IGFBP-1 correlated positively with age (Spearman rank correlation (Spearman): men: r=0·32, P=0·002; women: r=0·24, P=0·03). C-peptide correlated negatively (Spearman: men: r =−0·38, P=0·002; women: r =−0·49, P<0·000) and sex hormone binding globulin positively with IGFBP-1 (Spearman: men: r=0·50, P<0·0001; women: r =0·55, P<0·0001).

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81631 (URN)10.1530/eje.0.1360165 (DOI)
    Available from: 2012-09-19 Created: 2012-09-19 Last updated: 2017-12-07Bibliographically approved
    2. A dose titration model for recombinant GH substitution aiming at normal plasma concentrations of IGF-I in hypopituitary adults
    Open this publication in new window or tab >>A dose titration model for recombinant GH substitution aiming at normal plasma concentrations of IGF-I in hypopituitary adults
    Show others...
    2002 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 147, no 1, p. 49-57Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE: To evaluate a dose titration model for recombinant human GH substitution in adult patients with GH deficiency, aiming at normal plasma levels of IGF-I.

    DESIGN AND METHODS: Eighteen patients participated and a start dose of 0.17 mg GH/day was used except by two men who started with 0.33 mg/day. To demonstrate a clear GH effect the patients were first titrated, with steps of 0.17 mg GH/day every 6-8 weeks, to IGF-I levels in the upper range of age-adjusted reference values. The GH dose was then reduced 1 dose step and kept for a further 6 months. For comparison we investigated 17 healthy control subjects.

    RESULTS: Plasma IGF-I was increased after 2 weeks on the start dose and did not increase further for up to 8 weeks. Women had significantly lower GH sensitivity than men measured as net increment of IGF-I on the start dose of GH. GH sensitivity was not changed by age. The plasma IGF-I levels increased from 76.3+/-47.0 (s.d.) to 237+/-97 microg/l at the end of the study (P<0.001), and similar IGF-I levels were obtained in both sexes. The maintenance median GH dose was 0.33 mg/day in males and 0.83 mg/day in females (P=0.017). The GH dose correlated negatively with age in both sexes. Body weight, very low density triglycerides, lipoprotein(a) (Lp(a)), and fasting insulin increased, whereas insulin sensitivity index (QUICKI) decreased significantly. In comparison with the controls, the patients had lower fasting blood glucose, fasting insulin and Lp(a) levels at baseline, but these differences disappeared after GH substitution. The two groups had equal insulin sensitivity (QUICKI), but 2 h oral glucose tolerance test values of blood glucose and insulin were significantly higher in the patients at the end of the study.

    CONCLUSIONS: In conclusion our data suggest that the starting dose of GH substitution and the dose titration steps should be individualised according to GH sensitivity (gender) and the IGF-I level aimed for (age). The reduced insulin sensitivity induced by GH substitution could be viewed as a normalisation if compared with control subjects.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24897 (URN)10.1530/eje.0.1470049 (DOI)9300 (Local ID)9300 (Archive number)9300 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    3. Individualized growth hormone substitution with normalized IGF-I levels does not stimulate the renin–angiotensin–aldosterone system
    Open this publication in new window or tab >>Individualized growth hormone substitution with normalized IGF-I levels does not stimulate the renin–angiotensin–aldosterone system
    Show others...
    2002 (English)In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 57, no 4, p. 473-479Article in journal (Refereed) Published
    Abstract [en]

    objective To study the effects of individualized recombinant GH substitution, aiming at normal circulating IGF-I levels, in GH-deficient adults on blood pressure, the renin–angiotensin–aldosterone system (RAAS), natriuretic peptides and urine free cortisol.

    study design Open study with control group. The patients were titrated in dose steps of 0·17 mg GH/day every 6–8 weeks until an IGF-I level around the mean + 1 SD was attained (Tmax). After another month the dose was reduced by 0·17 mg (minimum dose 0·17 mg/day) to produce IGF-I levels at or slightly below the age-related mean (Tend), and this maintenance dose was held constant for 6 months.

    subjects Eighteen patients (11 males and seven females) with GH deficiency participated. For comparison we also prospectively evaluated 17 matched control subjects.

    measurements Blood pressure and heart rate, circulating levels of IGF-I, plasma renin activity (PRA), immunoreactive active renin (IRR), angiotensin II, aldosterone, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and 24-h urine aldosterone and urine free cortisol levels.

    results Blood pressure was unchanged by GH substitution but heart rate increased significantly (P < 0·03). PRA was elevated on the highest GH dose (Tmax) compared to baseline (P < 0·01), but returned to baseline and levels of controls at Tend. Four patients developed transient oedema and tended to have higher PRA levels than the rest of the subjects (P = 0·09). The circulating levels of IRR, angiotensin II, aldosterone, BNP and 24-h urine aldosterone and urine free cortisol levels were unchanged by GH substitution, and did not differ from the levels in the control subjects. Baseline ANP levels in the patients were lower than in the controls (P < 0·01), but increased after GH substitution (P < 0·01) to levels found in with the controls.

    conclusions We found no major changes of the variables in the circulating renin–angiotensin–aldosterone system and a normalization of atrial natriuretic peptide when an individualized dose of GH was titrated to near-normal IGF-I levels.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24919 (URN)10.1046/j.1365-2265.2002.01617.x (DOI)9323 (Local ID)9323 (Archive number)9323 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    4. Improved muscle function in GH substituted adults is related to increase in circulating IGF-I
    Open this publication in new window or tab >>Improved muscle function in GH substituted adults is related to increase in circulating IGF-I
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    We studied the effects of individualized growth hormone substitution, aiming at normal IGF-I levels, on biomechanical output and EMG of isokinetic muscle strength and endurance performance in 18 hypopituitary adults compared with matched controls. The muscle function tests consisted of isokinetic contractions of the dght knee extensors, and torque and EMG were recorded. Plasma levels of IGF-I were normalized, and peak torque at 90° s-1, and peak torque endurance level increased after dose titration and 6 months constant GH-dose. The change in IGF-I correlated positively with the changes in biomechanical output and EMG variables and a negative correlation existed with the perception of fatigue. Despite improvement during GH-substitution the patients still had about 10-20 % less muscle strength and endurance compared with the controls at the study end. In summary we found that individualized GH substitution improves muscle function and that the net increase in IGF-I levels indicates generally increases in biomechanical output and EMG variables and a lower perception of fatigue.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81632 (URN)
    Available from: 2012-09-19 Created: 2012-09-19 Last updated: 2012-09-19Bibliographically approved
    5. Circulating IGF-I concentrations are low and not correlated to glycaemic control in adults with type 1 diabetes
    Open this publication in new window or tab >>Circulating IGF-I concentrations are low and not correlated to glycaemic control in adults with type 1 diabetes
    2000 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 143, no 4, p. 505-510Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE: To study plasma concentrations of insulin-like growth factor-I (IGF-I) in adults with type 1 diabetes (IDDM) in comparison with a reference population, and the influence of glycaemic control, dose of insulin, and sex on the concentration of circulating IGF-I in IDDM.

    DESIGN AND METHODS: Patients with type 1 diabetes were recruited consecutively from our outpatient diabetes unit. In all, 79 men and 55 women aged 20-60 years with a disease duration >/=6 years (range 6-51 years) took part in the study. A reference population of 80 men and 83 women aged 20-60 years was randomly obtained from the population registry. IGF-I was measured with radioimmunoassay after acid-ethanol extraction.

    RESULTS: Mean +/- s. d. values of IGF-I were lower in patients with diabetes (146+/-66 microg/l) than in controls (238+/-83 microg/l, P<0.001). Those with diabetes had lower IGF-I concentrations in all age groups and the differences were highly significant in all decades except in women aged 50-59 years. IGF-I was negatively correlated with age in patients and controls. No correlation was found between IGF-I and glycaemic control measured as haemoglobin A(1c) (HbA(1c)) in the patients. IGF-I was positively associated with the dose of insulin/kg body weight in male patients independently of age, HbA(1c) and body mass index (P<0.03), but not in female patients (P=0.14).

    CONCLUSIONS: Our data show that IGF-I concentrations are low in adult patients with type 1 diabetes with a disease duration >/=6 years, independently of glycaemic control. This suggests that subcutaneous insulin substitution is inadequate to normalize circulating IGF-I concentrations in patients without endogenous insulin secretion.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26789 (URN)10.1530/eje.0.1430505 (DOI)11394 (Local ID)11394 (Archive number)11394 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
  • 23.
    Ekman, Bertil
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-endo.
    Gerdle, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-endo.
    Growth hormone substitution titrated to obtain IGF-I levels in the physiological range in hypopituitary adults: Effects upon dynamic strength, endurance and EMG2003In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 90, no 5-6, p. 496-504Article in journal (Refereed)
    Abstract [en]

    We studied the effects of individualised growth hormone (GH) substitution, aiming at normal insulin-like growth factor I (IGF-I) levels, on biomechanical output and surface electromyogram (EMG) of isokinetic muscle strength and endurance performance in 18 hypopituitary adults and compared with 17 matched healthy controls. The muscle function tests consisted of isokinetic contractions of the right knee extensors, from which torque and EMG were recorded. Three patients were excluded from the final analysis of the muscle function tests due to technical errors and one control subject moved from the area during the study. We found that GH-deficient adults without GH substitution were weaker and had less endurance than healthy control subjects. At the group level, plasma levels of IGF-I were normalised but generally no significant effects upon biomechanical output and EMG were found after dose titration and 6 months of a constant GH dose. However, subjects with the largest changes in IGF-I had significantly better biomechanical output and EMG compared to those with small changes in IGF-I. This finding may indicate that the net increase in IGF-I levels is critical for improvements in biomechanical output, EMG and perception of fatigue to occur.

  • 24.
    Ekman, Bertil
    et al.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Gerdle, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans J.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Improved muscle function in GH substituted adults is related to increase in circulating IGF-IManuscript (preprint) (Other academic)
    Abstract [en]

    We studied the effects of individualized growth hormone substitution, aiming at normal IGF-I levels, on biomechanical output and EMG of isokinetic muscle strength and endurance performance in 18 hypopituitary adults compared with matched controls. The muscle function tests consisted of isokinetic contractions of the dght knee extensors, and torque and EMG were recorded. Plasma levels of IGF-I were normalized, and peak torque at 90° s-1, and peak torque endurance level increased after dose titration and 6 months constant GH-dose. The change in IGF-I correlated positively with the changes in biomechanical output and EMG variables and a negative correlation existed with the perception of fatigue. Despite improvement during GH-substitution the patients still had about 10-20 % less muscle strength and endurance compared with the controls at the study end. In summary we found that individualized GH substitution improves muscle function and that the net increase in IGF-I levels indicates generally increases in biomechanical output and EMG variables and a lower perception of fatigue.

  • 25.
    Ekman, Bertil
    et al.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Olsson, Anders
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Toss, Göran
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    A dose titration model for recombinant GH substitution aiming at normal plasma concentrations of IGF-I in hypopituitary adults2002In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 147, no 1, p. 49-57Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate a dose titration model for recombinant human GH substitution in adult patients with GH deficiency, aiming at normal plasma levels of IGF-I.

    DESIGN AND METHODS: Eighteen patients participated and a start dose of 0.17 mg GH/day was used except by two men who started with 0.33 mg/day. To demonstrate a clear GH effect the patients were first titrated, with steps of 0.17 mg GH/day every 6-8 weeks, to IGF-I levels in the upper range of age-adjusted reference values. The GH dose was then reduced 1 dose step and kept for a further 6 months. For comparison we investigated 17 healthy control subjects.

    RESULTS: Plasma IGF-I was increased after 2 weeks on the start dose and did not increase further for up to 8 weeks. Women had significantly lower GH sensitivity than men measured as net increment of IGF-I on the start dose of GH. GH sensitivity was not changed by age. The plasma IGF-I levels increased from 76.3+/-47.0 (s.d.) to 237+/-97 microg/l at the end of the study (P<0.001), and similar IGF-I levels were obtained in both sexes. The maintenance median GH dose was 0.33 mg/day in males and 0.83 mg/day in females (P=0.017). The GH dose correlated negatively with age in both sexes. Body weight, very low density triglycerides, lipoprotein(a) (Lp(a)), and fasting insulin increased, whereas insulin sensitivity index (QUICKI) decreased significantly. In comparison with the controls, the patients had lower fasting blood glucose, fasting insulin and Lp(a) levels at baseline, but these differences disappeared after GH substitution. The two groups had equal insulin sensitivity (QUICKI), but 2 h oral glucose tolerance test values of blood glucose and insulin were significantly higher in the patients at the end of the study.

    CONCLUSIONS: In conclusion our data suggest that the starting dose of GH substitution and the dose titration steps should be individualised according to GH sensitivity (gender) and the IGF-I level aimed for (age). The reduced insulin sensitivity induced by GH substitution could be viewed as a normalisation if compared with control subjects.

  • 26.
    Ekman, Bertil
    et al.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Circulating IGF-I concentrations are low and not correlated to glycaemic control in adults with type 1 diabetes2000In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 143, no 4, p. 505-510Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study plasma concentrations of insulin-like growth factor-I (IGF-I) in adults with type 1 diabetes (IDDM) in comparison with a reference population, and the influence of glycaemic control, dose of insulin, and sex on the concentration of circulating IGF-I in IDDM.

    DESIGN AND METHODS: Patients with type 1 diabetes were recruited consecutively from our outpatient diabetes unit. In all, 79 men and 55 women aged 20-60 years with a disease duration >/=6 years (range 6-51 years) took part in the study. A reference population of 80 men and 83 women aged 20-60 years was randomly obtained from the population registry. IGF-I was measured with radioimmunoassay after acid-ethanol extraction.

    RESULTS: Mean +/- s. d. values of IGF-I were lower in patients with diabetes (146+/-66 microg/l) than in controls (238+/-83 microg/l, P<0.001). Those with diabetes had lower IGF-I concentrations in all age groups and the differences were highly significant in all decades except in women aged 50-59 years. IGF-I was negatively correlated with age in patients and controls. No correlation was found between IGF-I and glycaemic control measured as haemoglobin A(1c) (HbA(1c)) in the patients. IGF-I was positively associated with the dose of insulin/kg body weight in male patients independently of age, HbA(1c) and body mass index (P<0.03), but not in female patients (P=0.14).

    CONCLUSIONS: Our data show that IGF-I concentrations are low in adult patients with type 1 diabetes with a disease duration >/=6 years, independently of glycaemic control. This suggests that subcutaneous insulin substitution is inadequate to normalize circulating IGF-I concentrations in patients without endogenous insulin secretion.

  • 27.
    Ekman, Bertil
    et al.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Öhman, Peter K
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Individualized growth hormone substitution with normalized IGF-I levels does not stimulate the renin–angiotensin–aldosterone system2002In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 57, no 4, p. 473-479Article in journal (Refereed)
    Abstract [en]

    objective To study the effects of individualized recombinant GH substitution, aiming at normal circulating IGF-I levels, in GH-deficient adults on blood pressure, the renin–angiotensin–aldosterone system (RAAS), natriuretic peptides and urine free cortisol.

    study design Open study with control group. The patients were titrated in dose steps of 0·17 mg GH/day every 6–8 weeks until an IGF-I level around the mean + 1 SD was attained (Tmax). After another month the dose was reduced by 0·17 mg (minimum dose 0·17 mg/day) to produce IGF-I levels at or slightly below the age-related mean (Tend), and this maintenance dose was held constant for 6 months.

    subjects Eighteen patients (11 males and seven females) with GH deficiency participated. For comparison we also prospectively evaluated 17 matched control subjects.

    measurements Blood pressure and heart rate, circulating levels of IGF-I, plasma renin activity (PRA), immunoreactive active renin (IRR), angiotensin II, aldosterone, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and 24-h urine aldosterone and urine free cortisol levels.

    results Blood pressure was unchanged by GH substitution but heart rate increased significantly (P < 0·03). PRA was elevated on the highest GH dose (Tmax) compared to baseline (P < 0·01), but returned to baseline and levels of controls at Tend. Four patients developed transient oedema and tended to have higher PRA levels than the rest of the subjects (P = 0·09). The circulating levels of IRR, angiotensin II, aldosterone, BNP and 24-h urine aldosterone and urine free cortisol levels were unchanged by GH substitution, and did not differ from the levels in the control subjects. Baseline ANP levels in the patients were lower than in the controls (P < 0·01), but increased after GH substitution (P < 0·01) to levels found in with the controls.

    conclusions We found no major changes of the variables in the circulating renin–angiotensin–aldosterone system and a normalization of atrial natriuretic peptide when an individualized dose of GH was titrated to near-normal IGF-I levels.

  • 28.
    Ericson, Ann-Charlott
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Kechagias, Stergios
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Öqvist, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Sjöstrand, Sven-Erik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Morphological examination of the termination pattern of substance P-immunoreactive nerve fibers in human antral mucosa2002In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 107, no 1-3, p. 79-86Article in journal (Refereed)
    Abstract [en]

    The termination pattern of substance P (SP)-containing axons in human antral mucosa was examined using immunohistochemical techniques at the light and electron microscopic level. SP-immunoreactive (IR) axons were found to extend towards the pit region of the glands, where intraepithelial axons were observed. Electron microscopy showed immunostained axon profiles in close contact with the basement membrane of surface mucous cells. Membrane-to-membrane contacts between labeled axons and myofibroblast-like cells were identified, and SP-IR axons that were apposed to the epithelium were also in contact with subjacent myofibroblast-like cells. The anatomical relationship between SP-IR axons and the cells of the muscularis mucosae was investigated by light microscopy. Immunoreactivity for a-smooth muscle actin (a-sma) was used to visualize the smooth muscle cells, and the a-sma-IR cells were found to create a network that surrounded the gastric glands. Immunostained varicose axons ran alongside and in close apposition to the labeled muscle strands. Ultrastructural examination showed close contacts between SP-IR axon profiles and smooth muscle-like cells. In conclusion, SP-containing neurons may be important for sensory and secretomotor functions in the human antral mucosa.

  • 29.
    Eriksson, Per
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
    Renal disease in primary Sjögren's syndrome1996Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Primary Sjögren's syndrome (SS) is characterised by inflammation in the lacrimal and salivary glands. The kidneys may be involved, e.g. tubulointerstitial nephritis (TIN) and distal renal tubular acidosis (dRTA). dRTA is often associated with hypocitraturia, and both represent risk factors for the development of urolithiasis. The present investigations were undertaken to evaluate renal tubular function (including -dRTA), glomerular filtration rate (GFR), renal histopathology and mechanisms of stone formation, as well as the serum IgG subclass pattern in patients with SS. Furthermore, patients presenting with urolithiasis and dRTA in absence of sicca symptoms, as well as patients with urolithiasis andhypocitraturia, were studied with respect to autoantibodies and clinical features of SS.

    Renal tubular dysfunction, such as dRTA; impaired urine concentrating ability; hypocitraturia; and decreased tubular reabsorption of phosphate (1RP%), was conunonly detected in the SS-patients. Tubular proteinuria (al-microglobulin) and tubular enzymuria (NAG) were primarily associated with decreased GFR.

    GFR, investigated with 5Icr-EDTA plasma clearance, was below the reference limit in 33% of SS-patients. An inverse correlation was found between GFR and the extent of tubulointerstitial nephritis (adjusted CTIN score). Decreased GFR was mostly due to TIN, although urolithiasis and upper urinary tract infections may have contributed in some patients.

    TIN was demonstrated in most biopsied patients with SS, and the histopathological picture was characterised by mainly focal interstitial inflanunation, tubular atrophy, interstitial fibrosis and a varying extent of glomerular sclerosis.

    Fourty-one percent of the SS-patients had formed at least one stone, and calcium phosphate was the main constituent in most stones. All stone formers had dRTA, and most of them had hypocitraturia. Urinary calcium and urate excretion was also significantly higher than in non-stone formers.

    The SS-patients often had low serum levels of IgG2, despite high levels of total IgG. Low levels of IgG2 were sometimes associated with infections. A high IgG lngG2 ratio indicated autoimmune disease.

    Of 10 patients presenting with urolithiasis and dRTA, anti-SS-A antibodies were detected in eight. Subjective sicca symptoms subsequently developed l-48 years after the presentation of urolithiasis, and objective signs of SS were found in 7 patients.

    In a large population of hypocitraturic stone formers, ANA and anti-SS-A antibodies were commonly detected in the women but not in the men. Four of 14 evaluated hypocitraturic women with anti-SS-A antibodies or ANA, fulfilled the criteria for SS.

    In conclusion, the present investigations show that 24-hour urinary excretion of citrate is a valuable tool for detection of renal disease in SS, slightly-moderately decreased GFR is not unusual in SS-patients with. renal disease, the "adjusted CTIN score" can be a useful tool for quantifying the extent of tu'bulointerstitial nephritis, and the urine composition in stone formers with SS is similar to that of other dRT A-patients.

    The possibility of a Sjögren-related renal disease charcterised by urolithiasis and/or dRTA and antibodies to SS-A, regardless of whether subjective sicca symptoms are present or not, is hypothesised.

  • 30.
    Fyrenius, Anna
    et al.
    Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Linköping University, Faculty of Health Sciences.
    Wigström, Lars
    Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Linköping University, Faculty of Health Sciences.
    Bolger, Ann F.
    Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Linköping University, Faculty of Health Sciences.
    Ebbers, Tino
    Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Öhman, Peter
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Karlsson, Matts
    Linköping University, Department of Biomedical Engineering, Biomedical Modelling and Simulation. Linköping University, The Institute of Technology.
    Wranne, Bengt
    Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Engvall, Jan
    Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Linköping University, Faculty of Health Sciences.
    Pitfalls in Doppler evaluation of diastolic function: insights from three-dimensional magnetic resonance imaging1999In: Journal of the American Society of Echocardiography, ISSN 0894-7317, E-ISSN 1097-6795, Vol. 12, no 10, p. 817-826Article in journal (Refereed)
    Abstract [en]

    Ultrasound-Doppler assessment of diastolic function is subject to velocity errors caused by angle sensitivity and a fixed location of the sample volume. We used 3-dimensional phase contrast magnetic resonance imaging (MRI) to evaluate these errors in 10 patients with hypertension and in 10 healthy volunteers. The single (Doppler) and triple (MRI) component velocity was measured at early (E) and late (A) inflow along Doppler-like sample lines or 3-dimensional particle traces generated from the MRI data. Doppler measurements underestimated MRI velocities by 9.4% ± 8.6%; the effect on the E/A ratio was larger and more variable. Measuring early and late diastolic inflows from a single line demonstrated the error caused by their 3-dimensional spatial offset. Both errors were minimized by calculating the E/A ratio from maximal E and A values without constraint to a single line. Alignment and spatial offset are important sources of error in Doppler diastolic parameters. Improved accuracy may be achieved with the use of maximal E and A velocities from wherever they occur in the left ventricle.

  • 31.
    Garvin, Peter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science.
    Jonasson, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Kristenson, Margareta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science. Östergötlands Läns Landsting, Centre for Public Health Sciences, Centre for Public Health Sciences.
    Nijm, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology.
    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.
    Psychosocial factors in atherosclerosis2006In: XIV International Symposium on Atherosclerosis,2006, 2006Conference paper (Other academic)
  • 32.
    Hallberg, Inger
    et al.
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Rosenqvist, A. M
    Department of Geriatrics, Ryhovs Hospital, Jönköping, Sweden.
    Kartous, L
    Department of Geriatrics, Ryhovs Hospital, Jönköping, Sweden.
    Löfman, Owe
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society. Östergötlands Läns Landsting, Centre for Public Health Sciences, Centre for Public Health Sciences.
    Wahlström, Ola
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Toss, Göran
    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.
    Health-related quality of life after osteoporotic fractures2004In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 15, no 10, p. 834-841Article in journal (Refereed)
    Abstract [en]

    Objective: To estimate the impact of osteoporosis fractures on health-related quality of life (HRQOL) in postmenopausal women. Methods: To compare the impact on HRQOL of different osteoporotic fractures, 600 consecutive women 55-75 years old with a new fracture (inclusion fracture) were invited by mail. After exclusions by preset criteria (high-energy fractures, ongoing osteoporosis treatment, or unwillingness to participate), 303 women were included, 171 (56%) of whom had a forearm, 37 (12%) proximal humerus, 40 (13%) hip, and 55 (18%) vertebral fracture, respectively, and all were investigated and treated according to the current local consensus program for osteoporosis. In addition, HRQOL was evaluated by the SF-36 questionnaire and compared with local, age-matched reference material. Examinations were performed 82 days (median) after the fracture and 2 years later. Results: HRQOL was significantly reduced at baseline regarding all SF-36 domains after vertebral fractures and most after hip fractures, but only regarding some domains after forearm and humerus fracture. After 2 years, improvements had occurred after all types of fractures, and after forearm or humerus fracture, HRQOL was completely normalized in all domains. However, 2 years after hip fracture, HRQOL was still below normal regarding physical function, role-physical and social function, while after vertebral fracture, scores were still significantly lower for all domains, physical as well as mental. Patients with one or more previous fractures before the inclusion fracture had lower HRQOL at baseline and after 2 years, compared with those with no previous fracture. Patients with osteoporosis (T-score < - 2.5 in hip or spine) had lower HRQOL than those with normal BMD. Conclusion: Vertebral and hip fractures have a considerably greater and more prolonged impact on HRQOL than forearm and humerus fractures. The number of fractures was inversely correlated to HRQOL. These differences should be taken into account when making priorities in health care programs.

  • 33. Hallberg, P
    et al.
    Karlsson, J
    Kurland, L
    Lind, L
    Kahan, T
    Malmqvist, K
    Ohman, KP
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine.
    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.
    Melhus, H
    The CYP2C9 genotype predicts the blood pressure response to irbesartan: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial2002In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 10, p. 2089-2093Article in journal (Refereed)
  • 34. Hallberg, P
    et al.
    Karlsson, J
    Lind, L
    Michaelsson, K
    Kurland, L
    Kahan, T
    Malmqvist, K
    Ohman, KP
    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.
    Liljedahl, U
    Syvanen, AC
    Melhus, H
    Gender-specific association between preproendothelin-1 genotype and reduction of systolic blood pressure during antihypertensive treatment - results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA)2004In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 27, p. 287-290Article in journal (Refereed)
  • 35. Hallberg, P
    et al.
    Lind, L
    Billberger, K
    Michaelsson, K
    Karlsson, J
    Kurland, L
    Kahan, T
    Malmqvist, K
    Ohman, KP
    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.
    Liljedahl, U
    Syvanen, AC
    Melhus, H
    Transforming growth factor beta1 genotype and change in left ventricular mass during antipypertensive treatment - results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA)2004In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 27, p. 169-173Article in journal (Refereed)
  • 36. Hallberg, P
    et al.
    Lind, L
    Michaelsson, K
    Karlsson, J
    Kurland, L
    Kahan, T
    Malmqvist, K
    Öhman, KP
    Nyström, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-endo.
    Melhus, H
    B2 bradykinin receptor (B2BKR) polymorphism and change in left ventricular mass in response to antihypertensive treatment: Results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial2003In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 21, no 3, p. 621-624Article in journal (Refereed)
    Abstract [en]

    Objective: Hypertension is associated with a number of adverse morphologic and functional changes in the cardiovascular system, including left ventricular (LV) hypertrophy. Studies have demonstrated that bradykinin, through the B2 bradykinin receptor (B2BKR), mediates important cardiovascular effects that may protect against LV hypertrophy. Recently, a +9/-9 exon 1 polymorphism of the B2BKR was shown to be strongly associated with LV growth response among normotensive males undergoing physical training. We aimed to clarify whether the processes found in exercise-induced LV growth in normotensive people also occur in pathological LV hypertrophy. Design and methods: We determined the B2BKR genotype of 90 patients with essential hypertension and echocardiographically diagnosed LV hypertrophy, included in a double-blind study to receive treatment for 48 weeks with either the angiotensin II type 1 (AT1) receptor antagonist irbesartan or the ▀1 -adrenoceptor antagonist atenolol. Results: B2BKR +9/+9 genotypes responded poorly in LV mass regression, independent of blood pressure reduction or treatment, as compared to the other genotypes (adjusted mean change in LV mass index = -10.0 ▒ 4.6 versus -21.6 ▒ 2.2 g/m2, P = 0.03). Conclusions: Our results suggest an impact of the B2BKR polymorphism on LV mass regression during antihypertensive treatment. ⌐ 2003 Lippincott Williams & Wilkins.

  • 37. Hallberg, P
    et al.
    Lind, L
    Michaelsson, K
    Kurland, L
    Kahan, T
    Malmqvist, X?
    Öhman, KP
    Nyström, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-endo.
    Liljedahl, U
    Syvanen, AC
    Melhus, H
    Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy2003In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 3Article in journal (Refereed)
    Abstract [en]

    Background: Adipocyte-derived leucine aminopeptidase (ALAP) is a recently identified member of the M1 family of zinc-metallopeptidases and is thought to play a role in blood pressure control through inactivation of angiotensin II and/or generation of bradykinin. The enzyme seems to be particularly abundant in the heart. Recently, the Arg528-encoding allele of the ALAP gene was shown to be associated with essential hypertension. Methods: We evaluated the influence of this polymorphism on the change in left ventricular mass index in 90 patients with essential hypertension and echocardiographically diagnosed left ventricular hypertrophy, randomised in a double-blind study to receive treatment with either the angiotensin II type I receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol for 48 weeks. Genyotyping was performed using minisequencing. Results: After adjustment for potential covariates (blood pressure and left ventricular mass index at baseline, blood pressure change, age, sex, dose and added antihypertensive treatment), there was a marked difference between the Arg/Arg and Lys/Arg genotypes in patients treated with irbesartan, those with the Arg/Arg genotype responded on average with an almost two-fold greater regression of left ventricular mass index than patients with the Lys/Arg genotype (-30.1 g/m2 [3.6] vs - 16.7 [4.5], p = 0.03). Conclusions: The ALAP genotype seems to determine the degree of regression of left ventricular hypertrophy during antihypertensive treatment with the angiotensin II type I receptor antagonist irbesartan in patients with essential hypertension and left ventricular hypertrophy. This is the first report of a role for ALAP/aminopeptidases in left ventricular mass regulation, and suggests a new potential target for antihypertensive drugs.

  • 38.
    Hedman, Christina
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Insulin and IGF-I in type 1 diabetes2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Patients with type I diabetes have alterations in the GH/IGF system with reduced levels of circulating IGF-I, as well as other disturbances in the components of the IGF system.

    Alterations of both local and circulating IGF-I and its binding proteins (IGFBPs) have been associated with metabolic and vascular manifestations of diabetes and also with atherosclerosis. Short-acting insulin analogues have been developed in order to obtain more physiologic insulin profiles than with human regular insulin when injected subcutaneously.

    We examined the effects on the IGF system of good glycaemic control, of two diets with different amount of protein and of the short-acting insulin analogue lispro in continuous subcutaneous insulin infusion (CSII) (pump therapy). We also compared the free insulin profiles of the insulin analogues lispro and aspart. As a new tool we used the combination of two different insulin assays that detect human insulin only, or both human insulin and analogues.

    This thesis shows that the circulating IGF system exhibits several pronounced aberrations in patients with type I diabetes, even if glycaemic control is normal or near normal. These abnormalities are not, or are only weakly, related to glycaemic control estimated by HbA1c. In contrast, they are related to the presence of residual p-cell function, indicating that portal insulin delivery is required for a normal IGF system. Treatment with insulin analogue lispro, despite giving higher peripheral insulin peaks than human regular insulin, does not alter the levels of IGF-I and IGFBP-I in patients with good glycaemic control and longstanding, Cpeptide negative type 1 diabetes treated with CSII. Furthermore, IGFBP-I levels do not differ after a single s c injection of each of the insulin analogues aspart and lispro. A two-fold increase in protein intake, from 10E% to 20E%, in patients with longstanding type 1 diabetes does not affect the altered IGF system.

    The free insulin profiles of insulin analogues aspart and lispro resemble each other, but insulin lispro showed a slightly faster uptake, reached the maximum peak concentration earlier, and showed a more rapid decline than did insulin aspart. These differences are, however, small in comparison with the large differences in the insulin profiles between lispro and human regular insulin. The accumulated evidence suggests that possible differences between these insulin analogues are of little or no clinical importance.

    The combination of insulin assays that detect human insulin alone, or both human insulin and analogues provides a new tool for studying insulin pharmacokinetics. Using this technique, it is possible to separately assess the contribution of insulin analogues (lispro and aspart) and human insulin to the free insulin profiles.

    List of papers
    1. Treatment with insulin lispro changes the insulin profile but does not affect the plasma concentrations of IGF-I and IGFBP-1 in type 1 diabetes
    Open this publication in new window or tab >>Treatment with insulin lispro changes the insulin profile but does not affect the plasma concentrations of IGF-I and IGFBP-1 in type 1 diabetes
    2001 (English)In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 55, no 1, p. 107-112Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE IGF-I levels in patients with type 1 diabetes without endogenous insulin production are low. Our aim was to examine whether the plasma insulin profile obtained by treatment with the insulin analogue lispro has a different effect on plasma concentrations of IGF-I and IGFBP-1 than that seen during treatment with conventional human insulin (regular insulin).

    DESIGN AND PATIENTS Twelve patients with type 1 diabetes, age 47·8 ± 2·4 years (mean ± SEM), body mass index 26·5 ± 1·0 kg/m2, diabetes duration 30·5 ± 3·2 years participated in this open label randomized cross-over study. IGF-I and IGFBP-1 levels were measured at the end of 6 weeks treatment with each insulin being administered by a continuous subcutaneous insulin infusion. IGF-I was measured fasting while IGFBP-1, free insulin and blood glucose were measured fasting and repeatedly after a morning meal preceded by an insulin bolus dose.

    RESULTS Lispro gave a marked insulin peak of 135 ± 20 pmol/l 50 minutes after injection. After an initial rapid rise, human regular insulin reached a plateau of approximately 50 pmol/l. The plasma free insulin area under the curve (AUC) from 0710 h to 0910 h was more than twice as large on lispro as on regular insulin (P = 0·01). Plasma IGF-I concentration was 78·8 ± 10·9 µg/l on lispro and 82·3 ± 10·5 µg/l on human regular insulin (not significant). AUC for IGFBP-1 did not show a significant difference even when divided from 0710 h to 0910 h and from 0930 h to 1430 h. Blood glucose AUC after administration of the bolus was significantly lower during treatment with lispro (P = 0·006) but glycosylated haemoglobin (HbA1c) was 6·4 ± 0·2% on both therapies.

    CONCLUSIONS Our results indicate that the effect of lispro on IGF-I and IGFBP-1 in patients with type 1 diabetes does not differ from that of human regular insulin.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24910 (URN)10.1046/j.1365-2265.2001.01327.x (DOI)9313 (Local ID)9313 (Archive number)9313 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    2. Direct comparison of insulin lispro and aspart shows small differences in plasma insulin profiles after subcutaneous injection in type 1 diabetes
    Open this publication in new window or tab >>Direct comparison of insulin lispro and aspart shows small differences in plasma insulin profiles after subcutaneous injection in type 1 diabetes
    2001 (English)In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 24, p. 1120-1121Article in journal, Letter (Refereed) Published
    Abstract [en]

    No abstract available.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24916 (URN)10.2337/diacare.24.6.1120 (DOI)9320 (Local ID)9320 (Archive number)9320 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    3. Use of a novel double-antibody technique to describe the pharmacokinetics of rapid-acting insulin analogs
    Open this publication in new window or tab >>Use of a novel double-antibody technique to describe the pharmacokinetics of rapid-acting insulin analogs
    2002 (English)In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 25, no 6, p. 1049-1054Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE—To measure the contribution of bedtime intermediate-acting human insulin on the morning plasma insulin profiles after injection of the rapid-acting insulin analogs lispro and aspart in patients with type 1 diabetes.

    RESEARCH DESIGN AND METHODS—A total of 14 patients with type 1 diabetes, aged 35 ± 13 years (mean ± SD), participated in this single-blind, randomized crossover study. After taking their usual injection of human intermediate-acting insulin the night before, they were given insulin aspart or insulin lispro (10 units) before a standardized breakfast. The contribution of continuing absorption of the human insulin was measured using a monoclonal antibody not cross-reacting with insulin aspart or lispro, whereas the contribution of the analogs was estimated by subtraction after measurement of all plasma free insulin using an antibody cross-reacting equally with human insulin and both analogs.

    RESULTS—The correlation coefficient of the fasting free insulin concentrations measured with both insulin methods was 0.95. Fasting free insulin was 95 ± 25 pmol/l before administration of insulin aspart, when determined with enzyme-linked immunosorbent assay detecting only human insulin, and 71 ± 20 pmol/l before administration of insulin lispro (NS). Both insulin analogs gave marked peaks of free insulin concentrations, lispro at 40 ± 3 min and aspart at 55 ± 6 min after injection (P = 0.01). The later part of the profiles, from 4.5 to 5.5 h after injection, were similar and showed almost no contribution of the insulin analogs.

    CONCLUSIONS—The combination of insulin assays that detect human insulin only or both human insulin and analogs provides a new tool for studying insulin pharmacokinetics. Using this technique, we showed that 4.5 h after administration of the rapid-acting insulin analogs lispro and aspart, the free insulin levels are almost only attributable to the intermediate-acting insulin given at bedtime.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24906 (URN)10.2337/diacare.25.6.1049 (DOI)9309 (Local ID)9309 (Archive number)9309 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    4. Residual β-cell function more than glycemic control determines abnormalities of the insulin-like growth factor system in type 1 diabetes
    Open this publication in new window or tab >>Residual β-cell function more than glycemic control determines abnormalities of the insulin-like growth factor system in type 1 diabetes
    Show others...
    2004 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 89, no 12, p. 6305-6309Article in journal (Refereed) Published
    Abstract [en]

    The GH-IGF-I axis is disturbed in patients with type 1 diabetes. Our aim was to investigate whether abnormalities are found in patients in very good glycemic control and, if so, to estimate the role of residual β-cell function. Patients with hemoglobin A 1c (HbA 1c) less than 6% (reference range, 3.6-5.4%) were selected for the study. Twenty-two men and 24 women, aged 41.3 ± 13.8 yr (mean ± SD), with a diabetes duration of 17.8 ± 14.6 yr participated. Healthy controls (15 women and nine men), aged 41.3 ± 13.0 yr, were also studied. Overnight fasting serum samples were analyzed for HbA 1c, C peptide, free and total IGFs, IGF-binding proteins (IGFBPs), GH-binding protein, and IGFBP-3 proteolysis. HbA 1c was 5.6 ± 0.5% in patients and 4.4 ± 0.3% in controls. Total IGF-I was 148 ± 7 μg/liter in patients and 178 ± 9 μg/liter in controls (P < 0.001). Free IGF-I, total IGF-II, IGFBP-3, and GH-binding protein were lower, whereas IGFBP-1, IGFBP-1-bound IGF-I, and IGFBP-2 were elevated compared with control values. Patients with detectable C peptide (≥100 pmol/liter) had higher levels of total IGF-I, free IGF-I, and total IGF-II and lower levels of IGFBP-1 and IGFBP-2 than those with an undetectable C peptide level despite having identical average HbA 1c. IGFBP-3 proteolysis did not differ between patients and controls. Despite very good glycemic control, patients with type 1 diabetes and no endogenous insulin production have low free and total IGF-I. Residual β-cell function, therefore, seems more important for the disturbances in the IGF system than good metabolic control per se, suggesting that portal insulin delivery is needed to normalize the IGF system.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24672 (URN)10.1210/jc.2004-0572 (DOI)6905 (Local ID)6905 (Archive number)6905 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    5. The IGF-system is not affected by a twofold change in protein intake in patients with type 1 diabetes
    Open this publication in new window or tab >>The IGF-system is not affected by a twofold change in protein intake in patients with type 1 diabetes
    Show others...
    2005 (English)In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 15, no 4, p. 304-310Article in journal (Refereed) Published
    Abstract [en]

    Objective In type 1 diabetes the circulating IGF-system is altered with low IGF-I and changes in levels of IGF-binding proteins (IGFBPs) which may be of importance for the development of diabetes complications. Our aim was to study if IGF-I, as supported by experimental data in animals, can be affected by dietary protein intake.

    Design and methods Twelve patients with type 1 diabetes, age 37.5 ± 10.0 years (mean ± SD), diabetes duration 20.1 ± 9.3 years and HbA1c 6.3 ± 0.6% were allocated to isocaloric diets with either low normal protein content (LNP), (10 E%; 0.9 g protein/kg body weight) or high normal protein content (HNP) (20 E%; 1.8 g protein/kg body weight) in an open randomised cross-over study. Each diet was taken for 10 days with a wash-out period of 11 days in between. Circulating levels of total and free IGF-I and -II, IGFBP-1, -2 and -3 and GH-binding protein (GHBP) as well as ghrelin were measured with validated in-house immunoassays.

    Results At day 10, urinary urea excretion was 320 ± 75 mmol/24 h during LNP diet compared with 654 ± 159 mmol/24 h during HNP diet (p < 0.001). There were no changes in body weight or glycaemic control between the diets. Fasting levels of total IGF-I were 121 ± 33 μg/L after LNP and 117 ± 28 μg/L after HNP diet (ns) and the corresponding concentrations of IGFBP-1 were 142(141) and 132(157) μg/L [median (IQR)] (ns). There were no differences in plasma concentrations of total IGF-II, free IGF-I and -II, IGFBP-3, GHBP and ghrelin, whereas a small difference was found for IGFBP-2 (302 ± 97 vs. 263 ± 66 μg/L; LNP vs. HNP; p < 0.04).

    Conclusions A twofold change of the dietary protein intake does not influence the altered circulating IGF-system in type 1 diabetes. In order to affect the IGF-system other interventions must be used.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-31658 (URN)10.1016/j.ghir.2005.06.013 (DOI)17470 (Local ID)17470 (Archive number)17470 (OAI)
    Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13Bibliographically approved
  • 39.
    Hedman, Christina
    et al.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Frystyk, Jan
    Medical Research Laboratories, Clinical Institute and Medical Department, Aarhus University Hospital, Aarhus, Denmark.
    Fridell, Karin
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Jönsson, Anna
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Flyvbjerg, Allan
    Medical Research Laboratories, Clinical Institute and Medical Department, Aarhus University Hospital, Aarhus, Denmark.
    Lindström, Torbjörn
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    The IGF-system is not affected by a twofold change in protein intake in patients with type 1 diabetes2005In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 15, no 4, p. 304-310Article in journal (Refereed)
    Abstract [en]

    Objective In type 1 diabetes the circulating IGF-system is altered with low IGF-I and changes in levels of IGF-binding proteins (IGFBPs) which may be of importance for the development of diabetes complications. Our aim was to study if IGF-I, as supported by experimental data in animals, can be affected by dietary protein intake.

    Design and methods Twelve patients with type 1 diabetes, age 37.5 ± 10.0 years (mean ± SD), diabetes duration 20.1 ± 9.3 years and HbA1c 6.3 ± 0.6% were allocated to isocaloric diets with either low normal protein content (LNP), (10 E%; 0.9 g protein/kg body weight) or high normal protein content (HNP) (20 E%; 1.8 g protein/kg body weight) in an open randomised cross-over study. Each diet was taken for 10 days with a wash-out period of 11 days in between. Circulating levels of total and free IGF-I and -II, IGFBP-1, -2 and -3 and GH-binding protein (GHBP) as well as ghrelin were measured with validated in-house immunoassays.

    Results At day 10, urinary urea excretion was 320 ± 75 mmol/24 h during LNP diet compared with 654 ± 159 mmol/24 h during HNP diet (p < 0.001). There were no changes in body weight or glycaemic control between the diets. Fasting levels of total IGF-I were 121 ± 33 μg/L after LNP and 117 ± 28 μg/L after HNP diet (ns) and the corresponding concentrations of IGFBP-1 were 142(141) and 132(157) μg/L [median (IQR)] (ns). There were no differences in plasma concentrations of total IGF-II, free IGF-I and -II, IGFBP-3, GHBP and ghrelin, whereas a small difference was found for IGFBP-2 (302 ± 97 vs. 263 ± 66 μg/L; LNP vs. HNP; p < 0.04).

    Conclusions A twofold change of the dietary protein intake does not influence the altered circulating IGF-system in type 1 diabetes. In order to affect the IGF-system other interventions must be used.

  • 40.
    Hedman, Christina
    et al.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Frystyk, Jan
    Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark.
    Lindström, Torbjörn
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Chen, Jian-Wen
    Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark.
    Flyvbjerg, Allan
    Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark.
    Ørskov, Hans
    Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark.
    Arnqvist, Hans
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Residual β-cell function more than glycemic control determines abnormalities of the insulin-like growth factor system in type 1 diabetes2004In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 89, no 12, p. 6305-6309Article in journal (Refereed)
    Abstract [en]

    The GH-IGF-I axis is disturbed in patients with type 1 diabetes. Our aim was to investigate whether abnormalities are found in patients in very good glycemic control and, if so, to estimate the role of residual β-cell function. Patients with hemoglobin A 1c (HbA 1c) less than 6% (reference range, 3.6-5.4%) were selected for the study. Twenty-two men and 24 women, aged 41.3 ± 13.8 yr (mean ± SD), with a diabetes duration of 17.8 ± 14.6 yr participated. Healthy controls (15 women and nine men), aged 41.3 ± 13.0 yr, were also studied. Overnight fasting serum samples were analyzed for HbA 1c, C peptide, free and total IGFs, IGF-binding proteins (IGFBPs), GH-binding protein, and IGFBP-3 proteolysis. HbA 1c was 5.6 ± 0.5% in patients and 4.4 ± 0.3% in controls. Total IGF-I was 148 ± 7 μg/liter in patients and 178 ± 9 μg/liter in controls (P < 0.001). Free IGF-I, total IGF-II, IGFBP-3, and GH-binding protein were lower, whereas IGFBP-1, IGFBP-1-bound IGF-I, and IGFBP-2 were elevated compared with control values. Patients with detectable C peptide (≥100 pmol/liter) had higher levels of total IGF-I, free IGF-I, and total IGF-II and lower levels of IGFBP-1 and IGFBP-2 than those with an undetectable C peptide level despite having identical average HbA 1c. IGFBP-3 proteolysis did not differ between patients and controls. Despite very good glycemic control, patients with type 1 diabetes and no endogenous insulin production have low free and total IGF-I. Residual β-cell function, therefore, seems more important for the disturbances in the IGF system than good metabolic control per se, suggesting that portal insulin delivery is needed to normalize the IGF system.

  • 41.
    Hedman, Christina
    et al.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Direct comparison of insulin lispro and aspart shows small differences in plasma insulin profiles after subcutaneous injection in type 1 diabetes2001In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 24, p. 1120-1121Article in journal (Refereed)
    Abstract [en]

    No abstract available.

  • 42.
    Hedman, Christina
    et al.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Orre-Pettersson, A-C
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Treatment with insulin lispro changes the insulin profile but does not affect the plasma concentrations of IGF-I and IGFBP-1 in type 1 diabetes2001In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 55, no 1, p. 107-112Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE IGF-I levels in patients with type 1 diabetes without endogenous insulin production are low. Our aim was to examine whether the plasma insulin profile obtained by treatment with the insulin analogue lispro has a different effect on plasma concentrations of IGF-I and IGFBP-1 than that seen during treatment with conventional human insulin (regular insulin).

    DESIGN AND PATIENTS Twelve patients with type 1 diabetes, age 47·8 ± 2·4 years (mean ± SEM), body mass index 26·5 ± 1·0 kg/m2, diabetes duration 30·5 ± 3·2 years participated in this open label randomized cross-over study. IGF-I and IGFBP-1 levels were measured at the end of 6 weeks treatment with each insulin being administered by a continuous subcutaneous insulin infusion. IGF-I was measured fasting while IGFBP-1, free insulin and blood glucose were measured fasting and repeatedly after a morning meal preceded by an insulin bolus dose.

    RESULTS Lispro gave a marked insulin peak of 135 ± 20 pmol/l 50 minutes after injection. After an initial rapid rise, human regular insulin reached a plateau of approximately 50 pmol/l. The plasma free insulin area under the curve (AUC) from 0710 h to 0910 h was more than twice as large on lispro as on regular insulin (P = 0·01). Plasma IGF-I concentration was 78·8 ± 10·9 µg/l on lispro and 82·3 ± 10·5 µg/l on human regular insulin (not significant). AUC for IGFBP-1 did not show a significant difference even when divided from 0710 h to 0910 h and from 0930 h to 1430 h. Blood glucose AUC after administration of the bolus was significantly lower during treatment with lispro (P = 0·006) but glycosylated haemoglobin (HbA1c) was 6·4 ± 0·2% on both therapies.

    CONCLUSIONS Our results indicate that the effect of lispro on IGF-I and IGFBP-1 in patients with type 1 diabetes does not differ from that of human regular insulin.

  • 43. Hellström, L
    et al.
    Hellström, L
    Elinder, CG
    Elinder, C-G
    Dahlberg, B
    Dahlberg, B
    Lundberg, M
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL.
    Lundberg, M
    Järup, L
    Persson, Bodil
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Axelson, Olav
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Cadmium exposure and end-stage renal disease2001In: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 38, no 5, p. 1001-1008Article in journal (Refereed)
    Abstract [en]

    Environmental exposure to cadmium may cause kidney damage and tubular proteinuria. We investigated the relationship between low-level cadmium exposure and end-stage renal disease (ESRD), indicated by renal replacement therapy (RRT), in a Swedish population environmentally or occupationally exposed to cadmium. Based on records of all persons in the population previously or presently employed in cadmium-battery production or residing in cadmium-polluted areas near the battery plants, we defined exposure as high (occupational), moderate (domicile < 2 km from a plant), low (domicile 2 to 10 km from a plant), or no exposure (domicile > 10 km from a plant). Comprehensive data were available for all individuals undergoing RRT since 1978. The annual incidence of RRT increased from 41 per million in the age group 20 to 29 years to 243 per million in the age group 70 to 79 years and was greater in a priori-defined populations with cadmium exposure. Adjusting for age and sex gave an increased Mantel-Haenszel rate ratio (MH-RR) of 1.8 (95% confidence interval [CI], 1.3 to 2.3) for RRT in the cadmium-exposed population compared with the unexposed group, the MH-RR was even higher for women (MH-RR, 2.3, 95% CI, 1.5 to 3.5). Directly age-standardized rate ratios for RRT and cadmium exposure increased from 1.4 (95% CI, 0.8 to 2.0) in the low-exposure group to 1.9 (95% CI, 1.3 to 2.5) and 2.3 (95% CI, 0.6 to 6.0) in the moderate- and high-exposure groups, respectively. We conclude that exposure to occupational or relatively low environmental levels of cadmium appears to be a determinant for the development of ESRD. ⌐ 2001 by the National Kidney Foundation, Inc.

  • 44. Hirsch, Mark
    et al.
    O´Donnell, John
    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.
    Rosuvastatin is cost-effective compared with atorvastatin in reaching cholesterol goals2005In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 104, no 3, p. 251-256Article in journal (Refereed)
    Abstract [en]

    Background: Lowering low-density lipoprotein cholesterol (LDL-C) levels reduces the risk of coronary heart disease. The introduction of a highly efficacious new statin, rosuvastatin, may enable more patients to be treated to LDL-C goal within a fixed budget. Objectives: To compare the cost-effectiveness of rosuvastatin 10 mg and atorvastatin 10 mg in lowering LDL-C and achieving guideline goals after 12 weeks of treatment. The LDL-C goals were those recommended by the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III and the Third Joint European Task Force. Methods: The analysis was performed on pooled data from three clinical trials. Efficacy was measured as the percent reduction in LDL-C and the proportion of patients who reached guideline LDL-C goals following the first 12 weeks of treatment, prior to dose titration. Costs comprised drug acquisition costs only. The cost-effectiveness measures were cost per 1% reduction in LDL-C and cost per patient treated to their LDL-C goal. Results: Treatment with rosuvastatin 10 mg costs €1.85 per 1% reduction in LDL-C, compared with €2.37 per 1% reduction with atorvastatin 10 mg. The average costs per patient treated to the European LDL-C goals were €130.18 for rosuvastatin 10 mg and €242.44 for atorvastatin 10 mg. Treating to NCEP ATP III goals costs €115 per patient treated with rosuvastatin 10 mg vs. €163 per patient treated with atorvastatin 10 mg. Conclusions: Rosuvastatin has the same acquisition costs as and is more efficacious than atorvastatin in lowering LDL-C and treating patients to target LDL-C levels. © 2005 Elsevier Ireland Ltd. All rights reserved.

  • 45.
    Hjortswang, Henrik
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Ström, Magnus
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Almeida, R. T.
    Dept. of Biomedical Engineering/COPPE, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
    Almer, Sven
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Evaluation of the RFIPC, a disease-specific health-related quality of life questionnaire, in Swedish patients with ulcerative colitis1997In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 32, no 12, p. 1235-1240Article in journal (Refereed)
    Abstract [en]

    Background: We wanted to characterize a Swedish version of the Rating Form of Inflammatory Bowel Disease Patient Concerns (RFIPC) with regard to validity, reliability, and responsiveness.

    Methods: Two hundred and three consecutive patients with ulcerative colitis were studied. Health-related quality of life (HRQOL) was measured with the disease-specific questionnaire, the RFIPC, and a general questionnaire, the Sickness Impact Profile (SIP). Concerns about general well-being were also reported. Disease activity was measured by means of symptom cards, laboratory tests, and two clinical indices for disease activity.

    Results: Test-retest reliability using Spearman's r (rs) was 0.79, and internal consistency measured with Cronbach's alpha was 0.95. RFIPC had a fair correlation with concerns about general well-being (rs = 0.69, P < 0.001). There was also a stronger correlation with another measure of HRQOL, the overall SIP score (rs = 0.43), than with measures of disease activity such as stool frequency (rs = 0.28) and sigmoidoscopic grading (NS). The group of patients in relapse had a higher RFIPC sum score than patients in remission (P = 0.001). Measures of HRQOL had a low correlation with disease activity and did not respond to changes in disease activity.

    Conclusion: The Swedish version of the RFIPC is a valid and reliable measure of HRQOL. The SIP and the RFIPC have a good discriminative ability between groups of patients in remission and in relapse. However, they do not seem to be useful in predicting the disease activity or change in disease activity over time in the individual patient.

  • 46. Holdaas, Hallvard
    et al.
    Fellström, Bengt
    Holme, Ingar
    Nyberg, Gudrun
    Fauchald, Per
    Jardine, Alan
    Grönhagen-Riska, Carola
    Madsen, Sören
    Neymayer, Hans-Hellmut
    Cole, Edward
    Meas, Bart
    Thomas, Weinreich
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Pedersen, Terje
    Benghozi, Renée
    Hartmann, Anders
    Effects of fluvastatin on cardiac events in renal transplant patients: ALERT (assessment of Lescol in renal tranplantion) study design and baseline data2001In: Journal of Cardiovascular Risk, ISSN 1350-6277, E-ISSN 1473-5652, Vol. 8, p. 63-71Article in journal (Refereed)
  • 47.
    Hollman, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine.
    Att leva med ärftligt höga kolesterolvärden och ökad risk för kranskärlssjukdom2004In: Incitament, ISSN 1103-503X, Vol. 2, p. 133-136Article in journal (Other (popular science, discussion, etc.))
  • 48.
    Hollman, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine.
    Familjär hyperkolesterolemi. Att leva med ärftligt ökad risk för sjukdom2004In: Medikament, ISSN 1402-3881, Vol. 1, p. 46-49Article in journal (Other (popular science, discussion, etc.))
  • 49.
    Hollman, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine.
    Leva med ökad risk för sjukdom inom familjen2004In: Vårdfacket, ISSN 0347-0911, Vol. 3, p. 53-54Article in journal (Other academic)
  • 50.
    Hollman, Gunilla
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Living with familial hypercholesterolaemia2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis was to describe quality of life 1) in patients with heterozygous familial hypercholesterolaemia (FH), a genetic disorder with an increased risk of coronary heart disease (CHD), 2) in family members of patients with FH. Furthermore, the aim was to analyse the extent to which treatment goals were achieved, as well as adherence and disease knowledge in patients with FH. In order to describe quality of life, anxiety, depression and coping, patients with FH (n=185) and their non-affected family members (n=129) without FH completed the following questionnaires: the Quality of Life Index (QLI), the Hospital Anxiety and Depression Scale (HAD), the Mastery Scale and a questionnaire on health and lipids. A reference group (n=I485) completed the same questionnaires on quality of life, anxiety, depression and coping. In order to describe quality of life from a deeper perspective and identify its meaning, patients with FH (n=12) were interviewed and data were analysed according to the grounded theory method, using constant comparative analysis. The extent to which treatment goals had been achieved was documented (n=74) and patients completed a questionnaire on adherence and knowledge about FH (n=68). The patients were more satisfied with overall quality of life, family life, socio-economic life and psychological/spiritual life than the reference group, (p<0.05). Of the patients, 86 % felt anxiety about contracting CHD. Family members, particularly partners, were more satisfied with family life and psychological/spiritual life than the reference group, (p<0.05). Anxiety about the affected family member contracting CHD was expressed among 91% of the family members. The meaning of quality of life was harmony in life. Cognizance of the threat of CHD, impending mortality, satisfaction and togetherness were balanced to reach harmony in life. The treatment goals for low-density lipoprotein (LDL) (<3.0 mmol/L) and total cholesterol(<5.0 mmol/L) were reached in 23 % and 22 % of the patients, respectively. Adherence to medical treatment was significantly higher in patients who had reached the treatment goal for LDL cholesterol (< 3.0 mmol/L) than those on treatment with a LDL cholesterol ≥ 3.0 mmol/L, (p < 0.05). Out of 11 possible correct answers, there was a mean of 6.8±2.2 correct answers on knowledge about FH. Patients' knowledge was best with regard to what cholesterol is, self-care prevention and reason for drug treatment. Sixty-six percent of the patients did not know about the chance of getting FH and 79 % had no knowledge of the family history of FH. Quality of life in patients with FH and their family members was at least as good as in the reference group. In order to decrease the anxiety among patients and their family members, it is important to meet them at their knowledge level, to support understanding of FH, its risk and treatment, thus facilitating living with harmony in life.

    List of papers
    1. Quality of life in patients with familial hypercholesterolaemia
    Open this publication in new window or tab >>Quality of life in patients with familial hypercholesterolaemia
    Show others...
    2002 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 251, no 4, p. 331-337Article in journal (Refereed) Published
    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.

    Keywords
    adaptation, anxiety, familial hypercholesterolemia, personal health, quality of life
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26415 (URN)10.1046/j.1365-2796.2002.00963.x (DOI)11952884 (PubMedID)10956 (Local ID)10956 (Archive number)10956 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    2. Familial hypercholesterolaemia and quality of life in family members
    Open this publication in new window or tab >>Familial hypercholesterolaemia and quality of life in family members