| 1. |
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| 2. |
- Dunér, Pontus, et al.
(författare)
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Immune responses against fibronectin modified by lipoprotein oxidation and their association with cardiovascular disease.
- 2009
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; Feb 14., s. 593-603
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Tidskriftsartikel (refereegranskat)abstract
- Abstract. Dunér P, To F, Alm R, Gonçalves I, Fredrikson GN, Hedblad B, Berglund G, Nilsson J, Bengtsson E (Malmö University Hospital, Lund University, Lund, Sweden). Immune responses against fibronectin modified by lipoprotein oxidation and their association with cardiovascular disease. J Intern Med 2009; doi: 10.1111/j.1365-2796.2008.02067.xObjectives. Accumulation and subsequent oxidation of LDL in the arterial wall are considered as key events in the development of atherosclerosis. We have investigated the possibility that LDL oxidation results in release of aldehydes that modify surrounding matrix proteins and that this may target immune responses against the plaque extracellular matrix and modulate the disease progression. Results. Using custom-made ELISAs we demonstrate that human plasma contains autoantibodies against aldehyde-modified fibronectin (FN) and to a lesser extent also other extracellular matrix proteins including collagen type I, type III, and tenascin-C. Immunohistochemistry and western blot analysis showed that aldehyde-modified FN is present in human atherosclerotic plaques and that aldehydes generated by oxidation of LDL formed adducts with FN in vitro. We also demonstrate that aldehyde-modification of FN results in a loss of its ability to promote basal secretion of cytokines and growth factors from cultured macrophages without affecting the ability of the cells to respond to stimulation with LPS. A prospective clinical study demonstrated that subjects that subsequently developed acute myocardial infarction or sudden cardiac death had lower baseline levels of autoantibodies against aldehyde-modified FN than matched controls. Conclusions. These observations demonstrate that oxidation of LDL in the arterial wall may lead to aldehyde-modification of surrounding extracellular matrix proteins and that these modifications may affect macrophage function and activate autoimmune responses of pathophysiological importance for the development of atherosclerosis.
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| 3. |
- Cervin, Camilla, et al.
(författare)
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An investigation of serum concentration of apoM as a potential MODY3 marker using a novel ELISA.
- 2010
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 267, s. 316-321
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Tidskriftsartikel (refereegranskat)abstract
- Abstract. Cervin C, Axler O, Holmkvist J, Almgren P, Rantala E, Tuomi T, Groop L, Dahlbäck B, Karlsson E (Lund University, Malmö, Sweden, Steno Diabetes Center, Gentofte, Denmark, University of Helsinki; and Folkhälsan Research Centre, Helsinki, Finland). An investigation of serum concentration of apoM as a potential MODY3 marker using a novel ELISA. J Intern Med 2009; doi: 10.1111/j.1365-2796.2009.02145.x.Objective. To investigate the fitness of serum apolipoprotein M (apoM) concentration as a marker for maturity-onset diabetes of the young 3 (MODY3). Study design and subjects. This study consisted of two parts. A family study included 71 carriers of the P291fsinsC mutation in hepatocyte nuclear factor-1alpha (HNF-1alpha) from the Finnish Botnia study, 53 of whom were diabetic, and 75 matched family controls. A second, case-control study included 24 MODY3 patients, 17 healthy MODY3 mutation carriers, 11 MODY1 patients, 18 type 2 diabetes patients and 19 healthy control individuals. Subjects in the case-control study were recruited from the Botnia study or the Clinic of Endocrinology, Malmö University Hospital. Serum apoM levels were measured using a novel ELISA based on two monoclonal apoM antibodies. Results. In the family study, mean serum apoM was 10% lower in female carriers of the P291fsinsC mutation compared to the family controls (P = 0.0058), a difference which remained significant after adjustment for diabetes status. There was no observed difference between groups for men. In the case-control study, no significant difference in apoM concentration was observed between MODY3 and type 2 diabetes patients, neither before nor after adjustment for total cholesterol. Conclusions. Female carriers of the P291fsinsC mutation in HNF-1alpha displayed slightly lower apoM serum levels. This difference is too small for apoM to be reliably employed as a biomarker for HNF-1alpha mutation status.
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| 4. |
- Wigren, Maria, et al.
(författare)
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Evidence for a role of regulatory T cells in mediating the atheroprotective effect of apolipoprotein B peptide vaccine.
- 2011
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 269, s. 546-556
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Tidskriftsartikel (refereegranskat)abstract
- Abstract. Wigren M, Kolbus D, Dunér P, Ljungcrantz I, Söderberg I, Björkbacka H, Fredrikson GN, Nilsson J. (Malmö University Hospital, Lund University; Malmö University, Malmo; Sweden) Evidence for a role of regulatory T cells in mediating the atheroprotective effect of apolipoprotein B peptide vaccine. J Intern Med 2010; doi: 10.1111/j.13 65-2796.2010.02311.x. Objectives. Autoimmune responses against oxidized low-density lipoprotein are considered to play an important pro-inflammatory role in atherosclerosis and to promote disease progression. T-regulatory cells (Tregs) are immunosuppressive cells that have an important part in maintaining self-tolerance and protection against autoimmunity. We investigated whether aBp210, a prototype atherosclerosis vaccine based on a peptide sequence derived from apolipoprotein B, inhibits atherosclerosis through the activation of Tregs. Design. Six-week-old Apoe(-/-) mice were immunized with aBp210 and received booster immunizations 3 and 5 weeks later, as well as 1 week before being killed at 25 weeks of age. Results. At 12 weeks, immunized mice had increased expression of the Treg marker CD25 on circulating CD4 cells, and concanavalin A (Con A)-induced interferon-γ, interleukin (IL)-4, and IL-10 release from splenocytes was markedly depressed. At 25 weeks, there was a fivefold expansion of splenic CD4+ CD25+ Foxp3 Tregs, a 65% decrease in Con A-induced splenic T-cell proliferation and a 37% reduction in the development of atherosclerosis in immunized mice. Administration of blocking antibodies against CD25 neutralized aBp210-induced Treg activation as well as the reduction of atherosclerosis. Conclusions. The present findings demonstrate that immunization of Apoe(-/-) mice with the apolipoprotein B peptide vaccine aBp210 is associated with activation of Tregs. Administration of antibodies against CD25 results in depletion of Tregs and blocking of the atheroprotective effect of the vaccine. Modulation in atherosclerosis-related autoimmunity by antigen-specific activation of Tregs represents a novel approach for treatment of atherosclerosis.
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| 5. |
- Zöller, Bengt, et al.
(författare)
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Familial risks of unusual forms of venous thrombosis: a nationwide epidemiological study in Sweden.
- 2011
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 270, s. 158-165
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Tidskriftsartikel (refereegranskat)abstract
- Zöller B, Li X, Sundquist J, Sundquist K. (Center for Primary Health Care Research, Lund University, Malmö, Sweden; Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA). Familial risks of unusual forms of venous thrombosis: a nationwide epidemiological study in Sweden. J Intern Med 2010; doi: 10.1111/j.1365-2796.2010.02326.x. ABSTRACT.: Objective. This is the first nationwide study to determine familial risks of unusual forms of venous thrombosis amongst offspring of affected parents and amongst siblings. Design and settings. The Swedish Multigeneration Register of 0- to 75-year-old subjects was linked to the Hospital Discharge Register for the period 1987-2007. Standardized incidence ratios (SIRs) were calculated for individuals whose relatives were hospitalized for venous thromboembolism (VTE), as determined by the International Classification of Diseases, compared to those whose relatives were not affected by VTE. Results. The total number of hospitalized patients with VTE was 45 362, of which 1824 (4.0%) were affected by a rare thrombotic condition. The familial SIRs in cases with a history of VTE in parents or siblings were significantly increased for migrating thrombophlebitis (1.81; 95% confidence interval (CI) 1.40-2.31), portal vein thrombosis (2.35; 95% CI 1.77-3.06), vena cava thrombosis (1.96; 95% CI 1.42-2.64) and cerebral venous thrombosis (1.74; 95% CI 1.30-2.28). Budd-Chiari syndrome (SIR, 0.92; 95% CI 0.24-2.38) and renal vein thrombosis (SIR, 1.72; 95% CI 0.62-3.77) were not significantly associated with parental or sibling history of VTE; however, these two conditions were very rare, and therefore, we cannot draw any definite conclusions from this finding. Conclusions. Family history is an important risk factor for most unusual forms of VTE. Moreover, even the paraneoplastic phenomenon, migrating thrombophlebitis (Trousseau's syndrome), is associated with a family history of VTE. Thus, our data suggest that most rare forms of VTE have a familial background.
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| 6. |
- Akerstedt, T, et al.
(författare)
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Sleep as restitution: an introduction.
- 2003
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 254:1, s. 6-12
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Albiger, Barbara, et al.
(författare)
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Role of the innate immune system in host defence against bacterial infections: focus on the Toll-like receptors.
- 2007
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 261:6, s. 511-528
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Forskningsöversikt (refereegranskat)abstract
- The innate immunity plays a critical role in host protection against pathogens and it relies amongst others on pattern recognition receptors such as the Toll-like receptors (TLRs) and the nucleotide-binding oligomerization domains proteins (NOD-like receptors, NLRs) to alert the immune system of the presence of invading bacteria. Since their recent discovery less than a decade ago, both TLRs and NLRs have been shown to be crucial in host protection against microbial infections but also in homeostasis of the colonizing microflora. They recognize specific microbial ligands and with the use of distinct adaptor molecules, they activate different signalling pathways that in turns trigger subsequent inflammatory and immune responses that allows a immediate response towards bacterial infections and the initiation of the long-lasting adaptive immunity. In this review, we will focus on the role of the TLRs against bacterial infections in humans in contrast to mice that have been used extensively in experimental models of infections and discuss their role in controlling normal flora or nonpathogenic bacteria. We also highlight how bacteria can evade recognition by TLRs.
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| 8. |
- Almroth, Gabriel, 1953-, et al.
(författare)
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Detection and prevention of hepatitis C in dialysis patients and renal transplant recipients : A long-term follow up (1989–January 1997)
- 2002
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 251:2, s. 119-128
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Tidskriftsartikel (refereegranskat)abstract
- Background. Hepatitis C is frequent problem in dialysis wards.Design. A long time (1989–97) follow up of hepatitis C virus (HCV) infection in a Swedish nephrology unit was performed with anti-HCV screening, confirmatory antibody tests, viral RNA detection and molecular characterization. Case histories were reviewed with focus, onset of infection, liver morbidity and mortality.Results. In October 1991, 10% (19 of 184) of the patients in the unit (haemodialysis-, peritoneal dialysis and transplanted patients) were verified or suspected HCV carriers, whilst the number at the end of 1996 was 8% (13 of 157). Most patients were infected before 1991 but only in one case from a known HCV-infected blood donor. No new HCV infections associated with haemodialysis occurred during the study period. A total of 13 of 24 viremic patients had HCV genotype 2b, a pattern suggesting nosocomial transmission. This was further supported by phylogenetic analysis of HCV viral isolates in seven. HCV viremia was also common in patients with an incomplete anti-HCV antibody pattern as 8 of the 12 indeterminant sera were HCV-RNA positive.Conclusions. Awareness, prevention, identification of infected patients and donor testing limited transmission. Indeterminant recombinant immunoblot assays (RIBA)-results should be regarded with caution as a result of the relative immunodeficiency in uremic patients. Our data indicate nosocomial transmission in several patients.
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| 9. |
- Anwaar, I., et al.
(författare)
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Hormone replacement therapy in healthy postmenopausal women. Effects on intraplatelet cyclic guanosine monophosphate, plasma endothelin-1 and neopterin
- 2000
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 247:4, s. 463-470
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To evaluate beneficial effects of postmenopausal hormone replacement therapy (HRT) on endothelial function, measured as intraplatelet cyclic guanosine monophosphate (cGMP, mediator of nitric oxide), cyclic adenosine monophosphate (cAMP, mediator of prostacyclin) and plasma endothelin-1 (ET-1), and on monocyte activation, measured as plasma neopterin. Design. Part 1: double-blind randomized trial for 3 months; part 2: open study for 9 months. Setting. The study was performed at the Department of Endocrinology, University Hospital, Malmo, Sweden. Subjects. Fifty-one postmenopausal women participated in part 1 and 46 in part 2. Inclusion criteria included a history of amenorrhoea for at least 6 months before the study and body mass index ≥ 24 kg m-2 Intervention. Randomization for either placebo (n = 24) or HRT (n = 27). HRT was given as 2 mg oestradiol valerate for the first 3 months with the addition of 10 mg medroxyprogesterone for 10 days every third month thereafter. Measurements. Performed at baseline and after 3 and 12 months of the study. Results. In the HRT group, intraplatelet cGMP increased from 0.56 (0.35-0.94) to 0.61 (0.423.40) and 0.65 (0.43-1.08) pmol (109 platelets)-1 after 3 and 12 months, respectively (P = 0.01), whereas plasma ET-1 decreased from 3.2 (1.1.-6.8) to 2.0 (0.8-5.1) and 1.8 (0.4-15.4) pg mL-1 (P < 0.001). Intraplatelet cAMP and plasma neopterin were unchanged. When smokers (n = 15) and non-smokers (n = 12) in the HRT group were analysed separately, significant effects were seen only amongst smokers. The control group showed unchanged levels of cGMP, cAMP, ET-1 and neopterin. Conclusions. These data suggest beneficial effects of HRT on endothelial function which may account for anti-atherogenic effects of HRT in postmenopausal women, especially in smokers. No effects of HRT were seen upon monocyte activation.
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| 10. |
- Astermark, Jan, et al.
(författare)
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Low recurrence rate after deep calf-vein thrombosis with 6 weeks of oral anticoagulation
- 1998
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 244:1, s. 79-82
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate the recurrence rate after deep calf-vein thrombosis treated with 6 weeks of oral anticoagulation. DESIGN AND SUBJECTS: A 2 year follow-up of 126 consecutive patients admitted to the Department of Internal Medicine with venographically verified deep calf-vein thrombosis. RESULTS: One hundred and twenty-six patients were treated with warfarin for 6 weeks, 18 of them having had a previous episode of venous thrombosis (DVT). Eleven patients (8.7%) suffered a recurrent thromboembolic episode within 2 years, four of which were within the first 3 months. Eight of those without a history of DVT had a recurrence (7.4%). Three of these were activated protein C (APC)-resistant, one was protein C-deficient and one had malignant melanoma. Eight patients (6.3%) reported minor haemorrhagic complications, but no major bleeding was seen. CONCLUSION: Our data support the use of a 6 week regimen of secondary oral prophylaxis after a first episode of deep calf-vein thrombosis in patients without a permanent risk factor. Whether individuals with inherited thrombophilia require prolonged treatment remains to be evaluated.
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| 11. |
- Bajc, Marika, et al.
(författare)
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Ventilation/Perfusion SPECT for diagnostics of pulmonary embolism in clinical practice.
- 2008
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 264:4, s. 379-387
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The aim of this retrospective study is to illustrate clinical utility and impact of pulmonary embolism (PE) diagnostics of up to date Ventilation/Perfusion SPECT (V/P (SPECT)) applying holistic interpretation criteria. MATERIAL AND METHODS: During a 2-year period 2328 consecutive patients referred to V/P(SPECT) for clinically suspected PE were examined. Final diagnosis was established by physicians clinically responsible for patient care. To establish the performance of V/P(SPECT) negative for PE, patients were followed up by medical records for 6 months. RESULTS: Ventilation/Perfusion SPECT was feasible in 99% of the patients. Data for follow-up were available in 1785 patients (77%). PE was reported in 607 patients (34%). Normal pattern was described in 420 patients (25%). Pathology other than PE such as a pneumonia, left heart failure, obstructive lung disease, tumour was described in 724 patients (41%). Report was nondiagnostic in 19 patients (1%). Six cases were classified as falsely negative because PE was diagnosed at follow-up and was fatal in one case. Six cases were classified as falsely positive because the clinician decided not to treat. In 608 patients with final PE diagnosis, 601 patients had positive V/P(SPECT) (99%). In 1177 patients without final PE diagnosis 1153 patients had negative V/P(SPECT) (98%). CONCLUSIONS: Holistic interpretation of V/P(SPECT,) yields high negative and positive predictive values and only 1% of nondiagnostic findings and was feasible in 99% of patients. It is a responsibility and a challenge of nuclear medicine to provide optimal care of patients with suspected PE by making V/P(SPECT) available.
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| 12. |
- Berglund, Göran, et al.
(författare)
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Reply to gullberg and ranstam.
- 2009
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 266:6, s. 576-577
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Tidskriftsartikel (refereegranskat)
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| 13. |
- Beulens, J. W. J., et al.
(författare)
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Alcohol consumption and risk of type 2 diabetes in European men and women : influence of beverage type and body size The EPIC-InterAct study
- 2012
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Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796. ; 272:4, s. 358-370
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the association between alcohol consumption and type 2 diabetes, and determine whether this is modified by sex, body mass index (BMI) and beverage type. Design: Multicentre prospective casecohort study. Setting: Eight countries from the European Prospective Investigation into Cancer and Nutrition cohort. Subjects: A representative baseline sample of 16 154 participants and 12 403 incident cases of type 2 diabetes. Interventions: Alcohol consumption assessed using validated dietary questionnaires. Main outcome measures: Occurrence of type 2 diabetes based on multiple sources (mainly self-reports), verified against medical information. Results: Amongst men, moderate alcohol consumption was nonsignificantly associated with a lower incidence of diabetes with a hazard ratio (HR) of 0.90 (95% CI: 0.781.05) for 6.112.0 versus 0.16.0 g day-1, adjusted for dietary and diabetes risk factors. However, the lowest risk was observed at higher intakes of 24.196.0 g day-1 with an HR of 0.86 (95% CI: 0.750.98). Amongst women, moderate alcohol consumption was associated with a lower incidence of diabetes with a hazard ratio of 0.82 (95% CI: 0.720.92) for 6.112.0 g day-1 (P interaction gender <0.01). The inverse association between alcohol consumption and diabetes was more pronounced amongst overweight (BMI = 25 kg m-2) than normal-weight men and women (P interaction < 0.05). Adjusting for waist and hip circumference did not alter the results for men, but attenuated the association for women (HR=0.90, 95% CI: 0.791.03 for 6.112.0 g day-1). Wine consumption for men and fortified wine consumption for women were most strongly associated with a reduced risk of diabetes. Conclusions: The results of this study show that moderate alcohol consumption is associated with a lower risk of type 2 diabetes amongst women only. However, this risk reduction is in part explained by fat distribution. The relation between alcohol consumption and type 2 diabetes was stronger for overweight than normal-weight women and men.
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| 14. |
- Björkbacka, Harry, et al.
(författare)
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Weak associations between human leucocyte antigen genotype and acute myocardial infarction
- 2010
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Ingår i: Journal of Internal Medicine. - : Blackwell Publishing Ltd. - 0954-6820 .- 1365-2796. ; 268:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Human leucocyte antigens (HLAs) are polymorphic molecules involved in antigen presentation. Associations between HLA type and autoimmune diseases, such as type 1 diabetes and rheumatoid arthritis, are well established but the potential association of genetic variation affecting antigen presentation with cardiovascular disease has not been systematically investigated in large cohorts. The importance of such studies is stressed by recent experimental findings of an involvement of autoimmunity in the atherosclerotic disease process. Results: An SSP-PCR method was used for HLA genotyping to determine associations of HLA-DRB1, -DQA1 and -DQB1 with cardiovascular disease in a population-based cohort of 1188 acute myocardial infarction (AMI) patients and 1191 matched healthy controls. The HLA-DRB1*0101 allele, as well as the HLA-DRB1*0101-DQA1*01-DQB1*05 haplotype, was found to be associated with increased risk for AMI (OR 1.24; 95% CI 1.00–1.54 for both). In contrast, the DRB1*07 and DQA*02 alleles (OR 0.78; 95% CI 0.65–0.95 for both), as well as the DRB1*07-DQA*02-DQB*02 haplotype, conferred protection (OR 0.79; 95% CI 0.63–0.98). An HLA risk score taking each individual’s both haplotypes into account was higher amongst cases (2.43 ± 0.92 vs. 2.29 ± 0.95, P = 0.001). The association between HLA risk score and AMI was independent of other cardiovascular riskfactors assessed. Conclusions: This study demonstrates that the associations between HLA-DRB1 and DQA1 loci and cardiovascular disease exists but that they are considerably weaker than those previously reported for other diseases with an established autoimmune aetiology such as type 1 diabetes, systemic lupus erythematosus and rheumatoid arthritis.
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| 15. |
- Boerma, M, et al.
(författare)
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A genetic polymorphism in connexin 37 as a prognostic marker for atherosclerotic plaque development
- 1999
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 246:2, s. 211-218
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Atherosclerosis is a multifactorial disease, in part characterized by chronic inflammatory changes in the vessel wall and loss of normal physical and biochemical interactions between endothelial cells and smooth muscle cells. Previous studies [Hu J., Cotgreave IA. J Clin Invest; 99: 1-5] have provided molecular links between inflammation and myoendothelial communication via gap junctions, suggesting that these structures may be important in the development of the atherosclerotic vessel phenotype. In order to strengthen this premise, the aim of the present work was to probe for structural polymorphisms in connexin 37, a gap junctional protein uniquely expressed in endothelial cells, and to assess for potential genotypic segregation in individuals displaying atherosclerotic plaque. METHODS AND RESULTS: Computer-based comparisons of Expressed Sequence Tags (ESTs) predicted a polymorphism in the human gap junctional protein connexin 37 (cx37). The C1019-T mutation results in a proline to serine shift at codon 319 (cx37*1-cx37*2). A Restriction Fragment Length Polymorphism (RFLP) assay, involving the insertion of a novel Drd I cleavage site in the proline variant revealed a statistically significant over-representation of the cx37*1 allele in association with atherosclerotic plaque-bearing individuals (Odds-ratio for the homozygote = 2.38, Chi2 = 7.693, P = 0.006), in comparison to individuals lacking plaque, irrespective of a history of hypertension. CONCLUSIONS: These data suggest that the C1019-T polymorphism in cx37 may provide 'single gene marker', which could be useful in assessing atherosclerotic plaque development, particularly in cardiovascular risk groups such as those with borderline hypertension.
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| 16. |
- Borén, Jan, 1963, et al.
(författare)
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Kinetic Studies to Investigate Lipoprotein Metabolism.
- 2012
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Ingår i: Journal of internal medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 271:2, s. 166-173
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Forskningsöversikt (refereegranskat)abstract
- To develop novel strategies for prevention and treatment of dyslipidaemia, it is essential to understand the pathophysiology of dyslipoproteinaemia in humans. Lipoprotein metabolism is a complex system in which abnormal concentrations of various lipoprotein particles can result from alterations in their rates of production, conversion and/or catabolism. Traditional methods that measure plasma lipoprotein concentrations only provide static estimates of lipoprotein metabolism and hence limited mechanistic information. By contrast, the use of tracers labelled with stable isotopes and mathematical modelling provides a powerful tool for probing lipid and lipoprotein kinetics in vivo and furthering understanding of the pathogenesis of dyslipoproteinaemia.
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| 17. |
- Christensson, Anders, et al.
(författare)
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Serum cystatin C advantageous compared with serum creatinine in the detection of mild but not severe diabetic nephropathy.
- 2004
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 256:6, s. 510-518
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether serum cystatin C is more accurate than serum creatinine in the detection of diabetic nephropathy, also after adjustment for age.METHODS: Forty-one patients with type 1 and 82 patients with type 2 diabetes were evaluated with serum creatinine, serum cystatin C, and (51)Cr-EDTA clearance (reference method). Cystatin C was measured by a particle-enhanced turbidimetric method and creatinine by an enzymatic method. Statistical estimations were performed both without and with age adjustment created by z-scores for (51)Cr-EDTA clearance, creatinine, and cystatin C. The cut-off levels for glomerular filtration rate (GFR) ((51)Cr-EDTA clearance) were 60 and 80 mL min(-1) 1.73 m(-2), respectively, in absolute values and 80, 90 and 95% CIs, respectively, in age-adjusted values (z-scores).RESULTS: Estimations without age adjustment showed significantly (P = 0.0132) closer correlation for cystatin C (r = 0.817) versus (51)Cr-EDTA clearance as compared with creatinine (r = 0.678). However, when using age-adjusted values, the correlation for cystatin C and creatinine, respectively, versus (51)Cr-EDTA clearance did not differ. When comparing the diagnostic utilities for serum cystatin C versus serum creatinine in manifest renal impairment (GFR < 60 mL min(-1) 1.73 m(-2) or z-scores <-1.28 SD), there were no significant differences between the two markers whether age adjusted or not. However, for diagnosing mild nephropathy (GFR < 80 mL min(-1) 1.73 m(-2) or z-score -0.84 SD), serum cystatin C is significantly more useful.CONCLUSIONS: Serum cystatin C performed better compared with serum creatinine even when measured enzymatically, to detect mild diabetic nephropathy. However, serum creatinine was as efficient as serum cystatin C to detect advanced diabetic nephropathy.
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| 18. |
- Collste, O., et al.
(författare)
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Myocardial infarction with normal coronary arteries is common and associated with normal findings on cardiovascular magnetic resonance imaging: results from the Stockholm Myocardial Infarction with Normal Coronaries study
- 2013
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 273:2, s. 189-196
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Tidskriftsartikel (refereegranskat)abstract
- Collste O, Sorensson P, Frick M, Agewall S, Daniel M, Henareh L, Ekenback C, Eurenius L, Guiron C, Jernberg T, Hofman-Bang C, Malmqvist K, Nagy E, Arheden H, Tornvall P (Sodersjukhuset, Stockholm; Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden; University of Oslo, Oslo, Norway; Sankt Goran Hospital Capio, Karolinska Institutet, Stockholm; Huddinge, Stockholm; Danderyd Hospital, Karolinska Institutet, Stockholm; and Skane University Hospital, Lund University, Lund, Sweden). Myocardial infarction with normal coronary arteries is common and associated with normal findings on cardiovascular magnetic resonance imaging: results from the Stockholm Myocardial Infarction with Normal Coronaries study. J Intern Med 2013; 273: 189-196. Objectives Myocardial infarction with angiographically normal coronary arteries (MINCA) is an important subtype of myocardial infarction; however, the prevalence, underlying pathophysiology, prognosis and optimal management of this condition are still largely unknown. Cardiovascular magnetic resonance (CMR) imaging has the potential to clarify the underlying pathology in patients with MINCA. The objective of this study was to investigate the diagnostic value of CMR imaging in this group of patients. Design The prospective, multicentre, observational Stockholm Myocardial Infarction with Normal Coronaries (SMINC) study. Setting Coronary care units in the Stockholm metropolitan area. Subjects Patients between 35 and 70 years of age with MINCA were consecutively included in the screening phase of the SMINC study. All patients had a typical clinical presentation, fulfilling the universal definition of myocardial infarction and had normal coronary angiography finding. Patients with known structural or coronary heart disease or other known causes of elevated troponin levels were excluded. Results In total, 176 patients with MINCA were screened from 2007 to 2011. Of these, 152 underwent CMR imaging. The investigation was performed a median of 12 (interquartile range 628) days after hospital admission; 67% of the findings were normal, whereas 19% of patients had signs of myocardial necrosis and 7% had signs of myocarditis. The remaining patients (7%) had either unrecognized hypertrophic cardiomyopathy or could not be classified. Conclusion In this consecutive series of patients with MINCA, CMR imaging may help to differentiate between those with myocarditis, myocardial necrosis and normal myocardium. The incidence of MINCA was higher than previously reported. After excluding cases of myocarditis, MINCA consists of a large group of patients with normal CMR imaging results and a smaller group with myocardial necrosis. The aetiologies of these different imaging findings need to be explored.
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| 19. |
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| 20. |
- Dorkhan, Mozhgan, et al.
(författare)
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Independent measures of insulin secretion and insulin sensitivity during the same test: the glucagon-insulin tolerance test.
- 2008
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 264, s. 62-71
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Tidskriftsartikel (refereegranskat)abstract
- Background. To validate a test for independent assessment of insulin secretion and insulin sensitivity during the same occasion for metabolic studies in clinical practice, i.e. combined glucagon-stimulated C-peptide test and insulin tolerance test (GITT). Subjects and methods. We measured C-peptide response to 0.5 mg of intravenous glucagon followed 30 min later by administration of 0.05 U kg(-1) insulin (insulin tolerance test, ITT). Ten subjects with normal glucose tolerance participated on different days in an ITT, glucagon-C-peptide test, ITT followed by glucagon-C-peptide test and glucagon-C-peptide test followed by ITT to establish whether and how the tests could be combined. The test was then repeated in nine patients with type 2 diabetes to investigate its reproducibility. In 20 subjects with varying degrees of glucose tolerance, the test was compared with the Botnia clamp (an intravenous glucose tolerance test combined with a euglycaemic hyperinsulinemic clamp). Results. When ITT preceded the glucagon test, C-peptide response was blunted. Therefore, we first administered glucagon and then insulin (GITT). The K(ITT) from the GITT was reproducible (CV = 13 %) and correlated strongly with the glucose disposal rate from the Botnia clamp (r = 0.87, r(2) = 0.75, P < 0.001). The C-peptide response to glucagon was reproducible (CV = 13 %). The disposition index, providing a measure of beta-cell function adjusted for insulin sensitivity, calculated from the GITT showed good discrimination between individuals with varying degrees of glucose tolerance. Conclusions. The GITT provides simple, reproducible and independent estimates of insulin sensitivity and secretion on the same occasion for metabolic studies in individuals with normal and abnormal glucose tolerance.
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| 21. |
- Droyvold, WB, et al.
(författare)
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Weight change and mortality: The Nord-Trondelag Health Study
- 2005
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 257:4, s. 338-345
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. The prevalence of obesity is increasing. Overweight and obese people have increased mortality compared with normal weight people. We investigated the effect of weight change on mortality. Design. Prospective population study. Setting. We utilized data from two large population-based health studies conducted in 1984-86 and 1995-97 respectively. Cox proportional hazards models were used to calculate mortality rate ratios (RRs) with 95% confidence intervals (CIs) between people with a stable weight and people who lost or gained weight. Subjects. Totally 20 542 men and 23 712 women aged 20 years or more, without cardiovascular disease or diabetes at the first survey and without a history of cancer at the second survey were followed up on all-cause mortality for 5 years after the second survey. Results. We found no association between weight gain and mortality. People who lost weight had a higher total mortality rate compared with those who were weight stable [RR was 1.6 (95% CI: 1.4-1.8) in men and 1.7 (95% CI: 1.5-2.0) in women]. Similar associations were found for cardiovascular and noncardiovascular mortality. Additional analysis showed a linear increase in mortality rates across categories of weight loss for both men and women (P < 0.001). There was a statistically significant interaction between weight change and initial BMI, but only amongst men (P = 0.001). Conclusions. Weight loss, but not weight gain, was associated with increased mortality amongst men and women. Although underlying undiagnosed disease is the most plausible explanation for this finding, the similar associations found for total mortality, cardiovascular mortality, and noncardiovascular mortality makes the causal pathway somewhat enigmatic.
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| 22. |
- Edvardsson, N, et al.
(författare)
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Effects of low-dose warfarin and aspirin versus no treatment on stroke in a medium-risk patient population with atrial fibrillation.
- 2003
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 254:1, s. 95-101
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To assess the optimal stroke prevention treatment for patients with atrial fibrillation (AF) and a low-medium risk (<=4%) of stroke. Design. A total of 668 patients with persistent or permanent AF, without an indication for full dose and with adequate rate control on sotalol, were randomized to warfarin 1.25 mg + aspirin 75 mg daily (W/A, 334 patients) or no anticoagulation (C, 334 patients). The mean follow-up period was 33 months. The protocol intended to verify a 37% relative risk reduction provided a 4% stroke incidence in the C group. Results. The stroke incidence was less in the W/A group, although the reduction was not statistically significant (W/A 9.6% versus C 12.3%). Four haemorrhagic strokes were identified, two in each group. Secondary end-points were transient ischaemic attacks (TIA) (W/A 3.3% versus C 4.5%), all cause mortality (W/A 9.3% versus C 10.8%), cardiovascular morbidity (W/A 17.7% versus C 22.2%) and the combination of stroke + TIA (W/A 11.7% versus C 16.5%). Bleedings were documented in 19 versus four patients (W/A 5.7% versus C 1.2%) (P = 0.003), although none fatal. Sinus rhythm (SR) was recorded occasionally in 68 patients (W/A 9.6% versus C 10.8%). The stroke incidence tended to be higher in those with SR than without, 16.2% versus 10.4%. Conclusions. Our results were inconclusive, but consistent with a small beneficial effect of W/A for reduction of stroke and major vascular events in AF patients at moderate risk. The low-dose regiment produced, however, a significantly increased risk of bleedings. Documented SR occasionally recorded may represent a subpopulation that warrants full dose warfarin.
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| 23. |
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| 24. |
- Engelbertsen, Daniel, et al.
(författare)
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High levels of IgM against methylglyoxal-modified apolipoprotein B100 is associated with less coronary artery calcification in patients with type 2 diabetes.
- 2012
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 271:1, s. 82-89
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Advanced glycation end products (AGE) have been implicated in diabetic vascular complications through activation of pro-inflammatory genes. AGE-modified proteins are also targeted by the immune system resulting in the generation of AGE-specific autoantibodies, but the association of these immune responses with diabetic vasculopathy remains to be fully elucidated. The aim of this study was to determine whether antibodies against apolipoprotein B100 modified by methylglyoxal (MGO-apoB100) are associated with coronary atherosclerosis in patients with type 2 diabetes. Methods. We measured antibodies against MGO-apoB100 in plasma from 497 type 2 diabetic patients without clinical signs of cardiovascular disease. Severity of coronary disease was assessed as coronary artery calcium (CAC) imaging. Immunoglobulin (Ig)M and IgG levels recognizing MGO-apoB100 were determined by enzyme-linked immunosorbent assay. Results. Anti-MGO-apoB100 IgM antibody levels were higher in subjects with a low to moderate CAC score (≤400 Agatston units) than in subjects with a high score (>400 Agatston units; 136.8 ± 4.4 vs. 101.6 ± 7.4 arbitrary units (AU), P < 0.0001) and in subjects demonstrating no progression of CAC during 30 months of follow-up (136.4 ± 5.7 vs. 113.9 ± 6.2 AU in subjects with progression, P < 0.0001). Subjects with a family history of premature myocardial infarction had lower levels of anti-MGO-apoB100 IgM. Female subjects had higher levels of anti-MGO-apoB100 antibodies and lower CAC than men. Accordingly, high levels of IgM against MGO-apoB100 are associated with less severe and a lower risk of progression of coronary disease in subjects with type 2 diabetes. Conclusions. Although conclusions regarding causal relationships based on epidemiological observations need to be made with caution, our findings suggest the possibility that anti-MGO-apoB100 IgM may be protective in diabetic vasculopathy.
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| 25. |
- Engström, Gunnar, et al.
(författare)
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Lung function, insulin resistance and incidence of cardiovascular disease: a longitudinal cohort study.
- 2003
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 253:5, s. 574-581
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To explore whether a reduced lung function is a risk factor for developing diabetes and insulin resistance (IR), and whether such relationship contributes to the largely unexplained association between lung function and incidence of cardiovascular disease (CVD). Design. Forced vital capacity (FVC) was assessed at baseline. Incidence of diabetes and IR [according to the homeostasis model assessment (HOMA) model] was assessed in a follow-up examination after 13.9 ± 2.6 and 9.4 ± 3.6 years for men and women, respectively. After the follow-up examination, incidence of CVD (stroke, myocardial infarction or cardiovascular death) was monitored over 7 years. Setting. Populations-based cohort study. Subjects. Initially nondiabetic men (n = 1436, mean age 44.6 years) and women (n = 896, mean age 49.8 years). Results. Prevalence of IR at the follow-up examination was 34, 26, 21 and 21%, respectively, for men in the first (lowest), second, third and fourth quartile of baseline FVC (P for trend <0.0001). The corresponding values for women were 30, 29, 25 and 17%, respectively (P for trend <0.001). Adjusted for potential confounders, the odds ratio (OR) for IR (per 10% increase in FVC) was 0.91 (CI: 0.84-0.99) for men and 0.89 (CI: 0.80-0.98) for women. FVC was similarly significantly associated with the incidence of diabetes (OR = 0.90, CI: 0.81-1.00), adjusted for sex and other confounders. The incidence of CVD after the follow-up examination was significantly increased only amongst subjects with low FVC who had developed IR (RR = 1.7, CI: 1.02-2.7). Conclusion. Subjects with a moderately reduced FVC have an increased risk of developing IR and diabetes. This relationship seems to contribute to the largely unexplained association between reduced lung function and incidence of CVD.
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