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1.	Nilsson, Peter, et al. (författare) Developmental origins of adult disease: an introduction 2007 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 261:5, s. 1-410 Tidskriftsartikel (refereegranskat)
2.	Dunér, Pontus, et al. (författare) Immune responses against fibronectin modified by lipoprotein oxidation and their association with cardiovascular disease. 2009 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; Feb 14., s. 593-603 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.
3.	Cervin, Camilla, et al. (författare) An investigation of serum concentration of apoM as a potential MODY3 marker using a novel ELISA. 2010 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 267, s. 316-321 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.
4.	Wigren, Maria, et al. (författare) Evidence for a role of regulatory T cells in mediating the atheroprotective effect of apolipoprotein B peptide vaccine. 2011 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 269, s. 546-556 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.
5.	Zöller, Bengt, et al. (författare) Familial risks of unusual forms of venous thrombosis: a nationwide epidemiological study in Sweden. 2011 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 270, s. 158-165 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.
6.	Akerstedt, T, et al. (författare) Sleep as restitution: an introduction. 2003 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 254:1, s. 6-12 Tidskriftsartikel (refereegranskat)
7.	Albiger, Barbara, et al. (författare) Role of the innate immune system in host defence against bacterial infections: focus on the Toll-like receptors. 2007 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 261:6, s. 511-528 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.
8.	Almroth, Gabriel, 1953-, et al. (författare) Detection and prevention of hepatitis C in dialysis patients and renal transplant recipients : A long-term follow up (1989–January 1997) 2002 Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 251:2, s. 119-128 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.
9.	Anwaar, I., et al. (författare) Hormone replacement therapy in healthy postmenopausal women. Effects on intraplatelet cyclic guanosine monophosphate, plasma endothelin-1 and neopterin 2000 Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 247:4, s. 463-470 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.
10.	Astermark, Jan, et al. (författare) Low recurrence rate after deep calf-vein thrombosis with 6 weeks of oral anticoagulation 1998 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 244:1, s. 79-82 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.
11.	Bajc, Marika, et al. (författare) Ventilation/Perfusion SPECT for diagnostics of pulmonary embolism in clinical practice. 2008 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 264:4, s. 379-387 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.
12.	Berglund, Göran, et al. (författare) Reply to gullberg and ranstam. 2009 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 266:6, s. 576-577 Tidskriftsartikel (refereegranskat)
13.	Beulens, J. W. J., et al. (författare) 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 Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796. ; 272:4, s. 358-370 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.
14.	Björkbacka, Harry, et al. (författare) Weak associations between human leucocyte antigen genotype and acute myocardial infarction 2010 Ingår i: Journal of Internal Medicine. - : Blackwell Publishing Ltd. - 0954-6820 .- 1365-2796. ; 268:1, s. 50-58 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-DRB10101 allele, as well as the HLA-DRB10101-DQA101-DQB105 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 DRB107 and DQA02 alleles (OR 0.78; 95% CI 0.65–0.95 for both), as well as the DRB107-DQA02-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.
15.	Boerma, M, et al. (författare) A genetic polymorphism in connexin 37 as a prognostic marker for atherosclerotic plaque development 1999 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 246:2, s. 211-218 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 (cx371-cx372). 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.
16.	Borén, Jan, 1963, et al. (författare) Kinetic Studies to Investigate Lipoprotein Metabolism. 2012 Ingår i: Journal of internal medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 271:2, s. 166-173 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.
17.	Christensson, Anders, et al. (författare) Serum cystatin C advantageous compared with serum creatinine in the detection of mild but not severe diabetic nephropathy. 2004 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 256:6, s. 510-518 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.
18.	Collste, O., et al. (författare) 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 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 273:2, s. 189-196 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.
19.	Dahlbäck, Björn (författare) Blood coagulation and its regulation by anticoagulant pathways: genetic pathogenesis of bleeding and thrombotic diseases. 2005 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 257:3, s. 209-223 Forskningsöversikt (refereegranskat)
20.	Dorkhan, Mozhgan, et al. (författare) Independent measures of insulin secretion and insulin sensitivity during the same test: the glucagon-insulin tolerance test. 2008 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 264, s. 62-71 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.
21.	Droyvold, WB, et al. (författare) Weight change and mortality: The Nord-Trondelag Health Study 2005 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 257:4, s. 338-345 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.
22.	Edvardsson, N, et al. (författare) Effects of low-dose warfarin and aspirin versus no treatment on stroke in a medium-risk patient population with atrial fibrillation. 2003 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 254:1, s. 95-101 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.
23.	Eeg-Olofsson, Katarina, 1968, et al. (författare) New aspects of HbA1c as a risk factor for cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National Diabetes Register (NDR). 2010 Ingår i: Journal of internal medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 268:5, s. 471-82 Tidskriftsartikel (refereegranskat)abstract To analyse the association between glycosylated haemoglobin A1c (HbA1c) and cardiovascular disease (CVD) in patients with type 2 diabetes in the Swedish National Diabetes Register (NDR).
24.	Engelbertsen, Daniel, et al. (författare) High levels of IgM against methylglyoxal-modified apolipoprotein B100 is associated with less coronary artery calcification in patients with type 2 diabetes. 2012 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 271:1, s. 82-89 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.
25.	Engström, Gunnar, et al. (författare) Lung function, insulin resistance and incidence of cardiovascular disease: a longitudinal cohort study. 2003 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 253:5, s. 574-581 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.
26.	Engström, Gunnar, et al. (författare) Reduced lung function predicts increased fatality in future cardiac events. A population-based study.ture 2006 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 260:6, s. 560-567 Tidskriftsartikel (refereegranskat)
27.	Engström, Gunnar, et al. (författare) Trends in long-term survival after myocardial infarction: less favourable patterns for patients from deprived areas 2000 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 248:5, s. 425-434 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: New treatments have improved the prognosis for patients with acute myocardial infarction. However, studies on long-term survival are not unequivocally in favour of an improved long-term prognosis. This study aimed to analyse trends in 3-year survival in relation to sex, age and socioeconomic level of residential area. SETTING: The Malmo myocardial infarction register, Sweden. PARTICIPANTS: All men and women in the city who, between 1978 and 1995, were admitted for a first acute myocardial infarction (n = 11 226). MAIN OUTCOME MEASURES: Age-standardized 3-year survival rates. RESULTS: Both 28-day and 3-year survival rates improved markedly during the study period. Age-standardized 3-year survival (per 100 patients) amongst men and women who survived 28 days increased, between 1978-81 and 1991-95, from 64 to 78 in men and from 66 to 77 in women, an annual increase of 1.4% (95% CI = 1.1-1.7) and 1.2% (0.8-1.5), respectively. There were marked differences in survival between residential areas with different socioeconomic circumstances. The 3-year survival rates amongst men correlated significantly with the socioeconomic circumstances in the areas expressed in terms of a socioeconomic score (men: r = 0.60, n = 17, P = 0.01; women: r = 0.37, P = 0.15). Trends tended to be less favourable in deprived areas. CONCLUSION: Three-year survival after first myocardial infarction has continuously improved for men and women in all age groups. Prognosis was worse and trends tended to be less favourable for patients from deprived areas.
28.	Eriksson, JG, et al. (författare) Long-term beneficial effects of glipizide treatment on glucose tolerance in subjects with impaired glucose tolerance 2006 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 259:6, s. 553-560 Tidskriftsartikel (refereegranskat)abstract To assess the efficacy and long-term effects of glipizide treatment on glucose and insulin metabolism in individuals with impaired glucose tolerance (IGT). Thirty-seven first-degree relatives of patients with type 2 diabetes fulfilling WHO criteria for IGT were randomized to treatment with either glipizide 2.5 mg once daily or matching placebo for 6 months. A 75 g, 2-h oral (OGTT) and 60 min intravenous glucose tolerance test (IVGTT) were performed at baseline and after 6 months. The subjects were followed up for another 12 months after discontinuation of treatment and a repeat OGTT was performed at 18 months. Thirty-three subjects fulfilled the study. Markers of insulin sensitivity - i.e. fasting insulin and HOMA(IR)-index - improved in the glipizide group (P = 0.04 and 0.02 respectively) as well as HDL cholesterol (P = 0.05) compared with placebo group after 6 months. At 18 months, both fasting and 2 h glucose concentrations were significantly lower in the glipizide group compared with the placebo group (P = 0.04 and 0.03 respectively). The prevalence of type 2 diabetes was 29.4% in the placebo group and 5.9% in the glipizide group at 18 months. This equals an 80% relative risk reduction in the active treatment group. Short-term treatment with glipizide improves glucose and insulin metabolism in subjects with IGT primarily by improving insulin sensitivity mediated by lowering glucose toxicity, thereby providing the beta cells rest. Larger studies are needed to establish whether these effects are sufficient to prevent progression to manifest type 2 diabetes and associated cardiovascular morbidity in subjects at increased risk of developing type 2 diabetes.
29.	Eriksson, Per, et al. (författare) Improved outcome in Wegener's granulomatosis and microscopic polyangiitis? A retrospective analysis of 95 cases in two cohorts 2009 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 265:4, s. 496-506 Tidskriftsartikel (refereegranskat)abstract Mortality rates for Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) have decreased after the introduction of cyclophosphamide. Standardized mortality ratio (SMR) expresses the overall mortality of patients compared with the general population. The aims of this study were to compare survival in an old and a recent cohort of patients with WG and MPA using SMR and to determine predictors for death in both groups combined. Survival analyses were performed by Kaplan-Meier survival curves, SMR and proportional hazards regression models. The nephrology and rheumatology clinics at Linkoping University Hospital, Sweden. All patients diagnosed with WG or MPA in the catchment area during 1978-2005 were divided into two cohorts; patients diagnosed before (n = 32, old cohort) and after (n = 63, recent cohort) December 31, 1996. The two cohorts differed regarding the proportion of WG (75% vs. 56%, P = 0.03) and a tendency for more pronounced kidney involvement in the old cohort: 266 mu mol L-1 (16% dialysis-dependent) vs. 192 mu mol L-1 (5% dialysis-dependent), but were comparable regarding disease severity. SMR at 1 and 5 years were 2.1 (95% CI: 0.43-6.09) and 1.6 (95% CI: 0.6-3.2) in the recent cohort and 5.2 (95% CI: 1.07-15.14) and 2.5 (95% CI: 0.93-5.52) in the old cohort. Five-year survival was 87% and 81%. Serum creatinine, age, end-stage renal disease, diagnosis before 1997 and first relapse were independent predictors for death. Patient survival in WG and MPA analysed with SMR may be better than previously believed. Severe renal disease and disease relapse were the major predictors of reduced survival.
30.	Fadeel, B., et al. (författare) Nanomedicine: reshaping clinical practice 2010 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 267:1, s. 2-8 Tidskriftsartikel (refereegranskat)
31.	Fagerberg, Björn, 1943, et al. (författare) Low birth weight in combination with catch-up growth predicts the occurrence of the metabolic syndrome in men at late middle age: the Atherosclerosis and Insulin Resistance study 2004 Ingår i: J Intern Med. - : Wiley. - 0954-6820 .- 1365-2796. ; 256:3, s. 254-9 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: To study the combined effects of a low birth weight and a pronounced weight increase up to early adulthood on the presence of cardiovascular risk factors constituting the metabolic syndrome in late middle age. DESIGN AND SETTING: A structured sample of 396 men, 58 years old from the general population. Birth weight and weight at 18 years were obtained from medical records and registers. MAIN OUTCOME MEASURES: Body mass index (BMI), waist : hip ratio (WHR), blood pressure, serum concentrations of insulin, triglycerides, HDL cholesterol and LDL particle size at age 58 years. RESULTS: The ratio between weight at age 18 years and birth weight correlated with a number of characteristics at age 58 years: BMI (r = 0.24, P < 0.001), WHR (r = 0.24, P < 0.001), diastolic blood pressure (r = 0.13, P < 0.05), insulin (r = 0.14, P < 0.01), triglycerides (r = 0.10, P < 0.05), HDL cholesterol (r = -0.13, P < 0.01) and LDL particle size (r = -0.17, P < 0.05). The metabolic syndrome, according to current definitions, were more common at the age of 58 years in the third tertile of the weight at 18/birth ratio, than in the other tertiles (P = 0.008). CONCLUSIONS: The interaction between a low birth weight and an accelerated catch-up growth to early adulthood is associated with the occurrence of the metabolic syndrome in the late middle age. These findings are in accord with the concept that the effects of genes are conditioned by fetal growth, and that the effects of a small body size at birth are conditioned by growth during childhood and by environmental factors in childhood and adult life.
32.	Fedorowski, Artur, et al. (författare) Orthostatic hypotension and long-term incidence of atrial fibrillation: the malmo preventive project 2010 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 268:4, s. 383-389 Tidskriftsartikel (refereegranskat)abstract Fedorowski A, Hedblad B, Engstrom G, Gustav Smith J, Melander O (Department of Clinical Sciences, Lund University, Malmo; and Skane University Hospital, Malmo, Sweden). Orthostatic hypotension and long-term incidence of atrial fibrillation: the Malmo Preventive Project. J Intern Med 2010; 268: 383-389. Objectives. Orthostatic hypotension (OH), a common manifestation of autonomic dysfunction, has been identified as an independent risk factor for all-cause mortality and incident cardiovascular disease. However, the role of OH in the development of atrial fibrillation has not been studied. Design. We investigated the incidence of atrial fibrillation in relation to baseline presence of OH according to international consensus criteria in the Swedish population-based prospective cohort of the Malmo Preventive Project. The study sample consisted of 33 346 individuals (67.3% men; mean age, 45.6 +/- 7.4 years; range, 26-61 years). The association between OH and incidence of atrial fibrillation during follow-up was assessed using the Kaplan-Meier method and multivariable Cox proportional hazard models, taking into account conventional risk factors for atrial fibrillation. Results. At baseline, 1987 participants (6.1%) met the diagnostic criteria for OH. Over a follow-up period of approximately 24 years, 2312 individuals (3.0 events/1000 person-years) were diagnosed with new-onset atrial fibrillation. Of these, 196 had OH at baseline (4.6 events/1000 person-years amongst all OH-positive individuals). In a multivariable Cox regression analysis, OH predicted incidence of atrial fibrillation independently of other risk factors (hazard ratio [HR]: 1.30; 95% confidence interval [CI]: 1.05-1.61; P = 0.016), and this association was significant in hypertensive (HR: 1.44; 95%CI: 1.10-1.88; P = 0.008), but not in normotensive participants (HR: 1.10; 95%CI: 0.77-1.58; P = 0.60). Conclusions. The presence of OH predicts the incidence of atrial fibrillation in middle-aged hypertensive individuals, independently of conventional risk factors. Further studies of the association of autonomic dysfunction and OH with atrial fibrillation are needed.
33.	Fenyö, Eva Maria, et al. (författare) Human immunodeficiency virus type 1 biological variation and coreceptor use: from concept to clinical significance. 2011 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 270, s. 520-531 Tidskriftsartikel (refereegranskat)abstract There is ample evidence for intra-patient evolution of the human immunodeficiency virus type 1 (HIV-1) biological phenotype during the pathogenic process. Evolution often involves switch of coreceptor use from CCR5 to CXCR4, but change to more flexible use of CCR5 occurs over time even in patients with maintained CCR5 use. The increasing use of entry inhibitors in the clinic, often specific for one or the other HIV-1 coreceptor or with different binding properties to CCR5, calls for virus testing in patients prior to treatment initiation. Cell lines expressing CCR5/CXCR4 chimeric receptors are tools for testing viruses for mode of CCR5 use. It is conceivable that small-molecule entry inhibitors that differentially bind to CCR5 can be matched for best effect against HIV-1 with different modes of CCR5 use, thereby allowing an individualized drug choice specifically tailored for each patient.
34.	Gerward, Sofia, et al. (författare) Survival rate 28 days after hospital admission with first myocardial infarction. Inverse relationship with socio-economic circumstances. 2006 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 259:2, s. 164-172 Tidskriftsartikel (refereegranskat)abstract Objective. To study to what extent geographical differences of the mortality from ischaemic heart disease (IHD) can be accounted for by the 28-day case fatality rate (CFR) following first hospital admittance for acute myocardial infarction (MI) and whether the geographical pattern of survival has any relationship with socio-economic circumstances. Design. Register-based surveillance study. Setting. Seventeen residential areas in Malmo, Sweden. Subjects. All 5533 patients were admitted during 1986-1995 for a first acute MI at Malmo University Hospital. Main outcome measures. CFR is based on record linkage with national registers. Area-specific cardiovascular and socio-economic scores (SES) are based on previous cross-sectional studies. Results. In patients below 75 years of age, differences of the 28-day CFR accounted for 20-30% of the geographical variance in mortality from IHD. No corresponding association was found in older age groups. Patients from areas with low SES had the highest CFR, 23.8%. The odds ratios of fatal outcome for patients from areas with median and low SES (versus high SES) were 1.23 (95% CI: 1.01-1.50) and 1.25 (95% CI: 1.03-1.52), respectively (P for trend: 0.060). The strongest correlation was observed in men below 75 years of age (P for trend: 0.007). During the study period there was an improvement of the survival rate for patients from high and medium SES areas but no corresponding change for patients coming from areas having a low SES. Conclusions. In patients below 75 years, geographical differences of the mortality from IHD were related to differences of the 28-day CFR following hospital admittance for a first MI. Rates of survival were inversely related to socio-economic circumstances in the patient's residential area.
35.	Glader, Eva-Lotta, 1972-, et al. (författare) Large variations in the use of oral anticoagulants in stroke patients with atrial fibrillation : A Swedish national perspective 2004 Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 255:1, s. 22-32 Tidskriftsartikel (refereegranskat)abstract Objectives. To explore nation-wide use of anticoagulation in stroke patients with atrial fibrillation, in routine clinical practice in Sweden.Design. Cross-sectional cohort study.Setting. Patients included in Riks-Stroke, the Swedish national quality register for stroke care, during 2001.Subjects. Hospitals with incomplete coverage were excluded, leaving 4538 stroke patients with atrial fibrillation amongst 18 276 stroke patients from 75 hospitals in six health care regions.Main outcome measure. Treatment with oral anticoagulants.Results. At stroke onset, the proportion of patients with atrial fibrillation and first-ever stroke, receiving oral anticoagulants as primary prevention was 11.0% (range 8.4–13.5% between regions and 2.5–24.4% between hospitals). Younger age, male sex and diabetes at stroke onset independently predicted primary prevention with oral anticoagulants. The proportion of stroke patients with atrial fibrillation receiving oral anticoagulants as secondary prevention at discharge was 33.5% (range 29.9–40.6% between regions and 16.4–61.9% between hospitals). Independent predictors for secondary prevention were younger age, male sex and independent activities of daily life (ADL) function before the stroke, being discharged to home, being fully conscious on admission and health care region.Conclusion. There were variations between hospitals and regions that differences in age, sex, functional impairments and comorbidities could not fully explain. This indicates that evidence-based primary and secondary prevention of embolic stroke is insufficiently practised. Local factors seem to determine whether patients with atrial fibrillation gain access to optimal prevention of stroke or not.
36.	Gottsäter, Anders, et al. (författare) Interleukin-1 receptor antagonist is detectable in human carotid artery plaques and is related to triglyceride levels and Chlamydia pneumoniae IgA antibodies. 2002 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 251:1, s. 61-68 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: To investigate whether the interleukin-1 receptor antagonist (Il-1ra) and interleukin-1beta (Il-1beta) can be detected in human carotid artery tissue, and whether their presence is related to evidence of Chlamydia pneumoniae infection, risk factors for atherosclerosis, and clinical data. SETTING: Departments of Vascular Diseases and Surgical Pathophysiology, University Hospital, Malmö, Sweden. SUBJECTS: A total of 66 patients undergoing carotid endarterectomy (median age 74, range 53-89 years, 26 women). Il-1beta and Il-1ra were studied in carotid artery plaques and in Il-1ra in serum. RESULTS: Interleukin-1 receptor antagonist was detected in mononuclear cells in plaques from 37/66 (56%) patients. Patients with Il-1ra in plaques showed higher [2.04 (1.70-3.14) mmol x L(-1) vs. 1.69 (1.09-1.99) mmol x L(-1); P < 0.05] serum(s-)triglyceride(tg) levels, and a higher frequency of IgA seropositivity for C. pneumoniae (76% vs. 52%; P < 0.05) than those without. S-Il-1ra levels correlated with s-tg levels (r=0.38; P=0.047). There were no differences between patients with and without Il-1ra in plaques concerning s-Il-1ra, blood(b-)haemoglobin or leucocyte count, s-cholesterol, b-glucose, blood pressure, IgG seropositivity for C. pneumoniae, prevalence of neurological symptoms preceding operation, smoking, or diabetes mellitus. There were no differences in frequency of Il-1ra in plaques or in s-Il-1ra levels between patients with symptomatic and asymptomatic stenosis, between smokers and nonsmokers, or between diabetic and nondiabetic patients. Il-1beta was not detected in plaques in the current study. CONCLUSION: Interleukin-1 receptor antagonist can be detected in human atherosclerotic carotid artery plaques, and is related to s-triglyceride levels and IgA seropositivity for C. pneumoniae, but not to prevalence of neurological symptoms related to embolization.
37.	Groop, Leif, et al. (författare) The dysmetabolic syndrome 2001 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 250:2, s. 105-120 Tidskriftsartikel (refereegranskat)abstract The first unifying definition for the metabolic syndrome was proposed by WHO in 1998. In accordance to this, patients with type 2 diabetes mellitus or impaired glucose tolerance have the syndrome if they fulfil two of the criteria: hypertension, dyslipidaemia, obesity/abdominal obesity and microalbuminuria. Persons with normal glucose tolerance (NGT) should also be insulin resistant. About 40% of persons with impaired glucose tolerance (IGT) and 70% of patients with type 2 diabetes have features of the syndrome. Importantly, presence of the dysmetabolic syndrome is associated with reduced survival, particularly because of increased cardiovascular mortality. The dysmetabolic syndrome most likely results from interplay between several genes and an affluent environment. Compatible with the thrifty gene theory, common variants in genes regulating lipolysis, thermogenesis and glucose uptake in skeletal muscle account for a large part of such thrifty genes. However, hitherto unknown genes may still be identified by random gene approaches.
38.	Hallengren, Bengt, et al. (författare) No increase in fracture incidence in patients treated for thyrotoxicosis in Malmo during 1970-74. A 20-year population-based follow-up 1999 Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 246:2, s. 139-144 Tidskriftsartikel (refereegranskat)abstract Objectives. To study whether there is an increased fracture incidence following thyrotoxicosis. Design. A case-control study. Setting. Malmo University Hospital, Malmo, Sweden. Subjects: All patients (n = 333) from the population of Malmo who were treated for thyrotoxicosis for the first time during the 5-year period 1970-74. A total of 618 controls were selected from the local municipality registry in Malmo. For each case the aim was to randomly select two age- and gender-specific controls, alive in 1993 and born the same year and month as the case. Main outcome measures. Fracture incidence. Results. Comparing survivors, there were no differences in the percentage of individuals with fractures (all, fragility, non-fragility) between the patients and the controls. Comparing all individuals and including all fractures, the percentage of individuals with fractures in the entire female patient group (24.6%) was lower (P < 0.05) than in female controls (33.1%). There was a similar but non-significant pattern between male patients and controls. The mean number of all fractures was lower in male patients than in controls (P < 0.05), but no significant difference was noted between female patients and controls. For fragility fractures, there were no significant differences in the percentage of individuals with fractures or in the mean number of fractures between female or male patients and controls. Conclusion. In conclusion we found no increased incidence of fragility fractures in patients with previous thyrotoxicosis as compared with controls. Our results do not support the suggestion that screening for osteoporosis should be performed in patients with previous thyrotoxicosis.
39.	Hamrefors, Viktor, et al. (författare) A myocardial infarction genetic risk score is associated with markers of carotid atherosclerosis. 2012 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 271, s. 271-281 Tidskriftsartikel (refereegranskat)abstract Objective: To assess whether a genetic risk score that was previously shown to be associated with myocardial infarction and coronary artery disease is also associated with markers of carotid atherosclerosis. Design: A total of 4022 middle-aged subjects from the general Swedish population were genotyped and individually assigned a genetic risk score based on 13 single-nucleotide polymorphisms (SNPs), previously associated with myocardial infarction and coronary artery disease. The genetic score (Score-MI) was then related to carotid bulb intima-media thickness (IMT), common carotid artery IMT and to the occurrence of carotid plaques in the study population. Results: Score-MI was associated with IMT of the bulb (P<0.001) and the common carotid artery (P<0.001) in unadjusted analyses, and with IMT of the bulb after adjustment for cardiovascular risk factors (P=0.003). The effect size of Score-MI on IMT of the bulb was similar to that of LDL cholesterol. After adjustment for cardiovascular risk factors, Score-MI was also associated with the occurrence of carotid plaques (odds ratio per quintile of Score-MI=1.11; 95% confidence interval 1.04-1.18; P=0.001). In addition to SNPs with known effects on LDL levels, Score-MI showed nominal associations with increasing systolic blood pressure and decreasing C-reactive protein levels. Conclusions: This genetic risk score was independently associated with carotid bulb IMT and carotid plaques, providing evidence of an association with early markers of atherosclerosis. This might imply that the genetic myocardial infarction risk conferred by the score is related to early atherosclerosis and that the risk score may identify at an early stage candidates at risk of developing intermediate phenotypes of atherosclerosis. Further studies should test whether assessing the genetic score could be valuable for early treatment decisions in these subjects.
40.	Hansson, G K, et al. (författare) Introduction: Atherosclerosis as inflammation: a controversial concept becomes accepted 2008 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 263:5, s. 462-463 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
41.	Hardarson, A, et al. (författare) Adrenocorticotrophic hormone exerts marked lipid-lowering effects in simvastatin-treated patients 2001 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 250:6, s. 530-534 Tidskriftsartikel (refereegranskat)abstract Objective. Recently, it was reported that treatment with adrenocorticotrophic hormone (ACTH) has a strong lipid-lowering effect in healthy individuals. The mechanism behind this has not been established. The aim of the present investigation was to study the effect of ACTH on the plasma lipoprotein pattern in patients treated with a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor. Design. The ACTH treatment was given to 10 patients who were on long-term treatment with simvastatin 40 mg daily. ACTH1-24 was administered at the dose of 1 mg daily for four consecutive days. Blood samples for analyses of lipids, lipoproteins and apolipoproteins were collected before and after treatment. Second baseline was obtained 2 weeks after the end of treatment. Results. The serum concentrations of cholesterol, triglycerides, low density lipoprotein (LDL) cholesterol, apolipoprotein B and lipoprotein(a) fell significantly by 16, 23, 23, 10 and 38%, respectively. The serum apolipoprotein E concentration increased significantly by 39%; the fraction that was not associated with apolipoprotein B increased by 47% whereas the fraction that was did not change significantly. There were no changes in the serum concentrations of high density lipoprotein (HDL) cholesterol and apolipoprotein AI. At the second baseline, the lipid variables had generally returned to previous levels. Conclusions. In patients on long-term simvastatin treatment, ACTH had marked lowering effects on the lipoproteins that contain apolipoprotein B. Moreover, the serum apolipoprotein E concentration increased significantly in response to ACTH treatment.
42.	Hedblad, Bo, et al. (författare) Rosiglitazone and carotid IMT progression rate in a mixed cohort of patients with type 2 diabetes and the insulin resistance syndrome: main results from the Rosiglitazone Atherosclerosis Study. 2007 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 261:3, s. 293-305 Tidskriftsartikel (refereegranskat)abstract Objective. Insulin resistance is associated with progression of atherosclerosis. We assessed the effect of 12 months of treatment with rosiglitazone (RSG) on the progression of carotid intima-media thickness (IMT) in people with type 2 diabetes mellitus (T2DM) or the insulin resistance syndrome (IRS). Design. Randomized, double-blind, placebo-controlled trial. Setting. Malmo University Hospital, Malmo, Sweden. Subjects. 555 subjects (200 with T2DM and 355 nondiabetics with IRS according to EGIR criteria), aged 35-80 years. 447 subjects (165 T2DM and 282 IRS) completed the study. Intervention. Participants were allocated to placebo or RSG 4 mg for 2 months and then 8 mg daily. Main outcome measure. Change in composite IMT [mean IMT in the common carotid artery (CCA) and maximal IMT in the bulb] was the primary and various other IMT measures were secondary outcome variables. Results. There was no effect of RSG treatment in the mixed population. In T2DM patients there was a reduced progression of the composite IMT (mean change: 0.041 vs. 0.070 mm, P = 0.07), and of the mean IMT CCA (mean change: -0.005 mm vs. 0.021 mm, P = 0.007). RSG treatment led to significant reductions of HOMA-IR, fasting plasma glucose, HbA1c, PAI-1 activity, fibrinogen, C-reactive protein and matrix metalloproteinase-9. Conclusions. In a mixed study population of patients with T2DM and IRS RSG treatment was not associated with a statistically significant reduction of carotid IMT progression rate. Separate analyses of these two patient groups indicated, however, a significant beneficial effect on CCA IMT in T2DM patients but no similar effect in subjects with IRS.
43.	Hemminki, Kari, et al. (författare) Maternal and paternal transmission of type 2 diabetes. 2011 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 270, s. 293-294 Tidskriftsartikel (refereegranskat)
44.	Henricsson, M., et al. (författare) The frequency and severity of retinopathy are related to HbA(1c) values after, but not at, the diagnosis of NIDDM 1998 Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 244:2, s. 149-154 Tidskriftsartikel (refereegranskat)abstract Objectives. To examine the relationship between previous glycaemic exposure and prevalence of retinopathy 8 years after diagnosis of diabetes in 58 islet cell antibodies (ICA)-negative noninsulin-dependent diabetes mellitus (NIDDM) patients and in a group of 14 ICA-positive 'NIDDM' and insulin-dependent diabetes mellitus (IDDM) patients. Design and methods. The Wisconsin retinopathy scale was used to assess the retinopathy which was graded into mild, moderate and severe nonproliferative diabetic retinopathy (NPDR), or proliferative retinopathy (PDR). The frequency and severity of retinopathy was related to HbA(1c) levels at diagnosis, and 3 and 5 years later. Results. Thirty of the 58 ICA-negative NIDDM patients (52%) but only 2 of the 14 ICA-positive 'NIDDM' or IDDM patients (14%) had mild-moderate- severe NPDR 8 years after diagnosis (P = 0.02). None had PDR. Retinopathy 8 years after diagnosis in NIDDM (= 58 ICA-negative patients) was correlated with the degree of glycaemiC control (HbA(1c) levels) at 3 and 5 years after diagnosis, but not to HbA(1c) levels at diagnosis. The relative risk for a higher average HbA(1c) (per percentage) at 3 and 5 years was 1.56 for any retinopathy vs. no retinopathy (95% confidence interval 1.1-2.2; P = 0.01) and 1.68 for moderate to severe NPDR in comparison with no DR and mild NPDR (95% confidence interval 1.0-2.8; P = 0.04). Conclusions. Retinopathy after 8 years of diabetes in NIDDM patients was associated with impaired glycaemic control during previous years but not with glycaemic control at baseline. Good glycaemic control may prevent retinopathy in patients with NIDDM.
45.	Henriksson, K M, et al. (författare) Development of hypertension over 6 years in a birth cohort of young middle-aged men: the Cardiovascular Risk Factor Study in southern Sweden (CRISS). 2002 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 252:1, s. 21-26 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: To explore the development of hypertension (HT) in a cohort of young middle-aged men. DESIGN: Prospective birth-cohort study of men surveyed over 6 years. SETTING: Helsingborg County Hospital, Sweden, 1990-97. SUBJECTS: A total of 628 men born in 1953-54, all surveyed at 37, 40 and 43 years of age. MAIN OUTCOME MEASURES: Systolic blood pressure (SBP), diastolic blood pressure (DBP), S-cholesterol, body mass index (BMI), alcohol consumption, ethnicity. HT was defined as SBP > or = 140 mmHg and/or DBP > or = 90 mmHg, or ongoing treatment. Using SBP < 130 mmHg and DBP < 85 mmHg as reference, the odds of conversion to HT in men with high normal blood pressure (BP) (SBP 130-139 mmHg and DBP 85-89 mmHg) was investigated. RESULTS: At age 37, 243 men (39%) had reference BP, 167 (26%) had high normal BP and 218 (35%) were hypertensive. Corresponding numbers at age 40 were 265 (42%), 166 (27%) and 197 (31%); and at age 43, 180 (29%), 142 (22%) and 306 (49%), respectively. High normal BP at baseline was associated with the development of HT both at age 40 (odds ratio (OR)=2.45 confidence interval (CI): 1.42-4.22) and at age 43 (OR=2.46, CI: 1.59-3.80), independent of other cardiovascular disease risk factors and ethnicity. The progression to HT was predicted also by S-cholesterol, alcohol consumption, BMI and weight gain. CONCLUSIONS: Over a short-term period, a substantial proportion of young middle-aged men with high normal BP develop HT with overweight and alcohol consumption as important determinants. These findings have implications for the prevention, screening and medical care of HT in this target population.
46.	Herlitz, Johan, 1949, et al. (författare) Factors associated with development of stroke long-term after myocardial infarction: experiences from the LoWASA trial 2005 Ingår i: J Intern Med. - : Wiley. - 0954-6820 .- 1365-2796. ; 257:2, s. 201-7 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: To describe factors associated with the development of stroke during long-term follow-up after acute myocardial infarction (AMI) in the LoWASA trial. PATIENTS: Patients who had been hospitalized for AMI were randomized within 42 days to receive either warfarin 1.25 mg plus aspirin 75 mg daily or aspirin 75 mg alone. DESIGN: The study was performed according to the probe design, that is open treatment and blinded end-point evaluation. SETTING: The study was performed in 31 hospitals in Sweden. The mean follow-up time was 5.0 years with a range of 1.7-6.7 years. RESULTS: In all, 3300 patients were randomized in the trial, of which 194 (5.9%) developed stroke (4.2% nonhaemorrhagic, 0.5% haemorrhagic and 1.3% uncertain. The following factors appeared as independent predictors for an increased risk of stroke: age, hazard ratio and 95% confidence interval (1.07; 1.05-1.08), a history of diabetes mellitus (2.4; 1.8-3.4), a history of stroke (2.3; 1.5-3.5), a history of hypertension (2.0; 1.5-2.7) and a history of smoking (1.5;1.1-2.0). Most of these factors were also predictors of a nonhaemorrhagic stroke whereas no predictor of haemorrhagic stroke was found. CONCLUSION: Risk indicators for stroke long-term after AMI were increasing age, a history of either diabetes mellitus, stroke, hypertension or smoking.
47.	Holmqvist, M. E., et al. (författare) Rapid increase in myocardial infarction risk following diagnosis of rheumatoid arthritis amongst patients diagnosed between 1995 and 2006 2010 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 268:6, s. 578-585 Tidskriftsartikel (refereegranskat)abstract Holmqvist ME, Wedren S, Jacobsson LTH, Klareskog L, Nyberg F, Rantapaa-Dahlqvist S, Alfredsson L, Askling J (Institute of Environmental Medicine, Karolinska Institutet, Stockholm; Karolinska Institutet/Karolinska Hospital, Stockholm; Malmo University Hospital, Malmo; AstraZeneca R&D, Molndal; and Umea University Hospital, Umea, Sweden) Rapid increase in myocardial infarction risk following diagnosis of rheumatoid arthritis amongst patients diagnosed between 1995 and 2006. J Intern Med 2010; 268: 578-585. The risk of ischaemic heart disease (IHD), and in particular myocardial infarction (MI), is increased amongst patients with established rheumatoid arthritis (RA). Few studies have included contemporary patients with RA. We recently reported that the risk of IHD is not elevated before the onset of RA symptoms. However, when, in relation to RA diagnosis, the risk is increased is unknown. Objective. To assess the risk of MI and other IHD events amongst patients diagnosed with RA during the last decade and within 18 months following RA symptom onset, compared to the general population, by time since RA diagnosis, year of RA diagnosis and by rheumatoid factor (RF) status. Methods and patients. A Swedish inception cohort of RA (n = 7469) diagnosed between 1995 and 2006 and a matched general population comparator cohort (n = 37 024), was identified and linked to national registers of morbidity and mortality from IHD. Relative risks (RRs) of MI and other IHD events were estimated using Cox regression. Results. During follow-up, 233 patients with RA and 701 controls developed a first MI, corresponding to an overall RR of MI of 1.6 (95% confidence interval 1.4, 1.9). Increased risks of MI were already detected within 1-4 years following RA diagnosis, as well as in patients diagnosed with RA during the last 5 years, in RF-negative patients and for transmural as well as nontransmural MIs. Conclusions. MI risk increases rapidly following RA diagnosis, suggesting the importance of additional mechanisms other than atherosclerosis. The elevated short-term risk is present amongst patients diagnosed in recent years, underscoring the importance of MI prevention from the time of RA diagnosis.
48.	Janzon, Ellis, et al. (författare) Tobacco and myocardial infarction in middle-aged women: a study of factors modifying the risk. 2004 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 256:2, s. 111-118 Tidskriftsartikel (refereegranskat)abstract Background. Although myocardial infarction (MI) is strongly related to smoking, few have studied why some smokers are more vulnerable than others. This study explored how the risk of MI in current and former smokers is modified by other cardiovascular risk factors. Methods. Incidence of MI (fatal and nonfatal) amongst 10619 women, 48.3 ± 8.2 years old, were studied in relation to smoking, hypertension, hypercholesterolaemia, diabetes, marital status and occupational level over a mean follow-up of 14 years. Results. Of the 3738 smokers, one-third had at least one major biological risk factor besides smoking; 228 women had MI during follow-up. Smoking and hypertension showed a synergistic effect on incidence of MI. The adjusted relative risks (RR) were 12.2 (95% CI: 7.5-19.8) for smokers with hypertension, 5.3 (CI:3.3-8.1) for smokers with normal blood pressure and 2.4 (CI:1.4-4.3) for never-smokers with hypertension (reference: normotensive never-smokers). The corresponding RRs for diabetic smokers and diabetic never-smokers were 19.0 (CI: 10.2-35.4) and 8.8 (CI: 4.4-17.4), respectively (reference: nondiabetic never-smokers). In terms of attributable risks, hypertension, hypercholesterolaemia and diabetes accounted for 12.9, 11.5 and 7.2%, respectively, of MI in female smokers. Low socio-economic level and being unmarried accounted for 19.6 and 1.6%, respectively. Conclusions. Although smoking is a major risk factor for MI, the risk varies widely between women with similar tobacco consumption. The results illustrate the need of a global risk factor assessment in female smokers and suggest that female smokers should be targets both for intensified risk factor management and programmes to stop smoking.
49.	Landgren, O, et al. (författare) A prospective study on antibody response to repeated vaccinations with pneumococcal capsular polysaccharide in splenectomized individuals with special reference to Hodgkin's lymphoma 2004 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 255:6, s. 664-673 Tidskriftsartikel (refereegranskat)abstract Background. Splenectomy is accompanied by a life-long risk of overwhelming postsplenectomy infection (OPSI), mainly caused by polysaccharide (PS) encapsulated bacteria such as Streptococcus pneumoniae. Despite extensive prophylactic efforts the mortality and morbidity rates remain high. The present study was based on a strategy with a predefined vaccination algorithm including repeated 23-valent pneumococcal vaccinations and monitoring of pneumococcal antibody levels. The antibody levels of splenectomized Hodgkin's lymphoma (HL) patients were compared with those patients splenectomized due to immune-mediated cytopenias [autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenic purpura (ITP)] and also individuals who were splenectomized because of trauma (TRAUMA). Methods. A total of 311 splenectomized individuals were included in this prospective study (208 HL; 15 AIHA; 60 ITP; 28 TRAUMA). Depending on their individual anti-PS antibody levels measured by enzyme-linked immunosorbent assay technique the patients were revaccinated with 23-valent pneumococcal PS vaccine up to four times in accordance with the predefined algorithm. For each vaccination occasion, serum was collected at vaccination, after 1 month +/- 2 weeks (peak), and after 1 year +/- 6 months (follow-up). Patient files, a national population-based database, and microbiological databases were checked for 124 HL patients to identify OPSI. Results. A significant response was recorded on primary vaccination as well as on two revaccination occasions for HL, AIHA/ITP, as well as TRAUMA patients. None of the variables age, gender, or time elapsed between splenectomy and first pneumococcal vaccination was found to be associated with mean PS antibody levels at prevaccination, peak or follow-up. No severe adverse events were reported. Amongst 124 clinically monitored HL patients, 10 OPSI were recorded in seven patients during the study period. One of these patients, a middle-aged female, died as a result of fulminant pneumococcal bacteraemia, which was her third OPSI during a 7-year period. Conclusions. A significant response to pneumococcal PS vaccination was found in all three groups (HL, AIHA/ITP and TRAUMA) of splenectomized patients. Importantly, both primary and repeated vaccinations were safe. Until further knowledge is gained regarding the protective concentration of serotype-specific antibody concentrations we believe that the value of vaccination and frequent revaccination (every 1-5 years) in combination with education of patients and health care professionals and clinical monitoring is beneficial for these patients at risk for OPSI.
50.	Leosdottir, Margrét, et al. (författare) The association between total energy intake and early mortality: data from the Malmo Diet and Cancer Study. 2004 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 256:6, s. 499-509 Tidskriftsartikel (refereegranskat)

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