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- Glader, C A, et al.
(författare)
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Lipoprotein(a), Chlamydia pneumoniae, leptin and tissue plasminogen activator as risk markers for valvular aortic stenosis.
- 2003
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Ingår i: European Heart Journal. - 0195-668X .- 1522-9645. ; 24:2, s. 198-208
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The aim of the present study was to identify risk markers for the development of valvular aortic stenosis (AS). Lipoprotein(a) (Lp(a)) and Chlamydia pneumoniae IgG antibody titres in plasma and in circulating immune complexes as well as leptin and tissue plasminogen activator (t-PA) in plasma were studied.METHODS AND RESULTS: One hundred and one patients (41 women and 60 men, mean age 71+/-8 years) with significant AS and 101 age- and sex-matched controls were included in this study. All patients underwent aortic valve replacement at the University Hospital in Umeå, Sweden. The controls had no symptoms of cardiovascular disease and they were examined echocardiographically. An Lp(a) level >or=480 mg x l(-1), a C. pneumoniae-specific IgG titre >or=1/128, a high leptin level and a high t-PA mass concentration in plasma were identified as risk markers for AS. A strong synergism between Lp(a) and C. pneumoniae IgG antibodies in circulating immune complexes was found.CONCLUSION: Our data indicate that a chronic C. pneumoniae infection and a high plasma Lp(a) level might influence and aggravate aortic heart valve sclerosis via the formation of circulating immune complexes. The present study also strongly suggests an association between high plasma leptin, t-PA mass concentration and AS.
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- Smith, Margaretha E., et al.
(författare)
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Increase in Net Activity of Serine Proteinases but Not Gelatinases after Local Endotoxin Exposure in the Peripheral Airways of Healthy Subjects
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- We tested the hypothesis that activation of the innate immune response induces an imbalance in the proteolytic homeostasis in the peripheral airways of healthy subjects, towards excess serine or gelatinase proteinase activity. During bronchoscopy, 18 healthy human subjects underwent intra-bronchial exposure to endotoxin and contra-lateral exposure to vehicle. Bronchoalveolar lavage (BAL) samples were harvested 24 or 48 hours (h) later. We quantified archetype proteinases, anti-proteinases, inflammatory BAL cells, and, importantly, total plus net proteinase activities using functional substrate assays. As expected, endotoxin exposure increased the concentrations of polymorphonuclear leukocytes (PMN's) and macrophages, of proteinases and the anti-proteinases tissue inhibitor of metalloproteinase-1, alpha-1-antitrypsin and, to a lesser extent, secretory leukoproteinase inhibitor, at both time points. Notably, at these time points, endotoxin exposure substantially increased the quantitative NE/SLPI ratio and the net serine proteinase activity corresponding to neutrophil elastase (NE). Endotoxin exposure also increased the total gelatinase activity corresponding to matrix metalloproteinase (MMP)-9; an activity dominating over that of MMP-2. However, endotoxin exposure had no impact on net gelatinolytic activity at 24 or 48 h after exposure. Thus, local activation of the innate immune response induces an imbalance towards increased net serine proteinase activity in the proteolytic homeostasis of the peripheral airways in healthy subjects. Hypothetically, this serine proteinase activity can contribute to tissue remodelling and hypersecretion via NE from PMN's, if it is triggered repeatedly, as might be the case in chronic inflammatory airway disorders.
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- Glader, Eva-Lotta, 1972-, et al.
(författare)
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Differences in Long-Term Outcome Between Patients Treated in Stroke Units and in General Wards : A 2-Year Follow-Up of Stroke Patients in Sweden
- 2001
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Ingår i: Stroke. - : American Heart Association, Inc.. - 0039-2499 .- 1524-4628. ; 32, s. 2124-2130
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose— The long-term beneficial effects of stroke unit care have been proved in several randomized trials. However, there is a question of large-scale applicability in routine clinical practice of interventions used by dedicated investigators in small randomized trials. The objective of this study was to compare, 21/2 years after stroke, patients who had been treated in stroke units and those treated in general wards in routine clinical practice.Methods— This is a prospective cohort study based on 8194 patients who were included, during the first 6 months in 1997, in Riks-Stroke, the Swedish National Register for quality assessment of acute stroke. Two years after the event, 5189 patients were still alive and 5104 were followed up with a postal questionnaire to which 4038 responded.Results— Among the group of patients who were independent in activities of daily living (ADL) functions before the stroke, patients who were treated in stroke units were less often dependent in ADL functions, after adjustment for case mix (OR, 0.79; CI, 0.66 to 0.94). If they also lived at home before the stroke, then they had a lower case-fatality rate 2 years after the stroke (OR, 0.81; CI, 0.72 to 0.92).Conclusions— Long-term beneficial effects of treatment in stroke units were shown for patients who were independent in ADL functions before the stroke. No benefits were shown for patients who were dependent on help for primary ADL before the stroke. Further studies on this group of patients with more detailed outcome measures are needed.
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- Glader, Eva-Lotta, 1972-, et al.
(författare)
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Large variations in the use of oral anticoagulants in stroke patients with atrial fibrillation : A Swedish national perspective
- 2004
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 255:1, s. 22-32
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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.
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| 7. |
- Glader, Pernilla, 1975, et al.
(författare)
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Impact of acute exposure to tobacco smoke on gelatinases in the bronchoalveolar space.
- 2008
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Ingår i: The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. - : European Respiratory Society (ERS). - 1399-3003. ; 32:3, s. 644-650
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Tidskriftsartikel (refereegranskat)abstract
- Clinical studies have indicated increased gelatinase activity in the airways of patients suffering from chronic obstructive pulmonary disease caused by tobacco smoke. The present study aimed to determine whether acute exposure to tobacco smoke per se causes a substantial and lasting impact on gelatinases and their inhibitors in the peripheral airways of atopic and nonatopic human subjects. Bronchoscopy with bronchoalveolar lavage (BAL) was performed on occasional smokers with and without atopy before and after smoking 10 cigarettes over a 48-h period. Samples from a group of never-smokers not exposed to tobacco smoke served as controls. Gelatinase identity and activity were measured using zymography, and gelatinase activity assay and concentrations of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of MMP (TIMP)-1 and TIMP-2 were measured using ELISA. The results revealed no pronounced changes in identity, net activity or concentration of the gelatinases or changes in concentrations of TIMP-1 and TIMP-2 in BAL fluid before and after acute exposure to tobacco smoke. In conclusion, the present experimental study indicates that acute exposure to tobacco smoke does not cause any substantial impact on gelatinases or their inhibitors in the peripheral airways, irrespective of atopy status, a finding that is compatible with the fact that it takes many years of tobacco smoking to establish chronic obstructive pulmonary disease.
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