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Sökning: WFRF:(Wiklund Per Gunnar)

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  • Olofsson, P, et al. (författare)
  • Genetic variants of TNFSF4 and risk for carotid artery disease and stroke
  • 2008
  • Ingår i: Journal of Molecular Medicine. - New York : Springer. - 0946-2716 .- 1432-1440. ; 87:4, s. 337-346
  • Tidskriftsartikel (refereegranskat)abstract
    • In two independent human cohorts, the minor allele of SNP rs3850641 in TNFSF4 was significantly more frequent in individuals with myocardial infarction than in controls. In mice, Tnfsf4 expression is associated with increased atherosclerosis. The expression of TNFSF4 in human atherosclerosis and the association between genotype and cerebrovascular disease have not yet been investigated. TNFSF4 messenger RNA (mRNA) levels were significantly higher in human atherosclerotic lesions compared with controls (730 +/- 30 vs 330 +/- 65 arbitrary units, p < 0.01). TNFSF4 was mainly expressed by macrophages in atherosclerotic lesions. In cell culture, endothelial cells upregulated TNFSF4 in response to tumor necrosis factor alpha (TNF-alpha; 460 +/- 110 vs 133 +/- 8 arbitrary units, p < 0.001 after 6 h of stimulation). We analyzed the TNFSF4 gene in 239 patients who had undergone carotid endarterectomy and 138 matching controls from The Biobank of Karolinska Carotid Endarterectomies and Stockholm Heart Epidemiology Program cohorts and 929 patients and 1,382 matching controls from the Sahlgrenska Academy Study on Ischemic Stroke and Case Control Study of Stroke cohorts, limiting inclusion to patients with ischemic stroke. Participants were genotyped for the rs3850641 SNP in TNFSF4. Genotype associations were neither found with TNFSF4 mRNA levels nor with atherosclerosis associated systemic factors or risk for stroke. This study shows that TNFSF4 is expressed on antigen-presenting cells in human carotid atherosclerotic lesions but provides no evidence for an association of TNFSF4 gene variation with the risk for ischemic stroke.
  • Thulin, Helena, et al. (författare)
  • Defecation disturbances after cystectomy for urinary bladder cancer.
  • 2011
  • Ingår i: BJU international. - : Blackwell Publishing Ltd. - 1464-410X .- 1464-4096. ; 108:2, s. 196-203
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Type - Preference (prospective cohort)
Level of Evidence 4 OBJECTIVES: To describe and compare long-term defecation disturbances in patients who had undergone a cystectomy due to urinary bladder cancer with non-continent urostomies, continent reservoirs and orthotopic neobladder urinary diversions. PATIENTS AND METHODS: During their follow-up we attempted to contact all men and women aged 30-80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. During a qualitative phase we identified defecation disturbances as a distressful symptom and included this item in a study-specific questionnaire together with free-hand comments. The patients completed the questionnaire at home. Outcome variables were dichotomized and the results are presented as relative risks with 95% confidence interval. RESULTS: The questionnaire was returned from 452 (92%) of 491 identified patients. Up to 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). A sense of decreased straining capacity was reported by 20% of the men and women with non-continent urostomy and 14% and 8% of those with continent reservoirs and orthotopic neobladders, respectively. CONCLUSIONS: Of the cystectomized individuals 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). Those wanting to improve the situation for bladder cancer survivors may consider communicating before surgery the possibility of stool-emptying problems, and asking about them after surgery.
  • Wennberg, Maria, et al. (författare)
  • Fish consumption and risk of stroke : A second prospective case-control study from northern Sweden
  • 2016
  • Ingår i: Nutrition Journal. - : BioMed Central (BMC). - 1475-2891. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Fish consumption has been concluded to be associated with decreased risk of stroke in several reviews. However, among men, but not women, an increased risk of stroke was previously found at high fish consumption (>3 meals/week) in northern Sweden. This study investigates if previous results on elevated stroke risk with high fish consumption in men in northern Sweden can be confirmed in a larger study with new cases in the same population. Methods: A prospective nested case-control study was performed within the population-based Northern Sweden Health and Disease Study cohort. Information on fish consumption, other lifestyle and medical data was collected at baseline. Incident stroke cases (1987-2007, n = 735) were identified and 2698 controls matched for gender, age, year of baseline and geographical region. Results: There were no associations between total fish or fatty fish consumption and stroke risk; thus the previous finding of increased risk of stroke with high fish consumption in men could not be repeated. High intake of lean fish (>twice/week compared to < once/month) was associated with increased stroke risk in men [OR 1.80 (95% CI 1.00, 3.21), but not in women [OR 0.50 (95% CI 0.24, 1.10)]. The association was driven by men living alone. Conclusions: The previous association between high total fish consumption and risk of stroke in men could not be repeated. The increased risk found in men with high intake of lean fish may be due to chance or confounding specific for this group.
  • Wiklund, Per-Gunnar, et al. (författare)
  • Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke : replicated findings in two nested case-control studies based on independent cohorts.
  • 2005
  • Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 36:8, s. 1661-1665
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: Impaired fibrinolytic function secondary to elevated plasminogen activator inhibitor-1 (PAI-1) levels has been implicated in ischemic stroke. PAI-1 levels are determined by genetic factors and environmental factors, triglyceride levels in particular. The aim of this study was to investigate the common functional 4/5 guanosine (4G/5G) polymorphism in the promoter region of the PAI-1 gene and the risk of stroke. METHODS: A nested case-control study design was applied, using baseline data for 2 independent cohorts obtained at population-based surveys in northern Sweden. In study A, there were 113, and in study B, there were 275 individuals without major concomitant disease at baseline who later experienced a first-ever stroke. Blood samples obtained at baseline were analyzed for potential risk factors, including the 4G/5G polymorphism of the PAI-1 gene. RESULTS: The 4G allele of the PAI-1 polymorphism was associated with an increased risk of future ischemic stroke in both studies (odds ratio [OR] of 4G homozygosity, 1.87; 95% CI, 1.12 to 3.15 in study A; OR of 4G homozygosity, 1.56; 95% CI, 1.12 to 2.16 in study B). Individuals with the combination of hypertriglyceridemia and 4G homozygosity were at the greatest risk of developing stroke. Multiple logistic regression analysis identified 4G homozygosity, systolic blood pressure, and diabetes as independent predictors of ischemic stroke. CONCLUSIONS: Identical findings in 2 independent studies strongly suggest a true and clinically important association between PAI-1 4G/5G genotype and risk of future ischemic stroke. The observed modification of the genotype effect by triglycerides may be interpreted as a gene-environment interaction.
  • Andersson, J., et al. (författare)
  • C-reactive protein is a determinant of first-ever stroke: prospective nested case-referent study.
  • 2009
  • Ingår i: Cerebrovascular diseases (Basel, Switzerland). - 1421-9786 .- 1015-9770. ; 27:6, s. 544-51
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: C-reactive protein (CRP) is a determinant of stroke, but there are no prospective studies on CRP and first ischemic stroke divided into etiologic subtypes. Our primary aim was to study CRP as a determinant of ischemic stroke, classified according to Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria, and intracerebral hemorrhage (ICH) in a prospective study. A secondary aim was to study the relationship between the 1444C>T polymorphism, plasma levels of CRP and stroke. METHODS: The study was a prospective population-based case-referent study nested within the Northern Sweden Cohorts. We defined 308 cases of ischemic stroke and 61 ICH. Two controls for each case were defined from the same cohort. RESULTS: The OR for the highest (>3 mg/l) versus lowest group (<1 mg/l) of CRP was 2.58 (95% CI 1.74-3.84) for ischemic stroke and 1.63 (95% CI 0.67-3.93) for ICH. In a multivariate model including traditional risk factors, CRP remained associated with ischemic stroke (OR 2.06; 95% CI 1.29-3.29). Small-vessel disease was associated with CRP in the multivariate model (OR 3.88; 95% CI 1.10-13.7). The CRP 1444 (CC/CT vs. TT) polymorphism was associated with plasma levels of CRP but neither with ischemic stroke nor with ICH. CONCLUSIONS: This prospective population-based study shows that CRP is significantly associated with the risk of having a first ischemic stroke, especially for small-vessel disease. No significant associations were found between the CRP 1444C>T polymorphism and any stroke subtype.
  • Purins, Karlis, et al. (författare)
  • Standardized experimental brain death model for studies of intracranial dynamics, organ preservation, and organ transplantation in the pig
  • 2011
  • Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 39:3, s. 512-517
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES:: Brain death impairs organ function and outcome after transplantation. There is a need for a brain death model to allow studies of organ viability and preservation. For neurointensive care research, it is also of interest to have a relevant brain death model for studies of intracranial dynamics and evaluation of cerebral monitoring devices. Therefore, the objective was to develop a standardized clinically relevant brain death model. METHODS:: Six pigs of both sexes (10-12 wks old; mean weight, 24.5 ± 1.4 kg) were included. Mean arterial blood pressure, heart rate, intracranial pressure, intracranial compliance, cerebral perfusion pressure, and brain tissue oxygenation (BtiPo2) were recorded during stepwise elevation of intracranial pressure by inflation of an epidural balloon catheter with saline (1 mL/20 mins). Brain death criteria were decided to be reached when cerebral perfusion pressure was <0 mm Hg for 60 mins and at least 10 mL saline was inflated epidurally. BtiPo2 and arterial injections of microspheres were used for confirmation of brain death. RESULTS:: A gradual volume-dependent elevation of intracranial pressure was observed. After 10 mL of balloon infusion, mean intracranial pressure was 89.8 ± 9.7 (sd) mm Hg. Intracranial compliance decreased from 0.137 ± 0.069 mL/mm Hg to 0.007 ± 0.001 mL/mm Hg. The mean arterial pressure decreased and the heart rate increased when the intracranial volume was increased to between 5 and 6 mL. All animals showed cerebral perfusion pressure ≤0 after 7 to 10 mL of infusion. In all animals, the criteria for brain death with negative cerebral perfusion pressure and BtiPo2 ∼0 mm Hg were achieved. Only a negligible amount of microspheres were found in the cerebrum, confirming brain death. The kidneys showed small foci of acute tubular necrosis. CONCLUSIONS:: The standardized brain death model designed in pigs simulates the clinical development of brain death in humans with a classic pressure-volume response and systemic cardiovascular reactions. Brain death was convincingly confirmed.
  • Thorstenson, Andreas, et al. (författare)
  • Diagnostic random bladder biopsies: reflections from a population-based cohort of 538 patients.
  • 2010
  • Ingår i: Scandinavian journal of urology and nephrology. - 1651-2065. ; 44:1, s. 11-19
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To assess whether diagnostic random bladder biopsies and the detection of concomitant carcinoma in situ (CIS) have an impact on the frequency of intravesical bacille Calmette–Guérin (BCG) instillations or radical cystectomy; and whether this affects the cancer-specific survival in patients with pTaG3 or pT1G1–G3 transitional cell carcinoma of the urinary bladder. Material and methods. A population-based cohort of 538 patients with newly diagnosed bladder cancer was prospectively registered in the Stockholm County during 1995 and 1996 and followed for more than 5 years. Results. Random biopsies were recommended in all patients but the decision to take biopsies was made by the treating urologist and hence performed in 326 out of 538 patients (61%), which revealed concomitant CIS in 47 patients(14%). Sixty out of 103 (58%) patients with pTaG3 or pT1G1–G3 tumours, in whom random biopsies were performed, received intravesical BCG compared with five out of 22 patients (23%) where random biopsies were not taken (p = 0.004). Moreover, 23 out of 103 patients (22%) with pTaG3 or pT1G1–G3 tumours in whom random biopsies were performed underwent radical cystectomy compared with none out of 22 patients (0%) without random biopsies (p = 0.013). The Cox proportional hazard ratio for death due to bladder cancer in patients with pTaG3 or pT1G1–G3 tumours among patients not having versus having undergone random biopsies was 2.5 (95% confidence interval 1.1–5.6). Conclusion. Patients diagnosed in Stockholm in 1995 or 1996 with pTaG3 or pT1G1–G3 bladder tumours having undergone random bladder biopsies more frequently underwent BCG treatment and radical cystectomy and had higher cancer-specific survival than patients who did not undergo random biopsies.
  • Thulin, Helena, et al. (författare)
  • Hygiene and urinary tract infections after cystectomy in 452 Swedish survivors of bladder cancer.
  • 2010
  • Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 105:8, s. 1107-1117
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To determine whether or not an improved hygiene can lessen the incidence of symptomatic urinary tract infections (UTIs) in patients treated by cystectomy for urinary bladder cancer.PATIENTS AND METHODS: We attempted to contact during their follow-up all men and women aged 30-80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. During a qualitative phase we identified hygienic measures and included them in a study-specific questionnaire. The patients completed the questionnaire at home. Outcome variables were dichotomized and the results presented as relative risks (RR) with 95% confidence interval.RESULTS: We received the questionnaire from 452 (92%) of 491 identified patients. The proportion of patients who had a symptomatic UTI in the previous year was 22% for orthotopic neobladder and cutaneous continent reservoir, and 23% for non-continent urostomy diversion. The RR for a UTI was 1.1 (0.5-2.5) for 'never washing hands' before handling with catheters or ostomy material. Patients with diabetes mellitus had a RR of 2.1 (1.4-3.2) for having a symptomatic UTI.CONCLUSIONS: We could not confirm lack of hygiene measures as a cause of UTI for men and women who had a cystectomy with urinary diversion. Patients with diabetes mellitus have a greater risk of contracting a UTI.
  • Wiklund, Lars, et al. (författare)
  • Neuro- and cardioprotective effects of blockade of nitric oxide action by administration of methylene blue
  • 2007
  • Ingår i: Neuroprotective agents. - 9781573316859 ; , s. 231-244
  • Konferensbidrag (refereegranskat)abstract
    • Methylene blue (MB), generic name methylthioninium (C16H18ClN3 S · 3H2O), is a blue dye synthesized in 1876 by Heinrich Caro for use as a textile dye and used in the laboratory and clinically since the 1890s, with well-known toxicity and pharmacokinetics. It has experimentally proven neuroprotective and cardioprotective effects in a porcine model of global ischemia–reperfusion in experimental cardiac arrest. This effect has been attributed to MB's blocking effect on nitric oxide synthase and guanylyl cyclase, the latter blocking the synthesis of the second messenger of nitric oxide. The physiological effects during reperfusion include stabilization of the systemic circulation without significantly increased total peripheral resistance, moderately increased cerebral cortical blood flow, a decrease of lipid peroxidation and inflammation, and less anoxic tissue injury in the brain and the heart. The last two effects are recorded as less increase in plasma concentrations of astroglial protein S-100β, as well as troponin I and creatine kinase isoenzyme MB, respectively.
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