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| 2. |
- Olsson-Strömberg, Ulla, et al.
(författare)
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Comparison of busulphan, hydroxyurea and allogeneic bone marrow transplantation (BMT) in chronic myeloid leukaemia : BMT prolongs survival.
- 2004
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Ingår i: Hematol J. - 1466-4860. ; 5:6, s. 462-6
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Whether busulphan-treated patients develop blastic transformation earlier than hydroxyurea treated has been a controversial issue. In a randomised prospective study, we examined the busulphan versus hydroxyurea influence on time to blast crisis and on survival. When we opened our study in 1984, the clinical benefit of allogeneic bone marrow transplantation (BMT) was not well known, to follow up the long-time outcome of this treatment was therefore of great interest. Materials and methods: Previously untreated CML patients were randomly started on either hydroxyurea (30 mg/kg/day) or busulphan (0.1 mg/kg/day). The end points of the study were overall survival and time to blast crisis. A total of 26 patients subsequently underwent BMT. Results: A total of 179 patients were randomised, 90 to hydroxyurea, and 89 to busulphan treatment. There was no significant difference in survival between hydroxyurea- and busulphan-treated patients (P = 0.46), median survival was 3.5 and 3.2 years, respectively. In all, 85 of the patients were subsequently diagnosed with blast crisis, 41 in the busulphan and 44 in the hydroxyurea group. There was no significant difference between the two groups (P=0.91). The 26 patients who were allotransplanted survived significantly longer than those who were not transplanted (P=0.0001). The 5-year-survival rates were 50 and 22% and the 10-year-survival rates were 46 and 2%, respectively. The median survival was 4.7 years for the transplanted and 3.3 years for the nontransplanted patients. Conclusion: We did not find any difference between hydroxyurea and busulphan treatment, either in overall survival or in blast crisis-free survival, transplanted patients survived significantly longer than nontransplanted patients. © 2004 The European Hematology Association All rights reserved.
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| 3. |
- Almered-Olsson, G., et al.
(författare)
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Inte Bara Träd : Hållbart Mångbruk Av Skogslandskapet
- 2004
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Bok (övrigt vetenskapligt)abstract
- Skogslandskapen - hur skall vi värdera dem? Ska de betraktas som rekreationsområden och kulturlandskap eller som arena för konflikter och dragkamp om olika resurser?<br/><br/> Är skogsregionerna närande eller tärande?<br/><br/> Vilka viktiga samband finns mellan skandinaviska och tropiska landskap?<br/><br/><br/><br/>Detta är några av de teman som behandlas i denna spänannde bok om de många dimensionerna och resurserna som ryms i skogslandskapen.<br/><br/> Boken ger nya och stimulerande aspekter på framtidsmöjligheterna för en hållbar utveckling för boreala skogslandskap. Den tar också upp det nödvändiga mångbruket av skogens resurser liksom den förändrade synen på människans roll i skogen. Och inte minst behandlas den ekologiska paradoxen att störningar behövs för att bevara skogens ekologiska mångfald.<br/><br/><br/><br/>Boken är författad av samhällsvetare, miljöteknologer och ekologer inom den tvärvetenskapliga forskargruppen MiljöFocus vid Karlstads universitet
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| 4. |
- Eriksson, Ulf G, et al.
(författare)
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Pharmacokinetics of melagatran and the effect on ex vivo coagulation time in orthopaedic surgery patients receiving subcutaneous melagatran and oral ximelagatran : a population model analysis
- 2003
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Ingår i: Clinical Pharmacokinetics. - 0312-5963. ; 42:7, s. 687-701
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Forskningsöversikt (övrigt vetenskapligt)abstract
- OBJECTIVE: Ximelagatran, an oral direct thrombin inhibitor, is rapidly bioconverted to melagatran, its active form. The objective of this population analysis was to characterise the pharmacokinetics of melagatran and its effect on activated partial thromboplastin time (APTT), an ex vivo measure of coagulation time, in orthopaedic surgery patients sequentially receiving subcutaneous melagatran and oral ximelagatran as prophylaxis for venous thromboembolism. To support the design of a pivotal dose-finding study, the impact of individualised dosage based on bodyweight and calculated creatinine clearance was examined. DESIGN AND METHODS: Pooled data obtained in three small dose-guiding studies were analysed. The patients received twice-daily administration, with either subcutaneous melagatran alone or a sequential regimen of subcutaneous melagatran followed by oral ximelagatran, for 8-11 days starting just before initiation of surgery. Nonlinear mixed-effects modelling was used to evaluate rich data of melagatran pharmacokinetics (3326 observations) and the pharmacodynamic effect on APTT (2319 observations) in samples from 216 patients collected in the three dose-guiding trials. The pharmacokinetic and pharmacodynamic models were validated using sparse data collected in a subgroup of 319 patients enrolled in the pivotal dose-finding trial. The impact of individualised dosage on pharmacokinetic and pharmacodynamic variability was evaluated by simulations of the pharmacokinetic-pharmacodynamic model.RESULTS: The pharmacokinetics of melagatran were well described by a one-compartment model with first-order absorption after both subcutaneous melagatran and oral ximelagatran. Melagatran clearance was correlated with renal function, assessed as calculated creatinine clearance. The median population clearance (creatinine clearance 70 mL/min) was 5.3 and 22.9 L/h for the subcutaneous and oral formulations, respectively. The bioavailability of melagatran after oral ximelagatran relative to subcutaneous melagatran was 23%. The volume of distribution was influenced by bodyweight. For a patient with a bodyweight of 75kg, the median population estimates were 15.5 and 159L for the subcutaneous and oral formulations, respectively. The relationship between APTT and melagatran plasma concentration was well described by a power function, with a steeper slope during and early after surgery but no influence by any covariates. Simulations demonstrated that individualised dosage based on creatinine clearance or bodyweight had no clinically relevant impact on the variability in melagatran pharmacokinetics or on the effect on APTT. CONCLUSIONS: The relatively low impact of individualised dosage on the pharmacokinetic and pharmacodynamic variability of melagatran supported the use of a fixed-dose regimen in the studied population of orthopaedic surgery patients, including those with mild to moderate renal impairment.
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| 5. |
- Littorin, Bengt, et al.
(författare)
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Family characteristics and life events before the onset of autoimmune type 1 diabetes in young adults - A nationwide study
- 2001
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Ingår i: Diabetes Care. - American Diabetes Association, Inc.. - 0149-5992. ; 24:6, s. 1033-1037
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - To elucidate whether family characteristics and stressful life events were associated with onset of autoimmune type 1 diabetes in young adults. RESEARCH DESIGN AND METHODS - This investigation was based on a nation-wide study (Diabetes Incidence Study in Sweden) of newly diagnosed patients aged 15-34 years. Patients clinically classified as type 1 diabetic with antibodies to islet cells and/or to GAD65 were compared with age- and sex-matched control subjects via questionnaire. The questionnaire covered diabetes heredity, social environment, educational level, and life events experienced during the 12 months before diagnosis. RESULTS - The rate of response was 82% for the diabetic patients and 65% for the control subjects. Questionnaires from 349 diabetic patients and 979 control subjects were considered. Diabetes in relatives was more frequent in the patients (odds ratio OR2.6) who were born in Sweden and whose mothers were of Swedish origin. No major stress factors were detected in the diabetic patients; however, in comparison with the control subjects, the diabetic patients had experienced fewer conflicts with their parents and had less often broken contacts with friends. CONCLUSIONS - Young adults with recent-onset type 1 diabetes were more exposed to heredity for diabetes, but no major prediabetic stress factors were detected. Our study does not directly support the concept that psychosocial stressful life events are involved in the development of autoimmune type 1 diabetes in young adults.
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| 6. |
- Sandstedt, Bengt, 1951-, et al.
(författare)
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Genuine effects of ventricular fibrillation upon myocardial blood flow, metabolism and catecholamines in patients with aortic stenosis.
- 2004
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Ingår i: Scandinavian cardiovascular journal : SCJ. - 1401-7431. ; 38:2, s. 113-20
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Tidskriftsartikel (refereegranskat)abstract
- Objective-Ventricular fibrillation (VF) is life-threatening because of its haemodynamic and metabolic effects. The purpose was to examine if VF also has primary effects per se. We therefore investigated the early effects of VF on myocardial blood flow, metabolic characteristics and catecholamine concentrations in patients undergoing surgery for aortic stenosis. Design-The immediate effects of up to 5 min of VF were studied in 21 patients during cardiopulmonary bypass (CPB) before valve replacement. Results-During VF the global myocardial oxygen consumption, coronary blood flow and vascular resistance were unchanged, and the mean arterial pressure (on CPB) decreased from 70 to 51 mmHg (p<0.02). Fibrillation induced a high myocardial tone and a probable functional aortic insufficiency, which instantly equilibrated left ventricular and aortic pressures. Signs of myocardial ischaemia and acidosis developed after 4 min: a decrease in the pH of coronary sinus blood from 7.38 to 7.32 (p<0.001), an increased release of lactate from 32 to 137 mumol/min (p<0.001) and potassium from 29 to 73 μmol/min (p<0.05). The noradrenaline net release increased from 0.021 to 0.58 nmol/min (p<0.02) after 1.5 min of VF and then decreased. The adrenaline net uptake remained low and unchanged (17-28%). Conclusion-VF in patients with aortic stenosis was rapidly followed by myocardial ischaemia, acidosis and a transient increase in the myocardial noradrenaline net release despite sufficient coronary perfusion and unchanged global myocardial oxygen consumption. The VF instantly induced equilibration of left ventricular and aortic pressure and probably caused a relative underperfusion of the subendocardium. These factors all support persistence of VF.
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| 7. |
- Törn, Carina, et al.
(författare)
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Glutamic acid decarboxylase antibodies (GADA) is the most important factor for prediction of insulin therapy within 3 years in young adult diabetic patients not classified as Type 1 diabetes on clinical grounds
- 2000
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Ingår i: Diabetes/Metabolism Research Reviews. - 1520-7552. ; 16:6, s. 442-447
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Tidskriftsartikel (refereegranskat)abstract
- Background Differentiation between Type 1 and Type 2 diabetes in adults is difficult at diagnosis. In this study we tested the hypothesis that autoantibodies at diagnosis are predictive for insulin treatment within 3 years in patients initially not classified as Type 1 diabetes. Methods In a nationwide population-based study, blood samples were obtained from 764 patients, all diagnosed with diabetes during a 2-year period. At diagnosis, 583 (76%) were classified as Type 1, 110 (14%) as Type 2 and 71 (9.3%) could not be classified. Results Among patients not classified as Type 1 diabetes, 52 (47%) of Type 2 and 42 (59%) of unclassified patients were positive for islet cell antibodies CICA), glutamic acid decarboxylase antibodies (GADA) or tyrosine phosphatase antibodies (IA-2A). These patients (n=94) had lower body mass index (BMI) (p<0.001) and lower C-peptide (p<0.001) compared to the autoantibody negative patients (n=87). Compared to clinically classified Type 1 diabetes patients positive for autoantibodies (n=477), they have higher BMI (p<0.001), higher C-peptide (p<0.001) and the same levels of ICA, GADA and IA-2A. After 3 years, 93% of autoantibody positive patients initially not classified as Type 1 were on insulin. When ICA, GADA, IA-2A, BMI and C-peptide were tested in a multiple logistic regression, only GADA was signiificant for insulin treatment within 3 years (OR = 18.8, 95% CI 1.8-191) in patients treated with diet or oral drugs at diagnosis. Conclusions A correct classification is difficult in adult diabetic patients. The presence of pancreatic autoantibodies, especially GADA, at diagnosis of diabetes are highly predictive for insulin therapy within 3 years from diagnosis. Copyright ⌐ 2000 John Wiley & Sons, Ltd.
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| 9. |
- Ares, Mikko, et al.
(författare)
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Decreased inducibility of TNF expression in lipid-loaded macrophages.
- 2002
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Ingår i: BMC Immunol. - BioMed Central Ltd.. - 1471-2172. ; 3:1, s. 13-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Inflammation and immune responses are considered to be very important in the pathogenesis of atherosclerosis. Lipid accumulation in macrophages of the arterial intima is a characteristic feature of atherosclerosis which can influence the inflammatory potential of macrophages. We studied the effects of lipid loading on the regulation of TNF expression in human monocyte-derived macrophages. RESULTS: In macrophages incubated with acetylated low density lipoprotein (ac-LDL) for 2 days, mRNA expression of TNF in cells stimulated with TNF decreased by 75%. In cell cultures stimulated over night with IL-1beta, lipid loading decreased secretion of TNF into culture medium by 48%. These results suggest that lipid accumulation in macrophages makes them less responsive to inflammatory stimuli. Decreased basal activity and inducibility of transcription factor AP-1 was observed in lipid-loaded cells, suggesting a mechanism for the suppression of cytokine expression. NF-kappaB binding activity and inducibility were only marginally affected by ac-LDL. LDL and ac-LDL did not activate PPARgamma. In contrast, oxidized LDL stimulated AP-1 and PPARgamma but inhibited NF-kappaB, indicating that the effects of lipid loading with ac-LDL were not due to oxidation of lipids. CONCLUSIONS: Accumulation of lipid, mainly cholesterol, results in down-regulation of TNF expression in macrophages. Since monocytes are known to be activated by cell adhesion, these results suggest that foam cells in atherosclerotic plaques may contribute less potently to an inflammatory reaction than newly arrived monocytes/macrophages.
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