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- Axelson, Olav, 1937-, et al.
(författare)
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Regulatory toxicology and pharmacology.
- 2003
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Ingår i: International journal of occupational and environmental health. - 1077-3525 .- 2049-3967. ; 9, s. 386-389
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Berlow, E.L., et al.
(författare)
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Interaction strengths in food webs : Issues and opportunities
- 2004
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Ingår i: Journal of Animal Ecology. - : Wiley. - 0021-8790 .- 1365-2656. ; 73:3, s. 585-598
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Forskningsöversikt (refereegranskat)abstract
- 1. Recent efforts to understand how the patterning of interaction strength affects both structure and dynamics in food webs have highlighted several obstacles to productive synthesis. Issues arise with respect to goals and driving questions, methods and approaches, and placing results in the context of broader ecological theory. 2. Much confusion stems from lack of clarity about whether the questions posed relate to community-level patterns or to species dynamics, and to what authors actually mean by the term 'interaction strength'. Here, we describe the various ways in which this term has been applied and discuss the implications of loose terminology and definition for the development of this field. 3. Of particular concern is the clear gap between theoretical and empirical investigations of interaction strengths and food web dynamics. The ecological community urgently needs to explore new ways to estimate biologically reasonable model coefficients from empirical data, such as foraging rates, body size, metabolic rate, biomass distribution and other species traits. 4. Combining numerical and analytical modelling approaches should allow exploration of the conditions under which different interaction strengths metrics are interchangeable with regard to relative magnitude, system responses, and species identity. 5. Finally, the prime focus on predator-prey links in much of the research to date on interaction strengths in food webs has meant that the potential significance of nontrophic interactions, such as competition, facilitation and biotic disturbance, has been largely ignored by the food web community. Such interactions may be important dynamically and should be routinely included in future food web research programmes.
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| 3. |
- Leizorovicz, A., et al.
(författare)
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Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients
- 2004
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 1524-4539 .- 0009-7322. ; 110:7, s. 874-879
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Tidskriftsartikel (refereegranskat)abstract
- Background-Considerable variability exists in the use of pharmacological thromboprophylaxis among acutely ill medical patients, partly because clinically relevant end points have not been fully assessed in this population. We undertook an international, multicenter, randomized, double-blind, placebo-controlled trial using clinically important outcomes to assess the efficacy and safety of dalteparin in the prevention of venous thromboembolism in such patients. Methods and Results-Patients (n=3706) were randomly assigned to receive either subcutaneous dalteparin 5000 IU daily or placebo for 14 days and were followed up for 90 days. The primary end point was venous thromboembolism, defined as the combination of symptomatic deep vein thrombosis, symptomatic pulmonary embolism, and asymptomatic proximal deep vein thrombosis detected by compression ultrasound at day 21 and sudden death by day 21. The incidence of venous thromboembolism was reduced from 4.96% (73 of 1473 patients) in the placebo group to 2.77% (42 of 1518 patients) in the dalteparin group, an absolute risk reduction of 2.19% or a relative risk reduction of 45% (relative risk, 0.55; 95% CI, 0.38 to 0.80; P=0.0015). The observed benefit was maintained at 90 days. The overall incidence of major bleeding was low but higher in the dalteparin group (9 patients; 0.49%) compared with the placebo group (3 patients; 0.16%). Conclusions-Dalteparin 5000 IU once daily halved the rate of venous thromboembolism with a low risk of bleeding.
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| 4. |
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| 5. |
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| 6. |
- Vanholder, R, et al.
(författare)
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Uremic toxicity: present state of the art
- 2001
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Ingår i: The International journal of artificial organs. - : SAGE Publications. - 0391-3988 .- 1724-6040. ; 24:10, s. 695-725
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Tidskriftsartikel (refereegranskat)abstract
- The uremic syndrome is a complex mixture of organ dysfunctions, which is attributed to the retention of a myriad of compounds that under normal condition are excreted by the healthy kidneys (uremic toxins). In the area of identification and characterization of uremic toxins and in the knowledge of their pathophysiologic importance, major steps forward have been made during recent years. The present article is a review of several of these steps, especially in the area of information about the compounds that could play a role in the development of cardiovascular complications. It is written by those members of the Uremic Toxins Group, which has been created by the European Society for Artificial Organs (ESAO). Each of the 16 authors has written a state of the art in his/her major area of interest.
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| 7. |
- Young, J. B., et al.
(författare)
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Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials
- 2004
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Ingår i: Circulation. - 1524-4539. ; 110:17, s. 2618-26
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with symptomatic chronic heart failure (CHF) and reduced left ventricular ejection fraction (LVEF) have a high risk of death and hospitalization for CHF deterioration despite therapies with angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and even an aldosterone antagonist. To determine whether the angiotensin-receptor blocker (ARB) candesartan decreases cardiovascular mortality, morbidity, and all-cause mortality in patients with CHF and depressed LVEF, a prespecified analysis of the combined Candesartan in Heart Failure Assessment of Reduction in Mortality and morbidity (CHARM) low LVEF trials was performed. CHARM is a randomized, double-blind, placebo-controlled, multicenter, international trial program. METHODS AND RESULTS: New York Heart Association (NYHA) class II through IV CHF patients with an LVEF of < or =40% were randomized to candesartan or placebo in 2 complementary parallel trials (CHARM-Alternative, for patients who cannot tolerate ACE inhibitors, and CHARM-Added, for patients who were receiving ACE inhibitors). Mortality and morbidity were determined in 4576 low LVEF patients (2289 candesartan and 2287 placebo), titrated as tolerated to a target dose of 32 mg once daily, and observed for 2 to 4 years (median, 40 months). The primary outcome (time to first event by intention to treat) was cardiovascular death or CHF hospitalization for each trial, with all-cause mortality a secondary end point in the pooled analysis of the low LVEF trials. Of the patients in the candesartan group, 817 (35.7%) experienced cardiovascular death or a CHF hospitalization as compared with 944 (41.3%) in the placebo group (HR 0.82; 95% CI 0.74 to 0.90; P<0.001) with reduced risk for both cardiovascular deaths (521 [22.8%] versus 599 [26.2%]; HR 0.84 [95% CI 0.75 to 0.95]; P=0.005) and CHF hospitalizations (516 [22.5%] versus 642 [28.1%]; HR 0.76 [95% CI 0.68 to 0.85]; P<0.001). It is important to note that all-cause mortality also was significantly reduced by candesartan (642 [28.0%] versus 708 [31.0%]; HR 0.88 [95% CI 0.79 to 0.98]; P=0.018). No significant heterogeneity for the beneficial effects of candesartan was found across prespecified and subsequently identified subgroups including treatment with ACE inhibitors, beta-blockers, an aldosterone antagonist, or their combinations. The study drug was discontinued because of adverse effects by 23.1% of patients in the candesartan group and 18.8% in the placebo group; the reasons included increased creatinine (7.1% versus 3.5%), hypotension (4.2% versus 2.1%), and hyperkalemia (2.8% versus 0.5%), respectively (all P<0.001). CONCLUSIONS: Candesartan significantly reduces all-cause mortality, cardiovascular death, and heart failure hospitalizations in patients with CHF and LVEF < or =40% when added to standard therapies including ACE inhibitors, beta-blockers, and an aldosterone antagonist. Routine monitoring of blood pressure, serum creatinine, and serum potassium is warranted.
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| 8. |
- Campieri, M, et al.
(författare)
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Session II and III panel discussion
- 2000
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Ingår i: DRUGS OF TODAY. - 1699-3993. ; 36, s. 93-101
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 9. |
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| 10. |
- Linden, T, et al.
(författare)
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3,4-Dideoxyglucosone-3-ene (3,4-DGE): A cytotoxic glucose degradation product in fluids for peritoneal dialysis
- 2002
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Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 62:2, s. 697-703
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Tidskriftsartikel (refereegranskat)abstract
- Background. Bioincompatible glucose degradation products (GDPs) in fluids for peritoneal dialysis (PD) develop during sterilization and storage. Their biological activity has successfully been monitored through the use of various in vitro methods but their molecular and chemical nature is less well understood. Many GDPs are highly reactive carbonyl compounds. Although some of the identified GDPs are extremely cytotoxic, none of them actually possess cytotoxicity at the concentrations found in PD fluids. Thus, the GDP responsible for the toxicity in PD fluids has not yet been identified. The intention of the present work was to investigate to what extent the unsaturated dicarbonyl compound, 3,4-dideoxyglucosone-3-ene (3,4-DGE) was present in PD fluids, and if it could be responsible for the in vitro effects on L-929 fibroblast cells. Methods. A commercial preparation of 3,4-DGE and two different liquid chromatography methods were used for the chemical identification and quantification. In vitro bioincompatibility was determined as inhibition of cell growth using the L-929 fibroblast cell line. Results. 3,4-DGE was present in conventionally manufactured PD fluids at a concentration of 9 to 22 mumol/L. In the newly developed PD fluid, Gambrosol trio, the concentrations were 0.3 to 0.7 mumol/L. When added as synthetic 3,4-DGE to cell growth media at the concentrations measured in conventional PD fluids, the inhibition of cell growth was significantly lower than for that seen with the conventional fluids. However, in the conventional PD fluids the total amount of 3,4-DGE available for toxic reactions most probably was higher than that measured, because 3,4-DGE was freshly recruited from a molecular pool when consumed. The speed of this recruitment was high enough to explain most of the growth inhibition seen for heat-sterilized PD fluids. Conclusion. 3,4-DGE is present in conventional PD fluids at a concentration between 9 and 22 mumol/L, and is the most biologically active of all GDPs identified to date. Thus, it is the main candidate to be held responsible for the clinical bioincompatibility caused by conventionally manufactured PD fluids.
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