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- Mann, D. L., et al.
(författare)
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Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL)
- 2004
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Ingår i: Circulation. - 1524-4539. ; 109:13, s. 1594-602
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Studies in experimental models and preliminary clinical experience suggested a possible therapeutic role for the soluble tumor necrosis factor antagonist etanercept in heart failure. METHODS AND RESULTS: Patients with New York Heart Association class II to IV chronic heart failure and a left ventricular ejection fraction < or =0.30 were enrolled in 2 clinical trials that differed only in the doses of etanercept used. In RECOVER, patients received placebo (n=373) or subcutaneous etanercept in doses of 25 mg every week (n=375) or 25 mg twice per week (n=375). In RENAISSANCE, patients received placebo (n=309), etanercept 25 mg twice per week (n=308), or etanercept 25 mg 3 times per week (n=308). The primary end point of each individual trial was clinical status at 24 weeks. Analysis of the effect of the 2 higher doses of etanercept on the combined outcome of death or hospitalization due to chronic heart failure from the 2 studies was also planned (RENEWAL). On the basis of prespecified stopping rules, both trials were terminated prematurely owing to lack of benefit. Etanercept had no effect on clinical status in RENAISSANCE (P=0.17) or RECOVER (P=0.34) and had no effect on the death or chronic heart failure hospitalization end point in RENEWAL (etanercept to placebo relative risk=1.1, 95% CI 0.91 to 1.33, P=0.33). CONCLUSIONS: The results of RENEWAL rule out a clinically relevant benefit of etanercept on the rate of death or hospitalization due to chronic heart failure.
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- Bergman, Marie-Louise, et al.
(författare)
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CTLA-4-/- mice display T cell-apoptosis resistance resembling that ascribed to autoimmune-prone non-obese diabetic (NOD) mice
- 2001
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Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 16:2, s. 105-113
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Tidskriftsartikel (refereegranskat)abstract
- The genes conferring susceptibility to autoimmune (insulin-dependent) diabetes mellitus (IDDM) are, in most cases, not defined. Among the loci so far identified as associated with murine IDDM (Idd1-19), only the nature of Idd1 has been assessed. Here we show that thymocytes and peripheral lymphocytes of the non-obese diabetic (NOD) mouse are relatively resistant to apoptosis induced by gamma-irradiation. By linkage analysis of F2 progeny mice, we map this trait to a locus on chromosome 1 containing the Idd5 diabetes susceptibility region. By the use of congenic mice, we confirm the linkage data and map this locus to a 6 cM region on proximal chromosome 1. Ctla4, being localized in this chromosomal region and mediating crucial functions in T cell biology, is a logical candidate gene in the Idd5 susceptibility region. In line with this, we demonstrate that T cells from Ctla4(-/-)deficient mice show a similar resistance to gamma-irradiation-induced apoptosis as observed in the NOD mice. This reinforces the notion that CTLA-4 contributes to the pathogenesis of autoimmune diabetes.
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- Vasan, Ramachandran S, et al.
(författare)
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Relations of serum aldosterone to cardiac structure : gender-related differences in the Framingham Heart Study.
- 2004
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Ingår i: Hypertension. - 1524-4563. ; 43:5, s. 957-62
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Tidskriftsartikel (refereegranskat)abstract
- Aldosterone is associated with myocardial fibrosis in experimental studies and with left ventricular remodeling in heart failure patients. We hypothesized that aldosterone influences ventricular remodeling in people without congestive heart failure in the community. We examined the relations between serum aldosterone and echocardiographic left ventricular measurements in 2820 Framingham Study subjects (mean age 57 years, 58% women, 88% white) free of myocardial infarction and overt heart failure. Serum aldosterone levels were higher in women compared with men. In linear regression models (adjusted for age, systolic blood pressure, weight, height, diabetes, heart rate, hypertension treatment, and ethnicity), left ventricular wall thickness and relative wall thickness were positively related, and left ventricular diastolic dimensions were inversely related to serum aldosterone in women (P<0.05 for all), but not in men (P>0.20 for all). There was no effect modification of the relations observed in women by menopausal status. The gender-related differences in relations of serum aldosterone to relative wall thickness were consistent across subgroups defined on the basis of sex-specific median values of systolic blood pressure and body mass index. Fractional shortening, left ventricular mass, and left atrial dimensions were not related to serum aldosterone in either sex. In conclusion, in our community-based sample of individuals free of myocardial infarction and heart failure, serum aldosterone was positively associated with a left ventricular geometric pattern suggestive of concentric remodeling (increased left ventricular wall thickness and relative wall thickness but decreased internal dimensions) in women but not in men. Additional investigations are warranted to confirm these findings.
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