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81.
82.
Tardif JC Grégoire J Lespérance J Lambert J L'Allier PL Rodés J Anderson T Blue JW Imus J Heinonen T 《American heart journal》2002,144(4):589-596
Background Although statins have been shown to be beneficial in the management of hyperlipidemia and the reduction of cardiovascular morbidity and mortality, rates of major cardiovascular events remain high despite their use. Inhibition of the acyl coenzyme A: cholesterol acyltransferase (ACAT) enzyme in the arterial wall may prevent excess accumulation of cholesteryl esters in macrophages. In addition to ACAT inhibitor monotherapy, combination of a statin with an ACAT inhibitor may be a promising approach to further prevent the progression of atherosclerosis. Methods This report describes the design and methodologic features of a double-blind, randomized, placebo-controlled trial to assess the effect of the ACAT inhibitor avasimibe at 50-, 250-, and 750-mg daily dosages on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients receive background lipid-lowering therapy when necessary. The study population consists of patients with at least one 20% to 50% diameter stenosis in a coronary artery with a reference diameter of ≥2.5 mm. IVUS and coronary angiography are performed at baseline and repeated at 24 months. The primary study end point is the change from baseline in plaque volume in a 30-mm segment of the coronary artery assessed by 3-dimensional IVUS. Several other IVUS and angiographic end points are measured. Conclusions The Avasimibe and Progression of coronary Lesions assessed by intravascular UltraSound (A-PLUS) trial is among the first large imaging trials to use IVUS as a primary end point and assesses the effects of the ACAT inhibitor avasimibe on atherosclerosis progression. (Am Heart J 2002;144:589-96.) 相似文献
83.
Deletion of alanine 2201 in the FVIII C2 domain results in mild hemophilia A by impairing FVIII binding to VWF and phospholipids and destroys a major FVIII antigenic determinant involved in inhibitor development 总被引:1,自引:0,他引:1 下载免费PDF全文
d'Oiron R Lavergne JM Lavend'homme R Benhida A Bordet JC Negrier C Peerlinck K Vermylen J Saint-Remy JM Jacquemin M 《Blood》2004,103(1):155-157
The C2 domain of factor VIII (FVIII) mediates FVIII binding to von Willebrand factor (VWF) and phospholipids (PLs), thereby determining the stability and the activity of FVIII. A deletion of Ala2201 (Del2201) was identified in the FVIII C2 domain of 2 unrelated patients with mild hemophilia A (FVIII:C 11%-33%). This mutation prevents FVIII binding to a human monoclonal antibody recognizing the C2 domain and inhibiting FVIII binding to VWF and phospholipids. By comparison to healthy FVIII, Del2201 FVIII had a significantly reduced binding to VWF, which likely contributes to reduced FVIII levels in plasma. Del2201 FVIII interaction with phospholipids was evaluated in an FXa generation assay, using various concentrations of synthetic phospholipid vesicles mimicking an activated platelet surface. At the lowest phospholipid concentration allowing FXa generation, Del2201 FVIII activity was reduced 3-fold. This is the first report of a mutation altering FVIII binding to phospholipids and occurring in patients with hemophilia A. 相似文献
84.
Fala El Machhour Zela Keuylian Panagiotis Kavvadas Jean-Claude Dussaule Christos Chatziantoniou 《Journal of the American Society of Nephrology : JASN》2015,26(7):1561-1575
Notch3 expression is found in the glomerular podocytes of patients with lupus nephritis or focal segmental GN but not in normal kidneys. Here, we show that activation of the Notch3 receptor in the glomeruli is a turning point inducing phenotypic changes in podocytes promoting renal inflammation and fibrosis and leading to disease progression. In a model of rapidly progressive GN, Notch3 expression was induced by several-fold in podocytes concurrently with disease progression. By contrast, mice lacking Notch3 expression were protected because they exhibited less proteinuria, uremia, and inflammatory infiltration. Podocyte outgrowth from glomeruli isolated from wild-type mice during the early phase of the disease was higher than outgrowth from glomeruli of mice lacking Notch3. In vitro studies confirmed that podocytes expressing active Notch3 reorganize their cytoskeleton toward a proliferative/migratory and inflammatory phenotype. We then administered antisense oligodeoxynucleotides targeting Notch3 or scramble control oligodeoxynucleotides in wild-type mice concomitant to disease induction. Both groups developed chronic renal disease, but mice injected with Notch3 antisense had lower values of plasma urea and proteinuria and inflammatory infiltration. The improvement of renal function was accompanied by fewer deposits of fibrin within the glomeruli and by decreased peritubular inflammation. Finally, abnormal Notch3 staining was observed in biopsy samples of patients with crescentic GN. These results demonstrate that abnormal activation of Notch3 may be involved in the progression of renal disease by promoting migratory and proinflammatory pathways. Inhibiting Notch3 activation could be a novel, promising approach to treat GN. 相似文献
85.
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87.
Alain Putot Marianne Zeller Sophie Perrin Jean-Claude Beer Jack Ravisy Charles Guenancia Raphaël Robert Patrick Manckoundia Yves Cottin 《The American journal of medicine》2018,131(4):422-429.e4
Background
Red blood cell transfusion benefit during acute myocardial infarction remains unclear in the elderly. We aimed to assess the transfusion impact on 1-year mortality in acute myocardial infarction patients aged ≥65 years, according to their age and hemoglobin nadir.Methods
We included 3316 consecutive patients with acute myocardial infarction aged ≥65 years from the “obseRvatoire des Infarctus de Côte d'Or” (RICO) survey. They were categorized according to their hemoglobin nadir (≤8, >8 to ≤10, and >10 g/dL) and age (<80 or ≥80 years).Results
A total of 1906 patients (57%) were 65-79 years old, and 1410 (43%) were aged ≥80 years, of whom 103 (5%) and 145 (10%) patients received red blood cell transfusion, respectively (P < .001). In Cox regression analysis, transfusion was associated with increased 1-year mortality for hemoglobin nadir >10 g/dL but no significant effect for hemoglobin nadir between 8 and 10 g/dL. When hemoglobin nadir was ≤8 g/dL, transfusion did not influence 1-year mortality for younger patients (65-79 years). However, for older patients (≥80 years), transfusion was associated with lower mortality (hazard ratio 0.43 [95% confidence interval, 0.22-0.86], P = .016).Conclusion
Among older patients with acute myocardial infarction, the effect of transfusion was largely dependent on hemoglobin threshold and age. Transfusion was associated with increased 1-year mortality when hemoglobin nadir was >10 g/dL. However, in patients aged ≥80 years with hemoglobin nadir <8 g/dL, transfusion was associated with a 50% reduction in 1-year mortality. 相似文献88.
L'Huillier I Cottin Y Touzery C Zeller M Beel JC Fraison M Verges B Louis P Brunotte F Wolf JE 《International journal of cardiology》2003,90(2-3):165-173
Objective: This study was designed to assess the prognostic value of myocardial tomoscintigraphy perfusion imaging after percutaneous coronary intervention (PCI) in asymptomatic diabetic patients. Methods: One hundred and fourteen diabetic patients were followed up during 27±16 (mean±SD) months after the myocardial tomoscintigraphy. PCI-related events were studied after myocardial tomoscintigraphy stress testing and included major cardiac events (MACE) (cardiovascular death, myocardial infarction) and revascularization (bypass surgery or new PCI). Stress myocardial tomoscintigraphy imaging was performed 5±5 months after PCI and ischemia was considered as present if at least 2 contiguous segments were showing reversible defects. Results: Persistent silent ischemia was found in 49/114 (43%) patients. No difference was observed between the two groups for MACE: four among the 65 (6%) non ischemic patients versus 2 among the 49 (4%) ischemic patients (NS). In contrast, 15 (31%) among the ischemic patients and 4 (6%) among the non ischemic patients underwent iterative revascularization (p<0.01). The relative risk of revascularization for patients with significant ischemia was 5.5 versus non ischemic patients (p<0.001). Conclusion: After PCI, in asymptomatic diabetic patients followed by myocardial tomoscintigraphy a high frequency of persistent silent ischemia was found and associated with a high risk for repeat interventional procedure, although no increase in major cardiac events was observed. 相似文献
89.
Risk factors of fibrosis in alcohol-induced liver disease 总被引:17,自引:0,他引:17
Raynard B Balian A Fallik D Capron F Bedossa P Chaput JC Naveau S 《Hepatology (Baltimore, Md.)》2002,35(3):635-638
In patients with nonalcoholic steatohepatitis (NASH), age, obesity, and diabetes mellitus are independent predictors of the degree of fibrosis. The relative risk for fibrosis adjusted for sex was also associated with increasing grade of Perls stain. The aim of this study was to determine whether the risk factors for fibrosis described in NASH are also risk factors in alcohol-induced liver disease. A total of 268 alcoholic patients with negative hepatitis B virus and hepatitis C virus serology underwent liver biopsy. Fibrosis was assessed semiquantitatively by a score fluctuating between 0 to 8. Liver iron overload was assessed by Perls staining and graded in 4 classes. We have used multivariate regression with partial correlation analysis to assess the variability of fibrosis score according to the value of 7 variables: sex, age, body mass index (BMI) in the past year before the hospitalization when the patient was asymptomatic, daily alcohol intake over the past 5 years, total duration of alcohol abuse, Perls grade, and blood glucose level. In the multivariate regression, fibrosis score was positively correlated with age (P =.001), BMI (P =.002), female sex (P <.05), Perls grade (P <.05), and blood glucose level (P <.05). Twenty percent of the variability of fibrosis score was explained by the 7 variables. In conclusion, after adjustment for daily alcohol intake and total duration of alcohol abuse, BMI, Perls grade, and blood glucose are also independent risk factors for fibrosis in alcohol-induced liver disease, raising therapeutic implications for the management of these patients. 相似文献
90.
We thank Drs Michalsen and Dobos for their comments. Restingheart rate is indeed a strong predictor of mortality in patientswith coronary artery disease.1 相似文献