Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

2D crystallization: from art to science

The techniques as well as the principles of the 2D crystallization of membrane and water-soluble proteins for electron crystallography are reviewed. First, the biophysics of the interactions between proteins, lipids and detergents is surveyed. Second, crystallization of membrane proteins in situ and by reconstitution methods is discussed, and the various factors involved are addressed. Third, we elaborate on the 2D crystallization of water-soluble proteins, both in solution and at interfaces, such as lipid monolayers, mica, carbon film or mercury surfaces. Finally, techniques and instrumentations that are required for 2D crystallization are described

Milk flow and udder health in cows after treatment of covered teat injuries via theloresectoscopy: 52 cases (2000-2002)

OBJECTIVE: To determine milk flow, somatic cell counts (SCCs), and the incidence of clinical mastitis in cows that had undergone theloresectoscopy for treatment of teat stenosis caused by mucosal detachment in the region of the streak canal or Fürstenberg's rosette. DESIGN: Retrospective study. ANIMALS: 52 cows with teat stenosis that were treated via theloresectoscopy. PROCEDURE: Medical records of eligible cows were reviewed. Additional data regarding milking ease, SCC, development of clinical mastitis of the affected gland, and whether the cow remained in the herd were collected via owner-completed questionnaires. RESULTS: 49 of 52 questionnaires were completed. At referral, teat sinusitis was diagnosed in 29 of 52 cows. Milk flow was normal in 38 of 41 treated teats at discharge and in 24 of 40 during the next lactation. Thirteen of 49 cows were culled during the next lactation because of abnormal udder health. High SCC and teat sinusitis at referral and development of clinical mastitis during the 10-day period after surgery resulted in high SCCs in the remainder of the current lactation. The incidence of clinical mastitis during the remainder of the current and during the next lactation was higher in cows that had teat sinusitis at the time of surgery, compared with those that did not. CONCLUSIONS AND CLINICAL RELEVANCE: Teat stenoses resulting from mucosal lesions in the region of the streak canal or Fürstenberg's rosette may be successfully treated via theloresectoscopy. Inflammation of the teat sinus and gland at the time of surgery may adversely affect udder health