Risperidone in the treatment of psychosis of Alzheimer disease: results from a prospective clinical trial.

OBJECTIVE: The objective of this study was to evaluate efficacy and safety of low-dose risperidone for treating psychosis of Alzheimer disease (AD). METHOD: The authors conducted a randomized, eight-week, double-blind, placebo-controlled, multicenter trial involving nursing home residents diagnosed with AD and psychosis. Four hundred seventy-three patients were randomly assigned to placebo (N = 238) or 1.0 to 1.5 mg risperidone per day (N = 235). Coprimary efficacy end points were: changes in scores on the Behavioral pathology in Alzheimer's Disease (BEHAVE-AD) Psychosis subscale and Clinical Global Impression of Change (CGI-C). Protocol-specified subgroup analyses were performed by demographics and dementia severity. RESULTS: Efficacy analysis included 416 patients. Both groups improved significantly on the BEHAVE-AD Psychosis subscale and CGI-C with no significant difference between groups. In the subgroups analyses, a statistically significant treatment by Mini-Mental Status Examination (MMSE) interaction on the CGI-C (F([2,381]) = 3.90, p = 0.021) was observed with patients with more severe dementia (MMSE <10) showing significant differences at end point favoring risperidone treatment (chi(2) ([1]) = 5.11, p = 0.024). Mean risperidone dose was 1.03 +/- 0.24 mg per day. All-cause discontinuation rates were 25% for both risperidone and placebo. Treatment-emergent adverse events occurred in 74% risperidone versus 64% placebo patients, with somnolence occurring significantly more frequently with risperidone (16.2% versus 4.6%). Nine (3.8%) risperidone- and six (2.5%) placebo patients died during or within 30 days after treatment. CONCLUSION: This trial did not confirm earlier findings in this population.     

Doxorubicin concentrations in plasma and myocardium and their respective roles in cardiotoxicity

Summary Three hours after the intravenous infusion of doxorubicin (3 mg/kg over 15 min) to anesthetized dogs, the drug concentration was found much higher in the myocardium than in the plasma (about 4,000 ng/g, i.e., 50 times higher). After the intravenous infusion of doxorubicin (1.5 mg/kg over 15 min) to conscious dogs, the drug concentration appeared to decline very slowly in the myocardium, since it was close to 200 ng/g at the 7th day, whereas the plasma concentration had fallen to zero, and the drug was still detected in the cardiac tissue 21 days after the administration. As myocardial concentrations of doxorubicin persist long after plasma clearance is complete, the hazards of repeated administration, based on plasma kinetic patterns, must be emphasized.     

Right-Left Orientation and Significance of Systematic Reversal in Children

Shortly before the acquisition of right and left, which generally occurs around age 6-7 years, a very simple right/left discrimination task makes it possible to distinguish groups of children with strikingly different cognitive abilities. Preschool children aged from 5 to 6.4 years were asked to show their left hand, right eye, left ear and right hand. On a variety of simple cognitive tasks exploring verbal fluency, syntactic comprehension, working memory, visuo-spatial ability and number processing, children who made from 1 to 3 errors (14% of the sample) performed significantly worse than those who showed systematic reversal (30%) and those who made no error. Differential use of logical thinking can partially explain these differences. Neuropsychological implications of these developmental findings are discussed.     

Phase-contrast velocimetry with hyperpolarized 3He for in vitro and in vivo characterization of airflow.

This paper describes a technique that combines radial MRI and phase contrast (PC) to map the velocities of hyperpolarized gases ((3)He) in respiratory airways. The method was evaluated on well known geometries (straight and U-shaped pipes) before it was applied in vivo. Dynamic 2D maps of the three velocity components were obtained from a 10-mm slice with an in-plane spatial resolution of 1.6 mm within 1 s. Integration of the in vitro through-plane velocity over the slice matched the input flow within a relative precision of 6.4%. As expected for the given Reynolds number, a parabolic velocity profile was obtained in the straight pipe. In the U-shaped pipe the three velocity components were measured and compared to a fluid-dynamics simulation so the precision was evaluated as fine as 0.025 m s(-1). The technique also demonstrated its ability to visualize vortices and localize characteristic points, such as the maximum velocity and vortex-center positions. Finally, in vivo feasibility was demonstrated in the human trachea during inhalation.