Time course of the effects of diazepam and lorazepam on perceptual priming and explicit memory

The effects of diazepam and lorazepam on explicit memory and perceptual priming were studied 50, 130 and 300 min after drug administration. Sixty healthy volunteers were randomly assigned to one of five parallel groups (placebo, diazepam 0.2 or 0.3 mg/kg, lorazepam 0.026 or 0.038 mg/kg). The corresponding doses of benzodiazepines exerted a similar negative effect on explicit performance. Lorazepam markedly impaired priming performance, whereas the effect of diazepam was intermediate between that of placebo and that of lorazepam 0.038 mg/kg. The impairment was maximal at the theoretical peak plasma concentration. Contamination by explicit memory could account for the decrease in priming performance observed in the diazepam groups.     

An electrophysiological correlate of protein kinase C isozyme distribution in cultured cerebellar neurons.

Protein kinase C (PKC) is a family of at least seven closely related molecules (isozymes) that vary in terms of their requirements for activation and their distribution among cells of the brain. A striking example of this differential distribution is seen in the cerebellum, where Purkinje cells express PKC-I, an isozyme that is strongly activated by both phorbol ester (PE), and low doses of cis-unsaturated fatty acid (c-UFA), while granule cells predominantly express PKC-II, an isozyme that is strongly activated by PE but not c-UFA. Both Purkinje and granule cells have large, easily recorded voltage-gated K currents. These currents are attenuated by PKC activators in several other varieties of neuron. We hypothesized that the effects of these two PKC activators would be predicted by the distribution of the relevant PKC isozyme, and that the delayed outward rectifier current, IK, would be attenuated by both PE and c-UFA in Purkinje cells, but only by PE in granule cells. This hypothesis was confirmed in perforated-patch recordings. The attenuation produced by both activators could be blocked by application of a specific PKC inhibitor, RO-31-8220, and could not be mimicked by inert forms of PE or c-UFA. To our knowledge, this study represents the first report of an electrophysiological correlate of PKC isozyme distribution.     

Simultaneous flow cytometric detection of antibodies against platelets, granulocytes and lymphocytes

We present a time-saving and objective flow cytometric immunofluorescence assay for the simultaneous detection of antibodies against platelets, granulocytes or lymphocytes using a reconstituted mixture of these cell populations. Platelets, granulocytes and lymphocytes could be distinguished on the basis of their forward (FSC) and sideways (SSC) light scattering properties plotted on scales of 4 log orders. After setting FSC/SSC gates around the platelets, granulocytes and lymphocytes, the reactivity of the sera with the cell populations was determined by histogram analyses of immunofluorescence for each gate. The flow cytometric assay of reconstituted cell mixtures showed a strong, positive correlation with a reference microscopic immunofluorescence assay of separate cell suspensions. The reproducible procedures for the isolation and staining of the cells and the electronic stability of the flow cytometer permitted the use of the same gate and marker settings throughout the experiments. Consequently, the entire analysis of data stored in list mode could be performed using a keystroke, so that time consuming and subjective manual analyses were avoided.     

A school curriculum-based exercise program increases bone mineral accrual and bone size in prepubertal girls: two-year data from the pediatric osteoporosis prevention (POP) study.

This 2-year prospective controlled exercise intervention trial in 99 girls at Tanner stage 1, evaluating a school curriculum-based training program on a population-based level, showed that the annual gain in BMC, aBMD, and bone size was greater in the intervention group than in the controls. INTRODUCTION: Most exercise intervention studies in children, evaluating the accrual of BMD, include volunteers and use specifically designed osteogenic exercise programs. The aim of this study was to evaluate a 2-year general school-based exercise intervention program in a population-based cohort of girls at Tanner stage 1. MATERIALS AND METHODS: Forty-nine girls 7-9 years of age in grades 1 and 2 in one school were included in a school curriculum-based exercise intervention program of general physical activity for 40 minutes per school day (200 minutes/week). Fifty healthy age-matched girls in three neighboring schools, assigned to the general Swedish school curriculum of physical activity (60 minutes/week), served as controls. All girls were premenarchal, remaining in Tanner stage 1 during the study. BMC (g) and areal BMD (aBMD; g/cm2) were measured with DXA of the total body (TB), the lumbar spine (L2-L4 vertebrae), the third lumbar vertebra (L3), the femoral neck (FN), and the leg. Volumetric BMD (vBMD; g/cm3) and bone size were calculated at L3 and FN. Total lean body mass and total fat mass were estimated from the total body scan. Height and weight were also registered. Baseline measurements were performed before the intervention was initiated. Follow-up was done after 2 years. RESULTS: No differences between the groups were found at baseline in age, anthropometrics, or bone parameters. The annual gain in BMC was greater in the intervention group than in the controls: L2-L4, mean 3.8 percentage points (p = 0.007); L3 vertebra, mean 7.2 percentage points (p < 0.001); legs, mean 3.0 percentage points (p = 0.07). The intervention group had a greater annual gain in aBMD: total body, mean 0.6 percentage points (p = 0.006), L2-L4, mean 1.2 percentage points (p = 0.02), L3 vertebra, mean 1.6 percentage points (p = 0.006); legs, mean 1.2 percentage points (p = 0.007). There was also a greater mean annual gain in bone size in the L3 vertebra (mean 1.8 percentage points; p < 0.001) and in the FN (mean 0.3 percentage points; p = 0.02). CONCLUSIONS: A general school-based exercise program for 2 years for 7- to 9-year-old girls (baseline) enhances the accrual of BMC and BMD and increases bone size.     

The effect of oral appliance therapy on blood pressure in patients with obstructive sleep apnea

The objective of the study was to investigate the effects of oral appliance (OA) therapy on ambulatory blood pressure in patients with obstructive sleep apnea (OSA). Eleven OSA patients who received OA therapy were prospectively investigated. Ambulatory blood pressure was measured for 20 h from 4:00 p.m. to 12:00 noon the next day using an ambulatory blood pressure monitor. The Respiratory Disturbance Index (RDI) was measured in the pretreatment and posttitration periods. The OA was titrated to reach a therapeutic jaw position over 2 to 8 months, and posttitration measurements were repeated. At posttitration, the RDI was significantly decreased from a mean (SD) of 24.7 (20.1) to 6.1 (4.5). Significant reductions in diastolic blood pressure (DBP) and mean arterial pressure (MAP) were found for the 20-h periods, and systolic blood pressure (SBP), DBP, and MAP while asleep. The mean values were 79.5 (5.5) to 74.6 (6.0) for DBP and 95.9 (5.4) to 91.2 (5.9) for MAP, for over a 20-h period, and 118.4 (10.0) to 113.7 (9.1) for SBP, 71.6 (8.0) to 67.2 (7.9) for DBP, and 88.4 (8.0) to 83.9 (7.5) for MAP, while asleep. This study suggests that successful OSA treatment with an OA may also be beneficial to lower blood pressure in OSA patients, as previously suggested for nasal continuous positive airway pressure therapy. This study was conducted in the Division of Orthodontics, The University of British Columbia, Canada     

Phenotype of endomyocardial biopsy-derived T-lymphocyte cultures and chronic rejection after heart transplantation

Chronic rejection (CR) is a major problem in long-term survival in heart transplantation. We analysed whether the occurrence of CR correlates with the incidence of acute rejections (AR) or with characteristics of endomyocardial biopsy-derived cell cultures. CR was diagnosed by annual angiography and defined as all coronary vascular changes. One year after transplantation 24 of the 63 patients had CR (38%). The incidence of AR in CR + and CR — patients was comparable. The patients in both groups had similar individual median percentages of EMB-yielding cell cultures. During the first year the CR — patients had more cultures in which at least 60% of the cells were CD4 + T cells (50% vs 37%, P = 0.05), due to a stronger CD4 predominance in the first 6 months. In the second year the CD4 predominance in the patients diagnosed as CR + after 1 year tended to be higher (P = 0.08). The patients had comparable percentages of cultures predominated by CD8 + T cells, γδ T cells or NK cells, irrespective of the time interval. These results might indicate that CD4 + T lymphocytes play a dual role in the aetiology of CR.