Effects of risperidone on dopamine receptor subtypes in developing rat brain.

The atypical antipsychotic risperidone is often prescribed to pediatric patients with neuropsychiatric disorders, though its effects on the developing brain remain unclear. Accordingly, we studied the effects of repeated treatment of risperidone on dopamine receptors in brain regions of juvenile rat. Levels of dopamine receptors (D(1), D(2), D(3), D(4)) in forebrain regions of juvenile rats were quantified after 3 weeks of treatment with three different doses of risperidone (0.3, 1.0 and 3.0 mg/kg) and compared findings to those in adult rats treated with risperidone (3.0 mg/kg/day) previously. Risperidone (at 1.0 and 3.0 mg/kg/day) increased levels of D(1) receptors in nucleus accumbens and caudate-putamen of juvenile, but not adult rats. Conversely, all three doses of risperidone dose-dependently increased D(2) labeling in medial prefrontal cortex and hippocampus, and D(4) receptor in nucleus accumbens, caudate-putamen and hippocampus of juvenile animals as well as in adults. Only the high dose of risperidone (3.0 mg/kg) increased D(2) receptors in caudate-putamen in both juvenile and adult brain. D(3) receptors were not altered by risperidone in any brain region at any dose or age. The findings indicate dose-dependent effects of risperidone on dopamine receptors in developing animals, and that juvenile animals are more sensitive than adults to the cerebral effects of risperidone.     

The influence of in-season injury prevention training on lower-extremity kinematics during landing in female soccer players.

OBJECTIVE: To examine the influence of in-season injury prevention training on hip and knee kinematics during a landing task. DESIGN: Longitudinal pre-post intervention study. SETTING: Testing sessions were conducted in a biomechanics research laboratory. PARTICIPANTS: Eighteen female soccer players between the ages of 14 and 17 participated in this study. All subjects were healthy with no current complaints of lower extremity injury. INTERVENTIONS: Testing sessions were conducted prior to and following a season of soccer practice combined with injury prevention training. MAIN OUTCOME MEASUREMENTS: During each testing session three-dimensional kinematics were collected while each subject performed a drop landing task. Peak hip and knee joint angles were measured during the early deceleration phase of landing and compared between pre- and post-training using paired t-tests. RESULTS: Following a season of soccer practice combined with injury prevention training, females demonstrated significantly less hip internal rotation (7.1 degrees vs. 1.9 degrees; P = 0.01) and significantly greater hip abduction (-4.9 degrees vs. -7.7 degrees; P = 0.02). No differences in knee valgus or knee flexion angles were found post-season. CONCLUSIONS: Female soccer players exhibited significant changes in hip kinematics during a landing task following in-season injury prevention training. Our results support the premise that a season of soccer practice combined with injury prevention training is effective in altering lower extremity motions that may play a role in predisposing females to ACL injury.     

Age trends in femur stresses from a simulated fall on the hip among men and women: evidence of homeostatic adaptation underlying the decline in hip BMD.

Age trends in proximal femur stresses were evaluated by simulating a fall on the greater trochanter using femur geometry from hip DXA scans of 5334 white men and women in the NHANES III survey. Expansion of femur outer diameter seems to counter net bone loss so that stresses remain similar across age groups, but stresses are higher in older women than in older men. INTRODUCTION: The age decline in hip BMD is caused by both bone loss and expansion of outer diameter that increases the region size over which mass is measured in a DXA scan. Because expansion has an opposing effect on structural strength, it may be a homeostatic adaptation to net bone loss to ensure that load stresses are kept within a narrow range. MATERIALS AND METHODS: Age trends in femur stresses were evaluated with an engineering beam simulation of a fall on the greater trochanter. Hip geometry was extracted from hip DXA scans using the Hip Structure Analysis (HSA) software on 2613 non-Hispanic white men and 2721 women from the third National Health and Nutrition Examination Survey (NHANES III). Using body weight as load, stresses were computed on the inferior-medial and superior-lateral femur neck at its narrowest point and the medial and lateral shaft 2 cm distal to the midpoint of the lesser trochanter. Stresses and the underlying geometries in men and women >50 years oaf age were compared with those 20-49 years of age. RESULTS: Compared with men <50 years of age, stresses in older men were 6% lower on both surfaces of the shaft, 4% lower on the inferior-medial neck, and not different on the superior-lateral neck. In women >50 years of age, stresses on the proximal shaft and inferior-medial neck remained within 3% of young values but were 13% greater on the superior-lateral neck. Neck stresses in young women were lower on the superior-lateral than the inferior-medial neck, but lateral stress increased to the level on the medial surface in older women. Stresses were higher in women than in men, with a greater gender difference in those >50 years of age. CONCLUSIONS: We conclude that femur expansion has a homeostatic effect in men and women that opposes bone loss so that stresses change little with age. Because expansion preserves stresses with progressively less bone mass, the process may reduce structural stability in the femoral neck under fall conditions, especially in the elderly female.     

Effect of Ginkgo biloba (EGb 761) and aspirin on platelet aggregation and platelet function analysis among older adults at risk of cardiovascular disease: a randomized clinical trial.

Several case reports have implicated Ginkgo biloba in clinically adverse bleeding disorders. Ginkgo biloba has been reported to increase pain-free walking distance among patients with peripheral artery disease (PAD). Standard PAD therapy includes 325 mg/day aspirin. The objective of this study was to examine potential adverse effects of concomitant aspirin and Ginkgo biloba on platelet function. Ginkgo biloba (EGb 761, 300 mg/day) was compared with placebo for effects on measures of platelet aggregation among adults consuming 325 mg/day aspirin in a randomized, double-blind, placebo-controlled, parallel design trial of 4-week duration. Participants were adults, age 69 +/- 10 years, with PAD or risk factors for cardiovascular disease. Outcome measures included platelet function analysis (PFA-100 analyzer) using ADP as an agonist (n = 26 placebo; n = 29 ginkgo), and platelet aggregation using ADP, epinephrine, collagen and ristocetin as agonists (n = 21 placebo; n = 23 ginkgo). Participants kept daily logs of bleeding or bruising episodes. There were no clinically or statistically significant differences between treatment groups for any agonists, for either PFA-100 analysis or platelet aggregation. Reports of bleeding or bruising were infrequent and similar for both study groups. In conclusion, in older adults with PAD or cardiovascular disease risk, a relatively high dose of Ginkgo biloba combined with 325 mg/day daily aspirin did not have a clinically or statistically detectable impact on indices of coagulation examined over 4 weeks, compared with the effect of aspirin alone. No adverse bleeding events were observed, although the trial was limited to a small sample size.     

Popliteal artery pseudoaneurysm following total knee arthroplasty: a case report

Direct vascular injury after primary total knee arthroplasty is rare. This case report illustrates a 65-year-old female who was diagnosed with a pseudoaneurysm of the popliteal artery when she was investigated for increased leg swelling and pain 1 week after total knee arthroplasty. She had a percutaneous endovascular repair with a stent after thrombectomy.     

Clinical trials seen shifting overseas.

A Tufts University study released in mid-2003 indicates that increasing numbers of clinical trials for U.S.-produced pharmaceutical are being conducted outside the United States, mainly by contract research organizations. This process speeds up clinical trials, but raises ethical issues of the possible coercion or exploitation of more vulnerable and naive patient populations.