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.     

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.     

18 Graduate Medical Education and Knowledge Translation: One Problem-Specific Approach in Residency

Traditional graduate medical education approaches to improving clinical performance based upon the latest research have included Journal Club and didactic lectures. Unfortunately, these educational interventions have rarely been demonstrated to change practice behavior or improve patient-important outcomes. Using a structured approach to identifying a gap between best-evidence knowledge and clinical practice, an illustrative one-year residency-wide translational research project was developed in a four year emergency medicine training program. Step one (assigned to the second year residents): identify and quantitatively justify a Knowledge Translation (KT) deficit within our institution. They identified steroids in adult bacterial meningitis as an unequivocal therapeutic option. Based upon a structured one-year chart review, they next demonstrated that only 7% of meningitis patients received pre-antimicrobial steroids. The next step (assigned to the first year residents): identify and quantify the physician "leaks" within the pipeline of information from publication to bedside utilization via an online survey. The third year residents hypothesized plugs for these information leaks, including examples of other specialties or institutions which have successfully navigated this specific clinical scenario. Finally, at an end-of-year Journal Club, the fourth year residents formulated a protocol for the appropriate use of steroids in suspected adult meningitis and brought together individuals from within the institution contributing to the best-practice leak. Knowledge Translation involves multiple stages beyond simple evidence awareness and usually involves continuation beyond the emergency department. The Washington University KT project offers a structured, multidisciplinary example of moving beyond contemplation to implementation of an unequivocal therapy.     

Evaluation of clinical outcomes in anterior cruciate ligament surgery

Clinical outcomes data can be used to facilitate patient management decisions, assess clinician and organizational performance, and to provide evidence for the effectiveness of surgery and rehabilitation. The validity of the inferences made from outcomes data are dependent on the validity of the outcomes measures themselves and the circumstances under which the data were collected, analyzed, and interpreted. Clinical outcomes may include measures of impairment of body structure and function, activity limitation, and participation restriction. However, because the relationship between impairment and the resulting activity limitation and participation restriction is not direct, and because activity limitations and participation restrictions are of the utmost concern to the athlete, the primary clinical outcome should be measures of activity limitation and participation restriction. Activity limitation and participation restriction may be measured either through direct observation of performance or by general or specific measures of health related quality of life. Clinical outcomes data must be collected systematically to ensure valid inferences from the data.     

Pseudo-endophthalmitis caused by intravitreal lipid transudation in association with proliferative diabetic retinopathy and hyperlipidemia

A 20-year-old woman with a 13-year history of insulin-dependent diabetes mellitus presented with a history of malaise, fever, a non-healing ulcer of the great toe, and an insect bite incurred during recent travel to a foreign country. Milky white infiltrates accompanied by inflammatory cells located within close proximity to neovascular fronds in both vitreous cavities led to the suspicion of bilateral metastatic endophthalmitis. Studies conducted during hospitalization failed to show evidence of systemic blood born infection. A diagnostic vitrectomy in one eye failed to grow organisms, though lipid laden macrophages were identified by electron microscopy. The clinical appearance improved in both eyes during her hospitalization coincident with improved diabetic control. It was later concluded that the milky white infiltrates were associated with hyperlipidemia as a consequence of poorly controlled diabetes and a familial tendency toward hyperlipidemia.     

Long-term treatment of ventricular tachycardia with amiodarone in presence of severe left ventricular dysfunction.

A group of 34 consecutive patients with coronary artery disease (n = 29) or dilated cardiomyopathy (n = 5) (3 women, 31 men, age 38-80 yr) who had severely impaired left ventricular function (left ventricular ejection fraction less than or equal to 40%) and high-grade ventricular ectopic activity (sustained or nonsustained ventricular tachycardia or ventricular fibrillation) were treated with amiodarone (mean dose: 206 mg/d) and followed for 1-117 (mean: 49) months. In the total group, there were seven sudden deaths, five deaths due to pump failure, one non-cardiac death, and two successful heart transplantations during follow-up. Thus the annual cardiac mortality in these carefully selected and followed patients was 8, 6%, the annual cardiac event rate was 10, 1%. The cumulative cardiac survival-rate was 62% after 5 years and 41% after 10 years. In five patients, treatment was interrupted after 10 to 43 months, three of the patients were alive at follow-up and two suffered cardiac death, resulting in an annual cardiac death rate of 12% in this subgroup of treatment. Based on the results of this retrospective analysis we conclude that in patients with low left ventricular ejection fraction and nonsustained or sustained ventricular tachycardia treated with low dose amiodarone, mortality was unexpectedly low. Thus, it may be the antiarrhythmic treatment to be considered in patients with ventricular tachycardia and severe left ventricular dysfunction.