Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa and ropinirole in the MPTP-lesioned marmoset.

Long-term dopamine replacement therapy of Parkinson's disease leads to the occurrence of dyskinesias. Altered firing patterns of neurons of the internal globus pallidus, involving a pathological synchronization/desynchronization process, may contribute significantly to the genesis of dyskinesia. Levetiracetam, an antiepileptic drug that counteracts neuronal (hyper)synchronization in animal models of epilepsy, was assessed in the MPTP-lesioned marmoset model of Parkinson's disease, after coadministration with (1) levodopa (L-dopa) or (2) ropinirole/L-dopa combination. Oral administration of levetiracetam (13-60 mg/kg) in combination with either L-dopa (12 mg/kg) alone or L-dopa (8 mg/kg)/ropinirole (1.25 mg/kg) treatments was associated with significantly less dyskinesia, in comparison to L-dopa monotherapy during the first hour after administration. Thus, new nondopaminergic treatment strategies targeting normalization of abnormal firing patterns in basal ganglia structures may prove useful as an adjunct to reduce dyskinesia induced by dopamine replacement therapy without affecting its antiparkinsonian action.     

Liver transplantation for erythropoietic protoporphyria liver disease.

In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival.     

Evaluation of current extrication orthoses in immobilization of the unstable cervical spine

An experiment was designed to evaluate the comparative stabilizing efficacy of several widely used semi-rigid orthoses applied to unstable fresh cadaver cervical spines subject to load. Cadaver specimens were surgically destabilized at the C4-5 segment. Lateral radiographs of the destabilized spine were obtained before and after collar placement and after the application of a 5-pound flexion force. Data analysis employing a one-way analysis of variance showed no statistically significant difference in the Necloc's, Philadelphia Collar's, or the Stifneck's ability to stabilize the cervical spine against a deforming flexion force (P greater than 0.05). They all provide translational stability while allowing angular changes to occur with application of the flexion force. The Philadelphia Collar Halo System is statistically superior to all three of the aforementioned collars in prevention of both translation and sagittal rotation (P less than 0.05).     

A biometrical genetic approach to chromosome analysis inDrosophila: Detection of epistatic interactions in geotaxis

Chromosome analysis has been widely used as a first step in eclucidating the genetic architecture of several behaviors ofDrosophila melanogaster. These chromosome studies have generally used incomplete designs or fairly simple statistical analyses. Here I reanalyze two data sets on geotaxis from Pyle (1978) and Ksander (1966) using a biometrical genetic design. Results from the biometrical genetic reanalysis suggest that individual differences in geotaxis might be due to genes on all three major chromosomes which show extensive epistatic interactions.     

Self-evaluation and its relationship to clinical evaluation

An exploratory study was undertaken in a three-year nursing diploma program to determine instructor and student perceptions of self-evaluation (SE) and its relationship to clinical evaluation. A cross-section of instructors (n = 9) participated in three rounds of a Delphi survey. From this validated data base a questionnaire was developed and distributed to a stratified sample of 145 students. Combined results were then analyzed and compared. Results indicated that both students and instructors perceive self-evaluation more positively than negatively and they see the main purpose as providing direction for learning. Contrary to the literature and perceptions of surveyed instructors, students did not perceive self-evaluation as a factor in promotion of professional growth. Although students value a participatory role in clinical evaluation, the process of self-evaluation generates anxiety and underrating of performance. The authors conclude that self-evaluation is a developmental skill requiring guidelines and practice, and offer recommendations for its use.     

Safety profile and immunogenicity of an inactivated vaccine derived from an attenuated strain of hepatitis A.

To determine the safety and immunogenicity of an inactivated hepatitis A vaccine, 56 healthy adult volunteers were randomly assigned to receive an intramuscular injection of 6.3, 12.5 or 25 ng of inactivated hepatitis A vaccine or placebo at 0, 2 or 4, and 24 weeks. Adverse reactions occurred with similar frequency in vaccine and placebo recipients and consisted primarily of pain or tenderness at the injection site. By 4 weeks after a single 6.3, 12.5 or 25 ng injection, seven, nine and ten out of ten vaccinees, respectively, had antibody detectable by a HAV AB assay modified to increase its sensitivity tenfold. All vaccinees had antibodies detectable by this assay within 2 weeks of their second inoculation. Geometric mean antibody levels increased with higher doses of vaccine (p = 0.05). Neutralizing antibody was detected within 4 weeks of a single inoculation in all vaccinees. Neutralizing antibody was detected after the third inoculation at dilutions of greater than or equal to 1:2048 in all 12.5 and 25 ng vaccinees. All 19 vaccinees tested at 24 months still had HAV antibodies detectable by a modified HAV AB assay. This inactivated hepatitis A vaccine appears to be well tolerated and immunogenic at doses of 6.3-25 ng. The choice of dose and vaccination schedule may depend on the rapidity with which seroconversion is desired.