Analysis of clozapine response and polymorphisms of the dopamine D4 receptor gene (DRD4) in schizophrenic patients

We have examined the hypothesis that a variable number of tandem repeats in the third cytoplasmic loop of the dopamine D4 receptor influences clinical response to clozapine using a sample of 189 schizophrenic patients. Alleles of the 48-bp repeat, which range from two to ten copies in the normal human population, were analysed by the polymerase chain reaction using genomic DNA as template. Association between these alleles and response to clozapine was tested using the difference in pre-and post-treatment GAS scores as a measure of response. We found no statistically significant variation between genotypic groups and response by analysis of variance. We conclude that the variation of the number of 48-bp repeats alone does not determine response to clozapine. Larger studies are underway to determine if there is a more subtle relationship with sequence variation within the repeats or at other polymorphic sites within the gene that may provide evidence for a component of clozapine's action being at D4 receptors. © 1995 Wiley-Liss, Inc.     

Cortical Distribution of Eeg Activity for Component Processes During Mental Rotation

Alpha power (8–12 Hz) was monitored over the frontal, temporal, parietal and occipital lobes of the left and right cerebral hemispheres while participants mentally rotated three-dimensional shapes to match a specified target. By comparing the activational patterns generated during three experimental conditions, each designed to systematically isolate the involvement of the various subcomponents comprising this mental rotation task, it was suggested that the right frontal lobe mediates encoding and comparison/decision processes, while the left parietal and the left temporal region appear most involved in the generation of images and their mental rotation. A preliminary model describing the cooperative interaction of these cortical regions during mental rotation tasks is proposed.     

Models of Parkinson's disease.

Parkinson's disease (PD) is a heterogenous disease likely to be caused by more than one specific aetiological factor. In rare familial cases of PD with similar clinical features to the idiopathic form of the disease, the underlying genetic cause has been identified. These PD-associated genes have been manipulated to create animal and cell culture models of the disease that have helped to further our understanding of the pathogenesis of PD, particularly concerning causes of the selective loss of dopaminergic neurons at the molecular level. In addition, these models will aid the future development of rational therapeutic strategies. This study briefly reviews toxin-induced models and the genetics of PD. It focuses on recently developed animal models of PD, as well as in vitro approaches to model the disease.     

Outcome Following Bariatric Surgery in Super versus Morbidly Obese Patients: Does Weight Matter?

Background: Numerous investigators have attempted to identify prognostic indicators for successful outcome following bariatric surgery. The purpose of this study was to determine whether degree of obesity affects outcome in super obese [>225% ideal body weight (IBW)] versus morbidly obese patients (160-225% IBW) undergoing gastric restrictive/bypass procedures. Methods: Since 1984, 157 patients underwent either gastric bypass or vertical banded gastroplasty. Super obese (78) and morbidly obese (79) patients were followed prospectively, documenting outcome and complications. Results: Super obese patients reached maximum weight loss 3 years following bariatric surgery, exhibiting a decrease in body mass index (BMI) from 61 to 39 kg/m² and an average loss of 42% excess body weight (EBW). Morbidly obese patients had a decrease in BMI from 44 to 31 kg/m² and carried 39% EBW at 1 year. After their respective nadirs, each group began to regain the lost weight with the super obese exhibiting a current BMI of 45 kg/m² (61% EBW) versus 34 kg/m² (52% EBW) in the morbidly obese at 72 months cumulative follow-up. Currently, loss of 50% or more of EBW occurred in 53% of super obese patients versus 72% of morbidly obese (P < 0.01). Twenty-six percent of super obese patients returned to within 50% of ideal body weight (IBW) while 71% of morbidly obese were able to reach this goal (P < 0.01). Co-morbidities and complications related to surgery were similar in each group. Conclusions: Super obese patients have a greater absolute weight loss after bariatric surgery than do morbidly obese patients. Using commonly utilized measures of success based on weight, morbidly obese patients tend to have better outcomes following bariatric surgery.     

Biomechanics of the Ilizarov fixator for fracture fixation.

Compression, distraction, and torsion stiffness of the Ilizarov external fixator was measured in two fracture models in autopsy specimens of tibia and fibula. A transverse model was tested in six frame constructions with the osteotomy site preloaded in four different positions. An oblique model was tested in four frame constructions also with four preloaded positions. Stiffness was more dependent on bone preload than wire number, wire type, or frame design. High stiffness was achieved by bone preloading, by compressing the rings together, by increasing the number of wires, and by using olive wires. The stiffness can be decreased (dynamization) by separating the rings and by removing wires. This data is helpful for frame design of the Ilizarov fixator.     

Antisocial personality disorder, HIV risk behavior and retention in methadone maintenance therapy

In a sample of 55 consecutive methadone maintenance admissions to our clinic, 42% were diagnosed with antisocial personality disorder (ASPD) using the National Institute of Mental Health Diagnostic Interview Schedule NIMH DIS. Individuals with ASPD exhibited greater risk for HIV infection as defined by more sexual contacts, needle use and equipment sharing. Data at 1 year follow-up were obtained on this group of patients. The objective was to compare the ASPD and non-ASPD groups with regards to demographics, drug abuse history, outcome and retention in treatment. There were no significant differences between the groups on any demographic or treatment outcome variables. Survival analysis indicated that there were no group differences in treatment retention. In conclusion, although there were no differences in treatment outcome between ASPD and non-ASPD groups it is possible that ASPD patients who drop out of treatment will be at higher risk for contracting and spreading HIV within the IV drug using population. These data also suggest that in this population the diagnosis of ASPD using primarily behavioral traits as measured in the NIMH-DIS-III, has little utility in predicting treatment outcome.