Complex interactions in Parkinson's disease: a two-phased approach.

The identification of pathogenic mutations in the three genes alpha-synuclein, parkin, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) has elucidated the ubiquitin proteasome system (UPS) and its potential role as a causal pathway in Parkinson's disease (PD). In addition, polymorphisms of these three genes have been shown to be independently associated with PD. In a sample of 298 unrelated PD cases and 185 controls, we applied a two-phased approach of recursive partitioning and logistic regression analyses to explore complex interactions. For women only, we observed an epistatic interaction of UCHL1 and alpha-synuclein genotypes with significant effects on PD risk (odds ratio = 2.42; P = 0.003). Our findings are consistent with the hypothesis that PD is a multigenic disorder of the UPS.     

A new approach to selection and weighting of items in evaluative composite measurement scales

Evaluative composite measurement scales (CMS) are increasingly used in medicine to measure complex constructs in the absence of a reference criterion or ‘gold standard’. However, the level of measurement provided by these instruments has usually been given little attention. This paper explores the influence of the characteristics of the item set and weighting on the level of measurment of an evaluative CMS. The approach is illustrated with an application to the scoring system of the Nottingham Health Profile. Simulations are provided to indicate when the composite score of item responses, on an ordinal or pass—fail scale, could be considered to achieve the properties of an interval scale.     

Belt device for simplified CT-guided puncture and biopsy: A technical note

A new radiolucent device for increased accuracy of CT-guided fine-needle punctures permits precise determination of the optimum angle, depth, and position of the fine needle, which can be preset from the data supplied on the CT monitor. Puncture and repeat scans for controlling the tip of the needle can be performed with the patient in a stationary position. The device is designed as a belt that holds a needle holder sheath and a goniometric scale, both of which can be moved to varying positions around the patient.     

Upper gastrointestinal tract dysfunction in bulimia

Bulimia nervosa is a health problem of increasing magnitude that is estimated to affect 2–5% of the American adolescent and young adult female population. Because of the magnitude of this clinical problem and because of the importance of the upper gastrointestinal tract in its expression, a intradepartmental program of health care for patients affected with the disease was initiated. Eleven consecutive symptomatic bulimic individuals have been evaluated jointly by the gastroenterology and the psychiatry departments of the University of Pittsburgh. Five of these 11 individuals were found to have clinically important upper gastrointestinal pathology including ulcerative esophagitis, erosive gastritis, duodenal ulcer, and delayed gastric emptying. These gastrointestinal conditions could have been either a result of or have contributed to the symptomatology of these five patients. These data suggest that bulimic subjects have clinically important gastroenterological disease processes that require specific diagnosis and treatment independent of the psychiatric treatment provided for the bulimic condition.This work was supported in part by grants from NIDDK AM 32556.     

Threshold for occluded formaldehyde patch test in formaldehyde-sensitive patients

Our purpose was to investigate the eliciting threshold concentration of formaldehyde in formaldehyde-sensitive individuals in the occluded and non-occluded patch teat and to evaluate the relationship in repeated open application test (ROAT) with a product containing a formaldehyde releaser. 20 formaldehyde-sensitive patients and a control group of 20 healthy volunteer were included in the study. Occluded and non-occluded patch tests with formaldehyde solutions form 25 to 10,000 ppm. and ROAT for I week with a leave-on cosmetic product containing on average 300 ppm formaldehyde. Were carried out simultaneously on each subject. In the occluded patch test. 1/2 of the 20 patients only reacted to 10,000 ppm formaldehyde. 9 reacted to 5,000 ppm. 3 reacted to 1.000 ppm. 2 reacted to 500 ppm and I reacted to 25 ppm. No definite positive reactions were observed in the non-occluded patch test or in the ROAT No positive reactions were observed in the control group to any of the test procedures. We concluded that the threshold concentration for occluded patch test to formaldehyde in formaldehyde-sensitive patients was 250 ppm. The threshold in occluded patch test corresponded to the degree of sensitivity Definite positive reactions in the ROAT were not seen, either indicating that they are unlikely to happen with the type of product used or that the exposure time was too short.     

Growth modulation of hepatocytes and rat liver epithelial cells (WB-F344) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Modulation of DNA synthesis by 2,3,7,8-tetrachlorodi-benzo-p-dioxin(TCDD) was studied in primary cultures of hepatocytes and inrat liver epithelial cells (WB-F344) to develop models for studieson the interactions between the activated Ah receptor and cellulargrowth control. In hepatocytes TCDD either positively or negativelymodulated EGF-stimulated DNA synthesis. In the presence of ethlnylestradiol10^–12 M TCDD moderately increased EGF-stimulated DNA synthyesis(     

Improved Scoring System to Assess Adult Donors For Cadaver Renal Transplantation

We previously proposed a quantitative approach to assess donor organs for cadaver renal transplantation. To improve on our original scoring system, we studied 34 324 patients who received cadaver renal transplants from adult donors between 1994 and 1999 and were reported to the UNOS Scientific Renal Transplant Registry. A scoring system was developed from five donor variables (age, 0-25 points; history of hypertension, 0-4; creatinine clearance before procurement, 0-4; cause of death, 0-3; HLA mismatch, 0-3) that showed a significant correlation with renal function and long-term graft survival. Cadaver kidneys were stratified by cumulative donor score: grade A, 0-9 points; grade B, 10-19; grade C, 20-29; and grade D, 30-39. The influence of donor score on renal function and graft survival was most severe above 20 points, designated 'marginal' kidneys. In summary, a donor scoring system developed from a large population database was useful in predicting outcome after cadaver renal transplantation. The improved system provides a quantitative approach to evaluation of marginal kidneys and may improve allocation of these organs in cadaver renal transplantation.