Methodological aspects of follow-up studies on psychotic patients in a polydiagnostic perspective.

Polydiagnostic follow-up studies should explore whether certain definitions of a given disorder permit better prediction of the illness course than others and whether this good predictive validity is related to specific etiopathogenetic conditions. In order to carry out such studies successfully they should be based on broadly defined samples and comprise provisions for additional validation such as genetic data, neuropsychological testing etc. After an assessment at baseline and at discharge from hospital, the follow-up assessments should comprise five steps: (1) Identification of successful and unsuccessful diagnostic systems; (2) identification of features determining successful attribution; (3) analysis of successful systems; (4) analysis of unsuccessful systems, and (5) analysis of cases which have changed diagnostic attribution. The conclusions drawn from these analyses are intended to refine classification in psychiatry.     

Pharmacokinetic aspects of a combination of metoclopramide and paracetamol. Results of a human kinetic study and consequences for migraine patients]

An open trial was carried out in eight healthy male and female volunteers to examine the bioavailability as well as the main kinetic parameters of Migr?nerton (metoclopramide and paracetamol; CAS 364-64-5 and CAS 103-90-2, resp). in comparison with reliable literature data. The results reported here clearly show that the absorption of both active ingredients from the fixed combination is complete and that therapeutically relevant plasma concentrations are achieved within 30 min. Bioavailability as well as tmax, t1/2, and time-lag are comparable with data resulting from reliable and internationally acknowledged kinetic studies. The fixed combination was shown to be kinetically compatible with regard to all parameters determined for metoclopramide and paracetamol.     

Ethanol:water mutually enhanced transdermal therapeutic system. I: Nitroglycerin solution properties and membrane transport

The solution properties of aqueous ethanol donor solutions were characterized for the particular case of an increased flux nitroglycerin transdermal system. Permeation through porous and nonporous polymer membranes was investigated and modelled. While the permeation of ethanol through the porous membranes is adequately described by theory, clogging of pores occurs in the presence of lactose. Permeation through ethylene vinyl acetate membranes reflects interactions of the solute and solvent with the polymer.     

A model for assessing information retrieval and application skills of medical students.

PURPOSE: To develop and evaluate a model for assessing information retrieval and application skills, and to compare the performances on the assessment exercises of students who were and were not instructed in these skills. METHOD: The authors developed a set of four examination stations, each with multiple subtasks, and administered the exams to students at two medical schools. Students at one school had intensive instruction in literature searching and filtering skills for information quality (instructed group), and those at the other school had minimal instruction in these areas (uninstructed group). The stations addressed pediatrics content and the skills of searching Medline and the World Wide Web, evaluating research articles, evaluating the accuracy of information from the Web, and using the information to make recommendations to patients. The authors determined the psychometric characteristics of the stations and compared the performances of the two groups of students. RESULTS: Students in the instructed group performed significantly better and with less variability than the uninstructed group on four tasks and no differently on seven tasks. There was no task on which the uninstructed group performed significantly better than the instructed group. CONCLUSION: The prototype stations showed predictable differences across curricula, indicating that they have promise as assessment tools for the essential skills of information retrieval and application.     

The Relationship of pK a and Acute Skin Irritation in Man

The relationship between pK _a and skin irritation in man is studied for a homologous series of benzoic acid derivatives, which permeate through human skin at comparable rates (15–88 µg/cm²/hr). Skin irritation and pK _a are correlated for pK _a 4. Laser Doppler velocimetric assessment of skin blood flow, color meter readings, erythema, edema, and the primary irritation index are all linearly correlated and related to pK _a, erythema at 24 hr appears to be the most sensitive parameter to variation in pK _a when pK _a 4.     

TP53 mutations in prostatic cancer. Analysis of pre- and post-treatment archival formalin-fixed tumour tissue

The TP53 gene mutation pattern in prostatic cancer was examined in relation to progression and survival, using archival formalin-fixed pre-and post-treatment tumour specimens from 84 prostatic cancer patients. Thirty-four had hormone-sensitive tumours and 50 were hormone-resistant. Six of the 34 (18 per cent) therapy-responding tumours and 19 of the 50 (38 per cent) hormone-resistant tumours showed p53 protein accumulation in the post-treatment specimen. Both pre- and post-treatment specimens from these 25 patients were analysed for mutation of the conserved regions of the TP53 gene (exons 5–8), using constant denaturant gel electrophoresis (CDGE) followed by DNA sequencing. In the post-treatment samples, mutations were detected in three of the six patients with hormone-responsive tumours and in 11 of the 19 patients with hormone-resistant tumours. The three (100 per cent) patients with therapy-responsive tumours with mutations and nine of the 11 (82 per cent) patients with therapy-resistant tumours with mutations died of the disease. Thirteen of the 14 mutations in the post-treatment specimens were transitions, 11 occurring at CpG dinucleotides in which codon 273 was involved in ten. A significantly higher proportion of tumours with mutations were poorly differentiated compared with tumours without mutation (P<0·04). Our findings indicate that TP53 mutation is a late event in tumour development of the prostate gland and that codon 273 might be a ‘hotspot’ for mutation in the progression of the disease.