Didanosine (ddl) and stavudine (d4T): Absence of peripheral neurotoxicity in rabbits

Some 20 male New Zealand White rabbits (five/group) were given either didanosine (ddl) or stavudine (d4T) at 750 and 1500 mg/kg body weight/day by oral intubation for 24 wk. An additional group was given 300 mg/kg body weight/day zidovudine (AZT) as a negative control. After 13 weeks the high dose of ddl was lowered from 1500 to 1000 mg/kg body weight/day following the death of one rabbit and continued inappetence in the dose group. The rabbits were observed daily, plasma drug levels were monitored, and electrophysiological measurements of peripheral nerve conduction were performed during the study. Additionally, body weight and food intake were recorded, and clinicopathological parameters were evaluated. Sections of selected peripheral nerves, and dorsal and ventral spinal nerve roots were examined by light and transmission electron microscopy. Although peripheral neuropathy has been reported in rabbits with the nucleoside analogue zalcitabine (ddC), based on clinical observations, electrophysiological measurements, and light and electron microscopy, no evidence of peripheral neurotoxicity was observed in rabbits given either ddl or d4T.     

Attitudes toward prevention of cardiovascular diseases among first-year students at eight American medical schools, 1983-1985

First-year medical students at eight U.S. medical schools were surveyed by written questionnaire in 1983-1985 to determine their attitudes toward cardiovascular diseases prevention at medical school entry. An overall response rate of 92% was achieved (2,654 questionnaires), and 97% of responders provided complete and analyzable survey data. Response rates at five of eight medical schools were 98-100%, and one school each had rates of 67, 84, or 90%. Differences in mean attitude responses from school to school were small, as were differences between men and women or between blacks and whites. This survey found that entering medical students have generally positive attitudes toward the effectiveness of preventive cardiology practice as well as toward the importance of research efforts in cardiovascular disease prevention. Students frequently indicated, however, that it is "extremely difficult" to change patients' unhealthful habits and that "physician encouragement" may not be sufficient to help patients achieve more healthful behaviors. These findings could be helpful in directing educational efforts for medical students. The data suggest that major emphasis should be placed on conveying facts regarding the physicians' efficacy in clinical preventive cardiology and on teaching the skills of preventive cardiology practice. Less emphasis appears to be necessary on encouraging positive attitudes about the importance of prevention since current students' attitudes appear to be already positive in this dimension.     

A survey and critical evaluation of a dual isotope (Dicopac) vitamin B12 absorption test

The results of all dual isotope tests (2142) carried out on 1989 patients, 807 males (40.6%) and 1182 females (59.4%), during a 10 year period (1976–1985 inclusive) in the Grampian Health Board Area (population 497,272) have been reviewed. Patient age ranged from 5–95 years with 45.5% over 60 years. The referring specialities were Gastroenterology (47.6%), Haematology (11.3%), Paediatries (2.1%) and all others (39.9%). According to the manufacturer's recommended criteria, results were classified as normal in 1054 (49.2%), abnormal in 659 (30.8%), equivocal in 337 (15.7%) and unsatisfactory in 92 (4.3%) tests. Vitamin B₁₂ malabsorption of ileal type was indicated in 544 tests (25.4%) and of gastric type in 115 (5.4%). Of the latter, 76 were related to pernicious anaemia, 10 to previous gastric surgery and 2 to gastric carcinoma. Of the 337 patients with equivocal results, 138 patients were reviewed and 115 (83.3%) found to have a documented cause for gastric malabsorption (96 pernicious anaemia and 19 previous gastric surgery). In 172 patients with proven pernicious anaemia the manufacturer's recommended criteria for gastric malabsorption were completely satisfied in only 76 (44.3%) but 167 (96.5%) had an excretion ratio 1.3 and 127 (73.8%) a ratio 1.7. Unsatisfactory tests were mainly due to incomplete urine collection (91.3%) or contamination with another isotope (5.4%).     

Physicians' attitudes on advance directives

Advance directives provide means for competent individuals to influence treatment decisions in the event of serious illness and subsequent loss of competence, the "living will" being the best known example. Physicians in Arkansas who were identified to be currently engaged in general practice, family medicine, or internal medicine, including its subspecialities (N = 1293), were surveyed to assess attitudes toward and experiences with advance directives. Almost 80% of all respondents expressed a positive attitude and fewer than 2% expressed a negative attitude toward such documents. A majority (55.9%) had actual experience with the instruments in their practices, and 83.5% of these physicians said that their attitude had become more positive as a result of their experience. More frequent employment of advance directives in critical situations was associated with more positive attitudes and experiences. Most of the benefits claimed for advance directives--improved communication and trust, easier and more confident treatment decision, less stress and guilt, and promotion of patient autonomy--were substantiated by the results.     

Kallikrein 4 expression is up-regulated in epithelial ovarian carcinoma cells in effusions

We immunohistochemically analyzed kallikrein 4 protein (hK4) expression in patients with epithelial ovarian carcinoma (181 malignant effusions and 103 solid carcinoma lesions). Expression of hK4 was also studied in 32 effusions using immunoblotting. Carcinoma cells expressed hK4 in 144 (79.6%) of 181 effusions and 85 (82.5%) of 103 solid tumors. Expression was seen in 51% or more of tumor cells in 70 effusions but often was limited to 5% or fewer cells in solid tumors (P = .009, primary tumors vs effusions; P = .002, metastases vs effusions). Immunoblotting showed hK4 expression in 31 of 32 specimens. Stromal cell hK4 expression, seen in 48 (46.6%) of 103 lesions, was significantly higher in primary tumors than metastases (26/43 vs 22/60, P = .019). hK4 expression in tumor cells was significantly lower in International Federation of Gynecology and Obstetrics stage IV than stage III tumors (P = .004, all lesions; P = .012, primary tumors). hK4 expression in carcinoma cells was associated with longer overall survival (not significant; P = .14, peritoneal effusions). hK4 is expressed widely in ovarian carcinoma; levels in carcinoma cells are highest in effusions, which might be related to loss of stromal contribution and/or altered microenvironment. hK4 expression in carcinoma cells of effusions or solid tumors does not predict survival.     

P67L: a cystic fibrosis allele with mild effects found at high frequency in the Scottish population.

Only three mutant cystic fibrosis (CF) alleles have to date been established as conferring a dominant mild effect on affected subjects who are compound heterozygotes. We now add a fourth, P67L, which occurs on about 1.4% of Scottish CF chromosomes. Among 13 patients (12 unrelated) with this allele, the average age at diagnosis was 22.5 +/- 11.3 years. None of the cases had consistently raised sweat chloride concentrations, the average value being 57 +/- 9 mmol/l; 77% of the patients were pancreatic sufficient. When compared to three other established mild CF alleles, R117H, A455E, and 3849 + 10kb C-T, a compound heterozygote for P67L has minimal disease and clinical suspicions are unlikely to be confirmed other than by DNA typing.