Genotype-dependent effects of GABAergic agents on sedative properties of ethanol

Two lines of mice, selectively bred for differential sensitivity to the soporific effects of ethanol (ETOH), were administered GABAergic drugs in an effort to evaluate a role for GABA in ETOH sensitivity. ETOH sensitive Long-Sleep mice (LS) showed potentiated ETOH sedation when administered bicuculline, muscimol and aminooxyacetic acid (AOAA). ETOH-insensitive SS mice exhibited reduced ETOH sedation in the presence of the antagonists, bicuculline and picrotoxin, and potentiated sedation in the presence of muscimol and AOAA. These changes in narcosis duration were interpreted as central effects, since blood ethanol levels at waking from ETOH sedation varied with GABAergic drug treatment. Picrotoxin antagonized pentobarbital-induced nacrosis in both lines, but to a greater extent in SS mice. These and other experiments with a genetically heterogeneous stock suggest GABA involvement in genotype-dependent ETOH sensitivity, but do not support a simple role of GABA receptor involvement.     

Induction of ovulation with gonadotrophin-releasing hormone--life-table analysis of 50 courses of treatment

Ovulation induction by means of the pulsatile subcutaneous administration of gonadotrophin-releasing hormone by way of an infusion pump is described. The clinical outcome in 50 courses of treatment, which totalled 116 treatment cycles, was analysed and was compared with the pregnancy rates that were obtained with the administration of human pituitary gonadotrophins. We found that the pregnancy rates for these two treatments were similar. We also have shown that for those women who ovulated as a result of such treatment the conception rates were similar to those in ovulatory women who had discontinued contraception. We conclude that gonadotrophin-releasing hormone has an important place among the ovulation-induction agents.     

Cancer screening by primary care physicians: a comparison of rates obtained from physician self-report, patient survey, and chart audit.

OBJECTIVES. This study measured the cancer screening rates of family physicians and compared the measures obtained through physician self-reports, chart audits, and patient surveys. METHODS. A cancer screening survey was sent to 50% of the members of the Washington Academy of Family Physicians, with 326 family physicians (74% response rate) completing the survey. Sixty physicians were recruited for the patient survey and chart audit phase, with a 90% participation rate. Patient surveys were conducted with about 350 patients per physician, and chart audits were conducted on a subset of about 50 patients per physician. Each physician's rate of providing each service was computed from the self-report, the patient survey, and the chart audit. RESULTS. Physicians provided many of these services at rates different from those commonly recommended. Large discrepancies were found between the rates measured by different methods. Correlations between rates derived from chart audits and patient surveys were high; however, correlations between rates from physician self-report and either patient survey or chart audit were much lower for all services. CONCLUSIONS. Studies of physicians' provision of cancer prevention services should not rely on physician self-report, but should obtain the rates through patient surveys or chart audits.     

Effect of steel wire sutures on the incidence of chemically induced rodent colonic tumours

An experiment is presented which shows that colonic primary tumours cluster around a previously constructed anastomosis and that the choice of suture materials (but not the technique of their insertion) can influence this. In a rodent model where dimethylhydrazine was administered 2 months after surgery, anastomotic tumours were most often seen when wire sutures--as used in the staples of anastomotic stapling guns--had been employed (10 out of 16 large bowel tumours were anastomotic as compared with 2 of 12 in a silk sutured group, P = 0.019). An explanation may be that wire sutures persist much longer than silk (in the experiment, 10 months after insertion, 4 per cent of silk sutures were still present, 15 per cent of wire, P less than 0.01). This was translated into a greater degree of scarring at the anastomosis, being most severe in the presence of persisting sutures. Of the 12 anastomotic tumours found in both groups, 7 (58 per cent) were in the minority (17-26 per cent) who had persisting sutures and the remaining 5 in the 47 who had none. Techniques of suturing (needle always passed from the serosa in; needle from mucosa out--the latter in such a way that mucosal cells could be displaced into the bowel wall where it was supposed that they might be more susceptible to subsequent carcinogenesis) did not affect tumour yield. We suggest that non-absorbable sutures, and especially stainless steel wire, should not be used when constructing an anastomosis after large bowel cancer surgery.     

The 1986 McCollum award lecture. Fuel-mediated teratogenesis during early organogenesis: the effects of increased concentrations of glucose, ketones, or somatomedin inhibitor during rat embryo culture

Whole rat embryos were explanted at head-fold, late pre-somite stage (day 9.5 of gestation) and cultured in rat sera varyingly supplemented with glucose (3, 6, 9, or 12 mg/mL), D,L sodium beta-hydroxybutyrate (2, 4, 8, or 16 mM), or both (6 mg/mL D-glucose plus 8 mM beta-hydroxybutyrate). During 48 h culture, increasing glucose alone or beta-hydroxybutyrate alone effected growth retardation and faulty neural and extraneural organogenesis in dose-dependent fashion. Synergistic dysmorphogenic effects occurred when minimally teratogenic concentrations of glucose and beta-hydroxybutyrate were combined. Sera from diabetic animals containing somatomedin inhibitor bioactivity were also able to produce growth retardation and major developmental lesions in presence of amounts of glucose and ketones which of themselves were not teratogenic. Thus, aberrant fuels and fuel-related products can impair growth and organogenesis in early post-implantation embryo. Such fuel-mediated teratogenesis may be multifactorial and include possibilities for synergistic and additive interactions.