Evaluation of the teratogenic potential of pyrazinamide in Wistar rats.

We have tested Pyrazinamide (PZA), an essential component of modern short-course tuberculosis treatment regimen, for teratogenicity using Wistar rats. The drug was given by oral intubation from 6-15 days of gestation, at doses of 0, 25, 100 and 500 mg/kg body weight per day. Reduction in body weight and food consumption were observed in the treated dams. On day 20 of gestation, all the dams were killed by cervical dislocation and signs of maternal toxicity, reproductive indices and fetal measurements were recorded. Dams given doses of 100 and 500 mg/kg had significantly higher incidence of reabsorbed fetuses, reduced litter size, and impaired neonatal growth than those given no PZA or only 25 mg/kg dose. External visceral and skeletal examination of all fetuses of PZA-treated dams showed several types of variations which were neither dose related nor having a consistent pattern. However, these variations occurred mostly in the dams treated with the dose of 500 mg/kg. In conclusion, these data show that in Wistar rats, only high doses of PZA (100 and 500 mg/kg) produced fetotoxicity. No evidence of teratogenic effect of the drug was observed.

Comparison of the effects of three haemodialysis membranes on vancomycin disposition.

Polysulfone (PSF) and polyacrylonitrile (PAN) were recently introduced haemodialysis (HD) membranes. The effect of each on vancomycin disposition was compared with cuprophan (SCE) in 12 chronic HD patients who received 14 infusions. Vancomycin (1 g) was infused over 1 hour, followed by three 4-hour HD sessions over 5 days, beginning 1 hour after the end of infusion. The intradialytic clearances of vancomycin were 73, 54 and 15 ml/min for PSF, PAN and SCE, respectively. At the end of the third HD session, vancomycin concentration dropped to subtherapeutic level (< 7.5 micrograms/ml) only in patients dialysed with PSF and PAN. The corresponding elimination half-lives (t1/2 beta) were 61, 60 and 86 hours for the three membranes, respectively. According to these findings, vancomycin should be given every three HD sessions for PSF and PAN. The dosage interval should be extended up to every 5 HD sessions for patients on SCE. The peak (mean +/- S.D.) obtained one hour after the end of infusion was 34.2 +/- 11.4 micrograms/ml, which is within the therapeutic range.

Modeling organizational determinants of hospital mortality.

This study examines hospital characteristics that affect the differential in hospital mortality. Death rates for 1984 Medicare inpatients in acute care hospitals, released by the Health Care Financing Administration in 1986, were analyzed. A confirmatory statistical approach to organizational determinants of hospital mortality was formulated and validated through an empirical examination of 239 hospitals. The findings suggest that the effect of hospital size and specialization on mortality was a spurious one when the effects of other variables were simultaneously controlled. A positive association existed between service intensity and hospital mortality: the more hospital services consumed, the higher the mortality rate. Community attributes accounted for more variance in hospital mortality rates than did organizational attributes. The organizational and community factors studied explained 27 percent of the total variance in hospital mortality.