Influence of food on the pharmacokinetics of quinapril and its active diacid metabolite, CI-928

A randomized two-way crossover study was conducted in 12 healthy volunteers to assess the effect of food on the pharmacokinetics of quinapril (CI-906) and its active metabolite, CI-928, after quinapril dosing. Forty-milligram oral quinapril doses were administered in a fasted or a fed state with a one-week washout period between treatments. No significant treatment differences were observed in quinapril and CI-928 values for maximum plasma concentration, area under the plasma concentration-time curve, or percentage of dose excreted in the urine. Small but significant increases of less than 0.5 hour in quinapril and CI-928 tmax values were observed after consumption of food. The pharmacokinetic profiles of quinapril and CI-928 were not significantly altered by the administration of food.     

Peroxidative activation of o-phenylhydroquinone leads to the formation of DNA adducts in HL-60 cells.

Using 32P-postlabeling we studied DNA adduct formation in HL-60 cells treated with the o-phenylphenol metabolites o-phenylhydroquinone (o-PHQ) and o-phenylbenzoquinone (o-PBQ). Treatment with 25-500 microM o-PHQ for 8 h produced one principal and three minor adducts with a relative distribution of 80, 10, 6 and 4%. The relative adduct levels from these treatments were 0.26-2.31 adducts/10(7) nucleotides. Treatment with 25-250 microM o-PBQ for 2 h resulted in a similar level of DNA modification and adduct distribution. Reaction of purified calf thymus DNA with o-PBQ produced one DNA adduct, which did not correspond to the major adduct produced in HL-60 cells. These results show that o-PHQ and o-PBQ can form DNA adducts. Peroxidase activation of o-phenylphenol may therefore play a role in the carcinogenic effect of this compound.     

The functional pathology of hypophyseal adenomas

This review summarizes some aspects of pituitary adenoma pathology. A new embracing pituitary adenoma classification has been developed which correlates morphologic findings with endocrine activity. It is based on hormone content, histologic, immunohistochemical and ultrastructural features, cellular composition and cytogenesis, and separates pituitary adenomas into 7 distinct entities.     

Monitoring myocardial reperfusion injury with NADH fluorometry.

Using NADH fluorometry to monitor myocardial metabolism, the mechanism of reperfusion injury was investigated after the delivery of an experimental reperfusate. Using an isolated working heart preparation, rat hearts underwent 15 min of global ischemia at 37 degrees C. Following the ischemic insult, an oxygenated enriched reperfusion solution was given for 5 min. The hearts were then returned to a working state and aortic flow recorded to evaluate recovery. NADH levels were monitored throughout the experiment with a fluorometer and glycogen, AMP, ADP, and ATP were measured biochemically pre- and postischemia, after reperfusion and after recovery. In this study, reperfusion injury was best abated by an enriched reperfusate. Our results indicate the mechanism for this amelioration is not high-energy phosphate replenishment. Rather, as indicated by NADH fluorescence, the hearts attain an intermediate level of metabolism that permits glycogen to be restored and functional recovery to be improved.     

Favorable results of coronary artery bypass grafting in patients older than 75 years

There is controversy whether the short-term and long-term results of coronary artery bypass grafting in elderly patients justify performing the procedure. Between January 1977 and December 1986, 4580 patients underwent coronary artery bypass grafting, of whom 222 (4.9%) were 75 years old or older (mean 77 years). There were 143 men and 79 women and 139 (63%) were in New York Heart Association class IV. One hundred forty-six patients (66%) had had at least one preoperative myocardial infarction. Myocardial revascularization was performed under emergency conditions in 17 patients (18%). The mammary artery was used in 43%, 96% of the patients received two or more grafts. The mean number of bypass grafts was 3.1 per patient. The overall hospital mortality rate was 10.8% (24/222), 3.6% for elective procedures, 14.9% in urgent cases, and 35% in emergencies. In contrast, the overall early mortality rate was 3.1% in 4358 patients less than 75 years old. Complications occurred in 83 patients (37%). Of the patients discharged from the hospital, 198 were followed up for a mean of 48 months (1 to 130). Actuarial probability of survival was 75% at 48 months. Postoperatively 70% were in New York Heart Association class I or II and only 21% were rehospitalized for cardiac problems. During the follow-up period 77% of the patients were free from angina, and of those experiencing angina the mean time from operation to the first episode was 75 months. Although elderly patients have a somewhat increased operative mortality rate, particularly if operated on urgently or emergently, long-term survival and freedom from angina are excellent and justify continued performance of coronary bypass grafting in selected patients over 75 years of age.