A modified sleeve technique was developed for making microsurgical anastomoses using a commercially produced fibrinogen adhesive called Tisseel. A controlled study was then carried out to compare the new fibrinogen adhesive anastomoses with conventional suture anastomoses in a bilateral groin flap model using 50 consecutive rabbits. Statistical analysis of the results indicated that flap survival rate and vascular patency rate were comparable for the two techniques. The fibrinogen adhesive anastomoses took less time to complete and, subjectively, were less difficult technically. The suture anastomoses were more versatile. Histologic studies revealed that the adhesive did not flow through the sleeve into the lumen, and that, although there was a brief inflammatory response associated with healing, this inflammation was very localized and did not involve the inner layers of the vessel wall or lumen. It was concluded that the new technique was a useful addition to techniques already available.
The effect of cimetidine administration on the disposition of acetaminophen was evaluated in seven men and six women. One gram of acetaminophen was administered to each volunteer after an overnight fast on two occasions in a balanced crossover design with and without cimetidine, 300 mg every 6 hours beginning 50 hours before acetaminophen administration and continuing for 22 hours after. N-Acetylcysteine was administered on both occasions when acetaminophen was ingested to protect against glutathione depletion. Blood samples were collected serially for 12 hours after acetaminophen administration, and total urine volume was collected for 24 hours. Fractional clearances of acetaminophen through renal and metabolic routes (sulfation, glucuronidation, 3-hydroxylation, and glutathione conjugate formation) were not altered by cimetidine administration. Studies in microsomes prepared from two human organ donors indicated that cimetidine inhibited acetaminophen reactive metabolite formation noncompetitively, with Ki values of 0.35 mmol/L and 0.32 mmol/L for the respective livers, which is 5 to 10 times the putative cimetidine concentration required for therapeutic effect.
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