Rat muscle branched-chain ketoacid dehydrogenase activity and mRNAs increase with extracellular acidemia.

The rate-limiting enzyme in branched-chain amino acid catabolism is branched-chain ketoacid dehydrogenase (BCKAD). In rats fed NH4Cl to induce acidemia, we find increased basal BCKAD activity as well as maximal activity in skeletal muscle. Concurrently, there is a > 10-fold increase in mRNAs of BCKAD subunits in skeletal muscle plus an increase in cardiac muscle but not in liver or kidney. There was no increase in mRNA for malate dehydrogenase or for cytosolic glyceraldehyde-3-phosphate dehydrogenase. Evaluation of the translation capacity of BCKAD mRNAs in muscle of acidemic rats yielded more immunoreactive BCKAD whether the proteins were synthesized from muscle RNA using rabbit reticulocyte lysate or directly using postmitochondrial homogenates. Although the RNA from muscle of acidemic rats yielded twice as much BCKAD protein, we found no net increase in mitochondrial BCKAD protein in muscle by Western blotting. Because there is increased proteolysis in muscle of rats with acidemia, the increase in mRNA might be a mechanism to augment BCKAD synthesis and activity in muscle.

Biliary response to glucagon in humans.

Glucagon has been demonstrated to have profound effect on biliary secretion in several species. Glucagon's biliary effects were studied in humans following biliary tract surgery. Nine patients underwent common bile duct exploration and insertion of a balloon-occludable t tube. An aliquot of the collected sample was kept and the enterohepatic circulation was maintained by reinfusion of the collected bile via the distal t-tube port. Glucagon increased bile flow and decreased cholesterol and phospholipid output during stable bile acid output. Furthermore high-performance liquid chromatographic analysis of bile acid profiles revealed no significant changes in bile salt species or conjugation after glucagon infusion. Glucagon is probably important in the physiologic regulation of biliary secretion in humans.

Biliary response to glucagon and insulin following hepatic transplantation in humans.

Glucagon and insulin are postulated to be physiologic regulators of hepatic biliary secretion. Effects of these hormones were studied following orthotopic transplantation. Five adult hepatic graft recipients had triple lumen t-tubes placed at the time of surgery and were studied 3 months after surgery. Experiments were performed after cholangiographic confirmation of t-tube placement and function. After overnight fast, t-tubes were inflated and bile was collected. A small quantity was saved for analysis and the remainder was reinfused to maintain enterohepatic circulation. After 1 hr of observation, the patients received a 2-hr infusion of insulin (0.125 U kg-1 hr-1), glucagon (2 micrograms kg-1 hr-1), or 0.9% saline. During saline infusions, all parameters remained stable. As has been previously demonstrated in the canine model and intact patients, bile salt outputs were constant under all experimental conditions. Glucagon stimulated bile secretion by 30% (6.7 +/- 1.5 to 8.7 +/- 1.2 ml/15 min) and inhibited biliary cholesterol output by 47% (16.4 +/- 3.2 to 8.7 +/- 1.5 mg/15 min). Bile flow and lipid secretion were not affected by insulin. Glucagon had profound effects on bile flow and lipid secretion, suggesting effects independent of innervation, while insulin at this dose had no statistically significant effects.

Abdominal leiomyosarcoma: aggressive management.

We retrospectively reviewed 34 cases of intra-abdominal leiomyosarcoma treated between 1967 and 1986. Thirty-three patients had operation, and the primary tumor was removed in all but one. Fifteen patients had peritoneal implants at initial surgical exploration; 14 had tumor recurrence and had at least one reoperation. Five-year survival was 16% overall and 37% for patients without peritoneal implants at the initial procedure. This figure includes five patients in whom distant metastases developed after benign gastric or intestinal leiomyoma was diagnosed based on histologic and gross findings. All patients who have had five-year cures or more than two years of palliation after demonstration of peritoneal metastases had operation after 1978, a finding that probably reflects a more aggressive surgical approach to these tumors. Effective palliation, defined as three months of symptom relief and six-month survival in patients with widespread intraperitoneal tumor, was achieved significantly more often when the tumor causing the symptom was resected (eight of eight patients) than when it was not (five of six patients). These data indicate that an aggressive surgical approach is warranted in attempts to achieve either cure or palliation in patients with intra-abdominal leiomyosarcoma.

Toothbrush swallowing.

We encountered four cases of toothbrush swallowing and reviewed the literature on this subject. A total of 31 toothbrushes within the gastrointestinal tract have been reported. None have passed spontaneously. Several have caused significant complications related to pressure necrosis, including gastritis, mucosal tears, and perforation. The recommended treatment is endoscopic retrieval and postoperative monitoring for 24 hours in case of esophageal or gastric injury.

Bile flow--an index of ischemic injury.

Bile formation is an active secretory process involving bile salt-dependent and -"independent" mechanisms. This study was performed to determine the effect of selected periods of warm ischemia on biliary secretion. Rats were studied using an in situ liver perfusion system after stabilization of bile flow with intravenous sodium taurocholate. Bile flow remained stable in control livers and ceased during ischemic periods of 15 or 25 min. After reperfusion of 15-min ischemic livers, bile flow was depressed but returned to normal by 45 min of reperfusion. After 25 min of ischemia, bile flow remained depressed. A similar depression in bile salt secretion was observed. These studies indicate that both bile flow and bile salt secretion reflect the degree of ischemia in this isolated perfused system, and further use of this model for the investigation of biliary flow as an index of ischemic injury is warranted.

Effect of cyclosporine on bile secretion in rats.

Short-term effects of cyclosporine were studied in the isolated perfused rat liver model. Bile flow was inhibited by cyclosporine in 2 mg/kg and 20 mg/kg doses but not by a 0.2 mg/kg dose. Cholestasis was accompanied by a decrease in bile acid secretion, indicating an inhibitory effect on the bile acid-dependent fraction of bile flow. Perfusate bilirubin levels increased threefold in rat livers given 20 mg/kg of cyclosporine, but did not change in control animals. Alkaline phosphatase and transaminase levels did not differ from those of control animals. The isolated perfused rat liver was able to excrete cyclosporine, as demonstrated by a continual decrease in perfusate cyclosporine levels. No light microscopic evidence of cholestasis or hepatocellular damage was demonstrated on histologic staining. Our model appears to be a good one for the study of altered hepatic physiologic characteristics caused by administration of cyclosporine.