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.

Clinical significance of ultrasonographically detected coincidental gallstones.

The clinical profiles of 139 patients with gallstones found coincidentally during ultrasonography were reviewed and the patients followed prospectively for five years. Indications for ultrasonography included follow-up of abdominal malignancy (33%), evaluation of abdominal aortic aneurysm or other arteriosclerotic vascular disease (22%), renal insufficiency (12%), and lower abdominal pain (7%). At the time of gallstone detection, 14 patients (10%) had symptoms attributable to cholelithiasis. Over the next five years, only 15 patients (11%) developed episodes resembling biliary pain. Nine patients underwent cholecystectomy during this period. Three of the cholecystectomies were incidental to other abdominal procedures. Two cholecystectomies were performed as emergencies for gallstone complications with no perioperative mortality. Interestingly, 54 patients (40%) with coincidental gallstones died during the follow-up period. All the deaths were unrelated to gallstones. These data indicate that ultrasonographically detected coincidental gallstones rarely have clinical significance, leading strong support to the expectant management of most patients with purely coincidental gallstones.

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.

Deaths from gallstones. Incidence and associated clinical factors.

The purpose of this study was to determine the incidence of death as the initial manifestation of cholelithiasis. Records of patients who died or underwent cholecystectomy for gallstone-related disease at Duke University Medical Center between 1976 and 1985 were reviewed. Thirty patients died, six of whom (20%) had previous episodes of biliary pain and stone documentation. Twenty-four (80%) were asymptomatic (three with previous incidental diagnosis of cholelithiasis). Reason for admission included acute cholecystitis (nine), pancreatitis (eight), biliary pain (six), cholangitis (four), jaundice (one), and endocarditis (one). Three patients died of gallstone complications without surgical intervention; one patient had renal failure and two had septicemia. Other causes of death were: sepsis (seven patients), cardiac failure (six), pulmonary complications (four), renal failure (three), cerebrovascular accident (three), liver failure (two), pancreatitis (one), and gastrointestinal bleeding (one). During this period, 1731 cholecystectomies were performed without mortality. In this group, the patients were younger (50 +/- 8 years vs. 64 +/- 13 years, p less than 0.001), and had a lower incidence of cirrhosis (p less than 0.001) and diabetes (p less than 0.002). The sex ratio was inverted (p less than 0.001). This study demonstrates that death from gallstones is uncommon (three cases per year), as is death from their initial clinical manifestation (1.2%). The risk of death is two- and ninefold higher in patients with acute cholecystitis or acute pancreatitis. Age, cirrhosis, and diabetes are important determinants of outcome.

Regulation of biliary protein secretion in dogs.

The biliary secretion of protein in response to bile acids and other agents known to increase bile flow was examined in a chronic bile fistula dog model. Infusion of 25, 50, or 75 mumole/kg/hr sodium taurocholate after 3 hr of bile fistulization increased biliary protein output significantly by 52, 86, and 108% respectively compared to preinfusion values. A proportionate increase in biliary albumin output during taurocholate choleresis was demonstrated. Protein outputs during bile fistulization without taurocholate replacement were unchanged. The non-micelle-forming bile acid dehydrocholate markedly increased bile flow but did not change protein output. Similarly, the hormonal choleretics glucagon and secretin caused significant decreases in biliary protein concentration but no change in protein output. These data indicate a correlation between biliary protein secretion and bile acid-dependent bile flow. It is likely that regulation of certain proteins is dependent on the micelle-forming properties of bile acids.

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.

Gastric emptying, glucose tolerance, and insulin response after duodenojejunostomy.

We investigated the impact of direct jejunal delivery of various meals on gastric emptying, glucose tolerance, and insulin response in a chronic dog model following duodenojejunostomy. Ten beagle dogs underwent duodenal transection 2 cm distal to the pylorus and end-to-side duodenojejunostomy 20 cm distal to the ligament of Treitz. Three months after operation each dog underwent gastric emptying studies using radiolabeled normal saline, 20% glucose solution, and standardized mixed solid meal. Glucose tolerance tests with plasma insulin determinations were obtained using the glucose meal. After duodenojejunostomy both the rapid exponential pattern of emptying of normal saline and the slower linear pattern of glucose emptying seen in intact dogs were preserved. The linear gastric emptying of the solid meal which was slower than gastric emptying of either of the liquid meals was also preserved. Although integrated plasma glucose levels over 2 hr were 484.8 +/- 40.4 and 456.6 +/- 30.4 mg X hr/dl in intact and duodenojejunostomy dogs, respectively (P greater than 0.05), the initial rate of rise of plasma glucose was significantly delayed in the duodenojejunostomy dogs. But integrated plasma insulin levels over 2 hr differed significantly (P less than 0.05) between the intact (71.6 +/- 9.2 microU X hr/nl) and duodenojejunostomy (48.3 +/- 6.2 microU X hr/nl) dogs. We conclude that duodenojejunostomy (jejunal delivery) preserved the patterns of gastric emptying of saline, glucose, and mixed solid meals; retarded initial plasma glucose response to the glucose meal; and blunted plasma insulin response to the glucose load.

Characteristics of cat skeletal muscles grafted with intact nerves or with anastomosed nerves.

Grafting of 3-g extensor digitorum longus (EDL) muscles of cats may be made with (i) severence of the nerve with spontaneous reinnervation, termed standard grafts (ii) severence of the nerve with reinnervation facilitated by anastomosis of the nerve, termed nerve-anastomosed grafts; and (iii) preservation of the nerve, termed nerve-intact grafts. In previous studies, standard grafts developed a maximum isometric tetanic tension (P0) that was 22% of the value for control EDL muscles. We hypothesized that the low values of P0 resulted from incomplete reinnervation of muscle fibers. To test this hypothesis, EDL muscles were grafted in cats with nerves intact and with nerves anastomosed. In standard grafts differences were observed in both structure and function at 120 compared with 240 days after grafting. Characteristics of the nerve-intact and nerve-anastomosed grafts did not change significantly between 120 and 240 days and the data were pooled for comparisons with control EDL muscles. Nerve-anastomosed and nerve-intact grafts developed P0 values that were 34 and 64% of the control values, respectively. Nerve-intact grafts had a mass and fiber cross-sectional area not different from control EDL muscles. Compared with control values, all grafts had fewer fibers, more connective tissue, lower absolute and normalized P0, reduced capillary density, and increased fatigability. The greater P0 of nerve-intact compared with standard and nerve-anastomosed grafts supported our hypothesis that the degree of reinnervation is a factor that limits graft development. The presence of a necrotic core and the low tension development of even the nerve-intact grafts suggested that revascularization is a significant limitation as well.