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Biomedical subjects

L DenBesten

Publications and source records attributed to L DenBesten.

At least 37 records · Page 2Linked to original sources

Increased intragallbladder pressure response to cholecystokinin-octapeptide following vagotomy and pyloroplasty.

One of the late effects of truncal vagotomy is gallbladder dilatation. However, the early physiologic mechanisms responsible for this phenomenon have not been clearly elucidated. Therefore, the hypothesis that truncal vagotomy alters the gallbladder's or cystic duct's response to hormonal stimulation was tested. Adult male prairie dogs underwent either truncal vagotomy and pyloroplasty or sham laparotomy. All animals were then fed a trace-cholesterol (nonlithogenic) diet for 3 months. In acute terminal experiments the gallbladder was aspirated and cannulated with a pressure-monitored perfusion catheter. The common bile duct was cannulated with a drainage catheter. Aspirated gallbladder volume and cystic duct closing pressure were the same in vagotomized and sham animals. Unstimulated intragallbladder pressure and cystic duct outflow resistance were also the same in both groups. However, during an intravenous infusion (10 ng/kg/min) of cholecystokinin-octapeptide (CCK-OP), the maximal intragallbladder pressure increase was greater (P less than 0.01) in vagotomized animals (3.50 +/- 0.41 mm Hg) than in sham animals (1.63 +/- 0.36 mm Hg). Intragallbladder pressure remained significantly higher (P less than 0.05) in vagotomized animals throughout the 30-min infusion of CCK-OP. Despite increased intragallbladder pressure, gallbladder emptying was unaffected by vagotomy. It is concluded that altered gallbladder or cystic duct hormonal response is an early effect of vagotomy that may result in gallbladder dilatation.

Animals↗

Impaired gallbladder emptying before gallstone formation in the prairie dog.

Several human and experimental observations suggest that gallbladder stasis is an important link between the hepatic secretion of cholesterol saturated bile and the formation of cholesterol gallstones. In the cholesterol-fed prairie dog model, gallbladder stasis occurs before gallstone formation. In this study we sought to determine the specific defects in extrahepatic biliary physiology responsible for gallbladder stasis in this model. Adult male prairie dogs were fed either a trace cholesterol or a 0.4% cholesterol-enriched diet. In acute terminal experiments, gallbladder contents were examined for cholesterol crystals and gallstones, and gallbladder function was determined at rest and in response to intravenous cholecystokinin-octapeptide. The following alterations in gallbladder function developed concurrently with biliary cholesterol crystallization, but before gallstone formation: (a) decreased gallbladder emptying, (b) increased intragallbladder pressure in response to cholecystokinin-octapeptide, (c) increased cystic duct closing pressure, and (d) increased resistance to outflow through the cystic duct.

Animals↗

Gallbladder disease in patients on long-term parenteral nutrition.

Recent anecdotal reports suggest that total parenteral nutrition may be associated with an increased incidence of both acalculous cholecystitis and cholelithiasis. The validity of this association, however, has not been tested in a large population of patients on long-term total parenteral nutrition. Therefore, we assessed the incidence of gallbladder disease among our patients 15 yr and older who had received a minimum of 3 mo of total parenteral nutrition. Of the patients meeting these criteria, 128 were on total parenteral nutrition a mean of 13.5 mo. Nineteen had gallbladder disease before receiving total parenteral nutrition, leaving 109 patients at risk. Of these patients, 25 (23%) developed gallbladder disease after the initiation of total parenteral nutrition. Because of their known propensity for cholelithiasis, 94 of our patients with ileal disorders (Crohn's disease or ileal resection, or both) were considered separately. The 40% incidence of gallbladder disease in these 94 patients was significantly higher than expected from a series of similarly defined patients with ileal disorders not receiving total parenteral nutrition (p less than 0.05). We propose that the enhanced risk of gallbladder disease among patients on long-term total parenteral nutrition results from multiple factors working in concert to promote gallbladder stasis.

Adolescent↗

Increased risk of gallstones in children receiving total parenteral nutrition.

Twenty-one children receiving long-term total parenteral nutrition were prospectively evaluated for the presence of gallstones. Using ultrasonography, nine children (43%) were found to have cholelithiasis, and five have since undergone cholecystectomy. Only children with ileal disorders or previous resection developed stones. In the select group of patients with ileal disorders or previous resection, the prevalence of stones was 64%, nearly twice that which has been observed in similarly defined adults not receiving total parenteral nutrition. Data from this study suggest that the prolonged administration of parenteral nutrition significantly enhances the risk of gallstone formation already imposed by a previous ileal resection or disorder. Periodic ultrasonograms provide a safe and accurate means of monitoring high-risk patients during and after prolonged total parenteral nutrition therapy.

Adolescent↗

Interaction of chenodeoxycholic acid and dietary cholesterol in the treatment of cholesterol gallstones.

Standard doses of chenodeoxycholic acid (15 mg/kg/day) fail to dissolve gallstones in 30 to 50 percent of patients with radiolucent gallstones in a functioning gallbladder. In humans, increasing dietary cholesterol produces increased biliary secretion of cholesterol. Restriction of dietary cholesterol reduces the minimum effective dose of chenodeoxycholic acid and speeds gallstone dissolution. In this study we investigated the interaction of dietary cholesterol and chenodeoxycholic acid in the prevention of gallstones in the prairie dog gallstone model. In animals fed a moderately lithogenic diet, standard doses of chenodeoxycholic acid failed to prevent gallstones. Reduction of the cholesterol stimulus or doubling the dose of chenodeoxycholic acid prevented the formation of gallstones. These findings support the hypothesis that the formation and dissolution of cholesterol gallstones are an expression of the relative strengths of saturating and desaturating stimuli. Therefore, rational therapy for cholesterol gallstone dissolution and prevention requires both reduction of lithogenic stimuli and optimal titration of chenodeoxycholic acid.

Animals↗

Stasis before gallstone formation: altered gallbladder compliance or cystic duct resistance?

Gallbladder stasis occurs before gallstone formation and provides the link between the hepatic secretion of supersaturated bile and cholesterol cholelithiasis. We recently observed that cystic duct resistance increases while sphincter of Oddi resistance is unchanged in the presence of lithogenic bile without gallstones. Whether alterations in gallbladder function also lead to gallbladder stasis has been unclear. Therefore, we tested the hypothesis that before gallstone formation, stasis results from increased cystic duct resistance and altered gallbladder compliance. Adult, male prairie dogs were fed either a trace cholesterol (control) or a 0.4 percent cholesterol-enriched diet. Cystic duct resistance increased but gallbladder compliance was unchanged before gallstone formation. A significant correlation (p less than 0.001) was found between the lithogenic index and cystic duct resistance in pregallstone animals. We conclude that increased resistance to flow across the cystic duct, and not altered gallbladder compliance, is etiologically related to bile stasis, an important event in gallstone formation.

Animals↗

Amebic abscess of the liver: surgical aspects.

During the past five years, ten documented cases of hepatic amebic abscess have required surgical intervention at Olive View Hospital, Van Nuys, California. Three of the patients underwent laparotomy when an hepatic abscess ruptured into the peritoneal cavity, and two required surgical intervention when an abscess invaded adjacent organs. Another abscess continued to enlarge despite metronidazole therapy and still another became superinfected with bacteria. In the remaining three patients, surgical procedure would have been avoided if the correct diagnosis had been made. In fact, the preoperative diagnosis in five cases was acute appendicitis. All patients survived. The incidence of Entamoeba histolytica infestation is increasing in our community. Although most patients rapidly improve with metronidazole therapy, surgical complications do arise and diagnoses are missed. This series of cases emphasizes the need for surgeons working in Southern California to familiarize themselves with the clinical features, complications and appropriate surgical treatment of amebiasis.

Abdomen, Acute↗

The differing effects of early and chronic cholelithiasis on hepatic bile lithogenicity.

The hypothesis that increasing chronicity of cholelithiasis is associated with a progressive alteration of the enterohepatic circulation, resulting in a decrease in bile salt pool size and reversion of hepatic bile composition to a less lithogenic state, was tested in the prairie dog gallstone model. During the early phases of cholesterol cholelithiasis, both hepatic and gallbladder bile were saturated with cholesterol, and the bile salt pool size was normal. As stones became more chronic, the gallbladder was increasingly removed from the enterohepatic circulation, bile salt recycling increased and the pool size decreased. Despite this decrease in pool size and persistence of lithogenic gallbladder bile, hepatic bile composition reverted to a less lithogenic state. These data suggest that the sequelae of functional cholecystectomy are analogous to those of cholecystectomy, In addition, it appears that the liver and gallbladder interact in a dynamic manner, continually influencing the function of each other.

Animals↗

The role of altered extrahepatic biliary function in the pathogenesis of gallstones after vagotomy.

Several clinical studies have documented an increased incidence of gallstones after truncal vagotomy. Previous laboratory studies, however, have failed to establish a clear mechanism for this phenomenon. Whereas lithogenic bile is a prerequisite for cholesterol cholelithiasis, gallbladder stasis has also been shown to be a critical factor in stone formation. We tested the hypothesis that truncal vagotomy alters extrahepatic biliary function by performing either sham laparotomy or truncal vagotomy and pyloroplasty in the prairie dog. After operation, animals were fed a trace-cholesterol (nonlithogenic) diet for 3 months. In acute terminal experiments gallbladder bile was collected for determination of lithogenic index (LI). Resistance to flow through the sphincter of Oddi and cystic duct as well as gallbladder compliance were then determined. Sphincter of Oddi resistance was significantly elevated at 3 months after vagotomy (P less than 0.03). Cystic duct resistance, however, did not change significantly after vagotomy and pyloroplasty. Gallbladder compliance was significantly reduced in vagotomized animals (P less than 0.03). Gallbladder bile was unsaturated in both sham (LI = 0.47 +/- 0.09) and vagotomized animals (LI = 0.52 +/- 0.12), and gallstones did not develop in either group. Increased resistance to flow through the sphincter of Oddi after truncal vagotomy may represent the initial step leading to a gallbladder dilatation, bile stasis, and, ultimately, gallstone formation.

Animals↗

The prevention and treatment of the persistent perineal sinus.

There is a high reported incidence of persistent perineal sinus after proctectomy for inflammatory bowel disease. The cause and prevention are discussed. In a consecutive series, persistent perineal sinuses occurred in 4 of 17 patients with Crohn's colitis, and in none of 20 patients with ulcerative or unclassified colitis (1 died soon after operation). The technique is described for patients with a sinus persisting for more than 6 months, using total excision, primary closure, and suction drainage. Six of 7 patients so treated healed primarily and the seventh healed within 2 weeks. In males, sexual dysfunction was often decreased.

Adolescent↗

Chronic cholelithiasis and decreased bile salt pool size: cause or effect?

The hypothesis that the decreased bile salt pool size observed in humans with chronic cholelithiasis is a result rather than a cause of gallstones was tested in a prairie dog gallstone model. A decrease in bile salt pool size was observed in cholesterol-fed prairie dogs only after the chronic presence of stones had induced physiologic, anatomic and microscopic changes typical of human chronic cholecystitis. These data suggest that the decreased bile salt pool size associated with chronic cholelithiasis is a result rather than a cause of gallstones and that the link between the hepatic secretion of cholelithogenic bile and gallstones is altered gallbladder function.

Animals↗

Roles of lithogenic bile and cystic duct occlusion in the pathogenesis of acute cholecystitis.

The hypothesis that the elements essential for the induction of acute cholecystitis are the presence of lithogenic bile and cystic duct occlusion was tested in the prairie dog gallstone model. Neither the presence of gallstones alone nor acute cystic duct occlusion alone resulted in acute inflammation of the gallbladder. Acute cholecystitis developed in prairie dog gallbladders containing cholesterol-saturated bile, with or without gallstones, shortly after cystic duct occlusion. These data suggest that the factors essential for the induction of acute cholecystitis are the presence of lithogenic bile and cystic duct occlusion and that gallstones, although frequently present, are not an essential prerequisite to acute inflammation.

Acute Disease↗

The effects of a high-fiber diet on bile acid pool size, bile acid kinetics, and biliary lipid secretory rates in the morbidly obese.

A high-fiber diet has been suggested as one reason for the low incidence of gallstones in some populations. Therefore the authors tested the effects of a high-fiber diet on biliary secretory kinetics and bile salt kinetics in morbidly obese volunteers. Bile salt pool sizes were reduced by 50%, and their half-lives were decreased 70% after the subjects had spent 6 weeks on the high-fiber diet. Bile acid enterohepatic circulation times also were shortened dramatically. However, the lithogenicity of bile did not decrease, and bile remained supersaturated with with cholesterol. Fasting bile samples tended to be even more lithogenic than before the subjects follwed the diet. In these obese subjects, a high-fiber diet failed to reduce the tendency to secrete cholesterol-saturated bile.

Adult↗

Anesthesia for prairie dogs.

The combination of 20 mg xylazine/kg of body weight and 100-150 mg ketamine/kg of body weight provided satisfactory levels of anesthesia in 63 prairie dogs, and the combination was tolerated well with a mortality rate of 3.2%.

Acepromazine↗