cholecystokinin and Cholelithiasis

Several cases of cholelithiasis and cholecystitis have been reported in patients treated with glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) and GLP-2 receptor agonists (GLP-2RAs), respectively. Thus, the effects of GLP-1 and GLP-2 on gallbladder motility have been investigated. We have provided an overview of the mechanisms regulating gallbladder motility and highlight novel findings on the effects of bile acids and glucagon-like peptides on gallbladder motility.. The articles included in the present review were identified using electronic literature searches. The search results were narrowed to data reporting the effects of bile acids and GLPs on gallbladder motility.. Bile acids negate the effect of postprandial cholecystokinin-mediated gallbladder contraction. Two bile acid receptors seem to be involved in this feedback mechanism, the transmembrane Takeda G protein-coupled receptor 5 (TGR5) and the nuclear farnesoid X receptor. Furthermore, activation of TGR5 in enteroendocrine L cells leads to release of GLP-1 and, possibly, GLP-2. Recent findings have pointed to the existence of a bile acid-TGR5-L cell-GLP-2 axis that serves to terminate meal-induced gallbladder contraction and thereby initiate gallbladder refilling. GLP-2 might play a dominant role in this axis by directly relaxing the gallbladder. Moreover, recent findings have suggested GLP-1RA treatment prolongs the refilling phase of the gallbladder.. GLP-2 receptor activation in rodents acutely increases the volume of the gallbladder, which might explain the risk of gallbladder diseases associated with GLP-2RA treatment observed in humans. GLP-1RA-induced prolongation of human gallbladder refilling may explain the gallbladder events observed in GLP-1RA clinical trials.

Topics: Bile Acids and Salts; Cholecystitis; Cholecystokinin; Cholelithiasis; Diabetes Mellitus, Type 2; Gallbladder; Gallbladder Emptying; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide-2 Receptor; Glucagon-Like Peptides; Humans; Muscle Contraction; Muscle, Smooth; Obesity; Postprandial Period

A number of epidemiological studies has established obesity as a risk factor for gallstone disease. More recently, studies have suggested a relationship between gallstone disease and the metabolic syndrome linked to central adiposity, whose cardinal feature is represented by hyperinsulinaemia. Studies on fasting gall-bladder volume in obese subjects show that this parameter correlates with weight, body mass index (BMI) and body surface area; however, this is also true for large-sized non-obese subjects. Gall-bladder volume also correlates with abdominal fat and with impaired glucose tolerance. In contrast to the well-established role of bile supersaturation in the pathogenesis of gallstones in obesity, data are controversial on whether gall-bladder motor function is defective in obese subjects. However, studies were heterogeneous for subjects' BMI, emptying stimulus, technique used and parameters assessed to evaluate gall-bladder motor function. Also, differences in baseline gall-bladder volume may lead to wide differences in bile 'washout' effect despite apparently similar percentage changes in volume or content. Although post-prandial plasma levels of cholecystokinin (CCK) are normal in obese subjects, there is some evidence that a sub-group of obese subjects could have decreased sensitivity to CCK, possibly mediated by hyperinsulinaemia. Further studies using standard physiological stimuli and controlling for glucose tolerance, fasting insulin levels and baseline gall-bladder volume are needed to establish the role of gall-bladder motor function in the pathogenesis of gallstone disease in obesity.

Topics: Body Mass Index; Cholecystokinin; Cholelithiasis; Gallbladder; Gastrointestinal Motility; Humans; Hyperinsulinism; Muscle Contraction; Muscle, Smooth; Obesity; Postprandial Period

Although some controversy exists, diabetic patients generally are thought to have a two- to threefold increased risk of cholesterol gallstones. From previous studies there is no convincing evidence for a supersaturated bile in diabetics, whereas several reports indicate that impaired gall-bladder emptying could be one of the important factors in the increased incidence of gallstones in diabetics. However, studies of gall-bladder motility in diabetics have yielded conflicting results, probably because of substantial heterogeneity in the patients studied, emptying stimulus and technique used to assess gall-bladder motor function. The mechanism of the gall-bladder emptying abnormality in diabetics is not completely understood, although it has been proposed that it could represent a manifestation of denervation caused by visceral neuropathy. Based on normal post-prandial cholecystokinin release, it can be ruled out that impaired cholecystokinin release is the mechanism responsible for reduced gall-bladder emptying in diabetics. Other possible explanations for impaired gall-bladder contraction in diabetics include a decreased sensitivity of the smooth muscle of the gall-bladder to plasma cholecystokinin, and/or decreased cholecystokinin receptors on the gall-bladder wall.

Topics: Cholecystokinin; Cholelithiasis; Diabetes Complications; Diabetes Mellitus; Gallbladder; Gastrointestinal Motility; Humans; Muscle, Smooth; Postprandial Period; Receptors, Cholecystokinin

Topics: Cholecystectomy, Laparoscopic; Cholecystitis; Cholecystokinin; Cholelithiasis; Chronic Disease; Humans; Sensitivity and Specificity

Steatosis and steatohepatitis are associated with obesity. Despite florid histological changes, patients with non-alcoholic steatohepatitis generally remain asymptomatic, and it usually runs a relatively benign course. An elevated insulin level may be important in the pathogenesis. There is a marked regression of fatty changes after weight reduction. In obese subjects the risk of developing gallstones is increased due to an increased saturation of gallbladder bile with cholesterol and possible gallbladder stasis. During weight reduction with very low calorie diets the incidence in gallstones increases probably because of an increased saturation of bile during the loss of weight. Ursodeoxycholic acid appears to be a promising prophylactic agent. Chenodeoxycholic acid is not useful for these subjects. There is controversy over whether obesity contributes to gastroesophageal reflux and gastric emptying disturbances. There are changes in gastrointestinal peptide plasma levels in obesity but it is not clear if this contributes to its development. The risk for high-risk colorectal adenomas and carcinomas is reported to be increased in obese males. Vertical banded gastroplasty and gastric bypass procedures are nowadays the surgical options for the treatment of obesity. Nutritional deficiencies, particularly of vitamin B12, folate and iron are common after gastric bypass and must be sought and treated. Dumping is another potential complication of this operation. If stenosis and gastric outlet obstruction develop endoscopic dilatation is a good therapeutic option.

Topics: Animals; Bombesin; Cholecystokinin; Cholelithiasis; Diet Therapy; Fatty Liver; Fatty Liver, Alcoholic; Gastrointestinal Diseases; Gastrointestinal Motility; Gastrointestinal Neoplasms; Humans; Male; Obesity; Peptides; Peripheral Nervous System Diseases; Risk Factors

Topics: Acromegaly; Animals; Bile; Cholecystokinin; Cholelithiasis; Gallbladder Emptying; Humans; Incidence; Octreotide; Prevalence; Somatostatin

Gallbladder stones (GBS) are found in up to 50% of patients receiving octreotide, but the reported prevalence of cholecystolithiasis in patients treated with octreotide is variable and little is known about gallstone incidence, composition, pathogenetic mechanisms, dissolvability, and primary prevention. Octreotide treatment apart, in industrialised societies most GBS are mixed in composition, cholesterol-rich (arbitrarily greater than 70% cholesterol by weight), radiolucent (70%), and, given a patent cystic duct (70%), dissolvable in bile rendered unsaturated in cholesterol by oral ursodeoxycholic (UDCA) +/- chenodeoxycholic (CDCA) acid treatment. They form when (1) GB bile becomes supersaturated with cholesterol (as the molar ratio of cholesterol to phospholipids in biliary vesicles approaches 1:1, the vesicles become unstable); (2) there is an imbalance between pro- and anti-nucleating factors, which favors cholesterol crystal precipitation; and (3) there is stasis within the GB as a result of altered motor function and/or excess mucus that traps the crystals. These changes may be associated with altered (4) biliary bile acid composition (more DCA and less CDCA than normal), and/or (5) phospholipid fatty acid composition (arachidonyl-rich lecithin acting as a substrate for mucosal prostaglandin synthesis which, in turn, may influence both gallbladder motility, and mucus glycoprotein synthesis and secretion). During octreotide treatment, meal-stimulated cholecystokinin (CCK) release is impaired leading to GB hypomotility, but little is known about the effects of octreotide on biliary cholesterol saturation, crystal nucleation time, mucus glycoprotein concentration, bile acid or phospholipid fatty acid composition. Most, but not all, reports suggest that the prevalence of GBS in octreotide-treated patients is considerably greater than that in age-, sex-, and weight-matched controls, but proof (by pre-treatment and on-treatment ultrasound) that the GBS were absent before, but developed during, therapy is not always available. Furthermore, there are few data on analysis of GBS composition in patients developing stones during treatment, although initial reports suggest that octreotide-associated GBS are also radiolucent, cholesterol-rich, and dissolve with oral bile acid treatment. Maximum GBS attenuation values, measured in Hounsfield Units (HU) by localized computerized tomography scanning of the GB, predict stone composition and dissolvability: GBS with

Topics: Acromegaly; Cholecystokinin; Cholelithiasis; Cholesterol; Gallbladder; Gallbladder Emptying; Humans; Incidence; Octreotide; Prevalence; Somatostatin

Topics: Bile; Biliary Dyskinesia; Biliary Tract; Cholecystokinin; Cholelithiasis; Cholestasis; Humans; Middle Aged; Muscle Contraction

Topics: Adenoma, Islet Cell; Chenodeoxycholic Acid; Cholecystokinin; Cholelithiasis; Dehydration; Diabetes Mellitus; Duodenal Ulcer; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Motilin; Pancreatic Neoplasms; Secretin; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

The need to differentiate patients with acalculous gallbladder disease who would benefit from cholecystectomy and those who would not led to the search for a procedure that would be of value in this respect. For this purpose, cholecystokinin (CCK) has been used, and many reports have indicated that CCK does identify patients in whom the gallbladder is the source of pain. A review of papers dealing with CCK as a diagnostic aid suggests, however, that some radiographic evaluations have not been subjected to adequate, unbiased interpretation and that some follow-up studies have been incomplete and of short duration. Despite these objections there is evidence that CCK can be useful as a diagnostic aid, and further, continued, well-designed studies are indicated.

Topics: Cholecystography; Cholecystokinin; Cholelithiasis; Drainage; Gallbladder Diseases; Humans

Topics: Animals; Bile; Bile Acids and Salts; Bile Ducts; Blood Protein Disorders; Cholecystokinin; Cholelithiasis; Cholesterol; Female; Gallbladder; Humans; Hyperlipidemias; Lipoproteins, VLDL; Liver; Liver Circulation; Male; Phosphatidylcholines; Phospholipids; Pregnancy; Pregnancy Complications

Acalculous biliary pain has been related to gallbladder dysfunction that produces a gallbladder emptying defect-a condition which favours the development of lithiasis. It is therefore probable that microlithiasis is present in patients with gallbladder dysfunction. The aims of this study were to measure gallbladder emptying and investigate bile abnormalities in patients with acalculous biliary pain. In 92 consecutive patients, gallbladder emptying was assessed by quantitative cholescintigraphy (abnormal ejection fraction < or =40%). In 64 patients, a microscopic study was performed on duodenal bile, defining abnormality as the presence of cholesterol crystals in any amount and/or calcium bilirubinate granules and/or microspheroliths at a rate of >10 per slide. The ejection fraction was abnormal in 45 patients (49%) (median 25.1%, range 6.8-39.3%) and normal in the remaining 47 cases (median 71.3%, range 41.0-96.1%). Bile was abnormal in 32 of 64 patients (50%), the most frequent finding being calcium bilirubinate granules. In the patients with bile abnormalities, abnormal ejection fraction was more frequent (20 of 32) and the median ejection fraction was lower (30.9%, range 12.0-94.1%) than in the patients with normal bile (16 of 32 with an abnormal ejection fraction; median ejection fraction 50.7%, range 6.8-96.1%). Abnormal bile was frequent (55.5%) in patients with reduced ejection fraction, but was not uncommon in patients with normal ejection fraction (33.3%). Fewer patients showed no alteration (25%). It is concluded that in most patients, acalculous biliary pain coexists with gallbladder dysfunction or abnormal bile, the combination of both alterations being common.

Topics: Abdominal Pain; Acalculous Cholecystitis; Adult; Bile; Cholecystokinin; Cholelithiasis; Female; Humans; Male; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Statistics as Topic; Technetium Tc 99m Disofenin

The aim of this study was to unravel the mechanisms responsible for the increased risk of gall stone disease in hypertriglyceridaemia (HTG) and to compare the effects of triglyceride lowering therapy by bezafibrate and fish oil on determinants of cholelithiasis (biliary lipid composition and gall bladder motility) in HTG patients.. Gall bladder motility (ultrasonography) was studied postprandially and during infusion of cholecystokinin (CCK). Determinants of cholelithiasis and serum lipids were compared between nine HTG patients and 10 age, sex, and body mass index matched normolipidaemic controls. The effects of bezafibrate and fish oil in HTG patients were studied in a randomised cross over trial.. HTG patients showed 14-fold higher serum triglyceride (TG) levels than controls. Biliary lipid composition, fasting gall bladder volumes, and CCK levels did not differ between HTG patients and controls. Gall bladder emptying was reduced in HTG patients compared with controls during CCK infusion (-22%) as well as in response to a meal (-37%; both p<0.001). Postprandial CCK levels were significantly higher in HTG patients. Both bezafibrate and fish oil reduced serum TG levels (-68% and -51% v baseline, respectively; both p<0.01). Fasting CCK levels were not affected whereas CCK induced gall bladder emptying increased during bezafibrate (+29%; p<0.001) and tended to increase on fish oil therapy (+13%; p=0.07). Postprandial gall bladder motility improved on bezafibrate and fish oil (+47 and +25% v baseline, respectively; both p<0.02) at least partly due to increased gall bladder sensitivity to CCK (both p<0.05 v baseline). Bezafibrate but not fish oil increased the molar ratio of cholesterol to bile acids (+40%; p

Topics: Analysis of Variance; Bezafibrate; Bile; Case-Control Studies; Cholecystokinin; Cholelithiasis; Cholesterol; Cross-Over Studies; Fish Oils; Gallbladder; Gallbladder Emptying; Humans; Hypertriglyceridemia; Hypolipidemic Agents; Lipids; Male; Risk; Statistics, Nonparametric; Ultrasonography

Gallbladder removal is associated with an increased incidence of gastroesophageal reflux, but the mechanism is unclear. Cholecystokinin (CCK) release, which causes gallbladder contraction, is inhibited by bile in the duodenum. This study investigates the effect of cholecystectomy on meal-stimulated CCK secretion.. Three groups of patients were studied. Group 1 (n = 15) were normal controls. Group 2 (n = 27) were patients with symptomatic gallstones. Group 3 (n = 25) were patients who had undergone cholecystectomy. Meal-stimulated CCK levels were measured by radioimmunoassay at defined time points for 60 min after a standard corn oil-based meal.. Fasting CCK levels were similar in all three groups. In postcholecystectomy patients, meal-stimulated plasma CCK levels were significantly elevated compared with controls: median (range) integrated CCK values for 60 min were 116 (28-209) in controls, 123 (20-501) in gallstone patients, and 176 (63-502) after cholecystectomy.. This study suggests that cholecystectomy causes an exaggerated meal-stimulated CCK response. Because CCK is known to relax the lower esophageal sphincter. these findings may help explain the increased incidence of gastroesophageal reflux seen after cholecystectomy.

Topics: Adult; Aged; Cholecystectomy; Cholecystokinin; Cholelithiasis; Eating; Female; Gallbladder; Gastroesophageal Reflux; Humans; Male; Middle Aged; Postprandial Period; Radioimmunoassay; Time Factors

Acromegalic patients treated three times daily with subcutaneous injections of the somatostatin analogue octreotide frequently develop gallstones, due to suppressed cholecystokinin release and impaired gall-bladder emptying.. To elucidate the effects of a new long-acting octreotide formulation (Sandostatin LAR) on gall-bladder emptying, cholecystokinin release and gallstone formation.. Postprandial gall-bladder and gastric emptying were determined by ultrasonography and cholecystokinin release was measured in seven patients on days 0, 14, 28, and 75 (Sandostatin LAR, 20 mg intramuscularly on days 1, 30, and 60).. During treatment, fasting gall-bladder volumes increased from 26.5 +/- 3.2 mL to 61.4 +/- 7.5 mL, but postprandial cholecystokinin release and gall-bladder emptying (from 63.9 +/- 3.8% to 12.3 +/- 3.5%) were severely suppressed. Gallstones formed in six out of seven patients within 8 months of treatment. Gastric emptying did not change during the therapy.. The risk of gallstone formation is greatly increased during Sandostatin LAR. This is probably related to profound suppression of cholecystokinin release and gall-bladder emptying.

Topics: Acromegaly; Aged; Aged, 80 and over; Chemistry, Pharmaceutical; Cholecystokinin; Cholelithiasis; Female; Gallbladder Emptying; Gastrointestinal Agents; Humans; Male; Middle Aged; Octreotide; Postprandial Period; Risk Factors

Altered gallbladder motility is regarded as one of the important factors involved in the formation and recurrence of gallstones. Previous studies have suggested that cisapride increases postprandial gallbladder contraction and may therefore be theoretically useful in preventing stone recurrence. The aim of our study was therefore to investigate the effect of cisapride on gallbladder motility in stone-free patients after extracorporeal shock-wave lithotripsy, as compared to healthy volunteers pair-matched for age and sex.. Each subject received cisapride or placebo in a double-blind, cross-over, random order. Gallbladder volumes were measured by ultrasonography in the fasting state and after intake of a standard liquid meal. Plasma cholecystokinin levels were determined by radioimmunoassay.. Fasting gallbladder volumes were smaller in patients as compared to volunteers (20.7 +/- 1.3 ml vs. 46.0 +/- 9.2 ml; p < 0.05) but were not modified by cisapride (21.1 +/- 1.7 ml vs. 58.6 +/- 11.3 ml). The maximal postprandial decrease in gallbladder volume was similar in patients and volunteers (64.5 +/- 12% vs. 62 +/- 10%; NS) and was not significantly altered by cisapride (59 +/- 9.4% vs. 54 +/- 9%; NS). In patients, cisapride increased integrated postprandial gallbladder volume by accelerating gallbladder refilling as compared to placebo by 37 +/- 15% (p < 0.05). Integrated cholecystokinin plasma levels were similar in patients and volunteers and were 13.4 +/- 4.7% higher after cisapride as compared to placebo (p < 0.05).. The results of this study suggest that cisapride does not alter postprandial gallbladder contraction but accelerates gallbladder refilling in patients free from gallstones after extracorporeal shock-wave lithotripsy. This effect of cisapride is probably due to an acceleration of gastric emptying also causing a secondary enhanced cholecystokinin release.

Topics: Adult; Aged; Cholecystokinin; Cholelithiasis; Cisapride; Cross-Over Studies; Double-Blind Method; Female; Gallbladder; Humans; Lithotripsy; Middle Aged; Piperidines; Radioimmunoassay

The postprandial release of cholecystokinin (CCK) regulates gallbladder (GB) contraction but little is known about the role, if any, of the still-elevated CCK blood levels on subsequent GB refilling. To assess the role of CCK in GB refilling, a CCK-receptor antagonist, loxiglumide, or saline were infused intravenously in a random double-blind fashion after the ingestion of a liquid test meal in 16 healthy subjects. An identical study protocol was performed in 10 GB "contractor" patient with radiolucent stones to ascertain whether the reported reduced CCK effect on GB emptying also affects GB refilling. GB volumes were assessed ultrasonographically in the fasting state and for 150 min at 15-min intervals after meal ingestion. GB volumes during postprandial refilling were significantly greater during loxiglumide than placebo infusion (P < 0.01), but they did not differ between gallstone and control subjects. In conclusion, postprandial endogenous CCK has a relevant role in delaying GB refilling, and this effect is not altered in patients with radiolucent gallstones.

Topics: Adult; Cholecystokinin; Cholelithiasis; Double-Blind Method; Eating; Female; Gallbladder; Gallbladder Emptying; Humans; Male; Proglumide; Ultrasonography

In the present study, we adopted real-time ultrasonography to investigate the effect of atropine on the gallbladder emptying induced by CCK-OP in the normal subjects, and the difference of gallbladder emptying induced by CCK-OP between the "silent" gallstone patients and the controls. The results showed that: (a) CCK-induced gallbladder emptying in normal subjects was inhibited from 88.7% +/- 5.5% without atropine to 43.4% +/- 9.4% with atropine (P < 0.001). (b) The fasting gallbladder volume in the "silent" gallstone patients (26.7 +/- 10.9cm3) was significantly larger than that in the control (19.2 +/- 7.3cm3) (P < 0.05) and gallbladder emptying in the "silent" gallstones patients (44.0% +/- 8.7%) was significantly lower than that in the control (53.4% +/- 6.4%) (P < 0.01). We concluded that, significantly inhibited CCK-induced gallbladder emptying and there was significantly impaired gallbladder emptying in the patients with gallstones.

Topics: Adult; Atropine; Cholecystokinin; Cholelithiasis; Female; Gallbladder; Gallbladder Emptying; Gastrointestinal Agents; Humans; Male; Middle Aged; Muscarinic Antagonists; Sincalide; Ultrasonography

Jejunoileal bypass surgery for obesity increases the risk of gallstone formation, and, contrary to expectations, the incidence is greater in patients with a long as compared to a short ileum left in continuity. Impaired gallbladder motility due to reduced cholecystokinin (CCK) stimulation could be an explanation. The aim of this study was to investigate the CCK levels in such patients.. The randomized trial of bypass surgery named The Danish Obesity Project.. We compared plasma levels of CCK in obese patients at three, nine or 15 months after jejunoileal bypass surgery with either a 1:3 jejunoileal ratio (n = 14) or a 3:1 ratio (n = 15), and in unoperated obese patients (n = 7). Plasma CCK levels were determined during fasting and during 150 min following ingestion of a liquid test meal.. There were no significant changes over time following surgery. Basal CCK levels were significantly increased after surgery, and significantly higher in those with a 3:1 than in those with a 1:3 jejunoileal ratio. The postprandial AUC (mean +/- SEM) was 935 +/- 71 pM x min in the 3:1 ratio group and 891 +/- 100 pM x min in the 1:3 ratio group. This difference was not significant, but both bypass groups were significantly higher than the unoperated group (515 +/- 79 pM x min). The integrated increase in plasma CCK above basal level showed a similar pattern, but the difference between the unoperated and the bypass groups was insignificant.. Postoperative changes in plasma CCK levels neither explain the increased risk of gallstone formation after bypass surgery nor the higher incidence with a long compared to a short ileum left in continuity in the bypass.

Topics: Cholecystokinin; Cholelithiasis; Cross-Sectional Studies; Eating; Fasting; Food; Humans; Jejunoileal Bypass; Obesity, Morbid; Risk Factors

Patients receiving total intravenous nutrition have inert gallbladders; gallbladder sludge and gallstones often develop, but are preventable if gallbladder emptying can be improved. We measured the effect of giving rapid intravenous infusions of aminoacid solutions in eight normal subjects. Four regimens were tested (250 mL over 30 min, 250 mL over 10 min, 125 mL over 5 min, and 50 mL over 5 min). Gallbladder emptying, as measured by ultrasound and cholecystokinin release, depended on both the amount and the rate of aminoacid infusion. Rapid infusion of 125 mL of an aminoacid mixture (Synthamin 14 without electrolytes) over 5 min (2.1 g per min) produced a 64% reduction in gallbladder volume within 30 min, whereas a 50 mL infusion over 5 min produced only a 22% reduction. Intermittent rapid infusion of small amounts of aminoacids may prevent gallstones in patients receiving intravenous nutrition.

Topics: Adult; Amino Acids; Cholecystokinin; Cholelithiasis; Electrolytes; Female; Gallbladder; Gallbladder Emptying; Glucose; Humans; Infusions, Intravenous; Male; Parenteral Nutrition; Parenteral Nutrition Solutions; Solutions; Ultrasonography

This prospective study was undertaken to determine the effect of partial gastrectomy without vagotomy on postprandial gallbladder contraction and secretion of cholecystokinin (CCK) and pancreatic polypeptide (PP) in 22 peptic ulcer patients randomly assigned to either Billroth II (N = 11) or Roux-en-Y (N = 11) anastomosis. The patients were studied within two weeks before surgery and at six months postoperatively. After surgery basal gallbladder volumes were larger than preoperatively (P less than 0.02). Integrated postprandial gallbladder contraction was not significantly affected by gastrectomy, either in the patients with Billroth II anastomosis (2276 +/- 268 vs 1985 +/- 362%/60 min) or in those with Roux-en-Y anastomosis (2045 +/- 327 vs 2445 +/- 352%/60 min) when studied pre- and postoperatively, respectively. Similarly, integrated postprandial plasma CCK secretion was not significantly changed by either Billroth II gastrectomy (200 +/- 31 vs 166 +/- 21 pM/60 min) or Roux-en-Y gastrectomy (146 +/- 26 vs 147 +/- 12 pM/60 min). However, integrated postprandial PP secretion was significantly (P less than 0.05) lower after Billroth II gastrectomy (6.8 +/- 2.4 vs 2.2 +/- 1.0 nM/60 min), while the reduction in plasma PP after Roux-en-Y gastrectomy just failed to reach statistical significance (6.0 +/- 1.5 vs 3.4 +/- 0.9 nM/60 min). Similarly, the PP response, but not the gallbladder response, to an intravenous bolus injection of 1 IDU CCK/kg body weight was significantly decreased after gastrectomy independent of the type of anastomosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anastomosis, Roux-en-Y; Cholecystokinin; Cholelithiasis; Female; Food; Gallbladder; Gastrectomy; Humans; Jejunum; Male; Middle Aged; Muscle Contraction; Pancreatic Polypeptide; Peptic Ulcer; Postoperative Complications; Postoperative Period; Prospective Studies; Random Allocation

Cholecystokinin (CCK) was used in a randomized double-blind trial to evaluate its effect on post-operative paralytic ileus. Sixty patients were admitted to the study. The return of postoperative intestinal motility was registered with subjective and/or objective methods. No differences were found between the CCK group and the placebo group.

Topics: Adult; Aged; Cholecystectomy; Cholecystokinin; Cholelithiasis; Clinical Trials as Topic; Double-Blind Method; Female; Gastrointestinal Motility; Humans; Intestinal Obstruction; Male; Middle Aged; Postoperative Complications; Random Allocation

An estimated 20 million Americans have gallstones the majority asymptomatic. Yet traditionally many are often placed on low-fat or fat-free diets, presumably to reduce the risk of biliary colic. To assess the gallbladder dynamics in response to various meals, we studied 15 subjects (ages 21-54), each on 4 separate days. After an overnight fast, each subject was given, at random, either a breakfast containing greater than 30 g fat, less than 15 g fat, totally free of fat, or an infusion of C-terminal octapeptide of cholecystokinin. Gallbladder ejections at regular time intervals were measured using real time ultrasonography and the sum of cylinders technic corrected for the gallbladder shape. Considerable variability in the gallbladder dynamics and time response was noted with all the stimuli. However, among various meals, there were no statistically significant differences in the mean maximum ejection fraction or the mean maximum ejection time (p greater than 0.10). The mean maximum ejection fraction after cholecystokinin was somewhat greater (0.01 less than p less than 0.05) than that after meals, but the mean maximum ejection time was similar (p greater than 0.10). We conclude that the gallbladder dynamics in response to various meals are independent of a meal's fat content. Since the passage of gallstones into the cystic or common duct (biliary colic) is a random event unrelated to the type of food, fat-restricted diets offer no significant therapeutic advantage in the management of the large population with asymptomatic gallstones.

Topics: Adult; Cholecystokinin; Cholelithiasis; Dietary Fats; Female; Food; Gallbladder; Humans; Male; Middle Aged; Time Factors

Cholecystokinin cholescintigraphy is used clinically to quantify gallbladder ejection fraction as an indicator of functional gallbladder disorder. It can also provide the opportunity to quantify an individual's responsiveness to the physiologic stimulant of gallbladder contraction, cholecystokinin, which is a major regulator of appetite and postprandial satiety.

Topics: Adult; Aged; Body Weight; Cholecystokinin; Cholelithiasis; Cholesterol; Female; Gallbladder; Gallbladder Emptying; Humans; Indicators and Reagents; Kinetics; Male; Middle Aged; Protein Binding; Radionuclide Imaging; Receptors, Cell Surface; Sensitivity and Specificity

The level of cholecystokinin and secretin in 50 patients after cholecystectomy (from 1 to 10 years ago) was analyzed to study connection between cholecystectomy and gastrointestinal hormones concentration. 30 patients with gall bladder stone disease were included into the group of comparison. Cholecystokinin and secretin concentration in the groups of research was compared with indicated hormones concentration in the group of control formed of healthy volunteers. After anamnestical clinical and diagnostical features in every group had been studied we concluded, that cholecystokinin level changes depending on period after operation and outflow of bile conditions.

Topics: Adaptation, Physiological; Case-Control Studies; Cholecystectomy; Cholecystokinin; Cholelithiasis; Humans; Postcholecystectomy Syndrome; Secretin; Time Factors

A significant relationship exists among food intake and nutritional status and cholelithiasis, including gallstone and hepatolithiasis. Leptin is associated with obesity. This study was to investigate the differences in serum leptin levels in patients with gallstone and hepatolithiasis and to evaluate the relationships among leptin, cholecystokinin (CCK), lipid and lipoprotein concentrations.. Body mass index (BMI), serum leptin, CCK, insulin, lipid and lipoprotein concentrations, and liver function were measured in 382 patients with gallstone (GS group), 83 patients with hepatolithiasis (HS group) and 30 healthy controls (control group). The values of these indices were compared among the groups. In each group, Pearson's product-moment correlation coefficient among these indices were evaluated.. There were notable differences in serum leptin, CCK, total cholesterol, total triglycerides, apolipoprotein-a (APO-a), globulin, direct reacting bilirubin, and BMI between the GS and HS groups (P<0.05). Positive correlations between serum leptin and BMI, CCK, total cholesterol, gamma-glutamyl transpeptidase (GGT), aminotransferase, and insulin were found in the GS group (P<0.05). Positive correlations were observed between serum leptin and CCK, bilirubin, aminotransferase, GGT, in the HS group (P<0.05), but negative correlations between serum leptin and albumin or APO-a (P<0.05).. Leptin participates in modulating lipid metabolism. There are notable differences in leptin, serum lipid, and CCK between patients with gallstone and those with hepatolithiasis. The role of leptin in the pathophysiological course of cholelithiasis needs further investigation.

Topics: Adult; Aged; Apolipoproteins A; Bile Ducts, Intrahepatic; Bilirubin; Cholecystokinin; Cholelithiasis; Cholesterol; Female; Gallstones; Globulins; Humans; Leptin; Lipid Metabolism; Lipoproteins; Male; Middle Aged; Triglycerides

Patients with acalculous biliary-like pain present a difficult clinical challenge. Our aim was to evaluate the outcome of patients with recurrent biliary-like pain without gallstones who underwent testing of gallbladder ejection fraction (GBEF) by cholecystokinin-cholescintigraphy (CCK-CS) in order to determine clinical factors that may predict symptom resolution. We reviewed the records of patients with recurrent acalculous biliary-like pain who underwent CCK-CS from January 1995 to December 1999. For comparison, we also studied an age- and sex-matched group of patients who underwent cholecystectomy for symptomatic cholelithiasis. Outcome was obtained by telephone interview, using a scale from 0 to 3 where 0 = no improvement and 3 = clinical remission. Patient demographics, predominant symptom(s), method of management, gallbladder pathology, and response to treatment were recorded. One hundred twenty-nine patients underwent CCK-CS. Of 69 with an abnormal GBEF, 48 (70%) were available for interview. Forty patients underwent cholecystectomy. Twenty-seven patients reported symptom resolution after surgery while 4 nonsurgical patients reported the same (P = NS). Univariate analysis revealed no association between symptom outcome and presence of gastrointestinal symptom(s), severity and duration of abdominal pain, management, or gallbladder pathology. In addition, no GBEF cutoff level predicted symptom outcome. Of the remaining 60 patients with a normal GBEF, 30 (50%) were available for interview. Twenty-eight patients in this group were managed medically and 2 patients underwent cholecystectomy. Eighteen patients managed medically were asymptomatic, as were the 2 who underwent cholecystectomy. There was no difference in symptom outcome between patients who had GBEF >35% vs <35%. In conclusion, in a group of patients with recurrent acalculous biliary-like pain who underwent CCK-CS, we found a high rate of symptom resolution following cholecystectomy; however, this was not statistically different from a smaller cohort who did not undergo surgery. We were unable to determine any variable predictive of symptom resolution.

Topics: Abdominal Pain; Adult; Analysis of Variance; Biliary Dyskinesia; Cholecystectomy; Cholecystokinin; Cholelithiasis; Cohort Studies; Female; Gallbladder Diseases; Gallbladder Emptying; Humans; Male; Middle Aged; Probability; Prognosis; Radionuclide Imaging; Retrospective Studies; Sensitivity and Specificity; Severity of Illness Index; Technetium Tc 99m Disofenin

We studied the influence of the inflammatory state of the gallbladder with gallstones on its response to cholecystokinin (CCK). Responses to CCK were evaluated in isolated human gallbladder strips incubated with pharmacological antagonists. Gallbladders from patients with gallstones were classified as having mild and severe chronic cholecystitis. Healthy gallbladders were collected from liver donors. In donor gallbladders, the CCK contraction was abolished with the CCK-A receptor antagonist, L-364718, and significantly reduced by indomethacin. In gallbladders with gallstones, only mild cholecystitis showed a decreased contraction to CCK. In gallbladders with gallstones, no involvement of prostaglandins in the CCK response was observed. In severe cholecystitis, CCK contractile effect was reduced by the serotonin receptor antagonist methysergide. In healthy gallbladder, the contraction provoked by CCK is mediated by CCK-A receptors and modulated by prostaglandins. The presence of gallstones in the gallbladder is correlated with a loss of prostaglandins-modulated CCK contraction. However, the excessive release of serotonin in advanced cholecystitis normalizes the contraction to CCK, suggesting that the state of cholecystitis affects the pool of inflammatory mediators responsible for gallbladder CCK-altered motility.

Topics: Acetylcholine; Adult; Atropine; Cholecystectomy; Cholecystitis; Cholecystokinin; Cholelithiasis; Drug Interactions; Female; Gallbladder Emptying; Histamine; Humans; Indomethacin; Male; Middle Aged; Muscle Contraction; Organ Culture Techniques; Probability; Propranolol; Sensitivity and Specificity; Serotonin; Severity of Illness Index; Tetrodotoxin

To evaluate the effects of truncal vagotomy at the diaphragmatic level on the sphincter of Oddi (SO) motility.. Cholelithiasis is a well-known late complication after gastrectomy and/or vagotomy. The mechanism of gallstone formation is only partly understood, and few studies address the effects of vagotomy on SO cyclic motility in conscious subjects.. In conscious dogs, SO motility was recorded by retrograde infusion manometry through a duodenal cannula before and after bilateral truncal vagotomy at the diaphragmatic level. Effects of cholecystokinin-octapeptide and feeding were also evaluated before and after vagotomy.. SO cyclic motility and the gastroduodenal migrating motor complex continued to occur during postvagotomy fasting. Intermittent inhibitions of the SO and duodenal contractions disappeared during phase 3 of the migrating motor complex. SO basal pressure significantly decreased, whereas the amplitude significantly increased. Cholecystokinin-octapeptide inhibited SO contractions before and after vagotomy. The amplitude of SO contractions increased and their frequency decreased after feeding; however, these effects disappeared after vagotomy.. SO cyclic motility and the effects of feeding change after truncal vagotomy at the diaphragmatic level. These facts may at least partly explain gallstone formation after gastric surgery and/or vagotomy.

Topics: Animals; Cholecystokinin; Cholelithiasis; Consciousness; Dogs; Eating; Fasting; Gastrectomy; Gastrointestinal Motility; Manometry; Models, Animal; Myoelectric Complex, Migrating; Sphincter of Oddi; Vagotomy, Truncal

The incidence of gallbladder sludge or gallstone formation in bedridden patients with cerebrovascular disease (CVD) remains obscure. The aim of this study was to determine the incidence, relationship to feeding method, and mechanisms of gallbladder sludge and gallstone formation in elderly patients with CVD.. Using ultrasonography, we determined the development of gallbladder sludge and gallstone over a 12-month period, the area of the gallbladder, the gallbladder contractile response to cerulein, and fasting levels of plasma cholecystokinin (CCK) in 40 bedridden elderly patients with CVD. The patients were divided into three groups based on the feeding method: oral ingestion (OI), nasogastric feeding (NF), and total parenteral nutrition (TPN).. Gallbladder sludge and gallstone were not observed in any of the 14 OI patients, but occurred in 6 and 1 of the 11 NF patients, and in 14 and 3 of the 15 TPN patients, respectively. Fasting gallbladder areas were significantly larger in the TPN group than in the other two groups. The TPN group showed a marked decrease in cerulein-induced gallbladder contractility. Fasting plasma CCK levels were lower in the TPN group than in the OI group.. Our results indicate that elderly patients with CVD confined to bed over long periods are not necessarily at risk of gallbladder sludge or gallstone formation, and the development of these features may be associated with the feeding method. The predisposition of CVD patients on TPN to gallbladder disease is probably caused by failure of gallbladder contraction, resulting from insufficient secretion of CCK and impaired sensitivity of the gallbladder to CCK.

Topics: Aged; Aged, 80 and over; Ceruletide; Cholecystokinin; Cholelithiasis; Eating; Feeding Methods; Female; Follow-Up Studies; Gallbladder; Humans; Intubation, Gastrointestinal; Japan; Liver Function Tests; Male; Middle Aged; Parenteral Nutrition, Total; Stroke; Ultrasonography

Topics: Aged; Cerebrovascular Disorders; Cholecystokinin; Cholelithiasis; Feeding Methods; Gastrectomy; Humans

Human gallbladders with cholesterol stones (ChS) exhibit an impaired muscle contraction and relaxation and a lower CCK receptor-binding capacity compared with those with pigment stones (PS). This study was designed to determine whether there is an abnormal receptor-G protein coupling in human gallbladders with ChS using (35)S-labeled guanosine 5'-O-(3-thiotriphosphate) ([(35)S]GTPgammaS) binding, (125)I-labeled CCK-8 autoradiography, immunoblotting, and G protein quantitation. CCK and vasoactive intestinal peptide caused significant increases in [(35)S]GTPgammaS binding to Galpha(i-3) and G(s)alpha, respectively. The binding was lower in ChS than in PS (P < 0.01). The reduced [(35)S]GTPgammaS binding in ChS was normalized after the muscles were treated with cholesterol-free liposomes (P < 0.01). Autoradiography and immunoblots showed a decreased optical density (OD) for CCK receptors, an even lower OD value for receptor-G protein coupling, and a higher OD for uncoupled receptors or Galpha(i-3) protein in ChS compared with PS (P < 0.001). G protein quantitation also showed that there were no significant differences in the Galpha(i-3) and G(s)alpha content in ChS and PS. We conclude that, in addition to an impaired CCK receptor-binding capacity, there is a defect in receptor-G protein coupling in muscle cells from gallbladder with ChS. These changes may be normalized after removal of excess cholesterol from the plasma membrane.

Topics: Autoradiography; Cholecystokinin; Cholelithiasis; Cholesterol; Cross-Linking Reagents; Gallbladder; GTP-Binding Proteins; Guanosine 5'-O-(3-Thiotriphosphate); Humans; Immunoblotting; Immunosorbent Techniques; Iodine Radioisotopes; Muscle Contraction; Muscle, Smooth; Receptors, Cholecystokinin; Sincalide; Sulfur Radioisotopes; Vasoactive Intestinal Peptide

Nonsteroidal antiinflammatory drugs, inhibitors of prostaglandin synthesis, have different effects on gallbladder contractility in normal and diseased human gallbladders in vivo. We investigated this differential effect by comparing the effects of prostaglandins PGE2 and PGF2alpha, the thromboxane A2 mimetic U46619, and PGI2 on in vitro contractility in gallstone-free and gallstone-containing human gallbladders. Isometric tension was measured in gallbladder muscle strips mounted in organ baths. EC50 was calculated for each agonist. The rank order of potency in gallstone-free gallbladders was PGE2 > CCK > U46619 > PGF2alpha and in gallstone-containing gallbladders was U46619 > PGE2 > CCK > PGF2alpha. PGI2 produced contraction of gallstone-free gallbladder and relaxation of gallstone-containing gallbladder in the basal state. Further, PGI2 produced no relaxation in gallstone-free muscle strips precontracted with CCK, but significant relaxation in CCK precontracted gallstone-containing strips. PGE2, PGF2alpha, and U46619 are potent contractors of gallstone-free and gallstone-containing gallbladders, whereas PGI2 relaxes only gallstone-containing gallbladders. Since gallbladders containing cholesterol-supersaturated bile produce increased PGI2, this PGI2-induced relaxation may be a determinant of the impaired gallbladder motility of gallstone disease.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Cholecystokinin; Cholelithiasis; Dinoprost; Epoprostenol; Female; Gallbladder; Humans; In Vitro Techniques; Male; Middle Aged; Muscle Contraction; Muscle, Smooth; Prostaglandins; Thromboxane A2

During treatment with ursodeoxycholic acid (UDCA), the fasting gallbladder volume increases by a yet unknown mechanism. The present study tests whether in vitro human gallbladder contractility in response to acetylcholine and cholecystokinin is affected by UDCA therapy. Gallbladder tissue was obtained from 15 patients treated with UDCA (10 mg/kg/day) during three weeks prior to surgery, and from 15 comparable patients not treated. Data were correlated with in vivo contractility, bile composition, and gallbladder wall inflammation. The inflammation score was lower in the treated patient group. UDCA treatment enhanced gallbladder contractility in vitro: Dose-response curves for acetylcholine and cholecystokinin were both shifted to the left, and the maximal contractile stress generated in response to cholecystokinin was higher in the treated group, whereas the maximal acetylcholine-induced stress was not increased. Maximal cholecystokinin-induced stress correlated positively with fasting gallbladder volume and negatively with the biliary cholesterol saturation index, but not with bile salt hydrophobicity or gallbladder wall inflammation score. In conclusion, UDCA treatment improves in vitro gallbladder contractility, possibly related to a reduced biliary cholesterol saturation. Increased fasting gallbladder volumes during UDCA treatment thus do not appear to result from decreased gallbladder muscle contractile strength.

Topics: Acetylcholine; Adult; Aged; Cholagogues and Choleretics; Cholecystokinin; Cholelithiasis; Cholesterol; Female; Gallbladder; Humans; In Vitro Techniques; Male; Middle Aged; Muscle Contraction; Ursodeoxycholic Acid

To study the presentation for and outcome of cholecystectomy in patients with acalculous gallbladder pain.. Sixty-six consecutive patients with prospective documentation underwent cholecystectomy for putative acalculous gallbladder pain between December 1988 to April 1995. The diagnosis was made on clinical grounds, but in the majority, a CCK oral cholecystogram was performed. Outcomes were assessed by postal questionnaire mailed in October 1995 or by the last recorded follow- up.. Fifty-eight females and eight males, with a median age of 37.5 years had experienced abdominal pain, usually with associated nausea, for a median of three years. Preoperative investigations were non-contributory, with the exception of the CCK oral cholecystogram which was regarded as abnormal in all instances. At a median follow-up of 40 months, 48 patients (72.7%) described their symptoms as either totally relieved or much improved by cholecystectomy.. Though the pathophysiology remains poorly understood, there is clearly a group of patients who suffer from gallbladder pain in the absence of gallstones and who benefit from cholecystectomy.

Topics: Adult; Aged; Cholecystectomy, Laparoscopic; Cholecystography; Cholecystokinin; Cholelithiasis; Colic; Diagnosis, Differential; Female; Follow-Up Studies; Gallbladder Diseases; Gallbladder Emptying; Gastrointestinal Agents; Humans; Male; Middle Aged; Nausea; Patient Satisfaction; Prospective Studies; Surveys and Questionnaires; Treatment Outcome

Hepatocyte growth factor (HGF) has unique morphogenic activity for several cell types. Besides its major effect upon liver regeneration, its motogenic activity to enhance motility has not been verified for smooth muscles. Therefore we evaluated the impact of HGF in an in-vitro model of human gallbladder motility. Twelve stone-diseased and eight stone-free muscle strips were preincubated with HGF (100 ng/ml, 200 ng/ml). For the analysis of motility, cholecystokinin (CCK) was added (0.1 nM, 0.5 nM, 2 nM, 10 nM, and 100 nM). Twelve stone-diseased and eight stone-free strips without HGF incubation served as the control group. The tone of healthy (tone/100 nM CCK: control group, 12.4 +/- 3.6 mN; HGF group, 19.5 +/- 4.5 mN) and stone-diseased (tone/100 nM CCK: control group, 10.8 +/- 3.8 mN; HGF group, 17.3 +/- 4.8 mN) muscle strips, preincubated with HGF, was increased, with a higher sensitivity to CCK. Our results suggest that there is a clear motogenic response of stone-diseased human gallbladders to HGF.

Topics: Cholecystokinin; Cholelithiasis; Gallbladder; Hepatocyte Growth Factor; Humans; In Vitro Techniques; Muscle, Smooth

Gallbladder contractility plays an important role in the pathogenesis of gallstones and in the course of cholelithiasis. Furthermore, a functioning gallbladder is an important condition for performing a successful disolution of gallstones by bile acids. Therefore, a reliable simple physiological test is desired to assess gallbladder contractility. In ten volunteers gallbladder contraction was stimulated by 50 g chocolate, 330 ml cacao drink or in comparison by intramuscular injection of 0.3 microgram/kg ceruletide. Gallbladder volume was measured sonographically and CCK in serum was determined by radioimmunoassay (RIA) after 0, 15, 30 and 45 min. Additionally gallbladder contraction was determined in 20 patients with symptomatic gallstones using cacao drink on ceruletide. In health volunteers remaining gallbladder volume after 30 min was 28% +/- 5% using ceruletide and 37% +/- 7% using cacao. Stimulation by chocolate resulted in a remaining volume of 59% +/- 12% after 45 min only. Simultaneously to gallbladder contraction an increase of CCK in serum was registered. 30 min after cacao CCK had increased from 0.9 to 3.3 pmol/l. Using chocolate an increase of CCK amounted to 2.1 pmol/l after 45 min only. In patients with gallstones the positive predictive value of the cacao test for a functioning gallbladder was 91% and the negative predictive value was 78% in comparison to the unphysiologic stimulation by ceruletide injection.. Cacao test but not chocolate is suitable and reliable to assess gallbladder contraction in patients with symptomatic gallstones.

Topics: Adult; Aged; Aged, 80 and over; Beverages; Cacao; Ceruletide; Cholecystokinin; Cholelithiasis; Female; Gallbladder Emptying; Humans; Injections, Intramuscular; Male; Middle Aged; Reference Values; Sensitivity and Specificity; Treatment Outcome

To investigate whether total body fat mass or fat distribution and associated metabolic disturbances in glucose and lipid metabolism influence the well known gallstone pathogenetic factors in obese subjects in order to explain why some obese subjects develop gallstones and some do not.. Cross sectional study of gallstone pathogenetic factors, body composition, fat distribution, glucose and lipid metabolism.. 57 healthy overweight subjects (aged 26-64y, body mass index (BMI) 30-45 kg/m2).. Total and intra-abdominal fat masses were measured by dual X-ray absorptiometry and abdominal CT scanning, respectively. The lithogenic index was measured in aspirated bile. The gallbladder volume was determined by ultrasound and the gallbladder ejection fraction% by dynamic cholescintigraphy. Plasma cholecystokinin (CCK) concentrations during a meal were measured with a specific radioimmunoassay. Insulin sensitivity was measured by the Minimal Model and glucose tolerance by an oral glucose tolerance test (OGTT). Serum lipid concentrations were measured by standard methods.. The gallbladder volume in the fasting state increased with increasing intra-abdominal fat mass (P=0.006) and was increased in subjects with impaired glucose tolerance (41 vs 27 ml, P=0.001). The lithogenic index was > 1 in all subjects and correlated with total fat mass (P=0.04).. Gallstone pathogenesis in obesity seems to be influenced by the total body fat mass and its regional distribution possibly via mutual association with the glucose tolerance.

Topics: Abdomen; Absorptiometry, Photon; Adipose Tissue; Adult; Blood Glucose; Body Composition; Cholecystokinin; Cholelithiasis; Cohort Studies; Cross-Sectional Studies; Dietary Fats; Fasting; Female; Gallbladder; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Lipids; Male; Middle Aged; Obesity; Tomography, X-Ray Computed

Cholelithiasis is a common disorder occurring in over 20 million people in the United States and resulting in approximately 600,000 cholecystectomies annually. Although over 95% of biliary tract disease is caused by gallstones, the vast majority (>80%) of cholelithiasis cases are asymptomatic. The purpose of this study is to evaluate the utility of quantitative cholescintigraphy in detecting symptomatic biliary tract disease and predicting clinical relief after cholecystectomy.. Fifty-two patients with clinical symptoms of chronic cholecystitis were evaluated by cholescintigraphy with a gallbladder ejection fraction calculated after the intravenous administration of cholecystokinin. A gallbladder ejection fraction of > or =35% was considered a normal physiologic response. Forty-one of the patients subsequently underwent cholecystectomy, whereas the remaining 11 subjects were diagnosed and treated for non-biliary disorders that did not require cholecystectomies. After clinical follow-up including histopathological gallbladder findings, all subjects' final diagnoses were established and correlated with their quantitative cholescintigram study.. Twenty-six of twenty-eight patients who had an abnormal quantitative cholescintigram demonstrated evidence of chronic cholecystitis by histopathologic criteria after cholecystectomy. Furthermore, 27 of these 28 patients (96%) experienced complete relief of their clinical symptoms after surgery.. Functional cholescintigraphy is a safe, accurate, and useful test for detecting symptomatic gallbladder disease, and appears reliable in predicting symptomatic relief after cholecystectomy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cholecystectomy; Cholecystitis; Cholecystokinin; Cholelithiasis; Chronic Disease; Female; Follow-Up Studies; Forecasting; Gallbladder; Gastrointestinal Agents; Humans; Injections, Intravenous; Male; Middle Aged; Muscle Contraction; Predictive Value of Tests; Radionuclide Imaging; Remission Induction; Reproducibility of Results; Safety; Sensitivity and Specificity

Topics: Abdominal Pain; Cholecystectomy; Cholecystokinin; Cholelithiasis; Humans; Predictive Value of Tests

The diagnosis of cholecystitis and cholelithiasis is often straightforward, particularly when transabdominal ultrasound (TUS) reveals gallstones or other abnormalities of the gallbladder. There remain many patients, however, with typical biliary pain and normal findings on TUS. This latter group of patients, in which women constitute a large majority, often undergo considerable suffering. Their medical care can also be quite costly. Cholecystokinin cholescintigraphy and stimulated biliary drainage (SBD) have been proposed for difficult-to-diagnose gallbladder disease, but they both have limitations. Cholecystokinin cholescintigraphy may not predict postoperative outcomes with a high degree of reliability. The processing and interpretation of bile drainage specimens is not standardized, and the sensitivity of SBD is less than that of endoscopic ultrasound (EUS). Combined endoscopic ultrasound and stimulated biliary drainage (EUS/SBD) offers a high degree of sensitivity in the diagnosis of cholecystitis and microlithiasis. Positive EUS/SBD is also highly correlated with long-term symptom resolution or relief following cholecystectomy.

Topics: Bile; Cholecystitis; Cholecystokinin; Cholelithiasis; Endosonography; Female; Gallbladder; Humans; Male; Radionuclide Imaging; Treatment Outcome

The aim of the present study was to elucidate the effect of gastric and duodenal transection on biliary manometry in anesthetized dogs. The basal biliary pressure and increase in pressure during saline perfusion at rates of 1.0 and 1.5 ml/min were studied in intact controls, during infusion of cholecystokinin (CCK) alone, and after gastric and duodenal transection. CCK dose-dependently lowered the basal pressure and the increase in pressure during perfusion. Gastric transection 1.5 cm proximal to the pylorus did not affect these parameters. In contrast, duodenal transection 1.0 cm distal to the pylorus significantly increased these parameters compared to all other groups. These observations suggest that the proximal duodenal transection, as performed during conventional distal gastrectomy, may contribute to the pathogenesis of postgastrectomy gallstone formation by altering motor function of the sphincter of Oddi.

Topics: Animals; Cholecystokinin; Cholelithiasis; Dogs; Dose-Response Relationship, Drug; Duodenum; Gastrectomy; Manometry; Pressure; Sphincter of Oddi

Total parenteral nutrition (TPN) is associated with cholestasis and gallstones. Gallbladder stasis may be important in the development of gallstones, and cholecystokinin (CCK) to stimulate gallbladder contraction has been proposed as a treatment to prevent this complication. We studied in vivo bile acid synthesis and bile acid output in miniswine on TPN to test whether daily CCK improves bile acid output and normalizes bile acid profiles with TPN. Nine miniswine were nutritionally maintained with TPN for 4 weeks; four pigs received CCK (0.1 mg/kg) iv daily. In vivo bile acid synthesis was measured with injection of 7 alpha-tritiated cholesterol. An increase in tritiated water reflects the activity of 7 alpha-hydroxylation, the rate-limiting step in bile acid synthesis. At the end of 4 weeks, bile was collected and bile acid output and bile salt profiles were determined. One of five animals on TPN developed gallstones while two of four receiving daily CCK developed stones. In vivo bile acid synthesis decreased with TPN (controls, 63 +/- 9 mg/24 hr versus TPN, 13 +/- 4 mg/24 hr) and increased in TPN animals with CCK treatment (TPN-CCK, 105 +/- 35 mg/24 hr). Bile acid profiles are changed with TPN with more secondary bile acids, this was not improved with CCK. CCK improved bile acid synthesis and bile acid output but failed to prevent gallstone formation or normalize bile salt profiles. In addition to promoting gallbladder contraction, CCK may have a stimulatory effect on bile acid synthesis. CCK alone did not prevent gallstone formation.

Topics: Animals; Bile Acids and Salts; Cholecystokinin; Cholelithiasis; Parenteral Nutrition; Swine

Recent studies have shown that cholecystokinin (CCK) is involved in the induction and development of acute pancreatitis in experimental animals. In the present study we determined basal plasma CCK concentrations by a specific and sensitive radioimmunoassay using antiserum OAL656 in 17 patients with acute pancreatitis due to gallstone in the common bile duct (n = 7), alcoholic (n = 4), post endoscopic retrograde pancreatography (n = 1), and unknown causes (n = 4), and 37 patients with cholelithiasis (n = 18) and choledocholithiasis (n = 19). Plasma CCK concentrations in patients with gallstone pancreatitis on hospital day 1 (mean +/- SEM, 6.78 +/- 1.39 pM) were significantly higher than those in patients with other causes (1.33 +/- 0.16 pM) or in 20 healthy control subjects (1.55 +/- 0.11 pM). There was no relationship between plasma CCK and serum pancreatic enzyme levels, the severity of acute pancreatitis, or serum bilirubin concentrations. Plasma CCK levels in patients with acute symptomatic cholelithiasis (n = 7; 4.35 +/- 0.90 pM) and choledocholithiasis (n = 8; 4.52 +/- 1.17 pM) were significantly higher than those in patients without symptoms (cholelithiasis, n = 11, 1.40 +/- 0.17 pM; choledocholithiasis, n = 11, 1.88 +/- 0.49 pM) but tended to be lower than those in patients with gallstone pancreatitis. These present observations suggest that the increase in plasma CCK levels in gallstone pancreatitis appears not to be the cause but to be the result of gallstone pancreatitis probably due to a transient disturbance of bile flow into the duodenum by stones or edema of the bile duct. Our present results provide some evidence for the usefulness of CCK receptor antagonists for the treatment of biliary colics and acute pancreatitis.

Topics: Acute Disease; Adult; Aged; Bilirubin; Case-Control Studies; Cholecystokinin; Cholelithiasis; Female; Gallstones; Hormone Antagonists; Humans; Male; Middle Aged; Pancreatitis; Receptors, Cholecystokinin; Reference Values

Smooth muscle from gallbladders with cholesterol stones exhibits impaired response to cholecystokinin (CCK). This study investigated whether the impaired response is mediated by different signal-transduction pathways responsible for CCK-induced contraction in prairie dog and human gallbladders with cholesterol stones. Gallbladder muscle cells were isolated enzymatically to study contraction. Protein kinase C (PKC) activity was measured by examining the phosphorylation of a specific substrate peptide from myelin basic protein Ac-MBP-(4-14). Gallbladder muscle cells from high-cholesterol-fed prairie dogs contracted less in response to CCK octapeptide (CCK-8) than those from the control group. However, inositol-1,4,5-trisphosphate (IP3), diacylglycerol, and guanosine 5'-O-(3-thiotriphosphate) induced the same magnitudes of contraction in these two groups. In control prairie dog and human gallbladders, the maximal contraction caused by 10(-8) M CCK-8 was blocked by the calmodulin antagonist CGS9343B but not by the PKC inhibitor H-7. Conversely, in gallbladders with cholesterol stones from prairie dogs or human patients, the maximal contraction induced by 10(-8) M CCK-8 was blocked by H-7 and chelerythrine but not by CGS9343B. In these gallbladders CCK-8 caused a significant PKC translocation from the cytosol to the membrane. High CCK concentrations may activate the calmodulin-dependent pathway in functionally normal gallbladder muscle and the PKC-dependent pathway in muscle from gallbladders with cholesterol stones. The defect of gallbladder muscle after cholesterol feeding and stones might reside in the steps before G protein activation.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Alkaloids; Animals; Benzimidazoles; Benzophenanthridines; Biological Transport; Calmodulin; Cholecystokinin; Cholelithiasis; Enzyme Inhibitors; Gallbladder; Humans; Male; Muscle Contraction; Muscle, Smooth; Phenanthridines; Protein Kinase C; Reference Values; Sciuridae; Sincalide

The aim of the present study was to investigate in human subjects whether or not the ingestion of two liquid meals that differed only in their fatty acid composition (due to the addition of olive oil (group O) or sunflowerseed oil (group S) as the source of dietary fat) would lead to differences in the pancreatic enzyme activities secreted into the duodenum. The experiments were performed in eighteen cholecystectomized subjects who, during the 30 d period immediately before surgery, modified their habitual diets in such a way that their fat composition would reflect, as far as possible, that of the experimental meals. Lipase (EC 3.1.1.3), colipase, amylase (EC 3.2.1.1), chymotrypsin (EC 3.4.21.1) and trypsin (EC 3.4.21.4) activities were measured in duodenal contents aspirated before and after the ingestion of the test meals. The plasma levels of secretin and cholecystokinin (CCK) were also examined. Duodenal enzyme activities were similar in resting conditions. No significant differences were revealed in postprandial enzyme activities, except for lipase activity, which was higher in group O, probably in relation to the greater plasma CCK concentrations observed in this group. In the absence of enzyme output data, we should not exclude the possibility that the type of dietary fat will affect human pancreatic enzyme secretion to a greater extent than is evident from the present study, for instance through a flow-mediated effect, as we previously observed in dogs.

Topics: Amylases; Cholecystokinin; Cholelithiasis; Chymotrypsin; Colipases; Dietary Fats, Unsaturated; Humans; Lipase; Olive Oil; Pancreas; Peptide Hydrolases; Plant Oils; Secretin; Sunflower Oil; Trypsin

Gall bladder and sphincter of Oddi (SO) function are coordinated by hormonal and neuronal mechanisms. Nerve fibres pass between the gall bladder and the SO via the cystic duct. It is therefore possible that cholecystectomy may alter SO motility.. To investigate the effect of cholecystectomy on SO function.. SO manometry was performed in five women (median age 52 years), a few days before and six months after laparoscopic cholecystectomy which was undertaken for uncomplicated cholelithiasis. Basal and post-cholecystokinin (CCK) SO motility were measured.. All patients were symptom free after laparoscopic cholecystectomy. Prior to surgery common bile duct pressure, and tonic and phasic SO motility were normal and phasic contractions were inhibited by intravenous CCK (1 Ivy Dog Unit/kg). Six months later, common bile duct pressure and baseline tonic and phasic activity were unchanged but CCK failed to suppress phasic activity.. Cholecystectomy, at least in the short term, suppresses the normal inhibitory effect of pharmacological doses of CCK on the SO. The mechanism of this effect is unknown but it could be due to SO denervation.

Topics: Adult; Cholecystectomy, Laparoscopic; Cholecystokinin; Cholelithiasis; Female; Follow-Up Studies; Humans; Manometry; Middle Aged; Sphincter of Oddi

This study was designed to investigate the effect of cholestyramine on the formation of pigment gallstones in high carbohydrate diet-fed hamsters and whether that effect occurred because of cholecystokinin action. Forty seven hamsters were divided into three groups: group I(n = 16) was fed on normal rodent chow(43% carbohydrate), group II(n = 14) was fed on a high CHO diet(65% carbohydrate), group III(n = 17) was fed on a high CHO diet containing 4% cholestyramine. Gallstones developed in 0% of group I, 42.9% of group II and 5.9% of group III(P < 0.05, group II vs III). To evaluate the chronic status of cholecystokinin level, the wet weight of pancreas and the average area of pancreatic acinar in microscopic high power field were measured. There was no significant difference between group II and group III in pancreatic weight and average area of pancreatic acinar(P > 0.05). In gallbladder bile analysis, there was also no significant difference between group II and group III in cholesterol, phospholipid, total calcium, total bilirubin and bile acid levels. In conclusion, cholestyramine decreases the frequency of pigment gallstone formation in high CHO diet-fed hamsters, but it is not clear whether the mechanism of cholestyramine decreasing the gallstone formation is due to the action of cholecystokinin.

Topics: Animals; Bilirubin; Cholecystokinin; Cholelithiasis; Cholesterol; Cholestyramine Resin; Cricetinae; Dietary Carbohydrates; Female; Gallbladder; Male; Mesocricetus; Organ Size; Pancreas; Phospholipids; Pigmentation

Human gallbladders were used to investigate the mechanisms of the impaired contraction induced by cholecystokinin (CCK) associated with cholesterol stones. Single muscle cells were isolated enzymatically with collagenase. Inositol 1,4,5-trisphosphate was measured by high-performance liquid chromatography. Diacylglycerol was assayed by thin-layer chromatography. CCK stimulation showed decreased muscle contraction and production of inositol 1,4,5-trisphosphate and diacylglycerol in gallbladders with cholesterol stones compared with those with pigment stones. Exogenous calmodulin induced maximal contraction of 22.4 +/- 0.5 and 21.0 +/- 0.6% in gallbladders with cholesterol and pigment stones, respectively. Similar findings were observed with a synthetic diacylglycerol analogue. Two G protein activators, aluminum fluoride and guanosine 5'-O-(3-thiotriphosphate), evoked similar responses in these two types of gallbladders, with maximal contractions of 21.3 +/- 0.4 and 23.3 +/- 0.5%, respectively, in those with cholesterol stones and 20.9 +/- 0.8 and 22.6 +/- 0.4%, respectively, in those with pigment stones. These results suggest that receptor-dependent ligands like CCK cannot fully activate the intracellular pathways, which, however, can be fully stimulated by circumventing receptors with G protein activators or second messengers. After G protein activation, the pathways appear to be functionally intact. The defect might then reside in the receptor or in the interaction between receptors and G proteins.

Topics: Aluminum Compounds; Calmodulin; Cholecystokinin; Cholelithiasis; Cholesterol; Diglycerides; Dose-Response Relationship, Drug; Female; Fluorides; Gallbladder; GTP-Binding Proteins; Guanosine 5'-O-(3-Thiotriphosphate); Humans; Inositol 1,4,5-Trisphosphate; Male; Middle Aged; Muscle Contraction; Signal Transduction; Sincalide

The main aim of our study was the investigation of gallbladder motility prior to gallstone formation in vivo in guinea pigs fed a lithogenic diet. In a first experiment guinea pigs were fed a lithogenic diet for 5, 15, 30 and 45 days. First gallstones (pigment calculi) appeared after 30 days diet application. The in vitro contractility after lithogenic diet remained unchanged. In a second experimental part the in vivo gallbladder contractility was measured in two experimental animal groups (control group and 21 days lithogenic fed guinea pigs). The isovolumetric pressure rise inside the gallbladder following the intravenous injection of 10(-9) mol/kg body weight ceruletid was the essential contractility parameter (intraluminal basal pressure 5 mm hg). Due to lithogenic feeding of 21 days--that means prior to gallstone formation--the isovolumetric pressure rise was significantly elevated (p < 0.01). Moreover we observed passive distensibility changes of gallbladder muscle due to muscular hyperplasia. The main result of this investigation is the fact that gallbladder muscle in guinea pigs fed a lithogenic diet response to ceruletid application with hypercontractility prior to provable pigment gallstone formation. However gallbladder hypomotility--believed to be a causal factor in cholelithogenesis--was not observed in our experimental conditions.

Topics: Animals; Biliary Dyskinesia; Ceruletide; Cholecystokinin; Cholelithiasis; Cholesterol, Dietary; Disease Models, Animal; Female; Gallbladder Emptying; Guinea Pigs; Muscle Contraction; Muscle, Smooth

Impaired gallbladder emptying is a pathogenetic factor in gallstone formation. To test whether gallbladder motility can be improved by high-dose cholecystokinin (CCK), gallbladder emptying was measured sonographically in 21 patients with cholesterol gallstone disease and 6 healthy controls.. The effects of CCK infusions of 0.06 IDU/kg.min (group A, n = 11) and 0.12 IDU/kg.min (group B, n = 10) were compared with the response to a standard CCK infusion (0.02 IDU/kg.min). Controls received CCK at all infusion rates.. The ejection fraction was smaller after CCK infusion of 0.06 IDU/kg.min than after the standard stimulus (group A, 52 +/- 10 versus 64 +/- 10%, p < 0.05; controls, 66 +/- 10 versus 91 +/- 3%, p < 0.05). After infusion of 0.12 IDU/kg.min CCK ejection fractions decreased even more (group B, 44 +/- 16 versus 65 +/- 12%, p < 0.05; controls, 54 +/- 12 versus 91 +/- 3%, p < 0.05). High-dose CCK infusions shortened the ejection period markedly, whereas the ejection rate remained unaltered.. High-dose CCK does not improve gallbladder motility but blocks the ejection process early, leading to reduced gallbladder emptying in gallstone patients and healthy subjects.

Topics: Case-Control Studies; Cholecystokinin; Cholelithiasis; Cholesterol; Female; Gallbladder; Gallbladder Emptying; Humans; Infusions, Intravenous; Male; Middle Aged; Ultrasonography

Gallstone formation is frequently seen following gastric surgery. Since dysmotility and bile stasis of the gallbladder is considered as an important factor in the pathogenesis of gallstone formation, altered gallbladder motility due to gastric surgery may have a role in the development of post-gastrectomy gallstone formation. To test this hypothesis, the effect of distal partial gastrectomy on gallbladder motility were studied. Gastroduodenal and gallbladder contractions were recorded by chronically implanted strain gauge transducers under conscious state. Gallbladder volume changes were monitored using chronically indwelling gallbladder catheter. Fasted and fed motility were studied in control (n = 5) and gastrectomized (n = 3) dogs. Plasma concentration of putative hormone CCK was measured. Effect of CCK-OP and motilin on gallbladder emptying were also studied. In fasted state, gallbladder volume was periodically decreased synchronous with phase 3 of interdigestive migrating contractions (IMC) in the gastroduodenum in both group of dogs. The correlation between gastric and gallbladder contractions was preserved even following distal partial gastrectomy, though the frequency of phasic contractions during phase 3 of IMC was decreased in the gastrectomized dogs. Postprandial gallbladder emptying tend to decreased in the gastrectomized dogs, while there were no difference in the postprandial plasma CCK concentrations and CCK-OP induced gallbladder emptying between groups. Digestive period was shortened in the gastrectomized dogs, which resulted in early gallbladder refilling and prolonged interdigestive period. Decreased frequency of gallbladder phasic contractions during IMC and prolonged interdigestive period could cause bile stasis in the gallbladder, which may, in part, explain post-gastrectomy gallbladder formation.

Topics: Animals; Cholecystokinin; Cholelithiasis; Dogs; Gallbladder Emptying; Gastrectomy; Motilin

The search for cholesterol crystals in the bile, drawn during the endoscopy, represents a simple and reliable method in the diagnosis of the symptomatic biliary sludge. In our patients it was present in 82% of the cases. The injection of cholecystokinin appears to us absolutely necessary in order to obtain vesicular bile. The sensitiveness of abdominal sonography in the diagnosis of biliary sludge is weak, 13% of our cases. The clinical evolution with ursodeoxycholic acid treatment has been favourable in 83% of the treated patients.

Topics: Adult; Bile; Cholecystokinin; Cholelithiasis; Cholesterol; Duodenoscopy; Female; Humans; Male; Sensitivity and Specificity; Ultrasonography

Studies in humans and rodents indicate that gallstone development may be prevented by inhibiting gallbladder mucus hypersecretion with non-steroidal anti-inflammatory drugs or by preventing stasis of gallbladder bile with administration of cholecystokinin.. The effect of oral aspirin and pancreaticobiliary diversion with endogenous hypercholecystokininemia on crystal and gallstone formation was studied in Syrian golden hamsters fed a lithogenic diet for 8 weeks.. None of the control animals fed a normal diet developed gallstones or crystals in gallbladder bile. Gallstones developed in 67% of the animals fed a lithogenic diet only. The gallstone prevalence did not differ significantly in animals on a lithogenic diet and a daily aspirin dose of 6 mg/kg (gallstone prevalence, 60%) or 100 mg/kg (gallstone prevalence, 70%), whereas it was significantly lower in animals with endogenous hypercholecystokininemia on a lithogenic diet (gallstone prevalence, 29%). The prevalence of crystals in gallbladder bile did not differ significantly between any of the experimental groups.. It is concluded that in hamsters on a lithogenic diet, aspirin does not prevent gallstone formation, whereas endogenous hypercholecystokininemia reduces the prevalence of stones without affecting the occurrence of crystals in gallbladder bile.

Topics: Animals; Aspirin; Biliopancreatic Diversion; Cholecystokinin; Cholelithiasis; Cricetinae; Diet; Male; Mesocricetus

The present study investigated endogenous postprandial release of cholecystokinin (CCK) and pancreatic polypeptide (PP) in relation to gallbladder dynamics in healthy subjects and patients with gallstones.. Gallbladder volume (by ultrasonography) and plasma concentrations of CCK and PP (by radioimmunoassay) were evaluated in 18 patients with gallstones and 14 healthy controls before and after administration of a semi-liquid test meal (250 ml, 1450 kJ). Gallbladder contractility was previously assessed on a separate day by intravenous infusion of ceruletide (2.5 ng/kg/min).. Basal gallbladder volume was not different in patients (32 +/- 5.9 cm3) and controls (26 +/- 2.7 cm3). Postprandial gallbladder contractility was impaired in gallstone patients, who showed a reduced integrated response (-3718 +/- 349 vs. -5251 +/- 376 cm3/2 h, p < 0.01) and a delayed time to maximal gallbladder contraction (67 +/- 7.4 min vs. 37 +/- 2.4 min, p < 0.002). Maximal gallbladder contraction after ceruletide infusion was also reduced (44.1 +/- 5.0% vs. 72.5 +/- 3.2%, p < 0.001), but not delayed (15.8 +/- 2.4 vs. 15.7 +/- 1.4 min) in gallstone patients. Basal CCK and PP plasma levels were similar in both groups. Postprandial CCK release was impaired in gallstone patients, predominantly due to a decreased response over the first 30 min (3.8 +/- 1.8 vs. 20.0 +/- 4.9 pmol/L/30 min, p < 0.005). Postprandial PP release was not different between groups. A direct linear correlation between postprandial release of CCK and PP was found in healthy controls but not in patients with gallstones. Postprandial gallbladder volume at any moment was inversely correlated with CCK plasma levels in healthy subjects, but not in gallstone patients. No correlation between postprandial PP response and gallbladder dynamics was observed.. Based on a multivariate logistic approach, a reduced and delayed postprandial gallbladder contractility and an impaired CCK release in the early postprandial phase are significantly associated with gallstone disease. Our data provide further evidence for the predominant role of endogenous postprandial CCK release in gallbladder contraction. A role for PP in modulating postprandial gallbladder dynamics is not supported.

Topics: Cholecystokinin; Cholelithiasis; Female; Food; Gallbladder; Gallbladder Emptying; Humans; Male; Middle Aged; Multivariate Analysis; Pancreatic Polypeptide; Time Factors; Ultrasonography

This study describes the influence of endogenous and exogenous prostaglandins upon CCK-induced motility patterns of human gallbladders with and without stones (indomethacin and nocloprost; an exogenous PGE2-analogon). From 48 gallbladders with- and 22 gallbladders without stones (control group) longitudinal muscle stripes were dissected and transferred to an organ bath and CCK, indomethacin and nocloprost dose response curves were established. In another experimental protocol, the effect of CCK after indomethacin or nocloprost preincubation is demonstrated. Moreover, specimens of gallbladders were taken for histology and gallstones for analyse. The results demonstrate that gallbladders with stones have a significant higher basic tonus and phasic activities compared to the stone-free controls. Because of these different responses to CCK, gallbladders of the stone-diseased group were divided in two groups: 64% of the gallbladders show a sensitivity and tonic response to CCK like the controls (contractors), 36% demonstrate a reduced sensitivity to CCK and only a slight tonic response (non-contractors). Indomethacin causes a fall in tonus in both stone-diseased groups. It stops spontaneous activity in the contractor and non-contractor group. With indomethacin preincubation all three groups response to CCK with a significant reduced sensitivity. CCK-induced activity is reduced in the control and contractor group. In the non-contractor group, muscle strips do not contract after indomethacin preincubation. Nocloprost induces significant contractions in the control and contractor group. In both groups, the response to CCK after nocloprost preincubation is stronger than the reaction without preincubation. In the non-contractor group, a change in tonus after nocloprost application cannot be demonstrated, there also is no response to CCK after nocloprost preincubation. These results corroborate the notion of a significant contribution of the endogenous prostaglandin system to the regulation of gallbladder motility by CCK.

Topics: Adult; Aged; Aged, 80 and over; Cholecystokinin; Cholelithiasis; Culture Techniques; Dose-Response Relationship, Drug; Female; Gallbladder Emptying; Humans; Indomethacin; Male; Middle Aged; Muscle Contraction; Muscle, Smooth; Prostaglandins; Prostaglandins F, Synthetic; Sincalide; Vasodilator Agents

The usual technique of collecting gallbladder bile at laparotomy is not suitable for sequential studies of cholesterol nucleation time (NT) in patients receiving therapy to prevent or dissolve cholesterol gallstones. Our aim was to study the feasibility of measuring NT in bile obtained by nasobiliary or nasoduodenal intubation. We studied a total of 10 cholesterol gallstone patients; in 8 bile was collected by nasobiliary drainage, in 7 it was collected by nasoduodenal intubation, and in 3 it was collected at laparotomy the next day. Three patients developed abdominal pain and increased serum amylase after endoscopic retrograde cannulation. All three biles obtained at operation nucleated quickly (NT, 1-4 days), whereas duodenal biles were all beyond the expected range (NT, > 21 days). Chymotrypsin activity, as a marker of pancreatic juice contamination, was detected in five of eight nasobiliary biles and in all seven duodenal biles but in none of the surgical biles. Free fatty acids (reflecting lipolysis) were significantly higher in duodenal than in surgical biles, with nasobiliary bile showing intermediate values. Nasobiliary bile showed either a rapid (median NT, 3 days) or a slow (median NT, 22 days) NT, depending on whether chymotrypsin activity was absent or present (p < 0.05). We conclude that duodenal bile is never suitable for NT determination because of contamination by pancreatic enzymes, and that nasobiliary bile, if not contaminated by pancreatic enzymes, may be suitable for NT determination but that its collection via a nasobiliary tube after cholecystokinin injection carries a risk of pancreatitis.

Topics: Adolescent; Adult; Aged; Bile; Cholecystokinin; Cholelithiasis; Cholesterol; Crystallization; Drainage; Female; Humans; Intubation; Male; Middle Aged; Pancreatitis; Specimen Handling; Time Factors

To evaluate whether the extent of postprandial gall bladder emptying is correlated with gall bladder fasting volume, gall bladder motility was studied in 56 patients with cholesterol gall stone and 19 control patients. Gall bladder volumes were determined sonographically, while cholecystokinin plasma values were measured radioimmunologically. Twenty three per cent of gall stone patients were classified as pathological contractors (residual fraction > mean +2SD of controls) and 77% as normal contractors. Normal but not pathological contractor patients exhibited larger gall bladder fasting volumes (mean (SEM)) (24.7 (1.7) ml) than controls (15.3 (1.2) ml, p < 0.001). In normal contractor patients and controls fasting volume was closely related with ejection volume (r = 0.97, p < 0.001) and residual volume (r = 0.80, p < 0.001). Although ejection volume was enlarged in normal contractor patients it did not compensate the increase in fasting volume. Thus, residual volumes were considerably increased not only in pathological contractors (12.7 (2.5) ml, p < 0.001) but also in normal contractor patients (7.0 (0.5) v 4.6 (0.6) ml, p < 0.001). Postprandial cholecystokinin secretion did not differ between patients and controls. It is concluded, that in normal contractor patients gall bladder fasting volume is closely correlated with ejection and residual volume. Thus, fasting volume may be an essential factor affecting postprandial gall bladder emptying. Large fasting volumes in cholesterol gall stone disease could thereby contribute to bile retention, which facilitates gall stone growth.

Topics: Adult; Cholecystokinin; Cholelithiasis; Fasting; Female; Food; Gallbladder; Gallbladder Emptying; Humans; Male; Middle Aged

The hepatic secretion of supersaturated bile and gallbladder stasis are key events in cholesterol gallstone formation. The therapeutic value of cisapride, a prokinetic agent, was assessed in ground squirrels on a 1% cholesterol diet.. Biliary lipid secretion was measured directly and bile salt pool size assessed by isotope dilution ([14C]cholic acid). Gallbladder contraction was measured in vitro in response to cholecystokinin (CCK).. Cholesterol-fed animals had a combined hepatic secretory defect (a 53% decrease in bile salt secretion and also a 31% increase in cholesterol secretion). Adding cisapride restored bile salt secretion to control levels but did not affect cholesterol secretion. In cholesterol-fed animals, the cholesterol saturation index of gallbladder bile more than doubled and cholesterol crystals developed; cisapride markedly reduced cholesterol saturation, thus preventing crystal formation. Gallbladder contractility, measured in vitro in response to CCK, decreased 23% in animals on the 1% cholesterol diet; cisapride restored the CCK dose-response curve to normal. The bile salt pool as assessed by isotope dilution was similar in all groups.. Thus, lithogenic bile develops in this model because of reduced bile salt secretion and increased cholesterol secretion. Cisapride renders biliary lipid composition towards normal by enhancing gallbladder (and possibly intestinal) motility and cycling of the bile salt pool, thereby increasing bile salt secretion.

Topics: Animals; Bile; Bile Acids and Salts; Carbon Radioisotopes; Cholecystokinin; Cholelithiasis; Cholesterol, Dietary; Cholic Acids; Cisapride; Disease Models, Animal; Dose-Response Relationship, Drug; Gallbladder; Gallbladder Diseases; Gallbladder Emptying; Lipid Metabolism; Lipids; Male; Piperidines; Sciuridae; Serotonin Antagonists

To further elucidate the mechanism of impaired gallbladder emptying in diabetics with and without neuropathy, gallbladder function was assessed by ultrasonography following a medium-chain triglyceride (lipomul, 1.5 mg/kg) infusion into the duodenum and compared to that during intravenous infusion of cholecystokinin in diabetic women. Results were compared with five healthy control women. Mean (+/- SD) maximal percent gallbladder volume in diabetics following lipomul was reduced to 49 +/- 8% and after intravenous cholecystokinin to 47 +/- 9%, which was less than those in controls, 21 +/- 9% and 24 +/- 6%, respectively, but not significantly different. Further analysis of gallbladder emptying to lipomul differentiated two subgroups of diabetics: one subgroup (N = 5) had emptying comparable to controls (responders), while the other (N = 5) had very modest emptying (nonresponders). Two of the patients in the latter group had normal gallbladder emptying during exogenous cholecystokinin and their response would be compatible with visceral neuropathy. Blood levels of cholecystokinin, measured by bioassay, following lipomul and exogenous cholecystokinin were similar in controls and diabetics. Presence of diabetic neuropathy did not correlate with impaired gallbladder emptying. Follow up at 6 and 12 months of the three nonresponder diabetics revealed that no gallstones had developed and that two of them became responders to exogenous cholecystokinin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Autonomic Nervous System Diseases; Cholecystokinin; Cholelithiasis; Corn Oil; Diabetes Mellitus; Diabetic Neuropathies; Female; Follow-Up Studies; Gallbladder; Gallbladder Emptying; Humans

The role of gallbladder emptying in fragment disappearance following shock wave lithotripsy of gallstones is poorly understood. We studied gallbladder motility in two groups of patients who had been treated by electrohydraulic shock wave lithotripsy and bile acid dissolution therapy. Group I (n = 20) consisted of patients with fragment disappearance within 18 months after lithotripsy, while patients in group II (n = 20) still harboured fragments in the gallbladder 18 months after lithotripsy. Fasting gallbladder volume was 19 +/- 10 ml (mean +/- S.D.) in group I, and 24 +/- 12 ml in group II (not significant). The residual volume was 8 +/- 9 ml in group I, but 18 +/- 14 ml in group II (p < 0.005). Thus, patients in group I ejected nearly twice as much of the fasting gallbladder volume as patients in group II. This difference in gallbladder emptying was still present if only the patients with single stones were compared in both groups. From the results of this retrospective study we conclude that gallbladder emptying is an important factor for complete fragment disappearance after gallstone disintegration by extracorporeally generated shock waves. Further prospective studies are needed to confirm these observations.

Topics: Adult; Cholecystokinin; Cholelithiasis; Female; Follow-Up Studies; Gallbladder Emptying; Humans; Lithotripsy; Male; Middle Aged; Time Factors

Topics: Cholecystokinin; Cholelithiasis; Dietary Fats; Gallbladder; Humans; Muscle Contraction; Obesity

Five out of forty-five adult men, 50 years of age or less, who had received, for at least six months, medroxyprogesterone acetate (MPA, Depo Provera) IM, 200-400 mg/week, for prevention of sex-offending or genital-mutilating behavior developed symptomatic cholelithiasis. Thirty of these men were studied with gallbladder ultrasound prospectively off MPA and at six-month intervals while taking the medication and then six months off MPA. Gallstones recovered from two patients were found to have very high cholesterol content, suggesting they were formed in cholesterol supersaturated bile. These findings are consistent with the increased incidence of gallbladder disease related to high-progesterone states and suggest that MPA may be a causative agent in cholelithiasis. The physiologic studies on gallbladder contraction and cholecystokinin release in a subset of the patients failed to provide information on a mechanism for the possible increased incidence of gallbladder disease.

Topics: Adult; Cholecystokinin; Cholelithiasis; Corn Oil; Gallbladder; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Middle Aged; Prospective Studies; Sex Offenses; Testosterone

Because fatty acid composition of biliary phospholipids influences cholesterol secretion into bile, we investigated whether replacement of n-1 monounsaturated or n-6 polyunsaturated fatty acids with n-3 polyunsaturated fatty acids in biliary phosphatidylcholines reduces supersaturation with cholesterol and prevents precipitation of cholesterol crystals in bile of gallstone patients. Seven patients with radiolucent gallstones in functioning gallbladders were studied before (control) and after 5 wk of dietary supplementation with marine fish oil (11.3 gm/day = 3.75 gm n-3 polyunsaturated fatty acids/day). Duodenal bile was collected for analysis during intravenous infusion of cholecystokinin. Gallbladder emptying in response to cholecystokinin was comparable before and during intake of n-3 polyunsaturated fatty acids. Intake of n-3 polyunsaturated fatty acids increased (p less than 0.001) the fractions of eicosapentaenoic and docosahexaenoic acids and decreased the fractions of linoleic (p less than 0.001) and arachidonic acids (p less than 0.02) in biliary phospholipids. Concomitantly, the molar ratio of cholesterol to phospholipids decreased (-19%; p less than 0.05). As a consequence, the cholesterol saturation index was reduced by -25% (p = 0.01), from 1.60 +/- 0.44 to 1.24 +/- 0.38. However, in vitro nucleation time of duodenal bile was not prolonged. The decrease in cholesterol saturation was not sufficient to prevent nucleation of cholesterol crystals in bile of gallstone patients. In conclusion, our data suggest that cholesterol saturation can be influenced by the fatty acid composition of the phosphatidylcholines secreted in bile.

Topics: Adult; Bile; Bile Acids and Salts; Cholecystokinin; Cholelithiasis; Cholesterol; Crystallization; Dietary Fats; Fatty Acids, Unsaturated; Female; Fish Oils; Gallbladder Emptying; Humans; Lipids; Male; Middle Aged; Phospholipids

The purpose of this study was to measure differences in gallbladder sensitivity to cholecystokinin (CCK) in vivo during the early stages of gallstone formation and to correlate these findings to gallbladder CCK receptors. Guinea pigs were placed on either a normal diet or a two-week cholelithogenic diet, after which gallbladder emptying pressure to exogenously administered CCK was measured in vivo, according to the presence or absence of gallstones. At all doses of CCK tested (except 10(-10) mol/kg), the gallbladder response to CCK of guinea pigs that did not develop gallstones (on the cholelithogenic diet) was more sensitive than that of guinea pigs that did develop gallstones. Neither group was different from guinea pigs on a normal diet. In a second experiment, CCK receptors were measured on gallbladder muscularis from guinea pigs after two weeks on the same diet as in the first experiment. Those guinea pigs that did not develop gallstones had greater concentrations of CCK receptors (149 +/- 9 fmol/mg protein) than those that did develop gallstones (70 +/- 23 fmol/mg protein). Neither group was different from normal diet guinea pigs (119 +/- 57 fmol/mg protein). At the time point measured, there were no differences in the lipid chemistry or protein concentrations of gallbladder bile between the guinea pigs on the cholelithogenic diet that did or did not develop gallstones, or those on normal guinea pig chow. We conclude that the early stages of gallstone formation in guinea pigs are associated with decreased gallbladder sensitivity to CCK and that this change may be due to a lower concentration of CCK receptors on the gallbladder smooth muscle.

Topics: Animals; Bile; Cholecystokinin; Cholelithiasis; Diet; Gallbladder; Gallbladder Emptying; Guinea Pigs; Male; Mucous Membrane; Receptors, Cholecystokinin; Time Factors

Since abnormal gallbladder emptying may be a contributing factor in the development of gallstone disease, we determined fasting gallbladder volume and postprandial contraction in 20 gallstone patients and 20 normal subjects with the aid of ultrasonography. Moreover, basal plasma cholecystokinin levels and postprandial cholecystokinin (CCK) release were determined. Gallstone patients were divided into strong contractors (13 pts) and weak contractors (below 95% confidence interval for AUC contraction in % during 90 min: 7 pts). Strong contractor patients had significantly larger mean fasting volumes than normal subjects (mean +/- S.E.: 34.9 +/- 6.1 ml and 18.9 +/- 1.6 ml, respectively). This was not true for weak contractor patients (mean fasting volume 23.2 +/- 3.2 ml). Both strong contractor and weak contractor patients had significantly higher mean residual volumes than normal subjects (17.0 +/- 4.1 ml, 18.0 +/- 2.9 ml, and 8.8 +/- 1.1 ml, respectively). Absolute gallbladder emptying was significantly higher for strong contractor patients than for normal subjects, but relative emptying was the same. Opposite patterns of CCK release occurred in gallstone patients and normal subjects. In normal subjects, more CCK release was associated with stronger gallbladder emptying. In contrast, weak contractor gallstone patients had significantly higher CCK release than strong contractor patients. (AUC CCK: 304 +/- 89 pmol/l x 90 min and 106 +/- 29 pmol/l x 90 min, respectively). The present study indicates that strong contractor gallstone patients may have large residual gallbladder volumes due to large starting volumes, whereas weak contractor patients may have large residual volumes due to impaired contraction. Subjects with large fasting and residual volumes may be at increased risk for gallstone disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Cholecystokinin; Cholelithiasis; Eating; Fasting; Female; Gallbladder; Gastric Emptying; Humans; Male; Middle Aged; Muscle Contraction; Muscle, Smooth; Reference Values; Ultrasonography

Data about gallbladder motility in stone disease and stone free conditions are discussed controversially. This study is aimed at to evaluate in vitro the responses of human gallbladder muscle stripes to cholecystokinin, motilin and neurotensin. Following the results, a stratification of the "stone-disease-group" seems to be necessary: 41% of the gallbladders (stone disease) demonstrate a deep reduction in contractility to cholecystokinin ("non-contractors"), whereas 59% of the gallbladders contract in the same pattern like the controls ("contractors"). Interestingly, the majority of the gallbladders in the "contractor" group demonstrate a high spontaneous activity which is absent in stone free gallbladders. Motilin and neurotensin either do not induce any effect.

Topics: Adult; Aged; Aged, 80 and over; Cholecystokinin; Cholelithiasis; Dose-Response Relationship, Drug; Female; Gallbladder; Humans; In Vitro Techniques; Male; Middle Aged; Models, Biological; Motilin; Muscle Contraction; Muscle, Smooth; Neurotensin; Peristalsis

The relative amount of cholesterol and the fatty acid composition of phosphatidylcholines in bile can be influenced by the bile acid species secreted. To search for a contribution of secondary bile acids and of phosphatidylcholines to supersaturation of bile in gallstone disease, we compared the relative amount of cholesterol and the biliary composition of bile acids and of phospholipid fatty acids in cholecystokinin-stimulated duodenal bile of 22 female gallstone patients and 16 healthy controls and analyzed the interrelationships of these bile constituents. Gallstone patients had higher molar percentages of cholesterol than did controls (10.2 +/- 3.2 vs. 6 +/- 1.5 mol%; p less than 0.001) and demonstrated a trend toward larger fractions of deoxycholic and lithocholic acids. By linear models, variation of cholesterol saturation could be predicted (p less than 0.001) up to 53% by the bile acid pattern and up to 81% by the fatty acid pattern of phospholipids. Linear path analysis (goodness-of-fit index = 0.973) confirmed the tight relationship between phospholipid fatty acids (positive: oleic, arachidonic; negative: linoleic, palmitoleic) and the relative amount of cholesterol; more than half the influence of cholic, deoxycholic and lithocholic acids on the relative amount of cholesterol could be explained indirectly by their influence on the phospholipid fatty acid pattern. We conclude that the relationships examined by path analysis support the working hypothesis that secondary bile acids contribute to supersaturation of bile mainly by changing the fatty acid pattern of the secreted phospholipids (presumably the pattern of phosphatidylcholines), which increases the molar ratio of cholesterol/phospholipids in bile.

Topics: Adult; Analysis of Variance; Bile; Bile Acids and Salts; Cholecystokinin; Cholelithiasis; Cholesterol; Fatty Acids; Female; Gallbladder; Humans; Lithotripsy; Models, Biological; Phospholipids; Reference Values

The development of gallstones is a well recognized complication of therapy with the long-acting somatostatin analogue, octreotide in patients with acromegaly. A group of nine acromegalic patients was treated with octreotide at doses of 300-600 micrograms daily for 8 months and the changes in fasting and post-prandial cholecystokinin release, and gall bladder motor function (determined by a radiosotopic technique) were assessed at regular intervals. In addition the development of any gallstones was determined by serial ultrasonography. Fasting cholecystokinin levels showed no significant change over 6 months, whereas the post-prandial levels demonstrated a significant decrease (p less than 0.01) during therapy, yet remained significantly higher than fasting levels. Twenty-four hours after commencing therapy gall bladder ejection fraction was decreased by 57 +/- 23 per cent and gall bladder ejection rate decreased by 63 +/- 19 per cent compared to the pretreatment values, whereas after 6 months' therapy a marked reduction in gall bladder ejection fraction (greater than 35 per cent) and gall bladder ejection rate (greater than 40 per cent) persisted in only four of nine patients. Three of these four patients with persistently impaired gall bladder motor function were subsequently shown to have developed either gallstones or biliary sludge during the course of therapy. We conclude that treatment with octreotide is associated with an impaired post-prandial release of cholecystokinin in all acromegalic patients, but gallstones only develop in those patients who, in addition, have evidence of a persistently impaired gall bladder motor response to cholecystokinin.

Topics: Acromegaly; Adult; Aged; Cholecystokinin; Cholelithiasis; Female; Gallbladder; Growth Hormone; Humans; Male; Middle Aged; Motor Neurons; Octreotide; Pituitary Neoplasms; Prospective Studies

One hundred eighty-seven patients who presented with symptoms consistent with biliary colic but had no ultrasonic evidence of cholelithiasis were observed in an effort to identify those with a functional gallbladder disorder that might benefit from surgical intervention. All patients underwent quantitative evaluation of gallbladder emptying using cholecystokinin biliary scanning, and ejection fractions less than 35% were considered abnormal. One hundred twenty-nine patients (69%) had abnormal ejection fractions, and 88 (68%) of these subsequently underwent cholecystectomy. Sixty of the surgical specimens revealed pathologic changes. Eighty-four percent of patients successfully contacted for follow-up experienced complete relief, and another 13% had partial relief of preoperative symptoms. Only two patients reported no change in symptom complex. Twenty-nine patients with abnormal ejection fractions elected not to undergo surgery. Fifty-nine percent of these patients continued to experience symptoms of biliary colic at a mean follow-up of 22 months. Of the 44 patients with normal ejection fractions, 35 (80%) reported resolution of symptoms during follow-up of medical treatment. Cholecystokinin biliary scanning can help identify patients with acalculous, functional gallbladder disease who may benefit from cholecystectomy.

Topics: Adult; Biliary Dyskinesia; Cholecystectomy; Cholecystitis; Cholecystokinin; Cholelithiasis; Diagnosis, Differential; Female; Follow-Up Studies; Gallbladder; Gallbladder Diseases; Humans; Imino Acids; Male; Middle Aged; Organotechnetium Compounds; Prospective Studies; Radionuclide Imaging; Technetium Tc 99m Disofenin

Change in gallbladder contractility after biliary extracorporeal shock-wave lithotripsy (ESWL) may significantly influence the clearance of fragments after successful gallstone fragmentation. We assessed changes in gallbladder contractility in response to an oral fatty meal in 50 patients 1 month after biliary ESWL (all fragments were smaller than 3 mm) and also in a separate group of 10 patients 3 months after complete clearance of fragments. The prevalence of persistent lumen-obliterating contraction of the gallbladder after biliary ESWL also was analyzed in 325 patients. Gallbladder contractility remained unchanged in 30, increased in nine, and decreased in 11 of the 50 patients. The average reduction in the fasting gallbladder volume after lithotripsy was 28% (p less than .001). Gallbladder contractility remained unchanged 3 months after complete clearance of fragments in six of 10 patients studied separately. A decrease (n = 2) or increase (n = 2) in contractility was seen in the remaining patients. No significant difference occurred in the average ejection fraction of the gallbladder before lithotripsy and after complete clearance of the fragments. Thirty-four of the 325 patients who have so far undergone biliary ESWL had a completely contracted gallbladder with no lumen visible on sonography. The gallbladder returned to a relaxed state in half of these patients within 1-9 months. Thus, biliary ESWL did not significantly alter gallbladder contractility in 60% of patients. A significant reduction in the volume of the fasting gallbladder occurred after lithotripsy. Successful clearance of fragments did not improve the contractility of stonebearing gallbladders in the majority of patients.

Topics: Cholecystokinin; Cholelithiasis; Eating; Fasting; Gallbladder; Humans; Imino Acids; Lithotripsy; Organotechnetium Compounds; Radionuclide Imaging; Technetium Tc 99m Lidofenin; Ultrasonography

In the present article we report transitory severely impaired postprandial gallbladder emptying preceding biliary colic in a cholesterol gallstone patient. Gallbladder emptying 1 wk before and 3 wk after the biliary colic was normal. Treatment with ursodeoxycholic acid led to increased fasting gallbladder volumes, but the postprandial residual volume did not change. Postprandial cholecystokinin release appeared not to change during ursodeoxycholic acid treatment or during biliary colic.

Topics: Biliary Tract Diseases; Cholecystokinin; Cholelithiasis; Colic; Eating; Gallbladder; Humans; Male; Middle Aged; Ursodeoxycholic Acid

It has been previously suggested that treatment with ursodeoxycholic acid leads to decreased gallbladder emptying. The proposed mechanism is decreased release of cholecystokinin through negative feedback control by an increased amount of intraduodenal bile acids. In the present study we examined cholecystokinin release and gallbladder contraction after oral administration of a commercial fatty meal (Sorbitract; Dagra, Diemen, The Netherlands) using ultrasonography in eight normal subjects and eight gallstone patients before and after 1 and 4 weeks of treatment with ursodeoxycholic acid (10 mg kg-1.day-1). Fasting gallbladder volume increased in 15 of 16 subjects during treatment (P less than 0.01). Minimal volume did not change. Therefore, both absolute and relative gallbladder emptying increased during therapy. Maximal decrement of gallbladder volume in milliliters and percentage as well as integrated gallbladder contraction during 90 minutes in milliliters and percentage were significantly increased after 1 and 4 weeks of treatment with ursodeoxycholic acid when compared with data before therapy. Gallstone patients tended to have larger fasting and residual gallbladder volumes than normal subjects, whereas parameters for the amount of bile expelled (maximal decrement of gallbladder volume and integrated gallbladder contraction in milliliters and percentage) did not differ. Release of cholecystokinin did not change during treatment and did not differ significantly between patients and normal subjects. Mean relative percentage of ursodeoxycholic acid in bile during treatment in 13 subjects consenting to have duodenal intubation was 47% (range 31%-60%). Changes of fasting gallbladder volume after institution of bile acid treatment correlated significantly (r = 0.74, P less than 0.01) with changes of cholesterol saturation index but not with relative percentage of ursodeoxycholic acid in bile. This study indicates that gallbladder emptying does not decrease during treatment with ursodeoxycholic acid. Moreover, there is no evidence of decreased cholecystokinin release.

Topics: Adult; Aged; Bile; Cholecystokinin; Cholelithiasis; Cholesterol; Deoxycholic Acid; Female; Gallbladder; Humans; Male; Middle Aged; Muscle Contraction; Reference Values; Ultrasonography; Ursodeoxycholic Acid

Thirty gallbladders were studied in vitro; 5 had black pigment stones and 25 contained manifestations of excess cholesterol in bile. Of the 25, 14 had cholesterol stones, 7 had macroscopic cholesterolosis, and 4 had cholesterol crystals. There were no differences in basal active tension among these groups, but the force of spontaneous phasic contractions was reduced in gallbladders with cholesterol stones, cholesterolosis, and cholesterol crystals compared with specimens with pigment stones (p less than 0.001). The forces developed in response to cholecystokinin-8 (10(-10)-10(-6) M), acetylcholine (10(-7)-10(-3) M), and potassium chloride (20-60 mM) were greater in strips from specimens with pigment stones than in strips from specimens with cholesterol stones or cholesterolosis (p less than 0.001). In cholesterol stones and cholesterolosis specimens, relatively strong muscle strips had similar responses to 10(-6) M cholecystokinin-8 in normal calcium (2.5 mM) and in the absence of extracellular calcium. Weaker muscle strips had a reduced response to cholecystokinin-8 in the absence of extracellular calcium (p less than 0.01). It is concluded that muscle strips exposed to bile with excess cholesterol have a reduced contractility compared with muscle strips from specimens with pigment stones; this impaired contractility precedes gallstone formation, and results from muscle dysfunction.

Topics: Adult; Aged; Bile; Buffers; Cholecystokinin; Cholelithiasis; Cholesterol; Dose-Response Relationship, Drug; Female; Gallbladder; Humans; In Vitro Techniques; Male; Middle Aged; Muscle Contraction; Muscle, Smooth; Peptide Fragments; Pigments, Biological; Potassium Chloride

The authors applied scanning electron microscope with synchronization of EDAX to detect the ultrastructure of gallbladder mucosa, metallic elements and their oxides, to observe the bacteria of the core of the gallstone; applied cholecystokinin to observe the effects of abnormal gallbladder contraction on stone formation; applied biochemical, immunological criteria to determine the association between liver and gallbladder diseases and gallstone; applied scanning electron microscope to compare the analysis of mechanical structure of gallstone. According to the results of research, the authors conclude: (1) The basic condition of the formation of the gallstone was the disturbance of physiological reaction of "integration" and "homeostasis" of liver-biliary system. (2) The essential factor of the formation of gallstone was the infection of liver-biliary system. (3) The formation of the gallstone structure was caused by changed physical and chemical mechanics of bile. (4) The synchronization treatment of liver-biliary was the principle of preventing and treating gallstone.

Topics: Adult; Aged; Bile; Cholangitis; Cholecystokinin; Cholelithiasis; Female; Gallbladder; Humans; Male; Middle Aged; Mucous Membrane

To determine whether extracorporeal shock-wave lithotripsy of gallbladder stones alters gallbladder motility, gallbladder contraction in response to intravenous cholecystokinin was investigated by ultrasound. Twenty-one patients with symptomatic gallstones were studied before and after shock-wave lithotripsy, 12 with and 9 without concomitant litholytic therapy (combination of ursodeoxycholic acid and chenodeoxycholic acid). Gallbladder emptying was significantly delayed and less complete in both groups of patients before shock-wave treatment (with bile salts: residual volume, 51% +/- 10% and half-ejection time, 40 +/- 5 min; without bile salts: residual volume, 46% +/- 7%; half-ejection time, 30 +/- 4 min) compared with healthy controls (residual volume, 15% +/- 4%; half-ejection time, 18 +/- 2 min). Gallbladder motility was not altered in either group 1 day and 1 yr after lithotripsy. The findings indicate (a) that extracorporeal shock-wave lithotripsy has no immediate or long-term adverse effects on gallbladder motility and (b) that the defect of gallbladder motility associated with gallstone disease is not abolished by removal of the stone.

Topics: Adult; Chenodeoxycholic Acid; Cholecystokinin; Cholelithiasis; Female; Gallbladder; Humans; Lithotripsy; Male; Middle Aged; Muscle Contraction; Peristalsis; Ursodeoxycholic Acid

Impaired gallbladder emptying is one of the various factors suggested to be involved in the pathogenesis of gallstones. The present study was undertaken to determine whether gallbladder emptying, endogenous cholecystokinin (CCK) secretion, or their interrelation is altered in patients with gallstones. After intraduodenal administration of 60 ml corn oil, plasma CCK concentration was measured by a sensitive and specific radioimmunoassay and gallbladder emptying by cholescintigraphy. Patients with gallstones (N = 20) produced significantly less endogenous CCK (105 +/- 17 pmol/liter 60 min; P less than 0.001) than control subjects (191 +/- 11 pmol/liter 60 min, N = 20); gallbladder emptying in the patients was significantly decreased at 5, 10, 40, 45, and 50 min but the reduction in gallbladder emptying did not reach statistical significance at 60 min (patients 44 +/- 8%, control subjects 60 +/- 4%). In addition, the gallbladder responsiveness to intravenous infusion of the synthetic CCK analog cerulein was investigated. Based on the results of gallbladder emptying in response to endogenous and exogenous CCK, four subgroups of gallstone patients were identified: (1) a group (N = 7) with normal gallbladder sensitivity to CCK, (2) a group (N = 6) with significantly increased gallbladder sensitivity to CCK, (3) a group (N = 6) with impaired gallbladder emptying after corn oil due to a significantly reduced endogenous CCK secretion but with normal gallbladder sensitivity to CCK, and (4) one patient whose gallbladder was unresponsive to CCK and was found to have chronic cholecystitis at surgery.

Topics: Ceruletide; Cholecystokinin; Cholelithiasis; Corn Oil; Duodenum; Female; Gallbladder; Humans; Male; Middle Aged; Plant Oils

Cholecystectomy will not always relieve the abdominal symptoms of the patient with gallstones. The functional effects of gallbladder removal in a patient with a patent cystic duct are not known in detail. Studies of the function of the gallbladder and pancreas have suggested feedback mechanisms for the release of cholecystokinin (CCK). A disturbed regulation of CCK release after cholecystectomy might induce pancreaticobiliary and gastrointestinal dysfunctions. In our study the concentrations of CCK in plasma were measured in 17 patients with gallstones. The measurements were taken with gallbladders opacified at cholecystography and with patent cystic ducts at the operation, in the fasting state, and during stimulation before and 17 weeks after the cholecystectomy. The CCK assay used measures sulfated CCK-8, CCK-22, and CCK-33 with equimolar potency but neither nonsulfated CCK nor any gastrins. Emtobil (containing peanut oil and sorbitol) was used for peroral stimulation of the CCK release. The basal concentration of CCK was 4 pmol/L and rose five times during a "test meal." No significant differences were seen in fasting or stimulated concentrations of plasma CCK before and after the cholecystectomy. Thus cholecystectomy in gallstone patients with functioning gallbladders does not seem to influence the regulation of CCK release.

Topics: Adult; Aged; Cholecystectomy; Cholecystokinin; Cholelithiasis; Humans; Middle Aged; Radioimmunoassay

Fifteen patients with history of biliary colic, induceable by cholecystokinin, but normal oral cholecystogram and ultrasonogram were studied prior to and after cholecystectomy. Fasting duodenal bile, obtained preoperatively after administration of cholecystokinin, and gallbladder bile obtained at operation were analyzed. The lipid composition as well as the cholesterol saturation were within the range seen in gallstone-free subjects. The total lipid concentration of gallbladder bile was normal, whereas that of duodenal bile was reduced by about 50%, indicating a less efficient gallbladder emptying. In 10 of the 15 patients, the analysis of the excised gallbladder displayed macro- or microscopic abnormalities; two patients had cholesterol gallstones. At re-examination 9-27 months after the operation, 12 of the patients were completely symptom-free and two patients reported a clear improvement while on still had unchanged symptoms. It is concluded that cholecystectomy is the treatment to prefer in patients with "acalculous" biliary pain, induceable by cholecystokinin.

Topics: Adult; Bile; Bile Duct Diseases; Cholecystectomy; Cholecystokinin; Cholelithiasis; Colic; Female; Gallbladder; Humans; Lipid Metabolism; Male; Middle Aged; Pain

We studied gallbladder bile flow before, during, and after cholesterol gallstone formation in the prairie dog using infusion cholescintigraphy with 99mTc-diethyl iminodiacetic acid. In 18 fasting animals partitioning of bile between gallbladder and intestine was determined every 15 min for 140 min, and gallbladder response to cholecystokinin (5 U/kg X h) was calculated from the gallbladder ejection fraction. Ten prairie dogs were then placed on a 0.4% cholesterol diet and 8 on a regular diet, and the studies were repeated 1, 2, and 6 wk later. The proportion of hepatic bile that entered the gallbladder relative to the intestine varied from one 15-min period to the next, and averaged 28.2% +/- 5.1% at 140 min. Partial spontaneous gallbladder emptying (ejection fraction 11.5% +/- 5.6%) was intermittently observed. Neither the number nor the ejection fraction of spontaneous gallbladder contractions changed during gallstone formation. By contrast, the percent of gallbladder emptying in response to cholecystokinin decreased from 72.1% +/- 5% to 25.9% +/- 9.3% (p less than 0.025) in the first week and was 14.3% +/- 5.5% at 6 wk (p less than 0.01 from prediet values, not significant from first week). Gallbladder filling decreased from 28.2% +/- 5.1% to 6.7% +/- 3% (p less than 0.01), but this change was only observed after 6 wk, when gallstones had formed. This study shows that bile flow into the gallbladder during fasting is not constant; the gallbladder contracts intermittently; gallbladder emptying in response to exogenous cholecystokinin is altered very early during gallstone formation; and gallbladder filling remains unaffected until later stages, when gallstones have formed.

Topics: Animals; Bile; Cholecystokinin; Cholelithiasis; Cholesterol; Cholesterol, Dietary; Gallbladder; Imino Acids; Male; Muscle Contraction; Radionuclide Imaging; Sciuridae; Sincalide; Technetium; Technetium Tc 99m Diethyl-iminodiacetic Acid; Time Factors

We investigated the mechanism of humoral control of bile discharge into the duodenum. The actions of the GB, SO and duodenum were monitered by cinecholecystocholangiogrphy combined with manometry of the SO area using a hydraulic-capillary infusion system or MIKRO-TIP, and these were correlated with the plasma concentrations of GI hormones. We concluded that one of the most significant roles of the sphincter of Oddi is to limit bile flow. This postulation was favored by the observation of so-called 'spasm' of the SO where 8 to 10 contractions per min., in contrast to 'normal' contraction of 2 to 4 per min., were seen. On this special occasion, no discharge of the contrast material into the duodenum was noticed. Exogenous or endogenous CCK causes a coordinated action of the GB contraction, the SO relaxation and relaxation of the adjacent segment of the duodenum, resulting in an effective discharge of bile into the duodenum. The effect of Pancreozymin on bile discharge revealed by endoscopic cinematography was that Pancreozymin first made the orifice of the papilla of Vater widely open with a profuse bile flow and following this, caused a repeated shuttering action of the orifice with minimal discharge of bile. This observation opposes the opinion that active SO contractile activity is necessary to bile flow into the duodenum. Caerulein or CCK-33 caused no 'post-inhibition' enhancement of the SO activity that was seen in case of Pancreozymin administration. Motilin, calcium or other substances contained in Pancreozymin (Boots) might be causative for this enhancement.

Topics: Ampulla of Vater; Bile; Ceruletide; Cholecystokinin; Cholelithiasis; Gallbladder; Humans; Manometry; Muscle Contraction; Peristalsis; Sphincter of Oddi

Gallbladder contraction in response to a fatty meal is thought to be caused by release of cholecystokinin (CCK). We have previously demonstrated a close correlation between circulating concentrations of CCK and contraction of the gallbladder in normal humans and in gallstone patients. Recent studies in animals, however, have shown that other potentially cholecystokinetic hormonal agents are released by a fatty meal, which suggests that other hormones may be involved in postprandial gallbladder contraction. Neurotensin, a 13-amino acid peptide, is released by fat; we have shown it to cause gallbladder contraction in dogs. In the present study, we measured release of neurotensin in seven normal adult volunteers. We determined the effects of infused neurotensin (4 pmol/kg-min) on gallbladder contractility, measured by ultrasonography in 10 adult volunteers, and we evaluated release of neurotensin in eight patients with gallstones. After ingestion of fat, we found significant release of neurotensin in normal volunteers from a mean basal concentration of 15.9 +/- 3.5 pg/ml to a maximum of 34.7 +/- 0.2 pg/ml. In the gallstone patients after fat ingestion, neurotensin rose from a basal of 16.8 +/- 3.1 pg/ml to a maximum of 53.4 +/- 28.1 pg/ml, which was a significantly greater release than in controls. Intravenous infusion of neurotensin produced dilatation of the gallbladder (from a mean basal volume of 13.7 +/- 2.3 cc to 20.0 +/- 1.8 cc). Neurotensin causes relaxation of the gallbladder in humans and, by contributing to stasis, may be involved in the formation of gallstones.

Topics: Adult; Cholecystokinin; Cholelithiasis; Corn Oil; Female; Gallbladder; Humans; Male; Middle Aged; Muscle Contraction; Muscle, Smooth; Neurotensin; Oils; Pancreatic Polypeptide; Ultrasonography

Gallbladder stasis has been implicated in gallstone formation. Gallbladder filling and emptying were quantitated by computer-assisted cholescintigraphy in 41 normal subjects versus 26 patients with gallstones. Gallbladder contraction was induced by low-dose (1.2 U/kg . h) cholecystokinin infusion. Gallstone patients exhibited normal gallbladder filling, but emptying was significantly (p less than 0.01) reduced compared with controls. On closer inspection, the patients fell into two subgroups, separated by t1/2, the time to empty 50% of gallbladder contents, 19.1 min (mean + 2 SD of control). Fifteen patients (57.7%) with a normal t1/2 (less than 19.1 min) exhibited both normal filling and normal emptying. The remaining 11 patients (43.3%) with t1/2 greater than 19.1 min had grossly abnormal gallbladder emptying, significantly (p less than 0.001) different from both the previous patient subgroup and the controls. There was no significant difference in age, sex, prevalence of obesity, presence or absence of biliary colic, and gallstone size, number, or calcification between these two subgroups. Thus, defective gallbladder emptying is evident in a subgroup of gallstone patients, and is independent of clinical features, stone size, and number. Impaired emptying should be considered when assessing pathogenesis or medical therapy.

Topics: Cholecystokinin; Cholelithiasis; Gallbladder; Humans; Muscle Contraction; Radionuclide Imaging

Topics: Adult; Cholecystectomy; Cholecystokinin; Cholelithiasis; Exocrine Pancreatic Insufficiency; Female; Humans; Postoperative Complications; Secretin

Cholecystokinin (CCK)-like activities in the duodenal mucosa of the patients with cholecystolithiasis were determined with the bioassay method we established. The results obtained are as follows: The gall bladder of the patients with cholecystolithiasis following oral administration of egg yolk has contraction rates comparable to those of the normal subjects in the control group, whereas the contraction rate of the gall bladder of the patients with cholecystolithiasis following administration of caerulein was markedly lower than that of the normal subjects in the control group. The variations in the contraction of the gall bladder in time lapse following administration of caerulein to the patients with cholecystolithiasis strongly denied the possibility of either insufficient release of CCK or accelerated dissimilation of CCK in those patients. Based on the above findings, it was concluded that the sensitivity of the gall bladder to CCK decreases in the patients with cholecystolithiasis and that, in order to replenish it, the feed-back mechanism reacts to sufficiently promote the production of CCK in the duodenal mucosa. The similar mechanism was noted in the variations of the findings of normal subjects as age advanced.

Topics: Adult; Aged; Ceruletide; Cholecystography; Cholecystokinin; Cholelithiasis; Duodenum; Egg Yolk; Female; Gallbladder; Humans; Intestinal Mucosa; Kinetics; Male; Middle Aged; Muscle Contraction

We studied the effects of vagotomy on gallbladder (GB) motility in prairie dogs and humans with infusion cholescintigraphy. Twelve male prairie dogs were anesthetized and given an intravenous infusion of 120 microCi of diethyl-HIDA for 150 minutes. Images were acquired every 10 minutes. Then cholecystokinin (CCK)-8, 1.5 micrograms/kg, was given as a bolus, and images were acquired for another 30 minutes. We repeated the studies giving 300 micrograms/kg of atropine 20 minutes before administration of CCK-8. All animals underwent truncal vagotomy, and the studies were repeated 1 and 3 months later. The GB filled in a stepwise fashion; partitioning of bile varied from one 10-minute period to the next and averaged 20% +/- 2%/80% +/- 3% during the 150-minute period. Episodic partial GB emptying (ejection fraction 19% +/- 2%; intervals of 70 +/- 5 minutes) occurred during this phase. GB filling and partitioning of bile were unchanged after vagotomy. GB ejection fraction in response to CCK-8 was 69% +/- 6% in controls, 74% +/- 5% after atropine, 78% +/- 8% 4 weeks after vagotomy, and 66% +/- 6% 3 months after vagotomy. Sixteen human subjects were studied after parietal cell vagotomy (six patients) or truncal vagotomy and drainage (10 patients). GB filling average 2.5% +/- 2% per minute in patients who underwent truncal vagotomy and 3% +/- 1% per minute in patients who underwent parietal cell vagotomy. GB emptying in response to CCK-33 (0.02 U/kg/min) was 74% +/- 7% in patients who underwent truncal vagotomy and 82% +/- 4% in patients who underwent parietal cell vagotomy. Thus neither GB filling nor GB emptying in response to CCK was altered by cholinergic blockade or vagotomy.

Topics: Animals; Cholecystography; Cholecystokinin; Cholelithiasis; Gallbladder; Humans; Male; Muscle Contraction; Radionuclide Imaging; Sciuridae; Time Factors; Vagotomy; Vagotomy, Proximal Gastric

Topics: Cholecystokinin; Cholelithiasis; gamma-Glutamyltransferase; Humans; Liver Cirrhosis; Liver Diseases; Secretin

Topics: Adult; Biliary Tract; Cholecystokinin; Cholelithiasis; Female; Humans; Male; Middle Aged; Morphine; Movement

This study examines the effects of dietary cholesterol and subcutaneous indomethacin on gallstone formation, gallbladder motility, and bile composition in guinea pigs. Guinea pigs on cholesterol diets developed gallstones which were not primarily composed of cholesterol and were not prevented by indomethacin. Animals receiving cholesterol diets showed significant gallbladder enlargement which was inhibited by indomethacin. Cholesterol did not alter gallbladder pressure-volume relationships or the response to CCK, while indomethacin diminished gallbladder tone. Although cholesterol feeding did not appear to alter smooth muscle contractility in the guinea pig gallbladder, it caused significant gallbladder enlargement by a mechanism which may be dependent on prostaglandins.

Topics: Animals; Cholecystokinin; Cholelithiasis; Cholesterol, Dietary; Female; Gallbladder; Gastrointestinal Motility; Guinea Pigs; Indomethacin

Assessment of the clinical value of the pancreolauryl test (PLT) in the literature range from "useless" to a specifity of 95% and a sensitivity of 98%. In this work, our own data are presented in relation to various reference methods. The results are derived from the largest collective investigated to data, comprising 40 controls and 391 patients (108 with chronic pancreatitis and 283 with other gastrointestinal disorders). The specifity of the the PLT varies between 81% and 95% according to the "quality" of the control collective. The PLT is particularly frequently pathological in patients with diseases in the region of the gallbladder/bile duct and the gastrointestinal tract. The sensitivity of the PLT for chronic pancreatitis varies between 68% and 100%, depending on 9 different reference methods employed. Based on the prevalence of chronic pancreatitis with exocrine insufficiency in various patient collectives, the predictive value of the PLT for the presence of this disorder can be calculated using our data.

Topics: Cholangiopancreatography, Endoscopic Retrograde; Cholecystokinin; Cholelithiasis; Chronic Disease; Chymotrypsin; Diagnosis, Differential; Exocrine Pancreatic Insufficiency; Gastrointestinal Diseases; Humans; Liver Diseases; Pancreatic Diseases; Pancreatic Function Tests; Pancreatitis; Secretin; Tomography, X-Ray Computed

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.

Topics: Animals; Cholecystokinin; Cholelithiasis; Cholestasis, Extrahepatic; Cholesterol, Dietary; Cystic Duct; Gallbladder; Male; Peptide Fragments; Pressure; Rodentia; Sincalide; Stimulation, Chemical

To examine the effect of changes in bile lithogenicity on gallbladder muscle function, in vitro gallbladder contractility was studied in an animal model of cholesterol gallstones: Richardson ground squirrels fed either a trace (control) or a 1% wt/wt cholesterol (test) diet. Lithogenic index of gallbladder bile increased on the test diet from 0.52 +/- 0.03 to 0.81 +/- 0.04 (p less than 0.001). Isometric tensions generated in response to cholecystokinin-octapeptide, acetylcholine, or potassium depolarization, were all reduced greater than 50% in the test gallbladder muscles (p less than 0.05), without any significant shift of the normalized dose-response curves. Tension in response to cholecystokinin-octapeptide differed significantly (p less than 0.05) between each stage of stone formation compared with controls: 42% decrease in test animals before development of stones; 65% decrease in those with gallstones. Ileal muscle from these animals, when tested with the same three stimuli, showed no adverse effects of the high-cholesterol diet. Another animal model, the prairie dog, also demonstrated a similar in vitro defect in gallbladder contractility associated with increases in bile lithogenicity. Thus, in the ground squirrel, a progressive defect in smooth muscle contractility to three different stimuli coincides with early changes in bile lithogenicity. The defect is not associated with any loss of sensitivity to these stimuli, and appears to be localized specifically to the gallbladder muscle. Its presence in two animal models of cholelithiasis suggests that biliary stasis is an important factor in the early stages of cholesterol stone formation.

Topics: Acetylcholine; Animals; Cholecystokinin; Cholelithiasis; Cholesterol; Cholesterol, Dietary; Gallbladder; In Vitro Techniques; Intestines; Male; Muscle Contraction; Muscle, Smooth; Peptide Fragments; Potassium; Sciuridae; Sincalide

We used a Tc-99m-labeled hepatobiliary agent to measure the partition of hepatic bile between gallbladder and intestine in sixteen normal patients and nine patients with cholelithiasis. In normal subjects, the fractions of the hepatic bile that flow into the gallbladder and the small intestine were widely variable, with mean values of 69 +/- 7% (s.e.) and 31 +/- 7% respectively. Bile reflux into the common hepatic duct was rare, occurring during the first 2/3 of the gallbladder ejection period and only when the ejection fraction was greater than 59%. The gallbladder's mean latent period, ejection period, ejection fraction, and ejection rate were 2 +/- 1 min, 11 +/- 1 min, 59 +/- 4%, and 5.9%/min respectively. In patients with cholelithiasis, the fraction of hepatic bile flowing into the gallbladder was normal, but the ejection fraction was significantly reduced (p less than 0.005). For an equivalent dose of cholecystokinin, the gallbladder in cholelithiasis is less responsive than in normal subjects.

Topics: Adult; Animals; Bile Reflux; Cholecystokinin; Cholelithiasis; Female; Gallbladder; Hepatic Duct, Common; Humans; Imino Acids; Male; Middle Aged; Rabbits; Radionuclide Imaging; Technetium; Technetium Tc 99m Lidofenin; Technology, Radiologic

Topics: Adolescent; Adult; Aged; Cholagogues and Choleretics; Cholecystitis; Cholecystokinin; Cholelithiasis; Chronic Disease; Female; Humans; Kinins; Male; Middle Aged

Two tests of cystic duct patency were compared in 37 patients with suspected acute cholecystitis. Ultrasound (US) measurement of gallbladder contraction induced by 40 Ivy dog units of cholecystokinin (CCK) was followed by the radionuclide (RN) test for cystic duct patency. In all 13 patients in whom US showed significant gallbladder contraction after CCK, the cystic duct was proved to be patent by the RN test. The gallbladder did not contract significantly in 24 patients. Eleven of these patients had acute cholecystitis, with evidence of cystic duct obstruction, and 12 had patent cystic ducts and final diagnoses other than acute cholecystitis. The measurement of contraction of the gallbladder in response to CCK is a valuable improvement over simple US when cystic duct obstruction is excluded; failure of contraction is not specific, and independent evaluation of cystic duct patency is required.

Topics: Adult; Aged; Bile Duct Diseases; Cholecystitis; Cholecystokinin; Cholelithiasis; Cystic Duct; Gallbladder; Humans; Middle Aged; Radionuclide Imaging; Ultrasonography

The role of endogenously released cholecystokinin (CCK) in mediating gallblader (GB) contraction was evaluated in 12 normal volunteers and 24 patients with gallstones (11 additional gallstone patients were excluded because of failure of adequate ultrasonographic visualization). CCK concentrations before and after oral administration of fat (Lipomul((R))) were measured by a specific radioimmunoassay. CCK release was correlated with changes in GB volume determined simultaneously by ultrasonography. On the basis of gallbladder contraction and operative findings, gallstone patients were divided into "contractors" (14), "noncontractors" (6), and "hydrops" (4). Lipomul caused prompt release of CCK in normal volunteers and all groups of gallstone patients. The changes (basal to peak) in plasma CCK (pg/ml) for the different groups were as follows: normal volunteers (108 +/- 9 to 200 +/- 16), contractors (77 +/- 10 to 128 +/- 13), noncontractors (59 +/- 7 to 159 +/- 38), and hydrops (43 +/- 5 to 113 +/- 47). The total integrated output of CCK (0-60 min) was greater in normal volunteers (3975 +/- 762 pg-min/ml) than in contractors (1530 +/- 567 pg-min/ml). Lipomul caused similar GB contraction in normal volunteers and contractors (from basal volumes to maximal contraction); these changes were from 19.5 +/- 2.3 ml to 5.6 +/- 1.0 ml in normal volunteers, and from 19.6 +/- 3.2 to 5.2 +/- 1.0 in contractors. Plasma concentrations of CCK and GB volume were highly correlated in the 12 normal volunteers (r = -0.89, p < 0.01) and in the 14 contractors (r= -0.99, p < 0.01)), but the GB was significantly (p < 0.01) more sensitive to changes in plasma CCK in the gallstone contractors than in the normal volunteers. The authors suggest that there may be two groups of gallstone patients, noncontractors and contractors. Stasis may be important in the pathogenesis of gallstones in the noncontractors, whereas in contractors, the authors speculate that an abnormality in the CCK-gallbladder relationship (characterized by diminished CCK release and increased GB sensitivity to CCK) may be involved in the evolution of the disease.

Topics: Adult; Aged; Bile Acids and Salts; Cholecystokinin; Cholelithiasis; Cholesterol; Corn Oil; Female; Gallbladder; Humans; Male; Middle Aged; Muscle Contraction; Oils

Topics: Animals; Bile; Bile Acids and Salts; Cholecystokinin; Cholelithiasis; Cholestasis; Cholesterol; Dose-Response Relationship, Drug; Male; Sciuridae

Topics: Adult; Cholecystokinin; Cholelithiasis; Female; Humans; Male; Middle Aged; Pancreatic Function Tests; Pancreatitis; Secretin

Topics: Animals; Cell Division; Cholecystokinin; Cholelithiasis; DNA; Epithelium; Gallbladder; Humans; Mice; Mitosis; Pentagastrin

Size of gallbladder after overnight fasting and the kinetics of gallbladder contraction following i.v. injection of 1 I. U. of CCK was investigated in patients with chronic liver disease (liver cirrhosis: n = 26; chronic hepatitis: = 12; fatty liver: n = 5). The results were compared with those obtained in an age and sex matched control group of subjects without symptoms of diseases of the liver or gastrointestinal tract (n = 15). Ultrasound was used for continuous monitoring of gallbladder emptying. In the cirrhotics the cartographically determined initial area of the gallbladder was significantly greater than in the controls (p less than 0,01). The kinetic of gallbladder emptying following CCK-pancreozymin stimulation was similar in the groups of patients with liver diseases to that of the control subjects. However, the residual area of the gallbladder following maximal contraction was again significantly greater in the cirrhotics when compared to the control group (p less than 0.05). The area of the gallbladder in patients with chronic hepatitis exhibited similar changes of the values in the fasting state and after maximal contraction as seen in the patients with liver cirrhosis, although the differences when compared to the control group were not significant. The results show that in spite of distinct signs of a hypotonic state of the unstimulated gallbladder in patients with chronic liver disease the kinetic of contraction following an exogenous stimulus with CCK remains normal.

Topics: Adult; Aged; Cholecystokinin; Cholelithiasis; Fatty Liver; Female; Gallbladder; Hepatitis; Humans; Kinetics; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Muscle Contraction; Ultrasonography

Topics: Adult; Biliary Tract Diseases; Cholecystography; Cholecystokinin; Cholelithiasis; Colic; Female; Humans; Middle Aged; Pain

Cholesterol gallstones occur 600-1000 times more frequent in adults than in children. Seeking a possibility to explain this discrepancy, the molar concentrations of cholesterol, lecithin and bile acids as well as the bile acid pattern have been determined in duodenal juice, after an injection of 2 U/kg pancreocymin, of 33 children aged between 4 months and 14 years who were gastroenterologically healthy. The absolute values as well as the percentage composition were calculated. The lithoindices have been determined to be Li1=0.54 +/- 0.25 and Li2=1.06 +/- 0.50 according to the formulas of Thomas and Hofmann. Dependence on age in infancy and during childhood could be excluded. The main reason for the fact that hardly any gallstones occur among children, compared to the occurrence in adults seems to be the small concentration of cholesterol in the bile. Whereas there had been no deviations either of lithoindices or in the bile acid pattern in 10 patients with coeliac disease, 2 out of 6 children with mucoviscidosis and 3 out of 4 children with small bowel syndrome showed apparently increased lithoindices. Only in the last group a bile acid pattern was found which could reduce the higher risk of getting cholelithiasis.

Topics: Adolescent; Age Factors; Bile Acids and Salts; Celiac Disease; Child; Child, Preschool; Cholecystokinin; Cholelithiasis; Cholesterol; Cystic Fibrosis; Germany, West; Humans; Infant; Intestinal Secretions; Intestine, Small; Phosphatidylcholines

Topics: Administration, Intranasal; Animals; Cholecystography; Cholecystokinin; Cholelithiasis; Dogs; Female; Injections, Intravenous; Injections, Subcutaneous; Male; Rectum; Sincalide; Suppositories

Gall-bladder sensitivity to cholecystokinin (CCK) was determined by dynamic cholescintigraphy in 18 patients with radiolucent gall stones and 18 matched controls during an infusion of CCK in which the rate of infusion was increased. In 10 of the matched pairs the patient was more sensitive than the control, in one the control was more sensitive, and in seven no difference was detected (p = 0.012). It is concluded that patients with cholesterol gall stones have increased gall-bladder sensitivity to CCK, and that this may be important in the pathogenesis of this disease.

Topics: Cholecystokinin; Cholelithiasis; Female; Food; Gallbladder; Humans; Male; Middle Aged; Radionuclide Imaging; Stimulation, Chemical

The following tests were evaluated during biliary tract surgery: pressure controlled cholanlgiography, pressure measurement in the common duct, flow measurement through the papilla before and after administration of cholecystokinin. In a retrospective series of 122 patients with duct stones cholangiography was most accurate in detecting stones: 98%. In a prospective and retrospective series of totally 183 patients with obstruction at the papilla the following accuracy in detecting obstructions was achieved: cholangiography 72%, pressure measurement 72%, flow measurement 89%, combination of the tests 94%. In addition the importance of distinguishing a papillary spasm from an organic obstruction was shown with the cholecystokinin test. Cholangiography is adequate for the diagnosis of duct stones. However, additional measurement of pressure and flow is necessary for the diagnosis of obstructions at the papilla.

Topics: Ampulla of Vater; Cholangiography; Cholecystokinin; Cholelithiasis; Cholestasis, Extrahepatic; Common Bile Duct; Humans; Manometry; Rheology

CEA concentration in juice collected during the Secretin-Pancreozymin test, and cytology were evaluated in order to establish whether they may be used as an aid in the diagnosis of pancreatic carcinoma before resorting to x-ray examinations. Thirty-three subjects were studied: 6 normal subjects, 12 with chronic pancreatitis, 3 after recovery from acute pancreatitis, 8 with gall-stones, 3 with carcinoma of the pancreas and 1 with cancer of the biliary tract. Three duodenal juice samples (at 30, 60 and 90 mins of hormonal infusion) were taken in each subject for CEA, cytology, bicarbonate and trypsin determinations. Although a significant statistical difference was noted between normal subjects and patients with carcinoma of the pancreas in the 30-min-juice sample, CEA concentration in the duodenal juice did not seem a reliable index in the diagnosis of pancreatic carcinoma. The information provided by cytology was also very scanty and sometimes misleading. The clinical picture and radiological investigation still remain the surest basis for the diagnosis of pancreatic cancer.

Topics: Adult; Bile Duct Neoplasms; Carcinoembryonic Antigen; Cholecystokinin; Cholelithiasis; Female; Humans; Male; Middle Aged; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis; Secretin

Topics: Animals; Biological Assay; Cholecystokinin; Cholelithiasis; Duodenal Ulcer; Duodenum; Guinea Pigs; Humans; Intestinal Mucosa

The gallbladder can be visualized by ultrasound (cholecystosonography) and gallstones seen as echo producing densities. Under cholecystosonographic observation the gallbladder can be demonstrated to contract following stimulation by cholecystokinin. This establishes patency of the cystic duct and excludes a diagnosis of acute obstructive cholecystopathy. The gallbladder has been identified in 84 of 86 patients. Stones have been identified sonographically in 64% of 42 patients with proven gallstones (75% of the last 20 cases). The gallbladder contracted following stimulation in 18 of 20 cases with a patent cystic duct. Cholecystosonography is simple, safe and economical. Cholecystonography with cholecystokinin stimulation is the first diagnostic study to be performed when cholecystolithiasis is suspected and the following circumstances exists: a) an acute right upper quadrant (RUQ) syndrome consistant with acute obstructive cholecystopathy. b) cholestasis or hepatic dysfunction. c) a history of allergy to contrast media. Cholecystosonography may detect gallstones in a gallbladder visualized by oral cholangiography when stones are of the same density as the contrast media.

Topics: Cholangiography; Cholecystokinin; Cholelithiasis; Cholestasis; Drug Hypersensitivity; Evaluation Studies as Topic; Humans; Iodized Oil; Transducers; Ultrasonics; Ultrasonography

An approach to the diagnosis and treatment of patients with presumed functional disorders of the biliary tract (biliary dyskinesia) is described. The current diagnostic criteria are pain compatible with biliary pain in the absence of gallstones and other organic gastrointestinal disease, or other disorders which might produce abdominal pain, together with reproduction of the patient's symptoms by cholecystokinin, or morphine, or both. Other diagnostic methods are described together with their limitations. The results of operation in 38 of 45 patients seen in this Unit during the past six years are presented. The results were poor in 20% of patients, but two-thirds of the group have had good results in the short term.

Topics: Biliary Tract Diseases; Cholangiography; Cholecystectomy; Cholecystography; Cholecystokinin; Cholelithiasis; Diagnosis, Differential; Humans; Morphine; Pain; Pressure

The group of conditions variously termed biliary dyskinesia, acalculous cholecystitis, biliary pain without stones, or functional disorders of the biliary tract, is poorly defined clinically, and no consistent pathological abnormalities have been previously described in patients with this diagnosis. In this paper we report histological abnormalities encountered in operative live biopsies in such patients. The criteria for the diagnosis of a functional biliary tract disorders were: pain typical of biliary pain, negative results of investigations for organic biliary tract or other gastrointestinal disease, and reproduction of the patient's symptoms by cholecystokinin, or morphine, or both. Twenty of 45 patients with a presumptive diagnosis satisfied these criteria, and had a wedge liver biopsy at the time of operation. The 20 liver biopsy specimens were compared in a blind fashion with similar ones taken from patients having diagnostic laparotomies; patients with stones confined to the gallbladder; patients with gallstone pancreatitis; and patients with proven common bile duct stones. The biopsy findings were found to be similar to those in the latter two groups. Thus the abnormalities were similar to those found in partial or intermittent biliary obstruction, and it is suggested that they may be due to intermittent increases in biliary pressure.

Topics: Adult; Aged; Biliary Dyskinesia; Biliary Tract Diseases; Cholecystitis; Cholecystokinin; Cholelithiasis; Female; Humans; Liver; Male; Middle Aged; Morphine; Pain; Pancreatitis

The viscosity of duodenal juice obtained during the pancreocymin secretin test from patients with excretory pancreas insufficiency was significantly higher compared to the viscosity of duodenal secretions from a control group or from patients with gall bladder stones. Since the viscosity was inversely related to the total volume as well as the bicarbonate and trypsin concentrations, it is concluded that the increased viscosity is due to a reduction in the secretory activity of the pancreas. The viscosity measurements found for patients with cholelithiasis reflects merely the higher viscosity of the gall bladder bile.

Topics: Adult; Cholecystokinin; Cholelithiasis; Duodenum; Female; Humans; Intestinal Secretions; Male; Pancreas; Pancreatic Diseases; Secretin; Viscosity

Cholecystokinin (CCK)-like activities in the duodenal mucosa were measured by bioassay in patients with duodenal ulcer, cholelithiasis and some other gastrointestinal diseases as well as in healthy normal subjects. The mean CCK-like activity of the duodenal mucosa in patients with duodenal ulcer and cholelithiasis was 0.405 Ivy dog units per milligram and 0.376 Ivy dog units per milligram of dry weight of the duodenal mucosa (IDU/mg d.w.), respectively. Both these figures are significantly higher than 0.180 IDU/mg d.w. in normal subjects (p less than 0.005, p less than 0.005, respectively). It can be speculated that the CCK-level of the duodenal mucosa in patients with cholelithiasis may be regulated by a feedback mechanism and CCK in patients with duodenal ulcer may act physiologically for the cure of duodenal ulcer.

Topics: Adolescent; Adult; Aged; Animals; Biological Assay; Cholecystokinin; Cholelithiasis; Duodenal Ulcer; Duodenum; Female; Guinea Pigs; Humans; Intestinal Mucosa; Male; Middle Aged

Topics: Cholecystectomy; Cholecystokinin; Cholelithiasis; Duodenal Ulcer; Humans; Peptic Ulcer; Pylorus; Vagotomy

Topics: Biliary Tract Diseases; Cholangiography; Cholecystectomy; Cholecystokinin; Cholelithiasis; Humans

Peritoneoscopic puncture of the gallbladder for transvesical cholecysto-cholangiography and for aspiration of bile for chemical and bacteriological analysis is performed rather rarely because of a seemingly high rate of complications. The risk however is low if an appropriate technique is used. In our series the gallbladder was punctured in 110 cases; a local peritonitis subsiding under conservative treatment occured as a complication in only one case. Peritoneoscopic puncture of the gallbladder is indicated in the following conditions: extrahepatic occlusion of the bile duct system of unknown origin, nonvisualization of the gallbladder during cholangiography, biliary dyskinesia, typical biliary colics with normal X-ray findings. In addition, gallbladder puncture should be done if any suspicion of gallbladder disease arises during peritoneoscopy. The procedure as well as technical variations for cholecysto-cholangiography and for X-ray investigation of the pancreatic duct system are described.

Topics: Bile; Cholangiography; Cholecystokinin; Cholelithiasis; Chronic Disease; Female; Hepatic Duct, Common; Humans; Laparoscopy; Male; Middle Aged; Pancreatic Neoplasms; Pancreatitis

Using a duodenal perfusion technique, the biliary output of bile acids, phospholipid, and cholesterol was measured hourly during three meals and an overnight fast in seven Caucasians with radiolucent gallstones in a functioning gallbladder, and in seven health controls without gallstones, closely matched for age, sex, and weight. Before the perfusion, bile acid kinetics were defined by an isotope dilution procedure, and the biliary lipid composition of fasting gallbladder bile was determined. Total daily biliary lipid output was similar in gallstone and control subjects, and was unrelated to cholesterol saturation of fasting gallbladder bile and to bile acid pool size. There was an inverse relationship between the size and recycling frequency of the bile acid pool, so that secretion rate and hepatic return of bile acids remained constant, despite a wide range of pool sizes. The finding of a normal bile acid synthesis rate in subjects with a small pool size therefore indicated normal feedback regulation of bile acid synthesis. Hourly measurements of biliary lipid output showed a linear relationship between bile acid and cholesterol output, with a similar regression line for gallstone and control subjects, but a non-linear relationship between bile acid and phospholipid output. Consequently, samples from all subjects were consistently supersaturated with cholesterol at low bile acid outputs, especially during overnight fasting, but not at high bile acid outputs. These findings indicate that hepatic secretion of bile supersaturated with cholesterol is physiological in man at low bile acid outputs, that bile acid pool size is probably determined in part by its recycling frequency, and that cholesterol cholelithiasis in some Caucasians may be due to an underlying extrahepatic abnormality.

Topics: Adult; Aged; Bile; Bile Acids and Salts; Chenodeoxycholic Acid; Cholecystokinin; Cholelithiasis; Cholesterol; Diet; Duodenum; Eating; Enteral Nutrition; Fasting; Female; Gallbladder; Humans; Kinetics; Lipid Metabolism; Liver; Male; Middle Aged; Phosphatidylcholines; Phospholipids; Polyethylene Glycols

A cholecystokinin (CCK) test was performed on 13 female patients who were thought to be having attacks of gallbladder pain and in whom at least one cholecystogram had been normal. In 10 of these patients the CCK test was performed during the course of a repeat cholecystogram in order to assess the effect of CCK on gallbladder contraction. There was no constant relationship between a positive test and gallbladder contraction as measured radiographically. Cholecystectomy was undertaken in 9 patients and of these, 4 had been CCK positive, 4 had been CCK negative and 1 had reacted equivocally. None of the CCK positive patients had stones at operation, whereas 2 of the CCK negative patients had one or two small stones. In this small series cholecystectomy relieved both the CCK negative and CCK positive patients of pain with equal frequency. It is concluded that a negative CCK test by no means excludes the presence of symptomatic gallstones in patients with X-ray negative gallbladder pain.

Topics: Adult; Cholecystectomy; Cholecystography; Cholecystokinin; Cholelithiasis; Female; Gallbladder; Gallbladder Diseases; Humans; Middle Aged

Electrical spike potentials and intrauminal pressure variations were recorded from the human duodenum and distal ileum before and after i.v. administration of 80 log Ivy units of cholecystokinin. In the duodenum, quantitative calculations of motility gave identical values before and after drug administration, and results were identical in patients before and after cholecystectomy as well as in hernia patients without upper gastrointestinal disease. A decrease in amplitude of the spike potentials was observed in the duodenum during the first few minutes after drug administration in all groups. Recordings from the distal ileum in ileostomy patients showed a significant increase in motility after CCK administration whereas the spike potential amplitude was unchanged.

Topics: Action Potentials; Adult; Aged; Cholecystectomy; Cholecystokinin; Cholelithiasis; Depression, Chemical; Duodenum; Female; Gastrointestinal Motility; Hernia, Inguinal; Humans; Ileostomy; Ileum; Male; Middle Aged; Pressure; Stimulation, Chemical

Topics: Bile; Biliary Dyskinesia; Cholecystectomy; Cholecystography; Cholecystokinin; Cholelithiasis; Diagnosis, Differential; Gallbladder; Humans

The mechanisms of bile excretion are investigated in 27 experiments in 21 mini-pigs. The results confirm the known three fractions of bile flow for mini-pigs, too: a canalicular bile acid dependent, a canalicular bile acid independent and a ductular bile acid independent bile flow. These different fractions of bile flow may be stimulated either by taurocholate, by phenobarbital and ioglycamide or by secretin and pancreozymin. The total bile acid pool amounts 4,4 mMol. Measurements of its distribution over the gallbladder and the enterohepatic circulation after fasting for 18-24 hours emphasize the importance of the gallbladder resp. the fasting as factors that may be responsible for the secretion of lithogenic bile.

Topics: Animals; Bile; Bile Acids and Salts; Cholecystectomy; Cholecystokinin; Cholelithiasis; Cholestasis; Enterohepatic Circulation; Fasting; Gallbladder; Ioglycamic Acid; Phenobarbital; Secretin; Stimulation, Chemical; Swine; Taurocholic Acid

Topics: Adult; Cholecystography; Cholecystokinin; Cholelithiasis; Female; Gallbladder Diseases; Humans; Middle Aged

Topics: Adult; Aged; Cholecystokinin; Cholelithiasis; Duodenal Diseases; False Negative Reactions; False Positive Reactions; Female; Humans; Male; Middle Aged; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Parotid Gland; Saliva; Secretin

Topics: Acute Disease; Adult; Aged; Alcoholism; Biliary Tract Diseases; Blood Glucose; Cholecystokinin; Cholelithiasis; Chronic Disease; Diabetes Mellitus; Europe; Female; Glucagon; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Pancreatitis; Recurrence; Sex Factors; Stimulation, Chemical; United States

Topics: Cholecystokinin; Cholelithiasis; Duodenal Ulcer; Esophageal Achalasia; Gastrins; Gastritis; Gastrointestinal Hormones; Humans; Pancreatic Diseases; Peptic Ulcer; Secretin; Stomach Neoplasms; Stomach Ulcer

Topics: Adult; Amylases; Cholecystokinin; Cholelithiasis; Chronic Disease; Diagnosis, Differential; Duodenal Diseases; Endoscopy; Female; Glucose Tolerance Test; Humans; Liver Diseases; Male; Middle Aged; Pancreas; Pancreatic Ducts; Pancreatic Neoplasms; Pancreatitis; Radiography; Secretin

Topics: Cholecystokinin; Cholelithiasis; Duodenum; Humans; Intestinal Secretions; Pancreas; Pancreatic Diseases; Secretin

Topics: Animals; Bile; Cholecystitis; Cholecystokinin; Cholelithiasis; Common Bile Duct; Swine; Vagotomy; Vagus Nerve

Topics: Animals; Cholecystokinin; Cholelithiasis; Cholestanol; Cholesterol; Female; Gallbladder; Rabbits

Ileal disease or resection causes bile salt malabsorption and a reduction in the bile salt content of bile. Since cholesterol solubility requires adequate bile salt concentrations, depletion of the bile salt content of bile might, therefore, jeopardize cholesterol solubility and predispose to cholesterol gallstone formation. To study this, we examined biliary lipid composition in 10 patients with ileal dysfunction and in 25 healthy controls. Biliary lipid composition, as analysed in cholecystokinin-stimulated, bile-rich duodenal fluid, was shown to be representative of gallbladder bile and reproducible on repeat duodenal intubation. Nine of the 10 patients with ileal dysfunction had an abnormal, supersaturated bile in which the limits of cholesterol solubility were exceeded, and while nine of 25 control subjects also had an unstable bile, the mean bile composition in the ileal dysfunction group was significantly different from the control population. These studies provide a physicochemical explanation for the clinical observation that patients with ileal dysfunction have an increased incidence of gallstones.

Topics: Adult; Aged; Bile; Bile Acids and Salts; Cholecystokinin; Cholelithiasis; Cholesterol; Female; Humans; Ileum; Intestinal Diseases; Male; Middle Aged; Phospholipids

Topics: Adult; Aged; Cholecystitis; Cholecystography; Cholecystokinin; Cholelithiasis; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Vagotomy; Vagus Nerve

Topics: Adult; Aged; Bile; Bile Acids and Salts; Bile Ducts, Intrahepatic; Bilirubin; Cholecystectomy; Cholecystokinin; Cholelithiasis; Cholesterol; Common Bile Duct; Female; Humans; Liver; Male; Middle Aged; Phospholipids

Topics: Bile; Bile Acids and Salts; Body Weight; Cholecystokinin; Cholelithiasis; Cholesterol; Cholestyramine Resin; Chromatography, Gas; Clofibrate; Female; Gallbladder; Humans; Phosphatidylcholines

Topics: Adult; Age Factors; Biliary Tract Diseases; Cholecystectomy; Cholecystography; Cholecystokinin; Cholelithiasis; Colic; Cystic Duct; Female; Humans; Middle Aged; Nausea; Psychophysiologic Disorders; Sex Factors; Vomiting

Topics: Adolescent; Adult; Aged; Child; Cholecystitis; Cholecystography; Cholecystokinin; Cholelithiasis; Contrast Media; Female; Gallbladder Diseases; Gastrointestinal Motility; Humans; Intestine, Small; Male; Middle Aged; Time Factors

Topics: Adult; Asthenia; Cholecystectomy; Cholecystography; Cholecystokinin; Cholelithiasis; Colon; Colon, Sigmoid; Constipation; Desensitization, Immunologic; Diarrhea; Dyspepsia; Female; Headache; Histamine H1 Antagonists; Humans; Hypersensitivity; Middle Aged; Pain; Postoperative Complications; Sleep Wake Disorders; Stomach

Topics: Calcinosis; Cholecystitis; Cholecystokinin; Cholelithiasis; Cholesterol; Female; Gallbladder; Gallbladder Diseases; Humans; Male

Topics: Biliary Dyskinesia; Cholecystectomy; Cholecystitis; Cholecystokinin; Cholelithiasis; Gallbladder Diseases; Humans

Topics: Adult; Aged; Amylases; Celiac Disease; Cholecystitis; Cholecystokinin; Cholelithiasis; Gastrointestinal Diseases; Humans; Infusions, Parenteral; Middle Aged; Pancreas; Pancreatitis; Proteins; Secretin; Secretory Rate

Topics: Biliary Dyskinesia; Cholecystokinin; Cholelithiasis; Gallbladder Diseases; Gastrointestinal Diseases; Humans; Hypersensitivity; Muscle, Smooth; Radiography

Topics: Animals; Cholecystokinin; Cholelithiasis; Cholestanol; Cricetinae; In Vitro Techniques; Rabbits

Topics: Ampicillin; Bacteriological Techniques; Bacteriology; Carrier State; Cholecystokinin; Cholelithiasis; Feces; Gastric Juice; Humans; Intubation; Intubation, Gastrointestinal; New York; Penicillins; Salmonella typhi; Typhoid Fever