ceruletide and Cholelithiasis

Circumstantial evidence suggests that gallstone-induced pancreatitis is triggered by obstruction of the pancreatic duct. In this report I will review the results of studies conducted during the last decade that have employed the diet-induced, secretagogue-induced, and duct obstruction-induced models of experimental pancreatitis to investigate the early events that lead to the development of acute pancreatitis. In each of these models, digestive enzyme zymogens and the lysosomal hydrolase cathepsin B were found to become colocalized. These observations have led to the hypothesis that intra-acinar cell activation of digestive enzyme zymogens by lysosomal hydrolases may be an important critical event in the development of acute pancreatitis. Recent morphologic studies evaluating the initial 24 hours after ligation of the opossum pancreatic duct indicate that the earliest lesions in this model of hemorrhagic pancreatitis occur in acinar cells.

Topics: Acute Disease; Amino Acids; Amylases; Animals; Ceruletide; Cholelithiasis; Choline Deficiency; Disease Models, Animal; Edema; Enzyme Precursors; Ethionine; Hydrolases; Mice; Pancreatitis; Protein Biosynthesis; Proteins; Rabbits

Topics: Biliary Tract Diseases; Ceruletide; Cholangiography; Cholelithiasis; Duodenal Ulcer; Endoscopy; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Gastrointestinal Hormones; Humans; Intestinal Absorption; Lactose Intolerance; Pancreatic Diseases; Peptic Ulcer; Radionuclide Imaging; Secretin; Stomach Neoplasms

Twenty-six randomly selected patients 2-6 years (mean: 3.5) after rapid percutaneous catheteric litholysis at the Radiological Department were investigated by quantitative Ceruletide cholescintigraphy in this pilot study. The average EF of the patients with recurrent gallstones (Group II) was lower (55 +/- 23%) than that of the patients without stones (69 +/- 23%) (Group I). The authors conclude that this scintigraphic method could help not only to select the best method to make patient stonefree but has an important role in forecasting the prognosis of gallstone recovery after litholytic therapy.

Topics: Ceruletide; Cholecystography; Cholelithiasis; Female; Gallbladder; Humans; Male; Radionuclide Imaging

A randomized placebo-controlled double-blind trial was carried out in 24 patients with biliary colic pain in order to evaluate the analgesic effect of caerulein (CRL). Caerulein (1 ng/kg . min infused intravenously over 15 min) showed an analgesic effect that was significantly higher than placebo (p less than 0.001). The analgesic action of CRL was not inhibited by naloxone (0.4 mg intravenously, administered two times). Further, the effect of i.v. CRL or saline on artificially induced biliary tree hypertension was studied in 7 patients with a T-tube common bile duct drainage. During saline intravenous administration, increasing biliary tree pressure resulted in pain in 5 patients, with the threshold for pain being 40 cmH2O. During CRL intravenous infusion, significantly higher perfusion pressures were required to achieve a given common bile duct pressure and the pressure threshold for pain was not reached. Consequently, pain was prevented in all patients. These data suggest that CRL relieves biliary colic pain by reducing biliary tract pressure.

Topics: Adult; Bile Ducts; Biliary Tract Diseases; Ceruletide; Cholelithiasis; Clinical Trials as Topic; Colic; Double-Blind Method; Female; Humans; Infusions, Parenteral; Male; Middle Aged; Naloxone; Pressure; Random Allocation; Time Factors

24 gallstone patients were treated with cicloxilic acid, an agent endowed with choleretic activity, at the dose of 240 mg/day for 1 month. 24 comparable patients on placebo treatment acted as controls. Bile lipid composition was determined and the saturation index calculated before and after treatment, on samples collected by duodenal siphonage after caerulein stimulation, in both groups. In the cicloxilic group there was little or no change in bile salts and phospholipids, whereas biliary cholesterol concentration was significantly reduced (p less than 0.05) and consequently the lithogenic index lowered (from 1.5 to 1.2, p less than 0.01). Cicloxilic acid can have a place in gallstone disease therapy in association with the litholytic bile acids or in the prevention of gallstone formation in high-risk populations.

Topics: Adult; Aged; Bile; Ceruletide; Cholelithiasis; Cholesterol; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Double-Blind Method; Female; Humans; Lipids; Male; Middle Aged; Phospholipids; Random Allocation

There have been various studies of exocrine pancreatic function after acute pancreatitis, but few have examined the relationship between this function and the etiology of the pancreatitis. The aim of this work was to study pancreatic function in patients who had had acute alcoholic or acute biliary pancreatitis.. Seventy-five patients who had had a single attack of acute pancreatitis were studied. The etiology was alcohol in 36 and cholelithiasis in 39. Pancreatic function was studied between 4 and 18 months after pancreatitis by duodenal intubation in 18 patients (8 alcohol, 10 lithiasis) and by the amino acid consumption test (AACT) in the remaining 57 (28 alcohol, 29 lithiasis). For those who underwent AACT, the test was repeated 1 year after the first examination.. Among the 36 patients with alcoholic pancreatitis, most had impaired pancreatic function at both duodenal intubation (8/8, 100%) and at AACT (22/28, 78.6%); at the second test, the AACT remained pathological (18/23, 82.1%). Of the 39 patients with biliary pancreatitis, only 4 of the 10 (40%) who underwent duodenal intubation and only 5 of the 29 (17.2%) who performed AACT had pancreatic insufficiency; at the second test, only 4 of the 26 (15.4%) who repeated the AACT were pathological. The differences in the frequency and degree of pancreatic insufficiency between patients with alcoholic and those with biliary pancreatitis were statistically significant.. The results show that after alcoholic acute pancreatitis, the pancreatic insufficiency was significantly more frequent and more severe than after biliary pancreatitis. These findings together with the fact that the insufficiency was also more persistent suggest that acute alcoholic pancreatitis may occur in a pancreas that already has chronic lesions.

Topics: Acute Disease; Adolescent; Adult; Aged; Amino Acids; Bicarbonates; Ceruletide; Cholelithiasis; Chymotrypsin; Exocrine Pancreatic Insufficiency; Female; Humans; Lipase; Male; Middle Aged; Pancreas; Pancreatitis; Pancreatitis, Alcoholic

Little information is available on the pathogenesis of cholesterol microlithiasis, and it is not clear if biliary lipid composition in these patients is similar to changes seen in cholesterol gall stone patients.. To measure biliary lipid composition in patients with cholesterol microlithiasis.. Eleven patients with cholesterol microlithiasis, 20 cholesterol gall stone patients, and 17 healthy controls.. Duodenal bile was collected in the fasting state during ceruletide infusion. Biliary cholesterol, phospholipids, and total bile acids were analysed by enzymatic assays, and conjugated bile acids by high pressure liquid chromatography.. Patients with microlithiasis had a cholesterol saturation index significantly higher than controls (mean value 1.30 (95% confidence interval 1.05-1.54) v 0.90 (0.72-1.08)) but similar to gall stone patients (1.51 (1.40-1.63)). This was due to a significant decrease in per cent phospholipid (10.0% (7.1-12.8)) compared with controls (21.4% (18.1-24.6)) and gall stone patients (24.9% (20.5-29.3)). Per cent cholesterol was similar in patients with microlithiasis and controls (5.3% (4.5-6.1) and 5.6 % (4.3-6.8), respectively) but was significantly increased in gall stone patients (10.9% (9.3-12.4)). Bile acid composition in patients with microlithiasis was similar to controls whereas in gall stone patients deoxycholic acid was significantly increased: 27.3% (24.8-29.7) v 19.0% (15.7-22.2) in controls and 20.6% (14.9-26.2) in patients with microlithiasis.. Patients with cholesterol microlithiasis have biliary cholesterol supersaturation, similarly to cholesterol gall stone patients. Whereas in the latter this is due to increased per cent cholesterol, in patients with microlithiasis this is caused by phospholipid deficiency, with normal per cent cholesterol and normal biliary bile acid composition.

Topics: Adult; Aged; Bile; Case-Control Studies; Ceruletide; Cholelithiasis; Cholesterol; Chromatography, High Pressure Liquid; Deoxycholic Acid; Female; Humans; Linear Models; Lipids; Male; Middle Aged; Phospholipids

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

In animal studies cholecystectomy has been found to alter the normal effect of cholecystokinin (CCK) on sphincter of Oddi (SO) function. This could be of importance with regard to the development of postcholecystectomy biliary pain. We therefore investigated the effect of laparoscopic cholecystectomy on SO motility before and after infusion with CCK.. A prospective study of SO motility, under basal conditions and during CCK (ceruletide) infusion, was carried out in eight women with uncomplicated gallstone disease, before and after laparoscopic cholecystectomy.. Laparoscopic cholecystectomy increased common bile duct pressure (P = 0.01) and decreased the frequency of phasic contractions (P=0.05). However, the inhibitory effect of CCK was preserved as infusion of CCK was associated with a significant reduction in SO phasic amplitude and frequency, both before and after cholecystectomy.. Following laparoscopic cholecystectomy an indisputable inhibitory effect of CCK in the SO was found. Common bile duct pressure increased and minor modifications in basal SO motility were seen.

Topics: Ceruletide; Cholecystectomy, Laparoscopic; Cholelithiasis; Common Bile Duct; Female; Gastrointestinal Agents; Humans; Manometry; Middle Aged; Pressure; Sphincter of Oddi

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

In experimental animals, sphincterotomy facilitates passage of solids from the gallbladder and inhibits gallstone formation apparently by improvement in gallbladder emptying. In humans, however, gallbladder emptying has not been studied following endoscopic sphincterotomy (ES) in patients with gallstones. We therefore prospectively studied resting and cerulin-stimulated gallbladder volumes by real time ultrasonography in 15 patients of choledocholithiasis with gallbladder in situ (eight with and seven without gallbladder calculi) before and after (after bile duct clearance) ES. ES significantly lowered resting gallbladder volume (21.2 +/- 10.6 vs 11.1 +/- 5.0; P < 0.0001) and cerulin-stimulated residual gallbladder volume (10.8 +/- 5.6 vs 4.4 +/- 2.1; P < 0.0001). ES also significantly increased the gallbladder ejection fraction (47.3 +/- 12.1% vs 58.8 +/- 11.1%; P < 0.0001). The rate constant for gallbladder emptying after cerulin infusion also increased significantly after ES (-0.022/min vs -0.031/ min; P < 0.0001). Significant improvement in gallbladder motility was observed in both groups of patients with and without gallbladder calculi. ES significantly improves gallbladder motility in humans.

Topics: Adult; Case-Control Studies; Ceruletide; Cholelithiasis; Female; Gallbladder; Gallbladder Emptying; Gallstones; Gastrointestinal Agents; Humans; Male; Middle Aged; Prospective Studies; Sphincterotomy, Endoscopic; Ultrasonography

In a previous study, we have shown that caerulein relieves biliary colic pain in gallstone patients. This study was initiated to determine gallbladder and sphincter of Oddi behaviour during biliary colic and their response to caerulein. In 10 gallstone patients gallbladder volume was measured by real-time ultrasonography during a biliary colic episode and 72 hours after cessation of pain, before and after caerulein administration. Basal sphincter of Oddi pressure was determined by CPRE manometry in 10 gallstone patients during biliary colic and three days after cessation of pain, before and after caerulein. The results of this study show that, during biliary colic, gallbladder volume is 8 times greater than in the post-colic state. Basal sphincter of Oddi pressure was also significantly higher during biliary colic than in the post-colic state. Caerulein relieved in all cases the biliary colic pain while reducing gallbladder volume and decreasing the sphincter of Oddi.

Topics: Adult; Ceruletide; Cholangiopancreatography, Endoscopic Retrograde; Cholelithiasis; Colic; Data Interpretation, Statistical; Female; Gallbladder; Gastrointestinal Agents; Humans; Male; Manometry; Middle Aged; Sphincter of Oddi; Ultrasonography

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

Intraluminal pressure of sphincter of Oddi (SO) was measured in awake patients who had undergone cholecystectomy and T-tube drainage for cholecystocholedocholithiasis. Pressure measurement was carried out using microtransducer which was inserted through sinus tract under cholangioscopy after removing T-tube. Mean value of the basal pressure was 12.0 +/- 1.5 mmHg, the amplitude of the phasic contraction was 55.2 +/- 4.4 mmHg and the frequency of the phasic contraction was 4.2 +/- 0.3 cycle/min. Intravenous administration of caerulein or atropine caused marked decrease in the amplitude and the frequency of the phasic contraction of SO, whereas pentazocine caused marked increase in the basal pressure, the amplitude and the frequency of the phasic contraction of SO. Naloxone alone did not affect the phasic contraction of SO, but it reduced the increased amplitude and frequency of the phasic contraction of SO caused by pentazocine. In conclusion, cholinergic nerves, excitatory nerves mediated by opioid receptors and non-cholinergic non-adrenergic inhibitory nerves may modulate spontaneous motor activity of human sphincter of Oddi.

Topics: Adult; Aged; Aged, 80 and over; Atropine; Ceruletide; Cholelithiasis; Cholinergic Fibers; Female; Gallstones; Humans; Male; Middle Aged; Muscle Contraction; Postoperative Period; Receptors, Opioid; Sphincter of Oddi

The effects of single and repeated short-term (4 hr) obstruction of pancreaticobiliary duct (PBDO), with or without exocrine stimulation (intraductal hypertension) by cerulein infusion (0.2 micrograms/kg.hr), on the exocrine pancreas were evaluated in the rat. Single blockage of pancreaticobiliary duct for 4 hr caused a significant rise in serum amylase levels, pancreatic water content, and redistribution of lysosomal enzyme, cathepsin B from the lysosomal fraction to the zymogen fraction, which was considered to mean the colocalization of lysosomal enzymes with pancreatic digestive enzymes in the same subcellular compartment in acinar cells. In addition, the accelerated lysosomal and mitochondrial fragility was observed in the single pancreaticobiliary-duct-obstructed animals. Moreover, the repeated PBDO for 4 hr (2 hr in each obstruction and 1 hr of free flowing of pancreaticobiliary juice between two obstructions) caused more marked changes in almost the all parameters, and the repeated PBDO with intraductal hypertension caused an activation of trypsinogen in the pancreas, making more marked changes in almost the all parameters than the repeated PBDO only group. These results indicate that the present model of repeated PBDO with exocrine stimulation seems to be a pertinent model for gallstone pancreatitis in humans, and that redistribution of lysosomal enzymes and subcellular organellar fragility seem to play an important role in the pathogenesis of pancreatic injuries induced by PBDO, particularly by repeated PBDO with exocrine stimulation, probably via activation of trypsinogen to trypsin by lysosomal enzyme, cathepsin B.

Topics: Acute Disease; Amylases; Animals; Body Water; Cathepsin B; Ceruletide; Cholecystitis; Cholelithiasis; Male; Pancreas; Pancreatic Ducts; Pancreatitis; Rats; Rats, Wistar; Trypsin; Trypsinogen

The effects of short-termed (2 hours) obstruction of pancreatico-biliary duct (PBDO) and exocrine stimulation (IDH) by caerulein infusion (0.2 microgram/kg.hr) with systemic hypotension (SH) (30% reduction of mean arterial pressure for 30 min) on the exocrine pancreas were evaluated in the rat. PBDO and IDH with SH caused more significant rises in portal serum amylase, cathepsin B and malate dehydrogenase levels, and pancreatic water content as well as more significant redistribution of cathepsin B activity from the lysosomal fraction to the zymogen fraction in the subcellular fractionations than only PBDO, or PBDO with IDH, or PBDO with SH group. In addition, more accelerated lysosomal and mitochondrial fragility were observed in the PBDO and IDH with SH group. Moreover, PBDO and IDH with SH caused an activation of larger amount of trypsinogen in the pancreas compared with other groups (PBDO with IDH and PBDO with SH group). These results indicate that present model of short-termed PBDO and exocrine stimulation with systemic hypotension seems to be pertinent model for gallstone pancreatitis in humans, and that redistribution of lysosomal enzymes and subcellular organellar fragility seem to play an important role in the pathogenesis of pancreatic injuries by PBDO, particularly with exocrine stimulation and pancreatic ischaemia, probably via activation of trypsinogen to trypsin by lysosomal enzyme such as cathepsin B.

Topics: Animals; Bile Ducts; Ceruletide; Cholelithiasis; Disease Models, Animal; Hypotension; Male; Pancreas; Pancreatic Ducts; Pancreatitis; Rats; Rats, Wistar

Sphincter of Oddi motility was measured in 55 gallstone patients either through the sinus tract of percutaneous transhepatic biliary drainage or through the T tube. The influence of cholecystectomy and gastrectomy on the sphincter of Oddi was analyzed by comparing responses in patients with or without surgery to the administration of cerulein and the ingestion of dry egg yolk. When comparing cholecystectomized patients to nonsurgical subjects, cholecystectomy revealed no influence on the response to cerulein and feeding. Both groups showed relaxation of contraction waves after provocations. On the other hand, two thirds of the postgastrectomy patients showed an acceleration in the contractions of the sphincter of Oddi after provocations (one third showed no change), while all of the nongastrectomy group saw the disappearance of the wave after cerulein administration and 83% revealed complete suppression of the wave after feeding. It is suspected that this paradoxical response to CCK on the sphincter of Oddi is a lithogenic factor after gastrectomy.

Topics: Ceruletide; Cholecystectomy; Cholelithiasis; Egg Yolk; Gastrectomy; Humans; Incidence; Manometry; Peristalsis; Postgastrectomy Syndromes; Sphincter of Oddi

A nonoperative examination of the function of the sphincter of Oddi, involving percutaneous transhepatic manometry via the percutaneous transhepatic biliary drainage tract, was developed and clinically applied in 23 patients with biliary disease. Long-term recording of sphincter of Oddi motility, which was impossible using conventional intraoperative or endoscopic manometry, was made possible by means of this method and revealed various changes of sphincter of Oddi motility. The mean recording time was 131.33 +/- 9.77 min. The frequency of contractions of the sphincter of Oddi in basal fasting conditions varied from 0 to 13/min and high-frequency contractions (frequency 9.49 +/- 0.35/min, duration 5.77 +/- 0.54 min) were observed in 12 patients on a total of 19 occasions. In five patients, high-frequency contractions were observed twice during one session of continuous recording and the interval between burst contractions was 85.4 +/- 13.3 min. Long-term continuous recording is advantageous for the evaluation of the function of the sphincter of Oddi and short-term manometry may not be representative of overall sphincter of Oddi motility.

Topics: Adult; Aged; Aged, 80 and over; Ceruletide; Cholelithiasis; Common Bile Duct Diseases; Constriction, Pathologic; Dilatation, Pathologic; Eating; Gastrointestinal Motility; Humans; Manometry; Middle Aged; Sphincter of Oddi

In 10 patients with gall stone disease (eight women, two men; mean (SD) age 47.4 (13) years), bile was obtained by endoscopic aspiration after stimulation of the gall bladder with ceruletid and also by fine needle puncture of the gall bladder under local anaesthetic. The total lipid concentration of the puncture bile samples was mean (SD) 11.9 (4.7) g/dl, significantly higher than the endoscopic bile samples (3.9 (3.3) g/dl, p less than 0.001). Total bile acids, phospholipids, and biliary cholesterol (expressed in mol%) and cholesterol saturation index showed no significant differences between the two types of samples. The glycocholic acid concentration in the endoscopically obtained bile (27.7 (6.6) mol% v 23.3 (5.4) mol%; p less than 0.01) was significantly higher than the puncture bile samples. Puncture bile exhibited a significantly shorter nucleation time (3.5 (3.3) days v 19.6 (11.9) days; p less than 0.001). For determination of the nucleation time, endoscopic bile aspiration after gall bladder stimulation with ceruletid led to adequately concentrated samples in 50% of the study subjects. Cholesterol monohydrate crystal formation in native bile was observed in six samples of puncture bile and in three samples of the endoscopically obtained bile. The presence of cholesterol crystals and the determination of nucleation time in the puncture bile were the best discriminants between cholesterol and pigment gall stones and correlated well with computed tomogram analysis.

Topics: Adult; Aged; Bile; Bile Acids and Salts; Ceruletide; Cholelithiasis; Cholesterol; Drainage; Duodenoscopy; Duodenum; Female; Gallbladder; Glycocholic Acid; Humans; Male; Middle Aged; Phospholipids; Specimen Handling

Gallbladder emptying after intramuscular injection of cerulein was investigated by 99mTc-EHIDA hepatobiliary scintigraphy in 23 patients with biliary disease, 55 patients with chronic liver disease, and 21 normal controls. The mean gallbladder ejection fraction in patients with gallstones and liver cirrhosis was significantly reduced compared with normal controls. (gallstones: 56.3 +/- 21.3%, LC with gallstones: 50.8 +/- 29.6%, LC without gallstones: 55.9 +/- 26.7%, vs. normal controls: 74.4 +/- 12.9%, p less than 0.01). The mechanism for sluggish gallbladder emptying in liver cirrhosis is unknown, however impaired emptying with bile stasis provides a potential pathophysiologic basis for the high frequency of pigment stones.

Topics: Adult; Aged; Aged, 80 and over; Ceruletide; Cholelithiasis; Female; Gallbladder; Humans; Imino Acids; Liver Cirrhosis; Male; Middle Aged; Organometallic Compounds; Radionuclide Imaging; Technetium; Technetium Tc 99m Diethyl-iminodiacetic Acid

A new three-phase therapeutical approach to retained biliary stones (RBS) is designed to shorten the long treatment times with Monooctanoin (Mo). In the first phase, the litholytic agent is infused to soften the stones. In the second one the calculi are crushed, and in the last complete elimination of the fragmentary stones into the duodenum is obtained after 1-2 flushings with ceruletide. In 6 patients a complete clearance of the stones was obtained (success 100%) together with a reduction in the litholytic agent dose (52%) and the infusion time (62%), in comparison with the results of using Mo. alone.

Topics: Adult; Aged; Caprylates; Ceruletide; Cholangiography; Cholelithiasis; Drug Evaluation; Female; Glycerides; Humans; Male; Middle Aged; Solvents

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

The filling and emptying characteristics of the gallbladder in prairie dogs and rabbits were studied to assess the importance of the residual bile in the pathogenesis of gallstones. In prairie dogs under ketamine/xylazine anesthesia, a significantly larger fraction (p = 0.001) of hepatic bile entered the gallbladder (87 +/- 8%) than the intestine during fasting and very little bile emptied (0-3% ejection fraction) following ceruletide infusion. In rabbits under similar anesthesia, only a small fraction of hepatic bile entered the gallbladder (4 +/- 2%) during fasting, and the gallbladder emptied almost completely (85% ejection fraction) following ceruletide infusion. The resultant higher residual bile in the prairie dog gallbladder and lower residual bile in the rabbit gallbladder may explain why gallstones form so readily in prairie dogs but not in rabbits when fed a lithogenic diet. These similarities and differences in gallbladder function must be taken into account when considering any animal as a model for gallstone formation.

Topics: Animals; Bile; Ceruletide; Cholelithiasis; Gallbladder; Humans; Intestine, Small; Male; Rabbits; Sciuridae; Time Factors

Topics: Adult; Aged; Ceruletide; Cholelithiasis; Female; Humans; Male; Middle Aged

Topics: Ceruletide; Cholelithiasis; Humans; Therapeutic Irrigation

Topics: Ceruletide; Cholelithiasis; Gallbladder; Humans; Sphincter of Oddi; Ultrasonography

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

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

Topics: Ampulla of Vater; Ceruletide; Cholelithiasis; Cystic Duct; Gallstones; Humans; Sodium Chloride; Sphincter of Oddi; Therapeutic Irrigation

The functional activity of the sphincter of Oddi complex has been examined by ceruletide manometry in patients undergoing cholecystectomy with a normal peroperative cholangiogram. In Group I (n = 14), which included patients with previous acute cholecystitis/biliary colic, the sphincter activity appeared to be normal and responded to intravenous ceruletide by a marked relaxation with a significant fall in both the infusion and postinfusion pressures. In patients undergoing cholecystectomy for gallstone-associated pancreatitis (n = 8), the sphincter exhibited manometric features of hypotonia with low infusion and postinfusion pressures which were not significantly altered by intravenous ceruletide.

Topics: Acute Disease; Adult; Aged; Ampulla of Vater; Ceruletide; Cholecystectomy; Cholecystitis; Cholelithiasis; Colic; Common Bile Duct; Humans; Manometry; Middle Aged; Pancreatitis; Sphincter of Oddi

Topics: Adult; Ceruletide; Cholelithiasis; Chronic Disease; Female; Gallbladder; Humans; Male; Middle Aged; Pressure; Rest

The manometric post-operative cholangiography through external drainage is now a method of everyday use. However in some cases the substenotic appearance of the terminal bile tract and of the Oddi's sphincter gives rise to doubts as to the real cause of this alteration. Caerulein solves the functional hypertone. It also starts a good peristalsis of the terminal bile tract, reducing the intrabiliary pressure and causing an evident transpapillary passage. Thus, the use of this substance allows a differential diagnosis between organic or functional stenosis.

Topics: Ceruletide; Cholangiography; Cholelithiasis; Cholestasis; Diagnosis, Differential; Drainage; Humans; Manometry; Postoperative Complications

The Authors report their experience of postoperative cholangiomanometry carried out through a T-tube on 19 patients; in 13 of such patients the Oddi's sphincter was intact, while 6 of them underwent sphincterectomy. In 8 patient's a manometric study of the duodenum was associated. They performed both variable flow and pressure and constant flow manometry and their results show that such examination is a reliable test both for the functional evaluation of the surgical procedure, and for the study of the action of various drugs on Oddi's sphincter function and its correlation with duodenal motility.

Topics: Ampulla of Vater; Bile Ducts; Ceruletide; Cholelithiasis; Duodenum; Fentanyl; Gastrointestinal Motility; Humans; Manometry; Metoclopramide; Neostigmine; Nitroglycerin; Postoperative Care; Pressure; Sphincter of Oddi; Succinylcholine

The effect of intravenous and intramuscular administration of ceruletide on gallbladder contraction was investigated in 67 normal volunteers and patients. Of the 45 normal volunteers, 33 received the drug intravenously and 12 intramuscularly in graded ascending doses. By either means of injection, ceruletide produced a substantial contraction of the gallbladder with a measurable reduction in gallbladder area. Based on findings in these groups, the 22 patients requiring oral cholecystography for clinical evaluation received 0.3 microgram/kg intramuscularly. The intramuscular administration of synthetic ceruletide after oral cholecystography, in a dose of 0.o microgram/kg, afforded a safe and effective means of gallbladder contraction, with resultant cystic and common bile duct visualization. Side effects occurred less frequently when the drug was administered intramuscularly and were minimal and self-limiting. Peak contraction (40% or greater reduction in size) occurred as early as 5-15 min after after intramuscular injection and in most instances within 30 min.

Topics: Adult; Aged; Ceruletide; Cholecystography; Cholelithiasis; Dose-Response Relationship, Drug; Female; Gallbladder; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged