Peppermint oil improves the manometric findings in diffuse esophageal spasm.

BACKGROUND: Diffuse esophageal spasm (DES) is an uncommon condition that results in simultaneous esophageal contractions. Current medical treatment of DES is frequently unsatisfactory. We hypothesized that, as a smooth muscle relaxant, peppermint oil may improve the manometric findings in DES. STUDY: Eight consecutive patients with chest pain or dysphagia and who were found to have DES were enrolled during their diagnostic esophageal manometry. An eight-channel perfusion manometry system was used. Lower esophageal sphincter pressure and contractions of the esophageal body after 10 wet swallows were assessed before and 10 minutes after the ingestion of a solution containing five drops of peppermint oil in 10 mL of water. Each swallow was assessed for duration (seconds), amplitude (mm Hg), and proportion of simultaneous and multiphasic esophageal contractions. RESULTS: Lower esophageal sphincter pressures and contractile pressures and durations in both the upper and lower esophagus were no different before and after the peppermint oil. Peppermint oil completely eliminated simultaneous esophageal contractions in all patients (p < 0.01). The number of multiphasic, spontaneous, and missed contractions also improved. Because normal esophageal contractions are characteristically uniform in appearance, variability of esophageal contractions was compared before and after treatment. The variability of amplitude improved from 33.4 +/- 36.7 to 24.9 +/- 11.0 mm Hg (p < 0.05) after the peppermint oil. The variability for duration improved from 2.02 +/- 1.80 to 1.36 +/- 0.72 seconds (p < 0.01). Two of the eight patients had chest pain that resolved after the peppermint oil. CONCLUSIONS: This data demonstrates that peppermint oil improves the manometric features of DES.

Postprandial improvement of gastric dysrhythmias in patients with type II diabetes: identification of responders and nonresponders.

Using the technique known as electrogastrography, we studied the postprandial response of gastric myoelectrial activity in subjects with type II diabetes. Seventy-one subjects with type II diabetes underwent 1 hr of fasting electrogastrography recording. HbA1c and fasting serum glucose levels were obtained. Subjects then underwent an additional 2 hr of electrogastrography recording in the post prandial state. Sixty of the 71 patients (85%) had gastric rhythm abnormalities in the fasting state. Forty-six of 71 subjects (65%) responded to the test meal by improving their electrogastrography tracings (responders) while 35% did not respond (nonresponders). The time spent in bradygastria during the fasting state by responders was 26.3+/-12.8% vs 10.9+/-8.5% for nonresponders (P < 0.0001). The percent tachygastria during the fasting state in responders was 19.8+/-13.0%, which was less than nonresponders (38.3+/-29.7%) (P < 0.001). Fasting plasma glucose and HbA1c could not be used to predict the gastric myoelectrical response to meal. In conclusion, gastric rhythm disturbances are common in type II diabetes; there was no correlation between HbA1c levels, age, duration of diabetes, or fasting serum glucose and gastric dysrhythmia in response to meal; two groups of subjects emerged: those who became less dysrhythmic in the post pradial state (responders) and those who did not (non-responders); and fasting bradygastria was associated with responders and fasting tachygastria was associated with nonresponders.

Nucleation of biliary cholesterol, arachidonate, prostaglandin E2, and glycoproteins in postmenopausal women.

BACKGROUND & AIMS: Among dieting obese patients, cholesterol gallstone formation is preceded by increases in levels of biliary cholesterol saturation, arachidonate, prostaglandin E2, total glycoproteins, and rapid nucleation of cholesterol. The aim of this study was to determine if similar increases occur among postmenopausal women with cholesterol crystals in their bile. METHODS: In 101 postmenopausal women without gallstones, gallbladder bile was sampled via nasoduodenal tube and analyzed. RESULTS: Nineteen of the women had saturated bile and crystals. Levels of cholesterol saturation, arachidonate, prostaglandin E2, and total glycoprotein were highest among women with cholesterol-saturated bile and cholesterol crystals and lowest among women with unsaturated bile. Levels were intermediate among women with saturated bile but no crystals. CONCLUSIONS: Among postmenopausal women, increases in levels of biliary cholesterol saturation, arachidonate, prostaglandin E2, and total glycoproteins may be important pathophysiologically in the rapid nucleation of cholesterol crystals.

Effects of ursodiol or ibuprofen on contraction of gallbladder and bile among obese patients during weight loss.

Rapid loss of weight in obese patients is associated with increased saturation of bile with cholesterol, increased nucleation and growth of cholesterol crystals, and gallstones. The aims of this study were to determine the effects of rapid weight loss on contraction of the gallbladder and to evaluate the effects of ursodiol and ibuprofen on saturation, nucleation and growth, and contraction. Forty-seven obese patients entering a very low calorie dietary program were randomized to receive ursodiol, 1200 mg/day, ibuprofen, 1600 mg/day, or placebo for 12 weeks. Contraction of the gallbladder to a liquid meal was evaluated by ultrasonography, and duodenal bile was collected initially and after six and 12 weeks. Diet caused reduced contraction of the gallbladder, increased cholesterol saturation, and increased nucleation and growth of crystals. Ursodiol reduced saturation and prevented increases in nucleation and growth and contraction. Ibuprofen prevented the increase in saturation and the reduction in contraction with a trend opposing the increase in nucleation and growth. In conclusion, during dieting, contractility of the gallbladder to meals is reduced. The effectiveness of ursodiol in preventing gallstones may be explained partially by effects on contraction. Ibuprofen deserves further study because of its effects on saturation, nucleation and growth, and contraction.

The sequence of biliary events preceding the formation of gallstones in humans.

The aim of the present study was to determine the sequence of events leading to formation of gallstones among obese patients predisposed to cholesterol gallstones by a very low-calorie diet. Nine obese patients beginning a 520-kcal diet had gallbladder bile collected from the duodenum before beginning the diet and seven times during the first 56 days of the diet. Biliary cholesterol saturation index and levels of arachidonate, prostaglandin E2, and glycoprotein increased significantly; nucleation time decreased; and total lipid concentration did not change. Decreases in nucleation time preceded the appearance of cholesterol crystals. Significant (P less than 0.05) increases in prostaglandin E2 level were preceded by significant increases in arachidonate level and followed by significant increases in glycoprotein level. These observations support the hypotheses that in obese patients predisposed to gallstones by very low-calorie diets (a) decreases in nucleation time are necessary before cholesterol crystals form in the gallbladder; (b) biliary arachidonate, through its conversion to prostaglandins, promotes biliary synthesis and secretion of glycoprotein; (c) biliary glycoprotein promotes nucleation; and (d) increases in the concentration of gallbladder bile are not necessary for cholesterol nucleation to occur in vivo.

Factors affecting the measurement of cholesterol nucleation in human gallbladder and duodenal bile.

The study of cholesterol gallstone disease would be facilitated if the nucleation time of cholesterol crystals could be measured in duodenal bile and was correlated with nucleation occurring in vivo. Therefore, our aims were to determine (a) if nucleation time could be measured in duodenal bile, (b) the effect of bacteria, phospholipase, protease, and dilution on the measurement of nucleation time, and (c) the ability of nucleation time of duodenal bile to reflect changes occurring in vivo that promote the formation of gallstones and, therefore, the potential usefulness of nucleation time in predicting and studying the formation of gallstones. Gallbladder bile was obtained from 27 patients undergoing elective cholecystectomy and 19 patients undergoing diagnostic duodenal biliary drainage. Among the 14 bile samples collected by drainage that nucleated within 21 days, mean nucleation time was 6.3 +/- 2.8 days. The addition of inhibitors of phospholipase or protease prolonged nucleation time slightly. Bacteria were cultured from one bile sample at the time of collection and five samples at the time of nucleation. The addition of antibiotics had no effect on nucleation time. Dilution of bile collected at cholecystectomy to the concentration of duodenal bile prolonged nucleation time. In 4 of 5 obese patients receiving a very low calorie diet and predisposed to gallstones, the nucleation time in duodenal bile shortened, and the shortest nucleation times were associated with the formation of cholesterol crystals in vivo. Thus, measurement of nucleation time in duodenal bile may be useful in predicting and studying the formation of cholesterol gallstones.

Roles of deoxycholate and arachidonate in pathogenesis of cholesterol gallstones in obese patients during rapid loss of weight.

Our aim was to examine the relationship between biliary deoxycholate and arachidonate in obese patients and the relationship of deoxycholate and arachidonate to the stimulation of biliary mucous glycoprotein among obese patients predisposed to cholesterol gallstones. Thirty-four obese patients predisposed to cholesterol gallstones by a weight-reducing diet (520 kcal/day) received placebo, ursodiol (1200 mg/day), or aspirin (1300 mg/day). Duodenal bile was collected prior to beginning the diet and at four weeks. There was no correlation between deoxycholate and arachidonate among the 34 patients before beginning the diet. With placebo, deoxycholate decreased while arachidonate and glycoprotein increased. With ursodiol, deoxycholate decreased while arachidonate decreased and glycoprotein did not change. With aspirin, there was no change in deoxycholate but a decrease in arachidonate and no change in glycoprotein. Our data do not support a role for biliary deoxycholate in the regulation of biliary arachidonate. Our data do support a role for arachidonate, but not deoxycholate, in the regulation of biliary glycoprotein during the formation of cholesterol gallstones.

Effects of ursodeoxycholic acid and aspirin on the formation of lithogenic bile and gallstones during loss of weight.

We attempted to determine whether the administration of aspirin or ursodeoxycholic acid during loss of weight could prevent the development of lithogenic changes in bile and the formation of gallstones. Sixty-eight obese subjects without gallstones who were entered in a program (520 kcal per day) to lose weight were randomly assigned to receive ursodeoxycholic acid (1200 mg per day), aspirin (1300 mg per day), or placebo in double-blind fashion for up to 16 weeks. At entry, at four weeks of treatment, and at three weeks after the completion of treatment, the subjects underwent ultrasonography to detect gallstones and duodenal drainage of bile to detect cholesterol crystals and to determine the bile saturation index and glycoprotein concentration. No gallstones or cholesterol crystals formed in the patients treated with ursodeoxycholic acid. Among the patients given placebo, gallstones formed in five (P less than 0.05 vs. ursodeoxycholic acid) and cholesterol crystals in six (P less than 0.001 vs. ursodeoxycholic acid); among those given aspirin, gallstones formed in two and cholesterol crystals in one (no significant difference from ursodeoxycholic acid treatment). By the fourth week, the bile saturation index increased in the placebo group (from 1.07 +/- 0.26 to 1.29 +/- 0.27; P less than 0.001), decreased in the ursodeoxycholic acid group (from 1.11 +/- 0.34 to 0.91 +/- 0.24; P less than 0.001), and did not change significantly in the aspirin group. The concentration of glycoprotein in bile increased in the placebo group (27.9 +/- 14.5 percent; P less than 0.001) but did not change significantly in the groups treated with ursodeoxycholic acid or aspirin. We conclude that ursodeoxycholic acid prevents lithogenic changes in bile and the formation of gallstones in obese subjects during loss of weight.

The effect of diet on bile acid kinetics and biliary lipid secretion in gallstone patients treated with ursodeoxycholic acid.

Effects of specific dietary alterations in patients with radiolucent gallstones treated with ursodeoxycholic acid (UDCA, 750 mg at bedtime) were investigated. Patients were allocated randomly to one of four diets: standard (500 mg cholesterol/day), low-cholesterol (250 mg/day), added-bran (30 g/day), or substituted medium-chain triglycerides (MCT) oil (20% of fat). Dietary intake and good compliance were verified by computerized analysis of dietary diaries. Bile-acid kinetics (26 patients) or secretion of biliary lipids (23 other patients) were determined at enrollment and at 6 and 9 mo, respectively, during treatment. Although MCT further decreased the UDCA-induced decrease in the synthesis of chenodeoxycholic acid, it did not lessen desaturation of bile. Otherwise, compared to the standard diet, no experimental diet significantly altered the UDCA-induced increase of the pools of total bile acids and UDCA or the UDCA-induced decrease in synthesis of bile acids and in biliary secretion or saturation of cholesterol. If these dietary manipulations facilitate dissolution of gallstones by UDCA, they do so by other mechanisms.

Cyclic nucleotides and glycoproteins during formation of cholesterol gallstones in prairie dogs.

Male prairie dogs received in standard diets either 0.08% cholesterol (control, n = 30) or 1.2% cholesterol (lithogenic, n = 31). Animals were killed at days 2-4, 7, 10, 21, and 39 to determine the temporal sequence of changes in mucosal cyclic adenosine 3':5'-monophosphate in the gallbladder and of cholesterol saturation, glycoproteins, cholesterol crystals, and gallstones in bile of prairie dogs fed a cholesterol-rich lithogenic diet. Glycoprotein concentration in bile in the lithogenic group was significantly elevated compared to controls on all days of death. Saturation of bile and formation of cholesterol crystals occurred only in the lithogenic group, detected first after 7 days of feeding. Gallstones were found in the lithogenic group only. Elevation of cyclic adenosine 3':5'-monophosphate in the mucosa of gallbladders was found in the lithogenic group only, beginning at day 10. In summary, increased glycoproteins in bile preceded cholesterol saturation and crystallization which, in turn, preceded increased mucosal cyclic adenosine 3':5'-monophosphate.

Dissolution of cholesterol gallstones by bile acids in hamsters.

UNLABELLED: We previously reported a hamster model for cholesterol gallstone formation and prophylaxis. The aim of this study was to validate a model for dissolution of cholesterol gallstones by testing bile acids used in patients. Sixty hamsters were allocated to six groups of ten; Group I received the standard diet (.8mg cholesterol/gram food) and Groups II-VI received the lithogenic regime (2.4 mg cholesterol/gram food and 15 micrograms ethinyl estradiol) for twelve weeks. During the next eight weeks, Group I remained on the standard diet, Group II on the lithogenic regime, while Group III switched to the standard diet. Groups IV-VI remained on the lithogenic regime, and received 20 mg/kg/d of CDC (Group IV), UDC (Group V) or cholic acid (Group VI). Cholesterol gallstones were found in 90% of hamsters on the lithogenic regime, even after return to the standard diet, in 80% of those receiving cholic acid, and in none receiving the standard diet, CDC or UDC. CDC and UDC but not cholic acid inhibited hepatic HMG-CoA reductase activity (p less than 0.01) and desaturated bile (p less than 0.01). The highest HMG-CoA reductase (p less than 0.02) occurred after return from the lithogenic regime to the standard diet. CONCLUSIONS: 1) A new model for cholesterol gallstone dissolution has been validated; 2) CDC and UDC, in contrast to cholic acid, decreased HMG-CoA reductase, desaturated bile and dissolved gallstones as in patients; and 3) Return from the lithogenic regime to the standard diet did not desaturate bile or dissolve gallstones, but did increase HMG-CoA reductase as found in gallstone patients.

Effect of Zanchol and chenic acid on bile acid pool size and gallstones in hamsters.

After receiving a lithogenic regime for 12 weeks (Phase I), 60 hamsters were allocated to groups of 10 animals. During Phase II, except for one group which remained on the lithogenic regime, all groups were switched to a standard diet and chenic acid 20 mg/kg/day or Zanchol 5, 15 or 25 mg/kg/day or no other therapy. Half the animals in each group were sacrificed at 3 weeks and the remainder at 10 weeks. Gallstones were found in all animals except those receiving chenic acid for 10 weeks. At 3 weeks in Phase II, with chenic acid, the bile acid pool size was not significantly decreased and bile remained saturated despite a 38% lower rate of hepatic synthesis of cholesterol (p less than 0.01), but became unsaturated at 10 weeks at which time the bile acid pool size was increased by 37% (p less than 0.01). The highest at which time the bile acid pool size was increased by 37% (p less than 0.01). The highest dose of Zanchol increased the bile acid pool size by 74% (p less than 0.01) while increasing the hepatic synthesis of file acid by 38% (p less than 0.01). None of the doses of Zanchol, however, significantly changed biliary cholesterol saturation. In conclusion, chenic acid decreased the hepatic synthesis of cholesterol prior to increasing the bile acid pool, unsaturating bile and dissolving gallstones. Zanchol did not affect the biliary cholesterol saturation of dissolve gallstones despite an increase in the synthesis and pool size of the bile acids.

Sulfation of lithocholate as a possible modifier of chenodeoxycholic acid-induced elevations of serum transaminase in patients with gallstones.

Chenodeoxycholic acid (CDC), through its metabolite, lithocholic acid (LC), is hepatotoxic in certain species. The cause of elevations of serum transaminase in 25% of humans ingesting CDC, however, is unknown, but also may be due to LC. Because efficient hepatic sulfation of LC may protect against hepatic injury, the aim of this study was to determine if sulfation of LC might modify CDC-induced elevations of transaminase. Pretreatment sulfation fraction (SF) was estimated in 63 randomly selected patients with gallstones in a double-blind randomized trial of CDC, 750 mg/d, 375 mg/d, or placebo; in 27 of these, SF was repeated at 1 or 2 yr. In four other patients, the SF was measured at 2 yr only. Serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase were determined monthly for 3 mo and then every 3 or 4 mo; an elevation of transaminase was defined as > 150% of the normal upper limit in asymptomatic patients. 10 muCi of (3)H-glyco-LC (sp act 84 mCi/mol) was ingested 10-12 h before fasting duodenal biliary drainage. Bile acids in bile were separated by thin-layer chromatography. The SF was estimated as a percentage of total radioactivity (scintillation counting) in sulfated glyco-LC. The standard deviation for replicate SF determinations (n = 311) was 2.1% The pretreatment SF (mean 60.7+/-1.7 SEM) correlated inversely with age (r = 0.336, P < 0.005) and directly with the obesity index (r = 0.495, P > 0.001), but was independent of sex. The SF, remeasured at 1 or 2 yr, did not change significantly with time or CDC. Among CDC-treated patients, elevations of transaminase occurred in 75% of patients with a SF < 45% vs. 11% with a SF > 45% (P < 0.001). In conclusion, a SF < 45% occurred in patients with gallstones who had a high probability of developing elevated serum transaminase when treated with CDC. Thus, sulfation of lithocholate may modify CDC-induced elevations of serum transaminase.

Treatment of choledocholithiasis with oral chenodeoxycholic acid.

The aim of this study was to conduct a controlled trial of oral chenodeoxycholic acid in the management of radiolucent choledocholithiasis. Thirteen patients were randomized in double-blind fashion to receive either 750 mg/day of chenodeoxycholic acid (CDCA) or a placebo. After 4 months, those who had the placebo were administered CDCA; those who had received CDCA and showed a 25% or more decrease in the size of stones (evaluated blindly) received CDCA for an additional 4 months. Five of the 13 patients did not complete the study; four (one initially placebo and three CDCA) because acute biliary symptoms mandated operative intervention and one (initially placebo, then CDCA) because of asymptomatic elevations of the serum transaminase levels. Patients who were withdrawn from the study had significantly larger stones (P less than 0.02) (mean largest diameter, 11.4 mm +/- 1.6 SEM) than those who completed the study (6.5 +/- 0.5). Of the eight patients who completed the study, two of the three who received CDCA initially for 6 to 8 months experienced complete disappearance of stones; all five patients who took the placebo failed to show dissolution, and one of these subsequently had dissolution of stones after 8 months of CDCA. Biliary lipid analyses during treatment showed bile unsaturated with respect to cholesterol in the three patients whose stones dissolved with CDCA therapy. In conclusion, a patient with partial dissolution of stones and unsaturated bile after 4 months of CDCA probably will have complete dissolution of stones after 6 to 8 months of CDCA.

Biliary lipid synthesis and secretion in gallstone patients before and during treatment with chenodeoxycholic acid.

The interrelationships between biliary lipid secretion and the hepatic activities of the rate-limiting enzymes for bile acid and cholesterol synthesis have not been investigated in patients with gallstones before and during desaturation therapy. Liver biopsies for enzyme assays and biliary lipid secretion measurements were performed in 12 patients with gallstones before chenodeoxycholic acid therapy and in nine of these patients at 9 months of therapy. Six nongallstone control patients underwent only the lipid secretion measurements. In the patients with gallstones before treatment, all of whom had saturated bile, increased cholesterol secretion correlated directly with increased HMGCoAR activity, whereas bile acid and phospholipid secretion rates were significantly lower than in controls. During desaturation in response to chenodeoxycholic acid, biliary cholesterol and phospholipid secretion rates decreased significantly, and bile acid secretion was unchanged. Concomitantly, both HMGCoAR and cholesterol 7alpha-hydroxylase activities decreased significantly, but the correlation between HMGCoAR and cholesterol secretion was lost. Furthermore, no correlation was found between cholesterol 7alpha-hydroxylase activity and bile acid secretion during therapy. Enzyme assays were performed on single liver samples obtained at the same time of day but 48 hr before the lipid secretion measurements. That correlations between data obtained under these conditions are valid remains to be proved. In conclusion, the mechanism of biliary cholesterol saturation in patients with gallstones probably is related primarily to increased hepatic cholesterol synthesis, whereas desaturation during chenodeoxycholic acid therapy involves altered relationships among hepatic enzyme activities and biliary lipid secretions.

The effect of dihydroxy bile acids on intestinal secretion, cyclic nucleotides, and Na+-K+-ATPase.

The effects of dihydroxy bile acids on intestinal cyclic nucleotides, Na+-K+-ATPase, and net secretion, and of propranolol pretreatment on these actions were determined. Ileal and colonic loops were constructed in each of 12 rabbits, six of which were treated with propranolol preoperatively. In random order, normal saline, 6mM deoxycholic, chenodeoxycholic, or ursodeoxycholic acids were injected into the intestinal loops. Five hours after, net luminal secretion and mucosal adenylate cyclase, phosphodiesterase, cGMP, and Na+-K+-ATPase were determined. Deoxycholic and chenodeoxycholic acids each increased adenylate cyclase activity (< 0.01) and net secretion (p < 0.01), and decreased cGMP (p < 0.05). Ursodeoxycholic acid did not alter adenylate cyclase activity or secretion but increased cGMP (p < 0.05). Phosphodiesterase and Na+-K+-ATPase were unchanged. Propranolol reversed all of the bile acid effects. In conclusion, chenodeoxycholic and deoxycholic acid induce net intestinal secretion, probably via cAMP. Ursodeoxycholic acid does not affect cAMP but increases cGMP and does not promote net secretion.

Cholesterol gallstone formation and prevention by chenodeoxycholic and ursodeoxycholic acids. A new hamster model.

Prior animal models of cholesterol gallstone formation have been criticized for their dissimilarity to the conditions of humans with gallstones. We present a new hamster model of cholesterol cholelithiasis that more closely approximates the human situation. Sixty female Golden Syrian hamsters (average weight 83.2 +/- 3.4 g) were allocated to six groups of 10 animals each. Groups were fed standard diet (containing 0.8 gm cholesterol/g of food) or increased cholesterol diet (containing 2.4 mg cholesterol/g of food), with or without ethinyl estradiol, 15 micrograms/kg/d. Two groups receiving both increased cholesterol and ethinyl estradiol also received either chenodeoxycholic acid or ursodeoxycholic acid, 20 mg/kg/d. The animsl were sacrificed at 12 wk. Cholesterol gallstones (78.3 +/- 5.0% cholesterol by weight) formed in 30% of the animals fed ethinyl estradiol, 50% of those fed increased cholesterol, and 90% of those fed the combination of both. Bile was saturated in all three groups, with the saturation index of the combination group (2.08 +/- 0.17) being the highest. In both groups receiving bile acid therapy, no gallstones were found, and the bile remained unsaturated. For the bile acid-fed groups, both hepatic HMG-CoAR and hepatic cholesterol 7 alpha-hydroxylase activities were reduced (P less than 0.01) when compared to the group fed standard diet and to the grou fed the combination. Thus, a new animal model of cholesterol gallstone formation has been developed in which chenodeoxycholic acid and ursodeoxycholic acid therapy prevented gallstone formation through mechanisms similar to those reported in cholesterol gallstone patients.

Gallstone dissolution--a progress report.

Cholesterol gallstone formation occurs in three stages. First, the bile must be saturated with cholesterol, thereby allowing cholesterol crystals to form. Then, nucleation and growth of the gallstone can occur, although little is known about these latter two stages. Therapy for dissolution of gallstones is directed at desaturating the bile. Chenodeoxycholic acid (CDCA), the most extensively tested agent, is successful in dissolving 60 per cent of radiolucent gallstones; however, long-term safety remains to be demonstrated. Ursodeoxycholic acid (UDCA), the 7 beta epimer of CDCA, is a promising agent for cholesterol gallstone dissolution, but it, other potential agents, and dietary manipulations require more extensive study. An important problem, the prevention of recurrence of gallstones after dissolution, also needs resolution. Medical dissolution probably will be applicable as an alternative to cholecystectomy for most patients with radiolucent gallstones, but the specific relative indications remain to be determined. A variety of modalities, both medical and surgical, are being used for the treatment of retained or reformed bile duct stones. These include T-tube infusions, oral CDCA, and extraction either through the T-tube tract or after endoscopic papillotomy. Further studies, including controlled trials, are necessary to determine the relative indications for these methods.

Inhibition by propranolol of bile acid- and PGE1-stimulated camp and intestinal secretion.

Three colonic and three ileal loops were prepared in six rabbits pretreated with propranolol (PR) 4 mg./kg. I.V. and in five untreated rabbits. In random order, 1 ml. of either deoxycholic acid (DCA) 6 mM., prostaglandin E1 (PGE1) 20 microgram./ml., or saline was placed in each colonic loop and 1 ml. of either cholera enterotoxin (CE) 10 microgram./ml., PGE1 20 microgram./ml., or saline was placed in each ileal loop. In untreated animals, DCA and PGE1 in the colon and CE and PGE1 in the ileum stimulated (P less than 0.01) adenylate cyclase (AC) and net secretion. In the colon, PR abolished DCA-stimulation of AC and net secretion and decreased PGE1-stimulated AC (P less than 0.01) and net secretion. In conclusion, at the doses and times studied, colonic-AC and net secretion stimulated by PGE1 or DCA was distinguished from small bowel-AC and net secretion stimulated by PGE1 or CE.