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.

Slowing of gastrointestinal transit by oleic acid: a preliminary report of a novel, nutrient-based treatment in humans.

Chronic diarrhea may occur when gastrointestinal transit is abnormally rapid. We hypothesized that oleic acid given prior to a meal would slow gastrointestinal transit and reduce diarrhea by activating nutrient-triggered inhibitory feedback mechanisms in the small intestine. Transit time was measured in eight normal subjects following ingestion of a control emulsion (0 ml oleic acid), and in 45 patients with chronic diarrhea following ingestion of emulsions containing 0, 1.6, and 3.2 ml oleic acid. Stool volume and frequency on and off treatment were compared. Transit time in normal subjects was 102.4 +/- 11.2 min (mean +/- SE). Transit times in patients was shorter at 29.3 +/- 2.8 min with the 0-ml dose (P < 0.001), but increased to 57.2 +/- 4.5 min with the 1.6-ml dose and to 83.3 +/- 5.2 min with the 3.2-ml dose (P < 0.001). In the 18 patients who provided stool records, frequency of bowel movements decreased from 6.9 +/- 0.8 to 5.4 +/- 0.9 bowel movements/24 hr (P < 0.05) and stool volume decreased from 1829.0 +/- 368.6 to 1322.5 +/- 256.9 ml/24 hr with treatment (P < 0.05). An emulsion containing oleic acid slowed gastrointestinal transit and reduced diarrhea by activating nutrient-triggered inhibitory feedback mechanisms in the small intestine.

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.

Bile salt inhibits acid-promoting feeding tube occlusion.

Occlusion of feeding tubes is a common and costly complication of enteral feeding. Although the composition of feeding formulas, the size, design, and material of the feeding tube, and the rate of delivery have been considered as factors that determine the rate of tube occlusion, little information is available on the effect of the luminal content of the gut on tube occlusion. Enteral feeding tubes are placed either in the stomach or postpylorically, in the small intestine. The chemical composition of these regions including acidity and bile salt concentration may vary. Since acidity has been shown to promote tube occlusion and bile salts have detergent-like properties, these chemical differences in the luminal environment may be important to tube occlusion. To test the idea that bile salt inhibits acid-promoted occlusion of feeding tubes, in an in vitro study, we compared the time-to-complete occlusion of four groups of formula-filled feeding tubes (six tubes in each group) immersed in an acidic solution (pH 3.0) containing 0 (control), 10, 20, or 40 mM of taurocholate. We found that although 33% of the feeding tubes were occluded within 12 hours in the absence of exposure to bile salt, none were occluded when 20 or 40 mM of taurocholate was added to the acidic solution. After 24 hours, 40 mM of taurocholate inhibited acid-promoted occlusion of 67% of the feeding tubes. Thus 0 to 40 mM of taurocholate still inhibited acid-promoted tube occlusion in a dose-dependent fashion (p < .05). Acidity and the concentration of bile salt may work together, but in opposite directions, as luminal factors that determine the rate of occlusion of feeding tubes.

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.

Effect of dietary cholesterol on biliary lipids in patients with gallstones and normal subjects.

The purpose of this study was to determine the effect of dietary cholesterol on biliary lipids in subjects with and without gallstones. Twelve patients with asymptomatic gallstones (six men, six women) were assigned diets containing 500, 750, and 1000 mg cholesterol daily for 3-wk periods in random sequence. Seven healthy women similarly were assigned diets containing 500 and 1000 mg cholesterol daily. With increasing dietary cholesterol in patients with gallstones, biliary saturation indices and molar percents of cholesterol and phospholipids increased significantly while molar percent of biliary bile acids decreased significantly. With increasing dietary cholesterol in healthy women, the biliary saturation index and molar percent of cholesterol increased significantly; the mean saturation index exceeded unity on the diet containing 1000 mg cholesterol daily. In conclusion, augmented dietary cholesterol for brief periods increased biliary cholesterol saturation in subjects with and without gallstones.

Intermittency of cholesterol crystals in duodenal bile from gallstone patients.

The detection of cholesterol crystals in duodenal bile is of clinical value in the diagnosis of cholesterol gallstone disease; however, not all patients with cholesterol gallstones have crystals detected in their duodenal bile, thus limiting the value of examination of duodenal bile. The aims of this study were to (i) determine whether the lack of crystals in some patients with cholesterol gallstones was due to (a) the intermittent presence of crystals, (b) spontaneous crystal dissolution, or (c) changes in dietary cholesterol intake; (ii) determine whether incubation of duodenal bile for 24 h would result in crystal formation. Sixteen patients with radiolucent gallstones each underwent three duodenal biliary drainages. Thirty-one percent of patients had crystals in all three bile specimens, 12% in two specimens, 25% in one specimen, and 32% in no specimen. One of 31 specimens with small numbers of crystals initially had no crystals at 24 h, and five specimens initially devoid of crystals developed crystals by 24 h. Despite a significant increase in biliary cholesterol saturation index with increasing cholesterol intake, the prevalence of crystals in bile did not increase in gallstone patients. No crystals were identified in 18 specimens from normal subjects examined initially or in the 15 specimens that were examined after 24 h. We conclude that the intermittent presence of cholesterol crystals in duodenal bile is probably not due to dissolution of crystals or varying dietary cholesterol intake and that the frequency with which crystals are found increases with incubation. Determination of the diagnostic value of multiple duodenal biliary drainages or incubation of bile in patients with normal oral cholecystograms or gallbladder ultrasonograms, however, will require examinations of large numbers of patients.

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.

Enrichment of bile with tauroursodeoxycholic acid and biliary cholesterol saturation in hamsters.

Three groups of golden Syrian hamsters were fed equimolar amounts of taurine-conjugated ursodeoxycholic acid (TUDCA) or unconjugated ursodeoxycholic acid (UDCA) with or without excess taurine for 2 wk. They also received a lithogenic diet composed of standard rodent chow containing ethynylestradiol and increased cholesterol. Bile was obtained from the gallbladder after ketamine anesthesia and analyzed for biliary lipids. The percentage of biliary UDCA was higher with TUDCA (38.5 +/- 3.7) than with UDCA plus taurine (26.5 +/- 2.0, P less than 0.01). The glycine-to-taurine ratio of biliary UDCA conjugates was lower with TUDCA (0.9 +/- 0.1) than with UDCA plus taurine (2.1 +/- 0.2, P less than 0.01) and was highest with UDCA without taurine (4.1 +/- 0.1, P less than 0.01). Biliary cholesterol (molar percentage) and the cholesterol saturation indices with or without correction for UDCA-rich bile were significantly lower with TUDCA than with unconjugated UDCA with or without added taurine. In conclusion, administration for 2 wk of TUDCA, compared with an equimolar amount of unconjugated UDCA plus taurine, produced in the bile of hamsters a higher percentage of UDCA, a lower glycine-to-taurine ratio of UDCA conjugates, and a lower saturation index before and after adjustment for UDCA-rich bile.

Rowachol and ursodeoxycholic acid in hamsters with cholesterol gallstones.

Rowachol, a mixture of 6 terpenes in olive oil and under investigation for dissolution of gallstones in humans, was compared with UDCA in hamsters with induced cholesterol gallstones. Eighty hamsters were allocated to eight groups of ten animals each. One group received only standard rodent chow. The other seven groups received the lithogenic regime (standard chow containing ethinyl estradiol and increased cholesterol), either alone or with 20 mg/kg/day of UDCA, or 5, 10, or 20 mg/kg/day of mixed terpenes in olive oil or 10 mg ( of terpenes) kg/day of Rowachol or 0.2 cc/day of olive oil. The animals were sacrificed after 12 weeks. Two additional groups of six hamsters each received the lithogenic regime for 12 weeks, and then were switched to the standard diet, alone or with 10 mg/kg/day of Rowachol for eight weeks at the end of which time they were sacrificed. Rowachol decreased HMGCoA reductase activity 18%, but did not dissolve gallstones. Neither the terpenes nor Rowachol altered the biliary cholesterol saturation index, bile acid pool size or the activity of cholesterol 7-alpha hydroxylase or prevented formation of gallstones. UDCA unsaturated bile, increased the total bile acid pool size 38%, depressed the activity of HMGCoA reductase 29%, and prevented formation of gallstones.

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.