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J L Thistle

Publications and source records attributed to J L Thistle.

At least 37 records · Page 2Linked to original sources
PubMed1985

In vitro dissolution of cholesterol gallstones. A study of factors influencing rate and a comparison of solvents.

Models of the common bile duct and gallbladder were constructed to study conditions that affect the rate of cholesterol gallstone dissolution by monooctanoin and other potential solvents. In the bile duct model, the rate of monooctanoin infusion was not an important factor in accelerating dissolution time. In contrast, the exclusion of bile from interfering with solvent-stone contact or the enhancement of solvent-stone contact by stirring significantly accelerated stone dissolution. The combination of both bile exclusion and stirring increased the dissolution rate of gallstones by monooctanoin 15-fold. When compared with two other ethers and with monooctanoin, methyl tert-butyl ether was found to be the most potent gallstone solvent. Methyl tert-butyl ether completely dissolved 219-mg cholesterol stones within 60 min. In the gallbladder model, in the absence of stirring both methyl tert-butyl ether and monooctanoin floated on bile, whereas the gallstones sank resulting in minimal stone-solvent contact. To increase the stone-solvent contact, we used a pump to create sufficient turbulence to mix the solvent with bile. Pump stirring of monooctanoin in the presence of bile achieved rates of stone dissolution approaching that of stirred monooctanoin without bile. Stirring of methyl tert-butyl ether and bile, however, did not achieve sufficient solvent-stone contact to appreciably accelerate dissolution in the presence of 50% bile. Stone-solvent contact was a critical factor in determining the rate of gallstone dissolution in both gallbladder and common bile duct models. Efforts to enhance contact include bile exclusion and intraluminal stirring--both of which are clinically applicable. Methyl tert-butyl ether is a potent new cholesterol gallstone solvent with excellent potential for use in humans. Even with this potent agent, however, rapid gallstone dissolution is likely to require removal of most of the bile from the dissolution medium.

Bile↗
PubMed1985

Cholelitholysis using methyl tertiary butyl ether.

We tested methyl tertiary butyl ether both in vitro and in vivo to evaluate its efficacy as a potential cholesterol gallstone solvent for direct instillation into the human gallbladder or bile duct. Like diethyl ether, methyl tertiary butyl ether is an aliphatic ether with an excellent cholesterol-solubilizing capacity. However, unlike diethyl ether which vaporizes at body temperature, methyl tertiary butyl ether remains a liquid having a boiling point of 55.2 degrees C. In vitro, methyl tertiary butyl ether dissolved human gallstones (40%-94% cholesterol) within 60-100 min. In contrast, monooctanoin, an established gallstone solvent, required greater than 50 h to dissolve similar stones. By direct catheter instillation in 6 dogs, methyl tertiary butyl ether required only 4-16 h to dissolve gallstones surgically implanted in the gallbladder. The dogs tolerated methyl tertiary butyl ether with only minor clinical, biochemical, or histologic effects. We conclude that further evaluation of methyl tertiary butyl ether for dissolution of human gallbladder and biliary duct cholesterol stones is warranted.

Animals↗
PubMed1984

Development and validation of a method for measuring the glycine and taurine conjugates of bile acids in bile by high-performance liquid chromatography.

We developed and validated a simple method for measuring the individual glycine and taurine conjugates of bile acids in bile by high-performance liquid chromatography with a C18 reversed-phase column using an isocratic solvent system of acidified methanol--potassium phosphate. Without preliminary derivatization or purification, complete separation of the ten major conjugated bile acids present in bile could be achieved in 65 min. Total bile acid concentrations were identical when measured enzymatically and by summing the individual bile acids determined by high-performance liquid chromatography. Bile acid composition determined by gas-liquid chromatography correlated with results by high-performance liquid chromatography. Finally, measurements of individual glycine and taurine conjugates in human bile and in mixtures of bile acid standards by high-performance liquid chromatography and thin-layer chromatography gave similar results. This high-performance liquid chromatographic system permits simultaneous quantification of total and individual bile acids and their glycine and taurine conjugates in bile.

Bile↗
PubMed1984

Additional chenodiol therapy after partial dissolution of gallstones with two years of treatment.

During the National Cooperative Gallstone Study, therapy with chenodiol, 750 or 375 mg/d, for 2 years resulted in confirmed, complete gallstone dissolution in 14% and 5% of patients, respectively, and partial dissolution (greater than 50%) in 27% and 18%. The present study was done to determine the frequency with which complete dissolution occurs in patients having partial dissolution of gallstones who receive additional therapy. Eighty-six of one hundred thirty-eight eligible patients continued to receive 750 mg/d (61 patients) or 375 mg/d (25 patients) of chenodiol for 1 year. Patients whose oral cholecystogram at the end of the year showed further (greater than 50%) dissolution continued to receive chenodiol, (28 patients at 750 mg/d and 11 patients at 375 mg/d) for a second year (total duration of therapy, 4 years). A final oral cholecystogram was taken at the end of the fourth year. Complete dissolution occurred in 23% and 16% of patients receiving chenodiol, 750 or 375 mg/d, respectively, for an additional 1 or 2 years.

Chenodeoxycholic Acid↗
PubMed1984

The natural history of cholelithiasis: the National Cooperative Gallstone Study.

The National Cooperative Gallstone Study, a double-masked, placebo-controlled, therapeutic trial of chenodiol (chenodeoxycholic acid), provided an opportunity to study the natural history of cholelithiasis in patients who choose nonsurgical management. The major component of the study comprised 916 patients, 305 of whom were randomly assigned to receive a placebo for 24 months. Among these 305 patients, the probability of having biliary tract pain during the 24 months of prospective evaluation was significantly increased if the patient had had a history of biliary tract pain in the 12 months before entry into the study (69% versus 31%). Thirty-eight percent of patients had stone growth (greater than 0.5 cm3), and 18% had a spontaneous decrease in stone volume. Despite the high incidence of biliary tract pain, nonelective cholecystectomy was required in only 4% of patients during the 24 months.

Actuarial Analysis↗
PubMed1983

Ursodeoxycholic acid treatment of gallstones.

Although data must be gleaned from international studies representing a broad range of dosage, duration of therapy, and details reported, sufficient evidence exists to state that UDCA is approximately as effective as CDCA in dissolving gallstones. Complete stone dissolution can be expected in a majority of well-selected patients treated with 10 to 15 mg/kg/day. Additional data on potential toxicity are needed, but current evidence suggests that this is very low. Treatment will be required for 1 to 2 years in most patients. Recurrence is emerging as an important aspect which needs a solution. Clearly, stone dissolution therapy is the treatment of choice in patients with a high operative risk and stones with radiologic characteristics suggesting a high probability of success. The proper place of this management modality in the therapy of the remaining majority of patients with gallstones will require careful assessment of potential benefit in each individual patient, the known risks, and the potential of as yet unrecognized long-term toxicity.

Animals↗
PubMed1983

Diagnosis of Wilson's disease presenting as fulminant hepatic failure.

The clinical course, results of standard laboratory tests, parameters of copper metabolism, and hepatic morphology in 9 cases (3 of our own and 6 from the literature) of Wilson's disease presenting as fulminant hepatic failure were compared with the findings in 5 cases of idiopathic fulminant hepatic failure. Patients with Wilson's disease were usually younger, and 7 of the 9 patients had Kayser-Fleischer rings. Patients with idiopathic fulminant hepatic failure had elevated 24-h urinary copper, decreased ceruloplasmin, and low or normal serum copper. Fulminant hepatic failure with Wilson's disease differed from idiopathic fulminant hepatic failure by the following biochemical findings: (a) higher copper levels in serum, urine and liver; (b) less pronounced elevations of transaminase levels; (c) higher concentrations of total bilirubin; and (d) lower hemoglobin values. Serum copper was the most useful biochemical test in diagnosing Wilson's disease before death. At autopsy, only hepatic copper concentrations clearly separated the two groups. Serial serum copper levels (antemortem) and quantitative analysis of hepatic copper (after recovery or postmortem) in patients with fulminant hepatic failure should help to exclude Wilson's disease.

Adolescent↗
PubMed1983

Effect of litholytic bile acids on cholesterol absorption in gallstone patients.

We measured intestinal absorption of cholesterol by a plasma isotope ratio method and determined biliary bile acid and lipid composition of fasting gallbladder bile in 5 gallstone patients before therapy and during two randomized treatment periods with chenodeoxycholic or ursodeoxycholic acid (13 mg/kg . day). During chenodeoxycholic acid ingestion, biliary bile acids were composed predominantly (84%) of conjugates of chenodeoxycholic acid. During ursodeoxycholic acid administration, conjugates of ursodeoxycholic acid constituted half the bile acid pool (49%). Fasting gallbladder bile was supersaturated in cholesterol before treatment, but became unsaturated during administration of both chenodeoxycholic and ursodeoxycholic acids. In spite of these marked changes in biliary bile acid and lipid composition, cholesterol absorption was not significantly different before (45.4 +/- 4.3%, mean +/- SEM) or after chenodeoxycholic (42.7 +/- 5.1%) or ursodeoxycholic (46.8 +/- 3.7%) acid ingestion. We conclude that chenodeoxycholic and ursodeoxycholic acids unsaturate bile in cholesterol and dissolve gallstones by a mechanism other than the suppression of intestinal absorption of cholesterol.

Adult↗
PubMed1982

Cholelithiasis and carcinoma of the colon.

Cholelithiasis and carcinoma of the colon have similar geographic distributions and common dietary and chemical pathogenetic factors. A study was done to test whether an association between cholelithiasis and colonic cancer existed in the population of Rochester, Minnesota. During the period from 1950-1969, 2413 new cases of cholelithiasis were identified in this population. Because the age- and sex-specific prevalence rates of colorectal cancer in this population were also available, the authors calculated the expected number of cases of colorectal cancer at the time of diagnosis of cholelithiasis. The relative risk (observed/expected) of colonic cancer among persons of all ages and both sexes with cholelithiasis was 1.52 (95% confidence interval, 1.1-2.0). Although the association seems significant, there is a potential bias in that the identification of asymptomatic cases of cholelithiasis might be facilitated in patients who have an operation or frequent follow-up examinations for colonic cancer. When the analysis was repeated separately for symptomatic and asymptomatic cases of cholelithiasis, all the excess (and statistical significance) was confined to the asymptomatic group, and apparent confirmation of the suggested bias. Therefore, the authors believe that no real association exists between cholelithiasis and carcinoma of the colon.

Adult↗
PubMed1982

Differing effects of ursodeoxycholic or chenodeoxycholic acid on biliary cholesterol saturation and bile acid metabolism in man. A dose-response study.

A dose-response study comparing ursodeoxycholic and chenodeoxycholic acid was carried out in six men with asymptomatic radiolucent gallstones present in well-visualizing gallbladders. The study tested the effects of a low (averaging 6 mg/kg/day) or medium dose (averaging 11 mg/kg/day) of each bile acid on the cholesterol saturation of bile as well as on bile acid metabolism, as inferred from biliary and fecal bile acid composition. Ursodeoxycholic acid, at low or medium doses, induced bile desaturation in most patients, whereas chenodeoxycholic acid did not. Despite the greater desaturation efficacy of ursodeoxycholic acid, biliary bile acids became less enriched with the administered bile acid during ursodeoxycholic acid treatment than during chenodeoxycholic acid treatment. Both bile acids were nearly completely 7-dehydroxylated to lithocholic acid by colonic bacteria, but biliary lithocholic increased only slightly (and similarly) with each bile acid. Fecal bile acid composition suggested that administered ursodeoxycholic acid suppressed endogenous bile acid synthesis much less than chenodeoxycholic acid. The results indicate that ursodeoxycholic acid and chenodeoxycholic acid have similar but not identical effects on bile acid metabolism, but that for a given dose, ursodeoxycholic acid is a more potent desaturating agent than chenodeoxycholic acid. The results suggest that cholesterol gallstone dissolution with ursodeoxycholic acid should occur with a dose of 8-10 mg/kg in most nonobese patients.

Aged↗
PubMed1982

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Chenodeoxycholic Acid↗
PubMed1982

Selenium deficiency and fatal cardiomyopathy in a patient on home parenteral nutrition.

An adult patient with chronic idiopathic intestinal pseudo-obstruction maintained on home parenteral nutrition for 6 consecutive years died from cardiomyopathy and ventricular fibrillation. Postmortem examination of the heart revealed widespread myocytolysis and replacement fibrosis similar to that seen in the selenium deficient cardiomyopathy in China (Keshan disease) and animal models. Selenium deficiency in this patient was documented with extremely low concentrations of selenium and decreased activity of the selenoprotein, glutathione peroxidase, in blood, heart, liver, and skeletal muscle. Reports of selenium deficient diets causing myocardial damage in humans and animals and the findings in our patient strongly suggest that his fatal cardiomyopathy was caused by selenium deficiency.

Adult↗
PubMed1982

Pretreatment biliary lipid composition in white patients with radiolucent gallstones in the National Cooperative Gallstone Study.

Biliary lipid classes (bile acids, phospholipids, cholesterol) as well as individual biliary bile acids were measured in duodenal bile samples obtained before treatment from 284 white men and 264 white women participating in the National Cooperative Gallstone Study. The patients had radiolucent gallstones present in visualizing gallbladders. Calculated biliary cholesterol saturation was significantly higher in women (143 +/- 43, mean +/- SD, vs. 132 +/- 39 for men). Chenodeoxycholic acid was the major biliary bile acid in both sexes (40.0 +/- 9.9 in men; 38.8 +/- 9.3 in women, NS). Cholic acid was the second most common bile acid, constituting 32.9 +/- 8.8 in men and 31.8 +/- 8.9 in women (NS). When other demographic and clinical characteristics, including serum lipids, were related with biliary lipid composition, only percent ideal body weight correlated significantly. The partial correlation coefficient adjusted for percent ideal body weight indicated that the proportion of chenodeoxycholic acid correlated negatively with the mole fraction of cholesterol in bile in men, but not in women. Multiple regression analyses showed that bile saturation could not be predicted reliably from any clinical, chemical, or radiologic measurement in either sex. Published data for biliary lipid composition in individuals with biliary disease showed considerable overlap with the National Cooperative Gallstone Study data reported here, suggesting that cholesterol gallstone disease is not caused solely by increased biliary cholesterol saturation.

Adult↗
PubMed1981

Ursodeoxycholic acid ingestion after ileal resection. Effect on biliary bile acid and lipid composition.

The effect of ursodeoxycholic acid ingestion on biliary bile acids and biliary lipids was studied in six patients after ileal resection. All patients had bile acid malabsorption, as documented by increased breath and fecal excretion of 14C after oral administration of [1-14C] cholylglycine. Fasting duodenal bile was collected by intubation before and seven days after ursodeoxycholic acid administration (4 g/day), and biliary bile acid and lipid composition were determined. Ursodeoxycholic acid ingestion increased the percentage of ursodeoxycholic acid in bile tenfold (3.6 +/- 2.6% vs 38.6 +/- 12.0%) and decreased chenodeoxycholic acid in bile by approximately 40%. Before ursodeoxycholic acid ingestion, bile was supersaturated in all patients. After ursodeoxycholic acid ingestion, cholesterol saturation decreased in all six patients by an average of 43%, and bile became unsaturated in five. Ursodeoxycholic acid ingestion had no effect on stool frequency. We conclude that, as in subjects with an intact enterohepatic circulation, ursodeoxycholic acid therapy has litholytic potential in patients after ileal resection.

Bile↗