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Dieter Jüngst

Publications and source records attributed to Dieter Jüngst.

8 recordsLinked to original sources

Gallstone disease: Microlithiasis and sludge.

'Sludge' is the solid material which results from the slow settling of particles dispersed in a liquid medium. Biliary sludge in the gallbladder can be detected by transabdominal ultrasonography, and the typical echoes derive mainly from pigment precipitates mixed with cholesterol crystals. A portion of biliary sludge contains comparatively large particles (1-3 mm) called microliths, the formation of which is an obligatory intermediate step in the development of all types of gallstone. Microlithiasis and sludge in bile may cause colicky pain, cholecystitis, cholangitis, and acute pancreatitis, and are thus of clinical relevance. In these patients treatment follows the guidelines of symptomatic gallstone disease, and strategies include long-term application of ursodeoxycholic acid, endoscopic papillotomy, or preferably laparoscopic cholecystectomy.

Bile↗

Effects of ursodeoxycholic acid on synthesis of cholesterol and bile acids in healthy subjects.

BACKGROUND/AIMS: Ursodeoxycholic acid (UDCA) decreases biliary secretion of cholesterol and is therefore used for the dissolution of cholesterol gallstones. It remains unclear whether these changes in biliary cholesterol excretion are associated with changes in cholesterol synthesis and bile acid synthesis. We therefore studied the activities of rate-limiting enzymes of cholesterol synthesis and bile acid synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase and cholesterol 7alpha-hydroxylase, respectively, in normal subjects during UDCA feeding. METHODS: UDCA was given to 8 healthy volunteers (5 men, 3 women; age 24-44 years) in a single dose of 10-15 mg/kg body weight for 40 days. Before and during (days 3, 5, 10, 20, 30 and 40) UDCA treatment, urinary excretion of mevalonic acid and serum concentrations of 7alpha-hydroxy-4-cholesten-3-one (7alpha-HCO) were determined as markers of cholesterol and bile acid synthesis, respectively. The Wilcoxon signed rank test and Spearman's rank correlation coefficient were used for statistical analysis. RESULTS: Cholesterol synthesis and serum lipid concentrations remained unchanged during UDCA treatment for 40 days. However, synthesis of bile acids increased during long-term treatment with UDCA as reflected by an increase in 7alpha-HCO serum concentrations from 39.7 +/- 21.3 ng/ml (median 32.8 ng/ml) before treatment to 64.0 +/- 30.4 ng/ml (median 77.5 ng/ml) at days 30-40 of UDCA treatment (p < 0.05). CONCLUSIONS: UDCA treatment does not affect cholesterol synthesis in the liver, but does increase bile acid synthesis after prolonged treatment. This may represent a compensatory change following decreased absorption of endogenous bile acids as observed with UDCA therapy.

Adult↗

Solubility of cholesterol in the crystal-free gallbladder bile of gallstone patients.

Supersaturation of bile with cholesterol is generally considered the driving force of cholesterol precipitation. However, in most investigations the amount of cholesterol crystals is included in the calculation of the cholesterol saturation index (CSI). We therefore studied the solubility of cholesterol in crystal-free gallbladder bile from gallstone patients. Our results demonstrate significantly ( P <.05) higher CSIs (1.4 +/- 0.5 and 1.4 +/- 0.4 vs 1.1 +/- 0.4, mean +/- SD) in crystal-free gallbladder bile from 66 patients with cholesterol stones and 21 patients with mixed stones compared with those in 30 patients with pigment stones and a significant difference ( P <.001) in the amount of cholesterol in vesicles (19.2% +/- 13.7% and 14.3% +/- 11.6 % vs 4.2% +/- 5.9%) and of the crystal-observation time (COT; 1-21 days, median 2 days and 1-21 days, median 3 days, vs 3-21 days, median 21 days). We detected a positive correlation ( r =.24, P <.01) between the percentage of cholesterol in vesicles and the CSI and a negative correlation between COT and CSI ( r = -.23, P <.02 ) and COT and the percentage of cholesterol in vesicles ( r = -.52, P <.001 ). However, in 14 of 30 gallbladder-bile specimens from patients with pigment stones but in just 5 of 21 specimens from patients with mixed stones patients and 12 of 66 specimens from patients with cholesterol stones, the distribution of cholesterol in different phases (mixed micelles, vesicles, and crystals) was within the limits of solubility determined in previous studies of model bile. Therefore, in addition to the relative composition of biliary lipids, nonlipid components exert considerable influence on the solubility of cholesterol in the gallbladder bile of gallstone patients.

Adult↗

Ursodeoxycholic acid decreases viscosity and sedimentable fractions of gallbladder bile in patients with cholesterol gallstones.

OBJECTIVES: Ursodeoxycholic acid (UDCA) therapy is associated with reduced risk of biliary pain and acute cholecystitis or pancreatitis in patients with cholesterol gallstones. The underlying mechanisms are understood incompletely, which prompted us to study the influence of UDCA treatment on composition, viscosity and sedimentable fractions of gallbladder bile in 25 patients with symptomatic cholesterol gallstones. METHODS: In two randomised groups, either UDCA (750 mg daily) or placebo was given to each patient 10-12 days before cholecystectomy. Gallbladder bile was collected intraoperatively and analysed for protein, mucin, lipid composition, cholesterol crystal observation time, amount of cholesterol in vesicles, viscosity and sedimentable fractions (cholesterol, protein, mucin, bilirubin). RESULTS: UDCA-treated patients showed longer cholesterol crystal observation times and lower concentrations of total cholesterol and percentages of vesicular cholesterol in gallbladder bile. The concentrations of protein and mucin in gallbladder bile tended to be lower in the UDCA-treated group, but phospholipids, bile acids and bilirubin did not differ between the groups. Viscosity and the total sedimentable fractions of gallbladder bile decreased in the UDCA-treated patients. CONCLUSIONS: UDCA treatment reduces total and vesicular cholesterol, the formation of cholesterol crystals, viscosity, and the total amount of sedimentable fractions in gallbladder bile. These observations might explain, at least partially, why UDCA treatment attenuates the occurrence of biliary pain and complications in gallstone patients.

Adult↗

Effect of gallbladder mucin on the crystallization of cholesterol in bile.

OBJECTIVES: Mucin is supposed to accelerate the crystallization of cholesterol in model bile while studies in native human gallbladder bile revealed conflicting results. METHODS: Therefore, we determined the relation of mucin concentration and cholesterol crystal observation time in gallbladder bile of 73 patients with cholesterol and mixed and 21 patients with pigment stones. In addition, bile samples of 20 patients with cholesterol gallstones were supplemented with either 0 (control) or 0.5-4.0 mg/ml purified bovine mucin or human mucin isolated from gallbladder bile, to study the effect of variable mucin concentrations on the crystallization of cholesterol. RESULTS: Rapid nucleating biles (</= 4 days, n = 59) showed higher mucin concentrations (0.73 +/- 0.1 mg/ml vs 0.43 +/- 0.07 mg/ml) than biles with longer (> 4 days, n = 35) cholesterol crystal observation times (P < 0.05), but no correlation between mucin concentration and cholesterol crystal observation time was observed. Supplementation experiments with bovine purified mucin (up to 4.0 mg/ml) showed no significant effect on the total amount of newly formed cholesterol crystals within 21 days. However, higher amounts of newly formed cholesterol crystals were seen in bile samples supplemented with human mucin in comparison to negative controls. CONCLUSIONS: Our results demonstrate a dose-dependent effect of human but not of bovine gallbladder mucin on the formation of cholesterol monohydrate crystals in gallbladder bile of patients with cholesterol stones. Therefore, studies of cholesterol crystallization in model bile systems may be valuable but should always be confirmed in native gallbladder bile as the more physiological effector system.

Adult↗

Biliary pronucleating proteins and apolipoprotein E in cholesterol and pigment stone patients.

BACKGROUND/AIMS: Although cholesterol gallstone patients exhibit higher biliary cholesterol saturation than pigment stone patients, underlying mechanisms that affect stone type are unknown. We hypothesized that pronucleating proteins, hydrophobic bile salts or apolipoprotein E genotype affect stone type. We therefore compared these putative factors in cholesterol and pigment stone patients. METHODS: In 74 cholesterol and 12 pigment stone patients, bile lipids, various pronucleating proteins, crystallization and apolipoprotein E genotype were determined. RESULTS: Crystallization was enhanced, and cholesterol saturation higher in case of cholesterol stones, without any difference in bile salt composition. Concentrations of mucin (0.91+/-0.08 versus 0.31+/-0.06 mg/ml: P<0.0001), protein, IgM, IgG, IgA, haptoglobin, alpha1-acid glycoprotein and haptoglobin were 2-6-fold higher in cholesterol stone patients. Twenty cholesterol stone pts (27%) but only one pigment stone pt (8%) had at least one epsilon4 allele. There was a significant difference in allele frequencies between both groups (cholesterol stones similar to Dutch population: epsilon2 0.074, epsilon3 0.770, epsilon4 0.156: pigment stones: epsilon2 0.250, epsilon3 0.708, epsilon4 0.042). CONCLUSIONS: Various pronucleating biliary proteins are markedly higher in cholesterol than pigment stone patients. Also, apolipoprotein E genotype differs between cholesterol and pigment stone patients. These factors may affect gallstone type.

Adult↗

Bowel habits and bile acid malabsorption in the months after cholecystectomy.

OBJECTIVE: Bile acid malabsorption has been supposed to play a major pathogenetic role in postcholecystectomy diarrhea. Therefore, the aim of this study was to define the effect of cholecystectomy (CHE) on bowel habits and bile acid absorption. METHODS: Fifty-one patients were prospectively studied before, at 4 wk, and 12 wk after elective CHE for changes of bowel habits, occurrence of diarrhea, and signs of bile acid malabsorption. Bowel habits were assessed by interview. Serum concentrations of 7alpha-hydroxy-4-cholesten-3-one were used as a marker of bile acid malabsorption. Statistics were performed with the McNemar chi2 test for discrete values and Student's paired t test for continuous values. RESULTS: After CHE, there was an increase of patients reporting more than one bowel movement per day (from 22% before CHE to 51% [p < 0.001] and 45% [p < 0.005] at 1 month and 3 months after CHE, respectively) and of patients reporting loose stools (from 2% to 47% [p < 0.001] and 33% [p < 0.001], respectively). Three months after CHE, three patients (6%) reported intermittent diarrhea. Serum levels of 7alpha-hydroxy-4-cholesten-3-one increased from 25.4+/-14.5 ng/ml to 46.5+/-29.5 ng/ml (p < 0.001) and 52.5+/-33.0 ng/ml (p < 0.001), respectively. Unexpectedly, changes of 7alpha-hydroxy-4-cholesten-3-one in serum were unrelated to changes of bowel habits. CONCLUSIONS: CHE results in considerable changes of bowel habits and an increased loss of bile acids from the intestine in some patients. Bile acid malabsorption, however, may not explain changes of bowel habits after CHE.

Cholecystectomy↗