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G Paumgartner

Publications and source records attributed to G Paumgartner.

At least 55 records · Page 3Linked to original sources
PubMed1996

Reactive oxygen metabolites promote cholesterol crystal formation in model bile: role of lipid peroxidation.

In animal models of gallstone disease inflammatory alterations of the gallbladder mucosa are regularly found before the first appearance of cholesterol monohydrate crystals in bile. At sites of inflammation granulocytes generate reactive oxygen metabolites (ROM). The aim of our study was to investigate whether ROM may influence the cholesterol monohydrate crystal formation in supersaturated model bile. Superoxide anions (O2-), hydrogen peroxide (H2O2), and hydroxyl radicals (.OH) were generated by the interaction of Fe(3+)-EDTA with ascorbic acid (Asc). The influence of ROM on cholesterol crystal formation was studied by measurement of the nucleation time. To check whether lipid peroxidation was induced by the ROM generation, production of malondialdehyde equivalents was measured in bile with the thiobarbituric assay. Furthermore, the lipid pattern of bile after ROM exposure was analyzed by thin layer chromatography. Addition of Fe(3+)-EDTA/Asc to model bile markedly decreased the cholesterol nucleation time (NT) (p < 0.01), caused a significant increase in malonidialdehyde equivalents (p < 0.001) and induced the generation of 4-hydroxy-2,3-trans-nonenal (4-HNE). In an attempt to identify a specific oxygen metabolite responsible for the alterations in bile, the effects of various oxygen radical scavengers were tested. Desferal, which prevents -OH generation by chelation of ferrous iron, completely protected bile against Fe(3+)-EDTA/Asc-induced decrease in NT (p < 0.001), increase in lipid peroxidation (p < 0.001) and generation of 4-HNE. Our results indicate that formation of cholesterol crystals in model bile is enhanced by ROM. Hydroxyl radical induced lipid peroxidation appears to be the mechanism responsible for the crystallisation promoting activity of ROM.

Ascorbic Acid↗
PubMed1996

7 alpha-dehydroxylating bacteria enhance deoxycholic acid input and cholesterol saturation of bile in patients with gallstones.

BACKGROUND & AIMS: Excessive deoxycholic acid (DCA) in the bile acid pool with cholesterol supersaturation of bile is prevalent in patients with cholesterol gallstones (CGs). This study examined whether this is caused by enhanced conversion of cholic acid (CA) to DCA by intestinal bacteria. METHODS: Ten patients with CGs with DCA excess (DCA/CA pool ratio, > 1.5) and 10 patients with low DCA (ratio, < 1.0) were compared for CA and DCA kinetics, ileal absorption of 75-Se-homotaurocholic acid (75-SeHCAT), and CA-7 alpha-dehydroxylation activity of the fecal microflora; the effects of ampicillin treatment on DCA excess were studied in 7 patients. RESULTS: Patients with DCA excess and low DCA differed (P < 0.01) in the pool size of CA (mean, 5.8 vs. 34) and DCA (28 vs. 11 mumol/kg) and DCA input (8.8 vs. 3.5 mumol.kg-1.day-1. Whereas 75-SeHCAT excretion was similar, CA-7 alpha-dehydroxylation activity and levels of fecal 7 alpha-dehydroxylation bacteria were 3-fold and 1000-fold higher (P < 0.01) in patients with DCA excess, respectively. Ampicillin treatment decreased (P < 0.02) CA-7 alpha-dehydroxylation activity and DCA pool size, expanded the CA pool to normal size, and lowered cholesterol saturation of bile. CONCLUSIONS: Increased CA-7 alpha-dehydroxylation activity of the intestinal microflora may be an important factor for CG formation or growth in these patients.

Adult↗
PubMed1996

Assignment of the human organic anion transporting polypeptide (OATP) gene to chromosome 12p12 by fluorescence in situ hybridization.

BACKGROUND/AIMS: The organic anion transporting polypeptide (OATP) of human liver mediates the basolateral hepatocellular uptake of numerous cholephilic anions and steroidal compounds. The aim of this study was to clone the human OATP gene and to map its chromosomal localization by fluorescence in situ hybridization. METHODS: A polymerase chain reaction-amplified fragment of the human OATP gene was used to isolate a genomic OATP clone from a P1-derived artificial chromosome human genomic library. Human metaphase chromosomes were hybridized with digoxigenin-labeled DNA from the genomic OATP clone and incubated in fluoresceinated antidigoxigenin antibodies for in situ detection of specific hybridization signals. RESULTS: Sequence analysis revealed that the isolated P1-derived artificial chromosome clone contained a large portion of the human OATP gene. Fluorescence in situ hybridization of human chromosomes with the genomic OATP clone resulted in the specific labeling of the OATP gene on the short arm of chromosome 12 at band 12p12. CONCLUSIONS: Mapping of a genomic OATP clone to chromosome 12p12 represents a first step towards the molecular characterization of the human OATP gene. While no liver disease has so far been associated with cytogenetic abnormalities of the short arm of chromosome 12, the genomic OATP sequence provides the basis for studies on gene structure and on the tissue-specific regulation of OATP gene expression.

Anion Transport Proteins↗
PubMed1996

Tauroursodeoxycholic acid activates protein kinase C in isolated rat hepatocytes.

BACKGROUND & AIMS: Ursodeoxycholic acid (UDCA) improves liver function in patients with chronic cholestatic liver diseases by an unknown mechanism. UDCA is conjugated to taurine in vivo, and tauroursodeoxycholic acid (TUDCA) is a potent hepatocellular Ca2+ agonist and stimulates biliary exocytosis and hepatocellular Ca2+ influx, both of which are defective in experimental cholestasis. Protein kinase C (PKC) mediates stimulation of exocytosis in the liver. The aim of this study was to determine the effects of TUDCA on PKC in isolated hepatocytes. METHODS: The effect of TUDCA on the distribution of PKC isoenzymes within the hepatocyte was studied using immunoblotting and immunofluorescence techniques. In addition, the effect of TUDCA on the accummulation of sn-1,2-diacylglycerol (DAG), the intracellular activator of PKC, and hepatocellular PKC activity was studied using radioenzymatic techniques. RESULTS: Immunoblotting studies showed the presence of four isoenzymes (alpha, delta, epsilon, and zeta). The phorbol ester phorbol 12-myristate 13-acetate (1 mumol/L) induced translocation of alpha-PKC, delta-PKC, and epsilon-PKC from cytosol to a particulate membrane fraction, a key step for activation of PKC. TUDCA, but not taurocholic acid, selectively induced translocation of the alpha-PKC isoenzyme from cytosol to the membranes. In addition, TUDCA induced a significant increase in hepatocellular DAG mass and stimulated membrane-associated PKC activity. CONCLUSIONS: TUDCA might stimulate Ca(2+)-dependent hepatocellular exocytosis into bile in part by activation of alpha-PKC.

Animals↗
PubMed1996

Gallbladder emptying and gallstone formation: a prospective study on gallstone recurrence.

BACKGROUND & AIMS: Gallbladder emptying is reduced in many patients with cholesterol gallstones. To clarify the role of impaired gallbladder motility in recurrent gallstone disease, the effect of gallbladder emptying on the formation of recurrent stones was studied prospectively. METHODS: In 54 consecutive patients with single radiolucent gallbladder stones, postprandial gallbladder emptying was assessed sonographically before lithotripsy and 1.8 +/- 0.1 years (mean +/- SE) after gallstone disappearance. Patients were followed up for gallstone recurrence for 0.6-4.1 years (median, 2.6 years). RESULTS: After gallstone disappearance, gallbladder fasting volume (33.7 +/- 3.4 vs. 27.8 +/- 3.0 mL; P = 0.007) and residual volume (12.6 +/- 1.9 vs. 9.7 +/- 1.3 mL; P = 0.010) decreased, whereas the ejection fraction remained unchanged. However, gallbladder volume did not differ whether initial or recurrent stones were present. Gallbladder emptying was more impaired in patients with than patients without later recurrence (47% +/- 5% vs. 63% +/- 2%; P = 0.001). Cox analysis showed that gallbladder emptying was an independent determinant of the risk of gallstone recurrence (P = 0.002). Within 3 years, recurrent stones formed in 53% (actuarial analysis) of patients with an ejection fraction of < 60% but in only 13% of patients with an ejection fraction of > or = 60%. CONCLUSIONS: Gallbladder emptying is an important factor in the formation of recurrent gallstones.

Biliary Tract↗
PubMed1996

Serum concentrations of 7alpha-hydroxy-4-cholesten-3-one reflect bile acid synthesis in humans.

Serum concentrations of 7alpha-hydroxy-4-cholesten-3-one (alpha-HC) have recently been shown to reflect the activity of cholesterol 7 alpha-hydroxylase in humans. To evaluate the relationship between alpha-HC in serum and bile acid synthesis, serum concentrations of alpha-HC, and rates of bile acid synthesis, as measured by the isotope dilution technique using gas chromatography-mass spectrometry, were determined simultaneously. Regression analysis revealed a positive linear correlation of serum alpha-Hc with synthesis of cholic acid (CA) (r = .59, P = .02), chenodeoxycholic acid (CDCA) (r = .75, P = .001), and total synthesis of both primary bile acids (r = .83, P < .001) in patients with gallstones and normal liver function (n = 15). alpha-HC was also correlated to input rates of deoxycholic acid (DCA) (r = .53, P <.05). Addition of patients with chronic cholestatic liver disease (n = 5) improved the correlation between serum alpha-HC and synthesis of CA (r = .75, P < .001), CDCA (r = .77, P < .001), and both primary bile acid combined (r = .87), P < .001). Our data are in agreement with the concept that synthesis of bile acids is regulated by cholesterol 7 alpha-hydroxylase activity and that alpha-HC in serum may serve as a convenient marker for the semiquantitative assessment of bile acid synthesis in humans.

Adult↗
PubMed1996

Sedimentation of biliary sludge: effect on composition of gallbladder bile from patients with cholesterol, mixed, or pigment stones.

BACKGROUND: Ultracentrifugation of bile has been used extensively to remove insoluble material such as sludge from bile before further studies of cholesterol nucleation. Although it has been recognized that this procedure may affect the composition of gallbladder bile, it has not been studied systematically in different gallstone populations. Therefore, we investigated the concentration of biliary lipids, protein, mucin, and bilirubin before and after ultracentrifugation. METHODS: Gallbladder bile samples were aspirated during laparoscopic surgery from 66 patients (35 with cholesterol, 16 with mixed, and 15 with pigment stones). RESULTS: Whereas the concentrations of bile acids, phospholipids, protein, and bilirubin in gallbladder bile did not change significantly after ultracentrifugation, cholesterol (20.6 +/- 1.6 to 14.8 +/- 1.2 mmol/l) and mucin concentrations (0.99 +/- 0.2 to 0.67 +/- 0.1 mg/ml) and the cholesterol saturation index (1.68 +/- 0.12 to 1.31 +/- 0.10) decreased significantly in gallbladder bile from patients with cholesterol stones. CONCLUSIONS: Sedimentation of biliary sludge may profoundly affect the composition of gallbladder bile, which has to be considered in studies of cholesterol saturation and nucleation. The cholesterol concentration difference between native and ultracentrifuged bile reflects the insoluble crystalline fraction of cholesterol and may be useful for quantitation of the mass of cholesterol crystals in gallstone-associated bile samples.

Bile↗
PubMed1996

Acute effect of ursodeoxycholic acid on gallbladder volume in healthy subjects.

BACKGROUND: Although it has been shown that chronic administration of ursodeoxycholic acid increases gallbladder fasting and residual volume, it is unknown whether ursodeoxycholic acid exerts an acute effect on gallbladder volume. We therefore evaluated the effect of a single oral dose of ursodeoxycholic acid on gallbladder volume in healthy volunteers. METHODS: After the volunteers had fasted overnight, gallbladder volume was measured sonographically every 15 min for 5 h. Following a 1-h control period group I (n = 8) received ursodeoxycholic acid (1000 mg) orally with 100 ml of water, whereas group II (n = 8) received 100 ml of water (placebo) only. Gallbladder volumes were calculated, applying the sum-of-cylinders method. Serum levels of ursodeoxycholic acid were determined by gas chromatography at 1-h intervals. RESULTS: Gallbladder fasting volumes before ursodeoxycholic acid were similar in both groups (24.0 +/- 2.3 ml versus 25.4 +/- 3.3 ml; NS). After ingestion of ursodeoxycholic acid (group I) gallbladder volume increased rapidly, reaching 27.6 +/- 3.1 ml (p < 0.04) 1 h and 38.4 +/- 3.4 ml (p < 0.02) 4 h after ingestion of ursodeoxycholic acid. The individual gallbladder volumes after ingestion of ursodeoxycholic acid in group I increased to 146%-211% of pretreatment values. Ursodeoxycholic acid serum levels increased from 0.94 +/- 0.38 mumol/l to 10.51 +/- 1.36 mumol/l (p < 0.001) and correlated closely with gallbladder volumes (r = 0.80; p < 0.05). After ingestion of water only (group II) gallbladder volume decreased transiently from 15 min to 30 min after water intake and then remained at pretreatment values throughout the study period. CONCLUSION: Administration of a single oral dose of ursodeoxycholic acid causes a rapid increase in gallbladder volume, which reaches 163 +/- 10% of pretreatment volume at 4 h and is closely correlated with ursodeoxycholic acid serum levels.

Adult↗
PubMed1995

Long-term effects of cholecystectomy on bile acid metabolism.

Comparative studies between different patient groups have suggested that cholecystectomy enhances bacterial dehydroxylation of the primary bile acid cholic acid (CA) to the secondary bile acid deoxycholic acid (DCA). DCA may exert a cocarcinogenic effect on the colonic mucosa. In a short-term follow-up study on nine female patients we found no alterations of the CA or DCA pools after cholecystectomy. However, in the long term, cholecystectomy could promote changes of the intestinal bacterial flora and thereby lead to enhanced conversion of CA to DCA, causing an expansion of the DCA pool size and a reduction of the CA pool size. To test this hypothesis, pool sizes, fractional turnover rates (FTR), and synthesis or input rates of CA, chenodeoxycholic acid (CDCA) and DCA were determined in 12 female patients before and again 5 to 8 years after cholecystectomy. In the long term, pool size and synthesis rate of CA had not changed and DCA pool size had expanded by only 7.5% (not significant [NS]). DCA input increased by 32% (NS) but was balanced by an increase in FTR of 36%. Pool size (-17%) and synthesis rate (-5%) of CDCA were not significantly diminished. Overall, the sizes of the total bile acid pool (-6%, NS; 50 +/- 8 vs. 53 +/- 13 mumol/kg) and the pool fractions of CA (44.7 +/- 10.3% vs. 42.8 +/- 7.6%) and DCA (25.5 +/- 14.1% vs. 23.6 +/- 9.3%) remained similar. In conclusion, cholecystectomy causes no changes in bile acid pool composition and thus has no adverse effects on bile acid metabolism in the long term.

Adult↗
PubMed1995

Hepatitis C virus infection as a possible risk factor for ductopenic rejection (vanishing bile duct syndrome) after liver transplantation.

Irreversible ductopenic rejection (DR) after orthotopic liver transplantation (OLT) is a major cause of late hepatic allograft failure. A variety of risk factors for DR have been postulated, but they are controversial. All transplant recipients at our institution with graft survival of more than 1 month (n = 120) were examined retrospectively with a view to possible risk factors for DR. These factors included age, sex, underlying liver disease, hepatitis B and C infections, donor-recipient CMV status, post-OLT CMV infections, immunosuppressive regimen, ABO blood type, and HLA class I and class II mismatches. Statistical analysis was performed with the univariate chi-square test or the two-tailed Fischer's exact test. Ten patients (8.3%) developed DR. Seventeen patients had HCV infections after OLT. In this group, the incidence of DR was highest (4 of 17, or 23.5%). This was significantly higher than for all other OLT groups (6 of 103 patients, or 5.8%; P < 0.03). The other factors analyzed did not reach statistical significance, including those that other authors found important for the development of DR. It may well be that hepatitis C infection predisposes one to the development of DR after OLT.

Bile Duct Diseases↗
PubMed1995

Gallstone recurrence after direct contact dissolution with methyl tert-butyl ether.

To determine the rate and characteristics of gallstone recurrence after direct contact dissolution with methyl tert-butyl ether, 60 consecutive patients were followed for up to 4.5 years (median 2.2 years) after complete disappearance of all stone residues and debris and cessation of adjuvant bile acid therapy. Initial gallstones had been multiple in all but four patients. Twenty-eight of the 60 patients developed recurrent gallstones. The cumulative risk of gallstone recurrence (actuarial analysis) was 23 +/- 6%, 34 +/- 7%, 55 +/- 8%, and 70 +/- 9% at one, two, three, and four years, respectively. The recurrent stones were usually multiple and small (6 +/- 4 mm). Gallstone recurrence was associated with recurrent biliary pain in two patients, one of whom developed acute cholecystitis. Recurrent stones were cleared completely by bile acid medication with or without shock-wave lithotripsy in 61 +/- 15% of patients at one year (actuarial analysis). In conclusion, gallstone recurrence after successful contact dissolution of multiple stones with methyl tert-butyl ether has to be expected in a high percentage of patients. Most patients, however, remain free of biliary pain during long-term follow-up.

Actuarial Analysis↗
PubMed1995

Prolonged antagonism of alpha 1-adrenergic vasoconstriction in the rat liver by atrial natriuretic peptide.

BACKGROUND/AIMS: Vasodilator hormones that regulate hepatic circulation at physiological concentrations have not been sufficiently identified. The presence of atrial natriuretic peptide (ANP) and its receptors in the hepatic vascular bed suggest such vasorelaxing potential. METHODS: Livers of male Sprague-Dawley rats were perfused in a flow-constant fashion. The selective alpha 1-adrenergic agonist phenylephrine (PE) (1.5 mumol/L) was infused from 30 to 36 minutes and again from 70 to 76 minutes after starting perfusion (n = 5). ANP (0.1 pmol/L to 200 nmol/L), des-(Gln18, Ser19, Gly20, Leu21, Gly22)-ANP fragment (C-ANP) (20 nmol/L), or 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) (50 mumol/L) (each n = 4) were added from 20 to 40 minutes. RESULTS: During the first infusion of PE, portal pressure increased from 3.7 +/- 0.5 to 12.1 +/- 0.8 cm H2O maximally (mean +/- SD) and increased again to 11.5 +/- 2.0 during the second PE infusion. ANP at physiological concentrations reduced both PE-induced increases of portal pressure in a dose-dependent fashion, reaching half-maximal effects around 20 pmol/L and maximal effects (about 50% inhibition of PE-induced vasoconstriction) at 40 pmol/L. The cGMP analogue 8-Br-cGMP showed the same long-lasting vasodilating effect as ANP. In contrast, C-ANP, which binds only to the ANP C-receptor, had no effects. CONCLUSIONS: Physiological concentrations of ANP antagonize alpha 1-adrenergic vasoconstriction in the liver, suggesting an important function in the humoral regulation of hepatic circulation. The prolonged hemodynamic effect of ANP seems to be ANP A-receptor/guanylyl cyclase/cGMP-mediated.

Animals↗
PubMed1995

Dormia baskets impacted in the bile duct: release by extracorporeal shock-wave lithotripsy.

BACKGROUND AND STUDY AIMS: Endoscopic extraction of bile duct stones may be complicated by impaction of the Dormia basket with captured stones, or rupture of the traction wire of the basket during mechanical lithotripsy. In an attempt to release impacted baskets by nonoperative means, we studied the efficacy of extracorporeal shock-wave lithotripsy in this dangerous clinical situation. PATIENTS AND METHODS: Fourteen extracorporeal shock-wave treatments were performed in 12 consecutive patients (eight women and four men; mean age 73.2 +/- 13.2 years, range 46-86 years) with an electrohydraulic shock-wave lithotriptor, using fluoroscopy (n = 13) or ultrasound (n = 1) for targeting. A total of 1845 +/- 334 (mean +/- SD) shock-wave discharges at a voltage of 22 +/- 4 kV were delivered per treatment. Nine treatment sessions (64%) were performed while patients were under general anesthesia. An attempt to extract the Dormia basket was made after disintegration of the captured stone had been confirmed by fluoroscopy. RESULTS: It was possible to remove the Dormia basket by nonsurgical means in 11 of the 12 patients (92%) after one treatment session, and after three treatment sessions in the remaining patient. Thus, disintegration of the stones allowed extraction of the Dormia basket in all patients. None of the patients needed surgical intervention. All patients were rendered free of bile duct stones after extracorporeal shock-wave lithotripsy and subsequent endoscopic removal of the fragments. No adverse effects of shock-wave therapy with subsequent extraction of the Dormia baskets were observed. CONCLUSION: Shock-wave therapy represents a primary nonsurgical therapeutic option in patients with either impacted Dormia baskets or broken devices which cannot be extracted by endoscopic means.

Aged↗
PubMed1995

Unconjugated secondary bile acids in the serum of patients with colorectal adenomas.

A positive association between deoxcholic acid (DCA) in the serum and colorectal adenomas, the precursors of colorectal cancer has recently been found, which supported the hypothesis of a pathogenic role of DCA in colonic carcinogenesis. This approach was based on the hypothesis that DCA formed in the colon is absorbed into the portal venous blood and exhibits a constant spillover to the systemic circulation. To further substantiate this hypothesis this study investigated whether in the serum of adenoma patients DCA was higher in the unconjugated fraction, which originates directly from the colon. DCA was found to be 2.8-fold higher in the unconjugated fraction of patients with colorectal adenomas than in controls (0.89 v 0.32 mumol/l, p < 0.0025), 1.9-fold in the total DCA fraction (1.89 v 0.95 mumol/l, p < 0.0001), and 1.4-fold in the conjugated fraction (0.67 v 0.47 mumol/l, p < 0.05). It was further found that the bacterial isomerisation product 3 beta-DCA was twofold higher in the unconjugated fraction of adenoma patients than in controls (0.08 v 0.04 mumol/l, p = 0.27), 1.8-fold in the total iso-DCA fraction (0.11 v 0.06 mumol/l, p < 0.05), and 1.5-fold in the conjugated iso-DCA fraction (0.03 v 0.02 mumol/l, p = 0.68). The data suggest that the positive association between the serum DCA concentration and colorectal adenoma as described previously results from the DCA fraction that is absorbed from the colon. This further supports a pathogenic role of DCA in the carcinogenesis of colorectal cancer.

Adenoma↗
PubMed1995

Effect of dietary fiber on serum bile acids in patients with chronic cholestatic liver disease under ursodeoxycholic acid therapy.

During ursodeoxycholic acid therapy for chronic cholestatic liver disease, the serum levels of lithocholic acid increase about twofold. Lithocholic acid has been shown to be hepatotoxic in some animal species. Administration of psyllium hydrophilic mucilloid (PHM), a dietary fiber, has been reported to increase the bile acid mass excreted by the feces. We, therefore, studied the effect of PHM (3 x 3.25 g/day) on serum bile acids including lithocholic acid in 12 patients with primary sclerosing cholangitis (n = 7) and primary biliary cirrhosis (n = 5) receiving ursodeoxycholic acid therapy. After 2 and 6 weeks of treatment with PHM, the serum levels of ursodeoxycholic acid increased by 52.4 +/- 72.8% (p < 0.05) and 40.5 +/- 69.6% (NS), respectively. The absolute serum levels of lithocholic acid were not significantly changed. This led to a decrease of the relative amount of lithocholic acid as referred to total bile acids and to ursodeoxycholic acid in serum by 27.4 +/- 34.5% (p < 0.05) and 25.5 +/- 32.8% (p < 0.05), respectively, after 6 weeks of PHM treatment.

Adult↗
PubMed1995

Gallbladder emptying during high-dose cholecystokinin infusions. Effect in patients with gallstone disease and healthy controls.

BACKGROUND: Impaired gallbladder emptying is a pathogenetic factor in gallstone formation. To test whether gallbladder motility can be improved by high-dose cholecystokinin (CCK), gallbladder emptying was measured sonographically in 21 patients with cholesterol gallstone disease and 6 healthy controls. METHODS: The effects of CCK infusions of 0.06 IDU/kg.min (group A, n = 11) and 0.12 IDU/kg.min (group B, n = 10) were compared with the response to a standard CCK infusion (0.02 IDU/kg.min). Controls received CCK at all infusion rates. RESULTS: The ejection fraction was smaller after CCK infusion of 0.06 IDU/kg.min than after the standard stimulus (group A, 52 +/- 10 versus 64 +/- 10%, p < 0.05; controls, 66 +/- 10 versus 91 +/- 3%, p < 0.05). After infusion of 0.12 IDU/kg.min CCK ejection fractions decreased even more (group B, 44 +/- 16 versus 65 +/- 12%, p < 0.05; controls, 54 +/- 12 versus 91 +/- 3%, p < 0.05). High-dose CCK infusions shortened the ejection period markedly, whereas the ejection rate remained unaltered. CONCLUSIONS: High-dose CCK does not improve gallbladder motility but blocks the ejection process early, leading to reduced gallbladder emptying in gallstone patients and healthy subjects.

Case-Control Studies↗
PubMed1995

Simvastatin added to ursodeoxycholic acid does not enhance disappearance of gallstone fragments after shock wave therapy.

Inhibitors of the HMG-CoA reductase have been shown to further reduce the biliary cholesterol saturation in patients treated with oral bile acids for cholesterol gallbladder stones. It was the aim of our study to evaluate the efficacy of simvastatin in addition to ursodeoxycholic acid in the dissolution of gallstone fragments after shock wave lithotripsy and adjuvant bile acid dissolution therapy. Eighteen patients with a single radiolucent gallbladder stone and a serum cholesterol of more than 250 mg/dl were randomly assigned to receive either ursodeoxycholic acid alone (750 mg per day, group A, n = 9) or in combination with simvastatin (20 mg per day, group B, n = 9) for the dissolution of the gallstone fragments generated by extracorporeal shock wave lithotripsy. The two groups were well matched regarding their baseline characteristics. At the primary end point of the study 6 months after lithotripsy, there was no difference between the groups in the rate of gallstone disappearance with 4 of 9 patients being stone free in each group. As evaluated by life table analysis, even further follow-up showed no significant difference between the groups (P = 0.8). In group B, serum cholesterol levels decreased by 22% at 3 months (P = 0.01 vs. baseline) and by 24% at six months (P = 0.02) during treatment while no significant change was observed in group A. With both regiments, no adverse effects were observed. While simvastatin added to ursodeoxycholic acid resulted in a decrease of elevated serum cholesterol levels in gallstone patients, it did not enhance stone disappearance after shock wave lithotripsy and adjuvant bile acid dissolution therapy.

Anticholesteremic Agents↗