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G Paumgartner

Publications and source records attributed to G Paumgartner.

At least 73 records · Page 4Linked to original sources
PubMed1995

Specific inhibition of hepatitis C viral gene expression by antisense phosphorothioate oligodeoxynucleotides.

The inhibitory effect of antisense phosphorothioate oligodeoxynucleotides (S-ODN) on hepatitis C viral gene expression and analyzed in an in vitro test system and in cell culture. S-ODN were directed against different stem loop structures in the 5'noncoding region (NCR) of the hepatitis C virus, (HCV) RNA and against a nucleotide stretch, including the start codon of the polyprotein precursor. The inhibitory effect of these S-ODN was quantified employing a viral RNA consisting of the first 407 nucleotides of a HCV type 1b genome fused to the coding sequence of the firefly luciferase gene. For in vitro assays this RNA was generated by in vitro transcription and used as a template in a rabbit reticulocyte lysate in vitro translation system. The production of active luciferase in the absence or presence of S-ODN was monitored using an enzymatic assay. The best results were obtained with S-ODN 4 directed against nucleotides 326 to 348, comprising the start AUG of the polyprotein coding sequence. With this oligonucleotide, a specific and dose-dependent effect was observed with a maximal inhibition of 96 +/- 1% at a S-ODN concentration of 4.14 mumol/L. For cell culture experiments, the hepatoblastoma cell line HepG2 was transfected with a plasmid expressing the HCV-luciferase fusion RNA. In this assay system S-ODN 2, complementary to nucleotides 264 to 282 of the HCV RNA, and S-ODN 4 were most efficient and reduced the viral translation by 96 +/- 0.4% and 94 +/- 0.7%, respectively, at a concentration of 0.3 mumol/L. The inhibition was specific (1) because the expression of the HCV-luciferase fusion RNA was not significantly impaired by the control S-ODN and (2) because the expression of an unrelated messenger RNA was not or only slightly downregulated. These data suggest that HCV gene expression can be inhibited effectively by antisense S-ODN. Therefore, this approach represents a promising perspective for the treatment of hepatitis C.

Base Sequence↗
PubMed1994

Gallbladder emptying determines early gallstone clearance after shock-wave lithotripsy.

BACKGROUND/AIMS: Disappearance of gallbladder stones after shock-wave lithotripsy combined with bile acid therapy depends on mechanical evacuation and dissolution of fragments. Many patients with gallstones have impaired gallbladder emptying and may show delayed stone clearance after lithotripsy. METHODS: The effect of gallbladder emptying on gallstone clearance after lithotripsy was prospectively studied in 57 patients with one radiolucent gallbladder stone < or = 20 mm. Gallbladder emptying was assessed sonographically before and after 2 weeks of ursodeoxycholic acid (UDCA) treatment. RESULTS: UDCA increased gallbladder fasting and residual volume and decreased ejection rate but did not affect ejection fraction. Patients with an ejection fraction > 60% achieved complete gallstone clearance after lithotripsy in a higher percentage than patients with smaller ejection fractions (1 month, 31% vs. 7%, P = 0.022; 2 months, 55% vs. 18%, P = 0.003; 3 months, 66% vs. 29%, P = 0.005). Patients who became stone-free within 1 month showed larger ejection fractions than patients with retained fragments (67% +/- 4% vs. 56% +/- 3% before UDCA, P = 0.032; 65% +/- 4% vs. 53% +/- 3% with UDCA, P = 0.017). Further, ejection rate during UDCA therapy was larger in patients with complete gallstone disappearance within 1 month than in patients with delayed fragment clearance (1.57%/min +/- 0.36%/min vs. 0.76%/min +/- 0.09%/min; P = 0.002). CONCLUSIONS: Gallbladder emptying is a major determinant of early gallstone clearance after lithotripsy.

Adult↗
PubMed1994

Prevention of ischemia/reperfusion injury in the rat liver by atrial natriuretic peptide.

BACKGROUND/AIMS: Atrial natriuretic peptide (ANP) protects against hypoxia/reoxygenation-induced damage of cultured hepatocytes, thus suggesting a therapeutic potential in the liver. Therefore, the effects of ANP on hepatic ischemia/reperfusion injury after warm ischemia were studied. METHODS: Livers of male Sprague-Dawley rats subjected to 60 minutes of warm ischemia at 37 degrees C were perfused in the presence or absence of 200 and 20 nmol/L ANP. RESULTS: Sinusoidal lactate dehydrogenase efflux increased to 2000 +/- 264 and 126 +/- 50 mU.min-1.g liver-1 after 1 minute and 60 minutes of reperfusion, but it only increased to 1240 +/- 160 and 22 +/- 16 mU.min-1.g liver-1 in the presence of 200 nmol/L ANP during the preischemic and postischemic perfusion period. The postischemic bile flow (0.67 +/- 0.18 microL.min-1.g liver-1) was significantly improved with 200 nmol/L ANP (0.92 +/- 0.05) and showed a linear correlation to biliary glutathione excretion. In contrast, 20 nmol/L ANP had no protective effects. Administration of 200 nmol/L ANP during the preischemic perfusion period alone (but not after starting reperfusion) markedly preserved postischemic liver function. CONCLUSIONS: Continuous ANP administration or ANP pretreatment alone prevents hepatic ischemia/reperfusion injury, possibly because of influences on intracellular signal transduction processes. The correlation between bile flow and biliary glutathione excretion supports the hypothesis that biliary glutathione transport is one of the osmotic driving forces in postischemic bile formation.

Animals↗
PubMed1994

Pathogenic factors in early recurrence of cholesterol gallstones.

BACKGROUND/AIMS: Supersaturation of bile with cholesterol, rapid nucleation of cholesterol crystals, and/or incomplete emptying of the gallbladder are believed to be required for gallstone formation. The importance of these factors for the recurrence of gallbladder stones was studied. METHODS: Twenty patients, untreated after successful shock wave therapy, were studied in a matched case-control design for bile acid turnover, composition of duodenal bile, and gallbladder emptying. In 10 of them, gallstones had recurred within 12 +/- 2 months (X +/- SEM); the other 10 had been free of stones since 22 +/- 3 months. RESULTS: In each group, duodenal bile was supersaturated with cholesterol in 8 of 10 patients and showed abnormal nucleation time of cholesterol crystals in half of the patients. Patients with recurrent stones had smaller pool sizes of cholic acid (-43%) and enhanced conversion of cholic acid to deoxycholic acid. The odds for stone recurrence were ninefold increased in the presence of excessive deoxycholic acid (exceeding cholic acid) in the bile acid pool or incomplete emptying of the gallbladder (residual volume > 5 mL) in response to cholecystokinin. The odds ratio was over 20-fold increased when incomplete emptying of the gallbladder coincided with supersaturated bile or with excessive deoxycholic acid. CONCLUSIONS: Enhanced conversion of cholic acid to deoxycholic acid and incomplete emptying of the gallbladder could be important cofactors for the recurrence of gallstones.

Bile↗
PubMed1994

Gallstone recurrence after shock-wave therapy.

BACKGROUND/AIMS: The long-term outcome of nonoperative gallstone therapy depends on both absence of stones and absence of biliary pain. The aim of the present study was to determine the rate of stone recurrence and the rate of symptoms within 5 years after successful shock wave lithotripsy combined with bile acid therapy. METHODS: One hundred consecutive patients (single stones, n = 89; 2 or 3 stones, n = 11) were followed up for a median of 4.3 years after stone disappearance and discontinuation of bile acids. RESULTS: Twenty-three of the 100 patients developed recurrent stones. Calculated by actuarial analysis, the recurrence rate was 7% +/- 3%, 11% +/- 3%, 13% +/- 4%, 20% +/- 5%, and 31% +/- 7% (mean +/- SD) at 1, 2, 3, 4, and 5 years, respectively. The recurrent stones were small (6 +/- 5 mm) and were associated with recurrent biliary pain in 14 (61%) of the 23 patients. Repeated shock wave lithotripsy and/or bile acid medication resulted in stone disappearance in only 10 of 20 patients with recurrence. CONCLUSIONS: The long-term rate of stone recurrence after lithotripsy of primarily solitary gallbladder calculi is lower than expected from post-bile acid dissolution trials. Recurrence of stones frequently is associated with recurrence of biliary pain.

Adult↗
PubMed1994

Fibronectin in human gallbladder bile: cholesterol pronucleating and/or mucin "link" protein?

Some biliary proteins (pronucleators) seem to be essential factors for cholesterol crystal formation and crystal growth in bile. A recent study suggests that fibronectin is such a pronucleator in bile. Fibronectin also seems to closely interact with intestinal mucin. Since biliary mucin plays an important role in gallstone formation, such an interaction in bile may be of relevance in cholesterol gallstone formation. To more clearly elucidate the role of fibronectin in cholesterol gallstone disease, we measured the concentration of fibronectin in native bile of cholesterol gallstone patients and checked its influence on the cholesterol nucleation time of model bile. We further looked for a molecular interaction between biliary fibronectin and gallbladder mucin. We found that fibronectin is present in gallbladder bile of gallstone patients in low concentrations (2.6 +/- 1.2 micrograms/ml). Bile fibronectin did not interact with gallbladder mucin. Moreover, in a wide range of concentrations fibronectin had no influence on the nucleation time of model bile. We conclude that fibronectin does not seem to play a major role in cholesterol gallstone disease.

Bile↗
PubMed1994

Variation of serum bile acids in patients with colorectal adenomas during a one-year follow-up.

We were recently able to show that patients with colorectal adenomas have an increased serum level of the secondary bile acid deoxycholic acid [Bayerdörffer et al.: Gastroenterology 1993; 104:145-151]. The course of individual serum bile acids was followed for 1 year in a random subgroup of these patients. The individual serum bile acids of 39 patients, 10 men with adenoma, 12 men without adenoma, 8 women with adenoma, and 9 women without adenoma, were determined at 6-month intervals by gas liquid chromatography (GC). The mean individual differences in serum bile acids between baseline and 6-month follow-up and baseline and 12-month follow-up ranged from +19 to -15 nmol/l in men with adenoma, and from +66 to -64 nmol/l in men without adenoma. In women, the ranges were +73 to -74 nmol/l in those with adenoma and +33 to -81 nmol/l in those without adenoma. The variations of the relative percentages of the individual bile acids in the three investigations were lower than those of the absolute values. The differences between the baseline, the 6-month, and the 12-month follow-up were not significant for the major bile acids deoxycholic acid, chenodeoxycholic acid and cholic acid. The main finding, namely an increase in the serum levels and the relative proportion of deoxycholic acid in men with colorectal adenomas remained unchanged throughout the follow-up. The data indicate that measurement of the bile acid pattern by GC is a useful and reproducible parameter in investigating the role of secondary bile acids in the pathogenesis of colorectal cancer.

Adenoma↗
PubMed1994

Ursodeoxycholic acid treatment of cholesterol gallstone disease.

Bile acid dissolution therapy alone or in combination with extracorporeal shock-wave lithotripsy continues to be a safe and effective non-surgical treatment for highly selected patients with cholesterol gallstone disease. Its disadvantages are the duration of drug treatment and potential stone recurrence. Its advantages, however, are non-invasiveness, low rate of morbidity, and lack of mortality. Considering the variety of options in modern gallstone therapy, the careful selection of treatment should be tailored to the individual patient's clinical and personal situation. This will involve the patient in the decision-making process.

Cholelithiasis↗
PubMed1994

Combination of extracorporeal shock-wave lithotripsy and dissolution of gallbladder stones with methyl tert-butyl ether: a randomized study.

We conducted a prospective randomized study in gallstone patients to determine whether a combination of extracorporeal shock-wave lithotripsy and subsequent dissolution with methyl tert-butyl ether increases the success rate of methyl tert-butyl ether dissolution and shortens treatment time compared with monotherapy with methyl tert-butyl ether. Fifty patients were randomized into two groups. Twenty-five patients underwent extracorporeal shock-wave lithotripsy before contact dissolution with methyl tert-butyl ether, and 25 patients were treated with methyl tert-butyl ether alone. All patients had at least three stones or stones larger than 30 mm that were radiolucent on x-ray and had densities of less than 140 Hounsfield Units (HU) on computed tomography. Overall, the combined approach neither shortened the treatment time significantly vs. monotherapy with methyl tert-butyl ether nor reduced the time of hospitalization. The success rate was slightly but not significantly increased compared with that of methyl tert-butyl ether therapy alone. The recurrence rate was similar in the two groups after a median follow-up of 1 yr. However, when subgroups of patients with at least one stone larger than 15 mm or with stones with densities of more than 60 HU were analyzed, the clearance rate after 5 mo was significantly higher (p < 0.005 and p < 0.025, respectively) in patients subjected to a combination of extracorporeal shock-wave lithotripsy and methyl tert-butyl ether dissolution. Extracorporeal shock-wave lithotripsy and methyl tert-butyl ether did not expose patients to more adverse effects than did treatment with methyl tert-butyl ether alone.

Adult↗
PubMed1993

Decreased high-density lipoprotein cholesterol and increased low-density cholesterol levels in patients with colorectal adenomas.

OBJECTIVE: To study the relation between serum lipoprotein levels and the frequency of colorectal adenomas, the benign precursors of colorectal cancer. DESIGN: Cross-sectional. SETTING: University hospital in Germany. PATIENTS: The study included 822 of 1124 consecutive patients who underwent colonoscopy at our institution (302 patients were excluded because of malignant disease, chronic inflammatory bowel disease, familial polyposis, partial colectomy, or other chronic diseases). Of the 822 study patients, 194 had colorectal adenoma. MEASUREMENTS: Serum cholesterol fractions (high-density lipoprotein [HDL], low-density lipoprotein [LDL], and very low-density lipoprotein [VLDL]) and presence or absence of adenomas; univariate and logistic regression analyses were carried out to evaluate the association between serum HDL, LDL, and VLDL cholesterol levels and the frequency of colorectal adenoma. RESULTS: Univariate analysis of the total patient group showed that the HDL cholesterol level was inversely related to the frequency of colorectal adenoma (odds ratio, 0.36; 95% Cl, 0.21 to 0.62) and that LDL and VLDL cholesterol levels were positively associated with adenoma frequency (odds ratio, 2.31 [Cl, 1.36 to 3.92] and 1.72 [Cl, 1.03 to 2.86], respectively). Univariate analysis of the subgroup of 89 patients with high-risk adenomas showed an inverse association between such adenomas and HDL cholesterol (odds ratio, 0.37; Cl, 0.18 to 0.76). A logistic regression analysis that included age and body mass index showed an association between lipoprotein levels and the presence of adenomas. The relative strength (in descending order) of these associations was as follows: HDL, LDL, VLDL, and total serum cholesterol. A logistic regression analysis of patients with high-risk adenoma showed a significant association between such adenomas and the HDL cholesterol level. CONCLUSIONS: Patients with colorectal adenomas have lower HDL cholesterol levels and higher LDL and VLDL cholesterol levels; these lipoproteins may have prognostic significance for the development of colorectal adenomas.

Adenoma↗
PubMed1993

Serum bile acids in primary biliary cirrhosis: effect of ursodeoxycholic acid therapy.

Serum bile acid levels and distributions were studied every 6 mo in patients with primary biliary cirrhosis who were randomly assigned to receive ursodeoxycholic acid (13 to 15 mg/kg/day) (n = 73) or a placebo (n = 73) over a 2-yr period. In the ursodeoxycholic acid group, ursodeoxycholic acid was the predominant serum bile acid at 6 mo and throughout the 2-yr treatment period. The total concentration of endogenous bile acids decreased with a reduction in cholic acid (in the ursodeoxycholic acid group and the placebo group, respectively [mean +/- S.E.]: 13.0 +/- 2.2 and 12.6 +/- 2.5 mumol/L at entry vs. 3.5 +/- 0.6 and 9.0 +/- 2.2 mumol/L at 2 yr; p < 0.002), chenodeoxycholic acid (in the ursodeoxycholic acid group and the placebo group, respectively: 12.1 +/- 1.7 and 12.7 +/- 2.3 mumol/L at entry vs. 5.8 +/- 0.8 and 10.7 +/- 2.2 mumol/L at 2 yr; p < 0.02) and 3 beta-hydroxy-delta 5-cholenoic acid. The concentration of deoxycholic acid did not change, whereas that of lithocholic acid increased significantly (in the ursodeoxycholic acid group and the placebo group, respectively: 0.63 +/- 0.06 and 0.81 +/- 0.12 mumol/L at entry vs. 1.26 +/- 0.12 and 0.90 +/- 0.15 mumol/L at 2 yr; p < 0.001). These changes were independent of the histological stage of the disease. Thus during ursodeoxycholic acid administration the liver was exposed to a lower level of endogenous bile acids and to an increased concentration of ursodeoxycholic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Acids and Salts↗
PubMed1993

Increased risk of 'high-risk' colorectal adenomas in overweight men.

BACKGROUND: Epidemiologic studies have suggested that the incidence of colorectal carcinoma may be related to overnutrition, but retrospective analysis of its relation to the body mass index (BMI: kg/m2) has produced conflicting data. METHODS: To avoid as many sources of statistical bias as possible, the relation between BMI and the presence of colorectal adenomas was investigated in a cross-sectional study. RESULTS: Two thousand twelve consecutive colonoscoped patients were investigated (532 patients with malignancies or other conditions associated with weight loss were excluded). The relation between BMI and observed colorectal adenomas was evaluated by a logistic model controlling for other prognostic factors such as age, sex, and serum cholesterol level. The subgroup of "high-risk" adenomas with an increased risk of malignant transformation was positively associated with the BMI in men of the age group 50.5-68.1 years (quintiles III and IV: odds ratio for the top quintile vs. the lowest quintile, 3.21; 95% confidence interval, 1.15-8.98). CONCLUSIONS: It was concluded that the risk of developing high-risk adenomas tends to be increased in men who are overweight and that this association is independent of the positive association with the serum cholesterol level recently described.

Adenoma↗
PubMed1993

Increased serum deoxycholic acid levels in men with colorectal adenomas.

BACKGROUND: Epidemiological and animal studies have suggested that the secondary bile acid deoxycholic acid is cocarcinogenic in colorectal cancer, but this hypothesis was not confirmed by case-control studies investigating fecal bile acids. METHODS: Individual serum bile acid concentrations were investigated in 25 men and 25 women with colorectal adenomas and in an equal number of age- and sex-matched controls by gas-liquid chromatography. RESULTS: Deoxycholic acid levels were significantly higher in the sera of men with colorectal adenomas (1.70 +/- 0.59 vs. 1.16 +/- 0.39 mumol/L, P < 0.0005) and in a combined analysis of both sexes (1.47 +/- 0.78 vs. 1.08 +/- 0.39 mumol/L, P < 0.0025). Six- and 12-month follow-up measurements of deoxycholic acid concentrations in a subgroup of 22 men and 17 women showed higher serum levels in men with adenomas, indicating that measurement of deoxycholic acid concentration may be a reliable parameter to investigate its pathogenetic role in colonic neoplasia. CONCLUSIONS: The data of this study support the hypothesis that deoxycholic acid may play a role in the pathogenesis of colorectal cancer.

Adenoma↗
PubMed1993

Advantages of the new loop diuretic torasemide over furosemide in patients with cirrhosis and ascites. A randomized, double blind cross-over trial.

Torasemide is a new loop diuretic with a longer half-life and longer action than furosemide in healthy subjects. In order to evaluate the pharmacodynamic effects, single oral doses of furosemide (80 mg) and torasemide (20 mg), which were equipotent in healthy subjects, were given to 14 patients with cirrhosis and ascites. Before the study patients underwent an equilibration period of 4 days without diuretics. The drugs were alternated following a randomized double-blind cross-over design after a wash-out period of at least 2 days. Urine was collected at defined intervals for 24 h after drug administration and blood samples were taken before, 6 h and 24 h after medication. Torasemide induced greater cumulative 24 h diuresis (2863 +/- 343 vs. 2111 +/- 184 ml, p < 0.01) than furosemide. Torasemide did not differ from furosemide for cumulative 0-6 h sodium excretion (96 +/- 17 vs. 92 +/- 23 mmol sodium) but caused a more pronounced cumulative 6-24 h natriuresis (38 +/- 11 vs. 17 +/- 4 mmol, p < 0.05). Five patients exhibited a weak response to furosemide (0-36 mmol sodium/24 h, median 24 mmol; 690-1460 ml urinary volume/24 h, median 1325 ml). These patients showed significantly higher natriuresis and diuresis following torasemide (26-136 mmol sodium/24 h, median 78 mmol, p < 0.05; 1670-3610 ml urinary volume/24 h, median 2200 ml, p < 0.05). Twenty-four hours after administration of both drugs there were no significant changes in hemodynamic, renal or hormonal parameters. No adverse effects were noted with either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Increased frequency of CD8+ CD45R0+ memory T lymphocytes in acute hepatitis B virus infection.

CD8+ lymphocytes of the memory subset (= CD45R0+) encompass antigen-specific effector cells, which are believed to be decisive for virus elimination in several viral infections. To determine whether this can be extended to HBV infection naive and memory T cells were studied among CD(4+)- and CD(8+)-lymphocytes and used monoclonal antibodies in two-color flow cytometric analysis to quantitate functional T cell subsets in peripheral blood of patients with acute hepatitis B (n = 11), chronic hepatitis B (n = 24) and healthy individuals (n = 26). Compared to CD4+ populations of healthy individuals the number of total CD4+ lymphocytes in patients with both acute or chronic hepatitis was significantly reduced. In contrast CD8+ cells did not significantly change in either acute and chronic hepatitis. Analysis of naive and memory subsets demonstrated, however, a significant rise in CD45R0+ memory cells from 5 to 15% (70% of all CD8+ cells) in acute hepatitis. These changes within the CD8+ population were, however, restricted to the acute phase of hepatitis in that the frequency of CD8+CD45R0+ decreased within weeks post infection. Furthermore, patients with chronic hepatitis did exhibit normal values of CD8+ memory cells (30% of all CD8+ cells). These findings suggest that enrichment of CD8+CD45R0+ memory cells reflects an accumulation of functional effector cells, which may be specifically activated by viral antigens and determine the outcome of infection.

Acute Disease↗