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Biomedical subjects

G Paumgartner

Publications and source records attributed to G Paumgartner.

At least 253 records · Page 14Linked to original sources

[Bile acid concentration in serum after a test meal in hepatobiliary diseases. A comparison with quantitative liver function tests].

The concentration of bile acids in serum was measured by an enzymatic-fluorometric method under fasting conditions and 2 hours after a standardized meal in 26 patients with chronic liver disease (chronic hepatitis, liver cirrhosis, primary biliary cirrhosis) and compared with other tests of liver function. Postprandial bile acids and transaminases were false negative in only 12% and are thus the most sensitive tests after the BSP-retention test (3% false negative results). In comparison, fasting bile acids proved to be a relatively insensitive screening test for liver disease (38% false negative results). Postprandial bile acids were more closely correlated with BSP retention and BSP disappearance rate constant (Ki) than fasting bile acids. In view of these findings postprandial serum bile acid concentrations should be preferred to fasting bile acid concentrations in screening for liver disease and monitoring liver function.

Adult↗

[Procetophen--an alternative in the treatment of hypercholsterinemia?].

18 patients with primary hyperlipoproteinemia of type IIa and type IIb, on regularly controlled dietary treatment for 6 months and a 4 weeks placebo period, were given 300 mg procetofene per day for 12 weeks. The subjective tolerance of the drug was good. The serum triglyceride levels were lowered by about 35%, total cholesterol by 15%, LDL-cholesterol by 12% and Apo B by 20%. The HDL-cholesterol values remained unchanged. A slight increase in SGPT values indicates that liver function should be regularly checked in patients undergoing procetofene therapy.

Adult↗

Disparate Na+-requirement of taurocholate and indocyanine green uptake by isolated hepatocytes.

Uptake of both taurocholate and indocyanine green (ICG) by isolated rat hepatocytes was saturable and obeyed Michaelis-Menten kinetics. Only uptake of taurocholate exhibited Na+-dependence, a phenomenon compatible with active membrane transport. These findings suggest that the mechanisms responsible for hepatocellular uptake of bile acids and anionic dyes differ fundamentally.

Animals↗

[Effect of the lipid-lowering agent, procetofen, on the makeup of human biliary lipids].

The effect of lipid-lowering treatment with procetofen (3 x 100 mg/day for 4-6 weeks) on the cholesterol saturation index (S.I.) of bile has been studied in 6 patients with type IIa or IIb pattern hyperlipoproteinemia. Compared with a control period with placebo, the S.I. was increased by more than 20% during active treatment in 2 patients. Oversaturation was reached in one case. In the other 4 patients, the changes did not exceed 20% of the control value. Thus, increased lithogenicity of bile does not appear to be a frequent effect of procetofen. A larger number of patients should therefore be studied to establish its true incidence.

Adult↗

A highly specific 125I-radioimmunoassay for cholic acid conjugates.

Several modifications of the immunization procedure permitted development of a highly specific radioimmunoassay (RIA) for cholic acid conjugates. Antiserum was produced in guinea pigs using cholic acid-thyroglobulin complex as immunogen. 125-I-Cholyglycylhistamine was prepared as radioactive ligand according to a modification of the method of Spenney et al. (Spenney, J.G., Johnson, B.J., Hirschowitz, B.I., Mihas, A.A. and Gibson, R. (1977) Gastroenterology 72, 305--311). The association constant of the antisera to taurocholic acid was 1.8 x 10(7) l/mol, the working range of the assay between 9.5--890 pmol. Cross-reactivities of the antiserum to bile acids other than cholic acid species were less than 3%, which is lower than for any published bile acid RIA. Concentrations of cholic acid conjugates in sera obtained from 17 healthy fasting volunteers ranged from 0.4--1.9/mumul/l.

Animals↗

Determination of bile acids in serum by capillary gas-liquid chromatography.

A glass capillary column and an appropriate relatively simple procedure for sample preparation have been developed for determination of serum bile acids. Sample preparation involved extraction with Amberlite XAD-2, solvolysis of sulfates, enzymatic hydrolysis with cholylglycine hydrolase, methylation and silylation. Because of complete chromatographic separation of bile acid trimethylsilylether derivatives from cholesterol on the capillary column, an additional step for elimination of cholesterol could be omitted. Trimethylsilylether derivatives were separated on a 20 meter x 0.3 mm i.d. glass capillary column covered with a crystal layer of barium carbonate and coated with polyethyleneglycol 20,000 as liquid phase according to Grob, K. and Grob, G. (1976) J. Chromatogr.125, 471--485, and Grob, K., Grob, G. and Grob, Jr., K., (1977) Chromatographia 10, 181--187. Overall recovery of the major human conjugated bile acids ranged from 86 to 89%. Reproducibility of bile acid determination was satisfactory in both normal and pathological serum with elevated bile acid concentrations (coefficient of variation 7.6 to 10.0%). The mean concentrations of cholic, deoxycholic, chenodeoxycholic and lithocholic acid in the serum of healthy subjects were 0.9, 1.0, 1.7 and 0.2 mumol/l in males, and 1.0, 0.8, 1.4 and 0.2 mumol/l in females.

Adolescent↗

Cation-anion gap and choleretic properties of rat bile.

To investigate whether bile contains choleretic anion(s) other than bile salts (BS) that could account for the observed cation-anion gap in bile, the choleretic properties of bile were investigated in the rat. Infusion of bile increased bile flow significantly more than did taurocholate (TC) (P less than 0.005). By contrast, TC increased BS excretion more substantially (P less than 0.01). This effect was dose dependent for both bile and TC. The choleretic principle had a molecular weight of less than 1,000 as estimated by ultrafiltration of bile. Infusion of bile that had been chromatographed on BioBeads SM-2 still elicited choleresis, whereas bile that had been chromatographed on Dowex 1 x 50W did not. Administration of bile in vivo did not affect Na+-K+-stimulated ATPase activity in liver plasma membrane fractions. These results suggest that bile contains anion(s) other than 3-hydroxy-BS, which increase bile flow in a dose-dependent fashion without affecting the permeability of the biliary tree. This putative choleretic appears to be anionic in nature, heat stable, and has an apparent molecular weight of less than 1,000. This finding suggested that bile salt-independent bile flow partly depends on the excretion of a currently undefined anion.

Animals↗

[Hepatic extraction of taurocholate and indocyanine green in patients with liver disease (author's transl)].

Bile acids are increasingly used as test substances for the estimation of liver function and it has been postulated that radioactive labeled bile acids have advantages over indocyanine green (ICG) for measurement of hepatic blood flow. Therefore, the hepatic extractions of 14C-taurocholate and ICG were compared in 23 patients with liver disease and correlated with various parameters of hepatic function. The hepatic extractions of 14C-taurocholate (mean: 42 +/- SD 17%) and ICG (mean: 35 +/- SD 18%) were similar. The correlations with galactose elimination capacity and BSP plasma disappearance were closer for ICG than for 14C-taurocholate extraction. Hepatic blood flow measured with 14C-taurocholate (mean: 1.45 +/- SD 0.51 l/min) correlated well (r = 0.81) with the respective values obtained with ICG (mean: 1.17 +/- SD 0.49 l/min), but was about 22% larger. This study does not provide evidence that 14C-taurocholate is superior to ICG as an intravenous test substance for measurement of hepatic function or blood flow.

Adult↗

Hepatic handling of a gamma-emitting bile salt derivative, 123I-cholylglycylhistamine, in the dog.

The hepatic handling of the bile salt derivative 123I-cholylglycylhistamine has been compared with that of the physiologic bile salt taurocholate in boxer dogs equipped with a Thomas duodenal cannula. After intravenous injection of trace amounts, 123I-cholylglycylhistamine and 14C-taurocholate disappeared from plasma with nearly identical disappearance rate constants. Excellent scintiscans of the liver were obtained with the Anger camera after injection of 3 mCi of 123I-cholylglycylhistamine. Monitoring of radioactivity over a hepatic region of interest revealed rapid uptake of 123I-cholylglycylhistamine by the liver, which reached a maximum 5.7 +/- 0.4 min after injection. The biliary excretion rates of the compounds closely paralleled each other, reaching their maximum within 15 min after injection. Cumulative biliary excretion within 45 min was 58.5 +/- 2.9% and 61.4 +/- 5.0% of the dose for 123I-cholylglycylhistamine and 14C-taurocholate, respectively. Modification of the side chain and gamma-labelling of bile salts may provide scintigraphic agents for the study of the biliary system, which in the behaviour closely resemble the physiologic parent compounds.

Animals↗

Radioimmunological determination of serum 3 beta-hydroxy-5-cholenoic acid in normal subjects and patients with liver disease.

A radioimmunoassay for the determination of 3 beta-hydroxy-5-cholenoic acid in human serum has been developed, using 3 beta-hydroxy-5-cholenoyl-thyroglobulin as immunogen and 3 beta-hydroxy-5-cholenoylglycyl-125I histamine as radioactive ligand. The association constant was 6.3 X 10(8) l/mol. Cross reactivity with other bile acids of human serum was not detectable, but was 5.6% with cholesterol. Serum sample preparation included extraction of 3 beta-hydroxy-5-cholenoic acid from serum, solvolysis of sulfates, hydrolysis of conjugates, and separation from cholesterol by thin-layer chromatography. Serum concentrations of 3 beta-hydroxy-5-cholenoic acid were 0.23 +/- SD 0.12 mumol/l and 0.21 +/- SD 0.09 mumol/l in healthy males and females, respectively. In patients with primary biliary cirrhosis the serum concentration of 3 beta-hydroxy-5-cholenoic acid and the quotient 3 beta-hydroxy-5-cholenoic acid over total 3 alpha-hydroxy-bile acids (measured enzymatically) were significantly higher (P less than 0.02) than in patients with chronic active hepatitis or alcoholic cirrhosis. Analysis of 17 sera with elevated concentration of 3 beta-hydroxy-5-cholenoic acid by radioimmunoassay and capillary gas-liquid chromatography showed a close correlation (r = 0.91, slope = 0.97) between the results of the two methods.

Adult↗

[Comparison of the biliary excretion of the radiographic contrast media Iotroxamate and Ioglycamide in the dog].

Biliary excretion of iotroxamat (ITX) and ioglycamide (IGL) in cholecystectomized dogs fitted with a Thomas duodenal cannula is compatible with saturation kinetics exhibiting maximal excretory velocities of 2.23 +/- SD 0.18 and 1.22 +/- 0.19 mumol/min/kg, respectively. While biliary excretion of ITX obeyed classical Michaelis Menten kinetics, the data obtained with IGL suggested a more complex process. The choleretic effects of both contrast agents (23.6 +/- SD 2.29 and 25.8 +/- 2.21 microliter of excreted substance) were comparable. On the basis of these results and in view of the similar toxicity of the two contrast agents in animals, it may be expected that ITX will have advantages over IGL for intravenous cholangiography.

Animals↗

[Diagnosis and therapy of chronic active hepatitis].

Chronic active hepatitis (CAH) as an entity covers a histologically, biochemically, and clinically heterogenous group of patients. Hence, there is no justification for treating all patients with this diagnosis with corticosteroids. On the basis of histological, biochemical, and clinical criteria, different degrees of severity of CAH can be distinguished. While corticosteroids appear to be indicated in severe CAH, they should, in general, not be administered in mild CAH. However, the course of disease must be carefully followed in these patients. In moderate CAH, the risk should be carefully weighed against the benefit of therapy in every individual patient, taking into account the severity of symptoms. In HBsAg-negative cases, a therapeutic trial of at least 6 months' duration is worthwhile. In HBsAg-positive patients, treatment with corticosteroids should be delayed and the course of the disease followed. Once the decision for corticosteroid therapy has been made, administration of 10 mg prednisolone and 50 mg azathioprine daily as a maintenance dose represents the therapy of choice. This combination is approximately as effective as 15--20 mg prednisolone alone, but is associated with a lower incidence of side effects.

Azathioprine↗

Bile acid pattern in human amniotic fluid.

Individual bile acids were determined in twenty-nine amniotic fluid specimens obtained from twenty-six women between the 32nd and 41st week of gestation. Total bile acid concentration ranged from 0.4 to 4.8 mumol/l with a mean of 1.57 mumol/l. Besides the two major bile acids of man, cholic acid and chenodeoxycholic acid, 3beta-hydroxy-5-cholenoic acid was found in all, lithocholic acid in ten and deoxycholic acid in nine of the twenty-nine amniotic fluid samples. 3beta-Hydroxy-5-cholenoic acid averaged 39.8% of total bile acids during 32-37 weeks of gestation and 20.2% at term (P less than 0.01). These findings point towards important differences between fetal and adult bile metabolism and may reflect maturation of hepatic bile acid biosynthesis near term.

Amniotic Fluid↗

Analysis of bile acids in serum and bile by capillary gas-liquid chromatography.

Various liquid phases for glass capillary columns have been evaluated for gas-liquid chromatographic analysis of methyl ester trimethylsilylether derivatives of bile acids from serum and bile. Bile acid analysis is rapid and exhibits high separation efficiency with a 20 X 0.3 mm glass capillary column whose internal surface is covered with a crystal layer of barium carbonate and coated with polyethyleneglycol 20000 as liquid phase according to Grob et al.

Bile↗