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Biomedical subjects

G Paumgartner

Publications and source records attributed to G Paumgartner.

At least 235 records · Page 13Linked to original sources
PubMed1982

Inhibition of drug metabolism by cimetidine in man: dependence on pretreatment microsomal liver function.

The effect of cimetidine on hepatic microsomal drug metabolism was studied in six patients with normal liver and eleven patients with chronic liver disease using the aminopyrine breath test. Before administration of cimetidine, the elimination rate constant of 14CO2 from breath (Kb) was 28.3 +/- SD 1.3%/h in patients with normal liver and 13.5 +/- 7.7%/h in patients with liver disease (P less than 0.001). After 7 days of cimetidine therapy (1 g/day) Kb decreased to 23.3 +/- 5.2%/h (19.0 +/- 13.8% decrease; P less than 0.05) and 7.4 +/- 5.8%/h (50.5 +/- 14.4% decrease; P less than 0.001), respectively. Plasma levels of cimetidine were not significantly different (1.05 +/- 0.14% micrograms/ml v. 0.88 +/- 0.41; P greater than 0.05). The findings indicate that therapeutic doses of cimetidine lead to an inhibition of drug metabolism which is more pronounced in patients with impaired liver function than in liver normals. Therefore, patients with chronic liver disease may be at increased risk with respect to interactions between cimetidine and other drugs which are demethylated by the liver.

Aged↗
PubMed1982

Increased serum bile acids in cirrhosis with normal transaminases.

Fasting and postprandial serum concentrations of total conjugated primary bile acids determined by radioimmunoassay have been compared with conventional liver function tests in patients with cirrhosis of the liver and normal transaminases. While gamma-glutamyl-transferase had the highest sensitivity (69%) among the conventional liver function tests, it was much less sensitive for the detection of cirrhosis with normal transaminases than fasting (93% sensitivity) or postprandial (93% sensitivity) bile acid concentrations in serum. When a combination of fasting and postprandial bile acid concentrations was used, the sensitivity increased to 97%.

Adult↗
PubMed1982

Esophageal function after sclerotherapy of bleeding varices.

To study the effect of sclerotherapy of varices on esophageal function, the motility of the tubular esophagus and of the lower esophageal sphincter (LES) were recorded in 19 patients after 7 to 13 sclerotherapy sessions and in 15 healthy volunteers. In addition, esophageal functional scintigraphy (EFS) was performed in the patient group. Compared with the volunteers the patients had lower contraction amplitudes in the distal esophagus (30.5 +/- 17.5 mm Hg versus 43.6 +/- 9.1 mm Hg, p less than 0.01) and a higher percentage of non-propulsive simultaneous contractions (NPC) in the distal (33.4 +/- 23.2% versus 9.0 +/- 8.6%, p less than 0.005) and mid-esophagus (15.0 +/- 8.2% versus 8.3 +/- 8.1%, p less than 0.05). There was a negative correlation between the percentage of NPC in the distal and mid-esophagus and radionuclide transit (rs - 0.53, p less than 0.02). Three of 19 patients had a positive reflux index by EFS. The LES tone was only slightly lower in the patients than in the controls (10.7 +/- 3.2 mm Hg versus 13.4 +/- 3.6 mm Hg, p less than 0.05). Our findings indicate that sclerotherapy of esophageal varices may lead to a reduced peristaltic esophageal motility with an impaired transport function. This could contribute to the development of dysphagia or esophagitis.

Adolescent↗
PubMed1982

Retrograde colonic spread of sulphasalazine enemas.

In five patients with inflammatory bowel disease and in two healthy control subjects retrograde spread and colonic distribution of rectally introduced sulphasalazine (SASP) enema were investigated. The SASP enema was labeled with 99mTc and imaged by a gamma camera. In all patients the SASP enema reached the inflamed portion of the colon. From 73% to 84% of the total SASP enema were fairly homogeneously distributed beyond the patients' rectum. The results suggest that patients with inflammatory bowel disease may benefit from SASP enemas even if the total colon is involved.

Adult↗
PubMed1981

[Biliary excretion kinetics of the biliary contrast media ioglycamide, iodoxamate and iotroxamate in the dog].

The biliary excretion of meglumine iotroxamate (ITX) and meglumine iodoxamate (IDX), two new intravenous cholangiographic contrast materials, was compared with that of meglumine ioglycamide (IGL) in bile-fistula dogs following intravenous infusion in a steady state. With any equimolar infusion rate or plasma concentration, more ITX and IDX were secreted in the bile than IGL. The maximum rate of biliary excretion (Emax.) of either ITX (2.23 +/- SD 0.28 mumol/min/kg) or IDX (2.91 +/- SD 0.39 mumol/min/kg) was significantly greater than that of IGL (1.22 +/- SD 0.19 mumol/min/kg); the biliary concentration was always greater for ITX and IDX than for IGL.

Animals↗
PubMed1981

Nicotinic acid test in the diagnosis of Gilbert's syndrome: correlation with bilirubin clearance.

A provocation test with nicotinic acid (50 mg intravenously) was performed in 13 patients with Gilbert's syndrome and seven healthy volunteers to investigate the diagnostic value of several test parameters and to correlate them with the bilirubin clearance. The maximal increment of unconjugated serum bilirubin, the retention at four hours, and the area under the bilirubin concentration time curve. (AUC) were measured. Significant differences between patients and controls were found with regard to the AUC (7.95 +/- SD, 3.29 mmol/min/l vs. 3.08 +/- 0.57; P less than 0.001), the increment of unconjugated bilirubin (24.1 +/- 7.1 mumol/l vs. 10.2 +/- 3.2; P less than 0.001) and the retention (77.7 +/- 8.9% vs. 45.8 +/- 27.4%; P less than 0.02). Of those, the AUC discriminated best between patients and controls. Five patients with Gilbert's syndrome had normal serum bilirubin concentrations (less than 17.1 mumol/l = 1 mg%) at the time of the study, but abnormal AUC and bilirubin increment. A significant correlation was found between the bilirubin clearance and the retention (r = -0.96; P less than 0.001) as well as the AUC (r = -0.82; P less than 0.05) but not with the bilirubin increment. This simple test may be used to assess the disturbance of bilirubin clearance in Gilbert's syndrome.

Adult↗
PubMed1980

[Damage to liver and biliary tracts by long-term drug therapy (author's transl)].

Drug damage to the liver can be divided into two types: Type I damage is predictable, dose-dependent and appears in most patients treated. Type II lesions are not predictable, are not dose-dependent and occur in only a small percentage of patients. Clinically they can be differentiated into (1) a cytotoxic form (clinical picture: fatty liver, virus hepatitis), (2) a cholestatic form (clinical picture: obstructive jaundice) and (3) a mixed form. In the present study, liver damage due to the following drugs, as important examples of the different types of damage, are dealt with in greater detail: isoniazid (unpredictable damage of the cytotoxic type), methotrexate (predictable damage of the cytotoxic type) chlorpromazine (unpredictable damage of the cholestatic type) and finally estrogens or oral contraceptives (damage of the cholestatic type and other damage to the hepatobiliary system).

Chemical and Drug Induced Liver Injury↗
PubMed1980

[Disorders of bile secretion, Pathophysiological principles and therapeutic possibilities (author's transl)].

A number of disturbing factors may lead to total impairment of bile secretion by altering the physical chemical properties, enzyme activites of the number of available receptors of the hepatocyte plasma membrane or raise the permeability of the biliary tract. Other disturbing factors change the composition of the bile and may consequently favor the formation of gallstones. More recent information on the formation of gallstones has led in a relatively short time to a better recognition, prophylaxis and therapy of individual disorders of bile secretion. Thus the tendency to form cholesterol concrements can be detected by investigating the bile. Knowledge of risk factors makes prophylaxis possible and today the pharmacological control of biliary lipid secretion permits drug therapy of certain forms of gallstones disorders.

Animals↗
PubMed1980

Autoradiographic evidence for hepatic lobular concentration gradient of bile acid derivative.

Using an iodinated bile-acid analog with hepatic uptake and transport characteristics similar to conventional bile acids, the hepatic lobular gradient concept of Goresky was studied utilizing autoradiography. 125I-labeled cholylglycylhistamine (125I-CGH) was infused into the portal veins of male Sprague-Dawley rats and the livers were fixed for light microscopic autoradiography at 1 and 5 min after infusion. In two animals, sequential samples of bile were collected to assess the transport characteristics of 125I-CGH. By 1 min, virtually all (98%) of the injected 125I-CGH was taken up and retained by hepatocytes after perfusion fixation. Less than 15% of the label was lost during subsequent tissue processing. 125I-CGH appeared in bile within minutes, reaching maximum levels at 7 min. Quantitative autoradiography demonstrated that the first six to nine periportal hepatocytes were, by far, the most active (P less than 0.0005) in sequestering the bile-acid analog than were the remaining cells in the lobule. This study, therefore, provides the first autoradiographic evidence of a hepatic lobular concentration gradient for the uptake of a bile-acid analog.

Animals↗
PubMed1980

[The effect of clanobutin on bile excretion in rat and dog (author's transl)].

The effect of 4-[p-chloro-N-(p-methoxyphenyl)-benzamido] butyric acid (clanobutin, Bykahepar) on bile formation was studied in anesthetized male Sprague-Dawley rats and in non-anesthetized female boxer dogs. Following i.v. injection of 40 mg/kg body weight of clanobutin, a marked choleresis paralleling the biliary excretion of the drug was observed in both species. The biliary elimination of 1 mumol clanobutin (and metabolites) caused on the average an increment of bile flow of 90 microliter and 11.5 microliter in the rat and dog, respectively. Bile flow was linearly related to clanobutin excretion in rat and dog. Within the period of observation 55% of the dose of clanobutin in the rat, and 80% of the dose in the dog were eliminated via the bile; urinary excretion amounted to 3% of the dose. In rat bile, 32% of the clanobutin was present as the parent compound; the remaining 68% consisted of 3 metabolites. Measurement of the erythritol clearance in the dog suggests that clanobutin stimulates the bile salt-independent, canalicular bile formation. In addition, however, the observed changes in the bile/plasma concentration ratio of erythritol, as well as a predominant excretion of bicarbonate and chloride point to a possible ductular effect of clanobutin. In these acute studies, the drug did not influence the bile salt, phospholipid or cholesterol excretion. Cholesterol saturation of bile was unaffected.

Animals↗
PubMed1980

Analysis of serum bile acids by capillary gas--liquid chromatography--mass spectrometry.

A method for quantitative analysis of serum bile acids by capillary gas--liquid chromatography--mass spectrometry is described. The main features of this method are a Grob-type barium carbonate/polyethyleneglycol 20,000 glass capillary column, an all-glass capillary interface, use of the lipophilic anion exchanger DEAP-Sephadex-LH-20 for purification of the serum extract, and chenodeoxycholic-11,12-d2 acid as internal standard. Linearity of the response (ratio of intensities of the fragment ions diagnostic for the bile acid to be measured and for the internal standard) was demonstrated for four different bile acids. The method is sufficiently sensitive for measurement of bile acids in serum of healthy humans.

Bile Acids and Salts↗
PubMed1979

Inhibition of hepatic Na +, K + -adenosinetriphosphatase in taurolithocholate-induced cholestasis in the rat.

Na +, K + -adenosinetriphosphatase (Na +, K + -ATPase) activity was decreased in liver plasma membranes from rats in which cholestasis had been induced by i.v. administration of sodium taurolithocholate (5 mumoles/100 g b. wt). Incubation of liver plasma membranes with taurolithocholate (10--1300 muM) caused significant and dose dependent reductions of Na +, K + -ATPase activity at taurolithocholate concentrations above 100 muM. These findings lend support to the hypothesis that cholestasis induced by monohydroxy bile acids is at least partially the result of an inhibition of hepatic Na +, K + -ATPase activity.

Animals↗