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Biomedical subjects

G Paumgartner

Publications and source records attributed to G Paumgartner.

At least 217 records · Page 12Linked to original sources

Comparative pharmacokinetics of sulphasalazine and sulphapyridine after rectal and oral administration to patients with ulcerative colitis.

Rectal administration of sulphasalazine to patients with ulcerative colitis has recently been shown to have similar therapeutic activity but fewer side effects than oral treatment. The present study is a comparison of the pharmacokinetics of sulphasalazine (SASP) and its metabolite sulphapyridine (SP) after rectal and oral administration of SASP to 6 patients with ulcerative colitis. The areas under the concentration-time curves (AUC) and the maximum concentrations (Cmax) of SASP and SP were significantly lower after rectal than oral administration of SASP (p less than 0.05). These findings support the view that the lower frequency of side effects after rectal administration of SASP may result from the lower plasma levels of SASP and SP.

Administration, Oral↗

Adenomas of the large intestine after cholecystectomy.

The frequency of adenomas of the large intestine in 331 cholecystectomised patients who underwent total colonoscopy was compared with that of a control group of patients with asymptomatic cholelithiasis who were matched for age and sex. Whereas no significant difference in the frequency of adenomas was found between two groups, a subgroup of patients aged 60-80 years with a postcholecystectomy interval of 10 years or greater exhibited a significantly (p less than 0.05) greater frequency of adenomas (38.5%) than matched patients with a postcholecystectomy interval of less than 10 years (21.8%) and matched controls with cholelithiasis (23.7%). This increase in the frequency of adenomas was primarily accounted for by an increase in the percentage of tubular adenomas (p less than 0.05) and corresponded to an increase in the frequency of cancer (p less than 0.05) of the large bowel.

Adenoma↗

Studies on the in vitro interactions of cimetidine with commercial antacid preparations and chemically pure components.

Studies of the in vitro binding of cimetidine to commercial antacid preparations such as colloidal aluminium hydroxide-magnesium hydroxide, aluminium hydroxide-calcium carbonate and the chemical pure components Al(OH)3, Mg(OH)2 or Al2O3 showed no adsorption of cimetidine at cimetidine to antacid ratios employed in clinical practice. Small degrees of binding were observed with two silicate containing antacids (21.4 +/- 0.5 mumol/g and 12.3 +/- 1.9 mumol/g).

Adsorption↗

[Cholesterol content of bile-duct stones].

The cholesterol content of bile-duct stones from 40 patients after cholecystectomy was compared with 22 gall-bladder stones. There were 18 (82%) cholesterol-rich stones (cholesterol content more than 60% of dry weight) among gall-bladder stones, but only 12 (30%) among bile-duct stones. Eight bile-duct stones (20%) contained fibrous material, a further seven (18%) had a cholesterol-rich nucleus and cholesterol-poor outer layer. These findings indicate that residual fibres or small migrated gall-bladder stones can form the nidus for the growth of choledochal stones. The cholesterol content of bile-duct stones did not correlate with the age of the patient, time since cholecystectomy or cholesterol saturation of hepatic bile.

Aged↗

[Hepatology].

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Cholelithiasis↗

Measurement of bile acid kinetics in human serum using stable isotope labeled chenodeoxycholic acid and capillary gas chromatography electron impact mass spectrometry.

A non invasive method for measurement of bile acid kinetics in serum using (24-13C)chenodeoxycholic acid has been developed. After oral administration of 50 mg (24-13C)chenodeoxycholic acid, the exponential decay of the 13C atom percent excess was measured in serum using capillary gas chromatography mass spectrometry. This required that isotope ratios were measured with high accuracy and coefficients of variation less than 1% by means of selected ion monitoring and scan averaging. The clinical applicability was tested by repeated determination of pool size, fractional turnover and synthesis rate of chenodeoxycholic acid in one healthy volunteer. This method permitted the determination of pool size, synthesis and conversion of chenodeoxycholic acid into lithocholic acid in man without the use of radioactive tracers and without repeated duodenal intubation.

Bile Acids and Salts↗

Portal-systemic spill-over of bile acids: a study of mechanisms using ursodeoxycholic acid.

Portal-systemic spill-over of unconjugated ursodeoxycholic acid (UDCA) was assessed in ten healthy subjects, six patients with mild chronic liver disease and eight patients with cirrhosis. Following oral administration of UDCA (1.5 mg/kg body weight), serum concentrations of unconjugated UDCA were measured during 2 h using a capillary gas-liquid chromatographic method. Peak time of UDCA varied from 15 to 30 min, but was not significantly different in the three groups studied. Peak concentration was increased up to two-fold in patients with mild, and up to three-fold in patients with cirrhotic liver disease. Since, in addition, plasma disappearance rate (k) was markedly impaired in cirrhotics (1.7 +/- SD 0.5%/min, compared to 2.8 +/- 0.6 in healthy controls), the calculated area under the curve (AUC) was on the average five-fold that in controls. In two healthy and four cirrhotic subjects, the data obtained after oral administration were compared with those after i.v. loading with the same UDCA dose. The k-values after the two routes of administration were practically identical. Calculated systemic availability was 50% in normals, 78-87% in cirrhotics, 90 and 136% in two patients with surgical porta-caval shunt. It is concluded that the portal-systemic spill-over of UDCA in patients with liver disease is increased primarily due to portal-systemic shunting. Since in the normal liver hepatic extraction of conjugated, endogenous bile acids is greater than 80%, diminished first-pass elimination is expected to augment systemic concentrations even more, particularly when measured after a meal.

Adult↗

Bile acid pattern and cholesterol saturation of bile after cholecystectomy and endoscopic sphincterotomy.

The effect of endoscopic sphincterotomy on bile acid composition and cholesterol saturation of bile has been studied in cholecystectomized patients. Individual bile acids and biliary lipids were measured in hepatic bile of 13 cholecystectomized females aged 56.8 +/- 16.6 years more than 9 months (mean 16.7 +/- 8.8 months) after sphincterotomy and of 12 cholecystectomized females aged 59.3 +/- 11.5 years who served as controls. The sphincterotomy group exhibited a significantly (p less than 0.01) higher percentage of chenodeoxycholic acid in bile--39.2 +/- (SD) 7.7%--than the controls with cholecystectomy only (29.1 +/- 7.4%), but showed no differences in the proportion of cholic acid (32.4 +/- 6.2 vs. 33.6 +/- 7.8%). The percentages of the secondary bile acids, deoxycholic acid (25.0 +/- 8.8 vs. 32.3 +/- 8.3%), and lithocholic acid (1.7 +/- 0.8 vs. 2.6 +/- 2.3%) were lower, but these differences were not statistically significant. The biliary lipid composition in the sphincterotomy group was not different from that in the controls, resulting in a similar cholesterol saturation index in both groups (1.87 +/- 0.60 vs. 2.02 +/- 0.60 according to Carey and Small; 1.45 +/- 0.32 vs. 1.55 +/- 0.32 according to Hegardt and Dam). These findings do not demonstrate any alterations of the bile composition after sphincterotomy which may be expected to have undesirable effects on the biliary and/or gastrointestinal system.

Adult↗

Effect of endoscopic sphincterotomy on bile acid pool size and bile lipid composition in man.

The effect of endoscopic sphincterotomy on bile acid pool size and lipid composition was studied in 3 patients with an intact gallbladder and in 7 patients who had previous cholecystectomy. Measurements were made at two time intervals after endoscopic sphincterotomy, early (3-9 days) and late (6-9 months). Patients with an intact gallbladder showed a marked reduction in their total bile acid pool during follow-up examinations (95.3 +/- SD 14.0 vs. 18.6 +/- 8.1 mumol/kg), whereas in the cholecystectomized patients the pool size showed no significant change (29.4 +/- 13.4 vs. 26.6 +/- 11.4 mumol/kg). The reduction in bile acid pool size caused by sphincterotomy in patients with an intact gallbladder did not increase the degree of cholesterol saturation in hepatic bile.

Aged↗

Involvement of the cytotoxic/suppressor T-cell subset in liver tissue injury of patients with acute and chronic liver diseases.

So far, phenotypic and functional analyses of cytotoxic lymphocytes in viral hepatitis, as well as in primary biliary cirrhosis, have focused on circulating lymphocyte subpopulations, whereas their occurrence and distribution at the involved site, namely the liver, remain largely unknown. In the present study, monoclonal antibodies were used to characterize both circulating and liver-tissue-infiltrating lymphocyte subsets in acute cytomegalovirus hepatitis, in chronic B-virus hepatitis, and in primary biliary cirrhosis. Special emphasis was laid on the cytotoxic/suppressor T-cell subset. Total T cells were identified by the monoclonal antibody T411. The monoclonal antibody T811 was used to identify the cytotoxic/suppressor T-cell subset, which comprises virus-specific, altered self, and alloreactive cytolytic T lymphocytes and their precursors, a fraction of killer and natural killer cells. Furthermore, killer and natural killer cells were identified more specifically by the monoclonal antibody. HNK1. Irrespective of the number of cytotoxic/suppressor T cells in peripheral blood, these cells (T811 phenotype) were accumulated in the liver at the site of tissue injury. The preponderance of this lymphocyte subset at the site of tissue injury suggests an important role for these cells in the mechanism leading to tissue injury.

Adult↗

Absence of in vivo and in vitro interactions of an aluminum hydroxide, magnesium hydroxide containing antacid with cimetidine in patients with peptic ulcer.

In view of contradictory reports on the bioavailability of cimetidine in the presence of concomitantly administered antacids we studied the areas under the plasma concentration time curves (AUC) of cimetidine, the maximal concentrations (cmax) and the time, at which cmax was reached (tmax) in eight patients (five patients with duodenal ulcer, three patients with gastric ulcer) with and without the administration of an aluminum hydroxide magnesium hydroxide containing antacid (Maaloxan). No significant effects of the antacid on AUC, cmax and tmax of cimetidine were found. In vitro studies also showed no adsorption of cimetidine to aluminum hydroxide, magnesium hydroxide or the antacid.

Adult↗

Studies on the in vitro interaction of D-penicillamine with antacids.

Interactions of D-penicillamine with various antacids (aluminum hydroxide-magnesium hydroxide, AH-MH; aluminum hydroxide-calcium carbonate, AH-CC; dihydroxy sodium aluminum carbonate, DSAC; aluminum hydroxide, AH) were studied in vitro. Only a small binding to AH-MH (29.2 +/- 7.2 mumol/g antacid) and AH (13.6 +/- 4.0 mumol/g antacid) and no adsorption at all to AH-CC and DSAC were observed. Bile salts and bicarbonate as well as the pH did not influence binding. Although extrapolations from in vitro studies to in vivo conditions are hazardous, clinically relevant interactions of D-penicillamine with antacids in patients ingesting both drugs in the usual dose range simultaneously appear unlikely.

Adsorption↗

Studies on the in vitro binding of D-penicillamine to cholestyramine.

Adsorption of D-penicillamine to cholestyramine depends on the amount of the resin, the pH and the presence of other compounds such as bile salts. In the usual drug to resin ratio (150 mg D-penicillamine and 4-8 g cholestyramine per single dose) the percentage of D-penicillamine adsorbed to cholestyramine was about 10% of the applied dose; Bile salts (10 mmoles/l) inhibited this small adsorption by 87%.

Adsorption↗

Sclerotherapy of a bleeding duodenal varix.

A case of successful treatment of a bleeding duodenal varix in a patient with portal hypertension and compensated cryptogenic cirrhosis (Child A) is reported. The 42-year-old man had a history of recurrent gastrointestinal hemorrhage over 14 years. In 1966 he underwent a portocaval shunt operation. Angiography in 1968 revealed a thrombosis of the shunt as well as of the splenic vein. Splenectomy was performed because of hypersplenism. In 1980 bleeding from esophageal varices occurred and was treated by sclerotherapy. Seven weeks after sclerotherapy massive bleeding from a duodenal varix occurred. Sclerotherapy of the duodenal varix via a flexible endoscope proved successful. Since then, during a follow-up period of 15 months, the patient has had no further bleeding episodes.

Adult↗