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Biomedical subjects

G Paumgartner

Publications and source records attributed to G Paumgartner.

At least 181 records · Page 10Linked to original sources
PubMed1987

A new model to assess deoxycholic acid metabolism in health using stable isotope dilution technique.

A model has been developed that permits calculation of the absorption rates of newly formed and deconjugated deoxycholic acid (DCA) from the intestine, the fractional absorption rate of deconjugated DCA and the daily rate of formation of DCA. The model is based on steady state conditions and isotopic equalities of conjugated DCA in blood and in the enterohepatic circulation, as well as between unconjugated DCA in blood and in the intestinal content. The model requires measurement of isotopic enrichment in the conjugated and unconjugated fractions of DCA in serum after administration of an isotopic label. The measurements were carried out in seven healthy volunteers using capillary gas chromatography/mass spectrometry after oral administration of 24-13C-DCA. Intestinal absorption of deconjugated DCA exceeded that of newly formed DCA: (mean +/- SD) 7.4 +/- 5.6 vs. 4.5 +/- 2.1 mumol kg-1 d-1. Total absorption of unconjugated DCA (11.9 +/- 6.9 mumol kg-1 d-1) accounted for approximately 6% of estimated total intestinal DCA absorption. The fractional absorption rate of unconjugated DCA in the intestine averaged 55.5 +/- 15.1%; 8.2 +/- 3.3 mumol kg-1 d-1 DCA were formed daily by 7 alpha-dehydroxylation of cholic acid. This rate of DCA formation compares well with values for fecal DCA excretion (15 mumol kg-1 d-1) and cholic acid synthesis rate (11.9 mumol kg-1 d-1) obtained in comparable controls by the same laboratory.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Healthy controls have as much bile reflux as gastric ulcer patients.

Data on duodenogastric reflux of bile in gastric ulcer are conflicting. We therefore measured intragastric bile acid concentration and its composition from individual bile acids, duodenogastric bile acid reflux rate, gastric emptying rate, and secretion rates of volume and acid in 30 patients with gastric ulcer and in 66 healthy controls, both in the fasting state and after feeding a liquid meal. Patients had higher gastric bile acid concentrations (p less than 0.05) than controls in the fasting state, but the overlap between the groups was considerable. In fasting patients with corpus ulcer, gastric secretion rates were significantly decreased when compared with controls. There was no difference between patients and controls with respect to gastric emptying rate, bile acid reflux rate, intragastric amount of bile acids, and bile acid composition in the fasting state. Postprandially, all parameters tested were similar in patients and controls. Controls showed high reflux rates with similar frequency as did ulcer patients. We conclude that increased gastric bile acid concentrations in the fasting stomach of patients with gastric ulcer are the result of gastric hyposecretion and not of increased reflux. They probably are pathogenetically irrelevant.

Adult↗
PubMed1987

Intestinal involvement in progressive systemic sclerosis detected by increased unconjugated serum bile acids.

In patients with progressive systemic sclerosis, impaired motor function of the small intestine may lead to bacterial overgrowth causing diarrhoea, steatorrhoea and malabsorption. As unconjugated serum bile acids have been proposed as markers for small bowel bacterial overgrowth, we studied individual unconjugated serum bile acids in 36 patients with progressive systemic sclerosis. These patients had significantly higher serum concentrations of unconjugated cholic acid (median 0.18; range 0.05-30.75 v 0.09; 0.01-0.19 mumol/l, p less than 0.001) and chenodeoxycholic acid (0.10; 0.01-6.83 v 0.04; 0.01-0.39 mumol/l, p less than 0.025) than healthy controls (n = 16). This difference was mainly due to patients with diarrhoea (n = 10), who had significantly higher concentrations of unconjugated serum bile acids than patients with normal bowel habit (cholic acid median 0.55 v 0.16 mumol/l, p less than 0.001; chenodeoxycholic acid 0.75 v 0.07 mumol/l; p less than 0.005). All patients with raised unconjugated serum bile acids had oesophageal motility disorders. These results confirm a relationship between motility disorders and bacterial overgrowth in patients with progressive systemic sclerosis.

Bile Acids and Salts↗
PubMed1987

[Atrial natriuretic factor. Initial results of possible significance in liver cirrhosis].

The discovery of the first well-defined natriuretic hormone, the Atrial Natriuretic Factor (ANF), has prompted research on its impact on volume regulation in health and disease. The natriuretic, diuretic, and smooth muscle-relaxing properties suggest an important role of this novel hormone in pathophysiological states with sodium or volume retention, such as congestive heart failure or cirrhosis of the liver. Investigations on the implications of ANF in liver disease have been performed for a short period only, and results are still controversial in many respects. At present, it seems very likely that there is no absolute deficiency of plasma ANF in patients with cirrhosis. Moreover, elevated plasma levels in cirrhotics with ascites have been reported by several groups. However, as yet, a molecular characterization of this increased immunoreactivity is still lacking. There is disagreement on the reduced release of and renal response to ANF in subgroups of cirrhotics; however, stimulus-response-coupling might be impaired. Further studies are needed to elucidate the pathophysiological implications and therapeutical potential of ANF in patients with chronic liver disease.

Atrial Natriuretic Factor↗
PubMed1986

Relation between the frequency of colorectal adenoma and the serum cholesterol level.

Several investigators have reported an association between low serum cholesterol levels and an increased frequency of colorectal cancer. Because low cholesterol levels may be a result of an established cancer, we have investigated the relation between serum cholesterol levels and the frequency of colorectal adenomas, which are thought to be precursors of colon cancer. We prospectively studied 1083 consecutive patients who underwent colonoscopy (241 of whom were excluded because of malignant disease, chronic inflammatory bowel disease, familial polyposis, or partial colectomy). In the remaining 842 patients, analysis of covariance was performed to evaluate the contribution of serum cholesterol to the risk of colorectal adenoma. Serum cholesterol levels were significantly and positively associated with the frequency of colorectal adenoma in subjects of both sexes. After adjustment for age and body-mass index, this positive association remained significant between the top quintile and the lowest quintile for serum cholesterol, with regard to the total study group (odds ratio, 2.0; 95 percent confidence limits, 1.1 and 3.6) and men only (odds ratio, 2.2; 95 percent confidence limits, 1.0 and 4.8). We conclude that there is not an inverse correlation between serum cholesterol levels and the risk of colorectal adenomas; on the contrary, there appears to be a small positive association.

Adenoma↗
PubMed1986

Prophylaxis of first variceal hemorrhage in patients with liver cirrhosis.

Prophylaxis of bleeding from esophageal varices is a very tempting concept at first glance, especially under the assumption of a high mortality associated with first variceal hemorrhage. Up to now four different measures have been tried for prophylaxis: portacaval shunt operation, devascularization procedures, sclerotherapy, and drugs. With the exception of portacaval shunts, ongoing controlled trials show a weak trend toward reduction of variceal bleeding and prolongation of survival in selected patients with compensated cirrhosis and large varices. However, prophylaxis of first variceal bleeding must still be regarded as experimental and should be restricted to controlled clinical studies.

Adrenergic beta-Antagonists↗
PubMed1986

Muscarinic M2-receptors enhance polyphosphoinositol release in rat gastric mucosal cells.

Muscarinic receptor types and their effects on the inositol phosphate second messenger system were studied in enzymatically dispersed rat gastric mucosal cells. Radioreceptor binding studies indicated the presence of a single class of binding sites (4860 +/- 875 sites/cell) and affinities of 0.42 +/- 0.12 nM, 176 +/- 32 nM and 13 microM for N-methylscopolamine, pirenzepine and carbachol, respectively. In cells prelabelled with myo-[3H]inositol carbachol induced a dose-dependent increase in inositol-1-phosphate in the presence of lithium with an ED50 of 10 microM which was antagonized by atropine and pirenzepine (IC50 9 and 700 nM, respectively). Carbachol stimulated amino[14C]pyrine uptake, used as a measure of acid secretion, with an ED50 of 10 microM. The good correlation between these responses suggests a role for inositol phosphates in the muscarinic M2-receptor mediated acid secretion.

Aminopyrine↗
PubMed1986

[Therapy of cholelithiasis. Advances and disappointments in the last 50 years].

For many decades cholecystectomy has been the standard treatment for symptomatic cholecystolithiasis. In asymptomatic patients a waiting attitude can be taken. In recent years, non-surgical therapies have been developed for selected patients. Thus, in patients with mild or no symptoms medical dissolution of gallstones with ursodeoxycholic acid, chenodeoxycholic acid or a combination of these two bile acids can be tried if radiolucent stones with diameters below 15 mm are present in a functioning gallbladder (not more than half full of stones). Besides this therapy, cholelithotripsy with extracorporeal shock waves represents a new procedure, which, together with percutaneous or retrograde instillation of methyl tert-butyl ether, needs further evaluation. For elimination of stones from the common bile duct, endoscopic sphincterotomy and stone extraction have proved valuable non-surgical procedures. For choledochal stones not amenable to endoscopic extraction or dissolution by instillation of solvents, treatment by extracorporeal shock waves represents a valuable alternative to surgery. Thus, the past decades have not only brought progress in knowledge of gallstone disease but have also broadened the therapeutic armoury. Therefore, it is essential to select the most appropriate method for each situation.

Bile Acids and Salts↗
PubMed1986

Evidence for down-regulation of beta-2-adrenoceptors in cirrhotic patients with severe ascites.

The density and affinity of beta-2-adrenoceptors on mononuclear cells from peripheral blood were studied in fifteen patients with cirrhosis of different severity and in thirteen controls. There was no significant difference between cirrhotic patients and controls in density or affinity of beta-2 binding sites. Within the cirrhotic group, however, the number of binding sites per cell was significantly lower in patients with severe ascites than in patients with mild to moderate or no ascites. This down-regulation of beta-adrenoceptors could influence the haemodynamic response to beta-blockers.

Adrenergic beta-Antagonists↗
PubMed1986

Fragmentation of gallstones by extracorporeal shock waves.

We treated nine patients with functioning gallbladders containing one to three symptomatic radiolucent stones not larger than 25 mm in diameter, as well as five patients with stones in the common bile duct that were not removable by endoscopic procedures, by means of extracorporeally generated shock waves during general anesthesia. The patients with gallbladder stones received adjuvant treatment with a combination of ursodeoxycholic acid and chenodeoxycholic acid. All gallbladder stones were disintegrated into sludge or fragments with diameters of no more than 8 mm. In six of the nine patients the fragments disappeared completely within 1 to 25 weeks. No adverse effects were detected during a follow-up period of 10 to 34 weeks, except transient biliary pain in two patients, with mild pancreatitis in one. In four of the five patients with common-bile-duct stones, shock-wave treatment permitted stone disintegration and successful endoscopic extraction or spontaneous passage of fragments. We conclude that gallstone disease may be treated successfully and without serious adverse effects by extracorporeally generated shock waves in selected patients.

Adult↗
PubMed1986

Cytolytic T cell clones derived from liver tissue of patients with chronic hepatitis B.

To study the role of cell-mediated immunity in chronic hepatitis B (cHB) we have cloned T cells from liver biopsies of 14 patients with cHB. As a first step, T cell lines were established from lymphocytes infiltrating the liver by culturing the biopsied specimens with autologous feeder cells and interleukin 2 (IL2). Fifty-eight clones obtained by limiting dilution showed phenotypic stability over periods of 2-26 weeks. Of the 58 clones 50 were of the "cytotoxic/suppressor" T cell subset (CD8) as defined by the monoclonal antibody T811. Only 8 of 58 clones were of the "helper/inducer" phenotype (CD4) as defined by the monoclonal antibody T151. Functional studies on 9 clones (7 of CD8+ phenotype, 2 of CD4+ phenotype) revealed high cytotoxic activity of all of these clones in a lectin-dependent cell-mediated cytotoxicity assay reflecting the killing capacity of cytotoxic T lymphocytes. All 9 clones lacked significant natural killer activity, while two additional CD8+ clones that also expressed the VEP13 antigen showed significant natural killer activity. For none of the clones tested could killer cell activity (ADCC) be demonstrated. The studies demonstrate that the clonal expansion of T lymphocytes from liver biopsies of patients with cHB in the absence of detectable antigen is possible. The propagation of in vivo activated cytolytic T lymphocytes points to an active role of these cells in the pathogenesis of this disease.

Adult↗
PubMed1986

Inhibition of human colonic (Na+ + K+)-ATPase by arachidonic and linoleic acid.

The sodium pump, (Na+ + K+)-ATPase, which is involved in the transport of cations and water movement by the colonic mucosa, may be decreased in various diarrhoeal states. In this study, we have measured 3H-ouabain binding and (Na+ + K+)-ATPase activity in human colonic biopsy homogenates and the influence of various inflammatory and antiinflammatory compounds on these parameters. 3H-ouabain binds to one site of high affinity (KD 1.9 +/- 0.2 X 10(-9) mol/l) with a maximal binding capacity of 7.5 +/- 0.8 X 10(14) binding sites/g protein. Both arachidonic and linoleic acid inhibited (Na+ + K+)-ATPase activity (IC50 arachidonic acid: 7.5 X 10(-5) mol/l, linoleic acid: 6.5 X 10(-5) mol/l) and Mg2+-ATPase activity (IC50 arachidonic acid: 9 X 10(-5) mol/l, linoleic acid: 4 X 10(-5) mol/l). Arachidonic acid inhibited 3H-ouabain binding, (IC50 3.2 X 10(-5) mol/l). The following antiinflammatory compounds, at concentrations up to 1 X 10(-3) mol/l, did not influence ATPase activity directly nor reverse the arachidonic acid-induced inhibition: indomethacin (cyclooxygenase inhibitor), nordihydroguaiaretic acid (lipoxygenase inhibitor), sulphasalazine and its metabolites: 5-aminosalicylic acid, N-acetylaminosalicylic acid and sulphapyridine. These results indicate that human colonic (Na+ + K+)-ATPase is inhibited by the prostanoid precursors, arachidonic and linoleic acid. From a therapeutic point of view (effect on colonic (Na+ + K+)-ATPase and perhaps diarrhoea), the suppression of the production of these prostanoid precursors by drugs may, therefore, be beneficial in the treatment of inflammatory bowel disease.

Anti-Inflammatory Agents↗
PubMed1986

In vitro cholesterol gallstone dissolution after fragmentation with shock waves.

In order to test whether shock wave fragmentation of human gallstones increases their dissolution rates in a bile acid-lecithin solution, we carried out in vitro experiments. Stones comparable in size, weight and cholesterol content (86%) from the same human gallbladder were disintegrated by shock waves. A glycoursodeoxycholic acid (GUDC)-lecithin solution served as solvent. After 10 days incubation in this solvent, intact stones had lost only 4% of their cholesterol. This value increased to 92% after disintegration of the stones by 300 shock wave discharges. Fragments with a size of less than 2 mm had lost 55% of their cholesterol after day 1 and 99% after day 10. A large stone fragment cleaved off by shock waves lost much more cholesterol (42% after 10 days) than an intact untreated stone (4% after 10 days) comparable in size, weight and cholesterol content. These data show that shock wave lithotripsy of cholesterol gallstones considerably accelerates their dissolution rate in a GUDC-lecithin solvent, the desirable fragment size being 2 mm or less. However, even large fragments may lose much more cholesterol than comparable intact stones as a result of changes in surface structure as documented by scanning electron microscopy. The experiments favor the concept of a combined treatment of gallbladder stones by extracorporeally generated shock waves and bile salt therapy.

Cholelithiasis↗