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Biomedical subjects

G Paumgartner

Publications and source records attributed to G Paumgartner.

At least 199 records · Page 11Linked to original sources

Comparison of 75SeHCAT retention half-life and fecal content of individual bile acids in patients with chronic diarrheal disorders.

Measurement of the retention of 23-75Se-25-homotaurocholic acid (SeHCAT) has been suggested as a new test for ileal function. We investigated 31 patients with chronic diarrhea, 10 with ileal Crohn's disease and 21 with diarrhea but without ileal disease. The whole-body retention half-life of 1 mu Ci SeHCAT was determined and compared to the fecal content of total and individual bile acids. Patients with ileal disease had increased primary fecal bile acids (chenodeoxycholic acid: mean 6.95 mg/g dry weight, range 3.15-10.6 mg/g; cholic acid: mean 18.15 mg/g, range 10.3-33.9 mg/g) and a short SeHCAT retention (mean 11.9 h, range 2-24 h), whereas patients with intact ileum had normal fecal bile acids and a SeHCAT retention of 85.9 h (range 28-216 h). SeHCAT retention half-life differentiated well between patients with ileal disease and patients with normal ileum, thus indicating the SeHCAT test as a valid investigation method for detection of primary bile acid malabsorption in patients with chronic diarrhea and ileal dysfunction.

Adolescent↗

Altered fecal bile acid pattern in patients with inflammatory bowel disease.

Alterations of the enterohepatic circulation of bile acids in patients with Crohn's disease (CD) and ulcerative colitis (UC) are known, but fecal bile acid patterns are less well defined. In this study total and individual fecal bile acids of 10 patients with CD (8 patients without bowel resection) 6 patients with UC and 5 healthy volunteers (HV) were determined by capillary gas chromatography. In comparison to HV (782 + 82 mg) the daily fecal excretion rate of bile acids was increased in CD (2,739 +/- 877 mg) and decreased in UC (409 +/- 55 mg). CD (80 +/- 19%) and UC (83 +/- 7%) had mainly primary bile acids, while secondary bile acids were predominant (80 +/- 4%) in HV. Bacterial conversion from primary to secondary bile acids is likely to be altered by rapid mouth-anus transit time (52 +/- 21 min) in UC and in CD by acidic stool pH (5.2 +/- 0.5). This lack of intestinal secondary bile acids may have pathophysiologic significance.

Adult↗

Determination of deoxycholic acid pool size and input rate using [24-13C]deoxycholic acid and serum sampling.

We have developed an isotope dilution method for determination of deoxycholic acid pool size and input rate which employs oral administration of 50 mg of [24-13C]deoxycholic acid and serum sampling. The method has been validated by classical isotope dilution technique using [24-14C]deoxycholic acid and bile sampling in five patients with colonic adenomas. Excellent agreement between pool sizes and input rates determined with 13C/12C isotope ratio measurements in serum and 14C measurements in bile was obtained when isotope ratios were measured in the conjugated fraction of deoxycholic acid in serum. We conclude that pool size and input rate of deoxycholic acid can accurately be determined by blood sampling after oral administration of [24-13C]deoxycholic acid, therewith eliminating the use of radioactive tracers and the need for bile sampling.

Adenoma↗

Caffeine elimination: a test of liver function.

Fasting plasma caffeine concentration and various parameters of caffeine elimination from plasma obtained after a standardized oral dose of 140 mg caffeine have been compared in nine patients with liver cirrhosis, eight patients with non-cirrhotic liver disease and ten healthy volunteers with regard to their ability to discriminate between the different groups. Fasting plasma caffeine concentrations were significantly higher in cirrhotics (11.1 +/- 10.5 mumol/l) than in healthy volunteers (1.5 +/- 0.8 mumol/l). The respective values measured in patients with non-cirrhotic liver disease (3.1 +/- 3.1 mumol/l) did not differ significantly from the controls. Plasma disappearance rate and clearance of caffeine were significantly decreased in cirrhotics (0.11 +/- 0.02 h-1; 1.0 +/- 0.3 ml/min per kg) and in patients with non-cirrhotic liver disease (0.18 +/- 0.04 h-1; 2.2 +/- 0.7 ml/min per kg) as compared to healthy volunteers (0.23 +/- 0.04 h-1; 3.1 +/- 0.9 ml/min per kg). Plasma caffeine concentration determined 12 h after administration of the test dosage discriminated best between patients with cirrhosis (5.4 +/- 1.6 mumol/l), patients with non-cirrhotic liver disease (2.0 +/- 1.4 mumol/l) and healthy volunteers (0.8 +/- 0.2 mumol/l). These results, the safety of the test compound and the simplicity of a single caffeine determination in plasma 12 h after a standardized dose of caffeine make this test attractive for evaluation of liver function.

Adult↗

Measurement of isotope ratios in organic compounds at picomole quantities by capillary gas chromatography/quadrupole electron impact mass spectrometry.

Measurements of isotope ratios in organic compounds at nanomolar concentrations in biological fluids require sensitive and selective gas chromatographic/mass spectrometric methods. The efficiency of sample preparation procedures must be high and gas chromatographic conditions must assure high resolution chromatography producing narrow, intense peaks. Mass spectrometric conditions must create suitable mass fragments, preferably in the high mass range. Detection, controlled by selected ion monitoring (SIM), requires the use of small mass intervals and adequate acquisition times. However, the choice of optimal conditions is limited by the need to acquire multiple data points for the eluting compound. The effects of these variables on the precision of isotope ratio measurements have been investigated to develop an optimal method for isotope ratio measurements in serum bile acids at low concentrations (0.05-8 micromol l-1). With a 25 m X 0.32 mm fused silica capillary OV-1701 column and cold on-column injection, peak widths of 10 s were obtained. Quadrupole mass spectrometry in the electron impact ionization mode (70 eV) and selected ion monitoring (SIM)(mass interval 1/16 u, acquisition time 100 ms) allowed precise (cv less than 1.5%) isotope ratio measurements for chenodeoxycholic, cholic and deoxycholic acid in a single run at quantities as low as 5 pmol injected on the column. SIM switching during the run permitted isotope ratio measurements (cv less than 2.2%) for an additional six bile acids, normally detected in the serum of healthy subjects.

Bile Acids and Salts↗

Long-term sclerotherapy of bleeding esophageal varices in patients with liver cirrhosis. An evaluation of mortality and rebleeding risk factors.

Ninety-six liver cirrhosis patients with bleeding esophageal varices receiving long-term sclerotherapy with the flexible endoscope were studied prospectively to analyze mortality and rebleeding risk factors. The difference in the 1-year survival rates of Child's groups A (100%) and B (82%) versus Child's C patients (38%) was highly significant (p less than 0.001). Multivariate analysis revealed that, as single factors, serum bilirubin, grade of ascites, and prothrombin time and, as a combination, the four variables bilirubin, ascites, aspartate aminotransferase, and age distinguished best between survivors and non-survivors during the first 6 months after inclusion in the study. For the separation of rebleeders and non-rebleeders during the first 2 months, prothrombin time and grade of ascites gave the best distinction. Thus, cirrhotics with variceal hemorrhage, ascites, jaundice, and a prolonged prothrombin time remain a high-risk group also with long-term sclerotherapy.

Adolescent↗

Determination of the pK values of 5-aminosalicylic acid and N-acetylaminosalicylic acid and comparison of the pH dependent lipid-water partition coefficients of sulphasalazine and its metabolites.

Sulphasalazine (SASP), used in the treatment of inflammatory bowel disease, is split into sulphapyridine (SP) and 5-aminosalicylic acid (5-ASA) in the colon. Lower plasma levels of SASP and 5-ASA as compared to those of SP may be due to different absorption rates from the colon because of different pK values and pH dependent lipid-water partition coefficients. In this study we determined the pK values of 5-ASA and its major metabolite, N-acetyl amino-salicylic acid (AcASA), by 13C-NMR spectroscopy and compared the pH dependent apparent benzene-water partition coefficients (Papp) of SASP, SP and 5-ASA with respect to their different plasma levels. The COOH group of 5-ASA had a pK value of 3.0, the -NH3+ group had 6.0, the -OH group 13.9; the -COOH group of AcASA had 2.7 and the -OH group 12.9; The Papp of SASP (0.042 +/- 0.004) and 5-ASA (0.059 +/- 0.01) were significantly lower than that of SP (0.092 +/- 0.03) (at pH 5.5).

Aminosalicylic Acids↗

Simultaneous determination of cholic acid and chenodeoxycholic acid pool sizes and fractional turnover rates in human serum using 13C-labeled bile acids.

A method has been developed for simultaneous determination of pool sizes and fractional turnover rates (FTR) of chenodeoxycholic acid (CDCA) and cholic acid (CA) in man by 13C/12C isotope ratio measurements of bile acids in serum after oral administration of 20-50 mg of [24-13C]-labeled bile acids. 13C/12C isotope ratio measurements were performed by capillary gas-liquid chromatography/electron impact mass spectrometry. CA and CDCA kinetics in serum measured by this method exhibited first order kinetics and permitted calculation of pool size and FTR of CA and CDCA. The validity of the measurements in serum was tested by simultaneous measurements in bile in three healthy volunteers and in five patients with various hepatobiliary disorders (three patients with cirrhosis, one with cholecystectomy and sphincterotomy, and one with sphincterotomy only). No consistent differences were found between the pool sizes and FTR's obtained from serum and bile. In a total of five healthy volunteers bile acid kinetics were measured in serum. The values found for the pool sizes and FTR's of CA and CDCA in these subjects were in excellent agreement with data reported in the literature based on 14C or 3H measurements in bile. The pool sizes (mean +/- SD) of CDCA and CA were 32.6 +/- 9.9 and 31.8 +/- 16.0 mumol X kg-1, respectively. The corresponding values for the FTR's were 0.24 +/- 0.13 and 0.48 +/- 0.22 d-1. These data demonstrate that pool sizes and fractional turnover rates of cholic and chenodeoxycholic acid can be measured simultaneously by blood sampling after oral administration of the respective 13C-labeled bile acids.

Adult↗

[Mebendazole therapy in echinococcosis. Long-term study and course parameters in 8 patients].

Eight patients with inoperable echinococcosis, four each with the cystic or alveolar form, had received mebendazole (Vermox) at a daily dose of 1.5 g for an average of 27 months. In six patients with clinical symptoms the number of fever attacks fell by 60% and of hospital admissions by 54%, cholangitic and/or icteric attacks disappearing completely. Two patients had no recognizable symptoms, either before or after treatment. One woman with multilocular disease died of bleeding from esophageal varices. The immunological and morphological findings did not reveal any relationship to the clinical course. Apart from reversible leukopenia in one patient there were no serious side effects. These observations indicate a satisfactory effect of long-term treatment of inoperable echinococcosis with mebendazole.

Adult↗

[Long-term sclerosing therapy of bleeding esophageal varices. A prospective course study].

Longterm sclerotherapy by flexible endoscopy was done in 109 patients with acute bleeding from oesophageal varices in a prospective follow-up study. The severity of the liver disease was classified according to Child (Pugh's modification) at the beginning of treatment. Patients were followed-up for at least 12 months with a maximum of 44 months. The one-year survival rate for all patients was 67%. Child-A patients (100%) and child-B patients (84%) had a significantly better survival than Child-C patients (36%; P less than 0.001). The rate of haemorrhage per patient-month was significantly lower (P less than 0.001) in Child-A patients (0.4%) and Child-B patients (2.4%) than in Child-C patients (8.5%). After initial sclerosing of 8 weeks' duration the rate of recurrent haemorrhage was only 1.3% per patient-month. There was a significant difference (P less than 0.005) between Child-A patients (0.2%) and Child-B and -C patients (2%). The data show that Child-Pugh's classification permits a high prognostic accuracy in predicting results of sclerotherapy. Child-A and -B patients are suitable candidates for longterm sclerotherapy whereas Child-C patients show a clearly increased risk of recurrent bleeding during the early phase of treatment and have a markedly reduced survival rate.

Esophageal and Gastric Varices↗

Soybean lipoxygenase inhibition: studies with the sulphasalazine metabolites N-acetylaminosalicylic acid, 5-aminosalicylic acid and sulphapyridine.

Soybean lipoxygenase inhibition has been proposed as an in vitro biochemical model for the antiinflammatory action of certain drugs used in the treatment of ulcerative colitis. In an extension of a recent study which showed that therapeutically active compounds, such as sulphasalazine and its colonic metabolite 5-aminosalicylic acid were soybean lipoxygenase inhibitors, it has now been shown that N-acetylaminosalicylic acid, the principal metabolite of 5-aminosalicylic acid, also inhibits soybean lipoxygenase in a dose dependent and noncompetitive manner (Ki 3.0 X 10(-8) M, IC50 250 microM). Sulphapyridine, the other major metabolite of sulphasalazine, which has been demonstrated to be inactive in the treatment of ulcerative colitis, did not inhibit the lipoxygenase activity. The findings further support the hypothesis that only the therapeutically active compounds are soybean lipoxygenase inhibitors.

Aminosalicylic Acids↗