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F Stellaard

Publications and source records attributed to F Stellaard.

At least 91 records · Page 5Linked to original sources

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↗

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↗

Mass spectrometry identification of biliary bile acids in bile from patients with gallstones before and during treatment with chenodeoxycholic acid. An ancillary study of the National Cooperative Gallstone Study.

The chemical structure of individual bile acids in 255 duodenal bile samples obtained from patients with radiolucent gallstones before and during treatment with chenodeoxycholic acid (375 or 750 mg/day) was determined by coupled gas chromatography/mass spectrometry. The two primary bile acids, cholic acid and chenodeoxycholic acid, and their metabolic products, deoxycholic acid, lithocholic acid, and ursodeoxycholic acid, were present in all bile samples and constituted greater than 97% of all bile acids. In pretreatment samples, the 12-oxo derivative of deoxycholic acid (3 alpha-hydroxy-12-oxo-cholanoic acid) was the next most abundant bile acid, being present in 62% of the samples; the average concentration was 1%, but three individuals had 6% to 8% of this bile acid. The 7-oxo derivative of chenodeoxycholic acid was also present in the majority of samples, but at a lower proportion (0.3%); five individuals had 2% to 3%. The 7-oxo derivative of cholic acid was present in a minority of samples (37%) in trace concentrations; isodeoxycholic acid and the 3-oxo derivatives of chenodeoxycholic acid and deoxycholic acid were also present in trace amounts. Four patients had 1% to 11% ursocholic acid in bile. During treatment with chenodeoxycholic acid, bile became enriched in it in direct relation to dosage; the concentration of its bacterial metabolites increased, and the proportion of cholic acid and its bacterial metabolites showed a reciprocal decrease. No unusual bile acids appeared, indicating that treatment with these doses of chenodeoxycholic acid does not result in the occurrence of additional uncommon bile acids in bile. It is suggested that the paucity of uncommon bile acids in bile, which contrasts strikingly with the great variety of uncommon bile acids known to be present in urine and feces, is the result of two factors: (1) the conversion of uncommon bile acids to common bile acids by reduction, hydroxylation, or epimerization during hepatic passage; and (2) efficient hepatic transport of common but not uncommon bile acids into bile.

Bile↗

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↗

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↗

[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↗

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↗

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↗

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↗