PubMed Health⌕ Search

Biomedical subjects

F Stellaard

Publications and source records attributed to F Stellaard.

At least 73 records · Page 4Linked to original sources
PubMed1990

Stable isotope dilution analysis of very long chain fatty acids in plasma, urine and amniotic fluid by electron capture negative ion mass fragmentography.

A sensitive and selective stable isotope dilution electron capture negative ion chemical ionization mass fragmentography method applying pentafluorobenzyl derivatives was developed for the accurate quantitation of very long chain fatty acids. This technique allowed detection of 1-5 pg of each compound and was applied to plasma (100 microliters), amniotic fluid (1 ml) and urine (1 ml). Normal concentrations were established and the concentrations in samples of selected patients with classified peroxisomal disorders were determined. In plasma samples of all patients the C26:0/C22:0 ratios were elevated (range 0.03-0.43), compared to the control ratios (range 0.003-0.021). The ratio C26:0/C22:0 was elevated in four of five amniotic fluid samples from fetuses with peroxisomal disorders (range 0.18-0.54) when compared with controls (range 0.05-0.25). An elevation of the ratio C26:1/C22:0 was observed in all five amniotic fluid samples (range 0.22-0.60 vs. 0-0.08 in controls). Urinary C26:0 concentrations were lower than in plasma and amniotic fluid and diagnostic ratios were not elevated in patients with peroxisomal disorders.

Adolescent↗
PubMed1990

Prenatal diagnosis of inherited metabolic disorders by quantitation of characteristic metabolites in amniotic fluid: facts and future.

An attempt is made to summarize as completely as possible what is known about the prenatal diagnosis of amino- and organic acidurias by direct measurement of characteristic metabolites in amniotic fluid, and to indicate which disorders can potentially be diagnosed prenatally by direct quantitation of metabolites. Furthermore, the disorders are mentioned in which the prenatal diagnosis was proven to be unsuccessful by this approach. The prenatal diagnoses of a case of propionic acidemia and a case of tyrosinemia type I in the 11th and 12th week of gestational age, respectively, are reported and the prospects of performing amniocentesis in the first trimester for prenatal diagnosis are discussed.

Amniocentesis↗
PubMed1990

Plasma polyol levels in patients with cataract.

Galactitol and sorbitol concentrations in plasma were determined in patients (with or without cataract) in whom homo- or heterozygosity for galactokinase, galactose-1-phosphate uridyltransferase, systemic or peripheral UDP-galactose epimerase and sorbitol dehydrogenase deficiency was confirmed. For the above disorders it can be concluded that elevation of plasma polyols is not always related to the presence or absence of cataract. In all cases with cataract, however, the plasma galactitol or sorbitol levels were elevated. In another group of patients with unexplained congenital or infantile cataracts, but without apparent enzyme defects, mild to moderately elevated concentrations of plasma galactitol or sorbitol were found in about 45%. In 8% of this group the cataract and the elevated plasma galactitol concentration could possibly have been related to partial maternal enzyme deficiency. In all the other cases the elevated plasma polyol concentration remains unexplained but could indicate a further cause of cataract formation due to a hitherto unknown galactose or glucose metabolic aberration.

Carbohydrate Epimerases↗
PubMed1989

Serum unconjugated bile acids in patients with small bowel bacterial overgrowth.

Concentrations of total and unconjugated bile acids in serum were measured fasting and 2 h postprandially in 9 patients with a positive [14C]glycocholate breath test consistent with small bowel bacterial overgrowth and in 13 controls. Gas-liquid chromatography-mass spectrometry (GLC-MS) and enzymatic-fluorometric assays were both used. In contrast to previous work, total serum bile acids were only occasionally elevated in patients with bacterial overgrowth. Total 2 h postprandial unconjugated bile acids, however, were elevated in 7/9 patients when measured by GLC-MS and in 6/9 when measured by the enzymatic-fluorometric method. The best separation between patients and controls was achieved by GLC-MS determinations of 2 h postprandial unconjugated cholic acid or primary bile acids, which were abnormal in 8/9 patients. This study indicates that measurement of serum bile acids may be a useful approach to the diagnosis of bacterial overgrowth, but would require accessible methods for separating and measuring cholic acid or unconjugated primary bile acids in post-prandial sera.

Aged↗
PubMed1989

Bile acid metabolism in human hyperthyroidism.

Decreased levels of serum cholesterol are a well-recognized finding in hyperthyroidism. Since the conversion to bile acids is an important pathway for the elimination of cholesterol, we studied primary bile acid kinetics in seven hyperthyroid patients before and after medical treatment. Pool sizes, fractional turnover and synthesis rates of cholic acid and chenodeoxycholic acid were determined after oral administration of 50 mg [13C]cholic acid and 50 mg [13C]chenodeoxycholic acid. 13C/12C isotope ratios in serum were measured by capillary gas chromatography/electron impact mass spectrometry. Compared with the euthyroid state, serum cholesterol levels were distinctly lower in hyperthyroidism (150 +/- 33 vs. 261 +/- 51 mg per dl, p less than 0.01). Thyroid hormone excess caused a 34% reduction in cholic acid synthesis (5.8 +/- 2.8 vs. 7.9 +/- 4.2 mu moles per kg per day, p less than 0.02), which was associated with a 47% decrease in cholic acid pool size (11.7 +/- 3.4 vs. 22.0 +/- 5.2 mu moles per kg, p less than 0.01). Chenodeoxycholic acid kinetics exhibited no apparent changes. Thus, total primary bile acid synthesis was diminished by 20% in hyperthyroidism. After normalization of thyroid function, the ratio of cholic acid/chenodeoxycholic acid pool size increased in all patients. This was paralleled by a rise in the ratio of concentrations of cholic acid/chenodeoxycholic acid in serum. The depression of cholic acid synthesis in the presence of unaltered subjects is compatible with an inhibition of hepatic 12 alpha-hydroxylation by thyroid hormone. Furthermore, evidence is provided that, in man, the low serum cholesterol levels found during hyperthyroidism are not caused by an increased conversion of cholesterol to bile acid.

Aged↗
PubMed1989

Small intestinal transit, bacterial growth, and bowel habits in diabetes mellitus.

To investigate diabetic alterations of small intestinal transit and bacterial growth, we performed hydrogen breath tests (10 g lactulose via duodenal tube at the ligament of Treitz), bacterial cultures, and determinations of unconjugated serum bile acids in 19 patients with long-standing diabetes and 7 healthy controls. Asymptomatic diabetics had a late rise in breath hydrogen, indicating prolonged jejunal-cecal transit (86 +/- 10 min, p less than 0.05) as an early pathogenic event. Rise in breath hydrogen in symptomatic diabetics (constipation: 50 +/- 6 min; diarrhea: 41 +/- 11 min) was not significantly different from controls (57 +/- 8 min). Bacterial studies and increased unconjugated serum bile acids suggest bacterial overgrowth in some symptomatic diabetics. Bacterial overgrowth was associated more frequently (p less than 0.05) with a rise in breath hydrogen before 45 min or after 75 min. Changes in the hydrogen breath test, bacterial growth, or unconjugated serum bile acids did not correlate with gastrointestinal symptoms of diabetes.

Adult↗
PubMed1989

Effects of cholecystectomy on the kinetics of primary and secondary bile acids.

Removal of the gallbladder is thought to increase formation and pool size of secondary bile acids, mainly deoxycholic acid (DCA), by increased exposure of primary bile acids (cholic acid [CA], chenodeoxycholic acid [CDCA]) to bacterial dehydroxylation in the intestine. We have tested this hypothesis by simultaneous determination of pool size and turnover of DCA, CA, and CDCA in nine women before and at various intervals after removal of a functioning gallbladder. An isotope dilution technique using marker bile acids labeled with stable isotopes (2H4-DCA, 13C-CA, 13C-CDCA) was used. After cholecystectomy, concentration and output of bile acids relative to bilirubin increased (P less than 0.02) in fasting duodenal bile and cholesterol saturation decreased by 27% (P less than 0.05) consistent with enhanced enterohepatic cycling of bile acids. Three months after removal of the gallbladder bile acid kinetics were in a new steady state: pool size and turnover of CDCA were unchanged. Synthesis of CA, the precursor of DCA, was diminished by 37% (P = 0.05), probably resulting from feedback inhibition by continuous transhepatic flux of bile acids. The fraction of CA transferred after 7 alpha-dehydroxylation to the DCA pool increased from 46 +/- 16 to 66 +/- 32% (P less than 0.05). However, this enhanced transfer did not lead to increased input or size of the DCA pool, because synthesis of the precursor CA had decreased.

Bile Acids and Salts↗
PubMed1989

Determination of plasma bile acids by capillary gas-liquid chromatography-electron capture negative chemical ionization mass fragmentography.

Combined capillary gas-liquid chromatography-electron capture negative chemical ionization mass spectrometry of pentafluorobenzyl ester-TMSi ether derivatives of bile acids and isotope dilution using deuterated internal standards are introduced as a sensitive and selective analysis technique for plasma bile acids. As a result of the high ionization efficiency of pentafluorobenzyl derivatives under electron capturing conditions and minimal fragmentation, the detection limit of this technique is low: 1 pg for each bile acid. The high sensitivity enabled the detection and quantitation of atypical bile acids in 200-microliters aliquots of plasma from fasting healthy adults as exemplified by trihydroxycoprostanic acid (0.002 +/- 0.001 mumol/l) and dihydroxycoprostanic acid (0.013 +/- 0.002 mumol/l).

Adult↗
PubMed1987

Diagnostic sensitivity of fasting and postprandial serum bile acids determined by different methods.

The diagnostic sensitivities of serum bile acids determined by three different methods in the fasting and in the postprandial state were compared in 43 patients with cirrhosis of the liver. When a method with high analytical sensitivity (capillary gas-liquid chromatography, GLC, or radioimmunoassay, RIA) was used, the serum concentrations of bile acids exhibited similar diagnostic sensitivities in the fasting state (GLC, 98%; RIA, 93%) and in the postprandial state (GLC, 95%; RIA, 93%). By contrast, when an enzymatic method with limited analytical sensitivity was employed, the diagnostic sensitivity of fasting serum bile acids was lower (79%) than that of postprandial serum bile acids (93%). The measurement of individual serum bile acids by GLC did not add any further diagnostic information. The results of this study demonstrate that the diagnostic sensitivity of serum bile acids strongly depends on the analytical method used.

Adult↗
PubMed1987

Quantitation of serum bile acids by isotope dilution with 13C-labelled homologs.

Quantitation of individual bile acids in serum can be carried out with radioimmunoassays or with gas chromatography. The most specific measurements are obtained with combined gas chromatography/mass spectrometry employing stable isotope labelled bile acids as internal standards. So far only the use of deuterated internal standards has been described for this purpose. 24-13C-labelled bile acids have not been used since correction for the natural abundance of the 13C contribution has to be made. Furthermore, the maximal degree of labelling of 13C-labelled bile acids is about 90%. This requires additional correction for the percentage of unlabelled molecules. Using 13C-labelled bile acids as internal standards and adequate corrections for isotope interferences we have measured individual serum bile acids in healthy volunteers by inverse isotope dilution with coefficient of variation (CV) values of 5.4-6.2% determined for the total procedure of sample preparation and analytical technique. In fasting serum of 15 healthy volunteers chenodeoxycholic acid averaged 0.98 +/- SD 0.77 mumol/l, cholic acid 0.49 +/- 0.39 mumol/l and deoxycholic acid 1.07 +/- 0.68 mumol/l. Two hours postprandially these values increased to 2.42 +/- 1.46 mumol/l for chenodeoxycholic acid, 0.81 +/- 0.45 mumol/l for cholic acid and 1.66 +/- 1.02 mumol/l for deoxycholic acid. These data agree well with those described in the literature obtained with deuterated internal standards. It may be concluded that 24-13C-labelled bile acids are suitable as internal standards for quantitation of serum bile acids, if corrections for isotope interferences are made.

Adult↗
PubMed1987

Simultaneous determination of pool sizes and fractional turnover rates, of deoxycholic acid, cholic acid and chenodeoxycholic acid in man by isotope dilution with 2H and 13C labels and serum sampling.

This paper describes a method for simultaneous determination of the kinetics of the three major bile acids in man using (2,2,4,4-2H4) deoxycholic acid, (24-13C) cholic acid and (24-13C) chenodeoxycholic acid. The gas chromatographic/mass spectrometric-selected ion monitoring technique used provided complete separation of deoxycholic acid, cholic acid and chenodeoxycholic acid, which permitted simultaneous measurement of isotope ratios for all three bile acids. Since measurement of all three pool sizes and fractional turnover rates in a single experiment requires different isotopic labels for deoxycholic acid and cholic acid, we investigated the in vivo stability and applicability of (2,2,4,4-2H4) deoxycholic acid as a stable isotope marker for isotope dilution studies in man. No consistent differences were observed between deoxycholic acid pool sizes and fractional turnover rates determined in serum samples after administration of (2,2,4,4-2H4) deoxycholic acid and (24-13C) deoxycholic acid. Simultaneous administration of (2,2,4,4-2H4) deoxycholic acid, (24-13C) cholic acid and (24-13C) chenodeoxycholic acid and isotope ratio measurements in serum permitted determination of pool sizes and fractional turnover rates of the three major bile acid and the 7 alpha-dehydroxylation fraction. Pool sizes, fractional turnover rates and synthesis rates (input rates) agreed well with data obtained previously with (24-13C) labels in independent studies.

Carbon Isotopes↗
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↗