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F Stellaard

Publications and source records attributed to F Stellaard.

At least 55 records · Page 3Linked to original sources

The 13C-mixed triglyceride breath test in healthy adults: determinants of the 13CO2 response.

Defects in lipolysis due to pancreatic insufficiency can be diagnosed by the mixed triglyceride (MTG) 13CO2 breath test. However, the effects of various test conditions on the 13CO2 response have only been partially elucidated. In healthy adults, we performed the 13CO2 mixed triglyceride breath test and we compared (a) the inter- and intra-individual variation in the 13CO2 response; (b) the effect of two different test meals; (c) the effect of an additional meal during the test; and (d) the effect of physical exercise during the test. Upon repeating the test in the same individual (test meal cream), repeatability coefficients were large, with respect to either time to maximum 13C excretion rate (3.8 h). maximum 13C excretion rate (4.9% 13C dose h-1) or cumulative recovery of 13C over the 9-h study period (22.7% 13C dose). The cumulative 13C expiration over 9 h obtained with the test meal composed of cream was quantitatively similar to that obtained with bread and butter: 42.2 +/- 8.4% and 47.7 +/- 6.3% respectively. Fasting for 9 h during the test resulted in similar 13C expiration rates and cumulative 13C expiration (43.4% +/- 7.2%) when compared with consumption of an additional meal 3 h after the start of the test (38.3 +/- 5.3%). The 13CO2 response increased in five out of seven subjects, but decreased in the other two, when moderate exercise was performed (bicycle ergometer, 50 W for 5 h). We conclude that the repeatability of the MTG test in healthy adults is low. The present results indicate that a solid and a liquid test meal, containing a similar amount of fats, give similar cumulative 13CO2 responses, and that stringent prolonged fasting during the test is unnecessary. Standardization of physical activity seems preferable, since the unequivocal effects of moderate exercise on the 13CO2 response were observed in the individuals studied.

Adult↗

Evaluation of 13CO2 breath tests for the detection of fructose malabsorption.

Breath hydrogen (H2) studies have made clear that small intestinal absorption of fructose is limited, especially in toddlers. Malabsorption of fructose may be a cause of recurrent abdominal pain and chronic nonspecific diarrhea (toddler's diarrhea). Fructose absorption is facilitated by equimolar doses of glucose and, as we have found, amino acids (especially L-alanine); the mechanism underlying this effect remains unclear. To study fructose absorption in a more direct way, we combined breath H2 studies with breath 13CO2 studies. Gastric emptying was studied by using L-glycine-1-13C in 4 children from 12.1 to 16.0 years of age. After 25 gm of fructose and 27.5 gm of glucose, when given together, gastric emptying was significantly (p<0.05) slower than with either sugar alone. In a second series of experiments, 5 children from 12.0 to 15.9 years of age were tested with 25 gm of fructose, alone and with equimolar doses of glucose and L-alanine, and 4 younger children from 3.1 to 6.1 years of age were tested with 2 gm/kg (max 37.5 gm) fructose, alone or with an equimolar dose of L-alanine. All fructose solutions were enriched with 15 mg of D-fructose-13C-6. In all 9 children, fructose was malabsorbed as judged by breath H2 increases > or = 20 ppm, and the addition of glucose or L-alanine resulted in significantly lower breath H2 increases (p < or = 0.005 for glucose, p < or = 0.001 for alanine). In contrast, the addition of alanine or glucose did not change the pattern of breath 13CO2 excretion in the 5 older children, whereas in the 4 younger children (with relatively higher doses), L-alanine addition resulted in significantly lower increases in breath 13CO2. In the latter group, for each time point, breath H2 and 13CO2 concentrations after fructose were compared with those after fructose plus L-alanine; in 20 out of 24 points, both H2 and 13CO2 were higher after fructose. These results suggest that 13CO2 not only originated from the oxidation of absorbed substrate but also, at least in part, from colonic bacterial metabolism. For the detection of [correction of or] fructose malabsorption--as opposed to, for instance, lactose--the 13CO2 breath test seems to be of limited value.

Adolescent↗

Characterization of the cholesterol crystallization-promoting low-density particle isolated from human bile.

BACKGROUND & AIMS: Biliary concanavalin A-binding glycoprotein (CABG) contains cholesterol crystallization-promoting activity that is not accounted for by the pronucleators that have been characterized in this fraction. The aim of this study was to isolate and characterize the missing activity. METHODS: Biliary glycoprotein was isolated using concanavalin A-Sepharose. Promoting activity in CABG was purified using density gradient ultracentrifugation. RESULTS: Activity in CABG separated into two fractions at low (1.08) and high (1.29) density, which showed different crystallization kinetics in a model bile. The high-density fraction had a late onset time (49.2 +/- 17.8 hours) but a high crystal growth rate (13.4 +/- 5.2 micrograms. mL-1.h-1). The low-density fraction had a rapid onset time (33.9 +/- 20.9 hours) but a slower growth rate (6.5 +/- 3.8 micrograms.mL-1 .h-1). The high-density fraction was not further characterized in this study. The low-density fraction contained solid particles consisting of lipid and very little protein, and the activity was fully pronase resistant. Delipidation of the low-density fraction removed all activity. CONCLUSIONS: A potent pronase-resistant nucleation-promoting activity was activated from human bile and characterized. The low-density fraction may be responsible for the rapid nucleation in bile from typical patients with fast-nucleating gallstones.

Adult↗

Insulin-like growth factor-I fails to reverse corticosteroid-induced protein catabolism in growing piglets.

Corticosteroids such as dexamethasone (DEX) increase leucine turnover and oxidation in humans and animals, indicating whole body protein catabolism. Recently, interest has been growing in the use of recombinant polypeptides such as GH and IGF-I in reversing various states of catabolism. The aim of our study was to investigate whether IGF-I reverses corticosteroid-induced protein catabolism in rapidly growing piglets. Also, we wanted to determine whether IGF-I attenuates corticosteroid-induced hyperglycemia. To study these questions, we performed leucine kinetic studies and measured blood glucose in eight piglets under postabsorptive conditions. We did three studies in each piglet: baseline, DEX treatment (5 mg/kg/d for 4 d), and DEX plus IGF-I treatment (25 micro g/kg/h for 6 h). DEX increased leucine turnover by 18 +/- 14% (mean +/- SD, p < 0.05), and oxidation by 132 +/- 64% (p < 0.01) over baseline values. Adding IGF-I to DEX treatment failed to reverse these changes in leucine kinetics. Turnover again increased by 18 +/- 8% (p < 0.01), and oxidation by 107 +/- 68% (p < 0.05) over baseline values. Nonoxidative leucine disposal, an indicator for protein synthesis, did not significantly differ after treatment with DEX or with DEX plus IGF-I. Blood glucose values increased over baseline values after DEX treatment, and approached baseline values after DEX plus IGF-I. We conclude that IGF-I attenuates corticosteroid-induced hyperglycemia, but does not reverse corticosteroid-induced protein catabolism in growing piglets.

Animals↗

Diagnostic tests for Helicobacter pylori: a prospective evaluation of their accuracy, without selecting a single test as the gold standard.

OBJECTIVE: To assess the accuracy of six commonly used diagnostic tests for Helicobacter pylori in a prospective study without using any specific test as the gold standard (the patient was regarded as H. pylori-infected if two or more tests, whatever their nature, were positive). METHODS: In 105 outpatients undergoing upper GI endoscopy, 62 without significant abnormalities, 28 with gastroesophageal reflux disease, 19 with peptic ulcer, one with erosive gastritis, and one with atrophic gastritis (some patients had more than one diagnosis), antral biopsy specimens were taken for culture, polymerase chain reaction, histological examination (hematoxylineosin and Giemsa stains), and rapid urease test. Corpus biopsy specimens were taken for histological examination. Serology (ELISA) and a 13C-urea breath test were also performed. Consistency of diagnosis between two pathologists was assessed by kappa statistics. RESULTS: Sensitivity and specificity, respectively, were as follows: culture, 98.4 and 100%; polymerase chain reaction, 96.7 and 100%; histological examination (antrum), 96 and 98.8%; histological examination (antrum + corpus), 98.4 and 98.8%; rapid urease test, 90.2 and 100%; 13C-urea breath test, 100 and 100%; and serological examination, 98.4 and 88.4% (95% in those who had not been previously treated for H. pylori). All H. pylori-positive cases were detected by culture and rapid urease test. In 86.4% of these cases all antral biopsy-based tests were positive. Agreement between pathologists was good, with a kappa coefficient around 0.90 for antral biopsy specimens. CONCLUSIONS: All antral biopsy-based tests, as well as the 13C-urea breath test, are accurate for the diagnosis of H. pylori infection. Sampling error is a problem of minor importance. The lower specificity of serological tests may be largely explained by previous treatment of H. pylori.

Biopsy↗

Evaluation of clinical and home performance of the 13C-urea breath test for the detection of Helicobacter pylori.

OBJECTIVE: This study analyses the 13C-urea breath test with the aim of determining the optimal time interval between dosing and breath sampling and examines the feasibility of having patients perform the test without supervision at home. DESIGN: Prospective study comparing the 13C-urea breath test with four antral biopsy-based tests in a random population undergoing upper gastrointestinal endoscopy. SETTING: One university hospital and one general hospital. PATIENTS: One hundred and four patients were included; 61 were Helicobacter pylori-positive and 43 H. pylori-negative according to biopsy-based tests. INTERVENTIONS: The 13C-urea breath test was performed at home by collecting a baseline and two post-dosing samples; the next day it was performed clinically by collecting a baseline and six post-dosing samples. A 100 mg dose of 13C-urea and a test meal were used. OUTCOME MEASURES: The breath samples collected were analysed. Excess delta 13CO2/12CO2 values above five per million were considered positive. RESULTS: The specificity of the clinical test was 100% whereas that of the home-based test was 95.1%. The sensitivity of the clinical test depended on the time interval between dosing and collection of the evaluated sample. Sensitivity was 100% if the sample was taken 50 min or more after dosing. The home-based test had a sensitivity of 94.8%. CONCLUSION: To obtain maximum sensitivity (100%) using the single-sample technique the sample has to be collected at least 50 min after dosing. It is feasible to have the test performed at home. Patient selection and thorough instruction are necessary.

Biopsy↗

[Inborn errors of bile acid metabolism].

A review on inherited diseases caused by defects in the synthesis of bile acids is presented. In the first part the biochemical synthesis of bile acids from cholesterol, taking place in the liver, is described. Three consecutive events can be discerned: 1. modifications in the skeleton of cholesterol, 2. oxidation of the last carbon atom of the cholesterol side chain, 3. further oxidation of the side chain leading to shortening with three carbon atoms; this last step takes place in liver peroxisomes. In the second part a description of inborn errors (enzyme deficiencies) is given, which can occur in each of the above mentioned three steps, leading to serious aberrations. As a result abnormal metabolites, i.e. bile acids or sterols, are present in serum or urine, which can be detected using advanced analytical techniques like gas chromatography or mass spectrometry, leading to diagnosis. In contrast to defects in the first or third step in bile acid synthesis, giving rise to disorders already shortly after birth, symptoms of the disease cerebrotendinous xanthomatosis, caused by a defect in the second step, are only noticeable several years after birth. A number of these diseases can be treated successfully, but for peroxisomal defects no useful therapy exists.

3-Hydroxysteroid Dehydrogenases↗

Analysis of pipecolic acid in biological fluids using capillary gas chromatography with electron-capture detection and [2H11]pipecolic acid as internal standard.

A sensitive and accurate stable isotope dilution assay was developed for the measurement of pipecolic acid in body fluids using capillary gas chromatography with electron-capture detection. The method utilizes [2H11]pipecolic acid as the internal standard. Sample preparation consisted of derivatization in aqueous solution (pH 11.5) of the amine moiety with methyl chloroformate to the N-methylcarbamate, followed by acidic ethyl acetate extraction at pH less than or equal to 2 and further derivatization of the carboxyl moiety with pentafluorobenzyl bromide, the excess of which was removed by solid-phase extraction. Control values have been determined in the plasma of at-term infants, age greater than 1 week (n = 21, mean = 1.36 microM, range = 0.47-3.27 microM). The utility of the method was demonstrated by quantitating pipecolic acid in biological fluids derived from patients with peroxisomal disorders. The method was validated against an established electron-capture negative ion mass fragmentographic technique.

Body Fluids↗

In vivo study of phytanic acid alpha-oxidation in classic Refsum's disease and chondrodysplasia punctata.

A series of in vivo experiments is described in which [1-13C]phytanic acid was given as an oral substrate to a healthy subject and two patients showing an impairment in phytanic acid degradation, one with Refsum's disease and one with chondrodysplasia punctata. After intake of the substrate by the control in a dose of 20 mg/kg body weight, the production of 13CO2 was measured in exhaled breath air and the concomitant formation of labeled 2-hydroxyphytanic acid and of pristanic acid was demonstrated by plasma analysis. After application of a substrate dose of 1 mg/kg body weight to the control, no substantial amounts of 13CO2 were measured, whereas time-dependent analysis of labeled 2-hydroxyphytanic acid in plasma yielded a concentration curve superimposed upon the baseline value (0.2 mumol/L) of the unlabeled substance. Phytanic acid accumulated in plasma from the Refsum's disease patient [649 mumol/L, controls > 1 y (n = 100): < 10 mumol/L], whereas the pristanic acid concentration was within the control range [1.4 mumol/L, controls > 1 y (n = 100): < 3 mumol/L]. Low amounts of 2-hydroxyphytanic acid were found normally present [0.04 mumol/L, controls > 1 y (n = 11): < 0.2 mumol/L], and formation of labeled 2-hydroxyphytanic acid could not be demonstrated after ingestion of [1-13C]phytanic acid in a dose of 1 mg/kg body weight. In addition to phytanic acid accumulation (232 mumol/L), the chondrodysplasia punctata patient showed an elevated 2-hydroxyphytanic acid plasma concentration (0.4 mumol/L), whereas the plasma pristanic acid level was in the control range (0.7 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Pristanic acid and phytanic acid in plasma from patients with peroxisomal disorders: stable isotope dilution analysis with electron capture negative ion mass fragmentography.

A sensitive and selective stable isotope dilution method was developed for the accurate quantitation of pristanic acid and phytanic acid using electron capture negative ion mass fragmentography on pentafluorobenzyl derivatives. This technique allows detection of 1 pg of each compound and was applied to plasma from healthy controls and patients suffering from various peroxisomal disorders. The age-dependency of phytanic and pristanic acid levels in plasma from healthy controls was demonstrated. The involvement of peroxisomes in the beta-oxidation of pristanic acid was concluded from its accumulation in plasma from patients with peroxisomal deficiencies. Pristanic acid/phytanic acid ratios were markedly increased in bifunctional protein and/or 3-oxoacyl-CoA thiolase deficiency, indicating their role in the (differential) diagnosis of disorders of peroxisomal beta-oxidation.

Aging↗

[Changes in fecal composition, intestinal transit, bile acid metabolism and intestinal fermentation in long-term nutrition with high molecular weight formula diet].

Treatment with formula diets becomes more and more popular in many patients. The influence of those diets on gut functions is as yet poorly known. We studied in ten healthy volunteers the effects of a high molecular liquid diet. Despite of a sufficient energy supply the volunteers lost significantly weight which may be related to an acceleration of small bowel transit (60 +/- 9 min vs. 31 +/- 5 min; control vs. diet period). Whole gut transit did not change significantly (52 +/- 3 h vs. 56 +/- 3 h). The fecal excretion of bile acids decreased significantly (293 +/- 35 mg/24 h vs. 151 +/- 10 mg/24 h) which was particularly due to a decrease of primary bile acids. The serum bile acid concentrations behaved in a similar way (total bile acids: 3.19 +/- 0.66 mumol/l vs. 1.71 +/- 0.21 mumol/l). Neither the determination of unconjugated serum bile acids nor hydrogen breath testing did indicate increase of bacterial growth. In conclusion, chronic nutrition with formula diets causes significant changes of gut functions.

Adult↗

Stable isotope dilution analysis of N-acetylaspartic acid in CSF, blood, urine and amniotic fluid: accurate postnatal diagnosis and the potential for prenatal diagnosis of Canavan disease.

A sensitive and selective analytical technique is described for the determination of N-acetylaspartic acid in body fluids using stable isotope dilution in combination with positive chemical ionization mass spectrometry with selected ion monitoring. Control mean and ranges have been established: in urine 19.5 and 6.6-35.4 mumol/mmol creat.; in plasma 0.44 and 0.17-0.81 mumol/L; in cerebrospinal fluid 1.51 and 0.25-2.83 mumol/L; and in amniotic fluid 1.27 and 0.30-2.55 mumol/L. In a patient with Canavan disease, N-acetylaspartic acid concentration was elevated 80-fold in urine and 20-fold in plasma compared to the control means. A subsequent pregnancy of the mother was monitored and the N-acetylaspartic acid concentration in the amniotic fluid was within the control range and a healthy child was born.

Amidohydrolases↗

Effect of diets low and high in refined sugars on gut transit, bile acid metabolism, and bacterial fermentation.

Increasing consumption of refined sugar has been implicated in many gastrointestinal disorders on epidemiological grounds. Nine volunteers agreed to participate in a study comparing the effects of a diet containing 165 g refined sugar/day with a diet of only 60 g/day on gut transit, bile acid metabolism, and fermentative activity of the intestinal flora. The wet and dry weight, pH, and water content of the stools were similar on the two diets. On the high sugar diet mouth-to-anus transit time was significantly prolonged, despite a shortened mouth-to-caecum transit time. The faecal concentration of total bile acids and the faecal concentration of secondary bile acids increased significantly. Diet affected neither the serum bile acid pattern nor the concentration. Breath hydrogen tests showed significantly enhanced H2 production on the high sugar diet. We conclude that the quantity of refined sugar in the diet can significantly influence gut function and the composition of bowel contents.

Adult↗