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Biomedical subjects

Y Ghoos

Publications and source records attributed to Y Ghoos.

At least 19 recordsLinked to original sources

The urea breath test: a non-invasive clinical tool for detecting Helicobacter pylori infection.

The urea breath test exploits the urease enzyme of Helicobacter pylori. The hydrolysis of labelled urea releases labelled carbon dioxide that is excreted in the breath. Distribution of urea throughout the stomach prevents sampling errors and allows for semiquantitative assessment of the extent of Helicobacter pylori infection. The urea breath test is very specific and sensitive and can be proposed as the method of choice for detecting Helicobacter pylori infection in ulcer patients before and after eradicating treatment as well as in epidemiological studies.

Breath Tests

Screening method for the determination of volatiles in biomedical samples by means of an off-line closed-loop trapping system and high-resolution gas chromatography-ion trap detection.

A method is described for the analysis of volatile organic compounds in biological matrices (faeces and urine). The technique is based on off-line preconcentration by means of a closed-loop trapping system followed by high-resolution gas chromatography-ion trap detection (HRGC-ITD) for separation and identification of the compounds. The technique has been validated for pattern recognition in faecal and urine samples from healthy volunteers. It is considered a very promising tool in metabolic research.

Carbohydrates

Increased permeability of macroscopically normal small bowel in Crohn's disease.

To investigate permeability alterations of the macroscopically normal jejunum in Crohn's disease, the permeation of two probes was measured during perfusion of an isolated jejunal segment. The data were compared with the results obtained by the standard per oral test in the same patients. Test probes were PEG-400 and [51Cr]EDTA. Ten normal individuals, 12 patients with Crohn's ileitis or ileocolitis, and seven patients with isolated Crohn's colitis all with normal jejunum on x-ray series were studied. Upon perfusion of the proximal small bowel, the 3-hr [51Cr]EDTA excretion was significantly increased in ileitis patients (P = 0.023) as compared to normals. The excretion exceeded the highest value of normals in eight of 12 ileitis patients. The excretion in Crohn's colitis patients was not significantly increased (P = 0.24) and abnormal excretion was found only in one of the Crohn's colitis patients. PEG-400 permeation during perfusion did not differentiate between the groups, but five of the seven patients with isolated Crohn's colitis had PEG-400 excretion exceeding the highest value in normals. Overall, 13 of the 19 patients had increased permeation of one of the two probes through jejunal mucosa during perfusion. These data suggest that the permeability is increased in the majority of patients even in segments that seem normal on x-ray.

Adult

Test conditions greatly influence permeation of water soluble molecules through the intestinal mucosa: need for standardisation.

Permeability tests are widely used to investigate the pathogenesis of various gastrointestinal diseases including coeliac disease, infectious diarrhoea, and inflammatory bowel disease. In Crohn's disease they are used as activity parameters by some investigators. Lack of standardisation, however, makes it very difficult to compare data reported in different studies. The aim of this study was to gather permeation data in well controlled test conditions to standardise the methods. Nine healthy volunteers each received five consecutive permeability tests by mouth using polyethylene glycol-400 (PEG-400) and 51Cr-EDTA as probe molecules. The probes were dissolved in water, a glucose solution, a starch solution, a hyperosmolar lactulose-mannitol solution, and a liquid meal. A significantly decreased permeation for both probes was found when given with the hyperosmolar solution. The 51Cr-EDTA permeation was also decreased with water. The permeability index, 51Cr-EDTA/PEG-400, corrected for influencing factors, confirmed that the lactulose-mannitol solution and plain water yield lower values of macro-molecule permeation than starch, glucose or liquid meal. Hyperosmolarity was clearly accompanied by a decrease in permeability probably caused by reversed solvent drag. Interindividual variability of probe permeation and permeability index is very low with a standard liquid meal. It is proposed that for permeability studies a standard liquid meal is always used.

Adult

Effects of acarbose on starch hydrolysis. Study in healthy subjects, ileostomy patients, and in vitro.

The effect of acarbose on hydrolysis of a pure starch meal was investigated in normal subjects and ileostomy patients by means of 13CO2 breath tests and blood glucose levels as parameters of absorption, and of H2 breath tests, serum acetate levels, and ileal loss of carbohydrate as parameters of malabsorption. Additional information on the effect of acarbose on alpha-amylase activity was obtained by in vitro experiments. Acarbose (200 and 400 mg) significantly delayed starch absorption. Serum acetate was found to be a less sensitive marker of malabsorption than breath H2 excretion. After intake of 50 g starch plus 400 mg acarbose, 23-71% of the starch load was lost in the ileostomy effluent, for a large part as starch. This suggests that acarbose considerably inhibits alpha-amylase, and not only brush-border enzymes. In vitro experiments confirm that an inhibition of two thirds of alpha-amylase activity can be expected from pharmacologically used doses of acarbose.

Acarbose

Influence of nutritional substrates on the formation of volatiles by the fecal flora.

The influence of metabolic substrates on the formation of volatile compounds by the colonic flora was measured in a fecal incubation system. The presence of carbohydrates (0, 25, and 50 mg/20 mL fecal suspension) led to a dose-related increase in the formation of alcohols and H2 and to a dose-related decrease in the formation of toxic mercaptans. This effect seemed to be independent of pH. The presence of albumin or fat (50 mg/20 mL fecal suspension) as substrates for the colonic flora gave rise to the formation of significantly higher amounts of methanethiol. Small amounts of pentane were found in the headspace after incubation with oil. These data show that the formation of volatile metabolites by the colonic flora is greatly influenced by the available substrates.

1-Propanol

Effects on bowel motility of misoprostol administered before and after meals.

Prostaglandin analogues, used in the treatment of duodenal and benign gastric ulcer and in the prevention of gastric ulceration caused by non-steroidal anti-inflammatory drugs, are frequently associated with gastrointestinal side effects, particularly diarrhoea and abdominal cramps. We investigated the effects of misoprostol, a prostaglandin E1 derivative, on bowel motility and faecal loss of fat, water and bile acids in relation to its postprandial vs. preprandial administration. Twelve healthy subjects participated in a double-blind crossover study comparing three 5-day courses of therapy with a washout period of 1-2 weeks between courses. Following a Latin Square design, the dosing regimens were (a) 400 micrograms misoprostol b.d. after meals and placebo b.d. before meals; (b) 400 micrograms misoprostol b.d. before meals and placebo b.d. after meals; (c) placebo before and after meals. Orocaecal transit time measured by H2 breath tests following lactulose administration, was shortest during pre-prandial dosing but was also significantly decreased during post-prandial dosing. The overall treatment difference was highly significant (P less than 0.001), and the difference between each pair of treatments was also statistically significant. Whole bowel transit time studied by means of 3H-PEG 4000 determination in stools, was shorter for the two misoprostol regimens but statistical significance was borderline. The number of stools passed per day was similar in the three groups. During both misoprostol dosing periods, stools were less formed and their content of water, fat and bile acids was higher. There was also more urgency, flatulence, abdominal pain and nausea. It is concluded that the gastrointestinal side effects caused by misoprostol are mainly based on an increased orocaecal transit time. The effects are more important when the drug is administered before meals than after meals.

Adolescent

13CO2 breath test to measure the hydrolysis of various starch formulations in healthy subjects.

13CO2 starch breath test was used to study the effect of physicochemical characteristics of starch digestion. As starch is hydrolysed to glucose, which is subsequently oxidised to CO2, differences in 13CO2 excretion after ingestion of different starch products must be caused by differences in hydrolysis rate. To study the effect of the degree of chain branching, waxy starch, containing 98% amylopectin, was compared with high amylose starch, containing 30% amylopectin, and normal crystalline starch, containing 74% amylopectin. The effect of the extent of gelatinisation was studied by comparing extruded starch and crystalline starch. Finally, the possible inhibitory effect of adding wheat fibre to extruded starch on the hydrolysis rate was studied. The 13CO2 excretion from two to four hours after intake of crystalline starch was significantly lower than that of extruded starch. Waxy starch was hydrolysed much faster than high amylose starch, but there was no significant difference between waxy starch and normal crystalline starch. Addition of wheat fibre did not influence the hydrolysis rate. The 13CO2 starch breath test is an attractive test for the study of factors affecting carbohydrate assimilation.

Adult

Porous-layer open-tubular gas chromatography in combination with an ion trap detector to assess volatile metabolites in human breath.

A method is described for the quantification of major volatile substances in human breath without preconcentration. Methanol, ethanol, acetaldehyde and acetone are well separated by porous-layer open-tubular column gas chromatography. Low-level detection was possible by means of an ion trap detector. Halothane has been used as internal standard.

Acetaldehyde

Starch digestion in normal subjects and patients with pancreatic disease, using a 13CO2 breath test.

A 13CO2 starch breath test was developed to study starch digestion in 13 healthy volunteers and 16 patients with pancreatic disease. As starch is hydrolyzed to glucose that is subsequently oxidized to CO2, the excretion of 13CO2 after starch intake, compared with the excretion of 13CO2 after glucose intake, should be a measure of starch hydrolysis. In normal subjects both the hourly 13CO2 excretion rate and the cumulative percentage of 13CO2 excretion after starch ingestion were significantly different from those after glucose ingestion. Comparable differences were found with the patient group. In addition, the 13CO2 excretion after starch intake in normal subjects was markedly different from that of patients with pancreatic disease. Even after correction for endocrine pancreatic insufficiency by calculating the ratio of 13CO2 excretion after starch intake over 13CO2 excretion after glucose intake, the difference between the control group and the patient group was statistically significant. This study indicates that starch hydrolysis is the rate-limiting step in starch digestion. It also confirms recent findings suggesting that starch digestion is impaired in some patients with pancreatic disease. The 13CO2 starch breath test may prove to be useful in evaluating the digestibility of various starch preparations in physiologic and pathological conditions.

Adult

Measurement of 13C-glucose oxidation rate using mass spectrometric determination of the CO2: Ar ratio and spirometry.

A new method was developed and validated for measuring the CO2 concentration in the breath by mass spectrometric analysis. Argon, an inert gas that is present in air in a constant concentration of 0.923%, was used as an internal standard. By determining the ratio of CO2 (mass 44) to Ar (mass 40) in a breath sample, it was possible to read the CO2 concentration from a standard curve, relating CO2 concentration to CO2: Ar ratio. By combining mass spectrometric determination of CO2 concentration in breath with spirometric measurement of expired volumes, the CO2 production was determined in 67 subjects at rest. The mean value was 8.86 mmol kg-1 h-1, but there was considerable interindividual variation. This new method was applied to glucose oxidation studies in 10 normal subjects, 10 post-gastrectomy patients and 7 obese type II diabetic subjects. Measurement of the 13CO2 exhalation with quantitative determination of CO2 production allowed more accurate determination of the CO2 excretion rate in relation to blood levels of glucose, insulin and free fatty acids than assuming the constant CO2 production of 300 mmol unit body surface -1 h-1 or 9 mmol kg-1 h-1. It also resulted in a better discrimination between normal subjects and diabetics.

Adult

Measurement of the rate of assimilation of oligo- and polysaccharides by 13CO2 breath tests and isotope ratio mass spectrometry.

13CO2 breath tests were developed to study the digestion and absorption of (13C)lactose, (13C)sucrose, (13C)starch and (13C)glucose using naturally enriched substrates. Measurements of 13CO2 breath excretion were done in steady state conditions in order to study the assimilation rate of these carbohydrates as reflected by their oxidation rate. The reproducibility of the tests in the same individual was excellent. The excretion rate of 13CO2 after administration of (13C)glucose and (13C)sucrose was identical, while the excretion rate of 13CO2 after lactose was somewhat slower, although not significantly. In contrast, the excretion of 13CO2 after 50 g (13C)starch was significantly slower than the 13CO2 excretion after 50 g (13C)glucose or 50 g (13C)disaccharides. As the monosaccharide constituents used in this study have comparable absorption rates, the delayed excretion of 13CO2 after a (13C)starch load must be due to a slower digestion. It is concluded that (i) digestion and not monosaccharide transport is the rate-limiting step in the assimilation of polysaccharides and (ii) that the present breath tests are suitable to study the digestibility of naturally labelled carbohydrates.

Adult

The effect of long-term fibre and starch intake by man on faecal bile acid excretion.

Parameters of bile acid metabolism were studied in two populations with different dietary fibre and starch intake over a period of at least 5 years. Subjects with a high fibre and starch intake have significant increases in faecal wet weight (288.5 g day-1 vs. 136.1), faecal dry weight (39.3 g day-1 vs. 20.2), faecal bile acid excretion (393.0 mg day-1 vs. 115.4) and faecal bile acid:faecal dry weight ratio (13.6 vs. 5.8). There was no difference in bowel transit time measured with 3H-PEG 4000 as marker of the liquid phase. The cumulative 14CO2 excretion during the bile acid breath test was higher in the high-fibre group, compared with the low-fibre group (4.6% dose cumulative at 8 h vs. 2.5%). Serum triglyceride and cholesterol levels were comparable in both groups. It is suggested that increased faecal weight and bile acid secretion is due to the synergic effect of high fibre and starch intake upon colonic bacterial proliferation.

Adult

13CO2 breath test using naturally 13C-enriched lactose for detection of lactase deficiency in patients with gastrointestinal symptoms.

A 13CO2 breath test using naturally enriched 13C-lactose as a substrate was performed in 47 patients with chronic abdominal pain or chronic diarrhea, taken from a population with a low prevalence of primary acquired lactase deficiency. The cumulative 13CO2 excretion 4 hours after 13C-lactose intake was compared with the H2 breath excretion and with jejunal lactase activity. A physiologically significant relation was found between the cumulative 13CO2 excretion (at 4 hours) and lactase activity, 14.5% 13CO2 excretion being the best cutoff point for discrimination between patients with low and normal lactase activity. The 13CO2 breath test was found to be more sensitive (0.84 versus 0.68) and more specific (0.96 versus 0.89) than the H2 breath test in detecting low jejunal lactase activity. Concordant results of both breath tests performed simultaneously give a reliable picture of the lactose absorption status of the patient. Discordance in results of 13CO2 and H2 lactose breath tests, if not explained by history, indicates in which patients a jejunal biopsy should be performed. If lactase activity and morphology of the biopsy are normal, other causes of discordance must be investigated.

Abdomen

Effects of partial ileocolectomy and Crohn's disease on biliary lipid secretion.

The effects of interruption of the enterohepatic circulation of bile acids on biliary lipid secretion have only been studied experimentally, and quantitative data in patients are lacking. Therefore, biliary lipid secretion during steady-state meal perfusion of the duodenum was studied in six patients with partial ileocolectomy, five patients with Crohn's disease, and five normal subjects. Bile acid outputs in the resection patients were significantly lower than in normal controls, (6.87 +/- 2.10 mmol/6 hr and 13.5 +/- 2.16, respectively; P less than 0.001) and were also decreased in two of the five Crohn's disease patients. Bile acid outputs in patients with resection progressively decreased in the course of the perfusion study; phospholipid and cholesterol secretion did not decrease to the same extent, and cholesterol saturation gradually increased. Bile of these patients, therefore, was frequently supersaturated due to uncoupling of bile acid secretion and outputs of the other biliary lipids. Bile acid outputs, although decreased, did not reach very low values, which shows that the enterohepatic circulation was not totally interrupted. Chenodeoxycholic acid was the main bile acid component of bile in patients with ileocolonic resection. Deoxycholic acid was absent from bile of four resected patients and two Crohn's patients. Two patients with active Crohn's disease had low bile acid outputs despite only moderate fecal bile acid losses. Therefore, decreased outputs may be caused by decreased bile acid pool not compensated for by increased bile acid synthesis in severely ill patients.

Adult