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Biomedical subjects

J J Bernier

Publications and source records attributed to J J Bernier.

At least 37 records · Page 2Linked to original sources
PubMed1986

Gastric clearance of alpha-1-antitrypsin under cimetidine perfusion. New test to detect protein-losing gastropathy?

Gastric losses of plasma are usually measured with radiolabeled macromolecules. This method is expensive and cumbersome. Direct measurement of exudated plasma proteins are ineffective since proteins are denaturated by acidic gastric juice and pepsin. It was recently shown that albumin measurement after immediate neutralization allowed detection of gastric protein losses, but this method is quite complex and time consuming. We studied alpha 1-antitrypsin and 51Cr-labeled protein clearance in gastric juice during normal saline and cimetidine (1.5 mg/kg/hr) infusion in six healthy volunteers and six patients with exudative gastropathy. alpha 1-Antitrypsin was measurable in all samples during cimetidine infusion: alpha 1-AT and 51Cr losses were significantly correlated (P less than 0.001). The upper limit of gastric alpha 1-AT clearance in controls was 0.86 ml/hr (mean + 2 SD). Using this value, there was no overlapping between patients and controls. The upper limit of 51Cr test was 1.87 ml/hr (mean + 2 SD) in controls but gastric clearance of 51Cr was below this value in one patient. This suggests that the measurement of alpha 1-AT gastric clearance during cimetidine perfusion is a good test to detect an exudative gastropathy. This test is inexpensive and lasts only 3 hr.

Adult↗
PubMed1986

[Effect of the increase of the caloric load of a meal on gastric emptying of its solid and liquid phases].

Caloric regulation of gastric emptying was mainly assessed with artificial liquid meals. We thus studied the effects of glucidic and lipidic caloric loads on gastric emptying of a solid-liquid meal (400 ml; 480 kcal), measured by an isotopic technique. Sixteen healthy subjects were separated in 3 groups; solutions of identical volume (400 ml) were added to the meal: water in group I (N = 6), glucose polymers (Caloreen; 400 kcal) in group II (N = 5), and triglycerides (Intralipide; 400 kcal) in group III (N = 5). Gastric emptying was dramatically slower in groups II and III than in group I, whatever the parameter considered. The magnitude of this caloric brake was identical for the 2 caloric loads tested and concerned both phases of the meal. Therefore, 3 h after the end of the meal, intragastric percentages of ingested liquids were 50 +/- 4 in group II, 52 +/- 5 in group III, vs 14 +/- 1 p. 100 in group I (p less than 0.001); for solids these percentages were 56 +/- 6 and 68 +/- 2 vs 11 +/- 3 p. 100 (p less than 0.001). In all groups, emptying of solids was slower than that of liquids, but the kinetics of this discrimination was modified by the increase of caloric load. The pyloric output of calories, estimated for the 3 h of the study was close to 2 kcal/min for the 3 groups studied. Thus, the 2 fold increase of the caloric concentration in groups II and III as compared to group I, did not modify the delivery rate of energy to small bowel.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Effect of increased amounts of pectin on a solid-liquid meal digestion in healthy man.

The effect of three concentrations of high-methoxy apple pectin (5, 10, and 15 g), on solid-liquid meal digestion was studied in 12 healthy men by the gastrointestinal intubation technique. The gastric emptying of water and carbohydrates is significantly reduced only after 10 and 15 g pectin. The changes in gastric pH are similar for pectin-free and pectin-containing meals. Cumulative lipase and trypsin outputs are not significantly different with and without pectin. When gastric uronic acid concentration is above 6 g/l, the duodenal absorption of carbohydrates is significantly reduced (p less than 0.001). The mean blood glucose levels with 10 and 15 g pectin are significantly higher than the control values at 180 min (p less than 0.05). Pectin does not modify serum concentrations of secretin, cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), gastric inhibitory polypeptide (GIP), and somatostatin but serum motilin and gastrin levels are below the control values after high fiber meal.

Adult↗
PubMed1985

Investigation of drug absorption from the gastrointestinal tract of man. I. Metoprolol in the stomach, duodenum and jejunum.

Gastrointestinal (GI) absorption of the beta-adrenoceptor blocker metoprolol was investigated in five healthy subjects by means of an intubation method, employing a triple-lumen tube introduced into the intestine, and a twin-lumen tube in the stomach. Metoprolol was introduced into the stomach with a homogenized meal containing a nonabsorbable marker, [14C]-PEG 4000, and another marker, PEG 4000, was perfused continuously into the duodenum just below the pylorus. Samples of GI contents were collected at regular intervals over 4 h in the stomach and at two different levels in the upper small intestine. Metoprolol was not absorbed from the stomach. Approximately 60% of the amount of drug emptied from the stomach was absorbed from the duodenum; about 50% of that leaving the duodenum was absorbed from the first part of the jejunum. The delivery process was the rate-limiting factor of metoprolol absorption in these segments of the gut. Plasma concentrations reflected drug loss from the lumen and were higher in subjects exhibiting faster gastric emptying and higher absorption rates in the duodenum and jejunum. The intubation technique appeared to be a suitable method for investigating drug absorption from the GI tract in man.

Adult↗
PubMed1985

Investigation of drug absorption from the gastrointestinal tract of man. II. Metoprolol in the jejunum and ileum.

Absorption of metoprolol in jejunum and ileum was investigated in eight healthy subjects using an intestinal perfusion technique below an occlusive balloon. An isotonic saline solution, with or without metoprolol, was perfused at a flow rate of 10 ml/min, either at the angle of Treitz or in the middle part of the ileum. The absorption in a 30 cm intestinal segment was evaluated at metoprolol concentrations of 20, 40 and 60 mg/l. Metoprolol did not affect gut motility. Metoprolol was similarly absorbed in the jejunum and ileum. The absorption rates appeared to be linearly related to the perfusion rates and to the mean concentration in the segment, indicating a first-order kinetic process. The absorption rate of metoprolol perfused in the jejunum in a saline solution appeared to be lower than that observed after gastric administration of the drug incorporated in a meal. The findings in this and other studies in this series indicate that metoprolol is similarly absorbed throughout the small intestine.

Adult↗
PubMed1985

Investigation of drug absorption from the gastrointestinal tract of man. III. Metoprolol in the colon.

The colonic absorption of metoprolol was indirectly evaluated by measuring drug appearance in plasma following intravenous, jejunal or colonic infusion in six healthy volunteers. Plasma concentrations of alpha-hydroxymetoprolol and urinary excretion of the main metabolites were also measured. Plasma profiles of metoprolol after colonic and jejunal perfusion were similar, and the relative bioavailabilities of the drug from these two regions of the gut were not significantly different. The concentrations of alpha-hydroxymetoprolol, the major metabolite in plasma, were similar after jejunal and colonic perfusion, but higher than those observed after intravenous administration. The percentage of the dose recovered in urine over 24 h as two metabolites was not significantly influenced by the route of administration.

Adult↗
PubMed1985

Investigation of drug absorption from the gastrointestinal tract of man. IV. Influence of food and digestive secretions on metoprolol jejunal absorption.

The influence of nutrients and digestive secretions on the intestinal absorption and bioavailability of the beta-adrenoceptor antagonist, metoprolol, was investigated in an isolated segment of jejunum using an intestinal perfusion technique. Two solutions containing metoprolol, one with, and one without nutrients, were perfused into the jejunum with an occluding balloon inflated or deflated. Jejunal fluid, blood and urine samples were then collected for drug or metabolite estimation. In the segment studied, metoprolol absorption from the nutrient solution was four times that observed during perfusion of the saline solution. Bile salts did not enhance drug absorption. Both in the presence and absence of nutrients, a linear relationship was observed between the computed cumulative amount of drug absorbed from the gastrointestinal tract and the resulting plasma concentration at each sampling time, indicating that first-pass loss was not saturated. This result was also reflected in the similarity of the AUC:dose ratios, and in the lack of effect of nutrients on the metabolism of the drug.

Adult↗
PubMed1985

Investigation of drug absorption from the gastrointestinal tract of man. V. Effect of the beta-adrenoceptor antagonist, metoprolol, on postprandial gastric function.

The role of the adrenergic system in normal gastric function was assessed in five healthy volunteers by measuring gastric secretion and emptying after a mixed meal containing a non-absorbable marker, [14C]-PEG 4000, with and without 100 mg of metoprolol, a beta 1-adrenoceptor antagonist. Intraduodenal perfusion of PEG 4000, and gastric and jejunal sampling was achieved by means of a gastrointestinal intubation technique. Gastric function was assessed from the degree of dilution of the duodenal marker. Analysis of acid content by titration allowed the gastric acid secretory rate to be determined. Gastric emptying of a meal over 4 h was similar with and without metoprolol, the time to 50% emptying being 100 min. In the presence of metoprolol, gastric acid content was significantly increased during the late postprandial period producing a corresponding increase in acid load delivered to the duodenum. beta 1-adrenoceptor blockade appears to prolong the gastric secretory response to food without altering gastric emptying.

Food↗
PubMed1985

Measurement of gastric emptying in dyspeptic patients: effect of a new gastrokinetic agent (cisapride).

Symptoms suggesting gastroparesis in patients without gastric outlet obstruction are very common but their relation to an objective delay of gastric emptying has been poorly investigated. A dual isotopic technique was used to evaluate patients with non-obstructive dyspepsia (idiopathic and secondary) (part 1) and to assess the effects of a new gastrokinetic agent: cisapride, on gastric emptying in such patients (part 2). Sixty patients with postprandial dyspeptic symptoms (vomiting, nausea, gastric bloating or full feeling) and without lesions at upper endoscopy were studied. They were distributed into three groups: idiopathic dyspepsia (n = 31), postvagotomy dyspepsia (n = 16) and dyspepsia secondary to medical disorders (n = 13). All patients ingested the same ordinary meal; 99mTc sulphur colloid tagged egg white was the solid phase marker and 111In chloride was the liquid phase marker. In part 1, evaluation of gastric emptying in the first 50 patients shows a delay of gastric emptying rate of solids and liquids as compared with controls. Striking differences separate the three groups of patients, however, percentages of delayed gastric emptying rate of solids and or liquids averaged 90% in postvagotomy or secondary dyspepsia groups whereas it was 44% in idiopathic dyspepsia group. Moreover, liquid emptying rate was often the only one impaired in idiopathic dyspepsia, and in 12 of the 27 patients of this group the faster emptying rate of liquids as compared with that of solids (always found in normal subjects), could not be evidenced. In part 2, 10 patients entered a double blind cross over study of cisapride (8 mg intravenously). A significant increase of solid (p<0.01) and liquid (p<0.05) emptying rates was found in patients with initial gastric emptying delay. This study emphasises the importance of an objective evaluation of gastric emptying in the presence of symptoms of gastric stasis and suggests that specific local acting therapy may be useful in patients with identified abnormal gastric emptying.

Adult↗
PubMed1985

Influence of chronic lactulose ingestion on the colonic metabolism of lactulose in man (an in vivo study).

The effects of a chronic load of nonabsorbable sugars on intracolonic bacterial metabolism of carbohydrates and on H2 breath excretion are disputed. However, most of the discussion relies on indirect evidence or on results of in vitro studies. Thus, we attempted to assess directly and in vivo the effects on intracolonic metabolism of lactulose of a chronic oral load of this nonabsorbable disaccharide. 20 g of lactulose was given orally twice daily during 8 d to eight normal volunteers. In all, breath H2 concentration was measured on days 1 and 8 after ingestion of the morning lactulose dose. In four subjects, stools were collected during 2 d at the beginning and at the end of the lactulose maintenance period to measure fecal pH and daily outputs of carbohydrates and beta-galactosidase. The four other subjects were intubated on days 1 and 8 to measure the pH and the concentrations of carbohydrates, lactic acid, and volatile fatty acids (VFA) in the distal ileum and cecal contents. Moreover, 14C-lactulose was added to cold lactulose and 14CO2 breath outputs determined. Pulmonary H2 excretion fell from day 1 to day 8 (P less than 0.05), whereas 14CO2 excretion increased (P less than 0.01). Fecal water pH, lactic acid, and VFA concentrations did not vary between the two stool collection periods. 24-h fecal weight, fecal water, and carbohydrate outputs showed a trend to decrease between days 1 and 2 and days 7-8, whereas beta-galactosidase activity rose markedly (P less than 0.01). No significant variations were observed for all parameters measured in ileal fluid. In the cecum, areas under the concentration curves decreased from day 1 to day 8 for lactulose, galactose, and fructose (P less than 0.01), while an increase was found for lactic acid (P less than 0.001), acetic acid (P less than 0.0001), and total VFA (P less than 0.001). Cecal fluid pH dropped faster (P less than 0.05) and to a lower level (P less than 0.05) on day 8 than on day 1. These data clearly show that a chronic load of a nonabsorbable sugar induces changes in colonic bacterial metabolic pathways resulting in a better efficiency of the flora to digest the carbohydrate.

Adult↗
PubMed1985

[Effect of pentagastrin and cimetidine on gastric protein loss in exudative gastropathies].

The effectiveness of cimetidine in decreasing protein loss in protein-losing gastropathies has recently been questioned. The present investigation was designed to test the effects of pentagastrin and cimetidine on gastric protein loss in 6 patients with this type gastropathy: 4 with Ménétrier's disease and 2 with Stempien's disease. Fecal and gastric loss of 51Cr-labelled proteins were measured and expressed as ml of plasma per unit of time +/- SEM. Gastric protein loss was measured during intravenous infusion of normal saline, pentagastrin alone (6 microgram/kg/h), combined pentagastrin and cimetidine (1.5 mg/kg/h), and cimetidine alone. Each solution was perfused during 105 min to obtain a steady state effect upon gastric protein loss during one hour. Fecal clearance was increased in all patients: 193 +/- 16 ml/day (N less than 40 ml/day). Gastric 51Cr albumin loss was increased by pentagastrin stimulation (15.9 +/- 1.2 ml/h); cimetidine resulted in a reduction of the pentagastrin induced loss (7.0 +/- 3.8 ml/h) while cimetidine alone had no effect (3.8 +/- 0.6 ml/h) on basal loss. Our results suggest that cimetidine therapy may be of benefit in decreasing protein loss in patients with this type of gastropathy.

Blood Proteins↗
PubMed1984

Measurement of intestinal progression of a meal and its residues in normal subjects and patients with functional diarrhoea by a dual isotope technique.

A new double isotopic method was used to measure the gastrointestinal progression of a meal in nine healthy subjects and seven patients with functional diarrhoea. 51 Chromium chloride (colonic marker) was ingested eight hours before the beginning of the scintigraphic study so that it was by then located in the colon at that time. A second marker, 99m Technetium sulphur colloid labelled the meal. Scintigraphic images were taken before and after the meal for two hours, detecting simultaneously the two isotopes. In the 51 Cr window right colon was localised and intracolonic propulsion was studied; and in the 99m Tc window gastric emptying and colon filling of the meal marker was quantified. A propulsive gastrocolic reflex was evidenced in five of the seven patients with functional diarrhoea but in none of the normal subjects. Unabsorbed residues of the meal are propelled rapidly in the ileocaecal region. Small intestinal transit of the meal marker was twice as rapid in patients with functional diarrhoea as in normal subjects.

Adult↗
PubMed1984

Effect of pectin on jejunal glucose absorption and unstirred layer thickness in normal man.

The effect of high methoxy apple pectin, a carbohydrate gelling agent, on the intestinal absorption of glucose, water, and sodium was studied in man. The effect of intraluminal fibre was evaluated in 22 healthy volunteers by the intestinal perfusion technique under an occlusive balloon. The test solutions (NaCl 130 mM, KCl 5 mM, glucose or mannitol 30 mM, PEG 4000 5 g/l) were perfused just beyond the ligament of Treitz at a rate of 10 ml/min. A 25 cm segment was studied. Three concentrations of pectin were tested: 6, 10, and 15 g/l. The effect of this pectin at two concentrations, 6 and 10 g/l, on the jejunal unstirred layer thickness was evaluated in nine other healthy subjects by an electrical technique. In mannitol solution, pectin reversed water and sodium absorption, whatever its concentration was, while in glucose solution it significantly reduced absorption of water and sodium at 10 and 15 g/l only (p less than 0.01). It significantly reduced glucose absorption at all concentrations (p less than 0.01). This reduction was found to be correlated with the solution viscosity (p less than 0.01). Pectin did not alter the glucose dependent sodium transport but increased significantly (p less than 0.001) the unstirred layer thickness. These results suggested that, in healthy man, pectin acutely given may impair intestinal absorption by means of an increased unstirred layer resistance. This effect could contribute to the diminished postprandial glycaemia observed in human subjects fed pectin.

Body Water↗