[Effect of low-dose polyethylene glycol 4000 on fecal consistency and dilution water in healthy subjects]. / Effet du polyéthylène glycol 4000 à petites doses sur la consistance et l'eau de dilution des selles chez le sujet sain.

OBJECTIVES: The aim of the study was to assess in normal subjects the changes in stool consistency and dilution water during the ingestion of small doses of polyethylene glycol (PEG) 5.9 g/d. Dilution water is the water located outside solid structures (bacteria and food residue). METHODS: Each stool passed by 16 non-constipated male volunteers was collected during 3 weeks. PEG was ingested from days 1 to 7, and stools collected during the ingestion of PEG were compared with those collected at least 24 h after the last fecal excretion of PEG (control fecal data). Consistency, fresh and dry weight, dilution water, nitrogen, electrolytes and PEG were quantified in each stool. RESULTS: Stools were softer during the ingestion of PEG (P < 0.01) and dilution water increased significantly (49.4 +/- 1.7 vs 37.6 +/- 2.6 mL/100 g feces, mean +/- SD, P < 0.02). PEG induced variable effects among individuals according to the consistency and dilution water measured during the control period. CONCLUSION: Low doses of PEG (5.9 g/d) soften stools particularly when feces are harder. This effect is due to changes in dilution water (water outside fecal solid structures).

Gastrointestinal and biliopancreatic response to continuous nasogastric feeding in man: effect of increasing nutrient infusion rate.

Nasogastric feeding is a safe and inexpensive procedure used in various conditions to provide artificial nutritional support. However, the effects of increasing energy load of nutrients during continuous enteral nutrition on gastric physiology, biliopancreatic secretions and intestinal absorption of nutrients are unknown. A nutrient solution (1 kcal/ml, 15% proteins, 30% lipids, 55% carbohydrates) was randomly infused at three rates, 1.5, 3.0 and 4.5 ml/min, into the gastric antrum in 6 volunteers over a 6 h period. Gastric emptying, gastric and biliopancreatic secretion, and intestinal absorption were studied using a perfusion technique. Gastric emptying rate reached the infusion rate during continuous enteral nutrition at 1.5 and 3.0 ml/min although a steady state was not reached at 4.5 ml/min. During feeding at 1.5, 3.0 and 4.5 ml/min, the median gastric pH values were 1.9, 2.3 and 3.0 respectively and the total gastric volumes at the sixth hour were 78 +/- 13, 226 +/- 43 and 539 +/- 101 ml respectively. There was a significant increase in biliary and pancreatic secretion between 1.5 and 3.0 ml/min but not between 3.0 and 4.5 ml/min. Gastric emptying became the limiting factor in lipid and in carbohydrate absorption. Our study shows that, in healthy volunteers, the maximal infusion rate of a nutrient solution infused into the stomach should be approximately 3 ml/min to avoid complications such as nausea, vomiting, regurgitation and pulmonary inhalation.

Effect of jejunal infusion of different caloric loads on pancreatic enzyme secretion and gastro-intestinal hormone response in man.

It has recently been demonstrated that the infusion of a high caloric load (3.3 kcal min-1 = 14.0 kJ min-1) into human upper jejunum inhibited pancreatic enzyme and bile salt secretion. The aim of the present study was to investigate whether this phenomenon was mediated by gastrointestinal hormones which interfere with pancreatic secretion. In six healthy volunteers, jejunal infusion of 1.3 kcal min-1 (5.5 kJ min-1) did not modify secretion of lipase and chymotrypsin to any significant extent compared with saline infusion, but the rate of 3.3 kcal min-1 (14.0 kJ min-1) resulted in an inhibition. Somatostatin and pancreatic polypeptide, which are known to inhibit exocrine pancreatic secretion, remained unchanged during jejunal nutrient infusion. The inhibition of pancreatic enzyme secretion was observed in temporal relationship with an increase of the stimulators of pancreatic exocrine secretion such as secretin, neurotensin, and CCK. The existence of an hitherto undefined inhibitor and a feedback mechanism is postulated.

Intestinal absorption of amiodarone in man.

The jejunal absorption rate of amiodarone and the influence of lipids on it were studied in human volunteers using the intestinal perfusion technique. A nutrient solution (Realmentyl, Sopharga Laboratories, France) with 300 mg of the drug was infused for 120 minutes at the ligament of Treitz. The segment tested was 25 cm long. Two caloric loads of the nutrient solution, 3.3 Kcal/min (solution A) and 1.3 Kcal/min (solution B), A containing total lipid and caloric load 2.5 times higher than B, were administered. Minor interindividual differences in amiodarone absorption rate were observed (20.2 to 31.7%) with solution A. Amiodarone absorption correlated with lipid absorption significantly. Since the maximal plasma concentrations of the drug and the area under the curve (AUC/24 hours) did not correlate with the amount of amiodarone absorbed, the wide fluctuations of amiodarone pharmacokinetics must mainly be due to amiodarone tissue distribution and metabolic pathway.

Effect of jejunal infusion of nutrients on gastrointestinal transit and hormonal response in man.

The effects of jejunal infusion of nutrients on gastric emptying and secretion, intestinal transit and hormone release were studied in human volunteers. Two caloric loads, 1.3 and 3.3 kcal/min, of a nutrient solution consisting of 18 percent protein, 27 percent lipids, and 55 percent carbohydrates were tested. These were first used in random order in 6 subjects to assess the effects on intestinal transit. For the study of gastric emptying, jejunal infusion was started 1 h after intragastric instillation of a 490 kcal, 400 ml, homogenized meal. Intestinal transit time and gastric emptying half-time increased with the rate of nutrient infusion into the jejunum. Postprandial gastric secretion was reduced. The two caloric loads induced significant rises of plasma cholecystokinin and gastric inhibitory polypeptide concentrations. Plasma motilin decreased in relation to the jejunal caloric load. The other peptides were essentially not affected by jejunal nutrient infusion in fasting subjects. We conclude that in man, gastric emptying rate, gastric secretion, and intestinal transit are regulated by the presence of nutrients in the jejunum.

Inhibitory effect of high caloric load of carbohydrates or lipids on human pancreatic secretions: a jejunal brake.

Effects of jejunal infusion of a saline solution, a protein meal, and a mixed protein and carbohydrate meal on biliopancreatic secretions were compared in six healthy volunteers. Protein infusion stimulated biliopancreatic secretions whereas carbohydrate infusion inhibited these secretions compared with saline infusion. The roles of lipid, carbohydrate, and caloric load on the inhibition of pancreatic secretions by jejunal infusion of nutrients was investigated in six other healthy volunteers. Carbohydrate, lipid, and the mixed meal inhibited pancreatic secretions whereas the carbohydrate solution was the only one that inhibited biliary secretion. These studies indicate that the mechanism of jejunal brake seems mainly related to the jejunal caloric load. In malabsorption or in the short bowel syndrome, a high caloric load or unabsorbed nutrients in the jejunum further inhibits pancreatic secretion, contributing to the loss of nutrients from the intestinal tract.

Evaluation of the gastric absorption and emptying of drugs under various pH conditions using a simple intubation method: application to diclofenac.

Sodium diclofenac (50 mg) together with [14 C]-PEG as a non-absorbable marker were dissolved in 400 ml of water (A), phosphate buffer pH 7.5 (B) or a homogenized meal (C). Each of these was ingested in random order by six volunteers on 3 consecutive days. Some gastric absorption of the drug was established with C but the plasma drug concentration-time profiles mainly reflected the process of gastric emptying.

Symptomatic, radionuclide and therapeutic assessment of chronic idiopathic dyspepsia. A double-blind placebo-controlled evaluation of cisapride.

Twenty-eight patients with chronic idiopathic dyspepsia defined by the presence of chronic unexplained symptoms suggestive of gastric stasis and directly related to food ingestion were included in this prospective study. Gastric emptying of the liquid and solid phases of a meal was quantified by a dual-isotope method, and symptoms were evaluated by a diary and a visual analog scale. Delay in gastric emptying was evidenced in 59% of the dyspeptic patients; it occurred with liquids in more cases than solids. Quantitative and qualitative evaluation of symptoms was of no practical value in predicting the presence of objective stasis. The dyspeptic patients were included in a double-blind randomized controlled trial of cisapride, a new gastrokinetic drug devoid of central antiemetic effects. After six weeks of cisapride treatment, all patients with initially abnormal gastric emptying rates for liquids, and all but one for solids returned to normal ranges, and significant differences between cisapride and placebo groups were observed for half emptying times of both solids (136 +/- 16 min vs 227 +/- 32 min; P less than 0.02) and liquids (61 +/- 4 min vs 132 +/- 37 min; P less than 0.01). Cisapride also significantly improved dyspeptic symptom scores at weeks 3 and 6 of treatment as compared to those measured before treatment. Nevertheless, the decrease in global diary score was significantly higher than that seen with placebo at week 3 (-16 +/- 6 vs -1 +/- 9; P less than 0.05), but not at week 6 (-18 +/- 5 vs -10 +/- 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Almitrine bismesylate disposition in the human digestive tract.

The absorption of almitrine from the upper gastrointestinal tract has been evaluated in 6 healthy volunteers by an intubation technique. Almitrine bismesylate dissolved in malic acid was introduced into the stomach after homogenization with a meal containing the marker 14C-polyethylene glycol (PEG) 4000. Unlabeled PEG 4000 was infused into the second part of duodenum throughout the experiment. Samples of the luminal content were collected every 15 min for four hours from the stomach and at the ligament of Treitz. Blood was also collected. Almitrine was neither absorbed from nor metabolized in the stomach. About 37% of the quantity of drug emptied from the stomach was absorbed from the duodenum. Almitrine was detected in plasma 50 min after ingestion of the meal and its plasma concentration-time profile reflected the cumulative gastric emptying rate. The metabolite tetrahydroxy almitrine was found in intestinal samples as soon as unchanged drug was detected in plasma. The intraluminal rate of formation of the metabolite increased with time. The results suggest hepatic metabolism of almitrine followed by rapid excretion of the metabolite in the bile.

[Plasma insulin and glucagon after ingestion of meal enriched with increased doses of pectin in healthy man]. / Insulin et glucagon plasmatiques après ingestion d'un repas enrichi par des doses croissantes de pectine chez l'homme sain.

The effects of three doses of pectin (5, 10 and 15 g) included in a solid-liquid meal on the postprandial plasma insulin and glucagon responses were studied in 12 healthy men. The mean plasma glucagon level was significantly smaller with 5 g of pectin than the control values at 150 min (p less than 0.05) whereas plasma insulin values did not vary. No change in mean plasma glucagon and insulin levels was noted with 10 g and 15 g of pectin although the mean blood glucose levels were significantly higher than the control values at 180 min (p less than 0.05). Addition of pectin to a meal, even if the doses were relatively important, had little or no effect on the postprandial hormonal responses in healthy men. However, pectin could be of renewed interest because of the possibility of its action of satiety by means of sustained late blood glucose levels.

Pathophysiological study of diarrhoea in a patient with medullary thyroid carcinoma. Evidence against a secretory mechanism and for the role of shortened colonic transit time.

Intubation techniques and scintigraphic studies were used to determine the origin and mechanism of diarrhoea in a patient with medullary thyroid carcinoma, high plasma immunoreactive calcitonin and normal circulating serotonin, substance P and prostaglandins E2 and F2 alpha. Normal function of the small intestine was found for the following: (a) absorption tests; (b) water and electrolyte absorption in the proximal jejunum; (c) 24 hour flow rate and composition of fluid entering the colon and (d) gastric emptying rate and small intestinal progression of a normal meal. By contrast, colonic function was markedly impaired in three ways: (a) water absorption was decreased by half; (b) as the main excreted solutes were organic acids, a large electrolyte gap was recorded in faecal water, and (c) colonic transit time of the meal marker was very short, and was in agreement with the rapid transit of ingested radioopaque markers. These data strongly suggest that decreased absorption in the colon secondary to a motor disturbance is the main mechanism of diarrhoea in this case of medullary thyroid carcinoma, while calcitonin induced small intestinal fluid secretion suggested earlier is either non-existent, or only of minor importance.

Effect of different caloric loads in human jejunum on meal-stimulated and nonstimulated biliopancreatic secretion.

The effects on biliopancreatic secretion of two caloric loads (1.3 and 3.3 kcal/min of Realmentyl: proteins 18%, lipids 27%, carbohydrates 55%), infused into the jejuna of 10 healthy men, were compared with those of a control solution. In one set of experiments (six subjects) when biliopancreatic secretion was not stimulated before infusion, the rate 1.3 kcal/min resulted in mild stimulation whereas the rate 3.3 kcal/min brought about an inhibition of biliopancreatic secretion. In another set of experiments (six subjects) when biliopancreatic secretion was stimulated by ingestion of an homogenized meal (400 mL, 490 kcal) 1 h before the start of infusion, both loads resulted in strong inhibition of pancreatic secretions, the effect being more pronounced with the high caloric load.

Antibiotic-lock technique: a new approach to optimal therapy for catheter-related sepsis in home-parenteral nutrition patients.

During a cumulated survey of 286 months, covering 11 gastroenterological patients under nocturnal-cyclic home parenteral nutrition, 24 cases of catheter-related sepsis were observed (one/11.9 months). None of these were associated with focus of infection at the cutaneous entry point or at the subcutaneous tunnel of the catheters. In this study attempt was made to control sepsis without removal of the surgically implanted siliconed lines (Vygon code 180-20 with an internal filling volume of 1 ml). The first two catheter-sepsis were conventionally treated with systemic antibiotics for 3 weeks which meant a 1-month hospital admission each time. Consequently, we used a new antibiotic therapy consisting of locking 12 hr/day 2 ml of highly concentrated antibiotic solution within the catheter. After identification of bacterial strains by blood cultures, the antibiotic lock-technique was daily applied either alone for 16 days (group I, n = 11) or for 12 days following a 3-day course of systemic antibiotics (group II, n = 11). After starting antibiotics via the infected line, the time taken for fever abatement and for obtaining negative in-line blood cultures were 2 and 4 days, respectively, and identical in group I and II. Failure of antibiotic treatment leading to catheter withdrawal was observed once in each group (9%) and was due to secondary candida catheter-sepsis. The time for hospital stay was shorter p less than 0.02 in group I (4 days) than in group II (7 days). Antibiotic-lock technique was then applied by trained patients at home.(ABSTRACT TRUNCATED AT 250 WORDS)

Metformin in the digestive tract.

After ingestion of metformin, a drug of the biguanide class, there are gastrointestinal effects in the form of nausea and vomiting, and about 30% of the drug is recovered in feces. The purpose of this work was to explain these two phenomena. Two sets of experiments were carried out. Study I evaluated the gastroduodenal (GD) absorption in six healthy volunteers by means of an intubation method, employing a twin-lumen tube introduced into the intestine and another into the stomach. Metformin 1 g was introduced into the stomach with a homogenized meal containing a non-absorbable marker, 14C-PEG 4000; another marker, PEG 4000, was perfused continuously into the duodenum at the ampulla of Vater. Samples of GD contents were collected every 15 min during 4 h. Metformin was poorly absorbed from the stomach, about 10% over a 4-h period. It did not modify the gastric emptying of a meal but induced a duodeno-gastric reflux in five out of six subjects. About 20% of the amount of drug emptied from the stomach were absorbed from the duodenum. The delivery process was the rate-limiting factor for metformin absorption from the duodenum. The AUC/24 h increased as the absorption rate from the duodenum increased. Study 2 investigated in six healthy volunteers, using another intestinal perfusion technique, the jejunal and ileal absorption of metformin. Metformin 400 mg in saline solution was perfused, over a 2-h period, below an inflated balloon, directly into either the jejunum or the ileum.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects of enprostil on changes in the gastric transepithelial potential differential induced by aspirin]. / Effets de l'enprostil sur les modifications de la différence de potentiel transépithéliale gastrique induites par l'aspirine.

Enprostil (E), is a semisynthetic E2 prostaglandin with wide-range antisecretory properties. Administered orally E reduced mucosal injury in rats exposed to NSAID and gastric acid. The aim of the present study was to analyze the cytoprotective effect of 7 micrograms of E on the aspirin-induced (500 mg) decrease in gastric transepithelial difference of potential (DP) in a) five healthy volunteers and b) five patients with epigastric heartburn, normal endoscopy and a low gastric DP (mucosal barrier weakness). Aspirin-induced decrease of gastric DP was measured during two four hour periods separated by an interval of two days: a) during a one hour basal period and after three hours after 7 micrograms of E, and b) during a second basal period and one hour after aspirin, E, and then aspirin again. The following parameters were analyzed: maximal drop of DP DP Max (mV), area under the curve of DP drop, AUC (mV.min), and time to return to basal values, TRB (min). In the control group, when E was administered after aspirin, the decrease in DP Max (11.4 +/- 2.3 vs 6.6 +/- 2.1) and in AUC (68 +/- 22 vs 35 +/- 11) was significant (p less than 0.05) as compared with values obtained after aspirin alone. In the patient group, E produced a significant decrease in aspirin-induced DP Max (11.8 +/- 1.9 vs 6.8 +/- 2.4) (p less than 0.003) and in AUC (117 +/- vs 48 less than 22) (p less than 0.006) as well as in TRB (52 +/- 2 vs 37 +/- 10) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Jejunal and ileal absorption of oxprenolol in man: influence of nutrients and digestive secretions on jejunal absorption and systemic availability.

1 Study I evaluated the absorption of oxprenolol in the ileum, compared to jejunum, in healthy volunteers by an intestinal perfusion technique. Around 80 mg of drug were delivered as a saline solution directly in the small bowel. 2 Samples taken 30 cm distally to the site of perfusion showed that 63% of perfused oxprenolol was absorbed in the jejunum and 48% in the ileum; the differences were significant. 3 The plasma concentration-time profiles were similar for the two perfusions. The AUC and Cmax values of free and conjugated oxprenolol for the jejunal perfusion were significantly lower than those of ileum. They showed large but consistent intersubject variations in the two treatments. 4 Study II investigated, using the same technique, the influence of nutrients and digestive secretions on jejunal absorption and systemic availability of this drug. A saline (in treatments A and B) or a nutrient (in treatment C) solution containing oxprenolol was perfused into the jejunum below a balloon either inflated (A) or deflated (B and C). 5 The disappearance rate of oxprenolol from the jejunum was unaffected by endogenous secretions. The mean amount of drug absorbed along a 30-cm jejunal segment accounted for 52 (A) and 57% (B) of the total amount perfused. The intestinal absorption rate was markedly increased in the presence of nutrients (mean amount absorbed 96% for C). 6 The change in the rate of disappearance from the intestine had no effect on the systemic availability of oxprenolol (mean AUC values 8740, 8250 and 8020 nmol l-1 h for A, B and C, respectively) or its elimination from plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evaluation of the use of parenteral nutrition in chronic and severe radiation enterocolitis]. / Evaluation de l'utilisation de la nutrition parentérale au cours desentérocolites radiques chroniques et sévères.

The effects of parenteral nutrition in the treatment of patients with severe chronic radiation enterocolitis is not known. We retrospectively studied 19 adult patients who received parenteral nutrition during 8.6 +/- 2.4 months (mean +/- SEM), including 6 cases in our home-parenteral nutrition-program. Parenteral nutrition was started 49 +/- 12 months after radiation therapy; follow-up after parenteral nutrition was 22 +/- 7 months. Indication for parenteral nutrition was malnutrition (weight = 73 +/- 2 p. 100 of ideal body weight, serum albumin level = 27 +/- 1 g/l) due to multifocal gastrointestinal radiation injuries with stenoses (n = 12), fistulae (n = 3) and short bowel syndrome (n = 4). Parenteral nutrition was given during the peri-operative period in 15 patients. Neither fistulae nor stenoses resolved with parenteral nutrition alone (n = 7) or in association with steroids (n = 5). There was a 57 p. 100 mortality rate (11 patients): 10 p. 100 were postoperative (2 of the 3 patients with fistulae), 21 p. 100, due to radiation complications and 26 p. 100, due to progression of cancer. In those patients with severe and multifocal chronic radiation enteropathy, parenteral nutrition did not influence the lesions in the digestive tract. Nutritional support could, however, be considered as an useful adjunct with a low perioperative mortality rate. In the 14 patients without superimposed unresponsive cancer, parenteral nutrition followed by curative abdominal surgery seemed to be associated with the best prognosis and in 7 of the 8 survivors, parenteral nutrition has been discontinued without reappearance of clinical malnutrition.

[Effect of the increase of the caloric load of a meal on gastric emptying of its solid and liquid phases]. / Effet de l'augmentation de la charge calorique d'un repas sur la vidange gastrique de ses phases solide et liquide.

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)