[Hard stools, soft stools. New point of view of fecal water: structural water and dilution water].
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Biomedical subjects
Publications and source records attributed to J J Bernier.
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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).
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.
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.
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.
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)
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.
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.
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.
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)
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.
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.
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)
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.
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)
The influence of bile salts and lipids on the intestinal absorption of griseofulvin has been studied in 11 healthy male volunteers by the intestinal perfusion technique. The drug in a nutrient solution (Realmentyl) was perfused into the second part of duodenum at 5 ml/min. Intestinal samples were taken continuously at 1 ml/min, 20 cm (at the angle of Treitz) and 45 cm distal to the perfusion point. To study the effect of lipids on griseofulvin absorption, the drug was perfused with solutions A and B, of which B contained a total lipid and caloric load three times that of A. The influence of bile salts on griseofulvin absorption was examined by perfusing the drug on Day 1 with bile salts and again on the following day after bile salt depletion. Bile salts and a varying quantity of lipid perfusate had no significant influence on the duodeno-jejunal griseofulvin absorption rate per cm of intestine. Lipids, however, may still play a role in griseofulvin absorption along the entire intestine.
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.