Effects of posture on gastric emptying and satiety ratings after a nutritive liquid and solid meal.

To study the effects of posture and meal structure on gastric emptying and satiety, nine women ingested tomato soup and then immediately or 20 min later an egg sandwich, when seated and when supine. The lag time was not different, but the half-emptying time of the sandwich was 32% longer (P < 0.01) and the emptying rate after the lag phase was 39% slower (P < 0.01) when the subjects were supine than when they were seated. The half-emptying time of the soup was 50% longer (P < 0.01) when the subjects were supine and ingested the soup immediately before the sandwich than in the other three conditions. Postprandial hunger ratings recovered more slowly (P < 0.01) when the subjects ingested the soup 20 min before the sandwich than when they ingested the soup immediately before the sandwich. These results suggest that posture did not affect the intragastric distribution of the sandwich but affected propulsion of the meal into the intestine and that postprandial satiety was enhanced by the cumulative effect over time of a 20-min "head start" in stimulation of intestinal receptors by emptying of the soup.

Contribution of gastric and postgastric feedback to satiation and satiety in women.

Two parallel preload studies were conducted to determine the relative contributions of inhibitory feedback from the stomach and intestine to satiation (meal termination) and postprandial satiety. In the Gastric Emptying Study, five normal-weight women each ingested an egg sandwich (307 kcal) (1) immediately after a tomato soup preload (120 kcal), (2) 20 min after a tomato soup preload, and (3) with no preload. There was 125 g more of soup in the stomach when subjects began ingesting the sandwich immediately compared to 20 min after the soup, and the emptying of the sandwich was delayed when it was ingested immediately but not 20 min after the soup. The lag times for emptying of the sandwich were 76.5 (69.1-82.4), 47.2 (20.1-67.7), and 42.4 (17.8-65.1) min for the three conditions, respectively, p < 0.05. In the Food Intake Study, 16 normal-weight women ate significantly less (p < 0.01) in test meals offered immediately (978+/-246 kcal) and 20 min (1027+/-298 kcal) after the soup preload than in a test meal with no preload (1151+/-279 kcal). Despite the different amounts of soup in the stomach, subjects' test-meal intake in the two preload conditions was not significantly different. Subjects' fullness ratings following the preloads and the test meals were not different among the treatment conditions. The results suggest that feedback from neither the gastric nor the postgastric compartment is primary in determining meal size and postprandial satiety. Instead, signals from gastric and postgastric sources are combined to determine meal size and postprandial satiety.

Bioavailability of medication after laparoscopic cholecystectomy.

Bioavailability of medication after laparoscopic cholecystectomy has not been studied previously. There is concern about the ability of patients to tolerate oral medication postoperatively and the optimal timing of hospital discharge. In this study, each subject received 20 mg/kg acetaminophen (po) preoperatively, with a repeat dose at 6 (group 1), 12 (group 2), or 24 h (group 3) postoperatively. Serum levels were obtained 40 and 90 min after each ingestion. Bioavailability of medication was significantly decreased (p < 0.01) 6 h (group 1) and 12 h (group 2) postoperatively. Bioavailability returned to baseline by 24 h after laparoscopic cholecystectomy (group 3). This study indicates that oral medication should be used judiciously during the first 12 h after laparoscopic surgery.

Bioavailability of medication delivered via nasogastric tube is decreased in the immediate postoperative period.

BACKGROUND: A study was performed to determine bioavailability of medication delivered via nasogastric tube in patients after abdominal surgery. METHODS: Acetaminophen (20 mg/kg) was administered to each patient per os at least 48 hours prior to abdominal surgery and via nasogastric tube 3 hours postoperatively. The nasogastric tube was clamped for 30 minutes after drug administration, prior to resuming suction. Serum levels of acetaminophen were measured 0, 40, and 90 minutes after each dose. RESULTS: Acetaminophen levels were significantly lower (P < 0.001) when the drug was administered via nasogastric tube postoperatively. CONCLUSIONS: Decreased bioavailability of medications delivered via nasogastric tube may have important clinical implications and should be taken into consideration during the postoperative period.

Recall of informed consent after endoscopic procedures.

PURPOSE: The aim of this study was to determine if recall of informed consent is affected by the timing of obtaining informed consent before endoscopic procedures. METHODS: Sixty patients scheduled for colonoscopy or esophagogastroduodenoscopy were enrolled in this prospective, randomized study. Each patient received informed consent 24 to 72 hours or immediately before the procedure, and follow-up occurred one to three days postprocedure. RESULTS: There was no statistically significant difference in recall of informed consent or the individual elements of informed consent (indication, risks, benefits, alternatives) between the two groups. CONCLUSION: Recall of informed consent is similar whether consent is obtained immediately or several days before endoscopic procedures.

Conservative management of endoscopic sclerotherapy-induced esophageal perforation.

Esophageal perforation is a rare though potentially lethal complication of variceal sclerotherapy. Diagnosis is usually made after recognition of often subtle clinical symptoms. Surgical and nonsurgical modalities have been proposed, and nonoperative management can be successful even in patients thought to have absolute indications for surgery.

Oral administration of proteinase inhibitor II from potatoes reduces energy intake in man.

The effect of a proteinase inhibitor extracted from potatoes (POT II) which increases CCK release, on food intake was examined in 11 lean subjects. They received 1.5 g POT II in a high-protein soup vehicle (70 kcal), the soup vehicle alone, or a no-soup control five minutes before being presented with a lunchtime test meal, according to a double-blind, within-subjects design. Consuming the soup alone led to a nonsignificant 3% reduction in energy intake. The addition of 1.5 g POT II to the soup significantly reduced energy intake by a further 17.5%. Premeal ratings of motivation to eat and food preferences did not predict the reduction in energy intake by the proteinase inhibitor. These findings suggest that endogenous CCK may be important in the control of food intake and that proteinase inhibition may have therapeutic potential for reducing food intake.

Role of cholecystokinin in the control of food intake.

CCK appears to regulate short-term control of food intake by acting as a satiety signal. Larger doses of CCK may decrease food intake by aversive actions (malaise, nausea, cramps), presumably by effects on gastrointestinal motility. In rats and most likely humans CCK is released from the upper intestine after a mixed meal and appears to activate afferent vagal fibers by causing pyloric contraction with resultant gastric distention or directly binding to the gastric afferent vagus which courses to the nucleus solitarius with further projections to the paraventricular nucleus and ultimately the ventromedial hypothalamus. Peripherally released CCK may also bind to CNS receptors in the area postrema overlying the nucleus solitarius. Central nervous system CCK released from the paraventricular nucleus may also exert a satiety effect. The satiety effect of CCK appears to be a physiologic action of the peptide since antibodies to CCK and CCK receptor antagonists can increase food intake. CCK is probably just one of several satiety signals but can cause a profound decrease in food intake when administered exogenously in pharmacologic doses. Administration of exogenous CCK, as well as endogenous CCK released by oral protease inhibitors, can decrease food intake in humans. Studies designed to examine the effect of chronic administration of CCK on food intake will be necessary to determine if the peptide has a role in the management of obesity and bulimia.

Medical care of the surgical patient with gastrointestinal disease.

Common perioperative gastrointestinal disorders of surgical patients are presented. Recommendations for appropriate medical evaluation and management are described.

Role of pylorus in mediating cholecystokinin-stimulated satiety in the Zucker rat.

Obese Zucker rats are less responsive than their lean littermates to the effects of cholecystokinin-octapeptide on satiety and pancreatic growth and exocrine function. We hypothesized that the hyperphagia observed in obese Zucker rats may be caused by a decreased pyloric contractile response to cholecystokinin, resulting in an increased rate of gastric emptying, decreased postprandial gastric distention, and thus decreased satiety. Pyloric muscle strips from six obese Zucker rats and six lean littermates were mounted in separate tissue baths and isometric contraction was measured in response to acetylcholine and cholecystokinin-octapeptide. The dose-response curves for acetylcholine- and cholecystokinin-octapeptide-stimulated pyloric muscle contraction were similar for both the obese and the lean rats. (For cholecystokinin, D50 obese = 4.0 +/- 0.6 nM, D50 lean = 3.4 +/- 0.2 nM; P = 0.16). We conclude that the decreased satiety response to cholecystokinin-octapeptide observed in obese Zucker rats is not secondary to a decreased pyloric responsiveness to cholecystokinin.

Decreased pancreatic CCK receptor binding and CCK-stimulated amylase release in Zucker obese rats.

In Zucker obese rats the response to the effects of CCK on food intake and pancreatic exocrine function are decreased. However, it is unknown whether the decreased responsiveness is due to decreased receptor number and/or sensitivity or abnormal circulating concentrations of CCK. In these experiments percent total binding of 125I-CCK-33 to pancreatic acini from obese rats was one-half that in lean rats when data was expressed on a per microgram DNA basis (19.6 +/- 5.1 vs. 47.4 +/- 11.4, p less than 0.01). In a second experiment while the maximally effective dose of CCK for stimulating amylase secretion from dispersed pancreatic acini was similar in obese and lean rats (10(-10) M), less amylase was secreted in obese rats across the dose range tested (p less than 0.001). In contrast, carbachol had similar potency and efficacy in stimulating amylase release from obese and lean pancreatic acini. The increase of pancreas size by use of a trypsin inhibitor was greater in lean than obese rats (p less than 0.03). In addition, stimulation of amylase release by CCK from obese trypsin inhibitor-treated compared with control obese rats was greater than that from lean trypsin inhibitor-treated compared with control lean rats (p less than 0.002). However, overall, stimulation of amylase secretion by CCK was only 36% of control (p less than 0.001) and by carbachol was only 20% of control (p less than 0.001). Thus, increased size by increased cell number was associated with decreased response per cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Trypsin inhibitor effects on food intake and weight gain in Zucker rats.

Decreased body weight and increased pancreas weight which occur in rats fed raw soybeans are thought to be due to the presence of trypsin inhibitors in the soybeans (SBTI). Since trypsin is postulated to be a negative feedback signal for cholecystokinin (CCK) secretion, SBTI may have these effects by increasing secretion of CCK. CCK is a putative satiety signal; thus, increased secretion of CCK could decrease food intake, and, if maintained over a period of time, body weight. In these experiments the effects of a trypsin inhibitor [N,N-dimethyl-carbamoyl 4-(4-guanidino-benzylyloxy)-phenyl acetate methane-sulfate (DGPM)]on feeding pattern were investigated in Zucker obese and lean rats. Administration of 25-200 mg/kg DGPM to 6-hr fasted rats decreased daily food intake by dose-dependently decreasing average meal size in both obese and lean rats, but the response was greater in obese rats. Administration of 100 mg/kg DGPM twice daily for 7 days decreased food intake and body weight in obese but not lean rats. Thus, these results suggest that decreased body weight associated with SBTI is due to decreased food intake partly as a result of increased secretion of the putative satiety peptide CCK.

Food intake response to modulation of secretion of cholecystokinin in Zucker rats.

Exogenous administration of cholecystokinin (CCK) decreases food intake and elicits satiety behaviors. In the present experiments, feeding behaviors of Zucker obese and lean rats were measured in response to treatments that influence endogenous secretion of CCK from the duodenum. Secretion of CCK was increased by administration of phenylalanine, a stimulant of CCK release, and of trypsin inhibitor, which binds to trypsin, a negative-feedback signal for CCK release. Both of these treatments decreased the size of the first meal after a 6-h fast and average daily meal size and increased meal frequency. Administration of trypsin, proported to decrease secretion of CCK, increased average daily meal size and decreased meal frequency. Pancrease, a pancreatic enzyme concentrate, also hypothesized to act as a negative-feedback signal for CCK release, elicited feeding behaviors similar to those of trypsin. Thus the effects of these compounds on the feeding behavior of Zucker obese and lean rats may be related to their effects on CCK secretion. The feeding behaviors of obese rats were affected less than those of lean rats by exogenous administration of CCK, but in these experiments were affected more than in lean rats by modulation of endogenous release of CCK.

Hyperphagia during lactation: satiety response to CCK and growth of the pancreas.

Cholecystokinin (CCK) secreted from the duodenum during feeding has been shown to elicit satiety and stimulate growth of the pancreas in addition to affecting gastrointestinal function. In previous experiments hyperphagic Zucker obese rats were less sensitive to the effects of CCK on satiety and had a smaller pancreas than normal-weight rats. In the present experiments with hyperphagic lactating Zucker rats, the food intake response to exogenously administered CCK and the size and composition of the pancreas were measured. Food intakes after a 2-h fast were not decreased by 4.0 or 8.0 micrograms/kg CCK-8 during wk 1, 2, or 3 of lactation. However, in the same rats 2 wk after pups were weaned, 4.0 and 8.0 micrograms/kg CCK-8 decreased food intake 32% (2.1 +/- 0.4 vs. 3.1 +/- 0.3 g, paired t = 2.33, P less than 0.03) and 52% (1.5 +/- 0.2 vs. 3.1 +/- 0.5 g, paired t = 3.48, P less than 0.006). On day 18 of lactation, pancreas weight was increased 41% (1.38 +/- 0.05 vs. 0.98 +/- 0.02 g, paired t = 2.68, P less than 0.02) and contents of DNA, RNA, and protein were increased 57, 57, and 73%, respectively. Thus, hyperphagia in lactating female rats was associated with 1) decreased sensitivity to the satiety effect of CCK similar to that in hyperphagic obese rats and 2) hypertrophy of the pancreas in contrast to decreased pancreas size in obese rats.

Decreased pancreatic exocrine response to cholecystokinin in Zucker obese rats.

Cholecystokinin (CCK), one of the peptides secreted by the gastrointestinal tract during a meal, stimulates release of enzymes into pancreatic juice and is a trophic hormone for the pancreas. Administration of CCK also decreases food intake, and obese rats have been shown to have a higher threshold than lean rats for this apparent effect on satiety. In this study experiments were designed to compare the sensitivity of obese and lean rats to the effects of CCK octapeptide (CCK-8) on pancreatic structure and exocrine function. In both growing and adult Zucker rats DNA content of the pancreas from obese rats was decreased compared with that from lean rats [2.42 +/- 0.21 vs. 3.07 +/- 0.18 mg (P less than 0.01) and 2.46 +/- 0.25 vs. 3.01 +/- 0.19 mg (P less than 0.05), respectively], and in adult obese rats this was accompanied by decreased pancreas size on both absolute weight and percent of body weight bases. In adult obese Bar Harbor mice, although DNA content of the pancreas was also decreased [1.70 +/- 0.10 vs. 2.41 +/- 0.11 mg (P less than 0.01)], pancreas weight was not different (0.30 +/- 0.01 vs. 0.32 +/- 0.01 g). In young rats growth of the pancreas was stimulated by 2 micrograms/kg CCK-8 administered subcutaneously or 100 mg/kg of a trypsin inhibitor administered orally twice daily for 2 wk. Although both treatments increased weight and DNA and protein content of the pancreas, the increases in DNA and protein content were smaller in obese than lean rats, indicating a decreased responsiveness to both trophic agents. Administration of CCK-8 stimulated smaller increases in pancreatic juice volume and amylase release in obese compared with lean rats, indicating decreased pancreatic exocrine function in response to CCK. In adults the CCK-8 dose-response curve for amylase release from dispersed pancreatic acini of obese rats was similar to that of lean rats, indicating normal sensitivity in vitro. Thus, in obese rats and mice DNA content of the pancreas is decreased when compared with that of lean rats and mice, and this is accompanied by decreased in vivo responses to CCK in obese rats.

Role of Clostridium difficile in a case of nonantibiotic-associated pseudomembranous colitis.

A 57-yr-old woman with chronic diarrhea, mild azotemia, and red cell casts in her urine was found to have pseudomembranous colitis. She had not received antimicrobial agents for at least 2 yr. Membranoproliferative glomerulonephritis was found in kidney biopsy, and her renal function improved spontaneously. Pseudomembranous colitis was diagnosed by endoscopic biopsy. Her stool contained a cytophatic toxin that was neutralized by Clostridium sordellii antitoxin, and Clostridium difficile was cultured on selective media. This case indicates that C. difficile may be a cause of nonantibiotic-associated pseudomembranous colitis, as well as antibiotic-associated pseudomembranous colitis.