Effect of rectal distension on gallbladder emptying and circulating gut hormones

BACKGROUND: Abnormalities of upper gut motility, including a delay of gastric emptying and small bowel transit, found in patients with constipation may be secondary to factors originating in the colon or rectum as a result of faecal stasis. The aim was to determine if stimulation of mechanosensory function by rectal distension affects postprandial gallbladder emptying and release of gastrointestinal peptides participating in control of upper gut motility. MATERIALS AND METHODS: Eight healthy volunteers were studied with an electronic barostat and a plastic bag positioned in the rectum. Intrabag pressure was maintained at minimal distension pressure + 2 mmHg on one occasion and on a pressure that induced a sensation of urge on the other. Gallbladder volume and plasma concentrations of cholecystokinin (CCK), pancreatic polypeptide (PP) and peptide YY (PYY) were measured before and after ingestion of a 450-kcal mixed liquid meal. RESULTS: Rectal distension enhanced maximum gallbladder emptying from 66 +/- 7% to 78 +/- 5% (P < 0.05). Distension tended to increase integrated plasma PYY from 77 +/- 30 pM min to 128 +/- 40 pM min in the first hour after the meal (P = 0.08) and it suppressed integrated plasma PP from 1133 +/- 248 pM min to 269 +/- 284 pM min in the second hour (P < 0.05). Integrated plasma CCK concentrations were not significantly affected. CONCLUSION: Mechanosensory stimulation of the rectum enhances postprandial gallbladder emptying and influences postprandial release of gut hormones involved in the regulation of gastrointestinal motility in healthy subjects. These mechanisms may play a role in the pathogenesis of the upper gastrointestinal motor abnormalities observed in constipated patients.     

Role of the gastric phase in fat-induced gallbladder contraction and cholecystokinin secretion in humans

The present study was undertaken to investigate the role of the gastric phase of fat-induced gallbladder contraction and endogenous cholecystokinin (CCK) secretion in humans. Gallbladder emptying, measured by cholescintigraphy, and endogenous CCK secretion, measured by radioimmunoassay, were studied in healthy subjects after both intragastric and intra-intestinal administration of corn oil. In addition, patients with partial gastrectomy were investigated to study the effect of accelerated gastric emptying. In the healthy subjects, intragastric administration of fat resulted in a significantly (P less than 0.05) later increase in plasma CCK levels (20 +/- 2 min) compared to intraintestinal fat (5 +/- 1 min). Similarly, the onset of gallbladder emptying was significantly (P less than 0.05) delayed after intragastric fat (20 +/- 2 min) compared to intestinal fat (10 +/- 1 min). In the healthy subjects the integrated plasma CCK response to intragastric fat was significantly (P less than 0.005-P less than 0.01) reduced from 10 to 30 min. In the patients with partial gastrectomy the rise in plasma CCK (10 +/- 1 min) and the onset of gallbladder emptying (15 +/- 2 min) were in the same range after intra-intestinal and intragastric fat. No significant differences in plasma CCK levels, integrated CCK response or gallbladder emptying were found in the patients according to the site of fat application. It is concluded that endogenous CCK secretion and gallbladder emptying in response to intragastric fat are significantly delayed in healthy subjects but not in patients with partial gastrectomy, in whom gastric emptying is accelerated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of gastric emptying in humans by cholecystokinin.

In the present study we used a bioassay system for measuring plasma cholecystokinin (CCK) to evaluate whether CCK has a physiologic role in regulating gastric emptying in humans. Plasma CCK levels and gastric emptying after ingestion of a mixed liquid meal were determined in five normal male volunteers. Fasting CCK levels averaged 0.8 +/- 0.1 pM and increased to 6.5 +/- 1.0 pM within 10 min of drinking the mixed meal. CCK levels remained elevated for up to 90 min. Gastric emptying after a meal was slow; at the end of the 90 min 68% of the original volume remained in the stomach. The rate of gastric emptying of water was then measured in the same individuals with a simultaneous infusion of either saline, or one of two doses of CCK (12 pmol/kg per h and 24 pmol/kg per h). With the saline infusion, plasma CCK levels did not increase above basal and gastric contents emptied rapidly. At the end of 90 min only 7% of the original volume remained in the stomach. The lower dose of CCK resulted in a plasma level of 3.4 pM which both reproduced the average postprandial plasma level and caused a significant delay in gastric emptying. The higher dose of CCK achieved plasma levels of 8 pM and resulted in a delay in gastric emptying that was similar to that seen with the mixed meal. Since exogenous CCK at concentrations which occur postprandially delays gastric emptying, we conclude that CCK is a physiologic regulator of gastric emptying.     

Cholecystokinin bioactivity in human plasma. Molecular forms, responses to feeding, and relationship to gallbladder contraction.

A sensitive and specific bioassay for the measurement of cholecystokinin (CCK) in human plasma was developed to determine the molecular forms of CCK in circulation, CCK responses to feeding, and the physiologic role of CCK in gallbladder contraction. First, plasma was quantitatively extracted and concentrated with octadecylsilylsilica, and the extracts were then assayed for their ability to stimulate amylase release from isolated rat pancreatic acini. Acini were highly sensitive to CCK whereas gastrin reacted only weakly in this system. With the assay, plasma levels of cholecystokinin octapeptide (CCK-8) bioactivity as low as 0.2 pM were detectable. CCK bioactivity in plasma was inhibited by the CCK antagonist, bibutyryl cyclic guanosine monophosphate, and was eliminated by immunoadsorption with an antibody directed against the carboxyl terminus of CCK. Detection of fasting levels of CCK was possible in all individuals tested and averaged 1.0 +/- 0.2 pM (mean +/- SE, n = 22) CCK-8 equivalents. Plasma CCK biological activity was normal in patients with gastrin-secreting tumors. After being fed a mixed liquid meal, CCK levels rose within 15 min to 6.0 +/- 1.6 pM. The individual food components fat, protein, and amino acids were all potent stimulants of CCK secretion; in contrast, glucose caused a significant but smaller elevation in plasma CCK levels. Gel filtration studies identified three major forms of CCK bioactivity in human plasma: an abundant form that eluted with CCK-33, a smaller form that eluted with CCK-8, and an intermediate form that eluted between CCK-33 and CCK-8. Ultrasonic measurements of gallbladder volume indicated that this organ decreased 51% in size 30 min after feeding a mixed liquid meal. This contraction occurred coincidentally with the increase in plasma CCK levels. Next CCK-8 was infused to obtain CCK levels similar to postprandial levels. This infusion caused a decrease in gallbladder volume, similar to that seen with a meal. The present studies indicate, therefore, that CCK can be bioassayed in fasting and postprandial human plasma. These studies also suggest that CCK may be an important regulator of gallbladder contraction.     

Physiological role for cholecystokinin in reducing postprandial hyperglycemia in humans.

It is known that the ingestion of glucose alone causes a greater increase in plasma glucose levels than ingestion of the same amount of glucose given with other nutrients. Since physiological plasma concentrations of cholecystokinin (CCK) prolong gastric emptying, it is proposed that after a meal, CCK may modify plasma glucose levels by delaying glucose delivery to the duodenum. To evaluate the effect of CCK on oral glucose tolerance, plasma CCK, insulin, and glucose levels and gastric emptying rates were measured in eight normal males before and after the ingestion of 60 g glucose with the simultaneous infusion of either saline or one of two doses of CCK-8 (12 or 24 pmol/kg per h). Gastric emptying rates were measured by gamma camera scintigraphy of technetium 99m sulfur colloid and plasma CCK levels were measured by a sensitive and specific bioassay. Basal CCK levels averaged 1.0 +/- 0.1 pM (mean +/- SEM, n = 8) and increased to 7.1 +/- 1.1 pM after a mixed liquid meal. After glucose ingestion, but without CCK infusion, CCK levels did not change from basal, and the gastric emptying t1/2 was 68 +/- 3 min. Plasma glucose levels increased from basal levels of 91 +/- 3.9 mg/dl to peak levels of 162 +/- 11 mg/dl and insulin levels increased from 10.7 +/- 1.8 microU/ml to peak levels of 58 +/- 11 microU/ml. After glucose ingestion, with CCK infused at 24 pmol/kg per h, plasma CCK levels increased to 8 pM and the gastric emptying t1/2 increased to 148 +/- 16 min. In concert with this delay in gastric emptying, peak glucose levels rose to only 129 +/- 17 mg% and peak insulin levels rose to only 24.2 +/- 4.2 microU/ml. With CCK at 12 pmol/kg per h, similar but less dramatic changes were seen. To demonstrate that endogenous CCK could modify the plasma glucose and insulin responses to oral glucose, oral glucose was given with 50 g of lipid containing long-chain triglycerides. This lipid increased peak CCK levels to 3.7 +/- 0.9 pM. Concomitant with this rise in CCK was a delay in gastric emptying and a lowering of plasma glucose and insulin values. To confirm that CCK reduced hyperglycemia by its effect on gastric motility, 36 g glucose was perfused directly into the duodenum through a nasal-duodenal feeding tube in four subjects. With duodenal perfusion of glucose, there was no change in plasma CCK levels, but plasma glucose levels increased from basal levels of 93+/-5 to 148+/-6 mg/dl and insulin levels rose from 10.6+/-3.5 to 29.5+/-5.2 microU/ml. When CCK was infused at 24 pmol/kg per h, neither the plasma glucose nor insulin responses to the duodenal administration of glucose were modified. Thus we conclude that CCK, in physiological concentrations, delays gastric emptying, slows the delivery of glucose to the duodenum, and reduces postprandial hyperglycemia. These data indicate, therefore, that CCK has a significant role in regulating glucose homeostasis in human.     

The role of CCK caerulein, and CCK antagonists in nociception

The octapeptide form of CCK predominates in the central nervous system (CNS) of mammalian species, including man. Many of the physiological roles of CCK in the CNS are unknown, but it is believed to be involved in nociception. CCK is distributed throughout cortical grey matter, periaqueductal grey matter, ventromedial thalamus and spinal dorsal horn, all of which are areas known to be associated with pain modulation. CCK receptor subtypes have been identified and may be classified according to their affinity for the sulphated and desulphated forms of CCK-8 and the recently described selective antagonist. MK-329. CCK-A receptors have high affinity for sulphated CCK-8 and for MK-329 but low affinity for desulphated CCK-8 and CCK-4 whilst CCK-B sites bind MK-329 with low affinity and discriminate poorly between sulphated and desulphated CCK-8. CCK-A receptors are found predominantly in peripheral tissues but they also exist in discrete regions of the primate CNS, including the spinal cord. CCK-B receptors are found ubiquitously throughout other regions of the neuraxis. The results of studies on the effects of CCK-8 and the decapeptide analogue caerulein on pain thresholds are conflicting. Some workers suggest that large doses of CCK-8 and caerulein induce naloxone-reversible analgesia in certain pain models. However, it appears likely that analgesia induced by large doses of CCK and caerulein in animals may be a pharmacological rather than a physiological phenomenon. Accordingly, others have found that small (and most probably, physiological) doses of CCK-8 attenuate the analgesic effects of morphine, and of endogenous opioids. Thus, it has been proposed that CCK may act as an endogenous opiate antagonist. Studies in rats with the selective CCK antagonist MK-329 have helped clarify the interaction between CCK and morphine-induced analgesia. Treatment with MK-329 enhances morphine analgesia and chronic treatment with MK-329 prevents the development of tolerance to morphine analgesia. However, the antagonist does not prevent naloxone-precipitated withdrawal symptoms in morphine-dependent rats. In man, caerulein prevents pain associated with gall-bladder contraction, probably by relaxation of the sphincter of Oddi. Caerulein has also been shown to reduce renal colic and the pain of intermittent claudication. Preliminary clinical studies with the weak, non-selective, CCK antagonist proglumide, indicate an enhancement of morphine analgesia. As yet, no studies have demonstrated analgesic effects of CCK antagonists in man when administered alone.(ABSTRACT TRUNCATED AT 400 WORDS)     

Postprandial control of gallbladder contraction and exocrine pancreatic secretion in man

To explore the interactions between cholecystokinin (CCK) and the cholinergic system, we compared the effect of cholinergic or peptidergic CCK blockade on gallbladder contraction and pancreatic enzyme secretion using atropine and loxiglumide (a specific CCK antagonist) as pharmacological tools. Gallbladder contraction was measured by sonography and pancreatic secretion by a marker perfusion and aspiration technique. Graded doses of exogenous CCK8 induced dose-dependent contractions of the gallbladder and increasing enzyme outputs. Loxiglumide (10 mg kg-1 h-1) abolished the gallbladder response and prevented an increase in pancreatic enzyme secretion to CCK8. Atropine (5 micrograms kg-1 h-1), however, only reduced gallbladder contraction and enzyme output to CCK8. Gallbladder volumes decreased maximally to 12 +/- 4% after oral food, whereas enzyme output and plasma CCK levels increased 6- to 8-fold. Loxiglumide completely abolished gallbladder contraction and inhibited enzyme secretion by 30%. Atropine caused a small reduction in gallbladder volumes, but essentially blocked postprandial enzyme secretion. The results indicate that CCK is the major regulator of gallbladder contraction with the cholinergic system modulating the response, while the exocrine pancreas is crucially dependent on a cholinergic background with CCK modulating the secretory response.     

Effect of somatostatin on postprandial gallbladder relaxation

Although the inhibitory effect of somatostatin (SST) on gallbladder contraction is well known, the influence of SST on gallbladder motility during the late postprandial or relaxation phase has not been studied. We therefore investigated the effect of SST on gallbladder relaxation and gut hormone release during the late postprandial phase. Eight healthy volunteers participated in two experiments performed in random order during continuous infusion of either SST or saline (placebo) starting 2 h after meal ingestion. At regular intervals, gallbladder volumes were measured (ultrasonography) and blood samples were taken for determination of plasma cholecystokinin (CCK), pancreatic polypeptide (PP), peptide YY (PYY) and neurotensin levels (radioimmunoassay). Postprandial gallbladder contraction was similar in both experiments: 68 ± 4% vs. 66 ± 4%. During SST infusion, postprandial gallbladder contraction was significantly (P<0·01) reduced (2874 ± 813% *240 min) compared with saline (9391 ± 1595% *240 min). Plasma CCK, PP, PYY and neurotensin levels were in the same range in the early postprandial phase but were significantly reduced during SST infusion compared with placebo (late postprandial phase). Plasma levels of CCK correlated with gallbladder volumes during both the contraction and relaxation phase (r=0·68, P=0·01 and r=0·61, P=0·008, respectively). SST enhances gallbladder relaxation and reduces hormone secretion in the late postprandial phase. The results point to an association between CCK and gallbladder volume not only during the postprandial contraction phase but also during the relaxation phase.     

Effect of a single oral dose of two erythromycin ethylsuccinate formulations on gastric emptying in healthy volunteers: A scintigraphic study

Summary— Macrolides are potential gastrokinetic agents. The purpose of this study was to assess the effect of a single oral dose of two erythromycin formulations on gastric emptying of the solid and liquid phases in twelve healthy volunteers and to seek a correlation between pharmacokinetic parameters and changes in gastric emptying. The gastric emptying times of liquids and solids were measured simultaneously by means of a scintigraphic technique after a single oral administration of amorphous erythromycin ethylsuccinate (500 mg), crystalline erythromycin ethylsuccinate (1000 mg) or a placebo, in a double-blind crossover study in three separate weeks. Blood samples were obtained for erythromycin assay. The two oral formulations induced a similar acceleration of gastric emptying. When compared to the placebo, both erythromycin preparations significantly shortened the gastric transit time of solids and liquids (respectively 30% and 20% on average, p < 0.01). The incidence of gastrointestinal side-effects was similar with the two erythromycin forms and the placebo. No correlation was found between the peak serum erythromycin concentrations and the solid or liquid gastric half-lives. With the amorphous formulation, the area under the plasma time-concentration curves was small and solid and liquid gastric emptying were strongly accelerated, pointing to a direct effect on the gastrointestinal smooth muscle.     

Effects of cholestyramine on gallbladder and gastric emptying in obese and lean subjects

Abstract. Gallbladder stasis is frequent in obese subjects and may contribute to their increased risk for gallstone formation. The bile salt sequestrant cholestyramine acutely enhances postprandial gallbladder emptying in lean subjects, through dis-inhibition of a negative feedback between intraluminal bile salts and CCK release. In this study the effect of cholestyramine on both gallbladder and gastric antrum dynamics were studied by realtime ultrasonography in 12 obese and 15 lean subjects. For the acute study, on different days, subjects ingested a liquid meal (two egg yolks plus water 200 mL, 50 kJ) or a meal with 4g cholestyramine. Gallbladder emptying was impaired in obese patients who had significantly larger fasting gallbladder volume (39.4 ± 6.9 vs. 21.6 ± l.7mL, P <0.02), larger residual volume (12.3 ± 1.8 vs. 4.0 ± 0.5ml, P < 0.0006) and slower emptying time ( T /2: 33 ± 2 vs. 21 ± 2 min, P < 0.05) than lean subjects. Integrated antral emptying was also less in obese than lean subjects (5521 ± 578 vs. 7908 ± 491 % 120min^-1, P <0.02). Cholestyramine enhanced postprandial gallbladder emptying in both obese and lean subjects. Gastric emptying was delayed with cholestyramine in lean but not obese subjects. For the chronic study, after 1 month therapy with cholestyramine (4 g every 2 days), the motility tests were repeated in nine obese subjects. Gallbladder and gastric responses to a test meal, with or without cholestyramine, were preserved. We conclude that both gallbladder and antral emptying of a liquid test meal are impaired in obese subjects. Gallbladder emptying improves after acute administration of a low dose cholestyramine with test meal. This effect is sustained after 1 month treatment with a low dose of cholestyramine and does not interfere with gastric emptying of obese patients. Cholestyramine may improve gallbladder hypomotility in obese people.     

Effect of sucralfate and an aluminum hydroxide gel on gastric emptying of solids and liquids

Our purpose was to investigate whether an aluminum-containing compound (sucralfate) and an aluminum-containing antacid (Amphojel; Wyeth Laboratories), both of which are commonly used in peptic ulcer disease, affect gastric emptying. Gastric emptying was studied in ten healthy subjects with the double isotope technique to assess simultaneous emptying rates of the solid and liquid components of a meal. 99mTechnetium sulfur colloid-labeled chicken liver served as the solid component and 111indium diethylenetriamine penta-acetic acid-labeled water was the liquid component. In a randomized, double-blind fashion, 1 gm sucralfate and 30 ml aluminum hydroxide gel were compared with placebo on separate days. Subjects ate the isotope-labeled test meal after dosing, and gastric emptying was monitored for 3 hours by a gamma-camera interfaced with a computer. There was no significant change in gastric emptying of either solids or liquids after sucralfate. The aluminum hydroxide gel slowed the gastric emptying rate for solids more than did the placebo, but this difference was significant only at the intervals of 165 and 180 minutes after the meal. We conclude that aluminum in the form of therapeutic doses of sucralfate does not delay gastric emptying of solids or liquids in normal subjects, while the larger amount of aluminum in therapeutic doses of the antacid gel has some slowing effect on gastric emptying of the solid components of a meal.     

Dose-dependent gastrointestinal effects of the somatostatin analog lanreotide in healthy volunteers

OBJECTIVE: To investigate the gastrointestinal effects of intravenous lanreotide. METHODS: Twenty healthy male subjects participated in 2 subsequent placebo-controlled, double-blind crossover studies. The effects of 3 doses of lanreotide (50, 100, and 200 microg/h) were investigated on 24-hour intragastric acidity (study I), food-stimulated gallbladder contraction, and plasma cholecystokinin release (study II). RESULTS: Lanreotide showed linear pharmacokinetics. It raised median intragastric pH significantly and in a dose-dependent manner: from 1.4+/-0.2 (placebo) to 2.5+/-0.8 (P < .002) during administration of 50 microg/h lanreotide, to 3.2+/-0.7 (P < .001) during 100 microg/h lanreotide, and to 4.3+/-0.7 (P < .001) during 200 microg/h lanreotide. However, no significant inhibition of gastrin secretion could be established. All doses completely inhibited postprandial gallbladder contraction. CONCLUSION: Intravenous administration of lanreotide at rates applied in this study was able to significantly inhibit intragastric acid secretion and postprandial gallbladder contraction; under these conditions few untoward effects were noted.     

Sequential single doses of cisapride, erythromycin, and metoclopramide in critically ill patients intolerant to enteral nutrition: a randomized, placebo-controlled, crossover study

OBJECTIVE: To evaluate the comparative efficacy of enteral cisapride, metoclopramide, erythromycin, and placebo for promoting gastric emptying in critically ill patients with intolerance to gastric enteral nutrition (EN). DESIGN: A randomized, crossover study. SETTING: Adult medical intensive care unit at a university-affiliated private hospital and trauma intensive care unit at a university teaching hospital. PATIENTS: Ten adult, critically ill, mechanically ventilated patients not tolerating a fiber-containing EN product defined as a single aspirated gastric residual volume >150 mL or two aspirated gastric residual volumes >120 mL during a 12-hr period. INTERVENTIONS: Patients received 10 mg of cisapride, 200 mg of erythromycin ethylsuccinate, 10 mg of metoclopramide, and placebo as 20 mL of sterile water every 12 hrs over 48 hrs. Acetaminophen solution (1000 mg) was administered concurrently. Gastric residual volumes were assessed, and plasma acetaminophen concentrations were serially determined by TDx between 0 and 12 hrs to evaluate gastric emptying. MEASUREMENTS AND MAIN RESULTS: Gastric residual volumes during the study were not significantly different between agents. No differences in area under the concentration vs. time curve or elimination rate constant were identified between agents. Metoclopramide and cisapride had a significantly shorter mean residence time of absorption than erythromycin (6.3+/-4.5 [SEM] mins and 10.9+/-5.8 vs. 30.1+/-4.5 mins, respectively [p<.05]). Metoclopramide (9.7+/-15.3 mins) had a significantly shorter time to peak concentration compared with erythromycin and placebo (60.7+/-8.1 and 50.9+/-13.5 mins, respectively [p<.05]). The time to onset of absorption was significantly shorter for metoclopramide vs. cisapride (5.7+/-4.5 vs. 22.9+/-5.7 mins [p<.05]). CONCLUSION: In critically ill patients intolerant to EN, single enteral doses of metoclopramide or cisapride are effective for promoting gastric emptying in critically ill patients with gastric motility dysfunction. Additionally, metoclopramide may provide a quicker onset than cisapride.     

The effect of equicaloric medium-chain and long-chain triglycerides on pancreas enzyme secretion

It has been shown previously that medium chain triglycerides (MCT) do not affect gallbladder emptying and cholecystokinin (CCK) release. The effect of MCT on exocrine pancreas secretion in humans is unknown. We have compared the effect of enteral administration of MCT versus long chain triglycerides (LCT) on exocrine pancreatic secretion. Eight healthy subjects (three female, five male; mean age 22 +/- 1.9 years) participated in two experiments, performed in random order. Duodenal contents, obtained by aspiration, were used to calculated the output of pancreatic enzymes and bilirubin. An equicaloric amount of either MCT or LCT (2 kcal min-1) oil was continuously administered in the proximal jejunum for 2 h. Gallbladder volume was measured by ultrasonography and blood samples were drawn for determination of CCK. The experiments consisted of 1 h basal secretion, 2 h of continuous oil administration and 1 h poststimulation. During the LCT feeding the pancreatic enzyme secretion, bilirubin output, gallbladder emptying and CCK release increased significantly (P < 0.05) over basal levels. MCT had no effect on pancreatic enzyme secretion nor gallbladder emptying or CCK release. We conclude that enteral administration of MCT in the proximal jejunum does not stimulate exocrine pancreatic secretion nor gallbladder contraction or CCK release, in contrast to an equicaloric amount of LCT.     

Hyperglycemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in healthy subjects

BACKGROUND: Acute hyperglycemia has been associated with delayed gastric emptying of solid foods in healthy control subjects. Erythromycin has been found to be a gastrointestinal prokinetic agent in humans. We examined whether acute steady-state hyperglycemia reduces the erythromycin-induced acceleration of gastric emptying of a solid meal after a fasted state in healthy subjects. METHODS: Twelve healthy subjects ate standard solid meals that had been radiolabeled. Gastric emptying was measured by scintigraphy during normoglycemia (5-8.9 mmol/L glucose) and hyperglycemia induced by intravenous glucose (16-19 mmol/L glucose) after administration of placebo or 200 mg of erythromycin intravenously. Emptying was measured randomly on 4 different days. RESULTS: Administration of erythromycin during normoglycemia or induced hyperglycemia compared with placebo accelerated the gastric emptying of the solid meal but did not completely normalize the delay caused by hyperglycemia versus normoglycemia (p < 0.001). In both conditions, erythromycin versus placebo significantly reduced the lag-phase duration (9.7 +/- 2.3 min and 22.0 +/- 3.9 min vs. 38.3 +/- 5.7 min and 49.5 +/- 6.0 min, respectively; p < 0.001), gastric emptying of the half meal (39.2 +/- 4.0 min and 52.0 +/- 7.1 min vs. 75.7 +/- 11.8 min and 94.0 +/- 13.4 min, respectively; p < 0.001), and the percentage of meal retained in the stomach 120 min postprandially (p < 0.001). CONCLUSION: The erythromycin-induced acceleration effect on gastric emptying was related to the plasma glucose level. Hyperglycemia might have chosen a cholinergic antagonist pathway that delayed gastric emptying of solids. Even though induced hyperglycemia inhibited gastric emptying, erythromycin accelerated the gastric emptying rate through two distinct pathways: cholinergic and noncholinergic.     

Changes of gallbladder and gastric dynamics in patients with acute hepatitis A

Transient alterations of gallbladder morphology and dynamics have been reported in patients with during acute hepatitis A. The presence of dyspepsia also suggests involvement of gastric motility. During a 60-day follow-up, we investigated gallbladder and gastric motility in relation to dyspepsia in acute viral hepatitis A patients. Twenty patients were assessed at referral (day 0) and at days 7, 21, 42 and 60 and compared with 20 healthy volunteers. Gallbladder morphology and motility and gastric motility were assessed in the fasting and postprandial period by functional ultrasonography using a liquid test meal. Dyspeptic symptoms were scored. At day 0, fasting gallbladder volume was 5.9 +/- 1.3 mL, 32.6 +/- 4.6 mL, and 21.5 +/- 1.9 mL (mean +/- SE) in patients with gallbladder sludge (n = 7), without sludge (n = 13) and controls, respectively (P < 0.05 in sludge vs. no sludge and controls; P < 0.05 in no sludge vs. controls, ANOVA). Small fasting gallbladder volume in patients with sludge increased and sludge disappeared within 7 days. At day 0, patients with sludge also had increased thickness of fasting gallbladder wall and increased serum transaminase levels compared with patients without sludge and controls. Gallbladder contraction was similar in patients and controls. However, patients had delayed gastric emptying, which positively correlated with dyspepsia score. Gallbladder morphological changes observed in the acute phase of hepatitis A are transient and are associated with hepatocellular damage. Gastric emptying is delayed during the first week of disease and is associated with dyspeptic symptoms.     

Sonographic evaluation of gallbladder volume and ejection fraction in obese women without gallstones

PURPOSE: Obese people have an increased incidence of gallstones. Although the exact pathogenic mechanisms of gallstone development are unknown, impaired gallbladder emptying has been suggested as a possible underlying mechanism. Our aim was to investigate this possibility by evaluating gallbladder motility and related factors in obese and nonobese women without gallstones. METHODS: This study included 79 obese women and 25 nonobese healthy women. Using real-time sonography, we evaluated fasting and postprandial (15th-, 30th-, 45th-, 60th-, 75th-, 90th-, 120th-, and 150th-minute) gallbladder volumes and ejection fractions. The smallest postprandial volume was considered the residual volume. RESULTS: Mean (+/- standard deviation) fasting and residual gallbladder volumes were 43.2 +/- 18.3 cm(3) and 21.4 +/- 11.2 cm(3), respectively, in the obese women and 28.1 +/- 12.3 cm(3) and 7.9 +/- 3.4 cm(3), respectively, in the nonobese women. Maximal ejection fraction was 49 +/- 19% in obese women and 63 +/- 29% in nonobese women (p = 0.001). The fasting and residual volumes and the postprandial volumes at all time points were higher in obese women than in nonobese women (p < 0.001). In addition, 15th-, 30th-, 45th-, 60th-, 75th-, and 90th-minute postprandial ejection fractions were lower in obese women than in nonobese women (p < 0.001). Positive correlations were found between fasting gallbladder volume and body mass index and body fat weight and between residual volume and body mass index, waist circumference, body fat percentage, and body fat weight (p < 0.05 for all comparisons). CONCLUSIONS: Our results show that fasting and postprandial gallbladder volumes are higher and that postprandial gallbladder motility is lower in obese than in nonobese women. There are positive correlations between fasting gallbladder volume and body weight, body mass index, and body fat weight.     

Roles of endogenous cholecystokinin in biliary, pancreatic and gastric function: studies with L-364,718, a specific cholecystokinin receptor antagonist

A new, highly potent antagonist of gut cholecystokinin (CCK) receptors has been examined for effects upon postprandial biliary and exocrine pancreatic secretion in conscious dogs with chronic duodenal pouches. This drug (L-364,718) markedly inhibited the postprandial increases in biliary volume, bile acid and bilirubin secretion. However, even at high p.o. doses relative to its ability to antagonize the effects of exogenous CCK, no effects were observed upon the pancreatic secretion of either fluid volume or amylase and lipase under similar conditions. In additional studies, pretreatment with L-364,718 did not significantly reverse the inhibitory effects of a fatty acid salt (sodium oleate) upon gastric emptying in gastric fistula dogs. Moreover, pretreatment with L-364,718 had no significant effects upon postprandial acid and pepsin secretion in lesser curvature (vagally innervated) pouch dogs or did it affect basal (interdigestive) gastric secretion in rats. These results suggest that endogenous CCK plays a critical physiological role in regulating postprandial biliary outflow, but not pancreatic enzyme secretion or the gastric emptying of at least liquid fatty substances. The latter two findings stand in contrast with classical views regarding the physiological function(s) of this hormone.     

腹腔镜全胃切除术后不同消化道重建方式对胃癌患者胆囊收缩功能及术后并发症的影响

目的观察腹腔镜全胃切除术后采取不同消化道重建方式对胃癌患者胆囊收缩功能、术后并发症情况的影响。方法选取我院行腹腔镜全胃切除术治疗的胃癌患者98例,利用随机数字表法分为两组各49例,A组采取功能性空肠间置代胃重建术(FJI),B组采取Roux-en-Y重建术,比较两组手术指标、手术前后营养代谢情况体质量指数(BMI)、血红蛋白(Hb)、总蛋白(TP)、预后营养指数(PIN)、胆囊收缩功能胆囊容积、胆囊排空率、胆囊收缩素(CCK)水平、胃肠功能(代胃肠管最大径值与管内钡剂停留时长)及术后并发症情况等。结果两组患者手术重建时间与术中出血量比较差异无统计学意义(P>0.05);A组术后6个月BMI、Hb、TP、PIN均显著高于B组;术后胆囊容积、CCK水平低于B组,胆囊排空率高于B组;术后6个月代胃肠管最大径值大于B组,管内钡剂停留时间长于B组;术后R-S综合征与倾倒综合征发生率明显低于B组,差异均有统计学意义(P<0.05)。结论胃癌患者腹腔镜全胃切除术后采取FJI更益于胆囊收缩功能恢复,可更好促进机体营养代谢,提高消化吸收功能,降低术后并发症风险。     

Predictors of delayed gastric emptying in diabetes.

OBJECTIVE: To define the predictors of the rate of gastric emptying in patients with diabetes. RESEARCH DESIGN AND METHODS: A total of 101 outpatients with diabetes (79 type 1 and 22 type 2) underwent measurements of gastric emptying of a solid/liquid meal (scintigraphy), upper gastrointestinal symptoms (questionnaire), glycemic control (blood glucose concentrations during gastric emptying measurement), and autonomic nerve function (cardiovascular reflexes). RESULTS: The gastric emptying of solid and/or liquid was delayed in 66 (65%) patients. Solid (retention at 100 min 64 +/- 3.2 vs. 50.2 +/- 3.6%, P < 0.005) and liquid (retention at 100 min 22.7 +/- 1.7 vs. 16.0 +/- 1.8%, P < 0.001) gastric emptying was slower in women than in men. Of all upper gastrointestinal symptoms (including nausea and vomiting), only abdominal bloating/fullness was associated with slower gastric emptying (P < 0.005). A multiple regression analysis demonstrated that both abdominal bloating/fullness and female sex were predictors of slower gastric emptying of both solids and liquids. CONCLUSIONS: We conclude that the presence of abdominal bloating/fullness but not any other upper gastrointestinal symptom is associated with diabetic gastroparesis and that gastric emptying is slower in diabetic women than in diabetic men.