Effects of a novel cholecystokinin (CCK) receptor antagonist, MK-329, on gallbladder contraction and gastric emptying in humans. Implications for the physiology of CCK.

To explore the physiology of cholecystokinin (CCK) in humans, we investigated the effect on gallbladder contraction and gastric emptying of a recently developed CCK receptor antagonist, MK-329. In a double-blind, four-period crossover study eight subjects received single doses of 0.5, 2, or 10 mg MK-329, or placebo, followed by an intravenous infusion of CCK-8 (30 pmol/kg.h). In placebo-treated subjects gallbladder volumes decreased on average to 43% of initial volumes after 2 h of CCK infusion. MK-329 caused a dose-dependent inhibition of CCK-stimulated gallbladder contraction with 10 mg producing complete blockade (P less than 0.01, cf. placebo). Gallbladder contraction and gastric emptying rates after a mixed meal were then measured in a two-period crossover study. Subjects received placebo or 10 mg of MK-329 2 h before eating. Gastric emptying of both solids and liquids was measured simultaneously by gamma scintigraphy. In placebo-treated subjects plasma CCK levels increased postprandially to 2.3 pM, gallbladder volumes decreased 68.4 +/- 3.8% (SE), and the times for 50% emptying of liquids and solids from the stomach were 58 +/- 10 and 128 +/- 8 min, respectively. In MK-329-treated subjects there was a marked elevation in peak CCK levels to 13.8 pM (P less than 0.01, cf. placebo), and gallbladder contraction was completely inhibited. Solid and liquid emptying rates were unaffected. These findings demonstrate that (a) MK-329 is a potent, orally active antagonist of CCK in humans, and (b) CCK is the major regulator of postprandial gallbladder contraction. These data also support the concept of negative feedback regulation of CCK secretion and suggest that mechanisms other than CCK play a dominant role in the regulation of postprandial gastric emptying rates.     

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.     

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.     

Infusion of cholecystokinin octapeptide in man: relation between plasma cholecystokinin concentrations and gallbladder emptying rates

To establish the sensitivity of the gallbladder in relation to plasma concentrations of cholecystokinin, a dose-response study was performed in five normal volunteers. Cholecystokinin octapeptide was infused in ascending incremental dose sequence, interval blood samples taken for estimation of plasma hormone concentrations and gallbladder emptying rates monitored continuously using 99mTc-HIDA. In five other volunteers, gallbladder emptying rates following a liquid fat meal were measured. Infusion rates of 0.0, 0.75 +/- 0.2, 6.8 +/- 0.5, 23.8 +/- 1.6 and 66.1 +/- 2.5 pmol cholecystokinin kg-1 h-1 produced plasma concentrations of less than 3.0 (undetectable), less than 3.0, 6.6 +/- 1.8, 13.3 +/- 1.5 and 26.9 +/- 2.9 pmol l-1 respectively and gallbladder emptying rates (% min-1) of 0.0, 0.0, 0.14 +/- 0.15, 1.57 +/- 0.38 and 4.29 +/- 1.12. Following the fat meal, peak plasma cholecystokinin concentrations reach 30 pmol l-1 and gallbladder emptying rates (% min-1) are 3.86 +/- 1.01. We conclude that the threshold of the gallbladder to circulating cholecystokinin octapeptide is around 6 pmol l-1, but that infusions which result in plasma levels of around 25 pmol l-1 produce gallbladder emptying rates comparable with those seen after oral fat. This suggests that the gallbladder is equally sensitive to endogenous and exogenous cholecystokinin and that plasma concentrations observed after oral fat can entirely account for the gallbladder response.     

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.     

雌二醇对卵巢去势大鼠胃排空的调节作用及其机制研究

目的 探讨雌二醇（E2）对卵巢切除大鼠血浆胆囊收缩素（CCK）及胃组织内胆囊收缩素受体A（CCKA）表达水平的影响，以期阐明雌二醇调节胃肠道运动功能的机制。方法 给予卵巢切除大鼠殴替代治疗，用放射免疫分析法测定血浆CCK浓度、用孵mTc-DTPA液体试餐测定胃排空率，以及用Western blot法检测胃组织内CCKA的表达量。结果 E2呈剂量依赖性地抑制卵巢切除大鼠的胃排空，升高血浆CCK的浓度，同时引起胃组织内CCKA受体表达增高。结论 雌二醇对卵巢切除大鼠的胃排空具有抑制作用，这种作用是通过促进CCK的分泌以及上调胃内CCKA受体的表达实现的。     

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.     

Feed intolerance in critical illness is associated with increased basal and nutrient-stimulated plasma cholecystokinin concentrations

OBJECTIVE: Delayed gastric emptying and intolerance to gastric feeding occur frequently in the critically ill. In these patients, gastric motor responses to nutrients are disturbed. Cholecystokinin (CCK) slows gastric emptying. The aim of this study was to determine plasma CCK concentrations during fasting and in response to small-intestine nutrient infusion in critically ill patients. DESIGN: Randomized, controlled trial. SETTING: Level 3, mixed medical and surgical intensive care unit. SUBJECTS: A total of 31 mechanically ventilated, critically ill patients (23 men, 51 +/- 3 yrs) and 28 healthy subjects (21 men, 43 +/- 2 yrs). INTERVENTIONS: Subjects received two 60-min duodenal infusions of Ensure (complete balanced nutrition), at 1 and 2 kcal/min, in a randomized, single-blind fashion. The nutrient infusions were separated by a 2-hr "washout" period. Blood samples for measurement of plasma CCK concentrations were obtained immediately before and every 20 mins during nutrient infusion. MEASUREMENTS AND MAIN RESULTS: Baseline and nutrient-stimulated plasma CCK concentrations were higher in critically ill patients compared with healthy subjects (p < .001). The magnitude of the rise in plasma CCK in response to nutrients was also greater in the critically ill (p < .01). Of the 23 patients who received enteral nutrition before the study, nine were intolerant of gastric feeding. In these patients, both the baseline plasma CCK concentration and the magnitude of CCK increase during nutrient infusions were greater than in patients with feed tolerance (p < .002). Impaired renal function was associated with an increased baseline CCK concentration but had no effect on the CCK response to nutrients. CONCLUSIONS: Both fasting and nutrient-stimulated plasma CCK concentrations are increased in critically ill patients, particularly in those with feed intolerance. This may provide a humoral mechanism for delayed gastric emptying seen in critical illness.     

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.     

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.     

Increased plasma cholecystokinin levels and small gall bladders in adult patients with cystic fibrosis.

1. In patients with cystic fibrosis, abnormalities in plasma cholecystokinin level and gall-bladder emptying may contribute to the development of maldigestion and gall-stones. 2. Therefore, we have measured plasma cholecystokinin levels and gall-bladder volumes before and after ingestion of a standard breakfast in eight adult patients with cystic fibrosis and in eight normal control subjects. 3. In the patients with cystic fibrosis basal (2.8 +/- 0.4 pmol/l; P less than 0.05, t-test) and maximum post-prandial (5.7 +/- 0.5 pmol/l; P less than 0.05, t-test) plasma cholecystokinin levels were significantly higher than those in the control subjects (1.9 +/- 0.1 pmol/l, and 4.5 +/- 0.2 pmol/l, respectively). On the other hand, integrated plasma cholecystokinin secretion in response to the meal was similar (t-test, P = 0.4 versus control subjects). The increased plasma cholecystokinin levels in the patients with cystic fibrosis were accompanied by reduced gallbladder volumes in both the basal (7.8 +/- 2.1 cm3 versus 20.9 +/- 2.3 cm3 in control subjects; P less than 0.005, t-test) and the post-prandial state (2.2 +/- 1.0 cm3 versus 4.8 +/- 0.8 cm3 in control subjects; P = 0.06, t-test). Gall-bladder emptying in the patients with cystic fibrosis was well preserved (70 +/- 7% versus 78 +/- 9% in control subjects; P = 0.4, t-test). 4. In comparison with normal control subjects, patients with cystic fibrosis have an increased basal plasma cholecystokinin level and a reduced gall-bladder volume, whereas post-prandial gall-bladder emptying and plasma cholecystokinin secretion are not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)     

A pharmacological dose of glucagon suppresses gastric emptying of a radiolabelled solid meal in humans

The effect of glucagon (143 nmol i.v. bolus followed by 430 nmol infused at a constant rate over 90 min) vs placebo (normal saline) on gastric emptying was examined in a blind randomized study in eight healthy males. The gastric emptying of a radiolabelled solid meal was measured with the use of a gamma camera. Glucagon elicited a pronounced delay in gastric emptying in all subjects examined--mean gastric transit time MTT90 glucagon 44.2 +/- 0.22 min vs placebo 38.6 +/- 0.74 min, p less than 0.001.     

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.     

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.     

Prevalence of delayed gastric emptying in diabetic patients and relationship to dyspeptic symptoms: a prospective study in unselected diabetic patients

OBJECTIVE: Data on the prevalence of abnormal gastric emptying in diabetic patients are still lacking. The relation between gastric emptying and dyspeptic symptoms assessed during gastric emptying measurement has not yet been investigated. The aim was to investigate the prevalence of delayed gastric emptying in a large cohort of unselected diabetic patients and to investigate the relation between gastric emptying and gastrointestinal sensations experienced in the 2 weeks before and during the test meal, prospectively. RESEARCH DESIGN AND METHODS: Gastric emptying was evaluated in 186 patients (106 with type 1 diabetes, mean duration of diabetes 11.6 +/- 11.3 years) using 100 mg (13)C-enriched octanoic acid added to a solid meal. RESULTS: Gastric emptying was significantly slower in the diabetic subjects than in the healthy volunteers (T(50): 99.5 +/- 35.4 vs. 76.8 +/- 21.4 min, P < 0.003; Ret(120 min): 30.6 +/- 17.2 vs. 20.4 +/- 9.7%, P < 0.006). Delayed gastric emptying was observed in 51 (28%) diabetic subjects. The sensations experienced in the 2 weeks before the test were weakly correlated with the sensation scored during the gastric emptying test. Sensations assessed during the gastric emptying test did predict gastric emptying to some extent (r = 0.46, P < 0.0001), whereas sensations experienced in the previous 2 weeks did not. CONCLUSIONS: This prospective study shows that delayed gastric emptying can be observed in 28% of unselected patients with diabetes. Upper gastrointestinal sensations scored during the gastric emptying tests do predict the rate of gastric emptying to some extent and sensation experienced during daily life does not.     

Comparison of cisapride and metoclopramide for facilitating gastric emptying and improving tolerance to intragastric enteral nutrition in critically III, mechanically ventilated adults.

BACKGROUND: Placebo-controlled studies have indicated that both cisapride and metoclopramide promote gastric motility in critically ill patients. Objective: This study was conducted to compare cisapride and metoclopramide for facilitating gastric emptying and improving tolerance to intragastric enteral nutrition (EN) and to evaluate the relationship between aspirated gastric residual volume and gastric emptying function in this patient population. METHODS: In this double-blind study, critically ill, mechanically ventilated patients with an aspirated gastric residual volume > or = 150 mL while receiving intragastric EN were randomized to receive enteral cisapride 10 mg or metoclopramide 10 mg every 6 hours for a total of 7 doses. The acetaminophen-absorption method was used to assess gastric emptying at baseline and 30 minutes after the seventh dose by determining the area under the plasma concentration-time curve at 240 minutes (AUC240), maximum concentration (Cmax), and time to Cmax (Tmax). Gastric residual volume was measured every 6 hours before dosing. RESULTS: Fourteen patients were included in the study, 7 in each group. Patient characteristics were similar in the 2 groups. Compared with baseline, metoclopramide significantly accelerated Tmax (39.00 +/- 15.56 min with metoclopramide vs 103.71 +/- 47.35 min at baseline; P = 0.018) and increased Cmax (12.94 +/- 6.68 mg/L vs 6.97 +/- 4.78 mg/L; P = 0.018) and AUC240 (1,421.43 +/- 780.31 mg/L x min vs 839.00 +/- 545.58 mg/L x min; P = 0.043). Cisapride increased Cmax from baseline (12.27 +/- 8.95 mg/L vs 4.53 +/- 2.37 mg/L, respectively), but the difference was not statistically significant. Gastric residual volume was significantly reduced from baseline after 3 doses of metoclopramide (from 268.7 +/- 112.3 mL to 57.0 +/- 23.1 mL; P < 0.05) and was significantly lower after the seventh dose of metoclopramide than after the seventh dose of cisapride (5.3 +/- 8.2 mL vs 41.4 +/- 39.7 mL, respectively; P = 0.05). Cmax at baseline and residual volume at study entry were inversely correlated (r = -0.50; P = 0.049). Conclusions: Both cisapride and metoclopramide enhanced gastric motility and improved tolerance to intragastric EN. Metoclopramide reduced gastric residual volume to a significantly greater extent than did cisapride. Only Cmax at baseline was inversely associated with residual volume.     

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...     

Impaired fatty-meal-stimulated gallbladder contractility in patients with Crohn's disease.

1. The incidence of gallstones in patients with Crohn's disease is increased compared with that in healthy control subjects. This is in part due to reduced terminal ileal bile salt absorption and consequent increased cholesterol saturation in bile. The aim of this study was to evaluate gallbladder contractility, a second important factor in the pathogenesis of gallstones, in Crohn's disease. 2. Thirty patients with Crohn's disease and no known biliary tract disease and nine healthy control subjects were studied. After an overnight fast, gallbladder volume was determined by real-time ultrasonography before and 10, 20, 30, 40, and 50 min after ingestion of a standard liquid fatty meal. 3. Compared with healthy control subjects, patients with Crohn's disease had similar fasting gallbladder volumes (control, 18.7 +/- 2.3 ml; Crohn's disease, 18.2 +/- 2.3 ml). Percentage emptying was significantly impaired at 30, 40 and 50 min in patients with Crohn's disease compared with control subjects. Patients with Crohn's disease limited to the small bowel had gallbladder contractility that was comparable with that of control subjects, whereas in those with large-bowel disease, minimum residual gallbladder volume was significantly smaller than in control subjects. Patients with both large- and small-bowel Crohn's disease demonstrated the most marked abnormalities, with gallbladder volumes significantly larger than those of control subjects at 30, 40 and 50 min. Likewise, patients with Crohn's disease who had undergone previous bowel resection had impaired emptying at 30, 40 and 50 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cholecystokinin is a physiological hormonal mediator of fat-induced inhibition of gastric emptying in man

The effect of cholecystokinin-33 on gastric emptying was studied in eight healthy men. The test meal was a firm custard pudding, labelled with 99mTc-Chelex-100 particles. Gastric emptying rate was measured, using a dual-headed gamma camera, and was expressed as the half time of the emptying curve. Plasma cholecystokinin concentrations were determined by radioimmunoassay. Subjects were studied three times: (i) during infusion of saline; during cholecystokinin infusion, (ii) 0.375 IDU kg-1 h-1 and (iii) 0.75 IDU kg-1 h-1. Furthermore, plasma cholecystokinin was determined after a regular meal. During saline, plasma cholecystokinin increased minimally. After the regular meal it increased from 1.6 to 6.5 pmol l-1 at 30 min, decreasing to 5.3 pmol l-1 at 60 min. During the lower and higher doses of cholecystokinin it increased from 1.0 and 1.4 to 4.5 and 7.3 pmol l-1, respectively. The lower and higher doses significantly (P less than 0.05) increased half emptying time, from 45 +/- 8 to 86 +/- 17 and 198 +/- 50 min, respectively. Cholecystokinin is most likely a physiological hormonal mediator of fat-induced inhibition of gastric emptying.     

Elevated fasting cholecystokinin levels in pancreatic exocrine impairment: evidence to support feedback regulation

Previous studies have suggested that intraduodenal protease suppression of pancreatic exocrine secretion may be mediated through cholecystokinin (CCK) release. Our study compares basal plasma immunoreactive CCK concentrations in normal human subjects with those obtained in patients with chronic pancreatitis. Fasting plasma samples were collected from 18 normal subjects and from 18 patients with chronic pancreatitis. Eight patients had mild to moderate pancreatic exocrine impairment, and 10 had severe exocrine insufficiency. Venous plasma immunoreactive CCK concentrations were measured with two distinct peptide region-specific antibodies. Basal plasma CCK concentration in controls was 14.3 +/- 1.3 fmol/ml (mean +/- SEM), a value significantly less than that obtained in all patients with chronic pancreatitis, 30.1 +/- 4.0 fmol/ml (p less than 0.001). Patients with mild to moderate impairment had a fasting plasma CCK concentration of 32.8 +/- 7.9 fmol/ml (vs. control p less than 0.01), and those with severe disease 27.9 +/- 3.6 fmol/ml (vs. control p less than 0.001). In five patients with mild to moderate impairment of exocrine function and pancreatic extract-responsive abdominal pain, there was a 39 +/- 11% decrease in basal CCK levels during extract therapy (p less than 0.05). Results of this study indicate that pancreatic exocrine impairment is associated with elevated basal CCK levels, which may reflect a failure to provide feedback downmodulation of CCK release.