Fasting gallbladder volume, postprandial emptying and cholecystokinin release in gallstone patients and normal subjects

Since abnormal gallbladder emptying may be a contributing factor in the development of gallstone disease, we determined fasting gallbladder volume and postprandial contraction in 20 gallstone patients and 20 normal subjects with the aid of ultrasonography. Moreover, basal plasma cholecystokinin levels and postprandial cholecystokinin (CCK) release were determined. Gallstone patients were divided into strong contractors (13 pts) and weak contractors (below 95% confidence interval for AUC contraction in % during 90 min: 7 pts). Strong contractor patients had significantly larger mean fasting volumes than normal subjects (mean +/- S.E.: 34.9 +/- 6.1 ml and 18.9 +/- 1.6 ml, respectively). This was not true for weak contractor patients (mean fasting volume 23.2 +/- 3.2 ml). Both strong contractor and weak contractor patients had significantly higher mean residual volumes than normal subjects (17.0 +/- 4.1 ml, 18.0 +/- 2.9 ml, and 8.8 +/- 1.1 ml, respectively). Absolute gallbladder emptying was significantly higher for strong contractor patients than for normal subjects, but relative emptying was the same. Opposite patterns of CCK release occurred in gallstone patients and normal subjects. In normal subjects, more CCK release was associated with stronger gallbladder emptying. In contrast, weak contractor gallstone patients had significantly higher CCK release than strong contractor patients. (AUC CCK: 304 +/- 89 pmol/l x 90 min and 106 +/- 29 pmol/l x 90 min, respectively). The present study indicates that strong contractor gallstone patients may have large residual gallbladder volumes due to large starting volumes, whereas weak contractor patients may have large residual volumes due to impaired contraction. Subjects with large fasting and residual volumes may be at increased risk for gallstone disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of acute oral erythromycin on gallbladder motility and on upper gastrointestinal symptoms in gastrectomized patients with and without gallstones: a randomized, placebo-controlled ultrasonographic study

OBJECTIVE: Gastrectomy might be a risk factor for cholelithiasis and gallbladder stasis might play a major role. We studied fasting and postprandial gallbladder motility with 600 mg oral erythromycin or placebo in gastrectomized patients (with and without gallstones) and controls. METHODS: Seventeen patients operated on for gastric cancer (subtotal gastrectomy: n = 10, total gastrectomy: n = 7) were compared with 20 sex- and body-size matched healthy controls. Subjects randomly received erythromycin or placebo 30 min before the ingestion of a standard 200 ml liquid test meal. Gallbladder volume was estimated by ultrasonography until 120 min after test meal. A visual analog scale monitored GI perception of appetite, satiety, nausea, abdominal fullness and epigastric pain. RESULTS: Gastrectomized patients had increased fasting gallbladder volume (35.9 +/- 3.4 ml versus 21.0 +/- 1.4 ml, p = 0.0005) with faster postmeal emptying (T/2 14.8 +/- 1.1 min versus 23.5 +/- 1.5 min, p = 0.00019) than controls. Six patients developed small and asymptomatic gallstones, which did not influence gallbladder motility. In these patients, fasting gallbladder volume increased with time after surgery (r = +0.82, p = 0.047). Perception of satiety, abdominal fullness, and epigastric pain after ingestion of the test meal were all significantly greater in patients than in controls. Erythromycin significantly enhanced gallbladder emptying during fasting (p = 0.001) and postprandially in both patients and controls (0.002 < p < 0.017) and significantly reduced postmeal satiety and epigastric discomfort in gastrectomized patients. CONCLUSIONS: Increased fasting volume might be a form of stasis, predisposing patients to gallstone formation. Erythromycin improves fasting and postprandial gallbladder emptying and decreases upper GI symptoms in gastrectomized patients.     

Effect of calcitonin on gall-bladder volume in man

The effect of increasing intravenous doses of synthetic salmon calcitonin (0.0044, 0.0088, 0.0175, and 0.0350 iu/kg per min) versus placebo on the fasted gall-bladder volume was assessed in seven normal subjects according to a double-blind study protocol. In addition, the action of calcitonin on meal-induced gall-bladder emptying was examined. Gall-bladder volumes were measured by means of real-time ultrasonography. Calcitonin evoked a dose-dependent relaxation of the fasted gall-bladder. A statistically significant increase of the fasted gall-bladder volume was observed with 0.0175 (23.4 +/- 5.5 cm3 placebo versus 33.9 +/- 7.7 cm3 calcitonin, P less than 0.001) and 0.0350 (21.4 +/- 4.6 cm3 placebo versus 36.1 +/- 8.4 cm3 calcitonin, P less than 0.01) iu/kg per min calcitonin, whereas a mean increase of the gall-bladder volume amounted to 32.1% and 46.5%, respectively. A significant delay of the gall-bladder emptying after calcitonin was reflected by a decrease of the ejection fraction: 23.2 +/- 8.3% calcitonin versus 57.8 +/- 6.9% placebo (P less than 0.02) at 20 min, and 40.5 +/- 8.8% calcitonin versus 67.2 +/- 3.8% placebo (P less than 0.02) at 30 min after the test meal. Calcitonin is concluded to have a potent relaxing effect on the human gall-bladder.     

Oral administration of loxiglumide (CCK antagonist) inhibits postprandial gallbladder contraction without affecting gastric emptying

The effect of a single oral dose of loxiglumide, a cholecystokinin antagonist, on postprandial gallbladder contraction and on gastric emptying was evaluated in humans. Following a 12-hr fasting period, two tablets of loxiglumide (400 mg each) or placebo was administered on different days, in random order and in a double-blind fashion to 10 healthy volunteers 15 min before the ingestion of a 1050-kcal standard meal. Gallbladder and antral volumes were measured by real-time ultrasonography in basal conditions and at fixed time intervals after the meal. Oral loxiglumide administration was followed by a total inhibition of the gallbladder contraction for 60 min after the end of the meal ingestion. Thereafter, up to the end of the study period, gallbladder volume was larger than that of the placebo study (at 300 min after the meal 2.7±1.6 ml after placebo and 8.2±3.5 ml after loxiglumide; P<0.008). No difference between placebo and loxiglumide was found in the antral volumes at any time interval (postprandial 63.5±16.5 ml after placebo and 59.4±24 ml after loxiglumide; at 300 min after the meal 20.8±13.3 ml after placebo and 18.9±9.5 ml after loxiglumide). In conclusion, a single oral dose of loxiglumide at the dose of 800 mg can inhibit postprandial gallbladder contraction without affecting gastric emptying. It would therefore appear that in man endogenous CCK, released after a solid-liquid, caloric, nutrient-balanced meal, plays a major role in the contraction of the gallbladder but does not affect gastric emptying.     

Obesity does not increase effects of synthetic ghrelin on human gastric motor functions

BACKGROUND & AIMS: Ghrelin is secreted by the stomach and stimulates food intake. Obese individuals have lower fasting plasma ghrelin levels but increased appetite, suggesting greater responses to endogenous ghrelin in obesity. The aim of this study was to compare effects of exogenous ghrelin (at a dose that stimulates growth hormone [GH] release in the physiologic range) versus placebo on gastric emptying, gastric volume, and postprandial symptoms and determine whether body mass (ranging from normal weight to obesity) influences responses to ghrelin. METHODS: After intravenous bolus synthetic human ghrelin (0.33 mug/kg) or saline, we measured plasma GH, gastric volume, and gastric emptying by combined (99m)Tc-single-photon emission computed tomography and scintigraphy ((111)In egg meal, 300 kcal) and postprandial symptoms using visual analogue scales. RESULTS: In 25 obese subjects (5 men and 20 women; body mass index [BMI], 36 +/- 4 kg/m(2)) and 13 female normal-weight (BMI, 22 +/- 2 kg/m(2)) subjects of similar ages, ghrelin increased GH levels (15.0 +/- 2.4 ng/mL) at 40 minutes postinjection and tended to decrease fasting gastric volumes compared with placebo (P = .059). There were no effects of BMI on treatment response and no differences between ghrelin and saline on postprandial (P = .09) or change in (postprandial minus fasting) gastric volumes, gastric emptying, or aggregate postprandial symptoms. Effects of ghrelin did not differ between obese and normal-weight participants. CONCLUSIONS: At doses that stimulate physiologic GH plasma levels, synthetic ghrelin tended to decrease fasting gastric volumes without altering postprandial volumes or gastric emptying in a predominantly female cohort. The data are not consistent with the hypothesis that higher body mass is associated with increased gastric responsiveness to ghrelin.     

Induced-hyperglycemia attenuates erythromycin-induced acceleration of hypertonic liquid-phase gastric emptying in type-I diabetic patients

BACKGROUND: Erythromycin has been found to be a gastrointestinal prokinetic agent of hypertonic liquids, while acute hyperglycemia has been associated with delayed gastric emptying in diabetic patients. AIM: To investigate whether hyperglycemia, per se, reduces gastric motility during erythromycin-induced acceleration on gastric emptying of hypertonic liquids in diabetic patients. METHODS: In 12 type-I diabetic patients following a hypertonic radiolabeled liquid meal, gastric emptying was measured scintigraphically during normoglycemia (5-8.9 mmol/l glucose) or hyperglycemia induced by intravenous (16-19 mmol/l) glucose infusion. The tests were performed on 4 separate days in random order after administering either placebo or 200 mg i.v. erythromycin. RESULTS: In the hyperglycemic state compared to normoglycemia, the gastric emptying of the hypertonic liquid was reduced after placebo or erythromycin administration. The lag-phase duration (17.8+/-5.5 and 7.8+/-4.5 vs. 10.8+/-3.4 and 3.7+/-2.5 min, respectively, p<0.001), the overall gastric emptying time of the half meal (52.8+/-13 and 24.9+/-5.5 vs. 42.5+/-10.5 min and 16.6+/-6 min, respectively, p<0.001) and the retained percentage of liquid meal in the stomach at 60 and 100 min postprandially (p<0.001) were significantly increased. CONCLUSIONS: The erythromycin-induced acceleration on gastric emptying of hypertonic liquids in diabetic patients is related to the plasma glucose level. The induced hyperglycemia reduces the erythromycin-induced acceleration of liquid-phase gastric emptying, decreasing the overall gastric emptying rate. In spite of the inhibitory effect of induced hyperglycemia on the gastric emptying of hypertonic liquids, erythromycin is still able to accelerate the emptying rate and could prove to be a useful prokinetic agent under hyperglycemic conditions.     

Erythromycin accelerates gastric emptying by inducing antral contractions and improved gastroduodenal coordination.

Erythromycin has been shown to act as a motilin agonist by binding to motilin receptors on gastrointestinal smooth muscle and to improve the severely impaired gastric emptying in patients with diabetic gastroparesis. To elucidate the motor pattern that accounts for this accelerated emptying, the effect of 200 mg erythromycin vs. placebo on postprandial motility of the stomach and the upper small intestine was examined in 13 normal subjects. Erythromycin significantly increased the amplitude of the antral contractions during the 2-hour postprandial study period (maximal difference in mean amplitude of distal antral contractions between erythromycin and placebo recorded from 80 to 90 minutes after meal: 123 +/- 17 vs. 44 +/- 12 mm Hg; P less than 0.005). The total number of antral contractions was not affected, but the contractions could be recorded manometrically higher up in the stomach after erythromycin than after placebo (9-12 vs. 3-6 cm above the pylorus). Antroduodenal coordination was significantly improved during the first postprandial hour, and the first normal phase 3 of the migrating motor complex, indicating the reappearance of fasting motility, occurred earlier after erythromycin than after placebo (128.3 +/- 14.3 vs. 173.4 +/- 16.1 minutes; P less than 0.05). These changes in postprandial motility induced by erythromycin may well account for its accelerating effect on gastric emptying.     

Gallbladder Fasting Volume Is Reduced and Gallbladder Postprandial Emptying Is Enhanced by Intravenous Erythromycin

It has been recently shown that erythromycin, amacrolide antibiotic, exhibits prokinetic properties, byenhancing gastric emptying in health and disease and byinducing gallbladder contraction. The aim of the study was to further investigate theeffect of intravenous erythromycin on gallbladdermotility during fasting and postprandial states. In 10healthy male subjects gallbladder emptying was assessed by ultrasonography on three differentoccasions, each in a random sequence, as follows: (1)after giving 300 ml of fresh milk and infusing normalsaline as placebo (postprandial emptying), (2) afterinfusing 200 mg of erythromycin during the fastingstate, and (3) after infusing 200 mg of erythromycinalong with ingestion of 300 ml of fresh milk. Infusionof erythromycin and placebo lasted 10 min. From the emptying curves, the duration of the lag phaseof emptying, the ejection fraction of emptying, and thetime by which maximal emptying was achieved werecalculated. Infusion of erythromycin induced animmediate contraction [lag phase (±SD): 1.3± 2.6 SD min] of the gallbladder by 42.1 ±22% of its initial volume. Infusion of erythromycinduring the postprandial state significantly decreasedthe duration of the lag phase (1.3 ± 3.5 min after erythromycinplus test meal versus 3.6 ± 4.2 min after testmeal only, P < 0.04) and significantly increased theejection fraction (78 ± 8.5% after erythromycinplus test meal versus 60.6 ± 8.5% after test meal only, P <0.0008). It is concluded that intravenously givenerythromycin induces contraction of the gallbladderduring the fasting state and enhances postprandialgallbladder emptying by accelerating the initiation and increasingthe extent of emptying.     

Cisapride in children with chronic intestinal pseudoobstruction. An acute, double-blind, crossover, placebo-controlled trial

To assess the effect of cisapride on gastrointestinal motility and gastric emptying in children with chronic intestinal pseudoobstruction, 20 children (mean age, 4.9 years; 14 female and 6 male) who required special means of alimentation or who had severe symptoms confirmed by diary during 2 weeks before the study were studied. A motility catheter with recording sites in the antrum and duodenum was placed on the first day of the study and remained in place until the end of the 5-day study. Cisapride (0.3 mg/kg PO t.i.d.) or placebo was given in double-blind randomized crossover fashion, with a 2-day "washout" interval. Antroduodenal motility was recorded on days 2 and 5. Recording consisted of 4 hours of fasting and 2 hours after a complex liquid meal labeled with 99mTc. Gastric emptying was assessed for 1 hour after the meal. Based on manometry, 16 patients had neuropathic and 4 patients had myopathic disorders. Cisapride had no effect on the discrete, qualitative abnormalities found in individual records. Cisapride increased the postprandial duodenal motility index from 1180 +/- 256 mm Hg/30 min after placebo to 2385 +/- 430 mm Hg/30 min (P less than 0.05) but had no significant effect on the antral motility index. Cisapride did not alter the profound delay in gastric emptying; time to reach 50% of initial activity (T1/2) was 105 +/- 20 vs. 93 +/- 19 minutes and percentage of retention after 60 minutes (R60) 56% +/- 4% vs. 58% +/- 4% in control vs. cisapride, respectively. In summary, in children with chronic intestinal pseudoobstruction, cisapride increased postprandial duodenal motility but did not improve gastric emptying.     

Noninvasive measurement of gastric accommodation in patients with idiopathic nonulcer dyspepsia

OBJECTIVES: Postprandial symptoms are associated with impaired postprandial gastric accommodation. The aims of this study were to apply a noninvasive method to measure accommodation of the entire stomach in healthy subjects and in patients with idiopathic dyspeptic symptoms, and to assess the frequency of abnormal gastric accommodation and emptying of solids in these patients. METHODS: In 20 healthy volunteers and 32 tertiary referral patients, we used i.v. 99mTc-single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes; we expressed the volume response to feeding ("accommodation") as the change in gastric volume and the ratio of postprandial/fasting volumes. The stomach was identified in transaxial SPECT tomographic images using a semiautomated, intensity-based extraction algorithm. Whole gastric volumes were measured using AnalyzeAVW software. Gastric emptying in patients was measured by scintigraphy. We also assessed dyspeptic symptoms and the association with normal or reduced accommodation. RESULTS: SPECT imaging detects the postprandial change in gastric volume ("accommodation") in health and disease. Among healthy subjects (eight men, 12 women), the postprandial/fasting gastric volume ratio was 4.9+/-1.7 (mean +/- SD; fifth through 95th percentiles 3-8, median 4.6). Thirteen (41%) patients with idiopathic nonulcer dyspepsia had reduced postprandial "accommodation." Gastric emptying was fast in four (13%), normal in 25 (78%), and slow in three (9%) patients. Both tests were normal in 50% of patients. Weight loss of >10 pounds tended to be more frequently observed in those with reduced "accommodation" (62% vs 32%, p = 0.09). CONCLUSIONS: SPECT imaging noninvasively measures fasting and postprandial gastric volumes in humans. Half the patients with idiopathic nonulcer dyspepsia had impaired gastric accommodation or emptying. Reduced gastric "accommodation" was observed in 41% of a group with idiopathic nonulcer dyspepsia. Abnormal gastric emptying is less frequent (22%).     

Effects of amitriptyline on gastric sensorimotor function and postprandial symptoms in healthy individuals: a randomized, double-blind, placebo-controlled trial

BACKGROUND:  Low-dose tricyclic antidepressants have been used to treat chronic somatic and gastrointestinal pain disorders, including refractory functional dyspepsia. However, there are only limited data on the effects of these drugs on upper gastrointestinal function.
AIM:  To compare the effects of two doses of amitriptyline (AMT) and placebo on gastric accommodation, emptying, satiation, and postprandial symptoms in healthy volunteers.
METHODS:  Using a parallel-group, double-blind, placebo-controlled design, 41 healthy volunteers were randomized to AMT 25 mg, AMT 50 mg, or placebo for 2 wk. During the final 3 days of therapy, the following end points were assessed: fasting and postprandial gastric volumes, 2- and 4-h gastric emptying, time and volume to maximum satiation using a nutrient drink test, and postprandial symptoms 30 min later using 10-cm visual analog scales. AMT and metabolite levels were measured.
RESULTS:  AMT slowed gastric emptying at 2 h (median 75% for placebo, 57% for AMT 25 mg, 67% for AMT 50 mg; P = 0.037) and 4 h (median 98% for placebo, 96% for AMT 25 mg, 92% for AMT 50 mg; P = 0.003). AMT did not affect gastric volumes or satiation volume, but it did reduce nausea scores at 30 min in a dose-dependent manner (median 2.1 for placebo, 0.9 for AMT 25 mg, and 0.0 for AMT 50 mg; P = 0.009).
CONCLUSION:  In healthy volunteers, AMT slows gastric emptying of solids, but it does not significantly affect gastric volumes or satiation. AMT reduces nausea after challenge with a high calorie liquid load.     

Glucose control is not improved by accelerating gastric emptying in patients with type 1 diabetes mellitus and gastroparesis. a pilot study with cisapride as a model drug.

The present pilot study investigated whether acceleration of gastric emptying in patients with type 1 diabetes and delayed gastric emptying (a possible cause of poorly controlled diabetes) improves long-term glucose control. Eight outpatients with diabetes (age 28-63 years, mean diabetes duration 24.6+/-6.0 years) and delayed gastric emptying of radio-opaque markers were randomised and treated, for three months each, with a prokinetic drug (cisapride 20 mg twice daily) and placebo. Mean capillary glucose, glucose variability (M-values, MAGE), fructosamine, and HbA1c were assessed. Gastric emptying of a solid standard meal was measured by scintigraphy after each treatment period. Chronic administration of a prokinetic drug resulted in improved solid gastric emptying (percentage residual) at 120 min (p=0.025). The percentage residual was 43.6+/-9.6 % during prokinetic treatment and 59.7+/-9.9 % during placebo (standard error of paired differences 5.7 %). The mean gastric emptying time (t/2) of solids was 88 min during prokinetic treatment compared to 113 min in the placebo arm (SE of paired differences 14 min; p=0.09). Mean blood glucose values (9.0+/-3.8 vs. 8.8+/-3.7 mmol/l), daily glucose variability (MAGE 6.8+/-1.3 vs. 6.3+/-1.6 mmol/l; M-value 15.2+/-2.5 vs. 13.9+/-4.5), and HbA1c at 3 months (7.8+/-1.1 % vs. 7.6+/-1.0 %) were not statistically different between prokinetic drug and placebo treatment. Similarly, the frequency of hypoglycaemic episodes (< or = 3 mmol/l) was not different in both groups (78 vs. 68). Our pilot study showed that long-term acceleration of gastric emptying had no effect on overall glycaemic control, the magnitude of glucose excursions, and hypoglycaemic episodes in patients with diabetic gastroparesis. We do not recommend, therefore, acceleration of gastric emptying as treatment strategy for "brittle diabetes" in patients with type 1 diabetes.     

Effect of oral erythromycin on gallbladder motility in normal subjects and subjects with gallstones.

The action of the motilin receptor agonist erythromycin on human gallbladder contraction, measured by ultrasound, both in normal subjects and those with gallstone disease was studied. In 17 normal subjects, oral erythromycin administration (500 mg; vs. placebo) reduced fasting gallbladder volume at 2 hours (26.2 vs. 19.0 mL; P less than 0.001), and postprandial residual gallbladder volume (9.0 vs. 4.4 mL; P less than 0.001) and the rate constant of gallbladder emptying following the meal was significantly increased. Erythromycin also reduced fasting and residual gallbladder volumes in 13 patients with gallstone disease: in 6 who underwent cholecystolithotomy, fasting volume was 29.5 vs. 22.3 mL (P less than 0.05) and residual volume was 17.7 vs. 6.5 mL (P less than 0.05), and in 7 with gallstones in situ, fasting volume was 23.8 vs. 14.3 mL (P less than 0.05) and residual volume was 17.2 vs. 5.0 mL (P less than 0.05). In 7 of 8 subjects with gallstones and impaired gallbladder emptying, the gallbladder emptied normally following administration of erythromycin, and in 3 of the other 5 gallstone subjects gallbladder emptying was increased. In 6 normal subjects given erythromycin three times weekly for 1 month, the effect was maintained (fasting volume, 18.8 mL, P less than 0.001; residual volume, 3.7 mL, P less than 0.001). Oral erythromycin significantly reduces fasting and postprandial residual gallbladder volumes in both normal subjects and subjects with gallstones and reverses the gallbladder motility defect found in a proportion of subjects with gallstones. This effect is maintained for a month in normal subjects.     

Effect of gastric volume or emptying on meal-related symptoms after liquid nutrients in obesity: a pharmacologic study.

BACKGROUND & AIMS: Altered postprandial satiation influences food intake in obesity. The aim of this study was to evaluate the contribution of gastric motor functions to intra- and postprandial symptoms in obese, otherwise healthy, people. METHODS: In a randomized, parallel-group, double-blind design, 40 obese (body mass index>30 kg/m2) healthy volunteers (n=10/group) received intravenous saline (placebo), atropine (.02 mg/kg), or erythromycin (1 or 3 mg/kg) to alter gastric volume and emptying after liquid nutrient meals, measured by validated imaging methods. The nutrient drink test assessed the volume ingested at maximum satiation, and intra- and early postprandial symptoms. Relationships between gastric motor functions, meal size, and symptoms were assessed by using multiple regression. Circulating levels of candidate upper-gut hormones involved in satiation were measured. RESULTS: Relative to placebo, atropine retarded gastric emptying and increased gastric volumes; erythromycin accelerated gastric emptying and reduced gastric volumes during fasting. Although similar maximal tolerated volumes were recorded across treatments, intra- and immediate postprandial symptoms were increased by these perturbations, particularly nausea and bloating. Upper-gut hormonal profiles generally reflected changes in gastric emptying. Regression analysis showed that fasting predrug gastric volume was a significant predictor of intra- and postprandial bloating. Change in gastric volume postdrug or postmeal did not contribute additionally to predicting intra- or postprandial symptoms. There was significant (negative) association between gastric emptying and fullness score, and significant (positive) association with hunger score 30 minutes postprandially. CONCLUSIONS: In obese individuals, fasting gastric volumes and gastric emptying, but not postprandial gastric volumes, were associated with intra- and postprandial symptoms. Understanding the determinants of gastric volume may provide insights on mechanisms controlling satiation.     

Effects of ursodeoxycholic acid on splanchnic and systemic hemodynamics. A double-blind, cross-over, placebo-controlled study in healthy volunteers

BACKGROUND: Recently, the beneficial effects of ursodeoxycholic acid (UDCA) on the portal hypertensive state have been demonstrated in patients with primary biliary cirrhosis. However, it is not known whether UDCA has direct or indirect effects on the vascular smooth muscles in humans, thereby leading to a change in splanchnic or systemic hemodynamics. AIMS: We therefore evaluated the hemodynamic effects of UDCA as to its established effect on gallbladder motility under fasting and postprandial conditions in healthy volunteers. METHODS: In a double-blind, cross-over study of 20 healthy volunteers, placebo or UDCA (750 mg/d) were randomly administered over 4 weeks with an interim 4-week washout period. Portal blood flow, cardiac output and gallbladder motility were measured using echo-Doppler and b-mode sonography before and after placebo and verum, respectively. ECG, blood pressure, heart rate and blood chemistry were also measured. RESULTS: UDCA did not significantly change fasting portal flow or meal-induced portal hyperemia. Both fasting and postprandial gallbladder volumes increased (26.5 +/- 6.0 vs. 40.7 +/- 13.8 ml, p < 0.05, and 11.2 +/- 6.2 vs. 14.8 +/- 6.7 ml, p < 0.05). Diastolic blood pressure decreased under UDCA (71.2 +/- 8.7 vs. 66.5 +/- 6.5 mm Hg, p < 0.05). Serum levels of chloride and gamma-glutamyltransferase decreased slightly, while alkaline phosphatase increased. CONCLUSIONS: UDCA affected systemic but not portal hemodynamics. The increase in gallbladder volume is obviously mediated by factors that do not influence the splanchnic vascular bed.     

The effects of omeprazole on intragastric pH, intestinal motility, and gastric emptying rate.

BACKGROUND: The present study was designed to investigate whether omeprazole changes the characteristics and thereby the functions ascribed to fasting intestinal motility, postprandial motility, postprandial pH, and gastric emptying. METHODS: Ten healthy subjects were investigated. The studies were performed after 10 days of treatment with 40 mg omeprazole daily/placebo. Duodenal pressures and intragastric pH were detected by strain-gauge transducers and a pH electrode attached to a miniature computer. The meal consisted of an omelette labelled with 99mTc-sulphur colloids followed by 150 ml water labelled with 111In-diethylenetriamine pentaacetic acid. RESULTS: The difference in fasting intragastric pH between the two series was highly significant. The profile from the placebo series showed a relationship between phase activity and pH. The pH increased from phase I (median, 1.3; 95% confidence interval (CI), 0.9-1.6) to a maximum at 25% (1.8 (0.9-2.1)) and 50% (1.6 (1.1-3.8)) of cycle duration and decreased thereafter until the end of the cycle. The profile from the omeprazole series showed significantly higher values during the entire cycle but no relationship between phase activity and pH. Pretreatment with omeprazole was followed by a delay in gastric emptying of liquid at 30 min (64% (49%-66%) (omeprazole series) versus 78% (67%-83%); P < 0.01) and solid at 180 min (71% (48%-86%) (omeprazole series) versus 96% (87%-100%); P < 0.01). There was no significant difference in duration of postprandial motility (305 min (157-350 min) (omeprazole) versus 259 min (129-403 min)). CONCLUSIONS: Omeprazole eliminates the temporal relationship between intragastric pH and characteristics of the migrating motor complex and induces a delay in gastric emptying of both liquid and solid. A non-significant increase in duration of postprandial motility may represent a type-II error.     

Influence of gender on proximal gastric motor and sensory function

OBJECTIVE: Gender-related differences have been demonstrated with regard to GI motility: gallbladder contraction, colonic transit, and gastric emptying are delayed in women. It is not known whether gender influences proximal gastric motility and perception. METHODS: We have studied the influence of gender on proximal gastric motility and perception under fasting and postprandial conditions by retrospective analysis of data obtained in 99 healthy volunteers (42 men, 57 women) who participated in barostat studies performed according to standardized protocols at the Leiden University Medical Center (Leiden, The Netherlands) between 1996 and 2000. RESULTS: Minimal distending pressure (MDP) was significantly higher in women than in men (respectively, 6.8+/-0.2 vs 5.5+/-0.2 mm Hg; p < 0.001). During stepwise pressure distensions pressure-volume curves were similar in both sexes after correction for MDP, whereas perception of fullness and abdominal pressure increased significantly (p < 0.05) more rapidly in women. Before the meal intragastric volumes (at MDP + 2 mm Hg) did not differ between sexes. After the meal gastric relaxation in the first 30 min did not differ in women and men (respectively, 186+/-23 ml and 140+/-32 ml). However, from 30 until 90 min after the meal a significantly (p < 0.05) delayed return of intragastric volume to basal was seen in women. Perception of postprandial nausea was significantly (p < 0.01) increased in women. Perception of postprandial fullness remained increased for a longer period of time in women. CONCLUSIONS: Proximal gastric motility and perception are influenced by gender. Gender-related differences in postprandial proximal gastric motility and perception should be taken into account in barostat studies comparing patients with controls.     

The effect of the cholecystokinin receptor antagonist MK-329 on meal-stimulated pancreaticobiliary output in humans.

To determine the physiological role of circulating cholecystokinin (CCK), the effect of the CCK receptor antagonist MK-329 on upper digestive processes was investigated in six normal volunteers after a mixed meal. In a double-blind, two-period, randomized crossover design, the subjects received either 10 mg MK-329 or placebo orally 3 hours 15 minutes before the meal, which contained 51CrCl3 as food marker. A five-lumen tube with the tip in the distal duodenum allowed continuous marker infusion (57Co-B12) and duodenal aspiration as well as recordings of antral and duodenal motility patterns via three pressure sensors. Postprandially, MK-329 caused a significant reduction of 30%-60% (P less than 0.05) in pancreatic trypsin output during the initial three 15-minute periods; thereafter, the output was virtually the same than after placebo. Thus, the integrated enzyme response was only reduced by 15% (NS) during the 3-hour period beginning 15 minutes after the meal. In contrast, gallbladder contraction, determined by total bile acid excretion, was inhibited by 77% (P less than 0.05), indicating a crucial role of CCK in regulating gallbladder motility. Except for the initial 30 minutes postprandially, MK-329 also induced a significant reduction in duodenal pH with mean values ranging from 3.5 +/- 0.2 to 4.1 +/- 0.3 compared with 4.5 +/- 0.3 to 5.0 +/- 0.4 after placebo (P less than 0.05), probably because of lowered secretion of pancreatic bicarbonate. Gastric emptying rate was significantly accelerated by MK-329 during the initial 75 minutes after the meal, but the time for 50% emptying did not differ from placebo [127.5 +/- 7.7 vs. 140.0 +/- 9.0 minutes (NS)]. No changes were observed in the motility pattern of the proximal duodenum after feeding. Whereas MK-329 only caused a slight increase of the basal plasma CCK concentrations, the postprandial levels were markedly enhanced. Peak concentrations were 10.0 +/- 1.3 vs. 4.0 +/- 0.5 pmol/L after placebo (P less than 0.001), and the integrated response exceeded the control value by 175% (P less than 0.01). The results suggest that circulating CCK is not an essential mediator of the postprandial pancreatic enzyme secretion in humans, whereas it plays a critical role in gallbladder emptying.     

Hyperglycaemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in idiopathic and diabetic gastroparesis.

BACKGROUND: Erythromycin has recently been found to be a gastrointestinal prokinetic agent in humans. Acute hyperglycaemia has been associated with delayed gastric emptying in both healthy controls and diabetic patients. Our aim was to investigate in gastroparetic patients (diabetics and idiopathics) whether hyperglycaemia, per se, reduces gastric motility during erythromycin-induced acceleration of gastric emptying of solids. METHODS: In 12 gastroparetic patients, 6 diabetics and 6 idiopathics, gastric emptying of solids was measured scintigraphically after giving placebo in normoglycaemia (5-8.9 mmol/l glucose) or 200 mg erythromycin lactobionate intravenously in normo- or hyperglycaemia (16-19 mmol/l glucose) induced by intravenous glucose infusion in random order on separate days. RESULTS: Erythromycin in normoglycaemia accelerated solids gastric emptying compared with placebo in all patients by abolishing the lag-phase duration and by decreasing the retained percentage of a meal in the stomach at 120 and 150 min (14.5% +/- 5.3% versus 88.4% +/- 10.6% and 3.5% +/- 2.1% versus 70.1% +/- 15.4%, respectively) (P < 0.001). The retained isotopic percentage in the stomach after erythromycin in induced hyperglycaemia compared with erythromycin in normoglycaemia, at 120 and 150 min, was increased (51.9% +/- 9.8% versus 14.5% +/- 5.3%, and 24.5% +/- 5.9% versus 3.5% +/- 2.1%, respectively) (P < 0.001) but was decreased in comparison with placebo (P < 0.001). A significantly increased percentage of isotope was retained in the stomach of the diabetic patients at 120 and 150 min, compared with the idiopathics, only after giving erythromycin in the hyperglycaemic condition (57.6% +/- 8.7% versus 46.1% +/- 7.6% (P = 0.036) and 27.8% +/- 5.7% versus 21.1 +/- 4.4% (P = 0.040), respectively). CONCLUSIONS: Hyperglycaemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in idiopathic and diabetic gastroparesis and increases the retained isotopic meal in the stomach. Hyperglycaemia reduces gastric motility more in the diabetic patients with gastroparesis than in idiopathic patients.     

The Effects of Omeprazole on Intragastric pH,Intestinal Motility,and Gastric Emptying Rate

Background: The present study was designed to investigate whether omeprazole changes the characteristics and thereby the functions ascribed to fasting intestinal motility, postprandial motility, postprandial pH, and gastric emptying. Methods: Ten healthy subjects were investigated. The studies were performed after 10 days of treatment with 40 mg omeprazole daily/placebo. Duodenal pressures and intragastric pH were detected by strain-gauge transducers and a pH electrode attached to a miniature computer. The meal consisted of an omelette labelled with ^99mTc-sulphur colloids followed by 150 ml water labelled with ¹¹¹In-diethylenetriamine pentaacetic acid. Results: The difference in fasting intragastric pH between the two series was highly significant. The profile from the placebo series showed a relationship between phase activity and pH. The pH increased from phase I (median, 1.3; 95% confidence interval (CI), 0.9-1.6) to a maximum at 25% (1.8 (0.9-2.1)) and 50% (1.6 (1.1-3.8)) of cycle duration and decreased thereafter until the end of the cycle. The profile from the omeprazole series showed significantly higher values during the entire cycle but no relationship between phase activity and pH. Pretreatment with omeprazole was followed by a delay in gastric emptying of liquid at 30 min (64% (49%-66%) (omeprazole series) versus 78% (67%-83%); P &lt; 0.01) and solid at 180 min (71% (48%-86%) (omeprazole series) versus 96% (87%-100%); P &lt; 0.01). There was no significant difference in duration of postprandial motility (305 min (157-350 min) (omeprazole) versus 259 min (129-403 min)). Conclusions: Omeprazole eliminates the temporal relationship between intragastric pH and characteristics of the migrating motor complex and induces a delay in gastric emptying of both liquid and solid. A non-significant increase in duration of postprandial motility may represent a type-II error.