Interpretation of overall colonic transit in defecation disorders in males and females.

BACKGROUND: There is little information regarding gender-specific measurements of colonic transit and anorectal function in patients with defecation disorders (DD). To compare overall colonic transit by gender in DD. METHODS: In 407 patients with constipation due to DD diagnosed by a single gastroenterologist (1994-2012), DD was characterized by anorectal manometry, balloon expulsion test, and colonic transit by scintigraphy. The primary endpoint was overall colonic transit (geometric center, GC) at 24 h (GC24). Effects of gender in DD on colonic transit, and comparison with transit in 208 healthy controls were assessed by Mann-Whitney rank sum test. Secondary endpoints were maximum anal resting (ARP) and squeeze (ASP) pressures. We also tested association of the physiological endpoints among DD females by pregnancy history and among DD patients by colectomy history. KEY RESULTS: The DD patients were 67 males (M) and 340 females (F). Significant differences by gender in DD patients were observed in GC24 (median: M: 2.2; F: 1.8; P = 0.01), ARP (median: M: 87.8 mmHg; F: 82.4 mmHg; P = 0.04), and ASP (median: M: 182.4 mmHg; F: 128.7 mmHg; P < 0.001). GC24 was slower in DD compared with same-gender healthy controls. GC24 did not differ among DD females by pregnancy history. Anorectal functions and upper GI transit did not differ among DD patients by colectomy history. CONCLUSIONS & INFERENCES: Patients with DD have slower colonic transit compared with gender-matched controls. Among DD patients, males have higher ARP and ASP, and females have slower colonic transit. Although the clinical significance of these differences may be unclear, findings suggest that interpretation of these tests in suspected DD should be based on same-gender control data.

The effects of methylnaltrexone alone and in combination with acutely administered codeine on gastrointestinal and colonic transit in health.

BACKGROUND: The short-term effects of methylnaltrexone (MNTX), a peripherally acting mu-opioid receptor antagonist, on gastrointestinal and colonic transit remain unclear. AIM: To compare the effects of placebo, codeine, subcutaneous (s.c.) MNTX and codeine with s.c. MNTX on gastrointestinal and colonic transit of solids in healthy humans. METHODS: In a randomized, parallel-group, double-blind, placebo-controlled trial of 48 healthy volunteers, effects of 6 consecutive days of placebo [s.c. and p.o. (orally), n = 8], codeine (p.o. 30 mg q.d.s., n = 8), MNTX (s.c. 0.30 mg/kg, n = 16) and combined MNTX and codeine (same doses and routes, n = 16) on gastrointestinal and colonic transit were assessed. A validated scintigraphic method was used to measure transit during the last 48 h of treatment. Bowel function was estimated during treatment as well as 1 week preceding treatment using standard diaries. Analysis of covariance was used to assess treatment effects. RESULTS: Codeine delayed colonic transit [geometric centre at 24 h (P = 0.04) and ascending colon t(1/2) (P = 0.02)] and reduced stool frequency (P = 0.002), but had no effect on stool form. MNTX did not affect transit, stool frequency or stool form, either alone or with codeine (P > 0.3). No drug interaction effects were detected (P > 0.15). CONCLUSION: Methylnaltrexone does not alter gastrointestinal or colonic transit and does not reverse acute codeine-associated delayed gut transit in health.

Effects of bisacodyl on ascending colon emptying and overall colonic transit in healthy volunteers.

BACKGROUND: The mechanism of action of bisacodyl in the unprepared human colon remains unclear. AIM: To evaluate the effect of oral bisacodyl on the overall and regional colonic transit in humans. METHODS: In a double-blind, randomized, placebo-controlled study of 25 healthy participants, effects of oral bisacodyl (5 mg p.o. per day) and placebo on colonic transit were compared. A validated scintigraphy method was used to measure colonic transit. The primary transit endpoints, ascending colon emptying t(1/2) and geometric centre of colon isotope at 24 h (overall transit), were compared (Wilcoxon rank sum test). RESULTS: There were significant treatment effects on ascending colon t(1/2), with the bisacodyl group demonstrating accelerated emptying [median 6.5 h, interquartile range 5.0-8.0 h] relative to the placebo group [11.0 h (7.0-17.1); P = 0.03]. Numerical differences in colonic geometric centre 24 h [bisacodyl median 3.0 (2.2-3.8), placebo 4.0 (3.1-4.6)] were not significant (P = 0.19). There were no significant differences observed in geometric centre 4 h. CONCLUSION: Oral 5 mg bisacodyl accelerates ascending colon in the unprepared colon in healthy adults; this action may contribute to the drug's efficacy in constipation.

Effects of glucagon-like peptide-1 and sympathetic stimulation on gastric accommodation in humans.

In humans, glucagon-like peptide-1 (GLP-1) delays gastric emptying by inhibiting vagal activity and also increases gastric volumes, by unclear mechanisms. Because GLP-1 inhibits intestinal motility by stimulating the sympathetic nervous system in rats, we assessed the effects of a GLP-1 agonist and yohimbine, an alpha(2)-adrenergic antagonist, on gastric volumes in humans. In this double-blind study, 32 healthy volunteers were randomized to placebo, a GLP-1 agonist, yohimbine or GLP-1 and yohimbine. Gastric volumes (fasting predrug and postdrug, and postprandial postdrug) were measured by (99m)Tc single photon emission computed tomography imaging. Plasma catecholamines and haemodynamic parameters were assessed. Compared with placebo, GLP-1 increased (P = 0.03) but yohimbine did not affect fasting gastric volume. However, GLP-1 plus yohimbine increased (P < 0.001) postprandial gastric accommodation vs placebo and vs GLP-1 alone [postprandial volume change = 542 +/- 29 mL (mean +/- SEM, placebo), 605 +/- 31 mL (GLP-1), 652 +/- 54 mL (yohimbine) and 810 +/- 37 mL (GLP-1 and yohimbine)]. Plasma noradrenaline and dihydroxyphenylglycol concentrations were higher for yohimbine vs placebo and for GLP-1 and yohimbine vs GLP-1. Yohimbine stimulates central sympathetic activity and in combination with GLP-1, augments postprandial accommodation in humans.

Effect of a proton pump inhibitor on postprandial gastric volume, emptying and symptoms in healthy human subjects: a pilot study.

BACKGROUND: In consensus guidelines, proton pump inhibitors (PPIs) are recommended for the treatment of functional dyspepsia. It is unclear whether PPIs change gastric volume or emptying. AIM: To assess the effect of a PPI, rabeprazole, on gastric volume and emptying and postprandial symptoms. METHODS: In a double-blind, parallel-group placebo-controlled trial, 13 healthy participants were randomized to rabeprazole, 20 mg b.d., or placebo. On day 3, fasting gastric volume was measured using intravenous (99m)Tc-pertechnate and single photon emission computed tomography (SPECT). After the last dose of study medication, an (111)In-chloride egg meal (300 kcal) was ingested, and postprandial gastric volume and emptying were measured by SPECT. Symptom ratings using a visual analogue scale (fullness, nausea, bloating, abdominal pain, aggregate score) were obtained at baseline and 15, 30, 45, 60 and 75 min postprandially. Group comparisons were performed using Mann-Whitney rank sum test. RESULTS: There were no statistically significant differences in gastric volume or emptying in the two groups. However, there was a borderline increase in gastric volume with rabeprazole compared with placebo. Rabeprazole treatment reduced aggregate postprandial symptoms, particularly fullness, 30 min after the meal (P = 0.01). CONCLUSIONS: In healthy participants, rabeprazole, 20 mg b.d., did not significantly change gastric emptying, but reduced symptoms and had a borderline effect on gastric volume postprandially. The mechanism of reduced postprandial symptoms with a PPI requires further study.

Effect of female sex hormone supplementation and withdrawal on gastrointestinal and colonic transit in postmenopausal women.

Females are disproportionately affected by constipation, which is often aggravated during pregnancy. Bowel function also changes during the luteal phase of the menstrual cycle. The aim was to compare the effects of acute administration of female sex steroids on gastric emptying, small bowel transit and colonic transit in healthy postmenopausal subjects. A second aim was to determine whether withdrawal of the hormones was associated with a change in transit. Forty-nine postmenopausal females were randomized to receive for 7 days 400 mg day(-1) micronized progesterone, 0.2 mg day(-1) oestradiol, combination of the two, or placebo. Treatment groups were balanced on age. Participants underwent whole gut transit measurement by scintigraphy using a 99m-labeled technetium-egg meal and 111-labeled indium-charcoal via a delayed-release capsule. Transit measurement was repeated after withdrawal of the study medications. The primary endpoints were ascending colon (AC) emptying half-life time (t1/2) and colonic geometric centre (GC) at 24 h. Secondary analysis variables were GC at 4 and 48 h, gastric emptying t1/2 and colonic filling at 6 h. There was a significant overall effect of progesterone on colonic transit with shorter AC emptying t1/2 and significantly greater colonic GC at 48 h. No transit endpoints were altered by oestradiol or combined hormonal treatment relative to placebo. Oestradiol and progesterone resulted in looser stool consistency. Withdrawal of the hormone supplement was not associated with significant alteration in transit. Micronized progesterone does not retard colonic transit in postmenopausal females.

Effects of an osmotically active agent on colonic transit.

It is unknown if sorbitol, a widely used laxative agent, accelerates colonic transit, and if these effects are modified by concomitant meal ingestion. Colonic transit was assessed by (111)In scintigraphy in 40 healthy subjects. After a 24-h scan, subjects received sorbitol (30 mL of 70% solution) or dextrose (30 mL of 70% solution), administered with or without a meal. Colonic transit, breath hydrogen excretion, and symptom scores were recorded for 4 h thereafter. VAS scores for flatulence, but not other symptoms increased (P = 0.004) by 13.1 +/- 6.3 mm (mean +/- SEM) on a 100 mm scale after sorbitol alone or sorbitol with a meal (by 18.9 +/- 7.2 mm), but not after dextrose. After adjusting for GC(24), sorbitol accelerated (P < 0.001) colonic transit (GC(28) = 3.0 +/- 0.3) compared with dextrose (GC(28) = 2.2 +/- 0.2), regardless of meal ingestion. Breath hydrogen excretion was correlated with the change in colonic transit (r = 0.52, P < 0.01) and with flatulence (r = 0.45, P = 0.003) after sugar ingestion. In healthy subjects, sorbitol accelerated colonic transit and increased flatulence but not other symptoms within 4 h, regardless of meal intake.

A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating.

AIM: To evaluate the effects of a combination probiotic on symptoms and colonic transit in patients with irritable bowel syndrome (IBS) and significant bloating. METHODS: Forty-eight patients with Rome II IBS were randomized in a parallel group, double-blind design to placebo or VSL# 3 twice daily (31 patients received 4 weeks and 17 patients 8 weeks of treatment). Pre- and post-treatment colonic transit measurements were performed using scintigraphy with (111)In charcoal. Symptoms were summarized as an average daily score for the entire period of treatment and separately for the first 4 weeks of treatment. Weekly satisfactory relief of abdominal bloating was assessed. RESULTS: Treatment with VSL# 3 was associated with reduced flatulence over the entire treatment period (placebo 39.5 +/- 2.6 vs VSL# 3 29.7 +/- 2.6, P = 0.011); similarly, during the first 4 weeks of treatment, flatulence scores were reduced (placebo 40.1 +/- 2.5 vs VSL# 3 30.8 +/- 2.5, P = 0.014). Proportions of responders for satisfactory relief of bloating, stool-related symptoms, abdominal pain and bloating scores were not different. Colonic transit was retarded with VSL# 3 relative to placebo (colon geometric center 2.27 +/- 0.20 vs 2.83 +/- 0.19, P = 0.05 respectively). CONCLUSION: VSL# 3 reduces flatulence scores and retards colonic transit without altering bowel function in patients with IBS and bloating.

Effect of cyclooxygenase-2 inhibitors on gastric emptying and small intestinal transit in humans.

Endogenous prostaglandins regulate smooth muscle activity; prostaglandins and cyclooxygenase (COX) inhibitors influence gastrointestinal motility in inflammatory states such as postoperative ileus in animal models. The objective of this study was to evaluate the effects of two COX-2 inhibitors on gastric emptying and intestinal transit in healthy humans. In a double-blind, placebo-controlled, parallel-group study, 66 healthy volunteers were randomized to one of two commercially available oral COX-2 inhibitors (celecoxib and rofecoxib), cisapride (positive control), or placebo. Following 7 days on therapy, study participants underwent a test of gastric emptying and small bowel transit of liquids and solids using scintigraphy. Data were analysed using Kruskal-Wallis (ANOVA on ranks)and Mann-Whitney rank sum tests. There were significant group effects on transit of solids: gastric emptying (ANOVA, P = 0.005) and small bowel transit (ANOVA, P = 0.056). However, neither COX-2 inhibitor significantly accelerated the liquid or solid gastric emptying or small bowel transit compared with placebo. The positive control, cisapride, accelerated gastric emptying of solids (post-lag slope of gastric emptying, P < 0.05), and small bowel transit of solids (t10%, P = 0.016). At maximum clinically approved dosages, celecoxib and rofecoxib have no significant effects on gastric emptying or small intestinal transit in healthy humans. Cisapride accelerates gastric emptying and small bowel transit in healthy humans.

Effects of asimadoline, a kappa-opioid agonist, on satiation and postprandial symptoms in health.

AIM: To evaluate the effect of single administrations of asimadoline, a kappa-opioid agonist, on satiation volume, postprandial symptoms and gastric volumes. METHODS: Healthy subjects received oral placebo, or 0.5 or 1.5 mg asimadoline in a randomized, double-blind fashion 1 h prior to testing. We assessed effects on the volume of Ensure to achieve full satiation and postprandial symptoms 30 min after meal, and on gastric volume (fasting and postprandial) measured by 99mTc-single photon emission tomography (SPECT) imaging. RESULTS: Thirteen healthy subjects were studied in each treatment arm. Compared to placebo, asimadoline 0.5 mg decreased postprandial fullness (P = 0.027) without affecting the volume ingested at full satiation (P = 0.6). Asimadoline 1.5 mg decreased satiation during meal, allowing increased satiation volumes (P = 0.008) and tended to decrease postprandial fullness (P = 0.067), despite higher volumes ingested. There was a significant treatment-gender interaction in the effect of asimadoline on gastric volumes (P < 0.05). Asimadoline 0.5 mg (not 1.5 mg) increased fasting (P = 0.047) and postprandial (P = 0.009) gastric volumes in females but decreased fasting volumes in males (P = 0.008). The effect of asimadoline on gastric volume did not explain the effect observed on satiation volume (P = 0.371) or postprandial fullness (P = 0.399). CONCLUSION: A single oral administration of asimadoline decreases satiation and postprandial fullness in humans independently of its effects on gastric volume.

Effects of glucagon-like peptide-1 and feeding on gastric volumes in diabetes mellitus with cardio-vagal dysfunction.

Glucagon-like peptide-1 (GLP-1) increases gastric volume in humans possibly through the vagus nerve. Gastric volume response to feeding is preserved after vagal denervation in animals. We evaluated gastric volume responses to GLP-1 and placebo in seven diabetic patients with vagal neuropathy in a crossover study. We also compared gastric volume response to feeding in diabetes with that in healthy controls. We measured gastric volume using SPECT imaging. Data are median (interquartile range). In diabetic patients, GLP-1 did not increase gastric volume during fasting [5 mL (-3; 30)] relative to placebo [4 mL (-14; 50) P = 0.5], or postprandially [Delta postprandial minus fasting volume 469 mL (383; 563) with GLP-1 and 452 mL (400; 493) with placebo P = 0.3]. Change in gastric volume over fasting in diabetic patients on placebo was comparable to that of healthy controls [452 mL (400; 493)], P = 0.5. In contrast to effects in health, GLP-1 did not increase gastric volume in diabetics with vagal neuropathy, suggesting GLP-1's effects on stomach volume are vagally mediated. Normal gastric volume response to feeding in diabetics with vagal neuropathy suggests that other mechanisms compensate for vagal denervation.

A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome.

AIM: To investigate the effects of a probiotic formulation, VSL#3, on gastrointestinal transit and symptoms of patients with Rome II irritable bowel syndrome with predominant diarrhoea. METHODS: Twenty-five patients with diarrhoea-predominant irritable bowel syndrome were randomly assigned to receive VSL#3 powder (450 billion lyophilized bacteria/day) or matching placebo twice daily for 8 weeks after a 2-week run-in period. Pre- and post-treatment gastrointestinal transit measurements were performed in all patients. Patients recorded their bowel function and symptoms daily in a diary during the 10-week study, which was powered to detect a 50% change in the primary colonic transit end-point. RESULTS: There were no significant differences in mean gastrointestinal transit measurements, bowel function scores or satisfactory global symptom relief between the two treatment groups, pre- or post-therapy. Differences in abdominal bloating scores between treatments were borderline significant (P = 0.09, analysis of covariance). Further analysis revealed that abdominal bloating was reduced (P = 0.046) with VSL#3 [mean post- minus pre-treatment score, - 13.7; 95% confidence interval (CI), - 2.5 to - 24.9], but not with placebo (P = 0.54) (mean post- minus pre-treatment score, - 1.7; 95% CI, 7.1 to - 10.4). With the exception of changes in abdominal bloating, VSL#3 had no effect on other individual symptoms: abdominal pain, gas and urgency. All patients tolerated VSL#3 well. CONCLUSION: VSL#3 appears to be promising in the relief of abdominal bloating in patients with diarrhoea-predominant irritable bowel syndrome. This is unrelated to an alteration in gastrointestinal or colonic transit.

SPECT imaging of the stomach: comparison with barostat, and effects of sex, age, body mass index, and fundoplication. Single photon emission computed tomography.

BACKGROUND: Impaired gastric accommodation may lead to dyspeptic symptoms. A non-invasive method using single photon emission computed tomography (SPECT) has been developed to measure gastric volumes. AIMS AND METHODS: Our aims were: to assess the accuracy of SPECT with three dimensional image analysis to measure balloon volumes in vitro; to compare gastric barostat balloon volumes measured post-meal and post-distension with total gastric volumes measured simultaneously with SPECT; to present normal gastric volume data for healthy adults; and to compare SPECT data in health with symptomatic post-fundoplication patients. RESULTS: In vitro balloon volumes measured by SPECT were highly accurate (R(2)=0.99). When measured simultaneously by gastric barostat and SPECT, postprandial/fasting volume ratios (2.2 (0.12) (mean (SEM)) v 2.3 (0.15), respectively; p=0.6) and post-distension volume ratios (1.4 (0.1) v1.3 (0.1); p=0.2) were highly comparable. In females, postprandial gastric volumes (675 (14) v 744 (20) ml for males; p=0.004) and changes in gastric volumes (464 (14) ml v 521 (20) ml for males; p=0.01) measured by SPECT were significantly lower than in males. No effects of age or body mass index were noted. The postprandial/fasting gastric volume ratio by SPECT was lower in post-fundoplication patients (2.7 (0.2)) than in healthy controls (3.4 (0.1); p=0.003). CONCLUSIONS: SPECT provides a non-invasive estimate of the effect of a meal on total gastric volume that is comparable to changes in balloon volume observed with the gastric barostat. The SPECT technique is promising for investigation of gastric volumes in health and disease and the effects of pharmacological agents.

Performance characteristics of scintigraphic transit measurements for studies of experimental therapies.

BACKGROUND: The intra- and inter-individual reproducibility of gastrointestinal and colonic transit tests require full characterization. AIMS: (i) To characterize the normal values and reproducibility effects of age and gender on the scintigraphic transit of solids in health. (ii) To compare scintigraphic and radio-opaque marker measurements of colonic transit. (iii) To estimate demonstrable effect sizes for different transit end-points based on observed variations. METHODS: A scintigraphic gastrointestinal and colonic transit study and the mean colonic transit time were measured using radio-opaque markers in 37 healthy volunteers; 21 subjects had a repeat scintigraphic test 3 weeks later. RESULTS: Gastric emptying at 4 h was highly reproducible (coefficient of variation, 4%) on repeat testing. The colonic measurement varied by more than 1 geometric centre unit in 37% of subjects at 24 h and in 26% of subjects at 48 h. There were no age- or gender-related differences in transit. Effect sizes demonstrable with 14 subjects per group were in the range previously shown to be clinically relevant: 25% change in gastric emptying at 4 h; 1.5 geometric centre unit change in colonic transit at 48 h. CONCLUSIONS: These data demonstrate the reproducibility and performance to be expected of transit measurements and are essential for designing studies in experimental therapeutics.

Effects of pramlintide, an amylin analogue, on gastric emptying in type 1 and 2 diabetes mellitus.

Pramlintide delays gastric emptying, possibly by a centrally mediated mechanism. Our aim was to determine whether the effects of pramlintide on gastric emptying differ in people with type 1 or type 2 diabetes who had no history of complications. Using a randomized, three-period, two-dose, crossover design, we studied the effects of 0, 30, or 60 microg t.i.d. pramlintide subcutaneously for 5 days each in six type 1 and six type 2 diabetic subjects. Gastric emptying of solids was measured by 13C-Spirulina breath test. Plasma pancreatic polypeptide (HPP) response to the test meal was also measured. Relative to placebo [t 50% 91 +/- 6 min (means +/- SEM)], pramlintide equally delayed gastric emptying following 30 or 60 microg t.i.d. (268 +/- 37 min, 329 +/- 49 min, respectively; P < 0.01]. Postprandial HPP levels were lower in response to 30 and 60 microg pramlintide compared to placebo. There were no significant differences in the effects on gastric emptying or HPP levels between type 1 and type 2 diabetic subjects. Pramlintide delays gastric emptying in diabetes unassociated with clinically detected complications. Further studies are needed in diabetic patients with impaired gastric motor function.

Effects of an alpha(2)-adrenergic agonist on gastrointestinal transit, colonic motility, and sensation in humans.

To characterize alpha(2)-adrenergic control of motor and sensory functions of gastrointestinal tract and colon, we studied dose-related effects of clonidine (placebo or up to 0.3 mg po) by random assignment in 55 healthy humans. Gastrointestinal transit was measured in all subjects; in 35, we assessed colonic compliance, tone, and sensations of gas and pain during phasic distensions. Clonidine did not significantly alter gastrointestinal or colonic transit, but it increased colonic compliance and reduced fasting tone without altering colonic response to a meal. Clonidine significantly reduced aggregate sensation to distensions overall and had significant linear dose-related sensory effects at 8- and 24-mmHg distensions. Effect on pain (including dose-response relationship) was due to 0.3-mg dose for distensions at 24 mmHg. We confirmed that clonidine relaxes fasting colonic tone and reduces sensation of pain. In this study, gut transit was not altered by clonidine, and novel dose-response characteristics and clonidine's effect on gas sensation are provided. Doses as low as 0.05 mg may be effective and potentially useful in reducing colonic tone and gas sensation.

Is there a role for gastric accommodation and satiety in asymptomatic obese people?

OBJECTIVE: The relationships of gastric accommodation and satiety in moderately obese individuals are unclear. We hypothesized that obese people had increased gastric accommodation and reduced postprandial satiety. The objective of this study was to compare gastric accommodation and satiety between obese and non-obese asymptomatic subjects. RESEARCH METHODS AND PROCEDURES: In 13 obese (body mass index [BMI] > or = 30 kg/m(2); mean BMI, 37.0 +/- 4.9 kg/m(2)) and 19 non-obese control subjects (BMI < 30 kg/m(2); mean BMI, 26.2 +/- 2.9 kg/m(2)), we used single photon emission computed tomography to measure fasting and postprandial gastric volumes and expressed the accommodation response as the ratio of postprandial/fasting volumes. The satiety test measured maximum tolerable volume of ingestion of liquid nutrient meal (Ensure) and symptoms 30 minutes after cessation of ingestion. RESULTS: Total fasting and postprandial gastric volumes and the ratio of postprandial/fasting gastric volume were not different between asymptomatic obese and control subjects. However, the fasting volume of the distal stomach was greater in obese than in control subjects. Maximum tolerable volume of ingested Ensure and aggregate symptom score 30 minutes later were also not different between obese and control subjects. DISCUSSION: Asymptomatic obese individuals (within the BMI range of 32.6 to 48 kg/m(2)) did not show either increased postprandial gastric accommodation or reduced satiety. These data suggest that gastric accommodation is unlikely to provide an important contribution to development of moderate obesity.

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%).

Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder.

BACKGROUND & AIMS: Prucalopride (PRU) is a selective benzofuran 5-hydroxytryptamine(4)-receptor agonist with gastrointestinal and colonic prokinetic activities. We evaluated the effects of PRU on gastrointestinal and colonic transit in patients with constipation. METHODS: Gastrointestinal and colonic transit were measured over 48 hours in 40 patients who fulfilled modified Rome I criteria for functional constipation. Patients had no evidence of a rectal evacuation disorder. Subjects were randomized to receive a daily dose of 2 or 4 mg PRU or placebo in a double-blind, parallel-group design. Each treatment lasted 7 days. The transit test was performed over the last 48 hours of the study. Effects on gastric emptying, small bowel transit, and colonic transit were analyzed using Kruskal-Wallis and Wilcoxon rank sum tests. RESULTS: Of 61 patients screened, 40 were eligible and randomized. Two patients withdrew because of adverse events. PRU accelerated overall gastric emptying and small bowel transit. PRU tended to accelerate overall colonic transit with significantly faster overall colonic transit and ascending colon emptying with the 4-mg dose. CONCLUSIONS: PRU accelerates transit through the stomach, small bowel, and colon in patients with constipation unassociated with a rectal evacuation disorder.

Pharmacological modulation of human gastric volumes demonstrated noninvasively using SPECT imaging.

Three-dimensional single-photon emission computed tomography (SPECT) imaging allows noninvasive measurement of human postprandial gastric accommodation. The aim of this study was to determine whether 99mTCO4-SPECT demonstrates effects on pre- and postprandial gastric volumes of intravenous (i.v.) erythromycin lactobionate and sublingual isosorbide dinitrate, as predicted from previous literature. Twenty volunteers received no medication (controls), while 12 were randomized to either i.v. erythromycin 2 mg kg-1 over 20 min, or 10 mg sublingual isosorbide. After a 10-min preprandial SPECT measurement, a standard 300-mL, 300-kcal liquid meal was ingested, followed by a 20-min postprandial measurement. Gastric images were reconstructed from transaxial images and total volume was measured using the Analyseeth software system. Fasting gastric volume was greater with isosorbide [223 +/- 14 (SE) mL vs. 174 +/- 9 mL, control; P < 0.05], and postprandial volume was lower with erythromycin [393 +/- 27 mL vs. 582 +/- 17 mL, control; P < 0.05]. The ratio of postprandial over fasting volume and mean difference between pre- and postprandial volumes were significantly lower in both drug groups compared to controls. We conclude that 99mTCO4-SPECT imaging is able to semiquantitatively demonstrate pharmacological modulation of fasting gastric volume and postprandial accommodation in humans.