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.     

A synthetic prostaglandin E2 analogue, enprostil, hastens gastric emptying of solids in patients with an active duodenal ulcer

The effect of gastric emptying of two doses (35 and 70 micrograms) of enprostil given orally was evaluated in eight patients with endoscopically confirmed duodenal ulcer. Gastric emptying of a radiolabelled solid meal was assessed with the use of a gamma camera. Enprostil dose-dependently accelerated gastric emptying of solids; the gastric emptying index, Ix, increased from 1.62 +/- 0.38 min-1.10(-2) after placebo to 2.77 +/- 0.56 min-1.10(-2) after 35 micrograms enprostil (p less than 0.05 versus placebo) and to 3.65 +/- 0.64 min-1.10(-2) after 70 micrograms enprostil (p less than 0.005 versus placebo). The fraction of the radiolabelled food retained in the stomach at the end of the gastric emptying examination (that is, after 90 min) amounted to 50.5 +/- 6.9% after placebo, 35.2 +/- 7.4% after 35 micrograms enprostil, and 24.1 +/- 8.4% after 70 micrograms enprostil. It is concluded that enprostil elicits a significant speeding up of solid-phase gastric emptying in duodenal ulcer patients.     

Clinical relevance of scintigraphic measurement of gastric emptying of a solid-liquid meal in the dumping syndrome.

Gastric emptying of the solid and liquid components of an ordinary meal was evaluated by a dual isotopic technique in 36 patients referred to our hospital for early postprandial symptoms induced by various esophageal and/or gastric operations. Patients were classified as typical (n = 11), equivocal (n = 9) or improbable (n = 16) dumpers, in accordance with their presenting symptoms, as assessed before gastric emptying measurement. Patients with typical dumping symptoms displayed, as expected, significant acceleration of gastric emptying of liquids (t1/2: 18 +/- 6 min. vs. 48 +/- 7 min. in healthy controls; p less than 0.02), and also exhibited a dramatic enhancement of gastric emptying of solids (t1/2: 11 +/- 1 min. vs. 126 +/- 12 min. in healthy controls; p less than 0.001) and a complete loss of solid-liquid discrimination (7 +/- 6 min. vs. 78 +/- 7 min. in healthy controls; p less than 0.01). Mean gastric emptying rates for equivocal and improbable dumpers were not significantly different from those of healthy controls, but individual results were very heterogeneous; they included stasis, acceleration, or both disorders, and were not predictable by analysis of symptoms alone. Thus gastric emptying of solids as well as liquids is accelerated in symptomatic dumping patients, and objective evaluation of the emptying of both solid and liquid gastric emptying is essential in atypical dumpers, in order to characterize their disorders and prescribe the most rational treatment.     

Gallbladder emptying stimuli in obese and normal-weight subjects.

Gallbladder stasis may be an important factor in the pathogenesis of cholesterol-gallstone formation in some individuals. We investigated gallbladder function in a group of nondieting, gallstone-free, healthy subjects with normal (22 +/- 1 kg/m2) and high (36 +/- 1 kg/m2) body mass indexes. Fasting gallbladder volume (28.2 +/- 4.4 ml) and residual volume after maximal emptying (8.4 +/- 2.3 ml) in high-body-mass index subjects were not significantly different from those of normal-body-mass index subjects (20.5 +/- 2.5 ml and 4.2 +/- 1.3 ml, respectively). The percentage of gallbladder emptying (71% +/- 5%) and the rate of gallbladder emptying (-1.9 +/- 0.3 x 10(-2) min-1) in high-body-mass index subjects in response to a maximal emptying stimulus was similar to the percentage of emptying (78% +/- 6%) and rate of emptying (-2.3 +/- 0.6 x 10(-2) min-1) in normal-body-mass index subjects. A liquid meal containing less than 1 gm fat, 14 gm protein and 6 gm carbohydrate resulted in both a decreased rate of gallbladder emptying and an increased residual gallbladder emptying and an increased residual gallbladder volume in both groups. The addition of 10 or 20 gm (but not 4 gm) of fat to the liquid meal restored gallbladder emptying to the maximal-stimulus level. These results demonstrate that gallbladder emptying in response to a single liquid meal stimulus is not altered in obesity and that dose-response relationships to fat are similar in obese and normal-weight individuals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Liquid and solid gastric emptying in adults treated for Hirschsprung's disease during early childhood

OBJECTIVE: Dysmotility of the upper gastrointestinal tract has been reported in children with Hirschsprung's disease. In the present study, gastric emptying was studied in adult patients with Hirschsprung's disease to elucidate whether there is a persisting involvement of the upper gastrointestinal tract in this group of patients. MATERIAL AND METHODS: Gastric emptying of caloric liquids and solids was studied in 16 adult patients with surgically treated Hirschsprung's disease during early childhood and in age-matched controls. To examine liquid emptying, the paracetamol absorption test was applied using a meal containing glucose, lactose, maize oil, water (2020 kJ) and paracetamol. To examine solid emptying, the 13C gastric emptying breath test was applied using a meal containing white bread, margarine, a one-egg omelette (1050 kJ) and [13C]-octanoic acid. Gastrointestinal symptoms were recorded according to a standardized questionnaire. RESULTS: For liquid meal emptying, the time until emptying commenced was 8.1+/-1.9 and 2.9+/-0.9 min (mean+/-SE) in patients and controls, respectively (p=0.02). Thereafter, the first 25% of the meal emptied in 6.8+/-0.8 and 12.1+/-1.1 min in patients and controls, respectively (p=0.0005). The overall emptying rate tended to be delayed in patients compared with controls (p=0.06). For the solid meal, a delay in emptying was evident (p=0.02). The patients reported more symptoms from the upper gastrointestinal tract than the controls, but the symptoms were not significantly related to the emptying pathology demonstrated. CONCLUSIONS: The present study demonstrates that adult patients with Hirschsprung's disease have an abnormal pattern of gastric emptying, indicating persisting involvement of the upper gastrointestinal tract.     

Effects of Helicobacter pylori infection on gastric emptying rate in patients with non-ulcer dyspepsia

AIM: The pathogenesis of delayed gastric emptying in patients with non-ulcer dyspepsia (NUD) remains unclear. We aimed to examine whether gastric emptying rate in NUD patients was associated with Helicobacter pylori (H pylori) infection and whether it was affected by eradication of the infection. METHODS: Gastric emptying rate of a mixed solid-liquid meal was assessed by the paracetamol absorption method in NUD patients and asymptomatic controls (n=17). H pylori status was assessed by serology and biopsy urease test. H pylori-positive NUD patients (n=23) received 10-day triple eradication therapy. H pylori status was re-assessed by biopsy urease test four weeks later, and if eradication was confirmed, gastric emptying rate was re-evaluated. RESULTS: Thirty-three NUD patients and 17 controls were evaluated. NUD patients had significantly delayed gastric emptying compared with controls. The mean maximum plasma paracetamol concentration divided by body mass (Cmax/BM) was 0.173 and 0.224 mg/L.kg respectively (P=0.02), the mean area under plasma paracetamol concentration-time curve divided by body mass (AUC/BM) was 18.42 and 24.39 mg.min/L.kg respectively (P=0.01). Gastric emptying rate did not differ significantly between H pylori-positive and H pylori-negative NUD patients. The mean Cmax/BM was 0.172 and 0.177 mg/L.kg respectively (P=0.58), the mean AUC/BM was 18.43 and 18.38 mg.min/L.kg respectively (P=0.91). Among 14 NUD patients who were initially H pylori-positive, confirmed eradication of the infection did not significantly alter gastric emptying rate. The mean Cmax/BM was 0.171 and 0.160 mg/L.kg before and after Hp eradication, respectively (P=0.64), the mean AUC/BM was 17.41 and 18.02 mg.min/L.kg before and after eradication, respectively (P=0.93). CONCLUSION: Although gastric emptying is delayed in NUD patients compared with controls, gastric emptying rate is not associated with H pylori status nor it is affected by eradication of the infection.     

Gastric emptying after segmental gastrectomy for early cancer in the middle part of the stomach.

BACKGROUND/AIMS: We evaluated the quality of life and gastric emptying in patients who had undergone a segmental gastrectomy to treat early gastric cancer in the middle part of the stomach. METHODOLOGY: Thirty patients were considered in this study. Their mean age was 65.5 years (range: 44-83). All of the patients were free from recurrence of their cancer in the follow-up period. This ranged from 5 to 50 months (mean 30). Patients were interviewed at regular intervals to assess their quality of life and to note particular complaints. The upper gastrointestinal tract was assessed endoscopically. A gastric emptying study was performed at 3, 6, and 12 months after surgery. The meal used in this dual-phase study had solid and liquid phases. For the solid phase, 74 MBq of 99mTc sulfur colloid was injected into an egg, which was then hard-boiled. For the liquid phase, 18.5 MBq of (111)In-diethyltriaminopenta acetic acid (DTPA) were mixed into 150 ml of a commercial, elentary liquid diet. RESULTS: Three months after surgery, the patients' main complaints were gastric stasis (25%), heartburn (8%) and belching (8%). The patients gradually became asymptomatic following surgery. Fifty-nine percent were asymptomatic at the 3-month follow-up, 84% at 6 months, and 92% at 12 months. There was no evidence of reflux esophagitis or gastritis after the 3-month follow-up. One patient developed a complicated duodenal ulcer. Initially, the patients all had prolonged gastric emptying of the dual phase meal, compared to normal individuals. The T1/2 for liquid meal emptying was 87+/-18 min at 3 months, 77+/-20 min at 6 months and 50+/-5 min at 1 year after surgery. The last value is the same as for healthy individuals. Solid meal emptying was still prolonged, with an emptying rate of 36+/-9.7% at 2 hours, one year after surgery. CONCLUSIONS: Segmental gastrectomy patients experienced prolonged gastric emptying in the early post-operative period. This improved in the first year after surgery. The quality of life for patients who underwent segmental gastrectomy has been reasonably good in the follow-up period to date.     

Gastric emptying in patients with bulimia nervosa and anorexia nervosa

A dual radioisotope technique was used to measure gastric emptying of a mixed liquid and solid meal in 11 patients with bulimia nervosa, and was compared with 10 patients with anorexia nervosa and a sex-matched control population. The relationship of body weight and gastrointestinal symptoms to gastric emptying was also examined. Gastric emptying of solids in patients with bulimia nervosa was similar to that in controls (gastric T1/2 131 +/- 15 min vs 119 +/- 7 min; mean +/- SEM). In contrast, patients with anorexia nervosa had overall delayed emptying (182 +/- 31 min; p less than 0.05); six patients had normal emptying of the solid components of the meal and four had markedly delayed emptying. Gastric emptying of liquids was similar in the bulimics and controls (gastric T1/2 48 +/- 5 min and 49 +/- 4 min, respectively), whereas the anorexics tended to have prolonged gastric emptying (65 +/- 11 min, p = NS). There was no correlation between body weight, gastrointestinal symptoms, and gastric emptying in either group. These findings suggest that gastrointestinal symptoms are unreliable indicators of gastric emptying in patients with eating disorders, and that gastric emptying studies should be performed in such patients before treatment with prokinetic agents is considered.     

Opposite effects of kappa-opioid agonists on gastric emptying of liquids and solids in dogs

The influence of oral (p.o.) administration of kappa-(U-50488, tifluadom) and mu- (morphine, DAGO) opioid substances on gastric emptying of liquids and solids in a standard canned dog food meal was evaluated using a double-radiolabeled technique in dogs fitted with gastric cannulas. One hour after feeding, 28.6% +/- 3.6% (mean +/- SD) of the solid phase and 27.1% +/- 8.6% of the liquid phase of the meal had been emptied. Both U-50488 and tifluadom given orally (0.01-0.1 mg/kg) significantly increased (p less than 0.05) the 1-h emptying of the solid phase of the meal by 23.1%-49.6%. In contrast, both drugs significantly reduced emptying of liquids. These effects were not reproduced when similar doses were given intravenously. Oral administration of morphine or DAGO (0.01-0.1 mg/kg) did not affect gastric emptying, whereas an inhibited emptying of solids was observed for morphine at a higher dose (1 mg/kg p.o.). At a dose of 100 micrograms/kg i.v. both naloxone and MR 2266 (0.1 mg/kg) abolished the effects of orally administered U-50488 on gastric emptying of solids and liquids. It is concluded that kappa- but not mu-agonists act locally to alter gastric emptying of a standard meal in dogs, having opposite effects on solid and liquid phases. A selective local stimulation of kappa mucosal or submucosal receptors of the gastroduodenal area may explain such effects.     

Gastric emptying is accelerated in obese type 2 diabetic patients without autonomic neuropathy.

OBJECTIVE: To clarify the impact of type 2 diabetes mellitus on the gastric emptying rate. MATERIAL AND METHODS: Using a double-isotope scintigraphic technique, we assessed the gastric emptying of a standard liquid-solid meal in 13 obese type 2 diabetic patients without autonomic neuropathy (age: 47.4 +/- 8.6 yr, body mass index: 33.9 +/- 4.8 kg/m(2), glycaemia: 9.1 +/- 2.6 mmol/l) and in 7 controls with similar sex ratio, age, BMI and body fat distribution. RESULTS: The half gastric emptying time for the liquid phase was not significantly different between diabetic patients and controls (respectively: 52.7 +/- 14.5 min and 63.1 +/- 15.2 min). However, the half gastric emptying time for the solid phase was significantly shortened in diabetic patients versus controls (respectively 88.8 +/- 23.2 min in diabetic patients and 113.6 +/- 26.9 min in controls; p<0.04). Furthermore, a negative relationship was highlighted between the half gastric emptying time for the solid phase and basal glycaemia (r=-0.65, p<0.02) in diabetic patients. No significant relationship was found between gastric emptying parameters and cardiac autonomic nerve function, insulin or gastrin levels. CONCLUSION: Solid gastric emptying is accelerated in obese type 2 diabetic patients without patent autonomic neuropathy when compared to obese non diabetic patients.     

Gastric emptying and plasma neurotensin levels in untreated celiac patients

BACKGROUND: Upper gastrointestinal motor abnormalities could account for some of the dyspeptic symptoms of celiac patients. However, the data on gastric emptying time are conflicting, and the pathophysiology of motor disturbances is still unclear. Neurotensin modulates upper gastrointestinal motor activity, and its postprandial increase is a reliable index of nutrient delivery to the ileum. We therefore assessed both plasma neurotensin levels and gastric emptying in untreated celiacs. METHODS: The gastric antral area of nine untreated celiac patients and nine controls was measured with ultrasound at base line and every 30 min after a fatty meal (227 kcal, 45% fat); the base-line and postprandial neurotensin plasma levels were determined by means of radioimmunoassay. The data are mean values +/- standard deviation and were analyzed by using non-parametric tests. RESULTS: The overall and half gastric emptying time were significantly longer in the patients (203+/-32 versus 133+/-15 min, P = 0.0117, and 137+/-32 versus 78+/-11 min, P = 0.0001). The pattern of the changes in antral area was similar in both groups during the observation period as a whole but differed significantly in the first 120 min (P = 0.0343). Base-line neurotensin levels were significantly higher in the patients (41.6+/-23.9 versus 18.2+/-5.5 pg/ml, P = 0.0214) and their net postprandial increase was lower than in controls (15.0+/-15.9 versus 29.8+/-13.0 pg/ml, P = 0.046). In both groups the base-line neurotensin levels were related to the half gastric emptying time (P = 0.023). CONCLUSIONS: In untreated celiac patients gastric emptying time is longer than in controls and is concomitant with an increase in base-line plasma neurotensin levels.     

Estimation of B-cell function by the urinary excretion rate of C-peptide in diabetic patients: comparison with C-peptide response to glucagon and to a mixed meal

This study examined the relationship between the C-peptide response to intravenous glucagon and mixed meal stimulation and the 24 h urinary excretion rate of C-peptide and its urinary excretion during the glucagon test in nine control subjects, eighteen Type 1 (insulin-dependent) and twenty-two Type 2 (non-insulin-dependent) diabetic patients. Compared to controls (61.0 +/- 7.1 micrograms), the 24-h urine excretion rate of C-peptide was 8.2 +/- 3.1 micrograms (p less than 0.001) in Type 1 and 89.8 +/- 12.9 micrograms (p = NS) in Type 2 diabetic patients. C-peptide urinary excretion rate during the glucagon test was 6.92 +/- 1.11 micrograms, 0.42 +/- 0.10 microgram (p less than 0.001) and 6.47 +/- 1.13 micrograms (p = NS) respectively. Fasting serum C-peptide values were 1.53 +/- 0.16 ng/ml in controls, 0.42 +/- 0.09 ng/ml in Type 1 (p less than 0.0001) and 2.08 +/- 0.22 ng/ml in Type 2 diabetics (p = NS); C-peptide areas under the curve after glucagon stimulation were, respectively, 241.6 +/- 20.3 ng/ml, 29.2 +/- 5.9 ng/ml (p less than 0.0001) and 170.9 +/- 17.9 ng/ml (p less than 0.03) and after the meal test they were 204.7 +/- 15.6, 68.7 +/- 19.8 ng/ml (p less than 0.0001) and 265.5 +/- 32.9 ng/ml (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

An impaired accommodation of the proximal stomach to a meal is associated with symptoms after distal gastrectomy

OBJECTIVE: The aim of this study was to assess gastric emptying and postprandial proximal gastric tone variations depending on the presence of postoperative symptoms after Billroth II gastrectomy (BII). METHODS: A total of 16 consecutive patients were prospectively studied 10 +/- 3 months after distal gastrectomy for antral cancer. No evidence of cancer recurrence was detected at the time of the study. Ten patients were asymptomatic after surgery, whereas six patients were considered as symptomatic because of at least one weekly epigastric pain, postprandial fullness, nausea, or vomiting. The fasting fundus volume and tone, the onset of a gastric relaxation after a standard 200-kcal liquid meal, and the characteristics of this relaxation (delay of occurrence, amplitude) were determined with a barostat. Patient results were compared to normal values obtained in 12 healthy volunteers. Gastric emptying studies were performed in all patients using the C(13) acid octanoic breath test after a 250-kcal meal. RESULTS: In the patients, both fasting fundus tone (BII 7.0 +/- 0.5, controls 8.4 +/- 2.4 mm Hg) and volume (BII 108 +/- 11, controls 119 +/- 29 ml) were not different from controls. Fasting fundus tone was lower in asymptomatic patients than in symptomatic patients (6.5 +/- 0.4 vs 8.1 +/- 0.5 mm Hg, p < 0.04). Gastric relaxation was observed immediately after the meal in all asymptomatic patients as well as in controls. In contrast, gastric relaxation occurred in only two of six symptomatic patients (p < 0.01); when it occurred it was delayed by the meal and was observed only 23 +/- 1 min after food intake. When a relaxation occurred, its amplitude was higher than that observed in controls both in asymptomatic and symptomatic patients (294 +/- 21 vs 179 +/- 53 ml, p < 0.02). CONCLUSIONS: After distal gastrectomy, gastric accommodation is impaired (i.e., absent or delayed) in symptomatic patients. When relaxation exists in these patients, its amplitude is higher than in control subjects.     

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.     

Consequences of antral and duodenal acidification on acid secretion, gastrin response and gastric emptying in duodenal ulcer patients and normal subjects

The present study intended to investigate the effect of antroduodenal acidification on gastric acid secretion and emptying, gastrin and somatostatin release in response to food in healthy subjects as well as in duodenal ulcer patients. Ten duodenal ulcer patients and 9 normal controls were studied twice: the same 400 ml liquid protein meal (proteins: 10 g) was introduced into the stomach; then intragastric pH was either maintained at pH 4.5 or allowed to decrease in response to the meal. Acid secretion was calculated using the intragastric titration method (for which the intragastric pH is fixed at pH 4.5) and using the serial dilution indicator method (which allows antral acidification) respectively. Gastric emptying was estimated according to: a) iterative measurements of intragastric meal residual volume; b) volume passing through the pylorus. These two tests were performed in a random order and during each, plasma gastrin and somatostatin responses to the meal were determined. In healthy subjects, antral acidification following the meal was associated with a significantly lower acid secretion (17.3 +/- 0.9 mmol/h; m +/- SEM) than when the pH was maintained at pH 4.5 (20.2 +/- 1.3; p less than 0.05). Moreover, gastric emptying was slower when the pH was allowed to decrease (t 1/2: 26.2 +/- 1.4 min) than when the pH was constant (t 1/2: 20.5 +/- 2.2 min; p less than 0.05). By contrast, in the duodenal ulcer group, neither acid output nor gastric emptying were significantly different in the two situations.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Effects of Growth Hormone Deficiency and Recombinant Growth Hormone Therapy on Postprandial Gallbladder Motility and Cholecystokinin Release

In addition to cholecystokinin, other hormones have been suggested to be involved in regulation of postprandial gallbladder contraction. We aimed to evaluate effects of growth hormone (GH) on gallbladder contractility and cholecystokinin release. Gallbladder and gastric emptying (by ultrasound) and cholecystokinin release were determined before and after 6 months of recombinant human GH (rhGH) therapy in 12 patients with GH deficiency, after either a mixed (n = 5) or a liquid (n = 7) meal. Basal postprandial gallbladder contraction was severely impaired (19 +/- 2 and 26 +/- 3% of fasting volume after mixed and liquid meal, respectively). Histology and cholecystokinin sulfation patterns in duodenal biopsies from two patients were normal. After 6 months of rhGH therapy, fasting gallbladder volumes increased (from 20.8 +/- 0.9 to 25.9 +/- 1.1 mL, P < 0.05) and postprandial gallbladder emptying was restored (70 +/- 6 and 70 +/- 7% of fasting volume after mixed and liquid meal, respectively), without change of gastric emptying. Cholecystokinin secretion after a mixed meal and gallbladder sensitivity to cholecystokinin were significantly enhanced during rhGH replacement compared to the basal state. Postprandial cholecystokinin release, gallbladder responsiveness to cholecystokinin, and gallbladder emptying are severely impaired in the absence of GH. Reversibility during GH suppletion suggests its involvement in regulation of gallbladder contractility.     

Gastric emptying of realistic meals with and without gluten in patients with coeliac disease. Effect of jejunal mucosal recovery

BACKGROUND: Few data are available on disturbed gastric emptying in patients with coeliac disease. The aims of the study were to investigate (a) the presence of delayed gastric emptying: (b) the acute effect on gastric emptying of gliadin; and (c) the effect of jejunal recovery on gastric emptying of meals with or without gluten in such patients. METHODS: We measured gastric emptying of two meals in 16 patients with coeliac disease; one meal contained gliadin. Results were compared with those obtained in 24 controls. In 12 patients, both measurements were repeated after mucosal recovery. Statistical analysis was performed using the analysis of variance for repeated measurements and Student's t test. Mean +/- 1 s(mean) (standard error of the mean) are shown. RESULTS: No difference was found in fasting and in maximal antral sections after the two meals. On entry, gastric emptying was significantly (P < 0.001) delayed compared to controls both after the meal containing gluten (326.9 +/- 12.4 min versus controls 213.5 +/- 11.5) and after the gluten-free meal (315.3 +/- 16.7 min). After jejunal recovery, emptying of the meal containing gluten remained unchanged (337 +/- 18.9 min), whereas emptying of the gluten-free meal was significantly shortened (280.6 +/- 10.5 min; P < 0.001). CONCLUSIONS: In coeliac disease there is an impairment of gastric emptying which is at least partially reversible. This suggests either an immunological disorder or that unabsorbed meal constituents are responsible for an ileal-brake effect.     

The influence of the interdigestive migrating myoelectric complex on the gastric emptying of liquids

It is unknown how the interdigestive migrating motor complex influences the gastric emptying of liquids. Therefore, the gastric emptying rate of 50- and 200-mL volumes of phenol red solution were measured while monitoring contractile activity. Motor activity was recorded using a hydraulic manometric system and expressed as either the proximity of dosing time to time of appearance of phase III or as a motility index, defined as (contractile area)/(sampling interval time). After an initial lag period, emptying was log linear. With a 50-mL oral dose, the mean gastric emptying rate of the log-linear phase was successively faster during phase I (0.018 +/- 0.003 min-1), phase II (0.083 +/- 0.031 min-1), and late phase II/III (0.171 +/- 0.066 min-1) (P less than 0.05). Similarly, the mean lag time decreased successively with phases I, II, and late II/III (19.1 +/- 12.4, 7.6 +/- 5.6, and 3.8 +/- 2.8 minutes, respectively). At a 200-mL oral dose, there was no difference in the emptying rate between phase I and phase II (0.104 +/- 0.0014 vs. 0.110 +/- 0.041 min-1), but the emptying rate during late phase II/III was significantly greater (0.236 +/- 0.069 min-1); lag time was not dependent on phase. There was a statistical difference in the overall mean emptying rate between the 50- and 200-mL volumes. Also, during phase I, the emptying rate was faster for the 200-mL volume. This study shows a strong dependence of liquid gastric emptying rate and lag time on interdigestive antral motility, the emptying of small volumes being more dependent on motility phase than that of large volumes. Phase-related fluctuations in contractile activity can account for much of the reported variability in gastric emptying data. Furthermore, this study suggests that dose volume and interdigestive motor activity at the time of drug administration can affect absorption and onset of therapeutic response for some drugs.     

Gallbladder emptying and somatostatin and cholecystokinin plasma levels in celiac disease

OBJECTIVE: Gallbladder hypomotility in celiac disease has been attributed to decreased cholecystokinin secretion. The possible influence of somatostatin, which inhibits gallbladder motility, however, has never been evaluated. In this study gallbladder emptying and cholecystokinin and somatostatin plasma levels were evaluated in response to a fatty meal in patients with celiac disease at diagnosis and after long-term gluten-free diet and in controls. METHODS: Gallbladder volume and plasma levels of cholecystokinin and somatostatin were measured by ultrasonography and radioimmunoassay, respectively, at 0 time and 30, 60, 75, and 90 min after an oral fatty meal (227 kcal, 45% fat) in 10 celiac patients at diagnosis and after 18 months of successful gluten-free diet and in 10 healthy subjects. The pattern of gallbladder emptying was evaluated by mixed factorial analysis of variance and the curve fitting by multiple regression analysis. RESULTS: Patients at diagnosis had significantly greater fasting gallbladder volume and higher somatostatin plasma levels than controls (25.7 +/- SD 9.7 ml vs 16.8 +/- 7.0 ml, p = 0.021 and 9.3 +/- 4.6 vs 4.8 +/- 3.4 pmol/L, p = 0.023, respectively), significantly lower fatty meal-induced gallbladder ejection fraction (55 +/- 11.2% vs 76 +/- 7.2%, p = 0.005), and cholecystokinin peak and smaller area under the cholecystokinin secretion curve (3.1 +/- 2.3 pmol/L vs 10.5 +/- 6.9 pmol/L, p = 0.028 and 157 +/- 142 pmol/L/90 min vs 453 +/- 229 pmol/L/90 min, p = 0.028, respectively). The two groups had a similar emptying pattern (p = 0.8913) expressed by a significant quadratic term of the emptying function (p = 0.0001). The mean overall emptying volume was significantly greater in patients than in controls (p = 0.0007). Gluten-free diet normalized these findings. CONCLUSIONS: In patients at diagnosis, elevated somatostatin levels were associated with increased gallbladder fasting volume, whereas decreased cholecystokinin secretion was responsible for the reduced gallbladder emptying. Gluten-free diet reversed these abnormalities.