Demethylation of the progesterone receptor CpG island is not required for progesterone receptor gene expression

In a previous study we have shown that an intravenous infusion of pramlintide (an analogue of human amylin) delayed gastric emptying, but the dose of pramlintide was supraphysiological in relation to the amylin response to food in non-diabetic subjects. The purpose of this study was to examine the dose response relationship of subcutaneous injections of pramlintide on gastric emptying and to determine whether administration of the drug before one meal has an impact on the subsequent meal. Eleven men with insulin-dependent diabetes mellitus were studied in a double-blind, randomised, four-way crossover design. None had autonomic neuropathy. Euglycaemia was maintained overnight before the study day. At -30 min the patients self-injected their usual morning insulin and at -15 min they injected the study drug (either placebo or 30, 60 or 90 microg pramlintide) subcutaneously. At 0 min they ate a standard meal consisting of a pancake, labelled with 99mTc, and a milkshake containing 3-ortho-methylglucose (3-OMG). Gastric emptying images were obtained for the next 8 h. At 240 min the subjects ate a similar meal, but on this occasion the pancake was labelled with (111)In. All three doses of pramlintide delayed emptying of the solid component of the first meal (p < 0.004) with no significant difference between the drug doses. There were no differences between placebo and pramlintide after the second meal. All three doses of pramlintide resulted in a prolongation in the time to peak plasma 3-OMG level (p < 0.0001) after the first meal but there was no difference after the second meal.     

Gastric emptying in Mexican Americans compared to non-Hispanic whites

Mexican Americans, a group at high risk for type II diabetes mellitus, have higher postprandial insulin and glucose levels when compared to non-Hispanic whites. A rapid rate of gastric emptying contributes to an increased rate of nutrient absorption and subsequent greater elevation of postprandial glucose and insulin levels. A more rapid rate of gastric emptying and hyperinsulinemia have been observed in patients with recently diagnosed type II diabetes mellitus. In this study, we examined whether Mexican Americans have a more rapid rate of gastric emptying than non-Hispanic whites. Gastric emptying studies were performed on 32 nondiabetic Mexican Americans and on 31 nondiabetic non-Hispanic whites. The rate of gastric emptying following a liquid glucose meal was measured. Serum insulin, plasma glucose, and GIP levels were measured in fasting and postprandial blood samples collected at 15-min intervals for 2 hr. Adjusting for age, body mass index, and gender, the gastric half-emptying time of a glucose meal was significantly (P < 0.05) more rapid for the Mexican American subjects (56.5 +/- 3.4 min) compared to the non-Hispanic white subjects (66.4 +/- 3.5 min). Nondiabetic Mexican Americans empty a liquid glucose meal more rapidly from their stomachs than nondiabetic non-Hispanic whites. Rapid gastric emptying is associated with hyperinsulinemia as a normal physiologic response to increased nutrient availability. The rapid gastric emptying observed in nondiabetic Mexican Americans is associated with hyperinsulinemia and could be a contributing factor for the increased risk of obesity and type II diabetes in this population.     

Relationships between gastric emptying, intragastric meal distribution and blood glucose concentrations in diabetes mellitus

The aim of this study was to evaluate the prevalence of disordered intragastric meal distribution and the relationships between gastric emptying, intragastric distribution, glycemic control and gastrointestinal symptoms in diabetes mellitus. METHODS: Eighty-six patients with diabetes mellitus had measurements of gastric emptying and intragastric distribution of a radioisotopically labeled solid/liquid meal (100 g beef and 150 ml 10% dextrose), glycemic control (plasma glucose concentrations), upper gastrointestinal symptoms (questionnaire) and autonomic nerve function (cardiovascular reflexes). Results were compared to those obtained in 20 normal volunteers. RESULTS: Solid and liquid gastric emptying were delayed in the diabetic patients and correlated weakly. Intragastric meal distribution was also often abnormal, with increased retention of both solid and liquid in the proximal stomach and increased retention of solid but not liquid in the distal stomach. In all patients with increased retention of solid in the proximal stomach, emptying from the total stomach was delayed. Gastric emptying of liquid was slower in those subjects who had a mean plasma glucose > 15 mmol/liter during the gastric emptying measurement, when compared to the remainder of the group. CONCLUSION: In patients with diabetes mellitus, there is poor relationship between solid and liquid gastric emptying and intragastric meal distribution is frequently abnormal. Interpretation of the results of gastric emptying measurements should consider meal composition and plasma glucose concentrations.     

Epstein-Barr virus associated gastric carcinoma: the genetic alteration and the expression of CD44 variant

BACKGROUND: Chronic symptomatic gastroparesis occurs in 3-5% of patients following vagotomy and antrectomy. Erythromycin, a macrolide antibiotic, improves gastric emptying in patients with idiopathic and diabetic gastroparesis. Erythromycin's effect on gastric emptying in patients with post-vagotomy-antrectomy gastroparesis is unknown. The aim of this study was to determine if a single dose of intravenous erythromycin (1 mg/kg or 6 mg/kg) accelerates solid meal gastric emptying in patients with chronic symptomatic post-vagotomy-antrectomy gastroparesis. METHODS: Six patients were entered into the study, three males and three females, with a mean age of 50 years. Four patients were randomized to receive erythromycin 6 mg/kg and two patients 1 mg/kg. The mean time since initial surgery was 9.2 years (range 1-16 years) with five patients having undergone a Roux-en-Y revision. RESULTS: Intravenous erythromycin significantly lowered percentage gastric retention at 120 min, from a baseline of 90.5 +/- 6% (S.E.M.) to 40.1 +/- 4.8% after erythromycin (P = 0.0002). Erythromycin improved gastric emptying in each patient by at least 40%. Intravenous erythromycin significantly accelerated the rate of gastric emptying in the first 30 min after meal ingestion from a baseline rate of 0.072 +/- 0.06%/min to 0.96 +/- 0.31%/min after erythromycin (P = 0.028). For each of the subsequent 30 minute time periods, erythromycin had no significant effect on the rate of gastric emptying. CONCLUSION: Intravenous erythromycin significantly improves the initial phase of solid meal gastric emptying in patients with chronic symptomatic post-antrectomy-vagotomy gastroparesis.     

Abnormal progression of a liquid meal through the stomach and small intestine in patients with Chagas' disease

This study describes the abnormal pattern of gastrointestinal progression of a liquid meal in patients with the digestive form of chronic Chagas' disease. This condition is known as a natural model of intramural denervation of the gut. Sixteen patients with clinical and radiographic evidence of esophageal and/or colonic involvement and 18 healthy volunteers were studied. Orocecal transit time after the ingestion of a 10% lactulose solution (180 ml) tagged with 99mtechnetium was measured by a conventional H2 breath technique. Gastric emptying and the arrival of the front of the meal to regions of interest corresponding to proximal and distal areas of the small intestine were assessed by abdominal scintigraphy. Orocecal transit time was significantly greater (P < 0.05) in Chagas' disease patients (N = 13) than in control subjects (N = 18) (mean +/- SD: 100.7 +/- 48.7 min vs 62.9 +/- 18.2 min). Half-time for gastric emptying of liquids in chagasic patients (N = 9) was significantly lower (P < 0.01) than in controls (N = 7) (9.7 +/- 2.7 min vs 26.4 +/- 3.4 min). The time of arrival of the liquid meal to the proximal small intestine was also significantly shorter (P < 0.02) in patients than in controls (5.6 +/- 3.7 vs 11.4 +/- 5.5 min), but there was no difference between the two groups concerning the time the meal first arrived to the distal small intestine (15.0 +/- 11.0 min vs 23.5 +/- 11.4 min, P > 0.05). These results indicate that patients with Chagas' disease have a combination of exceedingly rapid gastric emptying and abnormally delayed transit of liquids through the more distal segments of the small bowel.(ABSTRACT TRUNCATED AT 250 WORDS)     

Does Helicobacter pylori infection affect gastric emptying in patients with functional dyspepsia?

The objectives of the study were first, to determine if gastric emptying was altered in patients with functional dyspepsia with and without Helicobacter pylori infection compared with normal healthy volunteers; and second, to determine if there were further alterations in gastric emptying when the infection was eradicated. Gastric emptying was measured using a 99mtechnetium radiolabelled solid meal and gastric emptying time was measured as t1/2, viz. time taken for half the radiolabelled meal to be emptied from the stomach. The mean gastric emptying time for H. pylori-positive patients (n=20) was 56.4+/-24.8 min; H. pylori-negative patients (n=19) 67.8+/-31.8 min; and normal controls (n=20) 58.8+/-18.8min. No significant difference was obtained between the groups (ANOVA; P=0.348). Thirteen of 18 H. pylori-positive patients successfully eradicated the infection following treatment with omeprazole 40 mg o.m. and amoxycillin 500 mg t.d.s. for 2 weeks. The mean difference in the gastric emptying time before and after H. pylori eradication was 23.9+/-13.2 min (P= 0.556). There was no significant difference in the frequency of specific dyspeptic symptoms as well as the overall mean symptom score between the H. pylori-positive and -negative patients. Gastric emptying was not different between patients with functional dyspepsia and normal controls. Helicobacter pylori infection does not appear to affect gastric emptying in patients with functional dyspepsia.     

Gastric myoelectrical activity, gastric emptying and correlations with dyspepsia symptoms in patients with gastroesophageal reflux

BACKGROUND: Delayed gastric emptying is a mechanism that contributes to the pathogenesis of gastroesophageal reflux. Electrogastrogram changes, gastric emptying rates, and Helicobacter pylori status were investigated, and a correlation was sought with dyspepsia symptoms in gastroesophageal reflux disease patients. METHODS: Fifty patients (27 females; mean age 43) with gastroesophageal reflux were studied. Electrogastrographic recordings were obtained 30 minutes before and simultaneously with a 2-hour radionuclide gastric-emptying test using an isotope-labeled solid meal. Symptoms of nausea, abdominal bloating, abdominal pain, and early satiety were graded from 0 to 5. RESULTS: Thirty-six percent of patients had delayed gastric eliminating. Thirty-eight percent (19/50) patients had abnormal electrogastrograms, and 11 of these 19 also had delayed gastric emptying. There was a significant difference in the electrogastrographic parameter of postprandial power change in patients with delayed versus normal gastric emptying (0.20 +/- 0.8 dB vs 3.17 +/- 0.8 dB, p < 0.05). In patients with an abnormal electrogastrogram, the mean symptom score was significantly higher than in patients with a normal electrogastrogram (2.18 +/- 0.26 vs 1.35 +/- 0.16, p < 0.05). Twenty-one percent (7/33) of patients were positive (+) for Helicobacter pylori overall, but this did not seem to affect electrogastrogram and gastric emptying findings. CONCLUSIONS: Fifty-two percent of gastroesophageal reflux disease patients have gastric motor or myoelectrical abnormalities that contribute to the pathogenesis of this entity and also help explain the high prevalence of dyspepsia in the clinical presentation of gastroesophageal reflux disease.     

Effects of cigarette smoking on solid and liquid intragastric distribution and gastric emptying

BACKGROUND: The acute effects of cigarette smoking on gastric emptying are controversial, whereas its effects on the intragastric distribution of solids and liquids are not established. METHODS: Dual isotope gastric scintigraphy was performed in 15 habitual smokers (studied twice, either sham smoking or actively smoking) and in 15 age- and sex-matched nonsmokers. RESULTS: Acute smoking was associated with an increased prevalence of episodes of retrograde intragastric movement of solids (3 of 15 sham subjects vs. 12 of 15 actively smoking subjects; P < 0.01) and of liquids (0 of 15 vs. 7 of 15; P < 0.01) from distal to proximal stomach. Fundal half-emptying time (T1/2) for liquids was also prolonged by smoking (43 +/- 19 minutes sham vs. 125 +/- 216 minutes active; P < 0.05). Acute smoking delayed solid lag time (13 +/- 6 minutes sham vs. 32 +/- 18 active; P < 0.05) and liquid T1/2 (46 +/- 21 vs. 90 +/- 50 minutes; P < 0.05). In the nonsmokers, such episodes of proximal intragastric redistribution did not occur, and intragastric and overall emptying parameters did not differ significantly from those of habitual sham smokers. CONCLUSIONS: Acute cigarette smoking produces excessive antrofundal redistribution of both solid and liquid contents and delays solid and liquid gastric emptying.     

Gastric emptying as an etiopathogenic factor in gastroesophageal reflux disease

The aim of this study is to evaluate gastric emptying change in patients with gastroesophageal reflux (GER). To this purpose, 36 patients with GER diagnosis and 18 control subjects have been studied. GER diagnosis was achieved by means of endoscopy, biopsy and 24 h continuous pH monitoring. Gastric emptying studies were performed on a two day basis, similar labelling meals were provided to patients and control subjects. Those consisted in a one-egg omelette, chicken (110 gr) and orange juice (200 ml). On first day liquid phase was labelled with 99mTc-diethylenetriamine pentaacetic acid (99mTc-DTPA), and on second day, the solid phase was labelled with 99mTc-sulfur colloid in the omelette (Labelling efficiency was 85.3 +/- 3.2%). The studies were carried out by imaging static anterior and posterior views every 20 minutes for a total of 180 minutes. Images were quantified obtaining solid and liquid gastric emptying curves. No statistical significative difference between patients and control subjects gastric emptying results were found. We can conclude that gastric emptying is not a main factor in the pathogenesis of gastroesophageal reflux.     

Glucagon-like peptide I enhances the insulinotropic effect of glibenclamide in NIDDM patients and in the perfused rat pancreas

OBJECTIVE: To investigate the acute effects of glibenclamide and glucagon-like peptide I (GLP-I) and their combination in perfused isolated rat pancreas and in patients with secondary failure to sulfonylureas. RESEARCH DESIGN AND METHODS: Rat islets were perfused with 10 nmol/l GLP-I in combination with 2 mumol/l glibenclamide. In human experiments, GLP-I (0.75 pmol. kg-1.min-1) was given as a continuous infusion during 240 min, while glibenclamide (3.5 mg) was administered orally. Eight patients participated in the study (age 57.6 +/- 2.7 years, BMI 28.7 +/- 1.5 kg/m2, mean +/- SE). In all subjects, blood glucose was first normalized by insulin infusion administered by an artificial pancreas (Biostator). RESULTS: GLP-I increased the insulinotropic effect of glibenclamide fourfold in the perfused rat pancreas. In human experiments, treatment with GLP-I alone and in combination with glibenclamide significantly decreased basal glucose levels (5.1 +/- 0.4 and 4.5 +/- 0.1 vs. 6.0 +/- 0.3 mmol/l, P < 0.01), while with only glibenclamide, glucose concentrations remained unchanged. GLP-I markedly decreased total integrated glucose response to the meal (353 +/- 60 vs. 724 +/- 91 mmol.l-1. min-1, area under the curve [AUC] [-30-180 min], P < 0.02), whereas glibenclamide had no effect (598 +/- 101 mmol.l-1. min-1, AUC [-30-180 min], NS). The combined treatment further enhanced the glucose lowering effect of GLP-I (138 +/- 24 mmol. l-1.min, AUC [-30-180 min], P < 0.001). GLP-I, glibenclamide, and combined treat-stimulated meal-induced insulin release as reflected by insulinogenic indexes (control 1.44 +/- 0.4; GLP-I 6.3 +/- 1.6, P < 0.01; glibenclamide 6.8 +/- 2.1, P < 0.01; combination 20.7 +/- 5.0, P < 0.001). GLP-I inhibited basal but not postprandial glucagon responses. Using paracetamol as a marker for gastric emptying rate of the test meal, treatment with GLP-I decreased gastric emptying at 180 min by approximately 50% compared with the control subjects (P < 0.01). CONCLUSIONS: In acute experiments on overweight patients with NIDDM, GLP-I exerted a marked antidiabetogenic action on the basal and postprandial state. The peptide stimulated insulin, suppressed basal glucagon release, and prolonged gastric emptying. The glucose-lowering effect of GLP-I was further enhanced by glibenclamide. This action may be at least partially accounted for by a synergistic effect of these two compounds on insulin release. Glibenclamide per se enhanced postprandial but not basal insulin release and exerted a less pronounced antidiabetogenic effect compared with GLP-I.     

The different components of gastric emptying after gastric surgery

Gastric emptying of liquid and solid meals was studied before and after operation in 22 male patients who were admitted to a prospective randomized trial of truncal vagotomy and antrectomy and proximal gastric vagotomy in the treatment of duodenal ulceration. After operation the emptying of both solid and liquid meals was biphasic, with a passive early phase and a later controlled active phase. A significant increase in early liquid emptying was produced by both operations, and after truncal vagotomy and antrectomy also with the solid meal. Active emptying of the liquid meals was unaffected by either operation, but both operations significantly prolonged the active emptying of the solid meals. The clinical symptoms of dumping were related to rapid early liquid emptying (cascading) and those of gastric retention were related to delayed active emptying of the solid meal. These findings explain how the same operation can produce the opposing symptom complexes of dumping and gastric retention and how both sets of symptoms can occur in the same individual.     

Mechanisms of the antidiabetic action of subcutaneous glucagon-like peptide-1(7-36)amide in non-insulin dependent diabetes mellitus

Twelve patients with non-insulin dependent diabetes mellitus (NIDDM) under secondary failure to sulfonylureas were studied to evaluate the effects of subcutaneous glucagon-like peptide-1(7-36)amide (GLP-1) on (a) the gastric emptying pattern of a solid meal (250 kcal) and (b) the glycemic and endocrine responses to this solid meal and an oral glucose tolerance test (OGTT, 300 kcal). 0.5 nmol/kg of GLP-1 or placebo were subcutaneously injected 20 min after meal ingestion. GLP-1 modified the pattern of gastric emptying by prolonging the time to reach maximal emptying velocity (lag period) which was followed by an acceleration in the post-lag period. The maximal emptying velocity and the emptying half-time remained unaltered. With both meals, GLP-1 diminished the postprandial glucose peak, and reduced the glycemic response during the first two postprandial hours by 54.5% (solid meal) and 32.7% (OGTT) (P < 0.05). GLP-1 markedly stimulated insulin secretion with an effect lasting for 105 min (solid meal) or 150 min (OGTT). The postprandial increase of plasma glucagon was abolished by GLP-1. GLP-1 diminished the postprandial release of pancreatic polypeptide. The initial and transient delay of gastric emptying, the enhancement of postprandial insulin release, and the inhibition of postprandial glucagon release were independent determinants (P < 0.002) of the postprandial glucose response after subcutaneous GLP-1. An inhibition of efferent vagal activity may contribute to the inhibitory effect of GLP-1 on gastric emptying.     

Contribution of gastric and postgastric feedback to satiation and satiety in women

Two parallel preload studies were conducted to determine the relative contributions of inhibitory feedback from the stomach and intestine to satiation (meal termination) and postprandial satiety. In the Gastric Emptying Study, five normal-weight women each ingested an egg sandwich (307 kcal) (1) immediately after a tomato soup preload (120 kcal), (2) 20 min after a tomato soup preload, and (3) with no preload. There was 125 g more of soup in the stomach when subjects began ingesting the sandwich immediately compared to 20 min after the soup, and the emptying of the sandwich was delayed when it was ingested immediately but not 20 min after the soup. The lag times for emptying of the sandwich were 76.5 (69.1-82.4), 47.2 (20.1-67.7), and 42.4 (17.8-65.1) min for the three conditions, respectively, p < 0.05. In the Food Intake Study, 16 normal-weight women ate significantly less (p < 0.01) in test meals offered immediately (978+/-246 kcal) and 20 min (1027+/-298 kcal) after the soup preload than in a test meal with no preload (1151+/-279 kcal). Despite the different amounts of soup in the stomach, subjects' test-meal intake in the two preload conditions was not significantly different. Subjects' fullness ratings following the preloads and the test meals were not different among the treatment conditions. The results suggest that feedback from neither the gastric nor the postgastric compartment is primary in determining meal size and postprandial satiety. Instead, signals from gastric and postgastric sources are combined to determine meal size and postprandial satiety.     

Gastric emptying of solid meals in diabetics

The gastric emptying rate of an isotopically labelled solid meal was compared in 29 insulin-dependent well-controlled diabetics and 18 normal controls. The diabetics were assessed for evidence of autonomic neuropathy. No significant difference in gastric emptying rate was found between controls and diabetics with or without autonomic neuropathy. Only three diabetics had greatly delayed gastric emptying, but in one of these the test had given a normal result on an earlier occasion.     

Comparison of total and compartmental gastric emptying and antral motility between healthy men and women

There is increasing evidence of gender-related differences in gastric emptying. The purpose of this study was first, to confirm the difference in gastric emptying for both solid and liquid test meals between healthy men and women, and secondly, to investigate the origin of this difference by studying regional gastric emptying and antral motility. A standard gastric emptying test with additional compartmental (proximal and distal) evaluation and dynamic imaging of the antrum was performed in 20 healthy women studied during the first 10 days of the menstrual cycle, and in 31 healthy age-matched men. In concordance with previous reports, women had a longer half-emptying time for solids as compared to men (86. 2+/-5.1 vs 52.2+/-2.9 min, P<0.05). In our observations this seemed to be related to a significantly prolonged lag phase and a significant decrease in terminal slope. Dynamical antral scintigraphy did not show a significant difference. The distribution of the test meal within the stomach (proximal vs distal) showed more early proximal retention in women as compared to men. The terminal slope of the distal stomach was significantly lower in women. We did not observe a significant difference in gastric emptying of the liquid test meal between men and women. Gastric emptying of solids is significantly slower in healthy women as compared to men. These findings emphasise the importance of using different normal values for clinical and research purposes in gastric emptying scintigraphy in men and women. The difference could not be explained by antral motility alone. Increased proximal retention and a lower terminal emptying rate in women are observations to be further investigated.     

Raising milk energy content retards gastric emptying of lactose in lactose-intolerant humans with little effect on lactose digestion

Lactose digestion improves when the energy content of a meal is raised, perhaps due to delayed gastric emptying; however, this has not been demonstrated directly. It is not known whether lactose-intolerant subjects should consume full-fat or high energy milk instead of half-skimmed milk. In this study, breath 13CO2 and hydrogen (H2) measurements were combined to assess simultaneously the effect of increasing milk energy content on gastric emptying, digestion, and tolerance of lactose. On two separate days, 11 adult lactose maldigesters ingested, in the fasting state, a single dose of 710 kJ half-skimmed milk or 1970 kJ high energy milk. Both contained 18 g lactose and were supplemented with 100 mg 13C-glycine for breath 13CO2 measurement. For 6 h after milk ingestion, samples of expired breath were collected, and subjects scored their symptoms on a four-grade questionnaire. Gastric emptying was measured from excretion of breath 13CO2. The mean gastric emptying half-time was significantly longer after ingestion of high energy milk than after half-skimmed milk (84 +/- 4 vs. 64 +/- 4 min, P = 0.004). The mean area under the breath H2 excretion curve measured for 6 h was 330 +/- 61 microL/L after subjects consumed high energy milk vs. 470 +/- 82 microL/L after they consumed half-skimmed milk (P = 0.07). Mean symptom scores did not differ after ingestion of the two milks, but only two subjects experienced disturbing symptoms after high energy milk ingestion compared with five subjects after ingestion of half-skimmed milk (P = 0.56). Although ingestion of high energy milk delayed the gastric emptying of lactose for significantly longer than the ingestion of half-skimmed milk (P < 0.01), it did not lead to significant improvement in symptoms and reflected only a trend toward improved lactose digestion (P = 0.07), as measured by the area under the breath H2 excretion curve. These results indicate that it is not beneficial for most lactose-intolerant subjects to replace consumption of half-skimmed milk by milk with a higher energy content.     

Improved computer analysis of solid phase gastric emptying scans

OBJECTIVES: The solid phase gastric emptying scan (GES) is used to confirm the clinical impression of abnormal gastric emptying. There is variability in the interpretation of GES. Determination of initial lag phase of the GES and the emptying half-time (t1/2) is generally performed by curve inspection and thus may suffer from lack of objectivity. The purpose of this study was to develop a physiological model for interpretation of the GES using nonlinear curve fitting. This model resulted in computer-generated best fits for lag time and t1/2, which were analyzed in a group of patients with suspected gastroparesis. METHODS: All gastric emptying scans performed at our institution over a 3.5-yr period were studied. Raw data from these studies were analyzed by nonlinear curve fitting. Using the equation: If (x < xo, plateau, plateau * exp( - K * (x - xo))) data were best fit to a function describing a lag followed by a log linear decay. This model generated four parameters; lag, K, t1/2, and T50%. Forty patients with less than 50% emptying at 1 h (group II) were compared with 31 patients with normal emptying (group I). RESULTS: The nonlinear model resulted in better curve fitting (higher r2) in 59 of 71 studies (81%) when compared with a monoexponential decay after a lag of 0 min. Mean lag for patients in group I was 8.5 +/- 1.2 min and was 25.9 +/- 3.1 min in group II (p < 0.0005). Mean t1/2 was 31.7 +/- 1.8 min in group I and 69.7 +/- 5.0 min in group II (p < 0.007). By adding 2 SD to lag and t1/2 in group I, normal values for these parameters were 21.9 and 52.2 min, respectively. Eleven patients in group II had a prolonged lag alone, 13 had a prolonged t1/2, and 13 had prolongation of both parameters. CONCLUSIONS: A new physiological model for the interpretation of GES is presented. Individual patients with delayed gastric emptying may have increased lag times, a decreased rate of antral emptying, or both abnormalities.     

Camostate- and caerulein-induced delay of gastric emptying in the rat: effect of CCK receptor antagonists

The effect of camostate, a potent releaser of endogenous cholecystokinin (CCK), and of caerulein, an amphibian peptide mimicking the biological actions of CCK, as well as of selective CCK receptor antagonists on gastric emptying of liquids was studied in the rat. Oral administration of camostate (200 mg/kg with the liquid test meal preceded by the same dose 10 min before the meal) significantly delayed gastric emptying of saline, an effect which was completely blocked by previous administration of the CCKA receptor antagonist, devazepide, at a dose (1 mg/kg i.v.) unable to modify the emptying rate when administered alone. Caerulein (0.03-30 nmol/kg i.v.) also delayed the emptying rate in a dose-dependent manner, with an ID50 of 3.94 nmol/kg. The effect of the peptide was also inhibited by devazepide. The CCKB receptor antagonist, L365,260 (3R-(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1, 4-benzodiazepine-3-yl)-N'-(3-methylphenyl)-urea; 3 mg/kg i.v.), was completely unable to modify the CCK (both endogenous and exogenous)-induced delay in gastric emptying. Repeated (7 days) camostate administration did not modify the gastric motor response to endogenous CCK, thus, suggesting that adaptation did not take place. These results demonstrate that endogenous and exogenous CCK delays gastric emptying of liquids through stimulation of CCKA receptors and suggest that adaptation of the gastric motor response to CCK does not occur.     

Gastric emptying in control subjects and patients with duodenal ulcer before and after vagotomy

The emptying of a solid meal labelled with Indium 113mDTPA from the stomach was studied with a gamma camera in 26 normal subjects, 27 patients with duodenal ulcer, on 41 occasions after truncal vagotomy and pyloroplasty and 38 times after highly selective vagotomy. Applying the method of principal component analysis to the results, differences were detected between control and duodenal ulcer subjects and two probable subgroups of duodenal ulcer were observed. Half emptying times did not reveal these patterns. After vagotomy, delayed emptying was general at one week. At one month, patients after highly selective vagotomy had a more normal result than those with truncal vagotomy and pyloroplasty (TV), but by six months no significant difference in overall emptying rate was found, although changes in the pattern of gastric emptying persisted in some patients after TV.     

A new operative technique of posttraumatic syringomyelia: thecoperitoneal shunt]

The aims of this study were to evaluate the gastric emptying of solids in patients with progressive systemic sclerosis, correlate the esophageal motility abnormalities with their gastric emptying status, delineate the symptoms suggestive of abnormal gastric emptying, and assess the effect of metoclopramide in patients with abnormally slow gastric emptying. Twenty patients underwent esophageal motility evaluation and gastric emptying studies with a radiolabeled solid meal. Gastric emptying was also measured in 13 healthy volunteers. Four patients in whom esophageal motility was normal also had an accompanying normal rate of gastric emptying. In 16 patients with abnormal esophageal motility, mean gastric emptying was significantly delayed as compared with that in normal subjects (67.4% vs 49.8% retention of isotope at 2 hours, P < .05). Ten patients had absolute criteria for slow gastric emptying (>+2 SD). However, only postprandial bloating and early satiety were symptoms that accurately predicted slow radionuclide emptying. In four of these patients in whom gastric emptying was slow, 10 mg intramuscular metoclopramide significantly (P < .05 vs baseline) accelerated the gastric emptying of the same test meal. We conclude that (1) gastric emptying of solids was delayed in approximately two thirds of patients with abnormal esophageal motility, whereas it was normal in patients with normal esophageal motor function; (2) metoclopramide significantly accelerated this slow gastric emptying; and (3) delayed gastric emptying contributes to the severity of the gastroesophageal reflux frequently present in patients with progressive systemic sclerosis, and promotility agents offer a valuable therapeutic approach.