James H. Meyer

Analysis of Gastric Emptying Data

How should gastric emptying data be summarized to allow comparisons between males or between groups of subjects within a study, and to facilitate comparisons of results from study to study. We review standardization issues for reporting gastric emptying data, discuss criteria for choosing a method of analysis, review methods which have been used to describe gastric emptying data, recommend trial of the power exponential curve, and illustrate its use in the analysis and interpretation of data from several studies involving different types of meals and different types of subjects. We show why nonlinear curves should be fit using nonlinear least squares.

Human postprandial gastric emptying of 1–3-millimeter spheres

Microspheres of pancreatin should empty from the stomachs of patients with pancreatic insufficiency as fast as food. The present study was undertaken in 26 healthy subjects to identify the size of spheres that would empty from the stomach with food and to determine whether different meals alter this size. Spheres of predefined sizes were labeled with 113mIn or 99mTc. Using a gamma-camera, we studied the concurrent gastric emptying of spheres labeled with 113mIn and of chicken liver labeled with 99mTc in 100-g, 154-kcal or 420-g, 919-kcal meals, or the concurrent emptying of 1-mm vs. larger spheres. One-millimeter spheres emptied consistently (p less than 0.01, paired t-test) faster than 2.4- or 3.2-mm spheres when ingested together with either the 420- or 100-g meals. Thus, in the 1-3-mm range of diameters, sphere size was a more important determinant of sphere emptying than meal size. Statistical analyses indicated that spheres 1.4 +/- 0.3 mm in diameter with a density of 1 empty at the same rate as 99mTc-liver. Our data indicate some commercially marketed microspheres of pancreatin will empty too slowly to be effective in digestion of food.

Effect of size and density on canine gastric emptying of nondigestible solids

Previous studies suggested that the food-containing canine stomach retains large, nondigestible spheres until all food has emptied; but it is not known whether there is a threshold size or a gradation of sizes that will empty along with food. Further, nothing is known of the effects of such parameters as density, shape, and surface energy on the emptying of nondigestible particles of any given size. To answer these questions 6 dogs with chronic duodenal fistulas were studied. Radiolabeled food and spheres were collected from the fistulas to compare the rate of gastric emptying of the spheres with that of the food. After a standard test meal of 99mTc-labeled liver, steak, and water, diverted chyme was collected over a stack of sieves in 30-min fractions over 5 postcibal hours. The percent of fed spheres and fed 99mTc-labeled liver in each collection was counted, and liquid chyme was returned to the distal duodenum. Spheres with a density of 1 emptied progressively faster as sphere diameters were decreased from 5 to 1 mm; but 0.015-mm spheres emptied at about the same rate as those with diameters of 1 mm. Emptying of the spheres became similar to emptying of the 99mTc-labeled liver at about 1.6 mm. Spheres with densities less than 1 or greater than 1 emptied more slowly than spheres of the same size with a density of 1, whereas paper squares emptied the same way as spheres of comparable size and density. Surface energy did not affect emptying. The findings indicated that both sphere size and density affect their emptying in the presence of food.

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.

Comparison of Gastrointestinal pH in Cystic Fibrosis and Healthy Subjects

The primary objective of this study was to define the pH conditions under which supplemental pancreatic enzyme preparations must function in the upper gastrointestinal tract. The hypothesis was that normal or greater gastric acid output in patients with cystic fibrosis (CF), combined with low pancreatic bicarbonate output, results in an acidic duodenal pH, compromising both dosage-form performance and enzyme activity. Gastrointestinal pH profiles were obtained in 10 CF and 10 healthy volunteers under fasting and postprandial conditions. A radiotelemetric monitoring method, the Heidelberg capsule, was used to continuously monitor pH. Postprandial duodenal pH was lower in CF than in healthy subjects, especially in the first postprandial hour (mean time greater than pH 6 was 5 min in CF, 11 min in healthy subjects,P<0.05). Based on the dissolution pH profiles of current enteric-coated pancreatic enzyme products, the duodenal postprandial pH in CF subjects may be too acidic to permit rapid dissolution of current enteric-coated dosage forms. However, the pH was above 4 more than 90% of the time on the average, suggesting that irreversible lipase inactivation in the duodenum is not likely to be a significant limitation to enzyme efficacy. Overall results suggest that slow dissolution of pH-sensitive coatings, rather than enzyme inactivation, may contribute to the failure of enteric-coated enzyme supplements to normalize fat absorption.

GASTRIC EMPTYING OF SOLID FOOD IN NORMAL MAN AND AFTER SUBTOTAL GASTRECTOMY AND TRUNCAL VAGOTOMY WITH PYLOROPLASTY

Alterations in gastric emptying are considered contributory to many sequelae of peptic ulcer surgery. The application of a validated method of firmly tagging solid food has enabled the measurement of the rates and patterns of gastric emptying in normal subjects, subtotal gastrectomy, and vagotomy and pyloroplasty (V&P). Normal persons emptied with a linear pattern at a mean rate of 27.96% per hr. Subtotal gastrectomy patients showed up to three phases in their emptying pattern, which, over all, approximated an exponential pattern with a mean rate constant of 0.030 min-1 and calculated t1/2 of 23.3 min. V&P subjects divided into two groups: (1) slow emptying with a linear pattern and mean rate of 17.64% per hr; (2) rapid emptying with exponential pattern and mean rate constant of 0.039 min-1, t1/2 of 17.7 min. The slow gastric emptying rate and slow passage of chyme through the small intestine in one-half of the V&P group presumably allows greater efficiency of digestion and absorption and may account for the over-all less severe nutritional disturbances after V&P.

THE EFFECT OF ACUTE HYPERGLYCEMIA ON MEAL-STIMULATED GASTRIC, BILIARY, AND PANCREATIC SECRETION, AND SERUM GASTRIN

The effects of hyperglycemia on pancreatic, biliary, and gastric secretory responses to meals have not been hitherto quantified in man. In the present study seven normal volunteers were fed on two occasions a 500-ml liquid test meal containing fat and protein. During one of the meals the subjects were made acutely hyperglycemic with intravenous glucose, whereas in control experiments, each subject received intravenous saline in place of glucose. A jejunal perfusion method was used to measure pancreatic outputs of trypsin and biliary outputs of bile salts for 150 min after the meal; the same method was used to quantify indirectly the amount of acid secreted by the stomach in the 150-min period. Serum gastrins were also measured basally and at intervals after the meal. Hyperglycemia suppressed serum gastrin, gastric acid production, trypsin secretion, and bile salt output in response to the test meal.

Effect of hydroxypropylmethylcellulose on gastrointestinal transit and luminal viscosity in dogs

The effects of hydroxypropylmethylcellulose on upper gastrointestinal transit, viscosity, and water flux were studied in six dogs fistulated at the proximal duodenum and/or mid-jejunum. Combinations of different grades of hydroxypropylmethylcellulose were prepared as 2% or 3.3% solutions to yield input viscosities of low (approximately 5000 cp at 37 degrees C and 1 s-1), medium (15,000 cp), or high (30,000 cp) viscosity. Hydroxypropylmethylcellulose modified intralumenal viscosity, with a linear relationship existing between input and lumenal viscosity. With regard to transit, the lag time before the onset of chyme recovery increased linearly as a function of luminal viscosity. There was also a pronounced decrease in the first-order emptying rate constant as lumenal viscosity increased from water to low-viscosity hydroxypropylmethylcellulose, but as viscosity was further increased there was little additional change. These results indicate that water-soluble fibers can exert a significant influence on both the lumenal viscosity and the transit profile in the upper gastrointestinal tract.

Gastric, pancreatic, and biliary secretion and the rate of gastric emptying after parietal cell vagotomy☆

We compared the gastric, pancreatic, and biliary secretory responses to a liquid test meal and the rates of gastric emptying of liquid and solid test meals in six patients at least 1 year after parietal cell vagotomy with eight unoperated subjects, one with duodenal ulcer disease and seven normal control subjects. Parietal cell vagotomy decreased gastric acid secretion to one third of normal, but total trypsin and bile salt secretion during the first 150 postcibal minutes were normal. The liquid test meal emptied from the stomach faster after parietal cell vagotomy, the pattern of emptying being exponential in the vagotomy patients and linear in the normal subjects. The rate of gastric emptying of a liquid meal, although faster than normal, was less precipitous after parietal cell vagotomy than after truncal vagotomy plus drainage or subtotal gastrectomy, and trypsin and bile salt concentrations were not diluted to abnormal levels, as occurs after these other procedures. Furthermore, emptying and dispersion of solid food remained normal after parietal cell vagotomy. These findings probably explain, at least in part, the decreased incidence of postprandial dumping and diarrhea that accompanies parietal cell vagotomy compared with the other popular operations for duodenal ulcer.

Nonabsorbable indicators. The effect of protein on phenol red and polyethylene glycol determination.

The effect of the proteins in milk powder and egg albumin on the determination of phenol red and polyethylene glycol (P.E.G.) has been determined. Both proteins bind phenol red as whole proteins and after partial digestion. Egg albumin interferes with the turbidimetric estimation of P.E.G. increasing the turbidity.