Terry J. Reedy

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.

Choosing Near-Linear Parameters in the Four-Parameter Logistic Model for Radioligand and Related Assays

Ten parameters extracted from six currently used parametrizations of the four-parameter logistic model, and one new proposal, were examined for their statistical behavior in nonlinear least-squares estimation in combination with ELISA and RIA data. Those which are adequately near-linear on the basis of the Lowry-Morton lambda statistic were identified and can be recommended for use in practice.

Healing of benign gastric ulcer with low-dose antacid or cimetidine. A double-blind, randomized, placebo-controlled trial.

We conducted a 12-week, double-blind, randomized, placebo-controlled trial to determine whether cimetidine (300 mg with meals and at bedtime) or a convenient, liquid aluminum-magnesium antacid regimen (15 ml one hour after meals and at bedtime) would expedite healing or relief of symptoms in patients with benign gastric ulcer. Of the 101 patients who completed the trial according to protocol, 32 received the antacid, 36 cimetidine, and 33 placebo. At 4, 8, and 12 weeks after entry, ulcers had healed in a larger percentage of patients treated with cimetidine than of those treated with placebo: 53, 86, and 89 per cent of the cimetidine group versus 26, 58, and 70 per cent of the placebo group (P = 0.02, 0.01, 0.05), respectively. Healing at the three intervals had occurred in 38, 70, and 84 per cent, respectively, of the antacid-treated patients. Neither cimetidine nor antacid was more effective than placebo in relieving symptoms. The presence or absence of symptoms during the fourth and eighth treatment weeks was a poor predictor of the presence of absence of an ulcer crater. We conclude that cimetidine significantly hastens the healing of benign gastric ulcer.

A Controlled Study of Ranitidine for the Prevention of Recurrent Hemorrhage from Duodenal Ulcer

BACKGROUND Hemorrhage is the most common complication of duodenal ulcer disease, but there is little information about the effectiveness and safety of long-term maintenance therapy with histamine H2-receptor blockers. METHODS We conducted a double-blind study in patients with endoscopically documented hemorrhage from duodenal ulcers. Patients were randomly assigned to maintenance therapy with ranitidine (150 mg at night) or placebo and were followed for up to three years. Endoscopy was performed at base line (to document that the ulcers had healed), at exit from the study, and when a patient had persistent ulcer symptoms unrelieved by antacids or had gastrointestinal bleeding. Symptomatic relapses without bleeding were treated with ranitidine; if the ulcer healed within eight weeks, the patient resumed taking the assigned study medication. RESULTS The two groups were similar at entry, which usually occurred about three months after the index hemorrhage. After a mean follow-up of 61 weeks, 3 of the 32 patients treated with ranitidine had recurrent hemorrhage, as compared with 12 of the 33 given placebo (P < 0.05). Half the episodes of recurrent bleeding were asymptomatic. One patient in the ranitidine group withdrew from the study because of asymptomatic thrombocytopenia during the first month. CONCLUSIONS For patients whose duodenal ulcers heal after severe hemorrhage, long-term maintenance therapy with ranitidine is safe and reduces the risk of recurrent bleeding.

A Randomized Study of Maintenance Therapy with Ranitidine to Prevent the Recurrence of Duodenal Ulcer

After an active duodenal ulcer has healed in response to medical therapy, the rate of recurrence during the subsequent year is relatively high. We therefore enrolled 140 patients with healed duodenal ulcers in a two-year randomized, double-blind trial comparing maintenance therapy (ranitidine, 150 mg nightly) with placebo for the prevention of recurrent duodenal ulceration. We performed endoscopy annually and when symptoms suggested the recurrence of ulcers. Verified recurrent ulcers in either group were treated for four or eight weeks with open-label ranitidine (150 mg twice a day). Patients whose ulcers healed within eight weeks resumed randomized treatment. Prophylactic therapy with ranitidine reduced the rate of ulcer relapses from 63 percent in the placebo group to 37 percent in the ranitidine group (P less than 0.05). Treatment with ranitidine extended the median ulcer-free interval from one to two years (P less than 0.05). The first recurrences of ulcer were asymptomatic in half the ranitidine group and in a quarter of the placebo group. Prophylactic therapy with ranitidine also reduced the frequency of recurrent ulcers that were unhealed by eight weeks, that were bleeding, that were in the stomach, or that were the second recurrent ulcer within six months, from 43 percent in the placebo group to 21 percent. Patients who drank alcohol, smoked, had a history of ulcer disease, or had duodenal scarring or erosion at the time of entry into the study were at the greatest risk for recurrence and benefited the most from prophylactic ranitidine. We conclude that prophylactic treatment with ranitidine is effective in preventing the recurrence of duodenal ulceration.

Simultaneous Gastric Emptying of Two Solid Foods

A variety of radionuclide-labeled, solid foods have been used to measure gastric emptying. Implicit is the idea that the nuclide label identifies the rate of emptying of meal contents. The present studies tested whether different foods empty from the human stomach at different rates. Eight volunteers were fed meals of 200 ml of water + 213 g of beef stew + 52 g of chicken liver, with half the liver as 0.25-mm particles and half as 10-mm chunks, labeled with 99mTc and 113mIn, respectively, or the reverse. Another 8 subjects ingested 200 ml of water + 75 g of noodles, labeled with 123I, + 30 g of liver, labeled with 113mIn. Gastric emptying of each radionuclide was determined for 3 h by measuring the decline of counts in the gastric region of interest, using an Ohio Nuclear S410 gamma camera interfaced to a DEC computer. In each case, appropriate corrections were made for nuclear decay, down-scatter from 113mIn, and septal penetration. Seven of 8 subjects emptied 0.25-mm liver particles more quickly than 10-mm chunks of liver, while 1 subject emptied the two sizes of liver at the same rate. The t 1/2 for the 0.25-mm liver was 70 +/- 10 min; and for the 10-mm liver, 117 +/- 19 min (p less than 0.05). Six of 8 subjects emptied noodles much faster than liver, while 2 emptied the two foods at similar rates. The t 1/2 for the noodles was 52 +/- 8 min; and for the liver, 82 +/- 5 min (p less than 0.02). Since different foods in the same meal were found to empty at different rates, we conclude the gastric emptying of every food in a meal is not accurately represented by the emptying of a single, nuclide-labeled food. The different t 1/2s for the emptying of 10-mm liver in the two meals (p less than 0.05) probably reflected the influence of other meal components on gastric motility.

Gastric Emptying and Sieving of Solid Food and Pancreatic and Biliary Secretion after Solid Meals in Patients with Truncal Vagotomy and Antrectomy

This study was undertaken to answer two questions: (a) does antrectomy disturb sieving or grinding of solid food, or both, and (b) how abnormal are jejunal flows and concentrations of pancreatic enzymes and bile salts after a meal of solid food. Six normal subjects and 9 subjects with truncal vagotomy plus antrectomy were intubated with a triple-lumen tube attached to a bubble trap sited in the jejunum, 60 cm from the stomach. All subjects ate a meal of 100 ml of H2O, 60 g of beefsteak, and 30 g of 99mTc-liver diced into 10-mm cubes. By previously validated techniques, the tube-bubble trap system allowed comparison of the rate of passage of 99mTc-liver particles smaller than 1 mm through the jejunum with the rate of entry of all sizes of eaten 99mTc-liver into the intestine described by gamma camera. The tube system also measured concentrations and rates of passage of enzymes and bile salts. 99mTc-liver emptied very rapidly from the stomach in the first 50 min in most subjects with truncal vagotomy plus antrectomy and thereafter emptied slowly, while in the normal subjects there was a 30 min lag before a steady, slow rate of emptying. Nearly 30% of the 99mTc-liver that emptied into the intestine in the subjects with truncal vagotomy plus antrectomy was larger than 1 mm, but in the normal subjects less than 3% of the liver entered the intestines as larger particles. In this study with a solid meal, jejunal flows in the subjects with truncal vagotomy plus antrectomy were lower than normal, and concentrations of bile salts and pancreatic enzymes were close to normal.

The Histology of the Stomach in Symptomatic Patients After Gastric Surgery: A Model to Assess Selective Patterns of Gastric Mucosal Injury

We assessed selective patterns of histological injury in the gastric mucosa of 25 patients (12 Billroth II, 8 Billroth I, 5 vagotomy and pyloroplasty) with symptoms of alkaline reflux gastritis. Each patient had 12 biopsies taken from standardised sites. Histology was scored separately for surface epithelial changes and for inflammatory cells. The traditional grading of gastritis was also done using the categories of superficial and atrophic gastritis. The main histological changes were epithelial, especially in the pits (foveolae) of Billroth II patients. Although mild to moderate atrophic gastritis was present, the inflammatory cell density was only mild. Differences between surgery types for any given histological parameter became apparent only upon the analysis of regional changes within the stomach. Conventional grading of gastritis is based mainly on degrees of gland loss and thus is mainly of value to study chronic changes. However, the type of histological evaluation used here, with standardised biopsy sites, and separate scoring of epithelial and inflammatory changes is potentially more suitable to study shorter term changes as might occur with cytoprotective or damaging agents.

Somatostatin may not be a hormonal messenger of fat-induced inhibition of gastric functions.

The present study was designed to evaluate somatostatin as a hormonal inhibitor of gastric functions in humans. Seven healthy volunteers were investigated on 6 separate days. Peptone meal-stimulated gastric acid secretion was measured by intragastric titration for 2 h and gastric emptying was estimated with a dye-dilution technique. The effect of intravenous administration of somatostatin at 0, 12.5, 50, 100, and 200 pmol/kg.h was investigated and related to the effect of intragastric administration of 100 ml of vegetable oil. Plasma somatostatinlike immunoreactivity was elevated during intravenous administration of somatostatin at 100 and 200 pmol/kg.h, whereas no increase was detected in response to the oil. Somatostatin infusion at 100 and 200 pmol/kg.h significantly inhibited the acid secretion by 25% and 65%, and the oil reduced the acid output by 41%. Somatostatin at 100 and 200 pmol/kg.h significantly enhanced gastric emptying, whereas the oil inhibited gastric emptying. These observations suggest that somatostatin may not be an important hormonal messenger of fat-induced inhibition of acid secretion or gastric emptying.

Pancreatobiliary responses to an intragastric amino acid meal: Comparison to albumin, dextrose, and a maximal cholecystokinin stimulus

Little is known about how gastric and pancreatobiliary responses differ after intake of elemental diets from responses to polymeric food. We therefore compared pancreatic and biliary secretions after gastric instillation of albumin (7 g%, with dextrose 21 g%) with an elemental diet in 6 healthy volunteers. The elemental diet contained amino acids (7 g%, with dextrose 21 g%) in the same molar composition as the albumin. Furthermore, we studied the effect of a pure intragastric dextrose solution (21 g%) on pancreatobiliary secretions, as glucose constitutes a major component of elemental diet formulas. The various pancreatobiliary responses were tested against a maximal i.v. cholecystokinin stimulus. The dextrose, amino acid, and albumin meals emptied at similar rates, and gastric emptying was completed within 3 h. Similar pancreatobiliary responses were observed after the albumin and amino acid meals, but response to both the amino acid and albumin meals was smaller than to the intravenous cholecystokinin stimulus. The glucose meal caused a marked and sustained stimulation of pancreatobiliary outputs, which did not differ significantly from the other test meals. However, lower cholecystokinin levels were observed after the glucose meal compared with distinct cholecystokinin release after the albumin and amino acid meals. We conclude first that there are no major differences in secretory responses between elemental (amino acid) and polymeric (protein) meals and second, that intragastric pure glucose meals strongly stimulate pancreatobiliary secretions. The marked pancreatic and biliary responses to intragastric dextrose cannot be fully explained on the basis of cholecystokinin release, suggesting that this response is probably mediated by neural mechanisms.