Janet D. Elashoff

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.

HEALING OF DUODENAL ULCER WITH AN ANTACID REGIMEN

To determine whether a large-dose antacid regimen is effective in promoting healing of duodenal ulcer, 74 patients with endoscopically proved duodenal ulcer completed a 28-day double-blind clinical trial comparing such a regimen with an inert placebo. The ulcer healed completely in 28 of the 36 antacid-treated as compared to 17 of the 38 placebo-treated patients (P less than 0.005). The antacid regimen was not more effective than placebo in relieving ulcer symptoms. Presence or absence of symptoms during the fourth treatment week was a poor predictor of presence or absence of an ulcer crater. Ulcers of placebo-treated patients who smoked cigarettes were less likely to heal than those of nonsmokers (P = 0.03). Except for mild diarrhea, no side effects of the antacid regimen were observed. We conclude that a large-dose antacid regimen hastens the healing of duodenal ulcer.

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.

Accuracy of ultrasonic pachymetry and videokeratography in detecting keratoconus.

Purpose: To compare the accuracy of ultrasonic pachymetry measurements‐ and videokeratography‐derived indices in distinguishing keratoconus patients from those with normal eyes. Setting: A subspecialty cornea practice (Los Angeles, California, USA) and the Keratoconus Genetics Research Project. Methods: Corneal thickness was measured by ultrasonic pachymetry at the center and inferior margins of the pupil of 142 normal and 99 keratoconus patients. The corneal surface topography of patients was studied with the Topographic Modeling System (TMS‐1). The videokeratographs obtained were analyzed with a computer program that automatically calculates two indices derived from data points in the central and paracentral cornea: central K and I‐S values. Linear discriminant analysis was used to determine the correct classification percentages using pachymetry measurements and indices derived from videokeratography as the independent variables. Results: The range of corneal thickness in normal and keratoconic eyes overlapped considerably. In the discriminant analysis, videokeratography indices provided a 97.5% correct classification rate and pachymetry data, an 86.0% rate (P < .01, McNemar’s test). Conclusion: Keratoconus is more accurately distinguished from the normal population by videokeratography‐derived indices than by ultrasonic pachymetry measurements. This may be due to the large variation in corneal thickness in the normal population or the inability of ultrasonic pachymetry to accurately detect the location of corneal thinning in keratoconus by measuring standard points on the cornea. Pachymetry should not be relied on to exclude or diagnose keratoconus because the false‐negative and false‐positive rates are unacceptably higher than those obtained by videokeratography.

Effects of Questioning Techniques and Recitation on Student Learning

Two experiments were done in which sixth-grade students participated in 10 ecology lessons, each involving reading/viewing of curriculum materials plus a teaching treatment. In Experiment I, four treatments were arranged in three equivalent Latin squares so that each of 12 trained teachers taught each treatment. The treatments varied presence-absence of recitation and presence-absence of probing (a follow-up question to improve a students initial response) and redirection (asking another student to respond to the question). Experiment II followed the same design, except the treatments varied presence-absence of recitation and percentage of higher cognitive questions (25%, 50%, and 75%) within recitations. Students information recall, attitudes toward curriculum topics, and ability to respond both in written and oral form to higher cognitive questions were assessed. In both experiments, recitation substantially improved learning, especially information recall and higher cognitive responding. Probing and redirection in Experiment I had no effect on learning. In Experiment II, recitations with 50% higher cognitive questions were unexpectedly the least effective in promoting information recall, relative to recitations with 25% or 75% higher cognitive questions.

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.

Effects of Prostaglandin and Indomethacin on Diet-Induced Acute Pancreatitis in Mice

This study was performed to determine the effects of exogenous prostaglandin and a prostaglandin synthetase inhibitor on experimental pancreatitis in mice. An ethionine-supplemented choline-deficient diet was used to induce pancreatitis in 4-6-wk-old Swiss Webster mice. Mice were injected subcutaneously with 16,16-dimethyl prostaglandin E2 (0.1, 1.0, 10 micrograms X kg-1 X day-1), indomethacin (0.05, 0.5, 5 mg X kg-1 X day-1), or saline for 7 days. The ethionine-supplemented choline-deficient diet was introduced 24 h after the first injection, and animals ate the test diet for 48 h. A 55% mortality was observed in control animals (n = 100) treated with carrier alone. Treatment with 10 micrograms X kg-1 X day-1 of 16,16-dimethyl prostaglandin E2 significantly decreased (p less than 0.01) mortality to 12% (n = 100). Improved survival was accompanied by a significant (p less than 0.05) decrease in the pancreatic content of free chymotrypsin and a decrease in histologic damage. Treatment with 5 mg X kg-1 X day-1 of indomethacin (n = 30) significantly (p less than 0.01) increased mortality in diet-treated rats from a control rate of 55% to 100%. These studies demonstrate a protective effect of prostaglandin on the pancreas and suggest a role for endogenous prostaglandins in the pathophysiology of pancreatitis.

Gastric emptying of oil from solid and liquid meals : Effect of human pancreatic insufficiency

Digestion of fat in pancreatic insufficiency (PI) is strongly affected by how rapidly fat enters the duodenum. We postulated that: (1) oil empties faster in PI than in normals and (2) in both, it empties in a load-dependent fashion. We used a gamma camera to test these ideas by comparing gastric emptying of iodine-123 iodinated oil in normal and pancreatic-insufficient subjects after 15 g of free oil were ingested in a small spaghetti meal and 60 g of oil were ingested in a large spaghetti meal and in a milk emulsion. Indium-113m marked gastric emptying of water in the milk. In both groups after all meals, oil emptied fastest initially, slowing later; and oil emptied three to four times faster when 60 g vs 15 g were ingested. There were no significant differences between the groups of subjects with respect to gastric emptying of the spaghetti meals, but the pancreatic-insufficient subjects emptied both oil and water faster from the milk emulsion than did the normal subjects. The slower emptying of oil in the normal subjects was associated with significantly more layering of oil to the top of the intragastric milk emulsion.

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.