Effect of intravenous infusion of ranitidine on intragastric acidity in fasting subjects: comparison with bolus or Gastrojet (pH-stat-adjusted) infusion.

This study was undertaken in nine fasting healthy volunteers to compare the effect of intravenous continuous infusion versus bolus injection of ranitidine on 12-h intragastric pH, and to compare the efficacy of these two modes of administration of pH-stat-adjusted infusion of ranitidine using the Gastrojet. Each volunteer had three study sessions with 12-h pH measurements. In the ranitidine infusion treatment arm (RAN-INF), ranitidine was continually infused intravenously using an IVAC-pump at a dose of 0.125 mg mg.kg over a 12-h period. In the ranitidine bolus treatment arm (RAN-BOL), ranitidine bolus 50 mg was given over 10 min, every 6 h. When ranitidine infusion was given by the pH stat method using the Gastrojet (RAN-JET), sufficient ranitidine was given to maintain a present value of pH > or = 5. The study was analysed with a 3 x 3 Latin square cross-over design with multiple measurements of each phase of the cross-over. No difference was found between RAN-INF and RAN-BOL in 12-h or in daytime (10.00-18.00 h) mean pH, median pH, or percentage of pH > or = 5. Using RAN-JET, 89.5% of the pH values were > or = 5., compared with 39.7% and 40.0% with RAN-INF or RAN-BOL. RAN-JET also gave higher (P < 0.05) mean and median 12-h or daytime pH values, as compared with RAN-INF or RAN-BOL. The mean doses of ranitidine given in the 12-h infusion periods were 100 mg, 109 mg and 112 mg (RAN-BOL, RAN-INF and RAN-JET, respectively). Thus, this superior inhibition of acid inhibition achieved with Gastrojet does not require higher mean doses of ranitidine. These findings cannot necessarily be applied to persons with duodenal ulcer disease or to patients in an intensive-care unit setting. However, the data do raise the possibility that much greater inhibition of acid inhibition can be achieved by individualizing the dose of ranitidine using the Gastrojet.

A single night-time dose of famotidine is equivalent to ranitidine in decreasing 24-hour gastric acidity in asymptomatic duodenal ulcer subjects.

Six asymptomatic, non-smoking men with endoscopically proven duodenal ulcer disease received single nocturnal doses of placebo, 40 mg famotidine and 300 mg ranitidine each for 1 week prior to serial measurement of pH, peptic activity and serum gastrin concentrations over 24 h and of acid output. The intragastric pH fluctuated between 1.53 and 5.07 when subjects were given placebo but within 2 h of taking famotidine or ranitidine it rose to 5.57 or higher; the effect lasted for 12 h from midnight. Peptic activity fell during famotidine and ranitidine treatment and the decline was somewhat greater 8-15 h after using famotidine. Serum gastrin levels did not change materially with any treatment. The study shows the equivalent effect of standard bed-time doses of famotidine and ranitidine on intragastric pH, acid output and serum gastrin concentrations in asymptomatic men with duodenal ulcer disease.

Inflammatory bowel disease in northern Alberta. An epidemiologic study.

The Medical Record departments of the five teaching hospitals in Edmonton, plus the 37 community hospitals in the eight census districts of the northern half of the province of Alberta, Canada, were contacted, and a search was made of all patients with a discharge diagnosis of Crohn's disease or ulcerative colitis. Also, the patient records of all Edmonton gastroenterologists were reviewed to discover patients with Crohn's disease or ulcerative colitis who had never been hospitalized within these census areas. From January 1, 1977, to December 31, 1981 (which was the prevalence date), the population was 1,295,360. Of the 2,419 patients with inflammatory bowel disease, 48.5% had definite Crohn's disease and 33% had definite ulcerative colitis. There were 1,716 (70.9%) patients analyzed in this study. The factorial analysis of disease prevalence per 10(5) population revealed that significant differences were found for location of residence, sex, and age. The prevalence of Crohn's disease was higher in urban than in rural areas and in females than in males, whereas the prevalence of ulcerative colitis was unaffected by these variables. The peak prevalence of Crohn's disease was below age 29 in males and females, and the prevalence in young women at this age was approximately twice that in males. The highest prevalence of Crohn's disease was in urban females aged 20-39 (greater than 234 cases/10(5) population), with similar prevalence rates in urban males and rural females, and with the lowest prevalence rates in rural males. The incidence of Crohn's disease was greater than for ulcerative colitis, began to increase in about 1965, and reached a plateau in the late 1970s. In conclusion, the demonstration of an age, location of residence, or effect of sex on the prevalence of inflammatory bowel disease requires multiple factorial analyses. When the sample is extrapolated to the total diseased population of the region, a prevalence value of 330/10(5) was derived for young female urban individuals residing in this northern area.

Discriminant function analysis to calculate a Crohn's activity group scale to predict future inactive or active disease.

A discriminant function analysis was performed on several demographic, anthropometric, clinical, and laboratory data of 685 observations performed over 12 months on 137 patients with Crohn's disease. A Crohn's activity group scale (CAGS) was calculated. The CAGS has two advantages over the usual Crohn's disease activity index: it is objective, but more important is the fact that the values, when calculated longitudinally, have predictive value. Thus, calculation of CAGS is useful for counseling purposes and may also be useful in the design of future trials assessing therapy for Crohn's disease by allowing prerandomization stratification of patients with high or low probability of future recurrences of symptomatic disease activity.

Twenty-four-hour intragastric measurements in twenty healthy subjects: effect of enisoprost, a novel and potent antisecretory and antipeptic synthetic E1 prostaglandin.

Gastric aspiration was performed continuously overnight and at hourly intervals during the daytime in 20 healthy male volunteers. Medications used included enisoprost 100, 200 or 400 micrograms, misoprostol 200 micrograms and placebo, given at bedtime. Each dose of enisoprost markedly inhibited nocturnal mean acid output, hydrogen ion activity, pH and peptic activity. The duration of these effects was up to 10 h. Misoprostol, given at bedtime, also decreased acid secretion, but the effect was significantly less than that observed with any of the doses of enisoprost. A dose-response effect for enisoprost was found for the mean nocturnal hydrogen ion activity and pH, as well as for maximum pH attained. Although enisoprost, given at bedtime, had a marked inhibitory effect on acid and pepsin secretion for the overnight interval, this did not result in rebound hyperacidity or a rise in serum total gastrin concentration. The results of this study suggest that enisoprost should be tested by clinical trial for the treatment of peptic ulcer disease.

Evaluation of antacid tablets and liquid in fasting and fed men and women.

In view of in vitro tests suggesting good performance of an experimental tablet formulation of an aluminum hydroxide-magnesium hydroxide antacid, a study was conducted to evaluate the efficacy in vivo. Twenty-three healthy men and women were enrolled in the study, which was carried out in two parts: fasting and postprandial. Eight of the volunteers failed to qualify because of repeated baseline pH greater than 2.5. In the 15 participants who qualified, the intragastric pH was monitored for up to 240 minutes after the administration of one or two experimental tablets, 5 or 10 ml of a commercially available liquid antacid, or placebo. In the fasting subjects (n = 10), the antacids rapidly increased the mean pH. One antacid tablet and 5 ml of liquid antacid yielded similar results, with mean peak pH values of 5.2 and 4.8 and durations above pH 3.5 of 25 and 40 minutes, respectively. When the doses were doubled, 10 ml of liquid produced a peak pH of 6.7 and maintained the pH above 3.5 for 40 minutes, whereas two tablets produced a peak pH of 4.8 and maintained pH above 3.5 for 15 minutes. In the fed subjects (n = 10), neither antacid formulation at either dose significantly raised intragastric pH. Further studies are needed to establish the optimal time for postprandial administration of antacids.

Diet counselling improves the clinical course of patients with Crohn's disease.

A prospective study was undertaken to establish the role of individualized diet counselling in the management of 137 outpatients with Crohn's disease. Individualized dietary counselling for 6 months was associated with a significant decrease in the Crohn's disease activity index, an increased incidence of disease remission, a decreased need for prednisone and Salazopyrin therapy, a reduction in the number of days spent in hospital, and a reduction in the amount of time lost from work due to Crohn's disease, when compared with control patients who did not receive dietary counselling but who were seen regularly in follow-up under similar circumstances. Improvement with diet counselling was more likely to occur in patients who had not previously been subjected to small bowel resection, and occurred in patients with active or inactive disease. The effect of counselling 58 patients was assessed over a further 6 months (for a total 12-month period); there was a persistently reduced Crohn's disease activity index and a continued decreased number of lost days of work. The mechanism for these beneficial effects of diet counselling was not established. It is suggested that individualized diet counselling, aimed at optimizing the patient's nutritional status, may play a role in the management of patients with Crohn's disease.

Iron, folate, vitamin B-12, zinc, and copper status in outpatients with Crohn's disease: effect of diet counseling.

Iron, folate, and vitamin B-12 status was found to be poor in a substantial proportion of outpatients with generally inactive Crohn's disease. Diet counseling was associated with a normalization of TIBC and serum folate over a 6-month period, but no other consistent benefits were noted despite moderate improvements in intake. The outpatients appeared to be at low risk of developing a zinc or copper deficiency.

Diet counseling modifies nutrient intake of patients with Crohn's disease.

The nutrient intake of 137 outpatients with Crohn's disease was recorded, and the effect of diet counseling was assessed. Half the patients received monthly diet counseling that was individualized and aimed at normalizing nutrient intake; the other half of the patients received no diet counseling and served as controls. Over the 6-month study period, the mean nutrient intakes met or exceeded the 1980 U.S. Recommended Dietary Allowances (RDAs) for all nutrients except folate in the men and iron and folate in the women. However, at study entry, for each nutrient there was a substantial proportion of patients whose intake did not meet the full RDA. Less than 50% of the men consumed the full RDA for energy and folate, and less than 50% of the women consumed the full RDA for energy, folate, calcium, iron, thiamin, and vitamin B-12. Monthly diet counseling sessions were associated with increases in the mean intake of most nutrients, whereas similar improvement was not observed in the control group members, who did not receive counseling. By 6 months, significantly more counseled than non-counseled patients were consuming the full RDA for protein, riboflavin, and vitamin C (p less than .05). Thus, diet counseling was found to be an important tool for improving the nutrient intake of outpatients with Crohn's disease.

Vitamin A status in 137 patients with Crohn's disease.

Serum retinol and serum carotene concentrations were determined over a 6-month period in 137 outpatients with Crohn's disease. Serum retinol measurements were within the reference range for all patients at each assessment period, while serum carotene levels were low in about one quarter of the patients. Of the 56 patients who completed 48-hour stool collections, 41% had stool fat values exceeding the reference value. Serum retinol concentrations were not significantly correlated with the serum carotene concentrations, with the 48-hour stool fat content, or with the Crohn's disease activity. In contrast serum retinol concentrations were correlated with the dietary levels of vitamin A. Serum carotene concentrations were inversely correlated with the stool fat content but were not related to Crohn's disease activity or dietary levels of carotene or total vitamin A. Thus: (1) serum retinol concentrations were normal in this moderately large group of patients with Crohn's disease and did not reflect a low dietary vitamin A intake by 34% of the population; (2) serum carotene levels were frequently low in patients with Crohn's disease, possibly due to the presence of steatorrhea, but were not related to low dietary intakes of carotene or to active Crohn's disease, and (3) a low serum level of carotene does not indicate that the patient is at risk of developing vitamin A deficiency.

Vitamin C status in 137 outpatients with Crohn's disease. Effect of diet counseling.

Vitamin C intake, and serum and leukocyte ascorbate levels were assessed serially over 6 months in 137 outpatients with Crohn's disease. Vitamin C intake was low in 18% of males and 37% of females. Serum ascorbate levels were suboptimal in 11% of males and 18% of females. Leukocyte ascorbate levels were low in 26% of males and 49% of females. Serum ascorbate levels were more frequently below the reference range in patients who smoked, but neither the serum nor the leukocyte ascorbate levels were affected by Crohn's disease activity, the use of an oral contraceptive agent, or by taking prednisone or sulfasalazine. Monthly diet counseling sessions significantly increased vitamin C intake, led to more patients consuming a normal ascorbate intake, and to a normalization of serum ascorbate values. We did not establish the importance of these ascorbate abnormalities on the clinical course of Crohn's disease. We conclude that low serum or leukocyte ascorbate levels are relatively common in patients with active or inactive Crohn's disease; these abnormalities are due in part to the reduced intake of dietary ascorbate; and the ascorbate status in patients with Crohn's disease may be normalized by improving the dietary intake of vitamin C.

Synergistic interaction between an H2-receptor antagonist and enprostil on 24-hour intragastric pH, serum gastrin concentration, and tissue immunoperoxidase staining for gastrin, somatostatin, and serotonin in a patient with metastatic gastrinoma.

A 56-year-old woman newly diagnosed as having Zollinger-Ellison syndrome due to a metastatic gastrinoma underwent 24-hour intragastric pH monitoring, serum gastrin (total, G-17 and G-34) measurements, and immunoperoxidase staining of duodenal, antral, and gastric body biopsies for gastrin, somatostatin, and serotonin. Determinations were made while the patient was given different doses of ranitidine, enprostil (a synthetic orally administered prostaglandin E2), or ranitidine plus enprostil. Following are the findings from this single-patient study: Intragastric pH was persistently low but varied in response to food when the patient was given ranitidine. Immunocytochemical staining of antral biopsies obtained before the patient was treated revealed a reduced number of cells containing G-17 and G-34 but an increase in the antral somatostatin-containing D-cells. Treatment with 35 micrograms of enprostil BID plus 300 mg of ranitidine BID for two and 11 weeks was associated with an increased number of duodenal G-cells, a decrease in antral D-cells, and a decrease in the number of antral serotonin-containing cells. Enprostil in a dosage of 35 or 70 micrograms BID had no effect on intragastric pH, but when enprostil was given in combination with ranitidine, postprandial and nocturnal intragastric alkalinity was accentuated along with a return of duodenal and antral G-cells and a loss of the antral D-cell hyperplasia. Optimal pH control was achieved with 300 mg of ranitidine BID; more frequent dosing with ranitidine did not further increase intragastric pH. Both the total serum gastrin concentration and G-17 levels fluctuated in response to meals. The serum concentrations of total gastrin, G-17, and G-34 were reduced with enprostil and with ranitidine.

Effect of Ensure, a defined formula diet, in patients with Crohn's disease.

A prospective controlled 6-month study was undertaken to compare the effect of Ensure, a defined formula dietary supplement, and diet counselling in 122 outpatients with Crohn's disease. The compliance to Ensure was poor due to a high incidence of side effects. Taking any amount of Ensure reduced the need for surgery and the amount of hospitalization. There was a trend for patients receiving Ensure to experience a decline in the value of their Crohn's disease activity index (p less than 0.10). No consistent effects of Ensure were seen on the amount of work missed due to Crohn's disease, in laboratory measurements, in the need for prednisone or Salazopyrin. The vitamin B12 intake was improved, but otherwise nutrient intake declined due to a decreased food intake. Thus, certain beneficial clinical trends were associated with taking Ensure, but larger numbers of compliant patients will need to be studied to better assess the long-term role of defined formula diets in the management of outpatients with Crohn's disease.

Postprandial changes in serum concentrations of gastrin-17, gastrin-34, and total gastrin in patients with duodenal or gastric ulcers and in normal subjects.

The fasting concentrations of total gastrin and gastrin-17 (G-17) were similar in healthy volunteers and in asymptomatic patients with gastric ulcers or duodenal ulcers. However, the fasting serum concentration of gastrin-34 (G-34) was higher in patients with gastric ulcers than in normal subjects, in whom it was higher than in patients with duodenal ulcers. In response to food, the increases in G-17, G-34, and total gastrin were greater in ulcer patients than in healthy subjects. Cimetidine administration was associated with further increases in G-17, G-34, and total gastrin in normal subjects and gastric ulcer patients after meals. The ratio G-17/G-34 was similar in placebo-treated normal subjects and placebo-treated patients with gastric or duodenal ulcers. Cimetidine produced an increase in G-17/G-34 in placebo-treated normal subjects and placebo-treated patients with gastric or duodenal ulcers, but the ratio G-17/G-34 was greater in patients with gastric ulcers than in normal subjects. These results indicate that: differences in serum gastrin concentrations between patient groups, treatment regimens, and time of day are better detected by measuring G-17 and G-34 rather than total gastrin; there are differences in fasting and food-stimulated gastrin concentrations between normal subjects and patients with gastric or duodenal ulcers; the fasting concentration of G-34 is higher than G-17 in normal subjects and patients with gastric ulcers but not in patients with duodenal ulcers; food increases G-17 in all subjects but G-34 only in subjects with gastric ulcers; cimetidine increases the fasting concentration of total gastrin in normal subjects and patients with gastric ulcers and increases G-17 and G-34 in normal subjects; cimetidine increases the ratio G-17/G-34 in normal subjects and patients with gastric ulcers, but decreases G-17/G-34 in patients with duodenal ulcers. It is proposed: that measurements of total gastrin concentration should be replaced by measurements of G-17 and G-34 and that such measurements of G-17 and G-34 indicate differences in serum gastrin concentrations between normal subjects and those with peptic ulcers and between those with gastric versus duodenal ulcers. The role of altered gastrin metabolism in the pathogenesis of ulcers needs to be established.

Interrelationship between gastric acidity and gastrin concentration in patients with duodenal or gastric ulcer and in healthy subjects.

Although increased gastric acidity may be important in the pathogenesis of duodenal ulcer, it has a less well-defined role in the formation of gastric ulcers. The present study was undertaken to determine (1) the 24-hour intragastric pH and serum gastrin profiles of 31 patients with duodenal ulcers, eight patients with gastric ulcers, and seven healthy volunteers and (2) the effect of 600 mg of cimetidine BID on these measurements. There was considerable overlap of basal acid output values in the three groups, and mean values did not differ significantly. In response to pentagastrin, the peak acid output was significantly higher in the duodenal ulcer group than in the gastric ulcer or healthy group. There were no intergroup differences in intragastric hydrogen ion (H+) activity after meals, overnight, and over 24 hours, when all subjects received placebo. However, the pH values remained at or above 4.0 for a longer period during the night in the gastric ulcer patients than in the duodenal ulcer patients or healthy subjects. There were no intergroup differences in basal gastrin concentration, but the postprandial gastrin response after each meal was higher in the gastric ulcer group than in the other two groups. In the gastric ulcer group, cimetidine suppressed H+ activity at all times; in the duodenal ulcer and healthy groups, cimetidine suppressed H+ activity only after breakfast, overnight, and over 24 hours. Cimetidine enhanced the serum gastrin response to food to a greater extent in the ulcer patients than in the healthy subjects. In the healthy subjects, the ratio of H+ to gastrin (H+:G) was higher than in the duodenal or gastric ulcer patients but was suppressed only minimally by cimetidine, whereas cimetidine markedly suppressed the H+:G ratio in both groups of ulcer patients. Patients with a history of duodenal or gastric ulcers differed from healthy volunteers in their food-stimulated gastrin response and in their H+:G ratio when treated with cimetidine. Intergroup differences in gastrin response to food, but not in intragastric pH in response to food, suggests that defective control of or response to gastrin may be important in the pathogenesis of acid-peptic disease. Cimetidine, which was effective in H+ suppression in all subject groups, may alter the sensitivity of the parietal cells to gastrin in patients with duodenal or gastric ulcers.