In 32 healthy male volunteers the effects on gastric secretion of three methyl analogues of prostaglandin (PG) E2 have been studied, namel, 15 (R) -15-methyl PGE2 methyl ester, 15 (S) -15-methyl PGE2 methyl ester, and 16, 16-dimethyl PGE2. Secretion was measured for 30 min and a PG analogue at doses ranging from 1.25 to 2.5 mug per kg or a placebo was administered. Gastric secretion was then stimulated either by an intravenous infusion of pentagastrin (2 mug per kg-hr) or by a peptone meal with acid secretion determined by intragastric titration technique. The tests were randomized and double blind. All three methyl PG analogues exhibited a profound and prolonged inhibitory action on gastric acid and pepsin secretion induced by pentagastrin. PG analogues caused almost complete inhibition of gastric acid response to a peptone meal accompanied by a significant reduction in the serum concentration of immunoassayable gastrin. Except with the highest dose of PG (S) -15-methyl PGE2 methyl ester, which caused abdominal discomfort and single episodes of diarrhea in some subjects, no symptoms or untoward biochemical effects were observed. It is concluded that these methylated PG analogues are very potent inhibitors of gastric acid and pepsin secretion stimulated by pentagastrin or a meal and may have clinical potential in the treatment of peptic ulcer.

Between 1968 and 1974, azathioprine has been used in a controlled prospective trial to treat patients with symptomatic but precirrhotic primary cirrhosis. Forty-five patients were admitted, of whom 22 were given azathioprine in a dose of 2 mg per kg of body weight. During the 1st year, serum aspartate transaminase levels showed a significant change in favor of the treated group, but improvement did not continue. Throughout the trial, serum alkaline phosphatase, bilirubin, cholesterol, albumin and immunoglobulin M values showed no significant change. Titers of serum mitochondrial antibodies tended to become negative more often in the treated than the untreated. Pruritus cannot be assessed objectively, but seemed less in the treated than in controls. Serial hepatic biopsy specimens showed the development of cirrhosis equally in the two groups. Survival, as judged by the life table method, was similar for the first 5 years of the trial. There was, however, a significant difference in favor of the treated group in the 6th year, although the number of patients available for assessment at that time was extremely small.

The effect of oral metoclopramide (15 mg), AlMgOH (30 ml), and placebo on the cumulative duration of gastroesophageal reflux induced by a protein-rich meal was compared in 15 patients with reflux esophagitis. Oral metoclopramide was found to be more effective than AlMgOH in reducing the cumulative duration of reflux after placebo over a 3-hr period. The same dose of oral metoclopramide increased resting lower esophageal sphincter pressures in all 15 patients for at least 1 hr and prevented gastroesophageal reflux after an intragastric acid load (300 ml of O.1 N HCl) in 8 of 10 of these patients. Oral metoclopramide, however, failed to increase the amplitude of esophageal contractions and acid clearing of the distal esophagus. These findings suggest that oral metoclopramide in the dose of 15 mg may be potentially valuable in the management of reflux esophagitis.

The standard preparation for cleansing the gastrointestinal tract for diagnostic studies such as barium enema usually involves dietary restrictions, purgatives, and cleansing enemas. This preparation is time consuming, often uncomfortable for the patient, and frequently unsuccessful. In this study, we examined the efficacy of saline lavage (without dietary restrictions or cleansing enemas) as a gentle, alternative method for cleansing the bowel, and compared lavage to the standard castor oil method of bowel preparation. Lavage cleansing was preferred by 75% of patients who had previously experienced a castor oil preparation. Although 11% of patients could not consume an adequate (4-liter) lavage volume, there was no significant difference in preparation success rate between the remaining lavage patients and the castor oil patients. Total preparation time for lavage (3 +/- 1 hr) was 60% less than for castor oil. The anticipated dehydration produced by castor oil and the hydration produced by lavage were confirmed. No significant changes were noted, however, in serum electrolytes with either method of preparation. Additional early studies are promising for the lavage method when used in inflammatory bowel disease patients and as a cleansing preparation for colonoscopy.

Bile acid kinetics were measured by isotope dilution, and hourly outputs of bile acid, cholesterol, and phospholipid were quantified by duodenal perfusion over 24 hr including three liquid meals and an overnight fast in 6 gallstone patients during a pretreatment period and two randomized treatment periods with chenodeoxycholic (chenic) acid or cholic acid. During chenic acid ingestion, bile contained predominantly chenyl conjugates. During cholic acid ingestion, bile was composed of about equal amounts of cholyl and deoxycholyl conjugates; chenyl conjugates decreased markedly due in part to a 50% decrease in chenic acid synthesis. Total bile acid pool size doubled in half the patients receiving either bile acid and was not different during treatment with chenic or cholic acid. Compared to cholic acid, chenic acid caused decreased cholesterol output with no difference in bile acid or phospholipid output. Therefore, bile unsaturated with cholesterol entered the duodenum for more hours per day during chenic acid ingestion than during the cholic or pretreatment periods. There was no relationship among bile acid pool size, bile acid output, and hours per day of supersaturated bile; there was an inverse relationship between total pool size and recycling frequency such that bile acid output remained stable over a wide range of pool sizes. Fasting-state gallbladder bile was supersaturated during the cholic and pretreatment periods, but became unsaturated during chenic acid ingestion. However, hours per day of supersaturated bile could not be reliably predicted from the degree of saturation of fasting-state gallbladder bile (r = 0.62). The efficacy of chenic acid and the lack of efficacy of cholic acid for gallstone dissolution appear related to their different specific effects on biliary cholesterol secretion and not to any effect on bile acid and phospholipid secretion or bile acid pool size.

To determine the efficacy of azathioprine in the treatment of ulcerative colitis, a 6-month double blind trial was carried out. Thirty patients with chronic ulcerative colitis who required the equivalent of at least 10 mg of prednisone per day over the 3 months prior to entering the study were randomized into placebo and azathioprine (1.5 mg per kg) treatment groups. Reduction of steriods was a major objective of the trial. Age and sex distribution, number of bowel movements, sense of well being, steroid dosage, and findings on proctoscopy, rectal biopsy, and colon X-ray initially were similar in the two groups. No side effects were associated with azathioprine. Although steroid dose was lower (p less than 0.05) in the azathioprine group at the termination of the study, no difference between the two groups could be detected in the number of bowel movements, sense of well being, and findings on proctoscopy during the first 3 weeks compared with the last 3 and during the first 3 months compared with the last 3. Although azathioprine does not confer dramatic benefit upon patients with chronic ulcerative colitis who require steroids, it does permit reduction of steroid dosage without apparent worsening of the disease. Its major value in ulcerative colitis may be in facilitating significant decreases or complete discontinuance of steroids.

This study compares the efficacy of intravenous adrenocorticotropic hormone (ACTH) with intravenous hydrocortisone in the treatment of patients with symptomatic inflammatory bowel disease. Drug doses were pharmacologically equivalent on the basis of achieved plasma cortisol levels and continuously monitored urinary corticoid excretion rates. Drug selection and patient evaluation were accomplished with a random double blind technique. Evaluation of 22 consecutive hospital patients indicates that ACTH and hydrocortisone, when administered intravenously in pharmacologically equivalent dosage, are therapeutically equivalent, that response to ACTH is rapid, with no therapeutic lag, and that differences in therapeutic responses cannont be corrrelated with differences in systemic steroid levels.

Chloroquine and metronidazole were compared in a randomized trial for the treatment of amoebic liver abscess in 36 patients. An additional 30 patients were treated without randomization. Chloroquine was given according to the standard protocol at Los tangeles County-University of Southern California Medical Center, which is 500 mg daily for 10 weeks, whereas metronidazole was given in a dose of 750 mg three times daily for 10 days. Criteria for the diagnosis of amoebic abscess included (a) a suitable clinical picture, (b) filling defect on hepatic scan, (c) high titer of antibody to Entamoeba histolytica by indirect hemagglutination, and (d) eventual complete recovery with treatment or appropriate findings on autopsy examination. Treatment failure, defined as illness that persisted beyond 10 days or recurred after that time, occurred in 1 of 28 patients treated with chloroquine and in 2 of 36 treated with metronidazole. In 2 patients who died it was difficult to assess the result of drug therapy. We conclude that both drugs are highly effective. Metronidazole has the advantage of effectiveness against intestinal amoebiasis and the probability of cure with a shorter course of treatment. Speed of response was slightly greater with metronidazole and was somewhat related to abscess size.

The effects of oral metoclopramide, 10 and 20 mg, bethanechol, 25 mg, and placebo on lower esophageal sphincter pressure (LESP) were studied in 15 men with symptoms of gastroesophageal reflux and basal LESP less than 11 mm Hg. Each drug produced a significant increase in LESP when compared to placebo. Metoclopramide, 20 mg, produced a greater increase than either metoclopramide, 10 mg, or bethanechol, 25 mg. Serum gastrin concentrations were not altered by any of the drugs. Side effects were unremarkable. The LESP increasing effect of metoclopramide might be useful in treatment of gastro-esophageal reflux.

The purpose of this study was to measure the effect of alkaline intragastric pH on lower esophageal sphincter pressure (LESP) and on serum gastrin concentration in man. One hundred ten milliliters each of 0.1 N NaHCO3 and control solution were instilled into the stomach for 30 min in random order. Neither LESP nor serum gastrin were higher during the alkali instillation than during the control instillation. Individual subject's peak gastrin and peak LESP during the alkali period were not significantly higher than the corresponding basal values. We conclude that intragastric alkalinization did not increase total radioimmunoassayable serum gastrin concentration or LESP.

Intraarterial vasopressin has been reported to be effective in the treatment of massive upper gastrointestinal hemorrhage. A prospective, controlled clinical trial comparing conventional treatment with conventional therapy plus intraarterial vasopressin was undertaken. Sixty episodes of upper gastrointestinal hemorrhage were evaluated during a 40-month period; 32 received conventional and 28 conventional plus vasopressin therapy. The two groups of patients were similar in type and severity of their bleeding lesions and in their underlying diseases. Vasopressin was more effective in controlling hemorrhage from nonvariceal lesions (P less than 0.05) and from varices (P less than 0.01) than conventional therapy. Transfusion requirements were significantly reduced in those patients who received vasopressin. Paradoxically, survival was not affected by vasopressin administration. The failure of cessation of hemorrhage to improve survival is thought to be due to the degree of advancement of the underlying disease, to the torrential nature of the hemorrhage, to the frequency of recurrent hemorrhage, and to the use of intraarterial vasopressin in some patients in the conventional treatment group in whom conventional therapy had failed.

The incidence of peptic ulcer is increased in cirrhosis and is widely believed to be even greater in cirrhotic patients with portacaval anastomosis (PCA). Two prospective, controlled investigations of prophylactic PCA were evaluated to compare the frequency of peptic ulcer in two groups of cirrhotic patients with similar clinical and laboratory manifestations of cirrhosis randomly selected to be an unoperated Control Group (60 patients) or to have PCA (Shunt Group, 48 patients). In addition, nonrandomized groups of cirrhotic patients, 77 of whom were excluded from the randomized study and 44 of whom had therapeutic PCA, were studied. A diagnosis of chronic peptic ulcer was based on the demonstration of an ulcer crater by X-ray, endoscopy, surgery, or autopsy. Prior to inclusion in these studies, approximately 10% of patients had had peptic ulcer. After inclusion, during a mean follow-up period of 45 months, 12% of both the Control and Shunt Groups developed peptic ulcers. The frequency of complications of peptic ulcer, of recurrence of peptic ulcer, or of acute or symptomatic (unproved) ulcer were similar in both groups. Ulcers tended to develop later in shunted than in unshunted patients. Similar data were obtained from three of four other controlled investigations of PCA. This investigation does not find an increased occurrence of peptic ulcer after PCA. The frequency of ulcer in cirrhosis appears to increase with the duration of the disease independent of the presence or absence of PCA.