Esophageal disease in patients with angina-like chest pain.

To assess the frequency of esophageal disease in patients with angina-like chest pain and normal coronary arteriograms, 16 patients underwent esophageal manometric studies, acid perfusion (Bernstein) tests, upper gastrointestinal series and cholecystograms. Five patients had evidence of esophageal diseases. Three of the five had manometric criteria of increased nonperistalsis; one patient had idiopathic diffuse esophageal spasm while the other two patients had acid infusion tests which reproduced the presenting chest pain and the manometric findings were regarded as a motor disturbance of the esophagus secondary to chronic gastroesophageal reflux. The remaining two patients had symptomatic gastroesophageal reflux--one with an acid infusion test positive for pressure like chest pain and the other with a decreased resting lower esophageal sphincter pressure associated with reflux of barium on upper gastrointestinal series. All five patients had improvement of symptoms during a follow up period of seven to 17 months. Manometric studies in 18 normal subjects of similar age revealed no evidence of esophageal disease. Since esophageal disorders capable of causing chest pain were diagnosed in one-third of the patients (5/16 or 31%), it is suggested that investigations for esophageal disease, specifically directed at gastroesophageal reflux-induced abnormalities and idiopathic diffuse esophageal spasm, be included in the evaluation of patients with angina-like chest pain of uncertain origin.

National Cooperative Crohn's Disease Study: adverse reactions to study drugs.

Adverse reactions to the drugs employed in the National Cooperative Crohn's Disease Study were sought prospectively at each patient visit and by retrospective review of all patient charts. Prednisone caused evident side effects in over 50% of patients on high-dose suppressive therapy and in approximately one-third of patients on prophylactic dose. Thirty-two percent of patients on high-dose, and 26% on prophylactic-dose prednisone required dose reduction or withdrawal because of side effects. Comparable figures for sulfasalazine were 14% and 12%, and for azathioprine 32% and 20%. The incidence of nausea, vomiting, or anorexia among patients taking sulfasalazine was 46% and 34%, on high and low dose respectively; however, this incidence was no different than that observed among patients taking placebo. These symptoms occasioned withdrawal from the study of only 4% and 3% of patients on high and low doses of sulfasalazine, respectively. Azathioprine produced leukopenia at a dose of 2.5 mg/kg body weight in 15% of patients and the mean white cell count, lymphocyte count, granulocyte count, and hematocrit all fell significantly in patients on this dose. Pancreatitis occurred in 5% of patients taking azathioprine but in no other patients. Sulfasalazine proved to be the safest effective suppressive drug for Crohn's disease. Prednisone toxicity, though substantial, is acceptable in view of its demonstrated suppressive efficacy. Azathioprine was approximately as toxic as prednisone but no more effective than placebo in suppressing active disease. None of the drugs was effective prophylactically, and all showed appreciable long-term toxicity.

Azathioprine-related pancreatitis in patients with Crohn's disease.

Pancreatitis developed in 6 patients in the National Cooperative Crohn's Disease Study. In five of these the diagnosis was confirmed by elevated levels of seum amylase or lipase. All cases were in the 113 patients who received azathioprine and occurred within the first 21 days of treatment. This incidence of pancreatitis was significantly greater than in the patients treated with sulfasalazine, prednisone, or placebo (P less than 0.01).

Effect of chronic metoclopramide therapy on serum pituitary hormone concentrations.

The effect of chronic (3--9 months) therapy with metoclopramide on serum levels of pituitary and thyroid hormones was studied in 4 males and 1 female. The mean serum prolactin concentration during metoclopramide therapy was significantly higher than after discontinuation of metoclopramide. Serum prolactin concentrations increased acutely after each dose of metoclopramide. Serum prolactin concentrations increased acutely after each dose of metoclopramide, and gradually returned to normal by 6--12 h. There was no sifgnificant differences in the serum TSH, T3, T4, GH, and gonadotrophin levels during and after metoclopramide administration. In the male subjects the mean serum testosterone was normal, but significantly lower during metoclopramide therapy.

Cimetidine versus intensive antacid therapy for duodenal ulcer: a multicenter trial.

In a randomized double blind multicenter trial, patients treated with cimetidine (800 or 1200 mg daily) or an intensive regimen of Al-Mg antacid (210 ml daily) had similar rates of duodenal ulcer healing and pain relief. After 4 weeks of treatment, the proportion of patients with ulcer healing by endoscopy were: cimetidine (1200 mg), 21 of 33 (64 percent); cimetidine (800 mg), 19 of 32 (59 percent); and antacids, 15 of 29 (52 percent). These proportions did not differ significantly. Eighty per cent of cimetidine-treated patients became asymptomatic by week 4, as did 63 percent of antacid-treated patients (P greater than 0.1). No untoward effects were observed during cimetidine treatment. Twenty-seven per cent of antacid-treated patients reported diarrhea.

Effect of one-month treatment with cimetidine on gastric secretion and serum gastrin and pepsinogen levels.

The inhibitory effects of cimetidine on gastric acid and pepsin secretion were studied before and after 1 month of treatment with 300 mg of cimetidine four times a day in 15 male duodenal ulcer patients. Cimetidine inhibited both pentagastrin- and peptone meal-stimulated acid secretion significantly better before, than after, 1 month of treatment. Similarly cimetidine inhibited pentagastrin-stimulated pepsin secretion significantly better before treatment. Meal-stimulated serum gastrin concentrations were significantly higher after treatment. The mechanism(s) of these effects was not apparent.

HLA-B5 associated with duodenal ulcer.

In a search for further genetic factors contributing to ulcer disease we undertook a study of the frequency of HLA antigens in patients with duodenal ulcer. Seventy-seven male patients (of two races) were typed for the HLA-A and-B loci. Thirteen of the 54 (24%) white males were found to have antigen B5 compared to 10% of controls. These results have a P value of 0.0016 which remains significant even when multiplied by the number of antigens tested (28). These results demonstrate a significant association between duodenal ulcer and HLA antigen B5 in white males, with a relative risk of 2.9, greater than that associated with the combination of blood group O and nonsecretor status.

Effect of cholestyramine on the symptoms of reflux gastritis. A randomized, double blind, crossover study.

Bile acids have been proposed to be important in the pathophysiology of the syndrome of "bile reflux gastritis" after surgery. To examine the role of cholestyramine, an ion exchange resin that binds bile acids, on symptoms of this syndrome, we did a randomized, double-blind crossover study on 16 patients. No differences in frequency of abdominal pain, nausea, vomiting, or bitter taste were observed among cholestyramine (4 g, three times daily for 3 weeks), placebo, and routine (dietary restriction and ad libitum antacid) treatment periods. We conclude that this regimen of cholestyramine was ineffective in symptomatic treatment of bile reflux gastritis.

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.

Accuracy of physicans' predictions of cholecystography results.

In the decision theory model of medical diagnosis and treatment, optimal choice of diagnostic tests requires accurate estimation of the probability that a given test will be positive. We assessed the ability of physicians to estimate the probability that a specific test (cholecystography) would be positive. For 102 patients, the predicted number of gallstone cases, 35.8, was significantly greater than the observed number, 15 (p less than 0.001), even though 13 of the 15 observed cases were patients with previous radiographic evidence of gallstones. The overestimation of probability of positive tests casts doubt on the correctness of decisions regarding selection of diagnostic tests when these decisions are derived from probability estimates based on intuition or expert opinion.

A controlled trial of metoclopramide in symptomatic gastroesophageal reflux.

Since metoclopramide increases lower-esophageal-sphincter pressure in patients with gastroesophageal reflux, we compared the effects of metoclopramide, 10 mg four times daily, with those of placebo on symptoms in 31 patients with chronic heartburn. Eighteen patients completed a random-order, double-blind crossover study of two consecutive eight-week periods. The final 13 patients crossed over only if their symptoms were not substantially improved after the first eight weeks. Response of low-esophageal-sphincter pressure to metoclopramide did not correlate significantly with symptomatic improvement. After the metoclopramide treatment period, mean basal pressure was unchanged from values before study. In both treatment periods, metoclopramide-treated patients had significantly more symptomatic improvement than the control group (P less than 0.05).

Antacid and placebo produced similar pain relief in duodenal ulcer patients.

The effectiveness of antacid and placebo in relieving single episodes of spontaneous duodenal ulcer pain were compared in two double blind, controlled, randomized trials. The trials compared the effects on ulcer pain of individual doses of a liquid antacid and placebo, rather than the effects of therapeutic regimens with antacid or placebo. Thirty patients were studied. There were no significant differences between antacid and placebo in time to onset, degree, or duration of pain relief. These results suggest that factors other than gastric acid neutralization are important in acute relief of spontaneous duodenal ulcer pain.

Experience with synthetic secretin in the treatment of duodenal ulcer.

Hospitalized male patients with endoscopically verified duodenal ulcer were studied to determine the effect of secretin on the clinical course of their disease. Seven patients received synthetic porcine secretin, 333 mug subcutaneously every 4 hr for 10 days, and 6 patients received placebo injections on the same schedule. Repeat endoscopy was performed within 48 hr of completing the 10-day treatment period. The trial was discontinued because of transient, asymptomatic, hyperamylasemia in secretin-treated patients. Although significant gastric alkalinization could be reproducibly demonstrated in secretin-treated patients, secretin was not more effective than placebo in relieving pain or healing duodenal ulcer. However, because the number of patients was small, definitive conclusions regarding efficacy of secretin in ulcer treatment could not be drawn.

Comparison of metoclopramide with other dynamic tests of prolactin secretion.

Metoclopramide, a derivative of procainamide, was compared with thyrotropin releasing hormone (TRH), N3im-methyl-TRH and chlorpromazine as a prolactin (PRL) releaser in 11 euthyroid males. The peak response of serum PRL and the maximum increment of serum PRL (max deltaPRL) were greater (P less than 0.0005) after the administration of metoclopramide (deltaPRL 24.1 +/- 1.5 (SE) ng/ml) than after either TRH (14.9 +/- 1.5 ng/ml) or chlorpromazine (7.0 +/- 2.1 ng/ml). There were no significant differences between the peak and max deltaPRL responses to metoclopramide or N3im-methyl-TRH. Metoclopramide produced a small increase in serum thyrotropin and small reductions of serum growth hormone, luteinizing hormone and follicle-stimulating hormone. Metoclopramide may be useful for dynamic testing of PRL release. It offers the advantage of oral administration; a 10 mg dose produces a larger, more sustained increment in serum PRL than other agents used to evaluate prolactin reserve.