Healing and recurrence of active duodenal ulcer with nizatidine.

Nizatidine, a new H2-receptor antagonist for treatment of duodenal ulcer disease, was evaluated in a unique two-phase, placebo-controlled, randomized, double-blind, multicenter clinical trial. Patients received either 150 mg nizatidine twice daily or placebo for 4 weeks (phase I). If ulcer healing did not occur during phase I, patients were randomly reallocated to receive either 150 mg nizatidine twice daily or placebo for an additional 4 weeks (phase II). Patients with a healed ulcer continued on the same therapy. All patients were endoscoped at week 8. Healing rates at week 2 were 93 of 265 (35%) nizatidine-treated patients and 55 of 260 (21%) placebo-treated patients (p less than 0.001); at week 4, healing rates were 198 of 259 (76%) nizatidine-treated patients and 95 of 243 (39%) placebo-treated patients (p less than 0.001). In phase II, ulcer healing occurred in 46 of 86 (53%) nizatidine-treated patients and in 23 of 90 (26%) placebo-treated patients (p = 0.002). In patients who had a healed ulcer at previous endoscopies, 18 of 178 (10%) nizatidine-treated patients and 10 of 81 (12%) placebo-treated patients had a recurrence of duodenal ulcer. Smokers who had histories of previous ulcers were more likely to have an early recurrence.

The laboratory response to glucagon dosages used in gastrointestinal examinations.

Laboratory studies occasionally are necessary for patients who have undergone hypotonic gastrointestinal examinations. To ascertain the effects of glucagon on these patients, we determined the biochemical and hematologic responses to doses of 0.25-2 mg of glucagon in a double-blind crossover study. When glucagon was given intravenously or intramuscularly in increasing doses, serum values for glucose and insulin increased linearly up to 1 mg with a slight decrease at 2 mg. After intravenous and intramuscular administration of glucagon, the white blood cell count and the percentage of neutrophiles and bands increased, and the percentage of lymphocytes decreased. Reports of side effects included one each of nausea and mouth dryness after intravenous glucagon and four reports of nausea and one of mouth dryness after intramuscular glucagon. No changes in the pulse and blood pressure could be attributed to glucagon administration.

Enteroclysis in partial small bowel obstruction.

In a 5 year period, 56 patients with suspected partial small bowel obstruction were evaluated by enteroclysis or the antegrade small bowel enema. Mechanical partial obstruction was diagnosed by enteroclysis in 38 of the patients, 24 of whom required surgery. The diagnosis by enteroclysis was confirmed in 23 of the patients. In the single patient with "false-positive" enteroclysis, the obstruction had been interpreted as minimal. The thirteen remaining patients were managed conservatively. The possibility of significant mechanical obstruction was excluded by enteroclysis in 19 patients. There were no complications associated with the procedure. Enteroclysis is a safe, rapid, and accurate method for the evaluation of patients with partial small bowel obstruction.

Detection of surgical lesions of the small bowel by enteroclysis.

Enteroclysis is an examination in which barium is infused directly into the small intestine, and compression radiographs are taken on each segment. This method eliminates many of the inherent limitations of the conventional small bowel follow-through examination. This report concerns 45 patients with 48 small bowel lesions. They were missed on the conventional examination but detected within 3 months by subsequent enteroclysis and confirmed surgically. There were 15 patients with Meckel's diverticula, 7 with obstructive adhesive bands, 5 with Crohn's disease, 5 with blind pouch syndrome (1 with a leiomyoma inside the blind pouch), 2 with other leiomyomas, 3 with metastatic carcinoma, two with primary carcinoma 3 with radiation stricture, two with sinus tract lesions and fistulas, and 1 with another lesion. Improved intubation techniques and better barium mixtures make enteroclysis possible in most hospitals. As surgeons appreciate the value of enteroclysis, they can request this examination for appropriate patients to sooner find many surgical lesions of the small bowel which frequently go undiagnosed.

GLC determination of ethinamate and its hydroxy derivative in biological fluids.

A sensitive, specific GLC assay was developed for the determination of ethinamate in plasma and its major metabolite, trans-4-hydroxyethinamate, in urine. The assay uses a mass internal standard of dimethylethinamate. Ethinamate is extracted from alkalinized plasma with dichloromethane. Urine samples require beta-glucuronidase hydrolysis prior to extraction of hydroxyethinamate. The dichloromethane is removed by evaporation, and the compounds are measured by GLC using a flame-ionization detector. By using GLC-chemical-ionization mass spectrometry, the compounds measured were identified as the intact ethinamates. Plasma and urine data are presented from a bioavailability study to demonstrate the utility of this method. From these data, the ethinamate plasma half-life was calculated as 1.9 +/- 0.3 hr.

Treatment of duodenal ulceration in the United States.

Nizatidine, a new H2-receptor antagonist for the treatment of duodenal ulcer disease, was compared with placebo in a dose-response, double-blind, parallel, multicenter clinical trial. Patients were randomly allocated to receive either nizatidine (25 mg b.i.d., 150 mg b.i.d., or 300 mg at bedtime) or placebo. At the end of 4 weeks, patients whose ulcer had not healed were randomly reallocated to receive either the nizatidine 150 mg b.i.d. dosage regime or placebo for an additional 4 weeks. Nizatidine doses of 300 mg at bedtime and 150 mg b.i.d. demonstrated similar healing frequencies. Both of these doses were statistically significantly superior in ulcer healing to the nizatidine 25 mg b.i.d. dose and to placebo at the end of 4 weeks. Patients randomly reallocated to receive nizatidine had significantly greater healing rates than patients randomly reallocated to receive placebo. In summary, nizatidine given as a single evening dose of 300 mg or as 150 mg b.i.d. proved to be equally safe and effective in the healing of active duodenal ulcers.

Nizatidine as maintenance therapy of duodenal ulcer disease in remission.

A new H2-receptor antagonist, nizatidine (150 mg h.s.), was compared with placebo as maintenance therapy in a randomized, parallel, double-blind, one-year study of 513 patients with recently healed duodenal ulcer. Endoscopies were performed at 0, 3, 6, and 12 months and at unscheduled times if symptoms of active peptic ulcer disease were present. Cumulative ulcer recurrence rates for nizatidine and placebo were 13 versus 40% at 3 months, 24 versus 57% at 6 months, and 34 versus 64% at 12 months. The differences were significant (p less than 0.001) at each treatment period. Smokers in both treatment groups had significantly greater recurrence rates than non-smokers. Symptoms of peptic ulcer disease were significantly less in nizatidine-treated patients in the first 3 months of treatment. Adverse events, including those related to peptic ulcer disease, occurred more frequently in placebo-treated patients. Nizatidine proved to be safe and effective in preventing recurrences of duodenal ulcer.

State-of-the-art barium examination in opportunistic esophagitis.

This report presents a comparison of state-of-the-art esophagography and endoscopy in the diagnosis of pathologically proven esophagitis. The modern multiphasic esophagogram is shown to have a sensitivity of 92% for the detection of opportunistic esophagitis in the immunocompromised patient. State-of-the-art esophagography provides a sensitive and inexpensive method for investigating patients in whom opportunistic esophagitis is suspected and for monitoring their response to therapy.

Gastrointestinal radiography with glucagon.

This report summarizes the results of nine diagnostic radiographic studies done double blind crossover comparing glucagon to placebo and to anticholinergic drugs in volunteers. In seven studies the subjects were administered drug intramuscularly and in two studies intravenously. There were five diagnostic studies of the upper gastrointestinal tract, one for esophageal varices and three of the colon. The results indicate that glucagon can be given intramuscularly and intravenously. When given intravenously it has a rapid onset and predictable length of action depending on the dose given. Reports of side effects were few consisting primarily of nausea and or vomiting. These results indicate that glucagon is the drug of choice for hypotonic diagnostic examinations.

A comparative double-blind study of esophageal barium pastes.

To demonstrate esophageal varices barium sulfate suspensions must coat the lower esophagus for as long as 5 to 10 minutes. This study compared the ability of five barium sulfate preparations to resist disappearance by inadvertent swallowing. Three of the special preparations for esophageal examination, Esophatrast, Barosperse Esophageal Paste, and HD-5000 performed satisfactorily. Examiner skill, persistence, and careful technique are the most important factors in examining the lower esophagus. The authors' procedure for examination of the esophagus for varices is described. It takes into account position, time, phase of respiration, occasional use of drugs, and procedures to insure good coating and relaxation of the lower esophagus.

Evaluation of the small intestine by enteroclysis for Crohn's disease.

We reviewed the records of 100 consecutive patients referred for enteroclysis by gastroenterologists because of suspected Crohn's disease of the small bowel to assess the clinical utility of the information obtained by this method. More than one-third of the patients in the study group had subtle lesions of early Crohn's disease, all patients who required surgery had severe disease by radiologic criteria, and none of the 34 patients clinically suspected of having Crohn's disease of the small bowel in whom the enteroclysis was normal developed Crohn's disease in two or more years of clinical follow-up. Enteroclysis provides gastroenterologists with accurate and detailed structural information relevant to the appropriate management of the disease and in our hands is a reliable test for excluding Crohn's disease of the small bowel.

The role of the physician in the late diagnosis of primary malignant tumors of the small intestine.

Survival from primary malignancies of the small intestine has not improved during the last four decades. One reason for this is the advanced stage of disease at the time of surgery. In order to determine why diagnosis is made late, we reviewed the records of all patients with small bowel malignancy diagnosed between 1967 and 1988. The time from the onset of symptoms to the first medical contact and the time from medical contact until diagnosis were evaluated in 77 patients. The average delay in diagnosis attributable 1) to the patient failing to report symptoms was less than 2 months, 2) to the physician not ordering the appropriate diagnostic test was 8.2 months, and 3) to the radiologist failing to make the diagnosis was 12 months. Thus, the major delay in diagnosis was after medical help was sought and not from the onset of symptoms to first medical consultation. Physicians must increase their sensitivity to the subtle but persistent symptoms that necessitate a small bowel evaluation.

Factors in the diagnostic delays of small bowel malignancy.

The overall survival from primary malignancies of the small intestine has not changed over more than four decades. This generally is ascribed to delays in establishing the diagnosis and the advanced stage of the disease when treatment is begun. There has been no critical analysis of these delays. To answer these questions, we reviewed the records of all patients diagnosed with small bowel malignancy from 1967 to 1988 at the Methodist Hospital of Indiana. The onset and duration of symptoms, first medical consultation, time of performance of diagnostic procedures and surgery were verified in 77 patients with histologically confirmed small bowel malignancies. The longest delay occurs from the time medical help is sought to the time the diagnosis is made, not from the onset of symptoms to the first medical consultation. The small bowel should always be considered as a source of unexplained, persistent subtle abdominal symptoms.

Dose response to intramuscular glucagon during hypotonic radiography.

In a study to determine a dose response to glucagon during hypotonic duodenography, 15 male and female volunteers received placebo and 0.25 mg 1 mg and 2 mg glucagon intramuscularly, double-blind and cross-over. When 0.25 mg glucagon was given, the onset of drug effect was approximately 13--18 min: the mean duration of moderate hypotonicity was approximately 4--7 min. The larger the dose, the greater the duration of drug action. When 2 mg glucagon was given, the onset of drug effect occurred in approximately 4--7 min; the mean duration of moderate hypotonicity was 22--32 min. There were no changes in pulse or blood pressure attributable to the drug with these doses, and reports of nausea and diarrhea did not increase significantly until a dose above 1 mg was given. One mg glucagon given IM is useful in hypotonic upper Gl radiographic examinations. The onset of hypotonicity was 8--10 min with a duration of 12--27 min when this dose was given. Few reports of side effects were attributable to this dose.

Double-blind radiographic study of dose response to intravenous glucagon for hypotonic duodenography.

This study was undertaken to determine a dose response to glucagon during hypotonic duodenography. Fifteen male and female volunteers received placebo and 0.25 mg, 0.5 mg, 1 mg, and 2 mg of glucagon intravenously, double-blind, and crossover. Onset of drug effect occurred in approximately 45 seconds, regardless of the dose of glucagon given. There was a significant (p less than 0.01) decrease in gastrointestinal tonicity with all doses. The larger the dose, the greater the duration of drug action. Satisfactory stomach, duodenal, and small bowel hypotonicity for radiography were obtained with 0.25 to 0.5 mg of glucagon given intravenously with few side effects.

Effect of D-Val1, D-Trp8-somatostatin on the motility of the stomach, duodenum and jejunum.

D-Val1, D-Trp8-somatostatin was given to seven volunteers to relax the gastrointestinal tract. Doses of drug ranging from 1-250 mcg. were given intravenously, single blind, as one bolus. The seven subjects had a total of 23 studies. The stomach never became hypotonic in any subject. The onset of drug effect on the duodenum and jejunum of moderate hypotonicity after 10-100 mcg. was 4.8 minutes and at 150-250 mcg., was 10.1 minutes. Onset of atonicity after 10-100 mcg. wa 5.7 minutes and at 150-2509 mcg., was 13.0 minutes. Duration of moderate hypotonicity after 10-100 mcg. was 20.9 minutes and at 150-250 mcg., was 22.4 minutes. Duration of atonicity at 10-100 mcg. was 11.5 minutes and at 50-250 mcg., was 14.1 minutes. Preliminary results suggest that the onset and duration of effect, relative to dose, were so variable that the drug appeared to be an unsatisfactory hypotonic agent for upper gastrointestinal radiography.

Acquired jejunoileal diverticular disease: subject review.

Of 519 consecutive patients examined by enteroclysis, 12 (2.3%) were found to have acquired diverticula of the jejunum and ileum. All except one patient had multiple diverticula, most occurring in the jejunum. In only one patient could symptoms be ascribed to the abnormality. The combination of intraluminal distention and extrinsic abdominal compression provided by the enteroclysis technique appears to be the most reliable method for the demonstration of small-bowel diverticula. A discussion of the complications that may result from acquired jejunoileal diverticulosis and a review of the literature are presented.

Early rectal tube removal for improved patient tolerance during double-contrast barium enema examination.

During a five year period, 62 patients each underwent two barium enema examinations. The length of time that the rectal tube remained in place varied in each subject. Early rectal-tube removal resulted in better patient acceptance of the double-contrast barium enema examination.

Comparison of gastrointestinal effects of aspirin and fenoprofen. A double blind crossover study.

Sixteen men received 3904 mg of aspirin, 2400 mg of fenoprofen, or placebo daily for 1 week in a double blind and crossover trial. Fecal blood loss was measured by 51Cr labeled red cells; gastric and duodenal pathology were observed endoscopically. There was more (P less than 0.05) blood loss (4.96 ml) after aspirin than after fenoprofen (2.46 ml) or placebo (0.79 ml). By endoscopic examination, aspirin induced more (P less than 0.05) gastrointestinal pathology than fenoprofen or placebo, and there was a correlation of 0.70 between the two methods used in this study.