A critical look at the clinical use of antacids in acid-peptic disease and gastric acid rebound.

Ancient man found that he could relieve dyspepsia by ingesting minerals that had antacid properties. Calcium carbonate was one of the first of these, as it occurred in relatively pure form in coral and limestone. Antacids were the keystone of medical management until the modern era of ulcer treatment. There has been a renewal of interest in antacids in recent years. Calcium as a component of the diet has come under scrutiny. Antacids have been found to be as effective in promoting healing of ulcer as H2 antagonists, sulcrafate, and colloidal bismuth. With regard to optimal dose in ulcer treatment, doses of antacids from 120 to 1008 mmol/day have been effective. A dose of 120 mmol/day given qid is effective. Low-dose antacids may increase mucosal resistance. The evidence for a specific gastric acid rebound with CaCO3 is based upon flawed assumptions and studies. Stimulation of gastric secretion occurs with all buffers, and this effect is compensated by the remaining buffer. When used properly, CaCO3 is an efficient, inexpensive, and safe antacid.

Ulcer pain mechanisms. The clinical features of active peptic ulcer disease and implications for therapy.

Pain is commonly the initial symptom in peptic ulcer, but the mechanism is controversial. Chemical irritation by hydrochloric acid (HCl) and disordered motor activity have been implicated. Questions have been raised as to whether pain is a good indicator of an active ulcer. We have studied the mechanism of ulcer pain, using intragastric administration of 0.1 N HCl, study of X-ray alterations, measurement of intraluminal pressures, and measurement of gastric acidity along with fluorocinematography. Ulcer pain was accompanied by a synchronous increase in motor activity; gastric emptying was rapid with duodenal ulcer and delayed with gastric ulcer; relief of pain occurred with emptying. Ulcer pain is not a good indicator of activity. Relief of ulcer pain before endoscopic healing with famotidine is due to the inhibition of HCl below the threshold required to initiate disturbances of motor activity. Recurrent 'silent' ulcer with complications occurs in 40% of patients.

Maintenance therapy of duodenal ulcer with famotidine. A multicenter United States study.

The decision to treat a patient with duodenal ulcer should be based upon the following: severity of disease; effectiveness of treatment; and risk and cost of treatment. A number of drugs are effective for this condition. When administration of the drug is discontinued, a recurrence of the ulcer occurs most often within three months, with the rate approaching 90 percent at one year. Maintenance therapy has evolved as a method of preventing recurrence. A double-blind, randomized, multicenter study was done to compare 40 mg of famotidine at bedtime, 20 mg of famotidine at bedtime, and placebo in the maintenance treatment of patients with recently healed duodenal ulcer. In 37 centers in the United States, 303 patients received randomly allocated treatment with 40 mg of famotidine at bedtime (107 patients), 20 mg of famotidine at bedtime (97 patients), or placebo (99 patients). The treatment groups were comparable as to the risk factors and other characteristics. Esophagogastroduodenoscopies were scheduled at three, six, and 12 months of treatment. Additional endoscopies could be done at any time if symptoms suggested a relapse. Cumulative relapse rates were significantly lower in the famotidine groups than in the placebo group at all time points (p less than 0.01). The cumulative life-table relapse rates at three, six, and 12 months were 9.2, 20.9, and 24.8 percent for the 40-mg famotidine group; 13.5, 16.1, and 23.3 percent for the 20-mg famotidine group; and 39.3, 51.5, and 56.8 percent for the placebo group. No significant difference between the two famotidine groups was observed. Within each period, the relapse rate was lower with famotidine than with placebo. Famotidine is more effective than placebo as maintenance therapy. It is generally well tolerated for periods of up to one year. A dose of 20 mg at bedtime is proposed as the maintenance dose. Fewer relapses occurred in non-smokers, in females, and in patients in whom healing occurred with placebo. More relapses occurred in patients under 40 years of age, patients with a long ulcer history, or patients who were younger than 40 years of age at onset of ulcer disease.

Role of delayed indium-111 labeled leukocyte scan in the management of Crohn's disease.

Comparison of nine patients with Crohn's disease who had a positive delayed (24 hr) 111indium leukocyte scan and 10 patients with negative scan showed no significant difference between the two groups for the Crohn's disease activity index, sedimentation rate, survival, complications, number of days in hospital, outpatient visits, or readmissions. Despite the apparent lack of statistical significance in Crohn's disease activity index, the scan was positive in nine of 16 patients with a Crohn's disease activity index more than 150, and none of three patients with Crohn's disease activity index less than 150. In the patients studied, there were no false-positive leukocyte scans. In nine of 10 patients with ileocolonic disease, scanning results correctly predicted the proper management. Six patients with positive scan and enteroclysis responded to medical treatment. Four patients had positive enteroclysis and negative scan; of these, three had radiographic features of chronic ileal stricture which was confirmed at operation. The results suggest that a negative delayed indium-111 leukocyte scan may be useful in diagnosis of chronic fibrotic ileal stricture.

Mechanisms of transport of L-histidine and beta-alanine in hamster small intestine.

Whole rings of hamster jejunum and ileum were used to study the uptake of L-histidine (L-His) and beta-alanine (beta-Ala), the constituents of the dipeptide carnosine. The rate of uptake of L-His and beta-Ala (1 mM) was not significantly different in the jejunum compared with the ileum. Results of total influx (2 min) of 0.5-100 mM L-His suggested that transport was by more than one pathway, and the contribution of nonmediated component was calculated to be 0.24 mumol X g-1 X 2 min-1 X mM-1 for both jejunum and ileum. The apparent affinity of L-His for a transporter was higher in the ileum (K iota, 8.0 mM) than the jejunum (Kt, 11.7 mM). Influx (2 min) of beta-Ala was found to be linearly related to substrate concentration over the range 0.5-100 mM. The Kd (rate constant for nonmediated uptake of beta-Ala) was 0.23 and 0.14 mumol X g-1 X 2 min-1 X mM-1 for jejunum and ileum, respectively. Steady-state (20-min) uptake of L-His was significantly higher in the ileum than jejunum at substrate concentrations of 75 mM. L-His accumulated in the tissue up to a medium concentration of 50 mM in the jejunum and 75 mM in the ileum. In contrast, no evidence of tissue accumulation of beta-Ala was found in 20-min incubations. beta-Ala steady-state uptake in the ileum was significantly higher than in the jejunum at substrate concentrations of 30 and 75 mM.

The efficacy and selectivity of pirenzepine. Review and commentary.

Pirenzepine is a new anticholinergic agent which selectively binds to gastric mucosal muscarinic receptors. We reviewed the double-blind, therapeutic studies on ulcer patients and the clinical pharmacology for evidence of healing and selectivity. Healing rates of ulcer at doses of 100-150 mg/day varied between 54-84% in trials with 718 duodenal ulcer patients and 630 patients with gastric ulcer. Total side effects incidence in these trials was 18.1%. At 150 mg/day, there was 13.5% incidence of dry mouth, 6.3% incidence of visual disturbance and 2.6% incidence of constipation. In clinical pharmacology trials, pirenzepine moderately inhibited gastric secretion with a slight inhibition of salivary secretion and esophageal motility at 100 mg/day. Higher doses produced the expected parasympatholytic profile, except for the absence of cardioacceleration. We conclude that pirenzepine in low doses, compared to classical antimuscarinic drugs, is relatively selective for gastric hyposecretion. It may be associated with a lower frequency of side effects in therapeutic trials at doses of 100-150 mg/day. Dry mouth and visual disturbance are the most common side effects. Selectivity is dose limited and has so far been demonstrated only at a daily dosage of 100 mg, in 2 divided doses.

Intraluminal pressure measurements during barium enema: full column vs. air contrast.

Intraluminal pressure measurements were made during enema examination of 10 patients undergoing full column studies and 10 patients receiving air-contrast studies. There was no significant difference between the pressure in the distal colon of the two groups. All pressures were less than those produced by Valsalva maneuver or straight leg raising, and were generally less than those previously found to be necessary to rupture the colon. The authors believe that the findings should dispel any fear that an air-contrast examination is more hazardous than a full column study. Perforations occurring during these procedures are more likely related to disease of the colon wall or local trauma.

Granular cell myoblastoma of the esophagus. Report of two cases.

Granular cell myoblastoma (GCM) of the esophagus is a rare, usually benign tumor, most often discovered incidentally during upper endoscopy, surgery, or autopsy. Although some reports have questioned the safety of endoscopic biopsy of granular cell tumors of the esophagus, we feel that the procedure can be performed safely and accurately. For the unwary, histological examination may lead to a misdiagnosis of squamous cell carcinoma. Although some reports of malignant esophageal tumors can be found, in general, if the histologic appearance of the tumor is benign, malignant transformation or metastasis is unusual. Surgical resection for malignant and for large symptomatic benign tumors is the treatment of choice. In, however, individuals with histologically benign tumors. who are asymptomatic or who are not considered good surgical candidates, careful observation with endoscopic follow-up can be safely done.

Nonsurgical diagnosis of pancreatic mass.

Because of recent advances made in various diagnostic procedures, it has become easier to diagnose cancer of the head of the pancreas. Chronic pancreatitis, however, may show morphologic mass findings similar to pancreatic cancer. Twenty-three patients with a pancreatic head "mass," identified through surgical exploration, have been reviewed retrospectively with regard to differential diagnosis by comparing the preoperative findings of duodenoscopy, endoscopic retrograde pancreatography (ERP), endoscopic retrograde cholangiography (ERC), and percutaneous transhepatic cholangiography (PTC). Emphasizing the findings, value, and limitations of each procedure, we used simple morphologic criteria for our differential diagnosis. Duodenoscopic findings gave information for accurate diagnosis in 66%, ERP was correct in 50%, and ERC in 88%. PTC in 88%. PTC was helpful in establishing the correct diagnosis in 90%. This study clarifies some technical and practical aspects of these procedures. We believe duodenoscopy must be used more often for direct histologic study, cytology, and needle biopsy in addition to ductal visualization in a pancreatic head mass. PTC is recommended more strongly for use in establishing the correct diagnosis of a pancreatic head "mass."

Fiberendoscopic removal of long foreign bodies from the stomach using a colon stiffening tube as a protective sheath.

A colonoscopic stiffening tube was effectively used as a protective sheath in the esophagus during the endoscopic removal of a long ballpoint pen and a writing pencil from the stomach.

Benign retroperitoneal emphysema associated with upper gastrointestinal endoscopy.

It is important to realize that retroperitoneal emphysema may be seen as a complication of upper gastrointestinal endoscopy. Because of the increased frequency of endoscopic and associated procedures, it is important to realize that these striking roentgenographic findings may be associated with a benign clinical condition that will resolve with expectant management alone. Clinically, we might be forced to differentiate this complication with pathological perforation from the original lesion or with free perforation by the instrument depending on the clinical conditions.