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We studied the effect of esophageal inflammation on lower esophageal sphincter (LES) pressure in cats by measuring LES pressure and taking mucosal biopsies before and after the development of experimental esophagitis, as well as after a 3 1/2-week recovery period. Perfusion of the esophagus with 0.1 N HCl for either 1 hr or 1/2 hr per day for 4 days produced inflammatory changes by mucosal biopsy and was associated with a marked decline in LES pressure. Upon resolution of the inflammation, LES pressure returned to normal. Biopsies were normal in control groups which underwent either esophageal perfusion with distilled water or intragastric perfusion with acid, 1 hr per day for 4 days, and LES pressures in these groups remained unchanged from pre-perfusion values. These studies indicate that lower esophageal inflammation per se adversely affects LES pressure in cats, and that experimental esophagitis may be a useful model for the study of LES function and its relation to esophageal inflammation.

Intravenous (IV) alimentation of experimental animals has been associated with an attenuation of the small bowel mucosa. To determine whether alterations in epithelial renewal accompany the morphological changes, we studied cell proliferation as well as the light and electron microscopic appearance of the small bowel in intravenously and orally alimented rabbits. After 10 days of either IV or oral alimentation, 3H-thymidine was given intravenously to all animals to label proliferating cells, and 1 hour later sections of duodenum, upper jejunum, and distal ileum were taken for autoradiography and light and electron microscopy. IV alimentation was accompanied by significant reductions in epithelial cell proliferation and mucosal thickness in the proximal small bowel. The density of goblet cells was greater in the duodenum and jejunum, but less in the ileum, of intravenously alimented rabbits than in corresponding areas of the oral controls. Furthermore, ultrastructural changes in the villous absorptive cells of intravenously alimented rabbits, such as lengthened microvilli and increased numbers of multivesicular bodies, suggested that epithelial migration also may be slowed during IV alimentation.

Agents such as ethanol, aspirin, bile acids, and hypertonic urea and glucose, are capable of breaking the physiological gastric mucosal barrier and may cause ultrastructural injury to the epithelial cells within several minutes of exposure. Ethanol at any pH, and aspirin and bile acids at acid pH, are lipid soluble and diffuse rapidly into surface epithelial cells where a sequence of injury can be documented by electron microscopy. First, the nuclear chromatin becomes clumped and the density of the cytoplasmic ground substance decreases. Second, mitochondria become swollen and the apical cell membrane is distorted. Finally, the apical cell membrane ruptures and the cell disintegrates. Throughout this sequence, the tight junctions between cells appear morphologically intact. In contrast to lipid soluble agents, hypertonic urea and glucose do not diffuse well into surface epithelial cells. Although these agents also cause rapid changes in transmucosal potential difference and ion fluxes, their ultrastructural effects are quite different. Hypertonic urea and glucose initially cause small blebs within the tight junctions and larger vacuoles within the cytoplasm of surface epithelial cells, while the remainder of the cell structure appears normal. More severe injury is characterized by more vacuolization and eventual disruption of epithelial cells. These changes presumably are secondary to osmotic shifts of fluid and electrolytes. Although the 'cytoprotective' effects of prostaglandins have been well described, there is virtually no information at the ultrastructural level concerning the protective effects of prostaglandins with regard to these ulcerogenic agents.

Bile salts have been implicated in the pathogenesis of gastritis and gastric ulcer. Because the bile salt binding agent cholestyramine has been suggested as a possible therapy for gastric ulcer, we studied the effects of cholestyramine, in the form of Questran, on bile salt-induced injury to mouse gastric mucosa. Solutions of taurocholate or of glycochenodeoxycholate, with or without added Questran, were instilled into the stomachs of fasted mice at pH 1, 3, 5, and 7. Taurocholate damaged the mucosa only at pH 1, whereas glycochenodeoxycholate caused injury at pH 1 and 3. Questran failed to prevent mucosal damage by either bile salt. The ineffectiveness of cholestyramine to prevent injury may be due to the nonionized fraction of bile salts at pH's below their pKa's which will not be sequestered by the anion exchange resin. This phenomenon may help explain the insignificant effect of Qestran treatment in promoting healing of gastric ulcers in a previous clinical trial.

The purpose of this study was to investigate the histogenesis of experimental tumors in the rat esophagus. Thirty rats received 0.0015% N-methyl-N-amylnitrosamine (MNAN) in the drinking water for 12 weeks. Another 30 rats received tap water. All rats then received tap water until sacrifice. Rats from each group were sacrificed immediately after MNAN administration, four weeks after, and eight weeks after. One hour before sacrifice, [3H]TdR was injected by tail vein to label proliferating cells. The entire esophagus and stomach were removed and processed for light and electron microscopy and autoradiography. The overall frequency of esophageal tumors after MNAN was 83% and did not differ significantly among the three experimental groups. Tumors were primarily papillomas and squamous cell carcinomas and occurred with equal frequency in the upper, middle, and lower thirds of the esophagus. No tumors were found in the squamous-lined forestomach. Electron microscopy revealed abundant tonofilaments, free ribosomes, and mitochondria accompanied by vacuoles. By autoradiography, esophageal epithelial proliferation was markedly stimulated in nontumorous mucosa from all three experimental groups. We conclude that MNAN ingestion for 12 weeks reliably produces papillomas and squamous cell carcinomas throughout the rat esophagus, but not in the squamous-lined forestomach, and that MNAN stimulated marked epithelial proliferation which is accompanied by thickening of the epithelium in nontumorous esophageal mucosa.

Eighteen opossums received 2250 rad 60Co to the entire esophagus and lower esophageal sphincter. Animals received treatment with 600 mg aspirin, 25 mg/kg hydrocortisone, or saline before irradiation and twice daily for 1 week after irradiation. At 10 days postirradiation, animals were evaluated for signs of acute esophagitis by esophagoscopy and barium esophagram. Each animal was then killed and the esophagus removed and evaluated histologically. Animals treated with either aspirin or hydrocortisone had significantly milder esophagitis than control irradiated animals.

We studied the effects on gastric fundic and antral epithelial proliferation of acute water immersion restraint stress in rats and of chronic indomethacin ingestion in rats and humans using autoradiographic methods. Acute stress appeared to inhibit fundic epithelial proliferation but had no effect on antral proliferation in rats. We conjecture that this inhibition of fundic epithelial proliferation may help explain the development of stress-related mucosal lesions, which are more likely to occur in fundic mucosa. Chronic indomethacin ingestion stimulated fundic epithelial proliferation but had no effect on antral proliferation in both rats and humans. From these observations we conjecture that the failure of antral epithelial proliferation to respond to indomethacin may account in part for the ulcerogenic action of this drug.

The marginal openings of single and twin foil-bonded aluminous porcelain crowns were compared in crowns fabricated indirectly for extracted teeth and directly on typodont teeth. The crowns were cemented with zinc phosphate, embedded in plastic, and sectioned. Marginal opening was measured directly with a traveling microscope. There was no significant difference between the marginal openings of twin- and single-foil crowns fabricated indirectly for extracted teeth. When the crowns were constructed directly on typodont teeth to eliminate the variables of impression-making and die fabrication, the single-foil crowns possessed a significantly smaller marginal opening than the twin-foil crowns. Both the twin- and single-foil complete porcelain crowns resulted in clinically acceptable margins. The single-foil crowns were easier to make.

Three aspects of the esophageal mucosal injury that occur in gastroesophageal reflux disease are discussed in this article. First, the histologic changes in the squamous epithelium-lined esophagus are variable. Some patients with reflux symptoms do not have histologic evidence of inflammatory cell infiltration within the mucosa, but rather may have more subtle effects of mucosal injury, namely, thickening of the basal regenerative layer, elongation of the papillae, or intraepithelial eosinophils. However, these more subtle findings often are merely confirmatory of other clinical indicators of gastro-esophageal reflux; they may have their most practical application to the research investigation of reflux disease. Second, the presence of esophageal mucosal inflammation may adversely affect lower esophageal sphincter function. This phenomenon can be demonstrated in the cat model. Whether it is operative in humans is unclear. Finally, the development of columnar metaplasia (Barrett's epithelium) is more than a histologic curiosity because this condition confers an increased risk of developing adenocarcinoma of the esophagus. Among several unanswered questions about Barrett's epithelium is what is an appropriate surveillance program for patients with Barrett's epithelium to detect the presence of, or predict the development of, cancer?

We studied the effect of chronic aspirin ingestion on gastroduodenal epithelial proliferation by feeding rats aspirin in the drinking water. A control group of rats received plain water. At the end of 4 wk, [3H]-thymidine was given intravenously to label proliferating cells, and the rats were killed 1 h later. Sections of fundus, antrum, and proximal duodenum were processed for light autoradiography. We found that chronic aspirin ingestion stimulated epithelial proliferation in fundic mucosa but had no effect in the antrum. In the duodenum, aspirin increased proliferation in the lowest four crypt-cell positions, which most likely indicates an increase in stem-cell production. None of the tissues contained evidence of inflammation or ulceration. The proliferative effects of aspirin may help explain the previously observed phenomenon of mucosal adaptation in the rat after repeated exposure to aspirin. Further, if human gastroduodenal epithelium responds in a similar manner to chronic aspirin exposure, the effects on proliferation may explain in part the distribution of aspirin-associated ulcers.

We performed upper gastrointestinal endoscopy in 60 rural Haitian patients who complained of chronic upper abdominal pain. Twenty-five of 37 men (68%) and 5 of 23 women (22%) had abnormal findings. In men the predominant abnormalities were severe duodenal ulcer, duodenitis, and pyloroduodenal obstruction; duodenal ulcer or duodenitis appeared to precede obstructive disease by about 20 years. In women the abnormal findings invariably were milder than in men and consisted of duodenal ulcer, duodenitis, and gastritis. These observations as well as the observations of others indicate that peptic ulcer disease is common in developing countries, particularly among men. We hypothesize that this familiar abnormality reported from unfamiliar places represents the ordinary spectrum of peptic ulcer disease, but that inadequate treatment of recurrent episodes over time leads to obstruction. Physicians need to learn more about the epidemiology of peptic disease in developing countries and to devise better methods of effective treatment to prevent the late complication of gastric outlet obstruction.