Incidence of gastric lesions in patients with rheumatic disease on chronic aspirin therapy.

Endoscopy was done in 82 patients with rheumatic disease who were receiving chronic aspirin therapy. Fifty-eight patients were taking at least eight aspirin tablets daily for 3 or more months; 24 patients were taking, in addition to the aspirin, a maximum of one other antiinflammatory, nonsteroidal medication. Endoscopy in 45 normal subjects not taking aspirin showed no ulcers or erosions and a 4% incidence of gastric erythema. In the 82 patients with rheumatic disease, 14 (17%) had gastric ulcers, 33 (40%) had gastric erosions, and 62 (76%) had gastric erythema. Regular aspirin and buffered aspirin users had an ulcer incidence of 23% and 31% respectively, compared with a 6% incidence in enteric-coated aspirin users (P less than 0.05). One third of all patients with gastric ulcer had no gastrointestinal symptoms. Patients taking chronic aspirin therapy for rheumatic diseases have a higher than suspected incidence of gastric ulcer and erosions. Gastric ulcer may exist without symptoms in such patients.

Morphological observations on the normal human cardiac glands.

The majority of human cardiac glands that lie immediately distal to the termination of esophageal epithelium are compound or branched tubular glands. They empty into overlying gastric pits. The glands of this region are often organized into lobule-like complexes by the surrounding connective tissue of the lamina propria. The secretory tubules contain mucous cells, parietal cells and endocrine cells. The mucous cell is the most common cell type observed and appears to comprise two populations. The majority are pyramidal in shape and show numerous spherical, electron-dense secretory granules. Profiles of rough endoplasmic reticulum are observed scattered throughout the cytoplasm and Golgi complexes occupy a supranuclear position in relation to forming secretory granules. Morphologically this cell type appears similar to the mucous neck cell of the fundus. Secretory granules of a second mucous cell type are mottled in appearance and show an area of increased electron density near the limiting membrane. Parietal cells are observed and appear identical to those in the fundus. The large number of endocrine cells present raises questions concerning the traditional concept of the function of these particular glands.

A scanning electron microscopic study of normal human oxyntic mucosa using blunt dissection and freeze fracture.

Biopsies from the fundic mucosa of healthy volunteers were examined by scanning electron microscopy following blunt dissection and freeze fracture. The mucosal surface exhibited a cobblestone appearance. With increased magnification, microvilli could be demonstrated on the luminal surface of individual surface cells. Blunt dissection of the gastric mucosa revealed tubular gastric pits descending from the surface until they opened into branched tubular gastric glands. The gastric glands are irregular in outline due to the knoblike projections of individual parietal cells. The internal structure of the component cells also was examined with the scanning electron microscope following freeze fracture. Mucous granules were observed in the apical portion of surface epithelial cells. Lumina of parietal cell canaliculi were found to be continuous with the lumen of the gastric glands. Pepsinogen granules could be seen throughout the cytoplasm of chief cells. The blunt dissection-freeze fracture technique utilizing the scanning electron microscope allows, for the first time, a three-dimensional view of human gastric mucosa, including the gastric pits and glands as well as some of the internal architecture of component cells.

Effect of cimetidine on ion fluxes and potential difference across the human stomach.

The H(2)-receptor antagonist, cimetidine, reduces acid output regardless of the means of stimulation. It is not known in man whether this is due entirely to a reduction in acid secretion or whether increased back diffusion of hydrogen ions is also occurring. We studied fluxes of H(+), Na(+), K(+), and Cl(-) ions after acid instillation into the human stomach in six healthy subjects with and without prior administration of 300 mg cimetidine orally. Potential difference across gastric mucosa was measured continuously throughout each study. Cimetidine caused a significant reduction in hydrogen ion secretion (5.05 mEq per 15 minutes controls versus 2.70 cimetidine, p < 0.05), and consequently a significant reduction in net hydrogen flux into the gastric lumen (2.01 mEq per 15 minutes versus 0.02, p < 0.05). There were no significant differences between sodium ion fluxes in control and cimetidine studies, suggesting that the gastric mucosal barrier remained intact. Cimetidine alone caused a highly significant rise in intragastric pH (to 7) and of potential difference (p < 0.001). Addition of intragastric acid (pH < 1.0) did not reverse the rise in potential difference caused by cimetidine, suggesting that factors other than change in intragastric pH were involved. In conclusion, our studies support the concept that reduction in acid output by cimetidine is due to inhibition of acid secretion, and not to increased permeability to hydrogen ion.

Protective effect of cimetidine on aspirin-induced gastric mucosal damage.

Aspirin alters the gastric mucosal barrier as measured by ionic flux and potential difference. The effect of cimetidine on aspirin-induced alterations in gastric mucosa was studied in five normal male volunteers. Aspirin effects were studied with and without previous treatment with cimetidine. Mean (+/- SEM) basal potential difference was -48 +/- 1 mV. After 600 mg of aspirin in 1 dl of isotonic saline, potential difference decreased in 10 min to -39 +/- 1 mV (P less than 0.001) and returned to baseline within 60 min. Control biopsies showed 2% damaged mucosal cells compared with 20% damaged at the time of maximal drop in potential difference (P less than 0.001) after aspirin. Recovery to 9% damage occurred by 60 min. In subjects pretreated with 300 mg cimetidine, potential difference rose during 1 h to -62 +/- 1 mV (P less than 0.001). After aspirin potential difference fell to -48 +/- 1 mV compared with -39 +/- 1 mV with aspirin alone (P less than 0.01) and returned to -62 +/- 1 mV at 60 min. The cimetidine-treated group showed 4% mucosal damage at the peak potential difference fall after aspirin, significantly less (P less than 0.02) than in the untreated subjects.