Chronic atrophic gastritis: early diagnosis in a population where Helicobacter pylori infection is frequent.

Chronic atrophic gastritis (CAG) is a premalignant condition characterized by loss of gastric antral deep glands. The histologic changes in antral gastric biopsy specimens from 54 Peruvian patients with dyspepsia were studied to detail the development and characteristics of CAG. Ninety-six percent of the biopsies revealed severe superficial mucosal inflammation and 89% showed deep inflammation. Moderate or severe CAG was present in 36 (67%) of the 54 patients. In the early stages of CAG, a glandular lymphoid adherence lesion was noted in 17 (31%) of the 54 biopsy specimens. This lesion consisted of lymphocytes adherent to the antral deep gland cells and was associated with glandular epithelium alterations. The late stage was characterized by small glands, remnants of glands, and gland replacement with a fibrocellular infiltrate or intestinal metaplasia. We propose that the development of CAG probably proceeds via a stereotyped sequence, with an early deep inflammatory component that may trigger local gland destruction and eventual permanent loss.

[Helicobacter pylori and gastric cancer]. / Helicobacter pylori y cáncer gástrico.

A review is done on the evidence in favor of a link between Helicobacter pylori infection and gastric cancer of the intestinal type. In countries at high risk of gastric cancer, like Perú, Hp infection begins early in life and is highly frequent and persistent. When Hp colonizes the gastric mucosa, it causes active chronic gastritis. Initially, the gastritis is of the superficial type. With time, and probably as a result of the concurrent action of nutritional, epidemiologic and immunologic modulating factors, chronic superficial gastritis may give rise to a progressive gastric pathology that leads to gastric premalignant lesions (chronic atrophic gastritis, intestinal metaplasia and dysplasia of the gastric mucosa) and increases the predisposition to gastric cancer. The principal modulating factors are described. The epidemiology of gastric premalignant lesions in Perú is also described. Finally, a discussion is done on the effect that eradication of Hp infection might have on the prevalence of gastric cancer.

Low prevalence of gastric metaplasia in the duodenal mucosa in Peru.

We compared the prevalence of gastric metaplasia of the duodenal mucosa (GM) and its characteristics in 204 Peruvian patients from a low socioeconomic level with the corresponding prevalence reported in dyspeptic patients from a developed country, the United Kingdom. Gastric metaplasia was significantly less prevalent in the Peruvian than in the United Kingdom series. However, when present, GM was not significantly different in extent or frequency of colonization by Helicobacter pylori or association with active duodenitis, despite a higher prevalence of H. pylori-associated gastritis. Hypochlorhydria was markedly more frequent in the Peruvian than in the United Kingdom series. The finding of a low prevalence of H. pylori-colonized GM in patients with previously reported low prevalence of duodenal ulcer gives further support to a pathogenic link between both conditions.

Low peptic ulcer and high gastric cancer prevalence in a developing country with a high prevalence of infection by Helicobacter pylori.

We compared the prevalence rates of peptic ulcer (duodenal and gastric) and gastric cancer in 1,796 dyspeptic Peruvian patients with those reported in 2,883 similar patients from developed countries. The prevalence of total peptic ulcer was significantly lower, and that of gastric cancer significantly higher, in the Peruvian patients. The prevalence of gastric ulcer was lower but not significantly so. We deduced that the significantly lower prevalence of total peptic ulcer was directly related to the low prevalence rate of duodenal ulcer. We hypothesize that the reason for these differences was probably a higher prevalence of Helicobacter pylori-associated chronic atrophic gastritis with hypochlorhydria in the Peruvian patients. Hypochlorhydria decreases the predisposition to peptic ulcer (especially duodenal ulcer), and chronic atrophic gastritis may predispose an individual to gastric cancer.

Helicobacter pylori and progressive gastric pathology that predisposes to gastric cancer.

Evidence is presented suggesting that infection by Helicobacter pylori triggers and continuously contributes to the pathophysiology of progressive gastric changes that can ultimately lead to gastric cancer. In Peru, especially in population groups of low socioeconomic status, infection by H. pylori begins earlier in life and is more prevalent and persistent than in developed countries. The infection produces a destructive lesion of the mucinous surface epithelium which probably enables other aggressive luminal factors to cause further mucosal damage. As a consequence, active chronic gastritis appears. The gastritis is of the superficial type at the beginning but may progressively change to atrophic. Chronic atrophic gastritis is found more frequently and at a younger age in dyspeptic patients with low socioeconomic status--that is, in patients having higher prevalence of persistent infection by H. pylori since earlier in life. When chronic atrophic gastritis becomes severe and extensive, hypochlorhydria ensues. Hypochlorhydria favors the appearance of bacterial overgrowth, nitrites, and N-nitroso compounds in the gastric lumen. N-nitroso compounds, because of their mutagenic-carcinogenic properties, probably induce gastric premalignant lesions like intestinal metaplasia and dysplasia of the gastric mucosa. Oral bismuth therapy apparently reverses H. pylori-associated gastric dysplasia. It is proposed that future programs designed for the control of gastric cancer would be incomplete if they do not include further evaluation of the many effects of infection by H. pylori on the gastric mucosa and of cost-effective methods to eradicate the infection.

Hypogammaglobulinemia due to abnormal suppressor T-cell activity in Crohn's disease.

Two patients are described who initially developed Crohn's disease followed by hypogammaglobulinemia. The immunologic profile of both was typical of acquired common variable hypogammaglobulinemia. The peripheral blood lymphocytes of neither patient were able to synthesize immunoglobulin when cultured with pokeweed mitogen in vitro nor were cultures containing mixtures of purified B cells and T cells. A potent suppressor T cell was present in the peripheral blood of both patients that was able to completely suppress immunoglobulin synthesis in cultures of normal B cells and T cells. When the patients' B cells were highly purified and appropriately stimulated in vitro, they were able to synthesize immunoglobulin, providing strong evidence that the circulating suppressor T cell was mediating the hypogammaglobulinemia. We have previously shown that many patients with Crohn's disease have a circulating "covert" suppressor T cell that is not expressed in cultures of unfractionated peripheral blood lymphocytes, but which becomes apparent after isolation of their T cells on antiimmunoglobulin columns. We conclude that these 2 patients represent instances in which the "covert" suppressor T cell of Crohn's disease has become overtly active in the systemic circulation and has resulted in hypogammaglobulinemia.

Species-specific binding of purified pili (AF/R1) from the Escherichia coli RDEC-1 to rabbit intestinal mucosa.

Species-specific colonization of rabbit intestine by RDEC-1 Escherichia coli is an accepted animal model for bacterial mucosal adherence. To determine whether RDEC-1 pili are functional as adherence factors for this organism, we grew the organism under conditions that promoted pilus expression; we isolated the pili, documented their purity, and compared their mucosal adherence properties with those of whole organisms using an indirect immunofluorescence technique. Frozen sections of rabbit, rat, guinea pig, and human small intestine were incubated with either piliated or nonpiliated RDEC-1 organisms or purified RDEC-1 pili and observed for the distribution and intensity (0-4+) of fluorescence. Piliated RDEC-1 organisms fluoresced brightly (4+) and were distributed along the entire mucosal surface of the rabbit ileum. Only a few nonpiliated RDEC-1 attached to rabbit ileum, and they were randomly scattered across the entire section of tissue. Rabbit ileum overlain with pure RDEC-1 pili showed a specific, D-mannose resistant (2-3+) fluorescence on the mucosal surface from the crypts to the villus tips. No fluorescence was seen on the guinea pig, rat, or human mucosal surface overlain with RDEC-1 pili. Purified RDEC-1 pili adhere to the rabbit intestinal mucosa in a species-specific manner and with the same distribution as whole piliated organisms. The data suggest that RDEC-1 produce pili (distinct from type 1 pili) that determine the specificity of the mucosal adherence of RDEC-1 to rabbit ileum.

Allopurinol hepatotoxicity. Report of two cases and review of the literature.

Allopurinol hepatotoxicity occurred in two patients. Data from the literature suggest that allopurinol can occasionally cause liver injury, particularly in persons receiving diuretic drugs or with compromised renal function. Clinical and laboratory findings are consistent with hepatocellular injury mediated by a hypersensitivity reaction. Most patients recover when the drug is withdrawn; the possible benefits of corticosteroid treatment remain to be established.

Esophageal hematoma. Four new cases, a review, and proposed etiology.

We report four cases of esophageal hematoma and emphasize that endoscopically and radiographically it may simulate a neoplasm. After a review of 26 cases, we found that patients with normal hemostasis often had esophageal hematoma occur distally after vomiting. Most of these hematomas probably originated from a Mallory-Weiss laceration. In contrast, patients with impaired hemostasis had esophageal hematoma occur proximally or at multiple sites. Many of these hematomas occurred spontaneously, without a history of vomiting, and probably resulted from impaired coagulation. Regardless of etiology most esophageal hematomas were associated with a benign course.