Omeprazole and ultrastructural modifications occurring in reflux esophagitis [1]

Dilated intercellular spaces are a sign of esophageal epithelial damage in acid-perfused rabbits. This alteration can be identified only by transmission electron microscopy (TEM).1,2 The same changes have also been demonstrated in reflux esophagitis in humans, occurring in patients with either erosive or nonerosive esophagitis.3 As yet, we do not know if successful medical therapy induces a regression of these ultrastructural changes. We observed a case of hematemesis and melena occurring in an 11-month-old child. Upper gastrointestinal endoscopy revealed a hemorrhagic erosive esophagitis (stage IV of Savary-Miller modified classification). Eight endoscopic biopsies were taken 5 cm above the Z line. Of these, 4 were stained with H&E, to assess general pathology, and 4 were selected for processing by TEM.4 The latter biopsies showed mean intercellular space diameters of $3.04 mm (mean normal values reported in humans, 0.46 6 0.06 mm SD)3 (Figure 1A). After 6 months of treatment with ranitidine (10 mg z kg21 z d syrup) upper GI endoscopy showed a stage II esophagitis. TEM demonstrated mean intercellular space diameters of$2.5 mm (Figure 1B). As a consequence, the patient was treated with omeprazole 10 mg/day for 18 months (the half granular content of the capsule of 20 mg was administrated in a few milliliters of orange juice, 30 minutes before breakfast). During this period, the patient was asymptomatic, growth was normal, and no side effects were recorded. Upper GI endoscopy at the end of therapy showed a normal esophageal mucosa both endoscopically and histologically. TEM also demonstrated the complete recovery of the ultrastructural changes (Figure 1C) with the mean intercellular space diameters being #0.40. This is the first demonstration that omeprazole is effective not only in inducing the regression of symptoms and macroscopic lesions but in the restoration of normal intercellular space dimensions, whose dilatation must be considered the first alteration of reflux esophagitis. Nevertheless, to date we do not know if such an outcome is achieved in every patient considered clinically and endoscopically cured, nor do we know details of the treatment time interval required to achieve complete ultrastructural recovery

HCV INFECTION AND CHRONIC ACTIVE HEPATITIS IN ALCOHOLICS

Histological signs of chronic active hepatitis were found in 11/41 (27%) patients with chronic alcoholic liver disease. All these 11 patients tested positive for antibodies to HCV and no other causes of chronic hepatitis were found

RECTAL CELL-PROLIFERATION AND COLON CANCER RISK IN ULCERATIVE-COLITIS

Cell proliferation kinetics of 30 patients affected by extensive ulcerative colitis in remission have been studied with autoradiography of rectal biopsies incubated with tritiated thymidine. The results have been compared with those of 20 control subjects without evidence of colonic diseases, and of 16 patients with multiple nonfamilial colonic adenomas. The labeling index was similar in the three groups (P = NS). On the contrary, the labeling frequency (SEM) in the upper 40% of the crypt (phi h value) was 0.04 +/- 0.01 in controls, 0.16 +/- 0.02 in ulcerative colitis, and 0.10 +/- 0.01 in adenoma patients (P less than 0.001 ulcerative colitis versus controls, P less than 0.01 adenomas versus controls, P = NS ulcerative colitis versus adenomas). The distribution of phi h values in ulcerative colitis showed a bimodal trend with 22 patients having mean phi h values similar to adenoma patients (0.10 +/- 0.01) and 8 with higher values (0.30 +/- 0.02). No relationship was found between phi h values and duration of colitis, age of patients, or age at onset of symptoms. These data show that cell kinetics studies can detect patients at particularly high risk of colon cancer, and that additional factors should determine colon cancer risk level in ulcerative colitis

Interplay between the Gastric Bacterial Microbiota and Candida albicans during Postantibiotic Recolonization and Gastritis

The indigenous bacterial microbiome of the stomach, including lactobacilli, is vital in promoting colonization resistance against Candida albicans. However, there are gaps in our understanding about C. albicans gastric colonization versus disease, especially during the postantibiotic recovery phase. This study compared the gastric responses to C. albicans strains CHN1 and SC5314 in microbiome-disturbed and germfree mice to elucidate the contribution of the indigenous microbiota in C. albicans colonization versus disease and yeast-bacterium antagonism during the post-cefoperazone recolonization period. C. albicans can prevent the regrowth of Lactobacillus spp. in the stomach after cefoperazone and promote increased colonization by Enterococcus spp. Using a culture-independent analysis, the effects of oral cefoperazone on the gastric bacterial microbiota were observed to last at least 3 weeks after the cessation of the antibiotic. Disturbance of the gastric bacterial community by cefoperazone alone was not sufficient to cause gastritis, C. albicans colonization was also needed. Gastritis was not evident until after day 7 in cefoperazone-treated infected mice. In contrast, in germfree mice which lack a gastric microbiota, C. albicans induced gastric inflammation within 1 week of inoculation. Therefore, the gastric bacterial community in cefoperazone-treated mice during the first week of postantibiotic recolonization was sufficient to prevent the development of gastritis, despite being ineffective at conferring colonization resistance against C. albicans. Altogether, these data implicate a dichotomy between C. albicans colonization and gastric disease that is bacterial microbiome dependent