Hepatitis in disseminated bacillus Calmette-Guérin infection.

Local immunotherapy with an attenuated live strain of Mycobacterium bovis, bacillus Calmette-Guérin (BCG), is an effective and frequently used treatment for in situ transitional cell carcinoma (TCC) of the bladder. Success rates are high, and serious side effects are infrequent but can affect every organ system. A 79-year-old patient with recently diagnosed TCC who was treated with intravesical BCG for a recurrence after initial surgical treatment is reported. After unsuccessful attempts at bladder catheterization with the creation of a false passage for his third treatment, BCG was instilled via a suprapubic catheter the same day and again a week later. Two weeks after the third BCG instillation, the patient presented with profound lethargy and weakness to the point of not being able to get up out of a chair. He was febrile, anorexic, icteric and had hepatosplenomegaly. Disseminated BCG infection was suspected on the basis of history, clinical examination and a liver biopsy that showed noncaseating granulomatous hepatitis. Empirical treatment was started with antituberculous combination therapy. A short course of an oral corticosteroid was given. Clinical improvement was marked and sustained so that the patient could be discharged home for the full six-month course of his treatment. Disseminated BCG infection with granulomatous hepatitis can be severe and life-threatening in cases where a large intravascular inoculum of BCG may have been given inadvertently.

A review of the possible bacterial determinants of clinical outcome in Helicobacter pylori infection.

Helicobacter pylori is present in 40-60% of the population and approximately 10-20% of these infected individuals suffer from a H. pylori associated disease such as peptic ulcer disease or gastric cancer. This article reviews the potential bacterial determinants responsible for and markers predictive of both the acquisition of H. pylori infection and subsequent clinical outcome; i.e., asymptomatic infection or disease. The acquisition of H. pylori infection depends on exposure (hence the increased risk in lower socioeconomic groups and developing nations) to viable bacteria with at least a functional urease gene in a susceptible host. Once infection occurs, bacterial virulence factors, including the vacuolating cytotoxin, and genes of the cag pathogenicity island, as well as nonbacterial factors may determine disease outcome. Future research is being directed at discovering other bacterial virulence factors responsible for the different clinical outcomes of H. pylori infection. This will be greatly enhanced by the recent release of the complete genome sequence of H. pylori. The determination of the relative importance of each of these recognized and other as yet unrecognized factors responsible for disease outcome will assist in the appropriate targeting of patients in the treatment of H. pylori infection.

Functional heterogeneity of colonic adenocarcinoma mucins for inhibition of Entamoeba histolytica adherence to target cells.

Mucins secreted from the gastrointestinal epithelium from the basis of the adherent mucus layer which is the host's first line of defense against invasion by Entamoeba histolytica. Galactose and N-acetyl-D-galactosamine residues of mucins specifically inhibit binding of the amebic 170 kDa heavy subunit Gal-lectin to target cells, an absolute prerequisite for pathogenesis. Herein we characterized the secretory mucins isolated from the human colon and from three human colonic adenocarcinoma cell lines: two with goblet cell-like (LS174T and T84) and one with absorptive cell-like morphology (Caco-2). By Northern blot analysis the intestinal mucin genes MUC2 and MUC3 were constitutively expressed by confluent LS174T and Caco-2 cells, whereas T84 cells only transcribed MUC2 and not MUC3 mRNA. 3H-glucosamine and 3H-threonine metabolically labeled proteins separated as high M, mucins in the void (Vo > 10(6) Da) of Sepharose-4B column chromatography and remained in the stacking gel of SDS-PAGE as depicted by fluorography. All mucin preparations contained high amounts of N-acetyl-glucosamine, galactose, N-acetyl-galactosamine, fucose and sialic acid, saccharides typical of the O-linked carbohydrate side chains. Mucin samples from the human colon and from LS174T and Caco-2 cells inhibited E. histolytica adherence to chinese hamster ovary cells, whereas mucins from T84 cells did not. These results suggest that genetic heterogeneity and/or posttranslational modification in glycosylation of colonic mucins can affect specific epithelial barrier function against intestinal pathogens.

Association of Helicobacter pylori genotype with gastroesophageal reflux disease and other upper gastrointestinal diseases.

OBJECTIVE: Helicobacter pylori (H. pylori) is a recognized pathogen, but it may also have a protective effect for gastroesophageal reflux disease (GERD). We compared the prevalence of potential virulence factors (cagA, cagE, vacA genotypes) in GERD to other upper gastrointestinal diseases and controls. METHODS: A total of 405 patients underwent gastroscopy with H. pylori isolation and serum testing. Patient diagnostic subgroups were prospectively defined. Genotypes were determined by amplification using polymerase chain reaction. CagA antibodies were determined by western blot, enzyme-linked immunosorbent, and flow microsphere immunofluorescent assays. RESULTS: Patients were grouped as follows: nonulcer dyspepsia (26%), GERD (20%), gastric ulcer (17%), duodenal ulcer (12%), gastric cancer (6%), or controls (19%). The cagA gene was present in 94-97% of subjects in all categories, but the cagA antibody was less prevalent in nonulcer dyspepsia (69%, 95% CI: 48-86%, p = 0.02) and GERD (69%, CI: 39-91%, p < 0.05) than in those with gastroduodenal pathology including gastric ulcer, duodenal ulcer, and gastric cancer (92%, CI: 81-98%). The cagE gene and vacA S1 genotype were more frequent in patients with gastroduodenal pathology (p < 0.01). GERD was associated with a significantly lower rate of vacA S1 genotype than controls (29% (CI: 10-56%) versus 80% (CI: 59-93%), p < 0.01). The vacA S1 genotype was associated with the presence of cagA antibodies. CONCLUSIONS: The cagE and vacA S1 genotypes are more prevalent in patients with peptic ulcer or gastric cancer, suggesting a potential function in virulence for these genes. However, the vacA S1 genotype was also more prevalent in controls than GERD, suggesting a potential protective effect against GERD.

Genetic variability determinants of Helicobacter pylori: influence of clinical background and geographic origin of isolates.

Helicobacter pylori has an unusual pattern of genetic variation, which complicates research on this organism. To gain a better understanding of the forces behind this phenomenon, the extent to which recombination and single point mutations affect genetic variability in H. pylori was quantified and the influence of both geographical distance and clinical background were assessed. Site-directed restriction-endonuclease digestion of 2 gene fragments was performed on 168 isolates from Montreal and Berlin. Allelic diversity was found to be much higher for H. pylori than for other bacterial species. This finding is consistent with those of previous studies on H. pylori that were conducted using other techniques. However, nucleotide diversity was within the range reported for other bacterial species. Phylogenetic analysis found no grouping of strains with clinical background or geographical origin. Recombination at a rate that resulted in linkage equilibrium within genes can explain these observations.