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H.M.T. El-Zimaity [1] J.G. Kim [2] D.Y. Graham [1] [7/07] Corpus Atrophy Occurs as Contiguous Sheets of Pseudo-pyloric Mucosa with Islands of Intestinal Metaplasia not as MAG Background: Gastric cancer [...]

M.P. Dore [1] G. Sanna [2] G.P. Cherchi [3] R. Negrini [4] S. Marras [5] L. Marras [5] L. Simula [3] D.Y. Graham [6] G. Realdi [5] [6/18] Helicobacter pylori [...]

Background: Helicobacter pylori remains a global health hazard, and vaccination would be ideal for its control. Natural infection appears not to induce protective immunity. Thus, the feasibility of a vaccine for humans is doubtful. Methods: In two prospective, randomised, double-blind, controlled studies (Paul Ehrlich Institute application nos 0802/02 and 1097/01), live vaccines against H pylori were tested in human volunteers seronegative for, and without evidence of, active H pylori infection. Volunteers (n = 58) were immunised orally with Salmonella enterica serovar Typhi Ty21a expressing H pylori urease or HP0231, or solely with Ty21a, and then challenged with 2×105 cagPAI- H pylori. Adverse events, infection, humoral, cellular and mucosal immune response were monitored. Gastric biopsies were taken before and after vaccination, and postchallenge. Infection was terminated with antibiotics. Results: Vaccines were well tolerated. Challenge infection induced transient, mild to moderate dyspeptic symptoms, and histological and transcriptional changes in the mucosa known from chronic infection. Vaccines did not show satisfactory protection. However, 13 of 58 volunteers, 8 vaccinees and 5 controls, became breath test negative and either cleared H pylori (5/13) completely or reduced the H pylori burden (8/13). H pylori-specific T helper cells were detected in 9 of these 13(69%), but only in 6 of 45 (13%) breath test-positive volunteers (p = 0.0002; Fisher exact test). T cells were either vaccine induced or pre-existing, depending on the volunteer. Conclusion: Challenge infection offers a controlled model for vaccine testing. Importantly, it revealed evidence for T cell-mediated immunity against H pylori infection in humans. [ABSTRACT FROM AUTHOR]

Background and Aims: The roles of the virD4 and the cagG genes in the cog pathogen icily island of Helicobacter pylon for gastroduodenal pathogenesis are unclear and their roles in vivo have not been examined. Methods: Seven week old male Mongolian gerbils were inoculated with the wild type H pylon TN2GF4, its isogenic virD4, or cagG mutants. Animals were sacrificed at 4, 12, and 24 weeks after inoculation. Gastric inflammation and H pylori density were evaluated by histology, inflammatory response (as measured by interleukin (IL)-1 β mRNA levels), proliferative activity (as assessed by 5'-bromo- E 2'deoxyuridine labelling indices), and host systemic reaction (as measured by anti-H pylon IgG antibody). Results: Degree of gastric inflammation, proliferative activity, and mucosal IL-1 β mRNA levels remained low throughout the first 12 weeks in gerbils infected with the virD4 mutants. Degree of gastric inflammation and proliferative activity increased at 24 weeks with the virD4 mutants reaching levels comparative with p those seen at four weeks with the wild-type strains. Mucosal IL-1 β mRNA levels were also increased at 24 weeks with the vinD4 mutants and levels at 24 weeks were similar between the wild-type and virD4 mutants. In contrast, gerbils infected with the cogG mutants had reduced ability to colonise gerbils, and no or little gastric inflammation or proliferative activity was observed. Conclusions: loss of the vinD4 gene temporally retarded but did not abrogate gastric inflammation. Loss of the cagG gene abolished gastric inflammation partially via reduced ability to colonise gerbils. Unknown factors related to the type IV secretion system other than CagA may influence gastric inflammation. [ABSTRACT FROM AUTHOR]

Background: A reliable challenge model is needed to evaluate Helicobacter Pylori vaccine candidates. Methods: A cog pathogen icily island negative, OipA positive, multiple antibiotic susceptible strain of H pylori obtained from an individual with mild gastritis (Baylor strain 100) was used to challenge volunteers. Volunteers received 40 mg of Famotidine at bedtime and 104-1010 cfu of H pylori in beef broth the next morning. Infection was confirmed by 13C urea breath test (13C-UBT), culture, and histology. Eradication therapy was given four or 12 weeks post challenge and eradication was confirmed by at least two separate UBTs, as well as culture and histology. Results: Twenty subjects (nine women and 11 men; aged 23-33 years) received a H Pylori challenge. Eighteen (90%) became infected. Mild to moderate dyspeptic symptoms occurred, peaked between days 9 and 12, and resolved. Vomitus from one subject contained >103 viable/mi H Pylori. By two weeks post challenge gastric histology showed typical chronic H Pylori gastritis with intense acute and chronic inflammation. The density of H Pylori (as assessed by cfu/biopsy) was similarly independent of the challenge dose. A minimal infectious dose was not found. Gastric mucosal interleukin 8 levels increased more than 20-Told by two weeks after the challenge. Conclusion: Challenge reliably resulted in H Pylori infection. Infection was associated with typical H Pylori gastritis with intense polymorphonuclear cell infiltration and interleukin 8 induction in gastric mucosa, despite absence of the cog pathogenicity island. Experimental H Pylori infection is one of the viable approaches to evaluate vaccine candidates. [ABSTRACT FROM AUTHOR]

The effectiveness of antacid maintenance therapy in preventing duodenal ulcer (DU) relapse was investigated. Two hundred and fifty one asymptomatic patients with healed DU were stratified into smokers and non-smokers and randomised to receive for one year either placebo, or Maalox TC three tablets (81 mmol) at bedtime (hs), or Maalox TC three tablets in the morning plus three tablets at bedtime (bd) (162 mmol), or cimetidine 400 mg at bedtime. A double dummy technique was used to render the study double blind. In 176 patients evaluable for efficacy, the cumulative relapse at one year was: placebo 57%; Maalox TC hs 39%; Maalox TC bd 23%; cimetidine 25%. Maalox TC bd and cimetidine were equally effective and superior to placebo (p less than 0.01) and bedtime Maalox TC (p less than 0.04). The benefit of treatment was significant for the overall sample and for the subgroup of smokers. The results for the non-smokers also supported efficacy for these two treatments but, perhaps because of small sample sizes, these comparisons were not significant. All 251 patients were assessed for safety. Approximately half the patients in each treatment group had adverse events, leading to withdrawal in three, seven, 12, and four patients on placebo, Maalox hs, Maalox bd, and cimetidine respectively. Diarrhoea occurred in 12 patients in Maalox TC bd and eight in each other group. Serum magnesium concentrations were unchanged; aluminium concentrations were higher than baseline at six and 12 months in both antacid groups and at 12 months in the cimetidine group but the differences were not significant. Maalox TC three tablets bd are as effective as cimetidine 400 mg at bedtime in reducing DU relapse and both are superior to placebo. [ABSTRACT FROM PUBLISHER]

Crohn's disease is a granulomatous form of enteritis superficially similar to Johne's disease (paratuberculosis) of ruminants. Recently, a Mycobacterium sp closely related to Mycobacterium paratuberculosis was cultured from tissues of patients with Crohn's disease suggesting that M paratuberculosis may be the aetiologic agent in some cases. In addition, greater seroreactivity to M paratuberculosis has been reported in patients with Crohn's disease. In the present study, we have evaluated the serum antibody response to disrupted M paratuberculosis using ELISA and serum specimens from 33 people with Crohn's disease, 21 with ulcerative colitis, and 12 non-inflammatory bowel disease controls. We failed to find a consistent IgG, IgM, or IgA antibody response to Mycobacterium paratuberculosis. The results indicate that, as in bovine paratuberculosis, serum seroreactivity is not a reliable tool for examining the relationship between human intestinal disease and mycobacteria. [ABSTRACT FROM PUBLISHER]