Is a long-term ranitidine-based triple therapy against Helicobacter pylori only a heritage of the past? A prospective, randomized clinicopharmacological study.

BACKGROUND: Acid suppression plus two antibiotics is currently considered the gold standard anti-Helicobacter pylori treatment, but the effective role of gastric antisecretory drugs is still poorly understood. AIMS: To compare a 14-day ranitidine-based triple regimen against Helicobacter pylori with one based on omeprazole, and to study the influence of antisecretory drugs on metronidazole pharmacokinetics in human plasma. METHODS: A total of 150 dyspeptic H. pylori-infected patients were randomized for ranitidine 300 mg b.d. (RCM group) or omeprazole 20 mg b.d. (OCM group) 14-day triple therapy, with clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. On the eighth day of therapy, metronidazole pharmacokinetics was studied in plasma by high-performance liquid chromatography. The pharmacokinetic parameters (terminal half-life, area under the curve, peak-plasma level, peak time) of metronidazole were computed using standard non-compartmental methods. H. pylori status was monitored before and 4 weeks after the end of therapy by histology, serology and rapid urease test. RESULTS: On an intention-to-treat basis, eradication rates were 91 and 76% for the RCM and OCM groups respectively (P < 0.02). Significantly different pharmacokinetic parameters of metronidazole were found between the groups: peak-plasma level (P < 0.01) and area under the curve (P < 0.02). CONCLUSION: Our results show that the RCM regimen was more effective than that based on OCM and that the antisecretory drugs affected metronidazole availability, increasing the efficacy of ranitidine-based regimens.

[Guidelines on intestinal dysmicrobism (SIBO Small Intestine Bacterial Overgrowth)]. / Linee guida sul dismicrobismo intestinale (SIBO: Small Intestinal Bacterial Overgrowth).

Bacterial flora consisting of Gram-positive and Gram-negative germs, aerobes and anaerobes, is distributed along the digestive tract in varying quantities from zero to a maximum of 10(12)/ml of endoluminal aspirate. This bacterial ecosystem counterbalances with the ecological niche of the host organism and harmonizes with the various digestive, secretory, motor, absorption and sensitivity functions of the entire intestine. This dynamic equilibrium between environment, bacterial flora and host may be interrupted due to a variety of complex reasons, leading to quantitative and qualitative modifications of the normal intestinal microbial flora that can cause Small Intestinal Bacterial Overgrowth (SIBO). SIBO is thus due to an invasion of the small intestine, from the upper part, by pathogenic strains of oro-alimentary origin, and from the lower part by colo-fecal germs through an incontinent Bauhin's valve. These germs alter the normal intestinal functions and give rise to a form of diarrhoea in which the characteristics of malabsorption prevail, with all the inherent diagnostic problems. The diagnostic gold standard is the culture of the duodenal-jejunal aspirate which, being difficult to perform and providing unreliable results, is not easily included in the daily clinical routine. Indirect tests include the breath test, which is widely accepted by patients but burdened by diagnostic doubts on the part of medical personnel. Diagnostic confirmation is therefore greatly conditioned by clinical subjectivity and objectivity, as well as by the response to medical therapy. In cases of declared malabsorption, medical therapy is necessary by means of appropriate diet, prebiotics, probiotics and antibiotics. The difficulty in identifying the specific bacterial population and the part of the digestive tract that is affected indicate the appropriateness of a broad-spectrum antibiotic therapy, capable of eradicating aerobes and anaerobes, preferably with a topical rather than a general action, frequently cause of undesired effects.

Intestinal histological and ultrastructural inflammatory changes in spondyloarthropathy and rheumatoid arthritis.

To determine the prevalence of morphologic bowel lesions in patients with inflammatory rheumatic diseases and to better define the interactions between intestinal and articular pathology, 177 patients [39 with reactive arthritis (ReA), 40 with psoriatic arthritis (PsA), 23 with ankylosing spondylitis (AS), 21 with undifferentiated spondyloarthropathy (USpA) and 54 with rheumatoid arthritis (RA)] underwent ileocolonoscopy followed by multiple biopsies of the large bowel and the ileum and ileocecal valve. Biopsies were then examined with light and electron microscopy. During the endoscopic examination various degrees of gut inflammation were observed in 13% of ReA, 5% of PsA, 26% of AS, 14% of USpA and 11% of RA patients. At the histological examination those percentages were respectively 51%, 45%, 48%, 38%, and 15%, and at the electron microscopic examination 76%, 53%, 90%, 60%, and 50%. Our results show that an involvement of the gut is a factor in a large percentage of patients with spondyloarthropathy and, to a lesser extent, with RA. The involvement of the intestine in RA manifests itself mainly in ultrastructural lesions, thus this involvement is not so obvious as in the spondyloarthropathies; however, it could nonetheless play an important role in the etiopathogenesis of this disease.

Helicobacter pylori-specific CD4+ T-cell clones from peripheral blood and gastric biopsies.

Colonization of human gastric mucosa with cytotoxic strains of the bacterium Helicobacter pylori is associated with peptic ulcer and with chronic gastritis. Since little is known about the T-cell response to H. pylori, we investigated the CD4+ T-cell response both in peripheral blood mononuclear cells (PBMCs) and at the site of infection. First, we compared the bulk PBMC proliferative response to the bacterium in individuals with and without symptoms of gastroduodenal disease. We found that the PBMCs from virtually all individuals proliferate in response to heat-inactivated bacteria. Second, we cloned H. pylori-specific CD4+ T lymphocytes from the PBMCs of three patients and from both the gastric mucosa and PBMCs of a fourth patient. We have found that CD4+ T-cell clones specific for H. pylori from peripheral blood samples and gastric mucosae of infected patients are major histocompatibility complex class II restricted and discriminate between several cytotoxic and noncytotoxic bacterial strains. Moreover, they are polyclonal in terms of T-cell receptor usage and major histocompatibility complex restriction. Our results demonstrate that the T-cell response to the whole bacterium in PBMCs does not correlate with antibody response, infection, or disease. However, H. pylori-specific CD4+ T cells are detectable, at the clonal level, in both the periphery and gastric mucosa of infected patients. Localization of these cells at the site of disease suggests they are effectors of the immune response to the bacteria.

Analysis of expression of CagA and VacA virulence factors in 43 strains of Helicobacter pylori reveals that clinical isolates can be divided into two major types and that CagA is not necessary for expression of the vacuolating cytotoxin.

Colonization of the mucosa of the stomach and the duodenum by Helicobacter pylori is the major cause of acute and chronic gastroduodenal pathologies in humans. Duodenal ulcer formation strongly correlates with the expression of an antigen (CagA) that is usually coeexpressed with the vacuolating cytotoxin (VacA), a protein that causes ulceration in the stomach of mice. However, the relationship between these two virulence factors is unknown. To define whether CagA and VacA are coexpressed in all clinical isolates and their relationships, we collected 43 clinical isolates of H. pylori and studied their genetic and phenotypic properties. Based on this analysis, most of the strains could be classified into two major types. Type I bacteria had the gene coding for CagA and expressed the CagA protein and the vacuolating cytotoxin. Type II bacteria did not have the gene coding for CagA and did not express either the CagA protein or the vacuolating cytotoxin. Type I and type II bacteria represented 56 and 16%, respectively, of the 43 clinical isolates, while the remaining 28% had an intermediate phenotype, expressing CagA independently of VacA or vice versa. This finding shows that although it is present in most cytotoxic strains, CagA is not necessary for the expression of the vacuolating cytotoxin.

Activity of omeprazole on Helicobacter pylori and relation to toxicity of strains.

AIMS: To see whether the activity of omeprazole on Helicobacter pylori is associated with toxicity of strains; to determine whether omeprazole inhibited vacuolisation of cells in culture induced by H pylori cytotoxin and by ureas, and if omeprazole prevented H pylori motility. METHODS: Minimal inhibitory concentrations (MICs) of omeprazole were determined for seven cytotoxic and five non-cytotoxic H pylori strains. Omeprazole at different concentrations was incubated with cytotoxic and non-cytotoxic extracts of H pylori, or with purified H pylori urease, and added to cells in culture. Inhibition of motility by omeprazole was tested in semi-solid medium. RESULTS: MIC90 of omeprazole was 40 micrograms/ml. MICs for cytotoxic and noncytotoxic organisms were similar. Omeprazole did not prevent vacuolisation induced by the cytotoxic extract, but at high concentrations it inhibited the formation of vacuoles induced by urease. Motility was not inhibited by the drug. CONCLUSIONS: H pylori cytotoxin is not the target of the antimicrobial activity of omeprazole. Should the drug reach clinically effective concentrations in vivo, it could potentially prevent the mucosal damage caused by the vacuolising activity of urease.

Comparisons between degree of histological gastritis and DNA fingerprints, cytotoxicity and adhesivity of Helicobacter pylori from different gastric sites.

Thirty-six isolates of H. pylori from up to three gastric biopsy sites (antrum, corpus and fundus) from 13 patients in Italy with different degrees of histological gastritis were investigated. All strains were tested for motility, cytotoxicity and degree of adhesion, and were typed by analysis of ribosomal RNA gene patterns (ribopatterns). Seventeen different DNA types (ribotypes) were identified, with each patient possessing H. pylori of one or more unique types. Only two patients had identical H. pylori at three sites. Most patients had H. pylori with different ribotypes or subtypes, but nine strains were not typable. Five patients had the same strain colonizing two of the three sites and atypical strains were mostly from the antrum. A complex pattern of H. pylori colonization in the stomach of some individuals was evident and suggested multiple sources of infection. No consistent associations were detected between degree of gastritis and adherence, cytotoxicity and motility but a 2.56Kb rRNA gene fragment that had a higher frequency in strains associated with severe gastritis than mild gastritis, may provide a useful molecular marker for future pathogenicity studies.

Two cases of Campylobacter mucosalis enteritis in children.

Two cases of Campylobacter mucosalis enteritis in children are reported. The patients recovered without antimicrobial therapy. Strains were isolated only by the feces filtration technique. In one child, bactericidal antibodies to the homologous strain were detected in a convalescent-phase serum sample. C. mucosalis should be considered a primary intestinal pathogen.

Growth of Helicobacter pylori in media containing cyclodextrins.

We show that solid and liquid media, supplemented only with cyclodextrins and free of blood and its derivatives, support the growth of Helicobacter pylori. These media can be used for primary isolation of the bacteria from biopsy samples, routine laboratory growth, and large-scale industrial fermentation.

[A retrospective clinico-endoscopic study of colorectal cancer. Personal case histories]. / Studio retrospettivo, clinico-endoscopico, sul cancro colorettale. Casistica personale.

Over a decade (1978-88), 180 cases of colorectal carcinoma were diagnosed. Twenty of the patients had shown no "precancerous" colonic conditions whereas screening had revealed various pathologies indicating risk in the remaining 160. The percentage distribution of the tumour in the large bowel was as follows: sigmoid colon 38%, rectum 25%, descending colon 21%, caecum 12%, transverse colon 4%. Dukes-type surgical staging of the screened patients revealed 42% in stage A, 48% stage B and 10% stage C. The sensitivity and specificity of the haemoccult test was 86% and 98% respectively while the diagnostic accuracy of double-contrast opaque enema was 79% compared to 84% for coloscopy alone and 98% for combined coloscopy and biopsy.

[Cancer of the stomach in Siena and province. Clinical, epidemiologic, endoscopic and bioptic findings]. / Il cancro gastrico in Siena e provincia. Rilievi clinici, epidemiologici, endoscopici e bioptici.

Hundred-nine patients suffering from stomach cancer of 2398 oesophago-gastroduodenoscopies performed in the period 1977-1986 have been considered. The frequency of advanced stomach cancer and early stomach cancer with respect to total endoscopies was respectively 4.5% and 0.36%, which is in agreement with the literature. The results of the study show that Siena and its province present a downward trend in this condition and current rates are two cases out of 100,000 inhabitants. Meantime, careful clinical observation of patients with stomach Ca. shows the absolute lack of predictive symptoms in the early stages and the considerable importance of endoscopy in diagnosis.

Gastrointestinal involvement in rheumatoid arthritis: a biopsy study.

Gastric, colonic and rectal biopsies were obtained from patients with rheumatoid arthritis. The histologic study demonstrated a greater incidence of pathological findings compared to normal subjects or in patients with gastrointestinal diseases. The histologic changes were characterized by partial or complete loss of superficial epithelium and glanmphocytes, plasma cells, granulocytes, and the presence of vasculitic lesions. These histologic findings suggest that a chronic rheumatoid inflammatory process may affect the gastrointestinal system, in keeping with the concept that rheumatoid arthritis is a systemic disease.