Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report.

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

Rabeprazole, amoxycillin and low- or high-dose clarithromycin for cure of Helicobacter pylori infection.

BACKGROUND: Rabeprazole sodium is a proton pump inhibitor. AIM: To evaluate the efficacy and safety of 1-week triple therapy with rabeprazole, amoxycillin and clarithromycin for the eradication of Helicobacter pylori. METHODS: A total of 100 subjects with H. pylori were randomly divided into two groups of 1-week triple therapy with rabeprazole 10 mg b.d., amoxycillin 750 mg b.d. and either clarithromycin 200 mg b.d. (RAC400, n=50) or clarithromycin 400 mg b. d. (RAC800, n=50). Endoscopic examination with four biopsies (two specimens from the antrum and two from the gastric body) was performed. The status of H. pylori infection was determined using culture and histology (Giemsa stain) of the biopsy specimens. Sensitivity to clarithromycin was determined using the E-test: MIC > 8 g/mL was considered to be resistant, whereas MIC < 2 g/mL was considered to be sensitive. Cure was defined as no evidence of H. pylori infection 1 month after completion of treatment. RESULTS: There were no significant differences in the clinical characteristics of the two groups. Eradication rates (intention-to-treat and per protocol, respectively) were: RAC400: 86% (95% CI: 76-95%) and 89% (95% CI: 80-97%); RAC800: 94% (95% CI: 87-100%) and 97% (95% CI: 94-100%). There was no significant difference between the eradication rates of either regimen. Three subjects with failed eradication in the RAC400 group were all infected with a clarithromycin-resistant strain before beginning the therapy. Haemorrhagic colitis was the only severe adverse event, which was observed in one patient in the RAC800 group. CONCLUSION: One-week triple therapy with rabeprazole, amoxycillin and low-dose clarithromycin is effective for the eradication of H. pylori infection.

Quantification of relative expression of genes with homologous sequences using fluorescence-based single-strand conformation polymorphism analysis--application to lactate dehydrogenase and cyclooxygenase isozymes.

The combination of reverse transcribed-PCR and fluorescence-based single strand conformation polymorphism analysis has been proposed for the quantitative determination of ratio of mRNA molecules with homologous sequences. We applied this procedure to lactate dehydrogenase subunits M and H, and cyclooxygenase 1 and 2. We designed fluorescence labeled common PCR primers in the sequences highly homologous between two subunit and isozyme cDNAs, and performed reverse transcribed-PCR and fluorescence-based single strand conformation polymorphism analysis. PCR efficiency was almost the same for the different target sequences, so analysis of mixtures of known amounts of lactate dehydrogenase M and H revealed linear and precise proportions of lactate dehydrogenase M mRNA. It was shown that template concentrations and number of PCR cycles did not affect the determination of proportions of lactate dehydrogenase M to total lactate dehydrogenase. The procedure was applicable to a determination of cyclooxygenase-2 proportion; furthermore, the present procedure could be easily applied to investigation of expression levels of genes encoding mRNAs with homologous sequences.

[Late phase II trial of high-dose l-leucovorin and 5-fluorouracil in advanced colorectal carcinoma. l-Leucovorin and 5-FU Study Group (Japan Eastern Group)].

A multicenter cooperative study was conducted from Dec. 1992 to April 1994 to evaluate the clinical efficacy of high-dose l-leucovorin (l-LV) and 5-fluorouracil (5-FU) treatment in 76 patients with advanced colorectal carcinoma. Treatment consisted of intravenous bolus injection of 5-FU (600 mg/m2) 1-hour after the initiation of a 2-hour infusion l-LV (250 mg/m2), 6 weekly treatments were administered followed by a two-week rest. These treatment were repeated until progressive disease or intolerable toxicity. Seventy patients were evaluated for response. Responses were the following: PR 21, NC 29, PD 20 and the overall response rate was 30%. Grade 4 hematological side-effect was observed in three cases, and severe diarrhea in one case. These data suggested that high-dose l-LV and 5-FU was effective for advanced colorectal carcinoma but showed some hematological toxicity, and a further investigation should be carried out.

[Early phase II trial of l-leucovorin and 5-fluorouracil in advanced colorectal cancer. l-Leucovorin and 5-FU Study Group].

We report the results of a multicenter clinical trial comparing three combination chemotherapeutic regimens including 5-fluorouracil (5-FU) and l-leucovorin (l-LV). One hundred and twenty-two patients were randomized to three regimens comprising 5-FU (600 mg/m2) plus high-dose l-LV (250 mg/m2) in six doses given weekly by i.v. injection midway during a 2-hr infusion of l-LV (regimen A), 5-FU (370 mg/m2) plus high-dose l-LV (100 mg/m2) given simultaneously for 5 consecutive days and a 23-day interval between treatments (regimen B) and 5-FU (370 mg/m2) plus low-dose l-LV (10 mg/m2) with the same dose administration schedule as regimen B (regimen C). The response rates were 32.4% (12/37 cases) in Regimen A, 20.0% (8/40) in regimen B and 11.1% (4/36) in regimen C. The most prominent side effects observed in regimen A were diarrhea (53.8%) and leukopenia (53.8%); however, they were within permissible levels. The combinations of high-dose l-LV and 5-FU (regimen A and B) had higher response rates than that of low dose l-LV and 5-FU (regimen C). Weekly administration of high-dose l-LV and 5-FU (regimen A) is now being expanded to late phase II trials.

[Enhanced effect of hepatic arterial infused anticancer drugs on rabbit VX-2 carcinoma by means of combination with Lipiodol. Adriamycin versus Lipiodol adriamycin sandwich method and adriamycin suspended in a Lipiodol].

To increase drug delivery to a hepatic malignant tumor, various tissue contents and serum levels of adriamycin (ADR) were evaluated in comparison with different intraarterial injection methods of oily or aqueous solution. VX-2 tumor was implanted in the rabbit liver. ADR was infused through the hepatic artery by the following three methods: Group 1: ADR with physiological saline; Group 2: ADR administered between lipiodol injection; and Group 3: urographin-dissolved ADR suspended in lipiodol. ADR concentrations of the tumor, liver, heart, kidney or bone marrow were compared between these three groups one hour after ADR administration. Tumor uptake and ADR concentration ratio of tumor to liver were higher in Group 3 than in the other two groups. ADR concentration ratio of tumor to liver was higher in group 2 than in group 1. Cardiac and renal uptake in group 3 was less than in group 1 and 2, and so infusion of ADR suspended in a lipiodol may serve to reduce side effects of ADR, especially cardiotoxicity.

Glycine-extended progastrin processing intermediates: accumulation and cosecretion with gastrin.

Glycine-extended intermediates of peptide processing serve as substrates for carboxyl-terminal amidation, hence activation, of many brain-gut peptides. To explore the dynamics of accumulation and secretion of these important intermediates we utilized primary cultures of canine antral mucosal G-cells as a model system. Glycine-extended progastrin processing intermediates (G-Gly) accumulated rapidly in G-cells cultured in ascorbate-deficient media, exhibiting a fourfold increase over a 51-h culture period, while gastrin content fell to less than half of the initial level. In contrast, G-cells cultured in ascorbate-supplemented media accumulated G-Gly at a relatively low rate, while gastrin was preserved at a higher level. Under either condition, G-Gly and gastrin were progressively released into the culture media. The release of both immunoreactivities could be stimulated by bombesin and inhibited by somatostatin in similar fashion. By electron microscopy, the cultured G-cells exhibited no ultrastructural alterations. These data suggest that 1) the cellular homeostasis of G-Gly is regulated by the activity of an ascorbate-dependent amidation enzyme similar to one previously described in pituitary tissues, 2) carboxyl-terminal amidation is not an obligatory step for secretion of gastrin, and 3) the proportions of gastrin and G-Gly cosecreted from G-cells reflect their proportional accumulation within G-cell secretory granules. The physiological relevance of the released G-Gly has yet to be determined.