Summary Background : Levofloxacin has been shown to be effective in Helicobacter pylori eradication. Two 10‐day levofloxacin‐based triple therapies were compared with standard 7‐ and 14‐day quadruple regimens in second‐line treatment. Methods : Two hundred and eighty consecutive patients who failed to respond to standard triple therapy (clarithromycin, amoxicillin, rabeprazole) were randomly assigned to four groups: (1) levofloxacin 500 mg o.d., amoxicillin 1 g b.d., rabeprazole 20 mg b.d. for 10 days (LAR, n = 70); (2) levofloxacin 500 mg o.d., tinidazole 500 mg b.d., rabeprazole 20 mg b.d. for 10 days (LTR, n = 70); (3) tetracycline 500 mg q.d.s., metronidazole 500 mg t.d.s., bismuth salt 120 mg q.d.s., rabeprazole 20 mg b.d. for 7 days (7TMBR, n = 70); and (4) for 14 days (14TMBR, n = 70). Helicobacter pylori status and side‐effects were assessed 6 weeks after treatment. Results : The eradication rate was 94% in the LAR group and 90% in the LTR group in both intention‐to‐treat and per protocol analyses. Helicobacter pylori eradication was achieved in 63 and 69% of the 7TMBR group and in 69 and 80% of the 14TMBR group in intention‐to‐treat and per protocol analysis, respectively. Side‐effects were significantly lower in the LAR and LTR groups than in the 14TMBR group. Conclusion : Ten‐day levofloxacin‐based therapies are better than standard quadruple regimens as second‐line option for H. pylori eradication.
Background: H. pylori infection is a major risk factor in gastric cancer development. The availability of cDNA microarrays creates the unprecedented opportunity to examine simultaneously dynamic changes of multiple pathways affected by H. pylori infection. Aim: In this study we examined broad patterns of gene expression induced by H. pylori in the gastric cancer cell line 1739‐CRL AGS cells in culture using the U95A microarray. Methods: H. pylori were cocultured with AGS cells for 4, 12, 24 and 48 h. Total RNA was extracted and after labelling was used for detection of genes represented in the human U95A microarray set. Data analyses were performed using GeneChip and CLUSFAVOR software. Results: Nearly 6000 genes present in the array were expressed by AGS cells. We report approximately 200 genes that showed the most marked changes. Our studies confirm the up‐regulation of c‐jun, jun‐B, c‐fos and cyclin D1 by H. pylori. We report for the first time the induction of the serine threonine kinase pim‐1 and ATF3 by H. pylori infection of AGS cells. Conclusions: In this microarray analysis of gene expression induced by H. pylori in gastric epithelial cells, we identified a large number of unsuspected genes affected by H. pylori. Further, we show that unsupervised hierarchical cluster analysis can provide useful insight into the possible contribution of genes in specific pathways, based on their profile of expression.
Hip osteoarthritis (OA) is usually managed with systemic treatments such as nonsteroidal anti-inflammatory drugs (NSAIDs) and/or symptomatic slow-acting drugs. Unfortunately, many patients either cannot tolerate NSAIDs or suffer serious, even fatal, NSAID-induced side effects, predominantly gastrointestinal ulceration and bleeding. Viscosupplementation, which aims to restore physiological and rheological features of the synovial fluid, is a well-accepted therapeutic option in knee OA patients, but limited data exist in the literature about its potential benefit for the treatment of hip OA. The purpose of this study is to observe the effects of hylan G-F 20 administered through ultrasound (US)-guided intra-articular (IA) injections in patients with symptomatic hip OA. We treated 30 patients with symptomatic hip OA. Under US guidance, 7 patients received one injection, 21 patients had two injections, and 2 patients received three injections, each with 2 ml of hylan G-F 20. Lequesne index, VAS scale of hip pain, and NSAID consumption were evaluated at baseline as well as 2 and 6 months after the beginning of the treatment. No systemic adverse events were observed. Lequesne index, VAS pain score, and NSAID consumption showed a reduction that was statistically significant to the baseline. The present observation suggests the potentiality for the safety and efficacy of hylan G-F 20 injected under US guidance in patients with symptomatic hip OA. Further controlled studies are needed.
Alterations in DNA mismatch repair (MMR) proteins result in microsatellite instability (MSI), increased mutation accumulation at target genes and cancer development. About one-third of gastric cancers display high-level microsatellite instability (MSI-High) and low-level microsatellite instability (MSI-Low) is frequently detected. To determine whether variations in the levels of MMR proteins or mutations in the main DNA MMR genes are associated with MSI-Low and MSI-High in gastric cancer cell lines, the MSI status (MSI-High, MSI-Low or MSStable (MSS)) of 14 gastric cancer lines was determined using multiple clone analysis with a panel of five microsatellite markers. Protein levels of hMLH1, hMSH2, hMSH6, hPMS2 and hPMS1 were determined by Western blot. Sequence analysis of hMLH1 and hMSH2 was performed and the methylation status of the hMLH1 promoter was examined. The cell lines SNU1 and SNU638 showed MSI-High, decreased to essentially absent hMLH1 and hPMS2 and reduced hPMS1 and hMSH6 protein levels. The hMLH1 promoter region was hypermethylated in SNU638 cells. The MKN28, MKN87, KATOIII and SNU601 cell lines showed MSI-Low. The MMR protein levels of cells with MSI-Low status was similar to the levels detected in MSS cells. A marked decrease in the expression levels of MutL MMR proteins (hMLH1, hPMS2 and hPMS1) is associated with high levels of MSI mutations in gastric cancer cells. Gastric cancer cell lines with MSI-Low status do not show significant changes in the levels of the main DNA MMR proteins or mutations in the DNA mismatch repair genes hMSH2 and hMLH1. These well-characterized gastric cancer cell lines are a valuable resource to further our understanding of DNA MMR deficiency in cancer development, progression and prognosis. Keywords: gastric cancer cell lines; microsatellite instability; mismatch repair genes; stomach cancer; mutations The DNA mismatch repair (MMR) system is essential for replication fidelity, correcting DNA base mismatches left uncorrected by DNA polymerase. Efficient DNA mismatch repair requires the combined function of MutL (hMLH1-hPMS2 and hMLH1-hMLH3) and MutS (hMSH2-hMSH6 and hMSH2-hMSH3) heterodimers.
Reports on Helicobacter pylori and extragastric diseases have almost doubled this year compared with last year, bearing witness to the persistent scientific interest in this branch of Helicobacter-related pathology. Data belong increasingly to the area of vascular medicine, as well as hematology, dermatology, pediatrics and other fields. Unfortunately, these studies show overall controversial results, due to the impact of several confounding factors, and to the difficulty of recruiting homogeneous patient populations. Furthermore, many studies continue to be conducted on Helicobacter species other than H. pylori, focusing on animal models of gastroenterological illnesses which may retain strong similarities with human diseases. In this paper, taxonomy, detection and characterisation of Helicobacter spp. will be reviewed, together with the most important data issued this year on other Helicobacters and animal models.
Symptomatic osteoarthritis (OA) patient management includes the use of non-pharmacological therapies, analgesics, physiotherapy and eventually surgery. Whereas local injections (e.g., corticosteroids, hyaluronan) are easily performed on the knee, hip injections are considerably more difficult 1 . Recent literature proves that ultrasound (US)-guided hip injections are safe and allow easy access to the hip joint space 2,3 . Steroids may be injected in this space, but the symptomatic benefit achieved by intra-articular administrations of hyaluronans appears to last longer.This open-label pilot study was aimed at investigating the safety and duration of benefit after the treatment of hip OA patients by US-guided intra-articular injections of 40 mg of Hyalgan Ò , equivalent to two 2-ml tubes. Hyalgan Ò is a natural hyaluronan with a molecular weight of 500e730 kDa that is able to reduce pain associated with OA and to ameliorate joint function. Recent clinical data have shown intra-articular hyaluronans to exert also a positive effect in reducing the progression of the joint disease 4 .
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