Effectiveness of ranitidine bismuth citrate and proton pump inhibitor based triple therapies of Helicobacter pylori in Turkey

Background : Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer disease, MALT lymphoma, and adenocarcinoma of the stomach. The reported prevalence of H. pylori in the adult population in Turkey is 67.6%–81.3%. A national meta-analysis showed that the average H. pylori eradication rate with proton pump inhibitor-based triple regimens in Turkey had decreased from 84% in 1997 to 55.3% in 2004, suggesting a need to evaluate alternative regimens. Materials and methods : The study was a prospective, single-center trial with a parallel group design. After the selection procedure, consecutive out-patients were assigned to one of six study groups using random sampling numbers. All patients received amoxicillin 1,000 mg b.i.d. and clarithromycin 500 mg b.i.d. along with ranitidine bismuth citrate 400 mg b.i.d., or omeprazole 20 mg b.i.d., or lansoprazole 30 mg b.i.d., or rabeprazole 20 mg b.i.d., or pantoprazole 40 mg b.i.d., or esomeprazole 40 mg b.i.d. for 14 days. Results : When we look at the eradication rates of the treatment groups, only two groups (ranitidine bismuth citrate and rabeprazole groups) had eradication rates greater than 80%, both at intention to treat and per protocol analyses. The other four groups (omeprazole, lansoprazole, pantoprazole, and esomeprazole groups) showed statistically significant lower eradication rates both at intention to treat (between 57.6 and 66.7%) and per protocol (between 60.3 and 72.1%) analyses when compared with ranitidine bismuth citrate and rabeprazole groups (p<.05). Conclusion : Ranitidine bismuth citrate and/or rabeprazole based triple therapies must be preferred for the first-line treatment of H. pylori infection

Evaluating elbow osteoarthritis within the prehistoric Tiwanaku state using generalized estimating equations (GEE).

OBJECTIVES:Studies of osteoarthritis (OA) in human skeletal remains can come with scalar problems. If OA measurement is noted as present or absent in one joint, like the elbow, results may not identify specific articular pathology data and the sample size may be insufficient to address research questions. If calculated on a per data point basis (i.e., each articular surface within a joint), results may prove too data heavy to comprehensively understand arthritic changes, or one individual with multiple positive scores may skew results and violate the data independence required for statistical tests. The objective of this article is to show that the statistical methodology Generalized Estimating Equations (GEE) can solve scalar issues in bioarchaeological studies. MATERIALS AND METHODS:Using GEE, a population-averaged statistical model, 1,195 adults from the core and one colony of the prehistoric Tiwanaku state (AD 500-1,100) were evaluated bilaterally for OA on the seven articular surfaces of the elbow joint. RESULTS:GEE linked the articular surfaces within each individual specimen, permitting the largest possible unbiased dataset, and showed significant differences between core and colony Tiwanaku peoples in the overall elbow joint, while also pinpointing specific articular surfaces with OA. Data groupings by sex and age at death also demonstrated significant variation. A pattern of elbow rotation noted for core Tiwanaku people may indicate a specific pattern of movement. DISCUSSION:GEE is effective and should be encouraged in bioarchaeological studies as a way to address scalar issues and to retain all pathology information

Relationship between intratumoral expression of genes coding for xenobiotic-metabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma

INTRODUCTION: Little is known of the function and clinical significance of intratumoral dysregulation of xenobiotic-metabolizing enzyme expression in breast cancer. One molecular mechanism proposed to explain tamoxifen resistance is altered tamoxifen metabolism and bioavailability. METHODS: To test this hypothesis, we used real-time quantitative RT-PCR to quantify the mRNA expression of a large panel of genes coding for the major xenobiotic-metabolizing enzymes (12 phase I enzymes, 12 phase II enzymes and three members of the ABC transporter family) in a small series of normal breast (and liver) tissues, and in estrogen receptor alpha (ERα)-negative and ERα-positive breast tumors. Relevant genes were further investigated in a well-defined cohort of 97 ERα-positive postmenopausal breast cancer patients treated with primary surgery followed by adjuvant tamoxifen alone. RESULTS: Seven of the 27 genes showed very weak or undetectable expression in both normal and tumoral breast tissues. Among the 20 remaining genes, seven genes (CYP2A6, CYP2B6, FMO5, NAT1, SULT2B1, GSTM3 and ABCC11) showed significantly higher mRNA levels in ERα-positive breast tumors than in normal breast tissue, or showed higher mRNA levels in ERα-positive breast tumors than in ERα-negative breast tumors. In the 97 ERα-positive breast tumor series, most alterations of these seven genes corresponded to upregulations as compared with normal breast tissue, with an incidence ranging from 25% (CYP2A6) to 79% (NAT1). Downregulation was rare. CYP2A6, CYP2B6, FMO5 and NAT1 emerged as new putative ERα-responsive genes in human breast cancer. Relapse-free survival was longer among patients with FMO5-overexpressing tumors or NAT1-overexpressing tumors (P = 0.0066 and P = 0.000052, respectively), but only NAT1 status retained prognostic significance in Cox multivariate regression analysis (P = 0.0013). CONCLUSIONS: Taken together, these data point to a role of genes coding for xenobiotic-metabolizing enzymes in breast tumorigenesis, NAT1 being an attractive candidate molecular predictor of antiestrogen responsiveness

Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview

The breast tissue is the site of major metabolic conversions of estradiol (E(2)) mediated by specific cytochromes P450 hydroxylations and methylation by catechol-O-methytransferase. In addition to E(2 )itself, recent findings highlight the significance of 4-hydroxylated estrogen metabolites as chemical mediators and their link to breast cancer development and progression, whereas, in opposition, 2-methoxylated estrogens appear to be protective. Recent data also indicate that breast tissue possesses enzymatic machinery to inactivate and eliminate E(2 )and its oxidized and methoxylated metabolites through conjugation catalyzed by UDP-glucuronosyltransferases (UGTs), which involves the covalent addition of glucuronic acid. In opposition to other metabolic pathways of estrogen, the UGT-mediated process leads to the formation of glucuronides that are devoid of biologic activity and are readily excreted from the tissue into the circulation. This review addresses the most recent findings on the identification of UGT enzymes that are responsible for the glucuronidation of E(2 )and its metabolites, and evidence regarding their potential role in breast cancer

Serum carnitine levels during oxcarbazepine and carbamazepine monotherapies in children with epilepsy

Prolonged antiepilepsy drug treatment can result in secondary carnitine deficiency. The effect of oxcarbazepine on carnitine metabolism has not been reported previously. In this study, serum concentrations of total and free carnitine were measured in 20 children with epilepsy treated with oxcarbazepine monotherapy and were compared with 20 children with epilepsy who were taking carbamazepine as monotherapy. The assays were performed between 3 and 6 months of anticonvulsant treatment. The mean values of serum total and free carnitine levels in patients receiving carbamazepine monotherapy were 63.0 +/- 20.7 mumol/L and 49.1 +/- 16.7 mumol/L, respectively. The mean values of serum total and free carnitine levels in patients receiving oxcarbazepine monotherapy were 64.2 +/- 17.4 mumol/L and 50.3 +/- 13.7 mumol/L, respectively. The values were all between normal ranges. No significant difference was observed in the level of total and free carnitine levels between the two groups. Our results suggest that neither oxcarbazepine nor carbamazepine as monotherapy causes carnitine deficiency in otherwise healthy children with primary idiopathic epilepsy