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São Paulo, Brazil

Chua D.,University of Hong Kong | Krzakowski M.,Centrum Onkologiinstitute of Oncology | Chouaid C.,AP HP | Pallotta M.G.,Laboratorio Central | And 3 more authors.
Clinical Lung Cancer | Year: 2010

Background: A previously published study of temozolomide concurrent with whole-brain radiation therapy (WBRT) reported significant improvement in response rates and a nonsignificant trend toward improved overall survival compared with WBRT alone in patients with brain metastases primarily from lung cancer. This study sought to confirm the benefit of adding temozolomide to WBRT in patients with non-small-cell lung cancer (NSCLC) with brain metastases. Patients and Methods: This planned phase III study (target = 380 events) was converted to a phase II study (target = 70 events) because of poor enrollment. Patients with NSCLC and ≥ 1 newly diagnosed brain lesion were randomized to WBRT (30 Gy in 10 fractions) alone or combined with temozolomide (75 mg/m 2/day) for 21 or 28 days. Endpoints included overall survival and time to central nervous system (CNS) progression. Results: Median overall survival and median time to CNS progression was 4.4 and 3.1 months in the WBRT + temozolomide arm (n = 47) versus 5.7 and 3.8 months in the WBRT arm (n = 48). However, there were imbalances in the percentages of patients receiving previous chemotherapy and with synchronous brain metastases. Adding temozolomide to WBRT increased the frequency of nausea, vomiting, alopecia, fatigue, anorexia, and constipation. Most adverse events were mild to moderate. Conclusion: The benefit of adding temozolomide to WBRT was not confirmed; however, the accrual goal for the planned phase III trial was not reached, and the study regimen differed from regimens used previously. Therefore, the role of temozolomide in treating brain metastases remains unresolved. Source

Alvarez Hayes J.,National University of La Plata | Erben E.,CONICET | Lamberti Y.,National University of La Plata | Ayala M.,National University of La Plata | And 5 more authors.
Vaccine | Year: 2011

Antigenic proteins whose expression is induced under iron starvation, an environmental condition that bacterial pathogens have to face during colonization, might be potential candidates for improved vaccine. By mean of immune proteomics we identified novel antigens of Bordetella pertussis maximally expressed under iron limitation. Among them, Bp1152 (named as IRP1-3) showed a particularly strong reaction with human IgG purified from pooled sera of pertussis-infected individuals. Computer analysis showed IRP1-3 as a dimeric membrane protein potentially involved in iron uptake. Experimental data revealed the surface-exposure of this protein and showed its increase under iron starvation to be independent of bacterial virulence phase. Immunization of mice with the recombinant IRP1-3 resulted in a strong antibody response. These antibodies not only recognized the native protein on bacterial surface but also promote effective bacterial phagocytosis by human PMN, a key protecting activity against this pathogen. Accordingly, IRP1-3 proved protective against B. pertussis infection in mouse model. Expression of IRP1-3 was found conserved among clinical isolates of B. pertussis and positively regulated by iron starvation in these strains. Taken together these results suggest that this protein might be an interesting novel vaccine candidate. © 2011 Elsevier Ltd. Source

Brance M.L.,Servicio de Reumatologia | Brance M.L.,Laboratorio Of Biologia Osea | Brance M.L.,CONICET | Brun L.R.,Laboratorio Of Biologia Osea | And 4 more authors.
Rheumatology International | Year: 2015

Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease with high prevalence of osteoporosis. Previous evidence indicates an association between vitamin D deficiency and autoimmune diseases. The aim of this study was to evaluate serum 25 hydroxyvitamin D [25(OH)D] levels, bone mineral density (BMD) and disease activity in RA patients living in Argentina. We studied 34 RA women and 41 healthy women as a control group. RA patients had lower 25(OH)D levels (20.4 ± 0.9 ng/ml) than controls (26.3 ± 1.9 ng/ml; p < 0.05). No significant differences were found in lumbar spine BMD between premenopausal (preM) or postmenopausal (postM) patients, but femoral neck BMD was significantly lower in postM RA patients (T score −2.5 ± 0.4) than in postM control subjects (T score −0.9 ± 0.3, p = 0.014). Although no linear correlation between 25(OH)D levels and disease activity (DAS-28) was found, patients with moderate-high disease activity had lower 25(OH)D levels than those with low disease activity: DAS-28 >3.2: 19.5 ± 0.88 ng/ml; DAS-28 ≤3.2: 23.7 ± 2.8 ng/ml (p = 0.047). After 1 year of vitamin D treatment 25(OH)D levels were increased while DAS-28 were decreased (n = 25; p < 0.05). We conclude that patients with RA had lower 25(OH)D levels than the control group. Low levels of 25(OH)D were associated with moderate-high disease activity suggesting the importance of optimal 25(OH)D levels in RA patients. Femoral neck BMD was lower in postM RA patients. No differences in lumbar BMD were found between preM and postM RA patients, suggesting that bone mass evaluation in RA patients should include femoral neck BMD regardless of age. © 2014, Springer-Verlag Berlin Heidelberg. Source

Da Conceicao-Machado M.E.P.,Federal University of Bahia | Silva L.R.,FAMED | Silva L.R.,Complexo Hospitalar Universitario Professor Edgard Santos | Santana M.L.P.,ENUFBA | And 6 more authors.
Jornal de Pediatria | Year: 2013

Objective: This study aimed to identify the prevalence of hypertriglyceridemic waist (HTW) phenotype, and to evaluate its association with metabolic abnormalities in adolescents of low socioeconomic status. Method: This was a cross-sectional study with a random sample of 1,076 adolescents between 11 and 17 years, of both genders, from public schools. The participants underwent anthropometric measurements (weight, height, and waist circumference), and levels of total cholesterol, low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), non-HDL cholesterol, triglyceride (TG), and fasting glucose were measured. Information regarding the socioeconomic status of the participants' families was obtained. The HTW phenotype was defined by the simultaneous presence of increased waist circumference (≥ 90th percentile for age and gender) and serum triglyceride levels (≥ 100 mg/dL). A logistic regression analysis was used to evaluate the associations of interest. Results: The prevalence of HTW phenotype was 7.2% among the adolescents, being higher in the presence of obesity (63.4%) and high levels of non-HDL cholesterol (16.6%) and LDL-C (13.7%). The bivariate analysis indicated that, of the metabolic variables, only blood glucose was not associated with the HTW phenotype. Multivariate analysis adjusted for age and gender indicated that the HTW phenotype was positively associated with high non-HDL cholesterol (odds ratio: 7.0; 95% CI: 3.9-12.6) and low HDL-C levels (odds ratio: 2.7; 95% CI: 1.5-4.8). Conclusions: This study demonstrated that the HTW phenotype was associated with an atherogenic lipid profile, and this phenotype is suggested as a screening tool to identify adolescents with metabolic alterations. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved. Source

Garcia-Fulgueiras V.,University of the Republic of Uruguay | Seija V.,Laboratorio Central | Aguerrebere P.,University of the Republic of Uruguay | Cordeiro N.F.,University of the Republic of Uruguay | Vignoli R.,University of the Republic of Uruguay
Journal of Global Antimicrobial Resistance | Year: 2014

Here we report the detection of a Leclercia adecarboxylata strain, isolated from a case of osteomyelitis, harbouring multiple antibiotic resistance genes encoded on a 450-kb IncHI1/HI2 conjugative plasmid (pLa12). The plasmid carried a complex class 1 integron with the genetic array intI1-aac(6′)-Ib-cr- blaOXA-1-catB3-arr3-qacEΔ1-sul1-ISCR1; in addition, a bla DHA-1-like allele linked to ampR-qacEΔ1-sul1 as well as blaSHV-12, blaTEM-1 and qnrB4-like genes were found. To the best of our knowledge, this is the first report of L. adecarboxylata harbouring transferable resistance genes to quinolones, chloramphenicol and rifampicin as well as a plasmidic class C β-lactamase. © 2014 International Society for Chemotherapy of Infection and Cancer. Source

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