13 research outputs found

    Overexpression of PIK3CA impacts global survival of patients with HER2 subtype breast carcinoma

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    Purpose: To investigate the expression of proteins fosfatidilinositol-4,5-bifosfate 3-quinase (PIK3CA) and phosphatase and tensin homolog (PTEN) in HER2-positive breast cancer and verify their associations with clinical and pathological variables. Methods: We assessed PTEN and PIK3CA status using immunohistochemistry (IHC), which was performed in formalin-fixed paraffin-embedded biopsies from 50 patients with HER2-positive breast cancer. Medical records were studied for collection of clinical-pathological information, including overall survival (OS). The HIC markers PTEN and PIK3CA were analyzed semi-quantitatively by two blinded independent researchers. The relationship between the variables were evaluated using the chi-square test and Kaplan-Meier curves plus log-rank test for survival. Results: In IHC, the expression level of PIK3CA was 86%, and loss of PTEN expression was observed in 46% of the cases. The expression of the markers showed no significant correlation with each other or with the clinical and pathological parameters studied: tumor grade, staging, ER, PR, Ki67 and recurrence. The highest expression of PIK3CA was associated with lower number of deaths (p=0.016) and longer OS of patients (p=0.001). The PTEN marker showed no significant effect on OS. Conclusions: The PIK3CA expression showed a protective effect in relation to the OS of patients with HER2-positive breast cancer

    Correlation between minimum inhibitory concentration and urinary levels of antimicrobials for treatment of infections in urinary tract

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    Introdução: As Infecções no trato urinário (ITU) estão entre as doenças infecciosas mais comumente diagnosticadas e são responsáveis por uma grande proporção do consumo de agentes antimicrobianos, sendo a Escherichia coli o microorganismo mais freqüentemente envolvido. Os antimicrobianos utilizados no tratamento das ITU sofrem concentração no processo de eliminação, ocasionando altos níveis de antimicrobiano na urina. No entanto, os testes que avaliam a susceptibilidade aos antimicrobianos são baseados em concentrações séricas. Assim, é de interesse a padronização de um teste que utilize níveis urinários (discos de alta potência) dos antimicrobianos frente aos uropatógenos. Objetivo: padronizar teste de susceptibilidade aos antimicrobianos para E. coli de ITU, com concentrações de antimicrobianos atingidas na urina. Métodos: foram utilizados 204 isolados bacterianos resistentes a pelo menos um dos seguintes antimicrobianos: ampicilina, cefalotina, ciprofloxacino, gentamicina, sulfametoxazol-trimetoprima(cotrimoxazol) para os quais foi determinada a MIC através de diluição em agar. Através da análise das MIC obtidas e das concentrações que os antimicrobianos atingem na urina, foram estabelecidas as concentrações dos discos de alta concentração. As seguintes concentrações de disco foram utilizadas: ampicilina (500, 400, 300 μg), cefalotina (200, 100 μg) e ciprofloxacino (200, 150 μg). Resultados: a ampicilina apresentou MIC ≥ 512μg/mL para cerca de 50% dos isolados. Dos discos testados, o de 500 μg mostrou melhor coeficiente de correlação de Spearman (rs: -0,659) e foi escolhido para a determinação do ponto de corte através de curva ROC (receiver operating characteristic). Pela curva, um diâmetro de halo de 9 mm separaria as amostras resistentes (R) das susceptíveis (S) a altos níveis de ampicilina com 100% de sensibilidade e especificidade de 50%. A cefalotina apresentou MIC inferior a 256μg/mL para 78% dos isolados sendo que o “rs” para os discos de 100 e 200 μg foi o mesmo: -0,744. Pela curva ROC, halos de 17mm (disco de 200μg) e 13mm (disco de 100μg) discriminariam amostras R de S com 100% de sensibilidade e 96,9% de especificidade. O ciprofloxacino apresentou MIC ≤ 128 μg/mL para mais de 50% dos isolados, sendo que o “rs” foi melhor com o disco de 200μg (rs:-0,916). Um halo de 21mm separaria as amostras S e R com 100% de sensibilidade e 78,9% de especificidade. Para o cotrimoxazol, 95% das amostras se mostraram resistentes a altos níveis e os testes com disco de alta potência não foram realizados. Para a gentamicina o baixo nº de amostras (n=22) prejudicou a análise, mas cerca de 63% dos isolados seriam susceptíveis a altos níveis. Conclusão: O presente estudo demonstrou que o uso de discos de alta concentração pode ser útil para avaliar a susceptibilidade de isolados urinários. Isto tem importância em laboratórios clínicos onde, embora haja dificuldade na realização da MIC, testes de disco-difusão estão incorporados na rotina.Introduction: The urinary tract infections (UTI) are among the most common infectious diseases and are responsible for a high antimicrobial usage. The Escherichia coli is the main microorganism involved in UTI. The antimicrobials used for treatment of UTI concentrate in the urinary tract and this leads to high levels of them in the urine. However, the susceptibility tests are based on the serum levels of the antimicrobials. Therefore, it is of interest to develop a test which correlates the urinary levels of antibiotics (discs with high levels) with the uropathogens. Objective: to propose a susceptibility test of E. coli from UTI using doses of the antimicrobials reached in the urine. Methods: a total of 204 clinical isolates of E.coli resistant, according to conventional antimicrobial susceptibility test to, at least, one of the following antimicrobials: ampicillin, cefalotin, ciprofloxacin, gentamicin and trimetoprima- sulfametoxazol. The MIC was determined by the agar dilution technique. According to the results of the MICs and the urinary levels of the antimicrobials it was possible to establish the concentration of the high potency discs. The following concentration of discs were used: ampicilina (500, 400, 300 μg), cefalotin (200, 100 μg) and ciprofloxacin (200, 150 μg). Results: ampicillin presented MIC ≥ 512μg/mL for around 50% of E. coli isolates. The disc containing 500 μg of ampicillin displayed the best coeficient of correlation (rs: -0,659) and it was chosen to establish diameter breakpoint according to the ROC curve. A diameter of 9 mm would discriminate high level ampicillin resistant isolates with 100% and 50% of sensitivity and specificity, respectively. Cefalotin presented MIC below 256 μg/mL for 78% of E. coli isolates. Its “rs” for discs containing 100 and 200μg was the same: - 0,744. According to the ROC curve zone diameters of 17mm (disk of 200μg) e 13mm (disk of 100μg) were able to discriminate isolates resistant with 100% and 96.9% of sensitivity and specificity, respectively. Ciprofloxacin presented MIC ≤ 128 μg/mL for more than 50% of isolates and the best “rs” was achieved with the 200μg (r:-0,916) disk. A zone diameter of 21mm would discriminate susceptible isolates with 100% and 78.9% of sensitivity and specificity. respectively. A total of 95% of E. coli isolates proved to be resistant to high levels of cotrimoxazole and, therefore, tests with high potency disks were not performed. Due to the small numbers of isolates resistant to gentamycin (n=22) we were not able to perform further analysis although 63% of E coli isolates proved to be susceptible to high levels of this antimicrobial. Conclusion: This study indicated that the susceptibility test with disks containing high levels of antimicrobials may be useful to evaluate the susceptibility of urinary tract isolates This may be of importance as the clinical laboratory may not be able to perform the MIC test for routine isolates
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