Indicación de antibióticos en niños con faringoamigdalitis aguda y test positivo para estreptococo beta hemolítico del grupo A atendidos en el Instituto Nacional de Salud del Niño, Lima – Perú / Indication of antibiotics for children with pharyngitis acute and positive test for beta hemolytic strepotococcus group A treated at the National Institute of Child Health, Lima – Per£

Objetivo: Conocer la frecuencia de la indicación de antibióticos en niños con diagnóstico clínico de faringoamigdalitis aguda (FAA) y test rápido positivo para estreptococo beta hemolítico del grupo A atendidos en consultorios externos de pediatría, y el tipo de antibiótico indicado con más frecuencia. Material y Métodos: Estudio descriptivo, transversal. La muestra fue de 351 niños de 3 a 15 años diagnosticados como FAA. Abordados a la salida de la consulta y con firma y consentimiento informado a quienes se les aplico una encuesta y se realizó toma de muestra de secreciones faringoamigdalianas, las fueron analizadas mediante el test de inmunoaglutinación para EbhGA (ACON) con una S=91% y E=98%. Resultados: la frecuencia de prescripción antibiótica fue de 42.7% (150). El antibiótico más usado fue la penicilina con 25.4 %, seguido de Macrólidos (14.2%). 15 casos (4.3%) de faringoamiggalitis bacteriana tuvieron Test EbhGA positivo. Nueve de ellos (60%) recibieron antibióticos, la inflamación y el exudado amigdalino se presentaron en 320 (93,4%). Hubo ausencia de tos en 46 casos (13,1%). Se indicó sintomáticos en 51.5% de pacientes. Conclusiones: La frecuencia de FA estereocoptocócica fue baja según el test de detección rápida, la prescripción antibiótica fue 10 veces más indicada que la positividad del test; el antibiótico más utilizado fue la penicilina.

Objective: Generally is to determine the frequency of indication of antibiotic for children with clinically diagnosed acute pharyngitis and positive test for beta hemolytic streptococcus Group A treated at pediatric, clinics, a specific objective is to determine the frequency with which it is negative test for the detection of beta-hemolytic streptococcus for type A (GABHS) in these patients. Material and Methods: We made across-sectional study. The sample was 351 children of 3-15 years diagnosed by his physician as FAA, the departure of your inquiry, the informed consent, they have participated in a survey of the study variables and underwent sampling pharyngeal secretions, these were analyzed using test for GABHS inmunoagglutination (ACON) with S=91%, E=98%. Results: The frequency of antibiotic prescriptions was 42.7% (150). The first common antibiotic was penicillin with 25.4%, the second one, macrolides with 14.2%. There was a 4.3% (15) case of GABHS bacteria pharyngeal confirmed by positive test. Inflammation and exudate tonsillar was presented in 93.4% (328). There was lack of cough in 13.1% (46). The other antibiotic was symptomatic indication in 51.5% of patients. Conclusions: The antibiotic prescription rate more than the actual by the positive test; the most common antibiotic was penicillin. The test was positive in percentage and the mostly is in the school group, the most common symptom was swelling and amygdaline exudate. The other symptomatic medications were given.

Delineation of a cellular hierarchy in lung cancer reveals an oncofetal antigen expressed on tumor-initiating cells.

Poorly differentiated tumors in non-small cell lung cancer (NSCLC) have been associated with shorter patient survival and shorter time to recurrence following treatment. Here, we integrate multiple experimental models with clinicopathologic analysis of patient tumors to delineate a cellular hierarchy in NSCLC. We show that the oncofetal protein 5T4 is expressed on tumor-initiating cells and associated with worse clinical outcome in NSCLC. Coexpression of 5T4 and factors involved in the epithelial-to-mesenchymal transition were observed in undifferentiated but not in differentiated tumor cells. Despite heterogeneous expression of 5T4 in NSCLC patient-derived xenografts, treatment with an anti-5T4 antibody-drug conjugate resulted in complete and sustained tumor regression. Thus, the aggressive growth of heterogeneous solid tumors can be blocked by therapeutic agents that target a subpopulation of cells near the top of the cellular hierarchy.

Preclinical pharmacologic evaluation of MST-997, an orally active taxane with superior in vitro and in vivo efficacy in paclitaxel- and docetaxel-resistant tumor models.

PURPOSE: Because resistance to paclitaxel and docetaxel is frequently observed in the clinic, new anti-microtubule agents have been sought. The aim of this study was to evaluate the efficacy and oral activity of a novel taxane (MST-997) in paclitaxel- and docetaxel-resistant tumor models in vitro and in vivo. EXPERIMENTAL DESIGN: Tubulin polymerization assays, immunohistochemistry, and cell cycle analysis was used to evaluate mechanism of action of MST-997. The effect of MST-997 on growth inhibition in a panel of paclitaxel- and docetaxel-resistant cell lines that overexpressed P-glycoprotein (MDR1) or harbored beta-tubulin mutations were assayed in vitro and in murine xenografts. RESULTS: MST-997 induced microtubule polymerization (EC50 = 0.9 micromol/L) and bundling, resulting in G2-M arrest and apoptosis. In addition, MST-997 was a potent inhibitor of paclitaxel- and docetaxel-sensitive tumor cell lines that did not have detectable P-glycoprotein (IC50 = 1.8 +/- 1.5 nmol/L). Minimal resistance (1- to 8-fold) to MST-997 was found in cell lines that either overexpressed MDR1 or harbored point mutations in beta-tubulin. Most notable, MST-997 displayed superior in vivo efficacy as a single i.v. or p.o. dose either partially or completely inhibited tumor growth in paclitaxel- and docetaxel-resistant xenografts. CONCLUSIONS: MST-997 represents a potent and orally active microtubule-stabilizing agent that has greater pharmacologic efficacy in vitro and in vivo than the currently approved taxanes. Our findings suggest that MST-997, which has entered phase I clinical trials, may have broad therapeutic value.

MAC-321, a novel taxane with greater efficacy than paclitaxel and docetaxel in vitro and in vivo.

The taxanes, paclitaxel (PTX) and docetaxel (DTX), belong to a novel class of anticancer drugs that stabilize microtubules and lead to tumor cell death. While both agents are widely used for the treatment of lung, breast, and ovarian cancer, many tumor types are refractory or develop resistance to these drugs. We describe here a novel analogue of DTX, designated MAC-321 [Microtubule/Apoptosis/Cytotoxic: 5beta, 20-epoxy-1, 2alpha-, 4-, 7beta-, 10beta-, 13alpha-hexahydroxytax-11-en-9-one 4 acetate 2 benzoate 7-propionate 13-ester with (2R,3S)-N-tertbutoxycarbonyl-3-(2-furyl)isoserine], that overcomes P-glycoprotein-mediated resistance to PTX and DTX in preclinical model systems. Similar to PTX or DTX, MAC-321 enhanced the rate of tubulin polymerization in vitro and caused the bundling of microtubules in cells. MAC-321 inhibited proliferation of a panel of 14 tumor cell lines with minimal variation in potency (IC(50) = 2.2 +/- 1.4 nM; range = 0.6-5.3 nM). Unlike PTX or DTX, the IC(50) of MAC-321 did not vary in cells that expressed low to moderate levels of P-glycoprotein. Even under extraordinary conditions in KB-V1 cells, which highly overexpress P-glycoprotein, resistance to MAC-321 was 80-fold compared with that of PTX (1400-fold) and DTX (670-fold). In addition, equivalent or less resistance to MAC-321 compared with PTX or DTX was observed in four cell lines that contain distinct point mutations within the taxane-binding site of beta-tubulin. Most importantly, MAC-321 displayed superior in vivo efficacy because: (a) MAC-321 either partially or completely inhibited tumor growth in three tumor models that overexpressed P-glycoprotein and were resistant to PTX; and (b) unlike PTX or DTX, MAC-321 was highly effective when given orally. MAC-321 was also highly effective when given as single i.v. dose. Our findings suggest that MAC-321, which is currently under clinical evaluation, may have broad therapeutic value.