RESUMEN
INTRODUCTION: The treatment of metastatic castration-resistant prostate cancer (mCRPC) has changed significantly in recent years. Inhibitors of androgen receptors have shown especially significant benefits in overall (OS) and progression-free survival (PFS), with a good toxicity profile. Treatment selection depends on the patient's individual clinical, radiological, and biological characteristics. OBJECTIVE: To describe treatment outcomes (efficacy, toxicity) in a cohort of patients with mCRPC in Spain. MATERIALS AND METHODS: Multicenter, retrospective study of patients with mCRPC included in a database of the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR). Metastatic CRPC was defined according to the prostate cancer working group 3 (PCWG3) criteria. The Kaplan-Meier technique was used to evaluate OS and the Common Terminology Criteria for Adverse Events (CTCAE, v.4.0) were used to assess toxicity. Univariate and multivariate Cox regression analyses were performed to identify the factors significantly associated with OS. RESULTS: A total of 314 patients from 17 hospitals in Spain diagnosed with mCRPC between June 2010 and September 2017 were included in this study. Mean age at diagnosis was 68 years (range 45-89). At a median follow-up of 35 months, OS at 1, 3, and 5 years were 92%, 38%, and 28%, respectively. Grades 1-2 and grade 3 toxicity rates were, respectively, 68% and 19%. No grade 4 toxicities were observed. On the multivariate analysis, the following factors were significantly associated with OS: age (hazard ratio [HR] 0.42, p = 0.010), PSA value at diagnosis of mCRPC (HR 0.55, p = 0.008), and Gleason score (HR 0.61, p = 0.009). CONCLUSIONS: Age, Gleason score, and PSA at diagnosis of mCRPC are independently associated with overall survival in patients with mCRPC. The efficacy and toxicity outcomes in this patient cohort treated in radiation oncology departments in Spain are consistent with previous reports.
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Factores de Edad , Antineoplásicos/uso terapéutico , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata Resistentes a la Castración , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Neoplasias Óseas/secundario , Progresión de la Enfermedad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Neoplasias de la Próstata Resistentes a la Castración/patología , Oncología por Radiación , Análisis de Regresión , Estudios Retrospectivos , Sociedades Médicas , España , Terminología como AsuntoRESUMEN
Insulin and the insulin-like growth factors (IGF-I, IGF-II) constitute a family of peptides capable of stimulating diverse cellular responses, including cell proliferation. In order to determine the effects of these peptides on malignant cells, we analyzed the expression and function of insulin, IGF-I, and IGF-II receptors on B-cell precursor acute lymphoblastic leukemia (BCP ALL) cell lines, utilizing competitive binding, affinity crosslinking, and cell proliferation assays. The BCP ALL cells bound to each peptide with mean specific binding for 125I-insulin, 125I-IGF-I, and 125I-IGF-II of 19.6%, 7.1%, and 4.3% of radioligand added, respectively. Competitive binding to intact cells demonstrated that 125I-IGF-I was displaced by IGF-I = IGF-II >> insulin, 125I-IGF-II was displaced by IGF-II > insulin = IGF-I, and 125I-insulin was displaced by insulin >> IGF-II > IGF-I. These data were remarkable for the potency of IGF-II displacement of 125I-IGF-I and 125I-insulin. Affinity crosslinking of radioligands to SUP-B2 cell membranes demonstrated the high affinity insulin and IGF-I (type 1 IGF) receptors. IGF binding proteins were also present in BCP ALL cell membrane preparations. In the cell proliferation studies, insulin stimulated a 50-130% increase in leukemic cell growth with a half-maximal concentration of 0.1-3.0 ng/ml in three BCP ALL cell lines. The proliferative response to insulin was blocked by the addition of an insulin receptor antibody. However, no response was observed with IGF-I, and IGF-II was only weakly mitogenic with a proliferative response noted at 100 ng/ml. Thus, while BCP ALL cells possess receptors for insulin and IGF-I, only the insulin receptor mediated a proliferative response.
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Linfoma de Burkitt/patología , Insulina/farmacología , División Celular/efectos de los fármacos , Reactivos de Enlaces Cruzados , Humanos , Técnicas In Vitro , Insulina/metabolismo , Cariotipificación , Mitógenos/farmacología , Receptor de Insulina/metabolismo , Receptores de Somatomedina/metabolismo , Proteínas Recombinantes/farmacología , Somatomedinas/metabolismo , Células Tumorales CultivadasRESUMEN
The bacteriocidal efficacy of Purogene, a stabilized aqueous solution of chlorine dioxide (ClO2) was examined using bacteria of concern to public health. The organisms tested were: Escherichia coli, Pseudomonas aeruginosa, Yersinia enterocolitica, Klebsiella pneumoniae, Streptococcus pyogenes Group A, Salmonella typhimurium and Bacillus subtilis. The test organisms responded differently to inactivation by Purogene. At least a 4 log reduction in bacterial counts was noted when Purogene was applied at a concentration of 0.75 mg/l. Since Purogene is a stabilized complex, it was necessary to provide a chemical environment suitable for the release of ClO2 in this solution. This was done by varying the pH of Purogene from 3.5 to 8.6 (pH of Purogene is 8.6) while keeping the pH of the experimental medium constant (pH 7.0). The results showed that Purogene was most efficacious at the lowest pH tested (pH 3.5). This indicates that as chlorine dioxide solutions were reduced to chlorite (which predominates at pH 8.6), their bacteriocidal efficacy was reduced, suggesting free chlorine dioxide as the active disinfecting species.
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Bacterias/efectos de los fármacos , Compuestos de Cloro , Cloro/farmacología , Desinfectantes/farmacología , Óxidos/farmacología , Bacterias/crecimiento & desarrollo , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Concentración de Iones de Hidrógeno , Cinética , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/crecimiento & desarrollo , Streptococcus pyogenes/efectos de los fármacos , Streptococcus pyogenes/crecimiento & desarrolloRESUMEN
Drug prescribing for the elderly is an important area of medical knowledge since inappropriate prescribing may lead to significant adverse drug events. The objective of this study was to evaluate the association between knowledge of drug use and quality of drug management by general practitioners in practice. A cross-sectional study design was used to evaluate a sample of 37 GPs in practice. A set of common musculoskeletal problems was chosen to evaluate doctors' knowledge of non-steroidal anti-inflammatory drug use, while performance in practice was assessed using elderly standardized patients. The reliability of knowledge test scores was evaluated using measures of internal consistency. The relationship between knowledge of drug use and quality of therapeutic management in practice was evaluated by rank order and linear correlation analysis. Demographic characteristics of participating and non-participating doctors were similar. The reliability of the knowledge test was 0.55. The reliability of performance scores was 0.66. The correlation between overall performance on the standardized patient cases and total knowledge test score was 0.22 (95% confidence interval = 0-0.63). Knowledge test scores were poorly correlated with quality of therapeutic management in office practice. This indicates that knowledge tests alone cannot predict quality of performance with regard to drug prescribing for the elderly in primary care office practice.
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Competencia Clínica , Quimioterapia/normas , Medicina Familiar y Comunitaria , Servicios de Salud para Ancianos/normas , Pautas de la Práctica en Medicina , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de la Atención de Salud , QuebecRESUMEN
A simplified method for isolating highly purified laterobasal membranes (LBM) from enterocytes is based on treatment of membranes with 8 mM CaCl2 concentration in order to aggregate intracellular membrane contaminants. The resultant LBM showed an average 15-fold enrichment and constituted 8% of the original K-stimulated phosphatase in the initial crude homogenate. It showed typical LBM migration on counter-current distribution (CCD) and was essentially free of contamination with endoplasmic reticulum and Golgi membranes. This method is highly efficient and yields sufficient purified LBM to allow comprehensive analysis of enterocyte membrane events.
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Membrana Celular/ultraestructura , Íleon/ultraestructura , Mucosa Intestinal/ultraestructura , Yeyuno/ultraestructura , Animales , Fraccionamiento Celular/métodos , Centrifugación por Gradiente de Densidad , Distribución en Contracorriente , Retículo Endoplásmico/ultraestructura , Epitelio/ultraestructura , Aparato de Golgi/ultraestructura , Membranas Intracelulares/ultraestructura , Masculino , Ratas , Ratas EndogámicasRESUMEN
El propósito de este artículo es la revisión y análisis del protocolo de valoración isocinética de la rodilla del deportista, así como de sus resultados y aplicaciones, a la luz de la bibliografía existente. Se proponen parámetros de estandarizamayor fiabilidad y validez, y se analiza el valor relativo de las diferentes variables extraídas. Por último, se realiza una revisión de la validez de estos procedimientos para la medida precisa de la fuerza muscular, la valoración de la condición física, la discriminación entre individuos o diferentes niveles de rendimiento, y la detección de cambios en este rendimiento inducidos por el entrenamiento, así como para otros propósitos, como la detección y seguimiento de talentos deportivos, la monitorización de la declinación de la capacidad física con la edad, o la detección de factores de riesgo lesional en el deportista (AU)