Impacto de la profilaxis secundaria en el manejo de pacientes con urolitiasis de alto riesgo de recidiva / Impact of secondary prophylaxis in the management of patients with high recurrence risk of urolithiasis

In a previous study, we showed our experience in a group of 54 patients with a high risk of urolithiasis recurrence, who were subjected to a complete metabolic evaluation. Aim: To report the evolution of these patients after 5 years of follow-up. Patients and Methods: All patients underwent a general management of urolithiasis plus specific treatments for underlying metabolic disorders. Each patient had an annual medical assessment including a clinical examination, urinalysis and imaging studies (non-enhanced computed tomography scan, ultrasonography and plain abdominal Rx rays). In every case, the underlying metabolic disorder, treatment adherence, stones on imaging studies and symptomatology were evaluated. Adherence of general and specific measures were evaluated subjectively. Failure of secondary prevention was defined as the recurrence of clinical or imaging urolithiasis (increase of the number of lithiasis) despite a correct treatment of the metabolic disorders. Results: Twenty nine patients completed the follow-up. Mean age was 45 years old. Nineteen patients (65%) had only one metabolic disorder, three patients (10%) two disorders, one patient (3%) four disorders, and six patients (21%) a normal metabolic study. The median of follow-up was 54 months (45-60). During that period, twenty-three patients (79%) kept the treatment as it was indicated. In this subgroup, 21 had no clinical or imaging recurrence of urolithiasis during follow-up (91%). Total adherence to treatment and follow-up was 42% (23/54) of the initial group of patients. Conclusions: A complete metabolic study allows to identify patients with a high risk of urolithiasis recurrence, enabling a specific treatment of the metabolic disorder. Our experience shows that 75% (21/29) of patients remain free of recurrence at five years of follow-up.

Expresión y actividad de proteínas de multirresistencia a drogas (MDR) en líneas celulares de cáncer de próstata / Expression and activity of multidrug resistance proteins in prostate cancer cell lines

Introducción: Nuestro grupo ha reportado previamente una asociación entre sensibilidad a quimioterapia y la expresión de proteínas MDR (P-Gp y MRP1) en líneas celulares y cultivos primarios de cáncer de próstata, quedando por estudiar la actividad de las mismas. Material y métodos: Se utilizó líneas celulares de cáncer de próstata PC3 y DU145. Se evaluaron los niveles de mARN de P-Gp y MRP1 mediante RT-PCR. La expresión de ambas proteínas se determinó mediante inmunofluorescencia. Se estableció un ensayo funcional en base a la acumulación de sustratos fluorescentes (DiOC2(3) para P-gp y CFDA para MRP1) y al uso de inhibidores específicos para cada proteína (Ciclosporina A para P-Gp y MK571 para MRP1). Las células se incubaron durante 60 minutos a 37ºC con o sin el inhibidor específico, seguido de otra incubación por 60 minutos agregando el sustrato fluorescente. La acumulación del sustrato fluorescente se determinó por citometría de flujo. Resultados: Las líneas celulares utilizadas sólo expresaron MRP1, mientras no se detectó P-Gp (mARN ni proteína). Mediante el ensayo funcional se observó que las células acumulaban más CFDA cuando eran tratadas con MK571. No se observó diferencias en la acumulación de DiOC(2)3 frente al tratamiento con Ciclosporina A. Conclusión: La mayor acumulación intracelular de CFDA frente al tratamiento con MK571 indica que la proteína MRP1 expresada en las líneas celulares utilizadas es funcional. P-Gp no se expresa en las líneas evaluadas. En estudios en curso nos encontramos evaluando la expresión y función de ambas proteínas en cultivos primarios.

Introduction: We have previously reported an association between sensitivity to chemotherapy and the expression of multidrug resistance proteins (MDR) (P-Gp and MRP1) in cell lines and primary cultures of prostate cancer. Activity remains to be studied. Material and methods: Prostate cancer cell lines PC3 and DU145 were used. Levels of mRNA of P-Gpand MRP1 using RT-PCR, were evaluated. The expression of both proteins was determined using immunofluorescence. A functional assay based on the accumulation of fluorescence substrates (DiOC2(3) for P-Gp and CFDA for MRP1) was established. Cells were incubated for 60 minutes at 37C with/without the specific inhibitor, followed by another 60 minutes incubation adding the fluorescence substrate. Accumulation of fluorescence substrate was determined by flow citometry. Results: Cell lines expressed only MRP1, whereas P-Gp (mRNA/protein) was not detected. Using the functional assay, we found that cells accumulated more CFDA when treated with MK571. No differences were seen in the accumulation of DiOC2(3) after treatment with ciclosporin A. Conclusion: The higher intracellular accumulation of CFDA after treatment with MK571 indicates that the MRP1 protein expressed in these cell lines is functional. P-Gp was not expressed in these cell lines. We are currently evaluating the expression and function of both proteins in primary cultures.

Interacciones genéticas y genético-ambientales como efecto modificador del riesgo de cáncer de próstata: un diseño case-only / Gene-gene and gene-environment interactions as modifier factors of prostatic cancer risk: a case-only design study

Background: The role of susceptibility low penetrance genes and environmental factors in the etiology of prostate cancer (PCa) is unclear, but may involve in some cases multiple alleles at multiple loci. Aim: To evaluate the association of gene-gene and gene-environment interactions with PCa. Patients and methods: One hundred three subjects with biopsy proven PCa were studied, using a case-only design. All were interrogated about smoking habits. Polymorphisms for Glutathione-S-transferase (GST) and Cytochrome P4501A1 (CYP1A1), were measured in DNA extracted from peripheral Iymphocytes, using a restriction fragment length polymorphism analysis. Results: Our findings suggest that gene-gene interactions between GSTT1 and CYP1A1 high risk genotypes were positive modifiers and had a high predictive value for the presence of PCa, compared with non-susceptibility genotypes. The interaction between susceptibility genotypes and smoking did not modify the risk for PCa. Conclusions: Gene-gene interactions may play a role modulating the susceptibility to PCa in a proportion of affected individuals (Rev Méd Chile 2004; 132: 961-66).

Artritis séptica y celulitis por Pasteurella multocida secundaria a mordedura de gato / Septic arthritis and cellulitis by Pasteurella multocida secondary to a cat bite

Las mordeduras por animales generan un número importante de consultas en los Servicios de Urgencia. Los perros y gatos son los animales más frecuentemente involucrados, con participación de estreptococos, estafilococos y bacilos Gram negativos como P. multocida. Se presenta un caso de infección por P. multocída secundario a mordedura de gato el que, a pesar de un manejo l'ni'cial adecuado, se complicó con celulitis de rápida aparición y artritis interfalángica distal de la mano derecha. La paciente debió ser hospitalizada, intervenida quirúrgicamente y manejada con antibiáticos parenterales. A los tres meses de seguimiento la paciente persiste con secuelas funcionales que limitan la extensión de la falange