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Preclinical data suggest that medroxyprogesterone acetate (MPA) has both anti-metastatic and anti-angiogenic activity in the absence of hormone receptors (HR). This phase II trial assessed the activity of MPA alone or in combination with low-dose chemotherapy in patients with metastatic HR-negative breast cancer. Postmenopausal women with HR-negative disease were eligible if they had not received more than 3 chemotherapy regimens for metastatic disease. All patients were treated with MPA 1,000���1,500 mg/day orally; patients in cohort two also received low-dose oral cyclophosphamide and methotrexate (ldCM, 50 mg/day and 2.5 mg twice daily on Days 1 and 2 each week). Tissue and circulating biomarkers were assessed serially. The primary endpoint was clinical benefit response defined as objective response or stable disease >6 months. Thirty patients were enrolled (14 MPA monotherapy; 16 MPA + ldCM); median age was 55 (35���80); nearly all had visceral involvement. Despite dose escalation in 90 % of patients, only 17 (57 %) patients ever achieved MPA trough concentrations >50 ng/ml. One patient developed grade 4 renal failure in the setting of rapid disease progression and dehydration. There were no objective responses. One patient in each cohort (~7 %) had stable disease for > 6 months. Skin Nm23 expression increased after 4 weeks of MPA + ldCM, but there were no significant changes in TSP-1, PAI-1 antigen, or PAI-1 activity. MPA had limited activity and does not warrant further development in patients with HR-negative advanced breast cancer. Poor bioavailability limited exposure despite dose escalation.

La hiperplasia lipomatosa del septum interauricular (HLSI) es una entidad benigna de naturaleza desconocida que se caracteriza por la acumulación de grasa no encapsulada en el interior del surco interauricular sin participación de la fosa oval. A pesar de su carácter benigno, clínicamente se ha asociado con arritmias cardiacas, generalmente de origen supraventricular, insuficiencia cardiaca y muerte súbita. Presentamos el caso de una mujer de edad media (47 años), con obesidad mórbida e insuficiencia cardiaca congestiva, que falleció súbitamente y la autopsia puso de manifiesto una HLSI. El estudio macroscópico de la pieza de resección mostró un tamaño de 5 x 2,5 cm y la histología típica de esta entidad, es decir, adipocitos maduros y pocos lipoblastos entremezclados con miocitos auriculares. Hemos analizado microscópicamente los nodos sinoauricular y auriculoventricular, lo que puso de manifiesto que la infiltración grasa los rodeada pero no los aislaba del miocardio auricular de trabajo circundante. El miocardio del ventrículo izquierdo y del tabique interventricular presentaba áreas con una intensa fibrosis intersticial por isquémica crónica y que esta fibrosis pudo ser la causa de una arritmia ventricular y muerte súbita. Aunque esta entidad es cada vez más frecuentemente reconocida gracias al desarrollo creciente de las técnicas de imagen no invasivas, rara vez necesita ser corregida quirúrgicamente. The lipomatous hyperplasia of the interatrial septum (LHIS) is a benign entity of unknown nature, characterized by the accumulation of fat tissue not encapsulated into the interatrial groove without participation of the fossa ovalis. Despite its benign nature, it has been clinically associated with cardiac arrhythmias, usually of supraventricular origin, heart failure and sudden death. We present the case of a woman of middle age (47 years), with morbid obesity and heart failure congestive who died suddenly and the autopsy revealed a LHIS. The macroscopic study of resection piece showed a size of 5 x 2.5 cm and the typical histology of this entity, i.e. mature adipocytes and few lipoblastos interspersed with atrial myocytes. We have analysed microscopically both sinoatrial and atrioventricular nodes, which they revealed fat tissue infiltration that surrounded them but not isolated from atrial working myocardium. The interventricular septum and left ventricle myocardium presented areas with severe interstitial fibrosis by chronic ischemic and this fibrosis may be the cause of ventricular arrhythmia and sudden death. Although this entity is most frequently recognized due to the development of noninvasive imaging techniques, rarely needs to be corrected surgically.

El objetivo de este trabajo fue el estudio de la posibilidad de criopreservar semen de verracos de la raza porcina autóctona Gochu Astur-Celta, que en la actualidad se encuentra en peligro de extinción, como herramienta en los planes de recuperación de la raza. Las dosis seminales obtenidas a partir de los eyaculados recogidos fueron envasadas, sometidas a congelación y posteriormente almacenadas en nitrógeno líquido, analizándose los siguientes parámetros: motilidad y calidad del movimiento, integridad funcional de la membrana, morfología y estado del acrosoma. Los resultados obtenidos muestran que es necesario seguir trabajando en la mejora de la calidad del semen congelado-descongelado para que esta técnica pueda contribuir a la conservación de la biodiversidad. The use of sperm cryoconservation technique could help to the preservation of genetic material for long term. This work was carried out in order to develop preliminary studies regarding boar sperm cryopreservation in the autochthonous endagered pig breed Gochu Astur-Celta. The seminal doses obtained from ejaculates of these boars, were cryopreserved and then stored in liquid nitrogen. Semen analysis were carried out on every sample, and the parameters studied were: sperm motility, movement quality, normal apical ridge (NAR), morphology and functional membrane integrity (hyposmotic swelling test). The results showed that further studies are needed to improve the quality of frozen-thawed sperm to make this technique a useful tool in the field of biodiversity preservation.

Un proyectil de arma de fuego puede penetrar en el organismo por cualquier parte, originando una lesión cuya morfología puede ser muy variada en función de múltiples factores. No obstante, en ocasiones el lugar de entrada del proyectil puede coincidir con un orificio natural del cuerpo, por lo que la lesión externa no existe. Presentamos un caso de muerte por un único proyectil de arma de fuego cuyo lugar de penetración es uno de los orificios nasales, con la particularidad de que la bala quedó alojada en el interior del cuerpo, no existiendo por tanto lesión de salida. En estas circunstancias se hacen indispensables las técnicas radiológicas como paso previo a la autopsia. A firearm projectile can penetrate through any place of the body, causing injuries whose morphology can be different depending on several factors. However, sometimes the shotgun entrance hole coincides with a body orifice, so the entrance wound could not exist. The authors present a case of a death caused by a single firearm projectile which penetrated through one of the nostrils. The bullet was lodged inside of the body without an exit wound. In those circumstances the radiological techniques are indispensable before to perform the autopsy.

Gastric cancer (GC) continues to be a highly aggressive malignancy with poor prognosis and low survival rates. The survival of patients with GC depends mainly on the stage of the disease, with early GC having a 5 year survival of 90-100% and advanced tumors a 5 year survival of 15-25%. The role of other prognostic factors in these tumors is still under investigation. 28 gastric dysplasia, 45 Early GC and 98 Advanced Gastric Cancers were evaluated for expression of the oncogenes p53, c-ErbB2, c-myc and the EGFr in paraffin-embedded material utilizing Avidin-Biotin immunohistochemistry techniques. In 34 cases of GC microvessel density (MVD) was determined in CD34 stained sections. Statistical correlations with stage, histologic type, differentiation degree, location, size, ploidy patterns and overall survival were done. The Mantel-Cox test was performed to evaluate which factors had an independent prognostic value. Both, tumor angiogenesis and p53 protein expression were statistically associated (95% confidence intervals) with overall survival in patients with GC. p53 protein expression was also correlated with cardial location, nodal involvement and tumor stage. c-ErbB2 may recognize a group of highly aggressive well differentiated adenocarcinomas with worse prognosis. c-myc was also significantly enhanced in well differentiated tumors. EGFr showed no significant associations. Mantel-Cox was performed to compare the prognostic value of tumor stage, p53 protein expression and tumor angiogenesis. Tumor angiogenesis was the most important prognostic indicator to predict overall survival in our series. p53 expression was not independent and did not provide additional prognostic information to tumor stage. Our study suggests that angiogenesis as demonstrated by microvessel counts in CD34 stained sections is a significantly important Offprint requests to: Julian Sanz Ortega, MD, Departamento de Anatomia Patolbgica, Hospital Universitario "San Carlos". Martin Lagos s.n., Madrid 28040, Spain. Fax: 34-913303032, e-mail: jsanz@ hcsc.insalud.es prognostic factor for predicting survival in gastric cancer.