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Andres-Belmonte A.,Hospital Universitario 12 Of Octubre
Resuscitation | Year: 2010

Objective: This study aims to determine the failure rate of transplanted kidney grafts in recipients of organs from non-heart beating donors (NHBDs) who have had mechanical chest compressions to maintain a circulation before organ retrieval. Methods: A retrospective observational study based on review of the emergency medical service database and case histories of NHBDs, and information periodically sent by transplant units about donors and organs. The following variables were studied: age, sex, transfer hospital, time to arrival on the scene of cardiopulmonary arrest, time to arrival in hospital, number and type of organs retrieved, use of mechanical chest compression devices, and kidney function in graft recipients. The study covered the period between January 2008 and November 2009. During 2008 standard manual chest compressions were used and during 2009 mechanical chest compression devices were used. Results: In 39 transplanted kidneys from donors receiving mechanical chest compressions primary failure was documented in recipients on two occasions (5.1%). Kidneys transplanted from donors who had manual chest compressions resulted in three primary failures in recipients (9.1%). The difference between the two groups was not significant (p=0.5). Three patients achieved successful return of spontaneous circulation in the mechanical chest compression group after initiation of the NHBD donor protocol. Conclusion: We have described our experience and protocol for non-heart beating donation using victims of out-of-hospital cardiac arrest in whom cardiopulmonary resuscitation has been unsuccessful as donors. Primary kidney graft failure rates in organs from non-heart beating donors is similar when manual or mechanical chest compression devices are used during cardiopulmonary resuscitation. © 2010 Elsevier Ireland Ltd. Source

Ciruelos Gil E.M.,Hospital Universitario 12 Of Octubre
Cancer Treatment Reviews | Year: 2014

Approximately 70-75% of breast cancers express the estrogen receptor (ER), indicating a level of dependence on estrogen for growth. Endocrine therapy is an important class of target-directed therapy that blocks the growth-promoting effects of estrogen via ER. Although endocrine therapy continues to be the cornerstone of effective treatment of ER-positive (ER+) breast cancer, many patients with advanced ER+ breast cancer encounter de novo or acquired resistance and require more aggressive treatment such as chemotherapy. Novel approaches are needed to augment the benefit of existing endocrine therapies by prolonging time to disease progression, preventing or overcoming resistance, and delaying the use of chemotherapy.The phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is a key intracellular signaling system that drives cellular growth and survival; hyperactivation of this pathway is implicated in the tumorigenesis of ER+ breast cancer and in resistance to endocrine therapy. Moreover, preclinical and clinical evidence show that PI3K/AKT/mTOR pathway inhibition can augment the benefit of endocrine therapy in ER+ breast cancer, from the first-line setting and beyond.This article will review the fundamental role of the PI3K/AKT/mTOR pathway in driving ER+ breast tumors, and its inherent interdependence with ER signaling. In addition, ongoing strategies to combine PI3K/AKT/mTOR pathway inhibitors with endocrine therapy for improved clinical outcomes, and methods to identify patient populations that would benefit most from inhibition of the PI3K/AKT/mTOR pathway, will be evaluated. © 2014 Elsevier Ltd. Source

Gil Borlado M.C.,Hospital Universitario 12 Of Octubre
PloS one | Year: 2010

In recent years clinical evidence has emphasized the importance of the mtDNA genetic background that hosts a primary pathogenic mutation in the clinical expression of mitochondrial disorders, but little experimental confirmation has been provided. We have analyzed the pathogenic role of a novel homoplasmic mutation (m.15533 A>G) in the cytochrome b (MT-CYB) gene in a patient presenting with lactic acidosis, seizures, mild mental delay, and behaviour abnormalities. Spectrophotometric analyses of the respiratory chain enzyme activities were performed in different tissues, the whole muscle mitochondrial DNA of the patient was sequenced, and the novel mutation was confirmed by PCR-RFLP. Transmitochondrial cybrids were constructed to confirm the pathogenicity of the mutation, and assembly/stability studies were carried out in fibroblasts and cybrids by means of mitochondrial translation inhibition in combination with blue native gel electrophoresis. Biochemical analyses revealed a decrease in respiratory chain complex III activity in patient's skeletal muscle, and a combined enzyme defect of complexes III and IV in fibroblasts. Mutant transmitochondrial cybrids restored normal enzyme activities and steady-state protein levels, the mutation was mildly conserved along evolution, and the proband's mother and maternal aunt, both clinically unaffected, also harboured the homoplasmic mutation. These data suggested a nuclear genetic origin of the disease. However, by forcing the de novo functioning of the OXPHOS system, a severe delay in the biogenesis of the respiratory chain complexes was observed in the mutants, which demonstrated a direct functional effect of the mitochondrial genetic background. Our results point to possible pitfalls in the detection of pathogenic mitochondrial mutations, and highlight the role of the genetic mtDNA background in the development of mitochondrial disorders. Source

Diaz Guzman J.,Hospital Universitario 12 Of Octubre
Neurologia | Year: 2012

Approximately one in four ischemic strokes is of cardioembolic origin. Non-valvular atrial fibrillation accounts for 50% of these cases, followed by myocardial infarction, intraventricular thrombus, valvular heart disease and a miscellany of causes. The incidence of embolic heart disease in the population could be about 30 cases per 100,000 inhabitants per year, and its prevalence between 5 and 10 cases per 1,000 persons aged 65 years or older. Hospital mortality is high, and 5-year survival is only one out of every five patients. The recurrence rate of this type of stroke is about 12% at 3 months, higher than that of non-cardioembolic stroke. The severity of cardioembolic strokes and the resulting disability are greater than with non-cardioembolic stroke. Age, a history of stroke or transient ischemic attack, hypertension, diabetes and heart failure play a role in stroke with atrial fibrillation as additional risk factors for future embolisms. Stroke rates can reach over 20% per year and therefore the prevention and treatment of these events are of paramount importance. © 2012 Sociedad Española de Neurología. Source

Barrientos A.,University of Miami | Ugalde C.,Hospital Universitario 12 Of Octubre | Ugalde C.,Research Center Biomedica En Red Of Enfermedades Raras Ciberer
Cell Metabolism | Year: 2013

The mitochondrial respiratory chain is believed to dynamically arrange in suprastructures known as supercomplexes or respirasomes, though their function remains elusive. A recent study in Science (Lapuente-Brun et al., 2013) now reports that dynamic supercomplex assembly determines electron flux from different substrates through the respiratory chain. © 2013 Elsevier Inc. Source

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