Jimenez Diaz Foundation

Madrid, Spain

Jimenez Diaz Foundation

Madrid, Spain

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Torres-Martin M.,University Institute of La Paz | Lassaletta L.,University Institute of La Paz | San-Roman-Montero J.,Rey Juan Carlos University | De Campos J.M.,Jimenez Diaz Foundation | And 7 more authors.
International Journal of Oncology | Year: 2013

Vestibular schwannomas are benign neoplasms that arise from the vestibular nerve. The hallmark of these tumors is the biallelic inactivation of neurofibromin 2 (NF2). Transcriptomic alterations, such as the neuregulin 1 (NRG1)/ErbB2 pathway, have been described in schwannomas. In this study, we performed a whole transcriptome analysis in 31 vestibular schwannomas and 9 control nerves in the Affymetrix Gene 1.0 ST platform, validated by quantitative real-time PCR (qRT-PCR) using TaqMan Low Density arrays. We performed a mutational analysis of NF2 by PCR/denaturing high-performance liquid chromatography (dHPLC) and multiplex ligation-dependent probe amplification (MLPA), as well as a microsatellite marker analysis of the loss of heterozygosity (LOH) of chromosome 22q. The microarray analysis demonstrated that 1,516 genes were deregulated and 48 of the genes were validated by qRT-PCR. At least 2 genetic hits (allelic loss and/or gene mutation) in NF2 were found in 16 tumors, seven cases showed 1 hit and 8 tumors showed no NF2 alteration. MET and associated genes, such as integrin, alpha 4 (ITGA4)/B6, PLEXNB3/SEMA5 and caveolin-1 (CAV1) showed a clear deregulation in vestibular schwannomas. In addition, androgen receptor (AR) downregulation may denote a hormonal effect or cause in this tumor. Furthermore, the osteopontin gene (SPP1), which is involved in merlin protein degradation, was upregulated, which suggests that this mechanism may also exert a pivotal role in schwannoma merlin depletion. Finally, no major differences were observed among tumors of different size, histological type or NF2 status, which suggests that, at the mRNA level, all schwannomas, regardless of their molecular and clinical characteristics, may share common features that can be used in their treatment.


Cubedo J.,Cardiovascular Research Center | Cubedo J.,Biomedical Research Institute Sant Pau | Padro T.,Cardiovascular Research Center | Padro T.,Biomedical Research Institute Sant Pau | And 6 more authors.
European Journal of Clinical Investigation | Year: 2014

Background: Many efforts in cardiovascular medicine have been focused in the identification of patients at risk of developing an acute ischaemic event. Biomarker discovery studies have become an essential research area, being proteomic technologies an excellent tool for biomarker identification. By applying proteomic approaches, we have detected changes in retinol-binding protein 4 (RBP4) in acute new-onset myocardial infarction patients (AMI) and in high-risk patients with heterozygous familial hypercholesterolaemia (FH). Materials and methods: Differential serum proteome was analysed by two-dimensional electrophoresis and MALDI-TOF/TOF. Validation studies were performed by ELISA, and functional effects of RBP4 were tested in cell culture experiments. Results: Retinol-binding protein 4 proteomic characterization depicted two spots (pI = 5·4;Mw = 23·01/22·78 kDa) with decreased intensity in AMI patients. Total serum RBP4 levels were decreased in AMI patients (N = 68) compared with controls (N = 132; P < 0·0001). RBP4 was also decreased in FH patients who had an ischaemic event 2 years (±0·3) after their inclusion compared with FH patients without any cardiovascular episode at follow-up (P < 0·001; N = 187). In both cases, changes were limited to men. RBP4 induced a significant increase in eNOS expression in human endothelial vascular cells and in prostaglandin I2 release in coronary vascular smooth muscle cells. Conclusions: We show decreased serum RBP4 levels in men in the acute phase of AMI, being this decrease already detected in men with FH previous to the presentation of an ischaemic event. The decrease in RBP4 levels could confer an increased susceptibility to the precipitation of an ischaemic event that could be mediated by the decrease in its vasculoprotective properties through NO and PGI2. © 2013 Stichting European Society for Clinical Investigation Journal Foundation.


Lopez-Gomez M.,San Sebastián University | Ortega C.,Virgen Of La Luz Hospital | Suarez I.,San Sebastián University | Serralta G.,San Sebastián University | And 7 more authors.
Annals of Oncology | Year: 2012

Background: Cancer patients search for information about prognosis and treatment. Internet has become a major source of medical information. Its impact on oncology patients is not well known. Patients and methods: Three hundred and eighty questionnaires were distributed to cancer patients and companions and 293 were returned. The type of information they obtained online, its usefulness, and its impact on the patient-physician relationship as well as other sources of searching were demanded. Student t-tests, chi-square tests, and multivariate regression logistic analysis were carried out. Results: Internet use was low (27% patients, 58% relatives). Cancer-specific information was the principal research (41% and 70%). For 61% patients, the information had been useful. Information provided by clinicians was the primary reason to not use Internet (37% and 67%). Twenty-two percent patients discussed it with clinicians. Among other sources, health professional (62% and 51%) and printed materials (18% and 25%) were the most demanded. Conclusions: Cancer patients and carers reported a low use of the Internet for searching medical information, although it helps patients to better cope with cancer. To discuss this information may strengthen the patient-physician relationship. Physicians should ensure that their patients receive reliable online information. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Purpose: To study the surgical applicability and clinical results of the Vira® System in treatment for severe fractures of the calcaneus. Methods: A total of 37 acute intra-articular fractures of the calcaneus treated by reconstruction and primary fusion with the minimally invasive Vira® System. Of them, 33 patients were analysed over a 2-year period. All fractures were classified, according to the Sanders criteria, as grade IV. The mean age was 42.08 years. Four were bilateral fractures and three were open fractures. All the patients were evaluated, in a prospective manner, using the American Orthopaedic Foot and Ankle Society (AOFAS) scale, plain radiographs and CT scan studies. Results: The average AOFAS score 12 months after surgery was 75.43 points (SD: 13.9). In 31 cases, the result was considered good and very good, and in five and one case mild and poor. Most of the patients (81%) could wear normal shoes; the footprint and the alignment of the heel were considered normal in all cases but seven patients showed a mild valgus deviation. The Böhler angle improvement after surgery was significant (p = 0.05) and it did not vary along the follow-up. Subtalar arthrodesis was achieved in all cases. Only one case needed bone grafting. Important post-surgical complications were not registered in this cohort. Conclusions: The Vira® System is a useful option for the surgical treatment of severe fractures of the calcaneus, yielding good clinical and radiological results with a surgical procedure that is only minimally aggressive and has a low rate of complications. © 2010 Elsevier Ltd. All rights reserved.


Suades R.,Cardiovascular Research Center | Suades R.,CIBER ISCIII | Padro T.,Cardiovascular Research Center | Padro T.,CIBER ISCIII | And 5 more authors.
Thrombosis and Haemostasis | Year: 2013

Hyperlipidaemia is a causal factor in the ethiopathogenesis of atherosclerosis. Statins are the cornerstone drug therapy for LDL-cholesterol (LDL-c) lowering, that exert beneficial effects beyond lipid lowering. Circulating microparticles (cMPs), microvesicles released by activated cells into the bloodstream, are markers of vascular and inflammatory cell activation with tentative role in disease progression. However, the role of statins on cMPs seems controversial. We aimed at the evaluation of the effects of lipid-lowering treatment (LLT) on cMP generation in patients in primary prevention of atherosclerosis. A case-control study was conducted in hypercholesterolaemic patients receiving LLT with statins and normocholesterolaemic controls (LLT+ and LLT-, respectively, n=37/group), matched by age, gender and LDL-c levels. cMPs were characterised by flow cytometry using annexin-V and cell-specific antibodies. In LLT+-patients overall numbers of cMPs (p<0.005) were lower than in controls. Levels of cMPs carrying parent al cell markers from vascular and circulating cell origin (platelet, endothelial cell, pan-leukocyte and specific-leukocyte subsets) were significantly lower in blood of LLT+ compared to LLT--patients. Moreover, MPs from LLT+-patients had reduced markers of activated platelets (αIIbβ3-integrin), activated inflammatory cells (αM-integrin) and tissue factor. The effect of LLT on cMP shedding was found to be accumulative in years. cMP shedding associated to cardiovascular risk in LLT+-patients. In summary, at similar plasma cholesterol levels patients on statin treatment had a significant lower number of cMPs carrying markers of activated cells. These findings indicate that statins protect against vascular cell activation. © Schattauer 2013.


Sanz-Fuentenebro J.,Hospital 12 Of Octubre | Sanz-Fuentenebro J.,Research Center Biomedica En Red Of Salud Mental Cibersam | Taboada D.,Hospital 12 Of Octubre | Palomo T.,Research Center Biomedica En Red Of Salud Mental Cibersam | And 7 more authors.
Schizophrenia Research | Year: 2013

In first-episode patients with psychosis, clozapine may be potentially valuable as an initial treatment seeking to limit early on clinical and cognitive deterioration. Nevertheless, until recently its restricted use has limited the study of this possibility. Our research group is developing a non-commercial, multicentric and open label study on the differential efficacy between clozapine and risperidone in first-episode schizophrenia. In this paper, we present the results related to clinical variables after a one-year follow-up. So far, we have recruited 30 patients diagnosed with schizophrenia or schizophreniform disorder with illness duration of less than two years. The patients had not received any previous treatment and they were randomized to treatment with clozapine or risperidone. Our results indicate that on average, patients on clozapine adhered to their original treatment for a longer time period than patients on risperidone. By last observation carried forward (LOCF) analysis, patients on clozapine and risperidone displayed similar clinical improvements, although marginally greater improvements in positive and total symptoms scores were found in the clozapine group. At the 12-month point we observed a marginal improvement in negative symptom scores in patients on clozapine. Subjective secondary effects, as measured with the Udvalg for KliniskeUndersøgelser (UKU) scale, correlated negatively with negative symptoms at follow-up. Our data, although preliminary, suggest that clozapine may have a slightly superior efficacy in the initial year of treatment of first-episode treatment-naïve patients with schizophrenia, and this can be explained for the most part by greater adherence to this treatment. © 2013 Elsevier B.V.


Collette J.,University of Liège | Bruyere O.,University of Liège | Kaufman J.M.,Ghent University | Lorenc R.,Childs Health Center | And 5 more authors.
Osteoporosis International | Year: 2010

Osteoporotic post-menopausal women patients in two randomised trials comparing the anti-fracture efficacy of strontium ranelate with placebo were separated into tertiles according to their baseline levels of biochemical markers of bone formation and resorption. The vertebral anti-fracture efficacy of strontium ranelate was shown to be independent of baseline bone turnover levels. Introduction: Bone turnover (BTO) levels vary among women at risk of osteoporotic fracture. Strontium ranelate is an anti-osteoporotic treatment increasing bone formation and reducing bone resorption. It was hypothesised that its anti-fracture efficacy would be independent of baseline BTO levels. Methods: Post-menopausal women with osteoporosis from two pooled studies were stratified in tertiles according to baseline levels of two BTO markers: bone-specific alkaline phosphatase (b-ALP, n=4995) and serum C-telopeptide cross-links (sCTX, n=4891). Vertebral fracture risk was assessed over 3 years with strontium ranelate 2 g/day or placebo. Results: In the placebo group, relative risk of vertebral fractures increased with BTO tertiles by 32% and 24% for patients in the highest tertile for b-ALP and CTX, respectively, compared to those in the lowest tertile. In the strontium ranelate group, incidences of vertebral fracture did not differ significantly across BTO tertiles. Significant reductions in vertebral fractures with strontium ranelate were seen in all tertiles of both markers, with relative risk reductions of 31% to 47% relative to placebo. Risk reduction did not differ among tertiles (b-ALP: p=0.513; sCTX: p=0.290). Conclusion: The vertebral anti-fracture efficacy of strontium ranelate was independent of baseline BTO levels. Strontium ranelate offers clinical benefits to women across a wide range of metabolic states. © 2009 The Author(s).


Olenik A.,Jimenez Diaz Foundation | Jimenez-Alfaro I.,Jimenez Diaz Foundation | Alejandre-Alba N.,Jimenez Diaz Foundation | Mahillo-Fernandez I.,Jimenez Diaz Foundation
Clinical Interventions in Aging | Year: 2013

Background: Dysfunction of the meibomian gland (MG) is among the most frequent causes of ophthalmological symptoms. The inflammation seen in meibomian gland dysfunction (MGD) is part of its pathogenesis, and evidence of the antioxidant-inflammatory properties of omega-3 fatty acids suggests this to be an appropriate treatment for MGD. Objective: We aimed to assess the effectiveness of omega-3 fatty acids versus placebo, in improving the symptoms and signs of MGD. Methods: We conducted a randomized and double-mask trial of 3 months duration. We enrolled 61 patients who presented with symptomatic MGD and no tear instability (defined as tear breakup time [TBUT]<10 seconds). Participants were randomly assigned to two homogeneous subgroups. For patients in group A, the study treatment included cleaning the lid margins with neutral baby shampoo and use of artificial tears without preservatives, plus a placebo oral agent. For patients in group B, the study treatment included cleaning the lid margins with neutral baby shampoo and use of artificial tears without preservatives, plus oral supplementation with omega-3 fatty acids. We performed the following tests: (1) TBUT; (2) Schirmer I test; (3) Ocular Surface Disease Index© (OSDI©; Allergan, Inc., Irvine, CA, USA); (4) MG expression; (5) evaluation of lid margin inflammation; and (6) interpalpebral and corneal dye staining. Results: After 3 months of evaluation, the mean OSDI, TBUT, lid margin inflammation, and MG expression presented improvement from the baseline values, in group B (P < 0.01, P < 0.001, P < 0.0001, P < 0.0001, respectively). The Schirmer test results were also improved and statistically significant (P < 0.01). Conclusion: Oral omega-3 fatty acids, 1.5 grams per day, may be beneficial in the treatment of MGD, mainly by improving tear stability. © 2013 Oleñik et al, publisher and licensee Dove Medical Press Ltd.


Ovejero S.,Jimenez Diaz Foundation | Caro-Canizares I.,Jimenez Diaz Foundation | De Leon-Martinez V.,Jimenez Diaz Foundation | Baca-Garcia E.,Jimenez Diaz Foundation
International Journal of Social Psychiatry | Year: 2014

Background: The Japanese term hikikomori means literally 'to be confined'. Social withdrawal can be present in severe psychiatric disorders; however, in Japan, hikikomori is a defined nosologic entity. There have been only a few reported cases in occidental culture. Material: We present a case report of a Spanish man with prolonged social withdrawal lasting for 4 years. Discussion: This is a case of prolonged social withdrawal not bound to culture, as well as the second case of hikikomori reported in Spain. We propose prolonged social withdrawal disorder as a disorder not linked to culture, in contrast to hikikomori. Conclusion: Further documentation of this disorder is still needed to encompass all cases reported in Japan and around the world. © The Author(s) 2013.


Gutierrez C.,University of Navarra | Rodriguez J.,University of Navarra | Patino-Garcia A.,University of Navarra | Garcia-Foncillas J.,Jimenez Diaz Foundation | Salgado J.,University of Navarra
Oncology Letters | Year: 2013

The present study describes an optimized method for isolating peripheral blood circulating tumor cells (CTCs) and performing KRAS mutation analysis. The approach combines isolation of peripheral blood mononuclear cells and immunomagnetic labeling with CD45 and CD326 human microbeads with KRAS analysis performed with a Therascreen KRAS kit by quantitative PCR. KRAS mutations were detected in the CTCs of patients with metastatic colorectal cancer (mCRC). CTCs may represent an alternative to invasive procedures and their analysis may be representative of the current disease status of the patient. This proposed analysis may be performed in a daily clinical practice.

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