Complexo Hospitalario Universitario Of Santiago

Santiago de Compostela, Spain

Complexo Hospitalario Universitario Of Santiago

Santiago de Compostela, Spain
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Gonzalez-Villar A.J.,University of Santiago de Compostela | Pidal-Miranda M.,University of Santiago de Compostela | Arias M.,Complexo Hospitalario Universitario Of Santiago | Rodriguez-Salgado D.,University of Santiago de Compostela | Carrillo-de-la-Pena M.T.,University of Santiago de Compostela
Brain Topography | Year: 2017

Fibromyalgia (FM) is a chronic syndrome involving widespread pain of unclear pathophysiology. FM patients frequently complain about cognitive symptoms that interfere with their daily life activities. Several studies have reported attentional deficits and working memory impairment in FM patients. Nevertheless, the mechanisms involved in these alterations are still poorly understood. In this study we recorded electroencephalographic activity in 32 women with FM and 30 matched controls while they performed a 2-back working memory task. We analyzed behavioural data, posterior alpha and midfrontal theta frequency power, and theta phase synchronization between midfrontal locations and the remaining scalp-recorded areas. Task performance was similar in patients and controls; however, time–frequency analysis showed a smaller decrease in the amplitude of the posterior alpha (related to attentional processing) and a smaller increase in midfrontal theta power (related to mental effort) in FM patients than in healthy controls. The FM patients also showed lower functional connectivity between midfrontal locations and rest of the scalp-recorded areas in the theta band (related to information transfer across distant brain regions when top-down control is required). To our knowledge, this is the first study relating alterations in oscillatory activity and impaired connectivity to attentional working memory complaints in FM patients. Reduced power in the theta band during performance of the task suggests that the medial frontal cortex may play an important role in the attentional deficits reported in FM. © 2017 Springer Science+Business Media New York

Pei Y.,University of Toronto | Wang K.,University of Toronto | Garcia-Gonzalez M.,Complexo Hospitalario Universitario Of Santiago | He N.,University of Toronto | And 3 more authors.
Kidney International | Year: 2012

Mutations of PKD1 and PKD2 account for most cases of autosomal dominant polycystic kidney disease (ADPKD). Compared with PKD2, patients with PKD1 typically have more severe renal disease. Here, we report a follow-up study of a unique multigeneration family with bilineal ADPKD (NFL10) in which a PKD1 disease haplotype and a PKD2 (L736X) mutation co-segregated with 18 and 14 affected individuals, respectively. In our updated genotype-phenotype analysis of the family, we found that PKD1-affected individuals had uniformly mild renal disease similar to the PKD2-affected individuals. By sequencing all the exons and splice junctions of PKD1, we identified two missense mutations (Y528C and R1942H) from a PKD1-affected individual. Although both variants were predicted to be damaging to the mutant protein, only Y528C co-segregated with all of the PKD1-affected individuals in NFL10. Studies in MDCK cells stably expressing wild-type and mutant forms of PKD found that cell lines expressing the Y528C variant formed cysts in culture and displayed increased rates of growth and apoptosis. Thus, Y528C functions as a hypomorphic PKD1 allele. These findings have important implications for pathogenic mechanisms and molecular diagnostics of ADPKD. © 2012 International Society of Nephrology.

Martinez E.,University of Barcelona | D'Albuquerque P.M.,University of Barcelona | Llibre J.M.,Hospital Germans Trias i Pujol | Gutierrez F.,University Miguel Hernández | And 8 more authors.
AIDS | Year: 2012

Background: Switching from boosted protease inhibitors (PI/r) to raltegravir (RAL) results in a better plasma lipid profile than continuing PI/r. Whether this strategy affects plasma biomarkers associated with atherosclerosis is unknown. Methods: We assessed 48-week changes in fasting lipids and several biomarkers including serum high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein 1 (MCP-1), osteoprotegerin, interleukin (IL) 6, IL-10, tumor necrosis factor alpha (TNF-α), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin and P-selectin, adiponectin, insulin, and D-dimer in otherwise healthy, virologically suppressed HIV-infected patients treated with PI/r who randomly switched from PI/r to RAL or continued with PI/r in the SPIRAL trial. Biomarkers and lipids at baseline and 48-week changes between both study arms were compared. Correlations between changes in biomarkers and changes in lipids were also evaluated. Results: Of 273 patients initiating study drugs in the SPIRAL trial, 233 (119 RAL, 114 PI/r) remained on allocated therapy for 48 weeks and had sera available for the purpose of this substudy. Triglycerides (-28%, P < 0.0001), total (-14%, P < 0.0001), low-density lipoprotein (-9%, P = 0.0069), and high-density lipoprotein (-10%, P = 0.0017) cholesterol decreased in RAL relative to the PI/r group. Among biomarkers, hsCRP (-40%, P < 0.0001), MCP-1 (-20%, P = 0.0003), osteoprotegerin (-13%, P = 0.0024), IL-6 (-46%,P < 0.0001), TNF-α (-27%, P = 0.0011), insulin (-26%, P < 0.0001), and D-dimer (-8%, P = 0.0187) decreased in RAL relative to PI/r group, whereas IL-10 (+1%, P = 0.7773), ICAM-1 (-6%, P = 0.1255), VCAM-1(0%, P = 0.8671), E-selectin (-9%, P = 0.2174), P-selectin (-6%, P = 0.3865), and adiponectin (+8%, P = 0.2028) remained unchanged. Biomarkers and lipids changes at 48 weeks were weakly correlated. Conclusion: Switching from PI/r to RAL induced significant changes in several cardiovascular biomarkers that were not completely explained by lipid changes. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Fernandez Y.,Hospital Universitario Central Of Asturias | Cueva J.,Complexo Hospitalario Universitario Of Santiago | Palomo A.G.,Hospital Of Leon | Ramos M.,Centro Oncologico Regional | And 6 more authors.
Cancer Treatment Reviews | Year: 2010

Metastatic breast cancer is ultimately an incurable disease, although recent data have shown that its incidence is decreasing and that patients with metastatic breast cancer live longer. This improvement in survival seems to be linked with the introduction of new therapeutic agents, novel combinations of existing therapies and targeted therapies. Our increasing understanding of the molecular biology of metastatic disease has allowed the development of therapies aimed at specific molecular targets. Some of these have already been approved for the treatment of metastatic breast cancer in combination with cytotoxics, and others have shown promising results regarding disease-free survival, overall response rates and time to disease progression. Given the enormous amount of information about drug discovery in cancer, it is important to be familiar with the present state of the treatment of metastatic breast cancer. The purpose of this review is to provide an update on the development of some of the most promising novel agents and treatment strategies in metastatic breast cancer. © 2009 Elsevier Ltd. All rights reserved.

Cruz-Ferro E.,Galician Tuberculosis Prevention and Control Programme | Ursua-Diaz M.I.,Galician Tuberculosis Prevention and Control Programme | Taboada-Rodriguez J.A.,Galician Tuberculosis Prevention and Control Programme | Hervada-Vidal X.,Galician Tuberculosis Prevention and Control Programme | And 2 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2014

SETTING: Galicia, Spain. OBJECTIVE: To describe changes in tuberculosis (TB) epidemiology and characteristics in Galicia, Spain, during the period 1996-2011. DESIGN: Retrospective observational descriptive study of data obtained from the Tuberculosis Information System. The Galician Tuberculosis Prevention and Control Programme, created in 1994, is based in seven tuberculosis units that actively collect data on case finding and follow-up of all cases of TB in the region. RESULTS: TB incidence fell from 72.9 cases per 100 000 population in 1996 to 24.6 in 2011 (respectively 40.5 and 14.2 in patients aged <15 years). In 2011, 49.8% (n = 343) of patients were aged between 25-54 years; 62.3% (n = 429) were male; 52.1% (n = 359) had pulmonary TB (PTB) alone, of whom 33.5% (n = 144) had cavitary lesions; 50.7% (n = 218 PTB cases) were sputum smear-positive and 80.5% (346 PTB cases) were culture-positive. The median diagnostic delay was 56 days; 4.6% (n = 32) were human immunodeficiency virus positive and 5.2% (n = 36) were immigrants. The treatment success rate was close to 90%. Contacts of 86.7% of the smear-positive index cases were evaluated. CONCLUSION: TB incidence in Galicia is progressively decreasing; however, it is still higher than that of neighbouring regions. A long diagnostic delay was observed, which may have contributed to the high incidence rate in children. © 2014 The Union.

Costas J.,Complexo Hospitalario Universitario Of Santiago | Sanjuan J.,University of Valencia | Ramos-Rios R.,Complexo Hospitalario Universitario Of Santiago | Paz E.,Complexo Hospitalario Universitario Of Santiago | And 5 more authors.
Journal of Psychiatric Research | Year: 2011

Catechol-O-methyltransferase (COMT) has been largely studied in relation to schizophrenia susceptibility. Most studies focused on the functional single nucleotide polymorphism (SNP) rs4680 that causes a substitution of Val by Met at codon 158 of the COMT protein. Recent meta-analyses do not support an association between allelic variants at rs4680 and schizophrenia. However, the putative role of overdominance has not been tested in meta-analyses, despite its biological plausibility. In this work, we tested the overdominant model in two Spanish samples (from Valencia and Santiago de Compostela), representing a total of 762 schizophrenic patients and 1042 controls, and performed a meta-analysis of the available studies under this model. A total of 51 studies comprising 13,894 schizophrenic patients and 16,087 controls were included in the meta-analysis, that revealed a small but significant protective effect for heterozygosity at rs4680 (pooled OR = 0.947, P=0.023). Post-hoc analysis on southwestern European samples suggested a stronger effect in these populations (pooled OR = 0.813, P=0.0009). Thus, the COMT functional polymorphism rs4680 contributes to schizophrenia genetic susceptibility under an overdominant model, indicating that both too high and too low levels of dopamine (DA) signalling may be risk factors. This effect can be modulated by genetic background. © 2010 Elsevier Ltd.

Costas J.,Complexo Hospitalario Universitario Of Santiago | Sanjuan J.,University of Valencia | Ramos-Rios R.,Complexo Hospitalario Universitario Of Santiago | Paz E.,Complexo Hospitalario Universitario Of Santiago | And 5 more authors.
Schizophrenia Research | Year: 2011

Cannabis use is one of the environmental factors with more solid evidence contributing to schizophrenia risk, especially in genetically susceptible individuals. One of the genes that may interact with cannabis is COMT, although available data are scarce. Here, we present a case-only study of the putative COMT-cannabis interaction in schizophrenia. Two Spanish samples from Santiago de Compostela and Valencia were screened for cannabis use. One hundred and fifty five individuals from a total of 748 patients were identified as cannabis users. Five SNPs in COMT, defining three common functional haplotypes with different enzymatic activities, were genotyped and analyzed for association at the SNP, haplotype and genotype levels. An association was detected between cannabis use and low activity variants (P < 0.01) in the joint analysis and results were consistent between the two samples. Schizophrenic subjects homozygous for the Met allele at rs4680 doubled the probability of lifetime prevalence of cannabis use in comparison to Val homozygous (Mantel-Haenszel OR = 2.07, 95% CI: 1.27-3.26, P = 0.0031, in the combined sample). These data are in contrast to those from Caspi et al. (Biol. Psychiatry 57 (2005)1117-1127) who found association between schizophrenia/schizophreniform disorder and homozygosity at the high activity Val variant of rs4680. The results of our study are discussed in the context of previous findings, suggesting the involvement of COMT polymorphisms in the association between cannabis use and schizophrenia as well as the existence of additional factors mediating this association. However, further research is needed to confirm the COMT-cannabis interaction. © 2011 Elsevier B.V.

Galan Bartual S.,University of Santiago de Compostela | Garcia-Doval C.,University of Santiago de Compostela | Alonso J.,Complexo Hospitalario Universitario Of Santiago | Schoehn G.,Joseph Fourier University | And 3 more authors.
Protein Expression and Purification | Year: 2010

Bacteriophage T4 recognises its host cells through its long tail fibre protein gene product (gp) 37. Gp37 is a protein containing 1026 amino acids per monomer, forming a fibrous parallel homotrimer at the distal end of the long tail fibres. The other distal half-fibre protein, gp36, is much smaller, forming a trimer of 221 amino acids per monomer. Functional and structural studies of gp37 have been hampered by the inability to produce suitable amounts of it. We produced soluble gp37 by co-expression with two bacteriophage T4-encoded chaperones in a two-vector system; co-expression with each chaperone separately did not lead to good amounts of correctly folded, trimeric protein. An expression vector for the bacteriophage T4 fibrous protein chaperone gp57 was co-transformed into bacteria with a compatible bi-cistronic expression vector containing bacteriophage T4 genes 37 and 38. A six-histidine tag is encoded amino-terminal to the gp37 gene. Recombinant trimeric gp37, containing the histidine tag and residues 12-1026 of gp37, was purified from lysed bacteria by subsequent nickel-affinity, size exclusion and strong anion exchange column chromatography. Yields of approximately 4 mg of purified protein per litre of bacterial culture were achieved. Electron microscopy confirmed the protein to form fibres around 63 nm long, presumably gp36 makes up the remaining 11 nm in the intact distal half-fibre. Purified, correctly folded, gp37 will be useful for receptor-binding studies, high-resolution structural studies and for specific binding and detection of bacteria. © 2009 Elsevier Inc. All rights reserved.

Bande M.F.,Complexo Hospitalario Universitario Of Santiago | Santiago M.,Complexo Hospitalario Universitario Of Santiago | Blanco M.J.,Complexo Hospitalario Universitario Of Santiago | Mera P.,Complexo Hospitalario Universitario Of Santiago | And 4 more authors.
Investigative Ophthalmology and Visual Science | Year: 2012

PURPOSE. There is substantial evidence that intraocular melanomas arise from benign nevi in the uveal tract. Previous studies performed by the authors revealed that uveal melanoma cells secrete the oncoprotein DJ-1/PARK7 into the extracellular environment and circulation. The aim of this study was to determine whether circulating DJ-1 serum levels correlate with known clinical risk factors of nevi growth. METHODS. Standardized ultrasonography, optical coherence tomography, and eye fundus examinations were used to evaluate the clinical risk factors of nevi growth. These clinical risk factors (including nevi size, distance of margins to the optic disc, detection of acoustic hollowness, presence of ocular symptoms, orange pigment, subretinal fluid, and absence of drusen) were examined in 53 consecutive patients from January 2009 to February 2011. Serum levels of DJ-1/PARK7 in these patients and in healthy age-and sex-matched controls (n = 32) were analyzed using ELISA. RESULTS. Within the choroidal nevi group, DJ-1 serum levels were higher in those with symptoms (P < 0.033), with a nevus thickness greater than 1.5 mm (P < 0.001), a large basal diameter greater than 8 mm (P < 0.001), and the presence of acoustic hollowness (P < 0.001), compared to those patients without these risk factors. Similar significant differences were found when these at risk nevi subgroups were compared to healthy persons. CONCLUSIONS. Elevated serum levels of DJ-1 are associated with choroidal nevi transformation risk factors. Therefore, DJ-1 appears to be a promising factor for predicting the growth of choroidal nevi and may be a potential biomarker of malignancy. © 2012 The Association for Research in Vision and Ophthalmology, Inc.

Fachal L.,Fundacion Publica Galega de Medicina Xenomica SERGAS | Gomez-Caamano A.,Complexo Hospitalario Universitario Of Santiago | Peleteiro P.,Complexo Hospitalario Universitario Of Santiago | Carballo A.,Complexo Hospitalario Universitario Of Santiago | And 5 more authors.
Radiotherapy and Oncology | Year: 2012

Background and purpose: We have performed a case-control study among prostate cancer patients treated with three-dimensional conformational radiotherapy (3D-CRT) in order to investigate the association between single nucleotide polymorphisms (SNPs), treatment and patient features with gastrointestinal and genitourinary acute toxicity. Material and methods: A total of 698 patients were screened for 14 SNPs located in the ATM, ERCC2, LIG4, MLH1 and XRCC3 genes. Gastrointestinal and genitourinary toxicities were recorded prospectively using the Common Terminology Criteria for Adverse Events v3.0. Results: The XRCC3 SNP rs1799794 (G/G OR = 5.65; 95% CI: 1.95-16.38; G/A OR = 2.75; 95% CI: 1.25-6.05; uncorrected p-value = 2.8 × 10-03; corrected p-value = 0.03; FDR q-value = 0.06) as well as the mean dose received by the rectum (OR = 1.06; 95% CI: 1.02-1.1; uncorrected p-value = 2.49 × 10-03; corrected p-value = 0.03; FDR q-value = 0.06) were significantly associated with gastrointestinal toxicity after correction for multiple testing. Those patients who undergone previous prostatectomy were less prone to develop genitourinary toxicity (OR = 0.38; 95% CI: 0.18-0.71; uncorrected p-value = 4.95 × 10-03; corrected p-value = 0.03; FDR q-value = 0.08). Our study excludes the possibility of a >2-fold risk increase in genitourinary acute toxicity being due to rs1801516 ATM SNP, the rs1805386 and rs1805388 LIG4 markers, as well as all the SNPs evaluated in the ERCC2, MLH1 and XRCC3 genes. Conclusions: The XRCC3 rs1799794 SNP and the mean dose received by the rectum are associated with the development of gastrointestinal toxicity after 3D-CRT. © 2012 Elsevier Ireland Ltd. All rights reserved.

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