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Navarro A.,Fundacion Hospital General Universitario | Marin S.,Consorcio Hospital General Universitario | Minana M.D.,Fundacion Hospital General Universitario
Stem Cell Research and Therapy | Year: 2014

Introduction. Adipose tissue has the unique property of expanding throughout adult life, and angiogenesis is required for its growth. However, endothelial progenitor cells contribute minimally to neovascularization. Because myeloid cells have proven to be angiogenic, and monocytes accumulate in expanding adipose tissue, they might contribute to vascularization. Methods. The stromal vascular fraction (SVF) cells from human adipose tissue were magnetically separated according to CD45 or CD14 expression. Adipose-derived mesenchymal stromal cells (MSCs) were obtained from SVF CD45- cells. CD14+ monocytes were isolated from peripheral blood (PB) mononuclear cells and then cultured with SVF-derived MSCs. Freshly isolated or cultured cells were characterized with flow cytometry; the conditioned media were analyzed for the angiogenic growth factors, angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), granulocyte colony-stimulating factor (G-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF) with Luminex Technology; their angiogenic capacity was determined in an in vivo gelatinous protein mixture (Matrigel) plug angiogenesis assay. Results: CD45+ hematopoietic cells within the SVF contain CD14+ cells that co-express the CD34 progenitor marker and the endothelial cell antigens VEGF receptor 2 (VEGFR2/KDR), VEGFR1/Flt1, and Tie2. Co-culture experiments showed that SVF-derived MSCs promoted the acquisition of KDR and Tie-2 in PB monocytes. MSCs secreted significant amounts of Ang-2 and HGF, but minimal amounts of bFGF, G-CSF, or GM-CSF, whereas the opposite was observed for SVF CD14 + cells.Additionally, SVF CD14+ cells secreted significantly higher levels of VEGF and bFGF than did MSCs. Culture supernatants of PB monocytes cultured with MSCs contained significantly higher concentrations of VEGF, HGF, G-CSF, and GM-CSF than did the supernatants from cultures without MSCs. Quantitative analysis of angiogenesis at 14 days after implantation demonstrated that neovascularization of the implants containing SVF CD14+ cells or PB monocytes previously co-cultured with MSCs was 3.5 or 2 times higher than that observed in the implants with SVF-derived MSCs. Moreover, immunofluorescence of Matrigel sections revealed that SVF CD14 + cells differentiated into endothelial cells and contributed to vascular endothelium. Conclusions: The results from this study suggest that adipose tissue-resident monocytes should contribute to tissue vascularization. Because SVF CD14+ cells were more efficient in inducing angiogenesis than SVF-derived MSCs, and differentiated into vascular endothelial cells, they may constitute a new cell source for cell-based therapeutic angiogenesis. © 2014 Navarro et al.; licensee BioMed Central Ltd.


Jantus-Lewintre E.,Fundacion para la Investigacion del Hospital General Universitario | Sanmartin E.,Fundacion para la Investigacion del Hospital General Universitario | Sirera R.,Fundacion para la Investigacion del Hospital General Universitario | Sirera R.,Polytechnic University of Valencia | And 6 more authors.
Lung Cancer | Year: 2011

Introduction: The vascular endothelial growth factor (VEGF) family of ligands and receptors (VEGFR) play an important role in tumor angiogenesis. Increased expression of angiogenic factors in tumors or in blood is associated with poor prognosis. The aim of this study was to investigate the role of VEGF-A and soluble VEGFR-2 (sVEGFR-2) as biomarkers in advanced non-small-cell lung cancer (NSCLC). Methods: We studied 432 patients with advanced NSCLC (stages IIIB-IV) treated with cisplatin and docetaxel and 89 healthy age-matched controls. Blood samples were collected before chemotherapy, and VEGF-A and sVEGFR-2 levels were determined by ELISA. Results: VEGF-A and sVEGFR-2 levels were higher in NSCLC patients than in the controls, but VEGF-A behaves as a better diagnostic biomarker. There were no significant associations between VEGF-A and sVEGFR-2 concentrations and clinical characteristics, such as ECOG-PS, gender, stage, histology, metastases, and treatment response. A patient subgroup characterized by a combination of high VEGF-A and low sVEGFR-2 levels exhibited the worst patient prognoses in terms of TTP and OS. Conclusions: VEGF-A and sVEGFR-2 levels were significantly higher in patients than in the controls. A combination of VEGF-A and sVEGFR-2 can be used as an independent prognostic biomarker in advanced NSCLC. © 2011 Elsevier Ireland Ltd.


Morales-Carpi C.,Agencia Valenciana de Salud | Morales-Carpi C.,Consorcio Hospital General Universitario Of Valencia | Estan L.,University of Valencia | Rubio E.,University of Valencia | And 3 more authors.
European Journal of Clinical Pharmacology | Year: 2010

Objective To describe the use of medicines and to determine the frequency of off-label use in emergency room paediatric patients. Patients and methods A prospective, observational and descriptive study was carried out in the setting of the paediatric emergency room of a Spanish general hospital. Medicines used by children <14 years prior to their emergency room visit were analysed based on information collected from parents/guardians and relatives for each drug prescription. Off-label use was defined as the utilization of a drug at an indication, dosage, frequency or route of administration that differed from the specifications in the Summary of Product Characteristics or by children outside the authorized age group. Results The patient cohort comprised 462 children, among whom 336 children had been prescribed 667 prescriptions. Of the medicines prescribed, 90% fell into only five 5 Anatomical Therapeutic Chemical Classification System groups. The most frequent active principles were ibuprofen and paracetamol. Of a total of 152 different formulations recorded, no paediatric information was provided for 40 formulations, and one formulation was contraindicated in children. Based on the established criteria, 338 prescriptions were off-label: no paediatric information or contraindication in children were available (82 prescriptions); the drug was used for an indication different from the authorized one (111 prescriptions); drug use was inconsistent with age recommendations (16 prescriptions); drug use was inconsistent with dose/frequency (129 prescriptions). Of the 152 formulations, 107 were occasionally used in an off-label manner. Conclusions Although the mean number of drugs used in children is small, off-label use is frequent. Research efforts should target paediatric studies that allow a rational drug use in children. © Springer-Verlag 2009.


Izquierdo M.,Hospital Clinic Universitari | Ruiz-Granell R.,Hospital Clinic Universitari | Ferrero A.,Hospital Clinic Universitari | Martinez A.,Hospital Clinic Universitari | And 5 more authors.
Europace | Year: 2012

AimsElectrical storm (ES) is a life-threatening condition that predicts bad prognosis. Treatment includes antiarrhythmic drugs (AAD) and catheter ablation (CA). The present study aims to retrospectively compare prognosis in terms of survival and ES recurrence in 52 consecutive patients experiencing a first ES episode.Methods and resultsPatients were admitted from 1995 to 2011 and treated for ES by conservative therapy (pharmacological, 29 patients) or by CA (23 patients), according to the physician's preference and time of occurrence, i.e. conservative treatments were more frequently administered during the first years of the study, as catheter ablation became more frequent as the years passed by. After a median follow-up of 28 months, no differences either in survival (32 vs. 29 P 0.8) or in ES recurrence (38 in ablated vs. 57 in non-ablated patients, P 0.29) were observed between groups. Low left ventricle ejection fraction (LVEF) was the only variable associated with ES recurrence in ablated patients. When including patients with LVEF > 25, ES recurrence was significantly lower in ablated patients (24 months estimated risk of ES recurrence was 21 vs. 62 in ablated and non-ablated patients, respectively); however, no benefit in survival was observed.ConclusionOur data suggest that in most patients, especially those with an LVEF > 25, catheter ablation following a first ES episode, decreases the risk of ES recurrence, without increasing survival. © 2012 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2012. For permissions please email: journals.permissionsoup.com.


Milara J.,Consorcio Hospital General Universitario | Milara J.,Polytechnic University of Valencia | Milara J.,General Hospital of Valencia | Peiro T.,General Hospital of Valencia | And 7 more authors.
Thorax | Year: 2013

Background: Cigarette smoking contributes to lung remodelling in chronic obstructive pulmonary disease (COPD). As part of remodelling, peribronchiolar fibrosis is observed in the small airways of patients with COPD and contributes to airway obstruction. Epithelial to mesenchymal transition (EMT) appears to be involved in the formation of peribronchiolar fibrosis. This study examines the EMT process in human bronchial epithelial cells (HBECs) from non-smokers, smokers and patients with COPD as well as the in vitro effect of cigarette smoke extract (CSE) on EMT. Methods: HBECs from non-smokers (n=5), smokers (n=12) and patients with COPD (n=15) were collected to measure the mesenchymal markers α-smooth muscle actin, vimentin and collagen type I and the epithelial markers E-cadherin, ZO-1 and cytokeratin 5 and 18 by real time-PCR and protein array. In vitro differentiated bronchial epithelial cells were stimulated with CSE. Results: Mesenchymal markers were upregulated in HBECs of smokers and patients with COPD compared with non-smokers. In contrast, epithelial cell markers were downregulated. In vitro differentiated HBECs underwent EMT after 72 h of CSE exposure through the activation of intracellular reactive oxygen species, the release and autocrine action of transforming growth factor β1, the phosphorylation of ERK1/2 and Smad3 and by the downregulation of cyclic monophosphate. Conclusions: The EMT process is present in bronchial epithelial cells of the small bronchi of smokers and patients with COPD and is activated by cigarette smoke in vitro.


Roig J.V.,Consorcio Hospital General Universitario | Cantos M.,Consorcio Hospital General Universitario | Balciscueta Z.,Hospital Universitario Arnau Of Vilanova | Uribe N.,Hospital Universitario Arnau Of Vilanova | And 5 more authors.
Colorectal Disease | Year: 2011

Aim The study evaluated the rate of reversal of Hartmann's operation after the initial surgery and its morbidity. Method A multicentre retrospective study was carried out in seven hospitals in the Valencia area of patients who underwent Hartmann's operation from 2004 to 2008. The incidence of reversal was determined. Results Four hundred and fifty-two patients of mean age 67.5±15.4years were included, of whom 78.8% had an emergency operation. The most common diagnosis was cancer (58.6%), although diverticulitis predominated in the emergency setting. At a median follow up of 44months, 159 (35.2%) patients had undergone reversal, including 16.6% after elective surgery and 40.4% after an emergency Hartmann's procedure (P<0.001). The most frequent reason why reversal was not done was death (74 [25%] patients). Patients undergoing reversal were younger and had a low ASA risk. Trauma was associated with a higher rate of reversal, followed by diverticular disease. Surgery was performed at a median of 10months. An open approach with stapled anastomosis was used in most cases. The mortality was 3.5%. Complications occurred in 45.2%, with a 6.2% rate of anastomotic leakage. Complications were associated with age, diabetes mellitus, arteriosclerosis, obesity, smoking, chemotherapy and COPD. Conclusion Hartmann's reversal was performed in a small percentage of patients, mostly including those with benign disease. It had a significant morbidity. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.


Gumbau V.,Consorcio Hospital General Universitario | Bruna M.,Consorcio Hospital General Universitario | Canelles E.,Consorcio Hospital General Universitario | Guaita M.,Consorcio Hospital General Universitario | And 7 more authors.
Obesity Surgery | Year: 2014

Different hormones and peptides involved in inflammation have been studied in and related to obesity. The aim of our work is to assess the variations of different molecules related to inflammation in obese patients during the first year following sleeve gastrectomy. This was a prospective study on patients who underwent sleeve gastrectomy. The variations in different clinical, anthropometric, and analytical parameters related to inflammation were determined and analysed in all patients at the preoperative visit and at the first and fifth days, first and sixth months, and 1 year following surgery. We enrolled 20 patients to the study. The median body mass index (BMI) before intervention was 48.5 kg/m2. With respect to comorbidities, 70 % of the patients had obstructive sleep apnoea syndrome (OSA), 65 % high blood pressure, 45 % dyslipidaemia, and 40 % diabetes mellitus (DM). The median percentage of BMI lost (%BMIL) 1 year after the intervention was 71 %. The dyslipidaemia healing or improvement rate was 100 %, whereas it was 87.5 % for diabetes, 84.6 % for hypertension, and 57.1 % for OSA. During the 1-year postintervention period, the average levels of adiponectin increased, although not significantly, whereas those of leptin significantly decreased. In addition, the blood levels of MCP-1, IL-6, CRP, ferritin, and PAI-1 significantly decreased in that period. Sleeve gastrectomy is a surgical technique that is associated with improvements in body weight and comorbid conditions from the first postoperative months, which lead to significant variations in the levels of different inflammation-related parameters and a decrease in the levels of leptin, IL-6, CRP, MCP-1, ferritin, and serpin (PAI-1). © 2014 Springer Science+Business Media New York.


Escutia B.,Hospital Universitario La Paz | Ledesma E.,Instituto Valenciano Of Oncology | Serra-Guillen C.,Instituto Valenciano Of Oncology | Gimeno C.,Consorcio Hospital General Universitario | And 3 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2011

Background: Human papilloma virus (HPV) is increasingly recognized as an important human carcinogen but its role in the aetiopathogenesis of basal cell carcinoma (BCC) in immunocompetent individuals is unclear. Objective: A prospective case-control study was designed to compare the prevalence of HPV in BCC and normal skin samples from immunocompetent subjects and to assess the influence of different clinical features on the risk of cutaneous HPV. Methods: A total of 142 samples from 70 BCC cases (superficial BCC 38 and nodular BCC 32) and 72 controls were analysed by a degenerated nested PCR technique. Clinical data were recorded and risk factors for HPV infection were assessed by multivariate analysis. Results: There were 31 HPV DNA-positive samples. HPV was detected more frequently in cases (25.7%) than in controls (18.1%) and in nodular (31.3%) than in superficial (21.1%) BCC lesions but differences were not statistically significant. Older age (OR 1.5; 95% CI: 1.02-1.09) and actinic keratosis (OR 2.62; 95% CI 1.15-5.96) were the only significant factors associated to the presence of HPV. Risk of HPV positivity was also higher in blond-haired subjects, fair/pale skin colour, history of sunburn, solar lentigines and seborrheic keratosis but the differences were not significant. Both in cases and controls, b -types were the most frequent. Conclusions: HPV does not seem to play a fundamental role in the aetiopathogenesis of either nodular or superficial BCC. The presence of HPV appears to be more related to actinic damage and possibly to an alteration of the barrier function associated with ageing. © 2010 The Authors Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.


Garcia-Rabasco A.,Consorcio Hospital General Universitario | Sanchez-Carazo J.L.,Consorcio Hospital General Universitario | Esteve A.,Consorcio Hospital General Universitario
Actas Dermo-Sifiliograficas | Year: 2010

The introduction of tumor necrosis factor (TNF) beta blockers has make it possible to obtain a significant advance in the control and knowledge of some inflammatory diseases, among them psoriasis. TNF is a cytokine that plays a key role in the control of infections and neoplasms. The increase of the risk of developing a neoplasm during the use of this group of drugs is one of the more debated adverse effects in the literature. We present the clinical case of one patient with long-course psoriasis who developed a breast adenocarcinoma after initiating treatment with etanercept. In this article, we provide a brief review on the possible associations existing between the use of anti-TNF therapy and the risk of the appearance of come neoplasms, among which leukemias, lymphomas and some solid tumors stand out. © 2010 Elsevier España, y AEDV.


Llagunes J.,Consorcio Hospital General Universitario
Revista española de anestesiología y reanimación | Year: 2011

We report a case of late-onset postpartum sepsis from endometritis due to group A streptococci (GAS) in a 37-year-old white woman. The patient developed septic shock, with mitral regurgitation and cardiac dysfunction. Early treatment with broad-spectrum antibiotics and hemodynamic support was essential for a favorable outcome. Because of the resurgence of virulent strains of GAS that can cause fatal infections, these pathogens should be included in the differential diagnosis of postpartum infections in the mother. Although cardiac dysfunction is rare in association with GAS infection, it should be ruled out by echocardiography when the condition of a patient with sepsis does not improve.

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