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Arango C.,Hospital General Universitario Gregorio Maranon | Giraldez M.,Hospital General Universitario Gregorio Maranon | Merchan-Naranjo J.,Hospital General Universitario Gregorio Maranon | Baeza I.,University of Barcelona | And 10 more authors.
Journal of the American Academy of Child and Adolescent Psychiatry | Year: 2014

Objective: To assess weight and metabolic effects of 6 months of treatment with secondgeneration antipsychotics in naïve/quasi-naïve youths. Method: This study looked at a nonrandomized, naturalistic, multicenter, inception cohort study of 279 patients aged 4 to 17 years (mean = 14.6 ± 2.9 years). Of those, 248 (88.8%) received a single antipsychotic (risperidone, olanzapine, or quetiapine) and completed 2 visits, and 178 (63.8%) completed the 6-month follow-up. Patients had schizophrenia-spectrum disorders (44.5%), mood-spectrum disorders (23.2%), disruptive behavioral disorders (17.3%), or other disorders (15.1%). Fifteen age- and gender-matched, healthy, nonmedicated individuals served as a comparison group. Results: From baseline to 1 month, 3 months, and 6 months, all anthropometric measures increased significantly with each antipsychotic, that is, 6-month changes with risperidone (n = 157; 7.1 kg and 0.66 body mass index [BMI] z score), olanzapine (n = 44; 11.5 kg and 1.08 BMI z score), and quetiapine (n = 47; 6.3 kg and 0.54 BMI z score), but not in healthy control participants (-0.11 kg and 0.006 BMI z score). Fasting metabolic parameters increased significantly with risperidone (glucose [3.8] mg/dL, insulin [4.9] mU/L, homeostasis model assessment of insulin resistance [HOMA-IR: 1.2], triglycerides [15.6] mg/dL), and olanzapine (glucose [5.0] mg/dL, total cholesterol [21.2] mg/dL, and low-density lipoprotein cholesterol [44.6] mg/dL), but not with quetiapine or in healthy control participants. The percentage of research participants considered to be "at risk of adverse health outcome" increased during the 6 months from 8.9% to 29.2% for risperidone (p <.0001), 6.8% to 38.1% for olanzapine (p <.0001), and 6.3% to 4.0% for quetiapine (p =.91). Conclusion: Olanzapine, quetiapine, and risperidone increase body weight but have different cardiometabolic side effect profiles and different temporal side effect patterns. © 2014 American Academy of Child and Adolescent Psychiatry. Source

Ramirez M.,Hospital Universitario Nino Jesus
Discovery medicine | Year: 2010

Metastatic neuroblastoma (NB) remains a clinical challenge for pediatric oncologists. Overall survival rates stay less than 40% despite intensive multimodal therapy, with the toll of toxicity being related to high-dose chemotherapy. These rates have shown minor improvements over the last years, and the development of newer therapeutic strategies is necessary. Oncolytic viruses bear the promise of killing cancer cells with low toxicities to healthy tissues. Acting through mechanisms different from chemo- and radiotherapies, a growing arsenal of genetically engineered viruses is being tested in preclinical models of human cancers. Viral infection and selective replication inside tumor cells are achieved by modification of the virus genome in order to target specific molecules or signal transduction pathways of cancer. Cell death may also activate antitumor immune responses to further amplify the beneficial effects. Clinical trials in humans have been conducted and initial results have been reported, giving the first glance of information on safety and efficacy in patients. In this review we will summarize information about how oncolytic virotherapy is being evaluated against NB in preclinical models and recent reports on the use of this new therapy in sporadic cases of children with refractory NB. Source

Garulo D.C.,Hospital Universitario Nino Jesus
Pediatria Integral | Year: 2013

Connective tissue diseases are a heterogeneous group of disorders caused by the development of autoantibodies or autoreactive T cells against differen body structures. They are characterized by multi-system involvement without apparent cause, with variables signs and symptoms that may appear simultaneously or in the course of several weeks and months. The presence of constitutional symptoms associated to certain clinical features (malar rash, Raynaud́s phenomenon, Gottrońs rash, sclerodactyly) should alert of a connective tissue disease. It is common to find anti-nuclear and other autoantibodies and helps to confirm the diagnosis. Though rare in childhood, early recognition is important to initiate appropriate treatment to achieve the control of the disease an improve the long term outcome of these patients. Source

Sainz T.,Hosp General Universitario Gregorio Maranon | Sainz T.,Hospital General Universitario Gregorio Maranon | Alvarez-Fuente M.,Hospital General Universitario Gregorio Maranon | Navarro M.L.,Hospital General Universitario Gregorio Maranon | And 10 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2014

Background: HIV-infected adults display increased cardiovascular disease, probably driven by inflammation and immune activation. These relationships have not been addressed in vertically HIVinfected children and adolescents, a population at very high risk for long-term non-AIDS complications. Methods: Carotid intima media thickness (IMT) was measured in a cohort of HIV-infected children and adolescents and healthy controls. C-reactive protein and markers of immune activation (CD38+HLA-DR+) and immune senescence (CD282CD57+) were determined. Results: One hundred fifty HIV-infected patients and 150 controls were included, 64.8% female. IMT was thicker in HIV-infected patients (0.434 mm 6 0.025 vs. 0.424 mm 6 0.018, P , 0.001). After adjustment by age, sex, body mass index, and smoking status, HIV infection was independently associated with thicker IMT (odds ratio, 2.28; 95% confidence interval: 1.25 to 4.13; P = 0.007). Among HIV-related variables, a low CD4 nadir was related to an increased IMT. Although HIV-infected subjects presented higher frequencies of activated CD4+ and CD8+ T cells (P = 0.002 and P = 0.087, respectively), no relation was found between IMT and inflammation, immune activation, or senescence. Conclusions: Structural changes of the vasculature present early in vertically HIV-infected subjects as well as immune activation and senescence. These patients should be carefully monitored for the prompt detection and early treatment of cardiovascular disease. Copyright © 2013 by Lippincott Williams & Wilkins. Source

Lopez E.,Hospital Universitario Nino Jesus | Cho W.C.S.,Queen Elizabeth Hospital
International Journal of Molecular Sciences | Year: 2012

Massive evidence suggests that genetic abnormalities contribute to the development of lung cancer. These molecular abnormalities may serve as diagnostic, prognostic and predictive biomarkers for this deadly disease. It is imperative to search these biomarkers in different tumorigenesis pathways so as to provide the most appropriate therapy for each individual patient with lung malignancy. Phosphoproteomics is a promising technology for the identification of biomarkers and novel therapeutic targets for cancer. Thousands of proteins interact via physical and chemical association. Moreover, some proteins can covalently modify other proteins post-translationally. These post-translational modifications ultimately give rise to the emergent functions of cells in sequence, space and time. Phosphoproteomics clinical researches imply the comprehensive analysis of the proteins that are expressed in cells or tissues and can be employed at different stages. In addition, understanding the functions of phosphorylated proteins requires the study of proteomes as linked systems rather than collections of individual protein molecules. In fact, proteomics approaches coupled with affinity chromatography strategies followed by mass spectrometry have been used to elucidate relevant biological questions. This article will discuss the relevant clues of post-translational modifications, phosphorylated proteins, and useful proteomics approaches to identify molecular cancer signatures. The recent progress in phosphoproteomics research in lung cancer will be also discussed. © 2012 by the authors; licensee MDPI, Basel, Switzerland. Source

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