Julia-Serda G.,Hospital Universitario Dr Negrin |
Cabrera-Navarro P.,Hospital Universitario Dr Negrin |
Acosta-Fernandez O.,Hospital Nuestra Senora de la Candelaria |
Martin-Perez P.,Hospital Universitario Dr Negrin |
And 4 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2011
OBJECTIVE: To evaluate the prevalence of and risk factors for asthma and related conditions in the Canaries, Spain. METHODS: From a randomised sample of 9506 adults aged 20-44 years who answered a short questionnaire, a random sample corresponding to 20% of the original was taken. Subjects classified as symptomatic in the previous survey and who were not included in the random sample were also invited to participate. The subjects completed a respiratory questionnaire, and underwent spirom etry, bronchial hyperresponsiveness (BHR) test, skin tests and immunoglobulin E (IgE) measurements. RESULTS: The random sample included 593 subjects. The prevalence of skin sensitisation to mites was 30.3% (95%CI 26.7-34.2) and the prevalence of IgE to mites 30.5% (95%CI 26.2-35.2). A prevalence of 40.6% (95%CI 35.9-45.5) was found for atopy, 14.1% (95%CI 11.1-17.1) for BHR and 4.2% (95%CI, 2.5-5.9) for asthma. The risk factors most strongly associated with asthma were atopy (OR 4.89, 95%CI 3.07-7.78) and respiratory infection before the age of 5 years (OR 2.78, 95%CI 1.66-4.67). CONCLUSION: This study shows a high prevalence of sensitisation to mites, atopy, BHR and asthma in the Canaries, similar to that observed in English-speaking countries. We suggest that these findings could partially result from climatic conditions. © 2011 The Union. Source
Castellano D.,Hospital Universitario 12 Of Octubre |
Virizuela J.A.,Hospital Universitario Virgen Of La Macarena |
Cruz J.,Hospital Nuestra Senora de la Candelaria |
Sepulveda J.M.,Hospital Universitario 12 Of Octubre |
And 2 more authors.
Cancer and Metastasis Reviews | Year: 2012
Pharmacogenomics is the study of how variation in the genetic background affects an individual's response to a specific drug and/or its metabolism. Using knowledge about the genes which produce the enzymes that metabolize a specific drug, a physician may decide to raise or lower the dose, or even change to a different drug. Targeted therapy with tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors has led to a substantial improvement in the standard of care for patients with advanced or metastatic renal cell carcinoma (RCC). Although few studies have identified biomarkers that predict the response of targeted drugs in the treatment of metastatic RCC, some associations have been found. Several studies have identified genetic polymorphisms with implications in the pharmacokinetics and/or pharmacodynamics of TKIs and mTOR inhibitors and which are associated with a prolonged progression-free survival and/or overall survival in patients with metastatic RCC. Among the genes of interest, we should consider IL8, FGFR2, VEGFA, FLT4, and NR1I2. In this review, we discuss single nucleotide polymorphisms (SNPs) associated with outcome and toxicity following targeted therapies and provide recommendations for future trials to facilitate the use of SNPs in personalized therapy for this disease. © 2012 Springer Science+Business Media, LLC. Source
Garin I.,Endocrinology and Diabetes Research Group |
Garin I.,Institute Salud Carlos III |
Edghill E.L.,University of Exeter |
Akerman I.,Institute Salud Carlos III |
And 48 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010
Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes. These dominantly acting mutations prevent normal folding of proinsulin, which leads to beta-cell death through endoplasmic reticulum stress and apoptosis. We now report 10 different recessive INS mutations in 15 probands with neonatal diabetes. Functional studies showed that recessive mutations resulted in diabetes because of decreased insulin biosynthesis through distinct mechanisms, including gene deletion, lack of the translation initiation signal, andalteredmRNAstability because of the disruption of a polyadenylation signal. A subset of recessive mutations caused abnormal INS transcription, including the deletion of the C1 and E1 cis regulatory elements, or three different single base-pair substitutions in a CC dinucleotide sequence located between E1 and A1 elements. In keeping with an earlier and more severe beta-cell defect, patients with recessive INS mutations had a lower birth weight (-3.2 SD score vs.-2.0 SD score) and were diagnosed earlier (median 1 week vs. 10 weeks) compared to those with dominant INS mutations. Mutations in the insulin gene can therefore result in neonatal diabetes as a result of two contrasting pathogenic mechanisms. Moreover, the recessively inherited mutations provide a genetic demonstration of the essential role of multiple sequence elements that regulate the biosynthesis of insulin in man. Source
Marin J.M.,Hospital Universitario Miguel Servet |
Alfageme I.,University of Seville |
Almagro P.,Hospital Universitari Mutua Of Terrassa |
Casanova C.,Hospital Nuestra Senora de la Candelaria |
And 6 more authors.
European Respiratory Journal | Year: 2013
Guidelines recommend defining chronic obstructive pulmonary disease (COPD) by airflow obstruction and other factors, but no studies have evaluated the ability of existing multicomponent indices to predict mortality up to 10 years. We conducted a patient-based pooled analysis. Survival analysis and C statistics were used to determine the best COPD index/indices according to several construct variables and by varying time-points. Individual data of 3633 patients from 11 COPD cohorts were collected, totalling the experience of 15 878 person-years. Overall, there were 1245 death events within our cohorts, with a Kaplan'Meier survival of 0.963 at 6 months, which was reduced to 0.432 at 10 years. In all patients, ADO (age, dyspnoea and forced expiratory volume in 1 s), BODE (body mass index, airflow obstruction, dyspnoea and exercise capacity) and e-BODE (BODE plus exacerbations) were the best indices to predict 6-month mortality. The ADO index was the best to predict 12-month (C statistic 0.702), 5-year (C statistic 0.695) and 10-year mortality (C statistic 0.698), and was significantly better than BODE (all p<0.05). The best indices to predict death by C statistics when adjusting by age were e-BODE, BODEx (substitution of exacerbations for exercise capacity) and BODE. No index predicts short-term survival of COPD well. All BODE modifications scored better than ADO after age adjustment. The ADO and BODE indices are overall the most valid multicomponent indices to predict time to death in all COPD patients. Copyright © ERS 2013. Source
Nugent D.J.,Childrens Hospital of Orange County CHOC |
Ashley C.,Alabama Clinical Therapeutics LLC |
Garcia-Talavera J.,Hospital Nuestra Senora de la Candelaria |
Lo L.C.,California Pacific Medical Center |
And 2 more authors.
Haemophilia | Year: 2015
Congenital factor XIII (FXIII) deficiency is a rare condition with substantial risk for life-threatening bleeding. Replacement of deficient FXIII with plasma-derived FXIII concentrate is a treatment option. The current 12-week study evaluated the steady-state pharmacokinetic (PK) and safety profile of prophylactic infusions of FXIII concentrate (human) in patients with congenital FXIII deficiency. Patients received FXIII concentrate (human) 40 IU kg-1 on Days 0, 28, and 56. FXIII levels were assessed before and after each infusion; steady-state PK parameters were assessed up to 28 days after the infusion on Day 56. Treatment effectiveness in maintaining trough FXIII activity levels ≥5% over 28 days and safety parameters were also assessed. Fourteen patients received FXIII concentrate (human) and 13 completed the study. Post-infusion, FXIII activity levels increased to within the range found in patients without congenital FXIII deficiency without reaching supra-therapeutic levels. Non-baseline-adjusted trough FXIII activity levels were maintained at or above 10% at all post-baseline visits in all patients. Steady-state PK parameters were baseline-adjusted; maximum FXIII activity was 87.7% at 1.72 h post-infusion, subsequently declining to a minimum of 5.0%. The half-life was 6.6 days. FXIII concentrate (human) was generally well tolerated. Two patients had possibly treatment-related adverse events. There were no reports of thromboembolism, viral transmission, bleeding events or treatment-related hypersensitivity. These findings support use of FXIII concentrate (human) 40 IU kg-1 every 28 days as an appropriate regimen for routine, long-term prophylaxis in children and adults with congenital FXIII deficiency. Clinical trial registration: www.clinicaltrials.gov/ct2/show/NCT00883090. © 2014 John Wiley & Sons Ltd. Source