J Sastre

Fundación Jiménez Díaz, Madrid, Madrid, Spain

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Publications (278)1625.02 Total impact

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    ABSTRACT: Shrimp are highly allergenic foods. Current management are limited to the avoidance of foods. Therefore, there is an unmet need for a safe and effective therapy using modified allergens. This study focuses on assessing the potential for modification of the allergenicity of shrimp proteins following heat treatment or simulated gastric digestion. Shrimp proteins do not reduce their IgE reactivity after heat treatment but it is reduced by simulated gastric digestion in a time- and dose-dependent manner. Tropomyosin in shrimp extract is worse digested than purified tropomyosin. After 60min of 10U/μg pepsin digestion, a strong inhibition was produced in the in vivo skin reactivity of shrimp extracts and in activation of basophils from allergic patients. Immunisation experiments performed in rabbits demonstrated that digested boiled shrimp extract is able to induce IgG antibodies that block the IgE binding to the untreated boiled shrimp extract in shrimp-allergic patients. Building on our observations, digestion treatment could be an effective method for reducing shrimp allergenicity while maintaining the immunogenicity. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Food Chemistry 04/2015; 173:475-81. DOI:10.1016/j.foodchem.2014.10.063 · 3.26 Impact Factor
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    ABSTRACT: The diagnosis of shellfish allergy remains a challenge for clinicians. Several shellfish allergens have been characterized and their IgE epitopes identified. However, the clinical relevance of this sensitization is still not clear. The objective of this study was to identify allergens and epitopes associated with clinical reactivity to shrimp. Shrimp-sensitized subjects were recruited and grouped based on the history of shrimp-allergic reactions and challenge outcome. IgE reactivity to recombinant crustacean allergens, and IgE and IgG4 reactivity to peptides were determined. Subjects sensitized to dust mites and/or cockroach without shrimp sensitization or reported allergic reactions, as well as nonatopic individuals, were used as controls. A total of 86 subjects were recruited with a skin prick test to shrimp; 74 reported shrimp-allergic reactions, 58 were allergic (38 positive double-blind placebo-controlled food challenge and 20 recent anaphylaxis), and 16 were tolerant. All subjects without a history of reactions had negative challenges. The individuals with a positive challenge more frequently recognized tropomyosin and sarcoplasmic calcium-binding proteins than those found tolerant by the challenge. Especially a sarcoplasmic-calcium-binding-protein positive test is very likely to result in a positive challenge, though the frequency of recognition is low. Subjects with dust mite and/or cockroach allergy not sensitized to shrimp recognized arginine kinase and hemocyanin. Several epitopes of these allergens may be important in predicting clinical reactivity. Tropomyosin and sarcoplasmic-calcium-binding-protein sensitization is associated with clinical reactivity to shrimp. Myosin light chain testing may help in the diagnosis of clinical reactivity. Arginine kinase and hemocyanin appear to be cross-reacting allergens between shrimp and arthropods. Detection of IgE to these allergens and some of their epitopes may be better diagnostic tools in the routine workup of shrimp allergy. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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    ABSTRACT: Abstract Diisocyanates are the most common cause of occupational asthma, but risk factors are not well defined. A case-control study was conducted to investigate whether genetic variants in inflammatory response genes (TNFα, IL1α, IL1β, IL1RN, IL10, TGFB1, ADAM33, ALOX-5, PTGS1, PTGS2 and NAG-1/GDF15) are associated with increased susceptibility to diisocyanate asthma (DA). These genes were selected based on their role in asthmatic inflammatory processes and previously reported associations with asthma phenotypes. The main study population consisted of 237 Caucasian French Canadians from among a larger sample of 280 diisocyanate-exposed workers in two groups: workers with specific inhalation challenge (SIC) confirmed DA (DA(+), n = 95) and asymptomatic exposed workers (AW, n = 142). Genotyping was performed on genomic DNA, using a 5' nuclease PCR assay. After adjusting for potentially confounding variables of age, smoking status and duration of exposure, the PTGS1 rs5788 and TGFB1 rs1800469 single nucleotide polymorphisms (SNP) showed a protective effect under a dominant model (OR = 0.38; 95% CI = 0.17, 0.89 and OR = 0.38; 95% CI = 0.18, 0.74, respectively) while the TNFα rs1800629 SNP was associated with an increased risk of DA (OR = 2.08; 95% CI = 1.03, 4.17). Additionally, the PTGS2 rs20417 variant showed an association with increased risk of DA in a recessive genetic model (OR = 6.40; 95% CI = 1.06, 38.75). These results suggest that genetic variations in TNFα, TGFB1, PTGS1 and PTGS2 genes contribute to DA susceptibility.
    Journal of Immunotoxicology 02/2015; DOI:10.3109/1547691X.2015.1017061 · 1.91 Impact Factor
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    ABSTRACT: The aim of the study was to investigate if adverse drug reactions (ADRs) during immunotherapy with a grass extract (AVANZ® Phleum, ALK-Abelló) are related to the different patterns of sensitization of patients to grass allergens.192 patients with rhinitis and/or asthma sensitized to grass pollen received a 4-week up-dosing with 5-injections. ADRs were evaluated following EAACI guidelines. A total of 432 ADRs in 133 (69%) patients were recorded, 64% local and 31% systemic. There was a significant association of the number of grass allergens sensitized by the patients and the total number of ADRs (p=0.004) occurred locally (p=0.003) and systemically (p=0.01) Sensitization to Phl p1+ Phl p5 or Phl p1+ Phl p5+ Phl p12 was significantly associated with a higher frequency of local or systemic reactions (p=0.001,both).Different patterns of sensitization to grass allergens may potentially be considered a risk marker to the development of ADRs to immunotherapy.This article is protected by copyright. All rights reserved.
    Allergy 01/2015; DOI:10.1111/all.12575 · 6.00 Impact Factor
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    ABSTRACT: Eosinophils secrete several granules that are involved in the propagation of inflammatory responses in patients with pathologies such as asthma. We hypothesized that some of these granules are exosomes, which, when transferred to the recipient cells, could modulate asthma progression. Eosinophils were purified from peripheral blood and cultured with or without IFN-γ or eotaxin. Multivesicular bodies (MVBs) in eosinophils were studied by using fluorescence microscopy, transmission electron microscopy (TEM), and flow cytometry. Exosome secretion was measured and exosome characterization was performed with TEM, Western blotting, and NanoSight analysis. Generation of MVBs in eosinophils was confirmed by using fluorescence microscopy and flow cytometry and corroborated by means of TEM. Having established that eosinophils contain MVBs, our aim was to demonstrate that eosinophils secrete exosomes. To do this, we purified exosomes from culture medium of eosinophils and characterized them. Using Western blot analysis, we demonstrated that eosinophils secreted exosomes and that the discharge of exosomes to extracellular media increases after IFN-γ stimulation. We measured exosome size and quantified exosome production from healthy and asthmatic subjects using nanotracking analysis. We found that exosome production was augmented in asthmatic patients. Our findings are the first to demonstrate that eosinophils contain functional MVBs and secrete exosomes and that their secretion is increased in asthmatic patients. Thus exosomes might play an important role in the progression of asthma and eventually be considered a biomarker. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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    ABSTRACT: Fluticasone propionate and formoterol fumarate have been combined in a single inhaler (fluticasone/formoterol; flutiform(®)) for the maintenance treatment of asthma. This pooled analysis assessed the efficacy of fluticasone/formoterol versus fluticasone in patients who previously received inhaled corticosteroids. Data were pooled from five randomised studies in patients with asthma (aged ≥12 years) treated for 8 or 12 weeks with fluticasone/formoterol (100/10, 250/10 or 500/20 μg b.i.d.; n = 528 delivered via pMDI) or fluticasone alone (100, 250 or 500 μg b.i.d.; n = 527). Fluticasone/formoterol provided significantly greater increases than fluticasone alone in mean morning forced expiratory volume in 1 second (FEV1) from pre-dose at baseline to 2 hours post-dose at study end (least-squares mean [LSM] treatment difference: 0.146L; p < 0.001) and in pre-dose FEV1 from baseline to study end (LSM treatment difference: 0.048 L; p = 0.043). Compared with fluticasone, fluticasone/formoterol provided greater increases in the percentage of asthma control days (no symptoms, no rescue medication use and no sleep disturbance due to asthma) from baseline to study end (LSM treatment difference: 8.6%; p < 0.001), and was associated with a lower annualised rate of exacerbations (rate ratio: 0.71; p = 0.014). In summary, fluticasone/formoterol provides clinically significant improvements in lung function and asthma control measures, with a lower incidence of exacerbations than fluticasone alone. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Respiratory Medicine 12/2014; DOI:10.1016/j.rmed.2014.10.019 · 2.92 Impact Factor
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    ABSTRACT: To date, no studies have assessed nasal and bronchial response to diisocyanates during specific inhalation challenges (SIC). This study was performed to assess nasal response during SIC with diisocyanates (nasal and oral breathing) in patients with suspected occupational asthma due to these agents. Fourteen patients with suspected clinical history of diisocyanate-induced asthma were challenged with diisocynates in a 7m3 chamber. Nasal response testing during challenges was assessed by acoustic rhinometry, peak nasal inspiratory flow (PNIF), and visual analog scale (VAS), alongside bronchial responses. Eleven patients had a significant asthmatic response to diisocyanates. None reported clear work-related nasal symptoms. In patients with positive bronchial response to diisocyanates, nasal mean minimal cross-sectional area (MCA) decreased by 26.9%, nasal volume at 5 cm decreased by 33.5%, and PNIF decreased by 28.3%, all from baseline. A positive nasal response was elicited in 45%, 54%, and 45% of patients, respectively. A significant increase in VAS was observed in 4 patients. Three patients with negative bronchial response had a negative nasal response. SIC revealed an objective nasal response in around 50% of patients with occupational asthma due to diisocyanates, in spite of the fact that none of them reported work-related nasal symptoms. The clinical significance of this finding is a poor association between nasal symptoms at work and an objective nasal response during positive SIC with diisocyanates.
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    ABSTRACT: In spite of being an old disease and apparently easy to diagnose, chronic spontaneous urticaria (CSU) is still perceived as an uncontrollable and difficult to manage disease. The perception of the patient is that his/her condition is not well understood and that is suffering from a disorder with hidden causes that doctors are not able to tackle. Sometimes patients go through a number of clinicians until they found some CSU expert who is familiar with the disease. It is surprising that myths and believes with no scientific support still persist. Guidelines are not widely implemented and recent tools to assess severity are infrequently used. European and American recent guidelines do not agree in several key points related to diagnosis and treatment, which further contributes to confusion. With the aim to clarify some aspects of the CSU picture, a group of allergists and dermatologists from the Spanish Dermatology and Allergy societies developed a Frequent Asked Questions leaflet that could facilitate physicians work in daily practice and contribute to a better knowledge of common clinical scenarios related to patients with CSU. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical & Experimental Allergy 11/2014; DOI:10.1111/cea.12465 · 4.32 Impact Factor
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    ABSTRACT: Aim To assess the evolution of occupational asthma (OA) depending on whether the patient avoids or continues with exposure to the offending agent. Methods Study in patients diagnosed with OA using a specific inhalation challenge. Patients underwent the following examinations on the same day: clinical interview, physical examination, forced spirometry, methacholine test and determination of total IgE. Clinical improvement, deterioration or no change were defined according to the changes seen on the GINA severity scale at the time of diagnosis. Results Of the 73 patients finally included, 55 had totally ended exposure and 18 continued to be exposed at work. Clinical improvement was observed in 47% of those who had terminated exposure and in 22% of those who remained exposed; clinical deterioration was observed in 14% and 17% respectively (p = 0.805). Logistical regression analysis, including the type of agent and the persistence or avoidance of exposure among the variables, did not show any predictive factors of clinical evolution. Similarly, the changes in FEV1 and in bronchial hyperresponsiveness were not associated with the avoidance or continuation of exposure to the causative agent. Conclusions Avoiding exposure to the causative agent in patients with OA does not seem to improve prognosis in this disease. Despite these findings, there is insufficient evidence to recommend a change in current management guidelines.
    Respiratory Medicine 09/2014; 108(9). DOI:10.1016/j.rmed.2014.08.001 · 2.92 Impact Factor
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    ABSTRACT: Scope: Shrimp is a seafood consumed worldwide and the main cause of severe allergenic reactions to crustaceans. Seafood allergy has been related to mite sensitization, mainly mediated by tropomyosin, but other proteins could be involved. The aim of the study was to identify new shrimp allergens implicated in mite-seafood cross-reactivity (CR) in two different climate populations: dry and humid climates. Methods and results: Shrimp and mite IgE-binding profiles of patients from continental dry and humid climates were analyzed by immunoblotting, and the most frequently recognized Solenocera melantho shrimp proteins were identified by MS as alpha-actinin, beta-actin, fructose biphosphate aldolase, arginine kinase, sarcoplasmic calcium-binding protein, and ubiquitin. Using inhibition immunoblot assays, we demonstrate that tropomyosin and ubiquitin were responsible for mite-seafood CR from both climates; but also alpha-actinin and arginine kinase are implicated in dry-and humid-climate populations, respectively. Reciprocal inhibition assays demonstrated that mites are the primary sensitizer in humid-climate, as shrimp is in continental dry-climate population. Conclusion: Several new shrimp allergens have been identified and should be considered in the diagnosis and treatment of shrimp allergy and mite-seafood CR. Differences in mite-seafood CR were founded to be based on the climate.
    Molecular Nutrition & Food Research 09/2014; 58(9). DOI:10.1002/mnfr.201400122 · 4.91 Impact Factor
  • Gianna Moscato, Gianni Pala, Joaquin Sastre
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    ABSTRACT: Purpose of reviewOccupational allergy represents a substantial health, social, and financial burden for the society. Its management is a complex task that, in selected cases, may also include allergen-specific immunotherapy. The purpose of this article is to review clinical data on allergen immunotherapy and biological treatments applied to occupational allergy in 2013.Recent findingsImmunotherapy in occupational allergic diseases has been scarcely used, and only for a few sensitizers, such as latex, flour, and Hymenoptera venom, partly due to the lack of standardized extracts. The recent use of the molecular diagnosis can improve the indication and selection of suitable allergens for preparing new standardized and powerful extracts for immunotherapy. Some recent reports suggest a beneficial role of treatment with omalizumab in workers with occupational asthma who continue to be exposed to the causal agent.SummaryAlthough scarce, available data suggest that immunotherapy and biological treatments may allow allergic workers to continue their work activity, but further studies are needed to standardize extracts and to evaluate the cost-effectiveness of these treatments, when exposure at the workplace cannot be avoided.
    Current Opinion in Allergy and Clinical Immunology 08/2014; 14(6). DOI:10.1097/ACI.0000000000000105 · 3.40 Impact Factor
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    ABSTRACT: The most frequent pet allergy is allergy to cat and dog, but in recent years, it has become increasingly popular to have other pets, and the risk of exposure to new allergens is increasing. The list of new pets includes hamsters, and one of the most popular hamster is the Siberian hamster (Phodopus sungorus). The aim of this study was the characterization and cloning of the major allergen from this hamster. The study of its allergenicity and cross-reactivity could improve specific diagnosis and treatment for hamster-allergic patients. Thirteen Siberian hamster-allergic patients were recruited at the outpatient clinic. Protein extracts were prepared from the hair, urine and salivary glands of 4 hamster species (European, golden, Siberian and Roborovski). IgE-binding proteins were detected by immunobloting and identified by mass spectrometry. The recombinant protein was produced in E.coli. and then purified by metal chelate affinity chromatography. The allergenic properties of the recombinant protein were tested by ELISA and immunoblotting and biological activity was tested according to capacity for basophil activation. Three IgE-binding proteins were identified in extracts obteined from the hair, urine and salivary glands of the Siberian hamster. All proteins correspond to the same protein, which was identified as a lipocalin. This lipocalin has no cross-reactivity with common and golden hamsters. The recombinant allergen was cloned and purified, showing similar IgE reactivity in vitro to protein extracts from Siberian hamster. Also, the recombinant allergen is capable of producing a biological activation in vivo. The major allergen from Siberian hamster was cloned and allergenic properties have been characterized, providing a new tool for specific diagnosis of allergy to Siberian hamster.
    Journal of Biological Chemistry 07/2014; 289(34). DOI:10.1074/jbc.M114.579060 · 4.60 Impact Factor
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    ABSTRACT: Although not yet widely implemented, fraction of exhaled nitric oxide (FeNO) has emerged in recent years as a potentially useful biomarker for the assessment of airway inflammation both in undiagnosed patients with non-specific respiratory symptoms and in those with established airway disease. Research to date essentially suggests that FeNO measurement facilitates the identification of patients exhibiting T-helper cell type 2 (Th2)-mediated airway inflammation, and effectively those in whom anti-inflammatory therapy, particularly inhaled corticosteroids (ICS), is beneficial. In some studies, FeNO-guided management of patients with established airway disease is associated with lower exacerbation rates, improvements in adherence to anti-inflammatory therapy, and the ability to predict risk of future exacerbations or decline in lung function. Despite these data, concerns regarding the applicability and utility of FeNO in clinical practice still remain. This article reviews the current evidence, both supportive and critical of FeNO measurement, in the diagnosis and management of asthma and other inflammatory airway diseases. It additionally provides suggestions regarding the practical application of FeNO measurement: how it could be integrated into routine clinical practice, how its utility could be assessed and its true value to both clinicians and patients could be established. Although some unanswered questions remain, current evidence suggests that FeNO is potentially a valuable tool for improving the personalised management of inflammatory airway diseases.
    Respiratory medicine 06/2014; DOI:10.1016/j.rmed.2014.02.005 · 2.33 Impact Factor
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    ABSTRACT: The term irritant-induced (occupational) asthma (IIA) has been used to denote various clinical forms of asthma related to irritant exposure at work. The causal relationship between irritant exposure(s) and the development of asthma can be substantiated by the temporal association between the onset of asthma symptoms and a single or multiple high-level exposure(s) to irritants, whereas this relationship can only be inferred from epidemiological data for workers chronically exposed to moderate levels of irritants. Accordingly, the following clinical phenotypes should be distinguished within the wide spectrum of irritant-related asthma: 1) definite IIA, i.e. acute-onset IIA characterized by the rapid onset of asthma within a few hours after a single exposure to very high levels of irritant substances; 2) probable IIA, i.e. asthma that develops in workers with multiple symptomatic high-level exposures to irritants; and 3) possible IIA, i.e. asthma occurring with a delayed onset after chronic exposure to moderate levels of irritants. This document prepared by a panel of experts summarizes our current knowledge on the diagnostic approach, epidemiology, pathophysiology, and management of the various phenotypes of IIA. This article is protected by copyright. All rights reserved.
    Allergy 05/2014; 69(9). DOI:10.1111/all.12448 · 6.00 Impact Factor
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    ABSTRACT: To investigate the association between single nucleotide polymorphisms (SNPs) located across the major histocompatibility complex and susceptibility to diisocyanate-induced asthma (DA). The study population consisted of 140 diisocyanate-exposed workers. Genotyping was performed using the Illumina GoldenGate major histocompatibility complex panels. The HLA-E rs1573294 and HLA-DPB1 rs928976 SNPs were associated with an increased risk of DA under dominant (odds ratio [OR], 6.27; 95% confidence interval [CI], 2.37 to 16.6; OR, 2.79, 95% CI, 0.99 to 7.81, respectively) and recessive genetic models (OR, 6.27, 95% CI, 1.63 to 24.13; OR, 10.10, 95% CI, 3.16 to 32.33, respectively). The HLA-B rs1811197, HLA-DOA rs3128935, and HLA-DQA2 rs7773955 SNPs conferred an increased risk of DA in a dominant model (OR, 7.64, 95% CI, 2.25 to 26.00; OR, 19.69, 95% CI, 2.89 to 135.25; OR, 8.43, 95% CI, 3.03 to 23.48, respectively). These results suggest that genetic variations within HLA genes play a role in DA risk.
    Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine 04/2014; 56(4):382-7. DOI:10.1097/JOM.0000000000000138 · 1.88 Impact Factor
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    ABSTRACT: This consensus statement provides practical recommendations for specific inhalation challenge (SIC) in the diagnosis of occupational asthma. They are derived from a systematic literature search, a census of active European centres, a Delphi conference and expert consensus. This article details each step of a SIC, including safety requirements, techniques for delivering agents, and methods for assessing and interpreting bronchial responses. The limitations of the procedure are also discussed.Testing should only be carried out in hospitals where physicians and healthcare professionals have appropriate expertise. Tests should always include a control challenge, a gradual increase of exposure to the suspected agent, and close monitoring of the patient during the challenge and for at least 6 h afterwards. In expert centres, excessive reactions provoked by SIC are rare.A positive response is defined by a fall in forced expiratory volume in 1 s ≥15% from baseline. Equivocal reactions can sometimes be clarified by finding changes in nonspecific bronchial responsiveness, sputum eosinophils or exhaled nitric oxide. The sensitivity and specificity of SIC are high but not easily quantified, as the method is usually used as the reference standard for the diagnosis of occupational asthma.
    European Respiratory Journal 03/2014; 43(6). DOI:10.1183/09031936.00180313 · 7.13 Impact Factor
  • Pneumologie 02/2014; 68(S 01). DOI:10.1055/s-0034-1368016
  • Silvia Uriarte, Joaquin Sastre
    Journal of Allergy and Clinical Immunology 02/2014; 133(2):AB175. DOI:10.1016/j.jaci.2013.12.628 · 11.25 Impact Factor
  • Joaquin Sastre, Silvia Uriarte
    Journal of Allergy and Clinical Immunology 02/2014; 133(2):AB243. DOI:10.1016/j.jaci.2013.12.864 · 11.25 Impact Factor

Publication Stats

3k Citations
1,625.02 Total Impact Points

Institutions

  • 1994–2015
    • Fundación Jiménez Díaz
      Madrid, Madrid, Spain
  • 2010–2014
    • Instituto de Salud Carlos III
      Madrid, Madrid, Spain
  • 2013
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
    • Università degli Studi di Genova
      Genova, Liguria, Italy
  • 2012
    • Centro de Investigacion Biomédica en Red de Enfermedades Respiratorias
      Bunyola, Balearic Islands, Spain
  • 2007–2012
    • Hospital Clínic de Barcelona
      Barcino, Catalonia, Spain
  • 1996–2012
    • Universidad Autónoma de Madrid
      • Department of Medicine
      Madrid, Madrid, Spain
  • 2011
    • University of California, Los Angeles
      Los Ángeles, California, United States
  • 2008–2011
    • Hospital Universitario La Paz
      • Servicio de Alergología
      Madrid, Madrid, Spain
  • 2007–2011
    • Universidad de Salamanca
      Helmantica, Castille and León, Spain
  • 2006–2011
    • Hospital de Basurto
      Bilbo, Basque Country, Spain
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2009
    • Hospital Universitario de Salamanca
      Helmantica, Castille and León, Spain
    • Clínica Universidad de Navarra
      Madrid, Madrid, Spain
  • 2006–2009
    • Clínica Dr. Lobatón
      Cádiz, Andalusia, Spain
    • Hospital de La Plana
      Vila-real, Valencia, Spain
  • 2005
    • National University of Cordoba, Argentina
      • Faculty of Medical Science
      Córdoba, Cordoba, Argentina
  • 2004
    • Hospital Universitario Marques de Valdecilla
      Santander, Cantabria, Spain
    • University of Oxford
      • Department of Public Health
      Oxford, ENG, United Kingdom
  • 1994–2004
    • Hospital del Niño Jesús
      Madrid, Madrid, Spain
  • 2000
    • Hospital Universitario Ramón y Cajal
      Madrid, Madrid, Spain
  • 1988–1990
    • Tulane University
      • Department of Medicine
      New Orleans, Louisiana, United States