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Dive into the research topics where Bernat Togores is active.

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Featured researches published by Bernat Togores.


Antimicrobial Agents and Chemotherapy | 2005

Hypermutation is a key factor in development of multiple-antimicrobial resistance in Pseudomonas aeruginosa strains causing chronic lung infections.

María D. Maciá; David Blanquer; Bernat Togores; Jaume Sauleda; José L. Pérez; Antonio Oliver

ABSTRACT Pseudomonas aeruginosa is the most relevant pathogen producing chronic lung infections in patients with chronic underlying diseases such as cystic fibrosis (CF), bronchiectasis, and chronic obstructive pulmonary disease (COPD). Hypermutable (or mutator) P. aeruginosa strains, characterized by increased (up to 1,000-fold) spontaneous mutation rates due to alterations of the DNA mismatch repair (MMR) system have been found at high frequencies in the lungs of CF patients, but their role in other chronic processes is still unknown. Sixty-two P. aeruginosa isolates from 30 patients with underlying non-CF chronic respiratory diseases (22 with bronchiectasis and 8 with COPD) and documented chronic infection were studied. Antibiotic susceptibility profiles and mutation frequencies were determined, and complementation assays using the cloned wild-type mutS gene and molecular epidemiology studies (pulsed-field electrophoresis, [PFGE]) were performed with these strains. Thirty-three (53%) of the isolates were hypermutable, and 17 (57%) of the 30 patients were colonized by hypermutable strains. Strains from 11 of the 17 patients were found to be defective in the MMR mutS gene by complementation assays. Interpatient transmission of strains was ruled out by PFGE. Multiple-antimicrobial resistance was documented in 42% of the hypermutable strains in contrast to 0% resistance in the nonhypermutable strains (P < 0.0001). Hypermutable P. aeruginosa strains are extremely prevalent in chronic infections in contrast to what has been described in acute processes, suggesting a role of hypermutation in bacterial adaptation for long-term persistence. Furthermore, hypermutation is found to be a key factor for the development of multiple-antimicrobial resistance, and therefore these findings are expected to have important consequences for the treatment of chronic infections.


European Respiratory Journal | 1996

Noninvasive ventilatory support does not facilitate recovery from acute respiratory failure in chronic obstructive pulmonary disease

Ferran Barbé; Bernat Togores; M. Rubi; S. Pons; A. Maimo; Alvar Agusti

This investigation evaluates, in a prospective, randomized and controlled manner, whether noninvasive ventilatory support (NIVS) with bilevel positive airway pressure (BiPAP) facilitates recovery from acute respiratory failure (ARF) in patients with chronic obstructive pulmonary disease (COPD). Twenty four patients (mean age (+/-SEM) 68 +/- 2 yrs) with COPD (forced expiratory volume in one second (FEV1) at discharge 33 +/- 2% predicted), who attended the emergency room because of ARF (pH 7.33 +/- 0.01; arterial oxygen tension (Pa,O2) 6.0 +/- 0.2 kPa; arterial carbon dioxide tension (Pa,CO2) 7.9 +/- 0.3 kPa), were initially randomized. Four out of the 14 patients (29%) allocated to received NIVS did not tolerate it. Of the remaining 20 patients, 10 received NIVS with BiPAP in a conventional hospital ward during the first 3 days of hospitalization (two daytime sessions of 3 h duration each). All 20 subjects were treated with oxygen, bronchodilators and steroids. On the first and third hospitalization days, before and 30 min after withdrawing oxygen therapy and/or BiPAP ventilatory support, we measured peak expiratory flow, arterial blood gas values, ventilatory pattern, occlusion pressure (P0.1), and maximal inspiratory (MIP) and maximal expiratory (MEP) pressures. All patients were discharged without requiring tracheal intubation and mechanical ventilation. Hospitalization time was similar in both groups (11.3 +/- 1.3 vs 10.6 +/- 0.9 days, control vs BiPAP, respectively). Arterial oxygenation, respiratory acidosis and airflow obstruction improved significantly throughout hospitalization in both groups. By contrast, the ventilatory pattern, P0.1, MIP and MEP did not change. NIVS with BiPAP did not cause any significant difference between groups. We conclude that noninvasive ventilatory support with bilevel positive airway pressure does not facilitate recovery from acute respiratory failure in patients with chronic obstructive pulmonary disease. Furthermore, a substantial proportion of patients (29%) do not tolerate noninvasive ventilatory support under these circumstances. From these results, we cannot recommend the use of noninvasive ventilatory support with bilevel positive airway pressure in the routine management of chronic obstructive pulmonary disease patients recovering from acute respiratory failure.


Chest | 2010

High Prevalence of Undiagnosed Airflow Limitation in Patients With Cardiovascular Disease

Joan B. Soriano; Fernando Rigo; Dolores Guerrero; Aina Yañez; Josep F. Forteza; Guillem Frontera; Bernat Togores; Alvar Agusti

BACKGROUND The prevalence of airflow limitation (AL) in patients with cardiovascular disease (CVD) is unknown, and whether AL is adequately diagnosed and treated in these patients has not been investigated before, to our knowledge. METHODS We compared clinical and spirometric data in three groups of individuals. Two of them were participants in the follow-up of an ongoing population-based study according to the presence or absence of CVD. The third group included patients with coronary artery disease (CAD) confirmed by coronariography regularly visited at a tertiary referral university hospital. AL was defined according to the Global Initiative for Obstructive Lung Disease guidelines. RESULTS We studied 450 population participants without CVD, 52 population participants with CVD, and 119 hospital patients with CAD. The prevalence of AL in these three groups was 17.5% (95% CI, 14.0-21.0), 19.2% (95% CI, 8.1-30.7), and 33.6% (95% CI, 25.0-42.2), respectively (P < .05). Underdiagnosis of AL ranged from 60% in population participants with CVD up to 87.2% in hospital patients with CAD. Sixty percent of those with spirometrically confirmed AL (in all three groups) did not receive any respiratory treatment. CONCLUSIONS AL is frequent in individuals with CVD, particularly in those with CAD attended in the hospital, is largely underdiagnosed and therefore is highly undertreated. TRIAL REGISTRATION Clinicaltrials.gov; Identifier: NCT00787748.


Hiv Medicine | 2014

Prevalence of and risk factors for pulmonary abnormalities in HIV‐infected patients treated with antiretroviral therapy

G Sampériz; Dolores Guerrero; Meritxell López; Jose Luis Valera; Amanda Iglesias; Angel Rios; A Campins; Ernest Sala; J Murillas; Bernat Togores; Joan Palmer; M Rodriguez; Joan B. Soriano; Jaume Sauleda; M Riera; Alvar Agusti

Pulmonary abnormalities are often present in patients infected with the human immunodeficiency virus (HIV).


PLOS ONE | 2013

Clonal dissemination, emergence of mutator lineages and antibiotic resistance evolution in Pseudomonas aeruginosa cystic fibrosis chronic lung infection.

Carla López-Causapé; Estrella Rojo-Molinero; Xavier Mulet; Gabriel Cabot; Bartolomé Moyá; Joan Figuerola; Bernat Togores; José Luis Pérez; Antonio Oliver

Chronic respiratory infection by Pseudomonas aeruginosa is a major cause of mortality in cystic fibrosis (CF). We investigated the interplay between three key microbiological aspects of these infections: the occurrence of transmissible and persistent strains, the emergence of variants with enhanced mutation rates (mutators) and the evolution of antibiotic resistance. For this purpose, 10 sequential isolates, covering up to an 8-year period, from each of 10 CF patients were studied. As anticipated, resistance significantly accumulated overtime, and occurred more frequently among mutator variants detected in 6 of the patients. Nevertheless, highest resistance was documented for the nonmutator CF epidemic strain LES-1 (ST-146) detected for the first time in Spain. A correlation between resistance profiles and resistance mechanisms evaluated [efflux pump (mexB, mexD, mexF, and mexY) and ampC overexpression and OprD production] was not always obvious and hypersusceptibility to certain antibiotics (such as aztreonam or meropenem) was frequently observed. The analysis of whole genome macrorestriction fragments through Pulsed-Field Gel Electrophoresis (PFGE) revealed that a single genotype (clone FQSE-A) produced persistent infections in 4 of the patients. Multilocus Sequence typing (MLST) identified clone FQSE-A as the CF epidemic clone ST-274, but striking discrepancies between PFGE and MLST profiles were evidenced. While PFGE macrorestriction patterns remained stable, a new sequence type (ST-1089) was detected in two of the patients, differing from ST-274 by only two point mutations in two of the genes, each leading to a nonpreviously described allele. Moreover, detailed genetic analyses revealed that the new ST-1089 is a mutS deficient mutator lineage that evolved from the epidemic strain ST-274, acquired specific resistance mechanisms, and underwent further interpatient spread. Thus, presented results provide the first evidence of interpatient dissemination of mutator lineages and denote their potential for unexpected short-term sequence type evolution, illustrating the complexity of P. aeruginosa population biology in CF.


FEBS Letters | 2000

Regulation of iNOS expression and glutathione levels in rat liver by oxygen tension

Cristina Miralles; Xavier Busquets; Carmen Santos; Bernat Togores; Sabah N. A. Hussain; Irfan Rahman; William MacNee; Alvar Agusti

Molecular oxygen (O2) regulates the expression of a variety of genes. We hypothesized that O2 tension may regulate iNOS expression in rat liver through the production of reactive oxygen species (ROS) and the reduction of intracellular glutathione (GSH) levels. To investigate this hypothesis, we determined the effects of hyperoxia upon iNOS induction (both at the protein and mRNA level) and the intracellular concentration of GSH in an isolated in vitro perfused rat liver preparation. To study the potential involvement of ROS in the intracellular signaling pathway linking changes in oxygen tension to gene expression, we repeated these determinations in the presence of the thiol antioxidant N‐acetyl‐L‐cysteine (NAC). We found that 95% O2 tension caused a significant induction of the iNOS protein and mRNA levels paralleled by a significant fall in intracellular GSH concentration. The addition of NAC (1 mM) to the perfusate during hyperoxia blocked the induction of iNOS and restored GSH levels. These results indicate that molecular O2 regulates the expression of iNOS in rat liver at the transcriptional level, most likely through the production of ROS and the reduction of intracellular GSH levels.


European Respiratory Journal | 2000

The measurement of exhaled carbon monoxide is influenced by airflow obstruction

Bernat Togores; M. Bosch; Alvar Agusti

The concentration of carboxyhaemoglobin (COHb) is often estimated from measurements of carbon monoxide in the exhaled air (COexh). This study investigates whether the presence of airflow obstruction significantly alters the relationship between COexh and COHb. Eighty-one regular smokers were prospectively studied and divided in four groups according to the presence and severity of airflow obstruction (none, mild, moderate, severe). In each subject, the authors measured in this order: 1) arterial blood gases; 2) haemoglobin concentration and COHb (by co-oxymetry); 3) COexh; 4) lung volumes; and 5) forced spirometry. The size of the measurement error (deltaCO) was calculated from the difference between COHb and COexh. Neither the smoking history nor COexh were different in the four groups of subjects studied. In contrast, deltaCO increased in parallel to the degree of airflow obstruction. DeltaCO was >2% (a threshold value normally used in the clinic to separate smokers from nonsmokers) only in patients with severe airflow obstruction. A stepwise multivariate analysis showed that both forced expiratory volume in one second (FEV1) (percentage reference) and COHb contributed significantly (p<0.0001) to predict deltaCO. This study shows that the estimation of carboxyhaemoglobin from exhaled carbon monoxide measurements can be inaccurate in patients with severe airflow obstruction. In these patients, the direct measurement of carboxyhaemoglobin seems advisable in clinical practice.


European Respiratory Journal | 1997

Effects of N-acetylcysteine on tissue oxygenation in patients with multiple organ failure and evidence of tissue hypoxia

Alvar Agusti; Bernat Togores; J. Ibañez; J. M. Raurich; A. Maimo; J. Bergada; P. Marse; R. Jorda

Covert tissue hypoxia, particularly of the splanchnic region, appears important in the pathogenesis of multiple organ failure (MOF). This investigation evaluates the effects of N-acetylcysteine (NAC) upon several measures of tissue oxygenation in 10 patients with severe MOF and evidence of splanchnic hypoxia (as suggested by a pathologically low value (< 7.32) of the pH of the gastric mucosa (pHi)). Patients were studied following a prospective, randomized, placebo-controlled, cross-over design. Measurements included pulmonary and systemic haemodynamics, cardiac output by thermodilution, arterial and mixed venous blood gas values, blood lactate concentration, whole-body oxygen uptake by analysis of the expired gases, and pHi by tonometry. A complete set of measurements was obtained before and 45 min after the infusion of NAC (150 mg.kg-1 in 250 mL of saline) and, also, before and 45 min after the infusion of an equivalent volume of saline. NAC increased the cardiac index and vasodilated the systemic circulation (p < 0.01). However, O2 delivery to the tissues did not increase because the arterial oxygen content fell after NAC (p < 0.01). Mean O2 extraction or lactate concentration did not change after NAC, and pHi fell slightly (from 7.11 +/- 0.21 to 7.07 +/- 0.21; p < 0.05). The infusion of saline did not modify any variable significantly. The O2 extraction fraction increased exponentially in those patients with reduced O2 transport to the tissues. These results argue against a beneficial effect of N-acetylcysteine upon tissue oxygenation in patients with severe multiple organ failure and evidence of splanchnic hypoxia. Furthermore, they suggest that the mechanisms controlling the extraction of oxygen by the peripheral tissues in these patients were not impaired.


Archivos De Bronconeumologia | 1999

Resultados de la actuación de una unidad de control de la oxigenoterapia domiciliaria

Miguel Carrera; Jaume Sauleda; F. Bauzá; M. Bosch; Bernat Togores; Ferran Barbé; Alvar Agusti

Objetivo Este estudio pretende: a) analizar la prevalencia de la oxigenoterapia domiciliaria en Mallorca; b) evaluar la relacion coste-beneficio de la unidad de oxigenoterapia, y c) describir la supervivencia de los pacientes con enfermedad pulmonar obstructiva cronica que reciben oxigenoterapia domiciliaria en la actualidad. Metodo En abril de 1994, al crearse la unidad de oxigenoterapia, se evaluaron todos los pacientes que recibian oxigenoterapia domiciliaria en Mallorca (estudio transversal). Durante los 3 anos siguientes, se ha seguido periodicamente a todos aquellos en los que se mantuvo la prescripcion de oxigenoterapia domiciliaria y se han evaluado todas las nuevas prescripciones (estudio longitudinal). Resultados Antes de la puesta en marcha de la unidad de oxigenoterapia, la prevalencia de oxigenoterapia domiciliaria en Mallorca era de 71/100.000 habitantes. Se retiro la oxigenoterapia domiciliaria al 31% de los pacientes evaluados en el estudio transversal. Al finalizar el estudio longitudinal la prevalencia de oxigenoterapia domiciliaria era 56/100.000 habitantes. La actuacion de la unidad de oxigenoterapia ha supuesto un ahorro aproximado de 38 millones de pesetas anuales. Ha aumentado el numero de pacientes con concentrador, que se ha convertido en la principal forma de administracion, y oxigeno liquido. La supervivencia de los pacientes con enfermedad pulmonar obstructiva cronica tratados con oxigenoterapia domiciliaria evaluados en este estudio parece superior a la referida clasicamente. Conclusiones a) La prevalencia de la oxigenoterapia domiciliaria en Mallorca antes de que la unidad de oxigeno-terapia iniciase su actividad era excesivamente alta; b) el analisis coste-beneficio de la actuacion de la unidad de oxigenoterapia es muy positivo porque ha optimizado la prescripcion de oxigenoterapia domiciliaria y ha supuesto un ahorro economico importante (~38 millones de ptas./ano), y c) la supervivencia de los pacientes con enfermedad pulmonar obstructiva cronica que reciben oxigenoterapia domiciliaria en la actualidad parece mejor que la referida clasicamente, posiblemente en relacion con la mayor eficacia de los tratamientos actuales.


European Respiratory Journal | 1996

Continuous positive airway pressure is effective in treating upper airway oedema

Ferran Barbé; S. Pons; Bernat Togores; Jaume Sauleda; R. Soler; Alvar Agusti

The case of a patient with diffuse idiopathic skeletal hyperostosis (DISH) and upper airway oedema, is described. The patient presented with alveolar hypoventilation and obstructive apnoeas during sleep. Intravenous steroids (methylprednisolone, 160 mg.day-1) for 5 days did not reduce the oedema. However, it was rapidly reversed by the use of nasal continuous positive airway pressure (nCPAP). In addition, daytime pulmonary gas exchange was improved and sleep apnoea abolished. This beneficial effect made tracheostomy unnecessary. This case report suggests that CPAP can be a potentially useful therapeutic alternative to tracheostomy in the clinical management of upper airway oedema.

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Alvar Agusti

University of Barcelona

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Ferran Barbé

Hospital Universitari Arnau de Vilanova

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Antonio Oliver

Instituto de Salud Carlos III

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Borja G. Cosío

Instituto de Salud Carlos III

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