Estimulació beta-adrenèrgica en la síndrome del destret respiratori agut (SDRA)

Estudi elaborat a partir d’una estada al Royal Brompton Hospital, Londres, Regne Unit, durant octubre i novembre del 2006.Els beneficis de la estimulació beta-adrenèrgica en pacients amb lesió pulmonar aguda (LPA) són coneguts, però no es disposa de dades sobre el possible efecte antiinflamatori. El condensat d'aire exhalat (CAE) és una tècnica no-invasiva de recollida de mostres del tracte respiratori inferior, podent ser útil en la monitorització de patologies respiratòries. S’ha usat marcadors biològics en el CAE de pacients ventilats mecànicament amb LPA per estudiar el possible efecte antiinflamatori que el salbutamol hi podria exercir. El CAE va ser recollit abans i després de l'administració de salbutamol inahalat. Inmediatament després es va mesurar la conductivitat i el pH abans i després de la desgasificació amb heli. Es va mesurar la concentració de nitrits i nitrats. Les mostres varen ser liofilitzades i guardades a -80ºC. La concentració de leucotriè B4 es va mesurar després de la reconstitució de la mostra. Els resultats s'expressen com a mitjana (error estàndard de la mostra). No s'han detectat diferències entre els valors de CAE basals dels pacients amb LPA i els de referència de la població sana de Barcelona. Es conclou doncs que el CAE és una tècnica no invasiva que pot ser usada en la monitorització de paceints ventilats mecànicament. El salbutamol inhalat incrementa de manera significativa el pH del CAE dels paceints amb LPA, tot i que un efecte directe de la inhalació de slabutamol no pot ser desestimat.

A new automated method versus continuous positive airway pressure method for measuring pressure-volume curves in patients with acute lung injury

Objective: To compare pressure–volume (P–V) curves obtained with the Galileo ventilator with those obtained with the CPAP method in patients with ALI or ARDS receiving mechanical ventilation. P–V curves were fitted to a sigmoidal equation with a mean R2 of 0.994 ± 0.003. Lower (LIP) and upper inflection (UIP), and deflation maximum curvature (PMC) points calculated from the fitted variables showed a good correlation between methods with high intraclass correlation coefficients. Bias and limits of agreement for LIP, UIP and PMC obtained with the two methods in the same patient were clinically acceptable.

Tropical diseases screening in immigrant patients with HIV infection in a European country.

Prospective observational study of all HIV infected immigrants visited at the Infectious Diseases Department of the Hospital Universitari Vall d’Hebron from June 2010 to May 2011. Screening of most prevalent tropical diseases was performed according to geographical origin. 190 patients were included. Overall, 36.8% (70/190) patients had at least one positive result for any parasitic disease, including Chagas disease, schistosomiasis, strongyloidiasis, leishmaniasis, intestinal parasitosis and malaria. We propose a screening and management strategy of latent parasitic infections in immigrant HIV infected patients.

Measuring the child mortality impact of official aid for fighting infectious diseases, 2000-2010

Aid for fighting infectious and parasitic diseases has had a statistically significant role in the under-five mortality reduction in the last decade. Point estimates indicate a country average reduction of 1.4 deaths per thousand under fives live-born attributable to aid at its average level in 2000-2010. The effect would be an average drop of 3.3 in the under-five mortality rate at the aid levels of 2010. By components, a dollar per capita spent in fighting malaria has caused the largest average impact, statistically higher than a dollar per capita spent in STD/HIV control. We do not find statistically significant effects of other infectious disease aid, including aid for the control of tuberculosis.

Analysis and Monte Carlo simulations of a model for the spread of infectious diseases in heterogeneous metapopulations

We present a study of the continuous-time equations governing the dynamics of a susceptible infected-susceptible model on heterogeneous metapopulations. These equations have been recently proposed as an alternative formulation for the spread of infectious diseases in metapopulations in a continuous-time framework. Individual-based Monte Carlo simulations of epidemic spread in uncorrelated networks are also performed revealing a good agreement with analytical predictions under the assumption of simultaneous transmission or recovery and migration processes

Induced sputum versus exhaled nitric oxide for the evaluation of airway inflammation in allergic paediatric asthma patients treated with omalizumab

Our purpose is to determine the inflammatory changes in the airways of allergic paediatric asthma patients treated with omalizumab, measured by the percentage of eosinophils in induced sputum and exhaled nitric oxide (FENO). We observed a progressive and statistically significant decrease of eosinophil count in the induced sputum meanwhile FENO, although very sensible, was a less reproducible and thus a less reliable method to evaluate chronic airway inflammation in this population. Induced sputum seems to be a better method to monitor chronic inflammation and thus the response to chronic omalizumab treatment while FENO measurement would be more useful to monitor acute events preceding exacerbations.

Gene transfer into the airway epithelium of animals by targeting the polymeric immunoglobulin receptor.

Genes of interest can be targeted specifically to respiratory epithelial cells in intact animals with high efficiency by exploiting the receptor-mediated endocytosis of the polymeric immunoglobulin receptor. A DNA carrier, consisting of the Fab portion of polyclonal antibodies raised against rat secretory component covalently linked to poly-L-lysine, was used to introduce plasmids containing different reporter genes into airway epithelial cells in vivo. We observed significant levels of luciferase enzyme activity in protein extracts from the liver and lung, achieving maximum values of 13,795 +/- 4,431 and 346,954 +/- 199,120 integrated light units (ILU) per milligram of protein extract, respectively. No luciferase activity was detected in spleen or heart, which do not express the receptor. Transfections using complexes consisting of an irrelevant plasmid (pCMV lacZ) bound to the bona fide carrier or the expression plasmid (pGEMluc) bound to a carrier based on an irrelevant Fab fragment resulted in background levels of luciferase activity in all tissues examined. Thus, only tissues that contain cells bearing the polymeric immunoglobulin receptor are transfected, and transfection cannot be attributed to the nonspecific uptake of an irrelevant carrier-DNA complex. Specific mRNA from the luciferase gene was also detected in the lungs of transfected animals. To determine which cells in the lungs are transfected by this method, DNA complexes were prepared containing expression plasmids with genes encoding the bacterial beta-galactosidase or the human interleukin 2 receptor. Expression of these genes was localized to the surface epithelium of the airways and the submucosal glands, and not the bronchioles and alveoli. Receptor-mediated endocytosis can be used to introduce functional genes into the respiratory epithelium of rats, and may be a useful technique for gene therapy targeting the lung.

Mechanical properties of cultured human airway smooth muscle cells from 0.05 to 0.4 Hz.

We investigated the rheological properties of living human airway smooth muscle cells in culture and monitored the changes in rheological properties induced by exogenous stimuli. We oscillated small magnetic microbeads bound specifically to integrin receptors and computed the storage modulus (G') and loss modulus (G") from the applied torque and the resulting rotational motion of the beads as determined from their remanent magnetic field. Under baseline conditions, G' increased weakly with frequency, whereas G" was independent of the frequency. The cell was predominantly elastic, with the ratio of G" to G' (defined as eta) being ~0.35 at all frequencies. G' and G" increased together after contractile activation and decreased together after deactivation, whereas eta remained unaltered in each case. Thus elastic and dissipative stresses were coupled during changes in contractile activation. G' and G" decreased with disruption of the actin fibers by cytochalasin D, but eta increased. These results imply that the mechanisms for frictional energy loss and elastic energy storage in the living cell are coupled and reside within the cytoskeleton.

Obesity and the incidence of chronic diseases: a seemingly unrelated probit approach

Western societies can reduce avoidable mortality and morbidity by better understanding the relationship between obesity and chronic disease. This paper examines the joint determinants of obesity and of heart disease, diabetes, hypertension, and elevated cholesterol. It analyzes a broadly representative Spanish dataset, the 1999 Survey on Disabilities, Impairments and Health Status, using a health production theoretical framework together with a seemingly unrelated probit model approach that controls for unobserved heterogeneity and endogeneity. Its findings provide suggestive evidence of a positive and significant, although specification-dependent, association between obesity and the prevalence of chronic illness

Outpatient Quick Diagnosis Units for the evaluation of suspected severe diseases: an observational, descriptive study

Background: Hospitals in countries with public health systems have recently adopted organizational changes to improve efficiency and resource allocation, and reducing inappropriate hospitalizations has been established as an important goal. AIMS: Our goal was to describe the functioning of a Quick Diagnosis Unit in a Spanish public university hospital after evaluating 1,000 consecutive patients. We also aimed to ascertain the degree of satisfaction among Quick Diagnosis Unit patients and the costs of the model compared to conventional hospitalization practices. DESIGN: Observational, descriptive study. METHODS: Our sample comprised 1,000 patients evaluated between November 2008 and January 2010 in the Quick Diagnosis Unit of a tertiary university public hospital in Barcelona. Included patients were those who had potentially severe diseases and would normally require hospital admission for diagnosis but whose general condition allowed outpatient treatment. We analyzed several variables, including time to diagnosis, final diagnoses and hospitalizations avoided, and we also investigated the mean cost (as compared to conventional hospitalization) and the patients' satisfaction. RESULTS: In 88% of cases, the reasons for consultation were anemia, anorexia-cachexia syndrome, febrile syndrome, adenopathies, abdominal pain, chronic diarrhea and lung abnormalities. The most frequent diagnoses were cancer (18.8%; mainly colon cancer and lymphoma) and Iron-deficiency anemia (18%). The mean time to diagnosis was 9.2 days (range 1 to 19 days). An estimated 12.5 admissions/day in a one-year period (in the internal medicine department) were avoided. In a subgroup analysis, the mean cost per process (admission-discharge) for a conventional hospitalization was 3,416.13 Euros, while it was 735.65 Euros in the Quick Diagnosis Unit. Patients expressed a high degree of satisfaction with Quick Diagnosis Unit care. CONCLUSIONS: Quick Diagnosis Units represent a useful and cost-saving model for the diagnostic study of patients with potentially severe diseases. Future randomized study designs involving comparisons between controls and intervention groups would help elucidate the usefulness of Quick Diagnosis Units as an alternative to conventional hospitalization.

Obesity and the incidence of chronic diseases: a seemingly unrelated probit approach

Western societies can reduce avoidable mortality and morbidity by better understanding the relationship between obesity and chronic disease. This paper examines the joint determinants of obesity and of heart disease, diabetes, hypertension, and elevated cholesterol. It analyzes a broadly representative Spanish dataset, the 1999 Survey on Disabilities, Impairments and Health Status, using a health production theoretical framework together with a seemingly unrelated probit model approach that controls for unobserved heterogeneity and endogeneity. Its findings provide suggestive evidence of a positive and significant, although specification-dependent, association between obesity and the prevalence of chronic illness

Role of JNK in neurodegenerative diseases

The c-Jun N-terminal kinases (JNK) are members of the MAPK family and can be activated by different stimuli such as cellular stress, heat shock and ultra-violet irradiation. JNKs have different physiological functions and they have been linked to apoptosis in different cell types. Therefore, the JNK signalling pathway is an important target to prevent cell death. In the present chapter, the role of JNKs in neurodegenerative diseases will be discussed, as well as the pharmacological compounds that inhibit this signalling pathway as therapeutic intervention to prevent neuronal death.

Role of JNK in neurodegenerative diseases

The c-Jun N-terminal kinases (JNK) are members of the MAPK family and can be activated by different stimuli such as cellular stress, heat shock and ultra-violet irradiation. JNKs have different physiological functions and they have been linked to apoptosis in different cell types. Therefore, the JNK signalling pathway is an important target to prevent cell death. In the present chapter, the role of JNKs in neurodegenerative diseases will be discussed, as well as the pharmacological compounds that inhibit this signalling pathway as therapeutic intervention to prevent neuronal death.

Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases

AbstractBACKGROUND: Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult.PRINCIPAL FINDINGS: We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell.CONCLUSIONS: For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases.AVAILABILITY: The gene-disease networks used in this study and part of the analysis are available at http://ibi.imim.es/DisGeNET/DisGeNETweb.html#Download