Transcriptional analysis of nasal polyps fibroblasts reveals a new source of pro-inflammatory signaling in CRSwNP.

BACKGROUND: Fibroblasts and others mesenchymal cells have recently been identified as critical cells triggering tissue-specific inflammatory responses. Persistent activation of fibroblasts inflammatory program has been suggested as an underlying cause of chronic inflammation in a wide range of tissues and pathologies. Nevertheless, the role of fibroblasts in the emergence of chronic inflammation in the upper airway has not been previously addressed. We aimed to elucidate whether fibroblasts could have a role in the inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODOLOGY: We performed whole-transcriptome microarray in fibroblast cultured from CRSwNP samples and confirmed our results by qRT-PCR. We selected patients without other associated diseases in upper airway. To investigate shifts in transcriptional profile we used fibroblasts from nasal polyps and uncinate mucosae from patient with CRSwNP, and fibroblasts from uncinate mucosae from healthy subjects as controls. RESULTS: This study exposes activation of a pro-inflammatory and pro-fibrotic transcriptional program in nasal polyps and CRSwNP fibroblasts when compared to controls. Our Gene-set Enrichment Analysis (GSEA) pointed to common up-regulation of several pro-inflammatory pathways in patients-derived fibroblasts, along with higher mRNA expression levels of cytokines, growth factors and extracellular matrix components. CONCLUSIONS: Our work reveals a potential new source of inflammatory signaling in CRSwNP. Furthermore, our results suggest that deregulated inflammatory signaling in tissue-resident fibroblasts could support a Type-2 inflammatory response. Further investigations will be necessary to demonstrate the functionality of these novel results.

Aportación europea a la especialidad de cirugía torácica general. II parte: contribución británica / European contribution to the general thoracic surgery speciality. Part II: British contribution

Es a principios de la Primera Guerra Mundial cuando se multiplicaron las técnicas quirúrgicas en el Reino Unido. Los drenajes, el tratamiento de las heridas abiertas y las complicaciones como los empiemas eran el inicio de nuevas técnicas, innovadoras y resolutivas en estos casos. En esos años, muchos de los cirujanos britanicos abandonaron el país. Hemos de reseñar que se crearon nuevos hospitales, como el Brompton en Londres. Fue fundado por la Reina Victoria como "hospital para enfermedades del tórax". Hemos de mencionar al Dr. Barret que, procedente de Adelaida (Australia), forma parte del equipo quirúrgico de este hospital. En 1971, MacArthur consiguió una supervivencia de dos meses en un trasplante de pulmón, y se recuerda la influencia de R. Abbey Smith en estos años. Ya en años más recientes, el Dr. Peter Goldstraw ocupó la plaza de especialista en cirugía torácica del Brompton y desarrolló, entre otras técnicas, la cirugía del enfisema bulloso y estudios prospectivos sobre carcinoma broncogénico y estadificación ganglionar en cancer de pulmón (AU)

It was at the beginning of the First World War when the surgical techniques multiplied in the United Kingdom. Drainages, treatment of open wounds and complications such as empyemas were the initiation of new, innovating and resolving techniques in these cases. During these years, many of the British surgeons left the country. We must state that new hospitals, such as the Brompton in London, were created. It was founded by Queen Victoria as a "Hospital for diseases of the chest." Mention should be made of Dr. Barrett, who was from Adelaida (Australia) and who formed a part of the surgical team of this hospital. In the year 1971, Mac Arthur achieved a two-month survival after a lung transplantation and the influence of R. Abbey Smith during these years is remembered. In more recent years, Dr. Peter Goldstraw occupied the post of chest surgery consultant in Brompton and developed, among other techniques, surgery in bullous emphysema and prospective studies on bronchogenic carcinoma and lymph node staging in lung cancer (AU)

Aportación europea a la especialidad de cirugía torácica. Contribución de los países del continente / European contribution to the thoracic surgery speciality. Contribution of the countries of the continent

En anteriores trabajos, hemos analizado la contribución germana y británica a la Cirugía Torácica general y a continuación desarrollaremos lo que fue ocurriendo durante este mismo tiempo en el resto de Europa. Examinaremos la falta de una Sociedad profesional adecuada al desarrollo de la Cirugía Torácica, a pesar de la existencia de cirujanos que comenzaban a desarrollar técnicas novedosas durante estos años. En el norte de Europa la Cirugía Torácica se había iniciado con el Dr. Jacobeus de Estocolmo . En los Países Bajos se llevó a cabo la primera neumonectomía por cuadro de bronquiectasias en el año 1940. Durante este tiempo, se llevaron a cabo tratamientos quirúrgicos de cerca en 1.200 pacientes con procesos tuberculosos con una mortalidad operatoria en torno al 2%. La aportación en Bélgica evolucionó de manera favorable desde el año 1 930 y posteriormente se produjo una separación de la Cirugía General y Digestiva de la Cardiaca, Osteoarticular, Urología y Neurocirugía. Es en 1970 cuando se comienza a desarrollar el plombaje extrafascial con grasa, y el Dr. LeBrigand aporta nuevas tecnicas para el tratamiento tuberculoso, así como en los traumatismos torácicos y lesiones traqueobronquiales. Mientras tanto, en Marsella se llevaron a cabo las primeras prácticas de broncografías y se comienza sobre trabajos de trasplante pulmonar experimental. La contribución Ibérica y la Cirugía Italiana están recogidas en España con nombres como Dr. González Duarte o Gil Turner y la participación italiana se inicia fundamentalmente entre los años 1.900 y 1.976 con la realización de la cirugía pulmonar y esofágica destacando, entre otros, el Dr. Erino A Rendina. En Austria se comenzó con la colapsoterapia llevando a cabo toracoplastias, neumotórax artificiales y frenicectomías. En Turquía y en Grecia la equinocosis era un serio problema de salud y se desarrollaron numerosas técnicas para su tratamiento. De la misma manera, se llevaron a cabo funduplicaciones de esófago distal y se desarrolló la Escuela de Cirugía Torácica en Antalaya (Antalaya School of Thoracic Surgery). En cuanto a los bloques del Este ha sido difícil recopilar datos de dicha área. Hasta que no se produjo la caída del muro de Berlín, el problema fue encontrar fuentes fidedignas de información. Es en estos países donde se produce el desarrollo de la cirugía pulmonar y se va asimilando la cirugía esofágica, así en los años 30 se propone el abordaje mediastínico a través del abdomen y se realizan anastomosis esofagogástricas torácicas por Uglov. Finalmente señalaremos que la escuela de San Petersburgo se considera como la representante de la cirugía en la Federación Rusa y se comienzan importantes periodos de desarrollo, que han llegado hasta nuestras citas bibliográficas actuales (AU)

In previous works, we have analyzed the German and British contribution to general Thoracic Surgery and then we developed what had been occurring during the same time in the rest of Europe. We will examine the lack of a Professional Society suitable for the development of Thoracic Surgery, in spite of the existence of surgeons who had begun to develop novel techniques during these years. In the north of Europe, Thoracic Surgery had been initiated with Dr. Jacobeus of Stockholm. In the Netherlands, the first pneumonectomy was performed due to a picture of bronchiectasis in the year 1940. During that time, surgical treatment was performed in approximately 1200 patients suffering tuberculosis conditions with approximately 2% surgical mortality. The contribution in Belgium evolved favorably after the year 1930 and there was a subsequent separation of General and Digestive Surgery from Cardiac, Osteoarticular, Urology and Neurosurgery. In 1970, when extrafascial plombage with fat was begun, Dr. LeBrigand contributed new techniques for treatment of tuberculosis and in thoracic traumas and tracheal-bronchial lesions. Meanwhile, in Marcela, the first practices of bronchographies were conducted and works on experimental lung transplants were begun. The contribution of Iberia and of Italian Surgery were collected in Spain with names such as Dr. González Duarte or Gil Turner and the Italian participation was fundamentally begun between the years 1,900 and 1,976 with the performance of pulmonary and esophageal surgery, standing out, among others, Dr. Erino A Rendina. In Austria, they began with colapsotherapy, performing thoracoplasties, artificial pneumothorax and phrenicectomies. In Turkey and in Greece, the equinococosis was a serious health problem and many techniques were developed for its treatment. Similarly, distal esophageal fundoplications were performed and Antalaya School of Thoracic Surgery was developed. It has been difficult to gather data in regards to the said area of the Eastern Bloc. Until the Berlin Wall fell, the problem was to find reliable sources of information. It was in those countries in which pulmonary surgery was developed and in which esophageal surgical was assimilated. Thus, in the 1930's, the mediastinal approach through the abdomen was proposed and thoracic esophageal-gastric anastomeses were performed by Uglov. Finally, we point out that the School of St. Petersburg is considered as the representative of the surgery of the Russian Federation and in which important periods of development were begun, which have been included in our current bibliographic citations (AU)

Cirugía torácica videoasistida en el tratamiento del cáncer de pulmón / Video-assisted thoracic surgery in the treatment of lung cancer

Resumen. Pese a las preocupaciones e incertidumbres iniciales respecto a las resecciones pulmonares mayores por cirugía torácica videoasistida, esta técnica ha demostrado ser una opción válida en el tratamiento del carcinoma broncogénico de células no pequeñas en estadios iniciales. Tanto la lobectomía como la linfadenectomía mediastínica por cirugía mínimamente invasiva son técnicamente factibles y seguras. No se aprecia un aumento de las tasas de morbi-mortalidad. Asimismo, la técnica permite mantener los principios oncológicos, logrando buenos resultados reflejados en supervivencias similares o incluso superiores a las alcanzadas por cirugía abierta. Pese a estos resultados, aún está muy poco extendida en la práctica quirúrgica habitual de los servicios de Cirugía Torácica. Por lo tanto, dado que se trata de una técnica factible, segura y con buenos resultados oncológicos, debería comenzar a ser una práctica rutinaria en aquellos centros en que pueda iniciar un programa de lobectomía por cirugía mínimamente invasiva (AU)

Abstract. In spite of the initial concerns and uncertainty regarding major lung resections by video-assisted thoracic surgery, this technique has been demonstrated to be a valid option in the treatment of non-small cell bronchogenic carcinoma in initial stages. Both the lobectomy and the mediastinic lymphadectomy by minimally invasive surgery are technically feasible and safe. No increase in the rates of morbidity-mortality is observed. Furthermore, the technique makes it possible to maintain the oncological principles, achieving good results reflected in similar or even greater survivals than those reached by open surgery. In spite of these results, it is still not very extended in the usual surgical practice of the Thoracic Surgery services. Therefore, given that it is a feasible and safe technique with good oncological results, it should begin to become a route practice in those sites that can initiate a program of lobectomy by minimally invasive surgery (AU)

Aportación europea a la especialidad de Cirugía Torácica. Contribución alemana / European contribution to the thoracic surgery specialty. German contribution

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Abnormal mitochondrial function in locomotor and respiratory muscles of COPD patients.

Several cellular and molecular alterations have been described in skeletal and respiratory muscles of patients with chronic obstructive pulmonary disease (COPD), but information on potential abnormalities of mitochondrial function is scarce. The aim of the present study was to investigate mitochondrial function in the vastus lateralis (VL) and external intercostalis (EI) of COPD patients. Biopsies from VL and EI were obtained during surgery for lung cancer in 13 patients with mild to moderate COPD (age 68+/-6 yrs, forced expiratory volume in one second (FEV(1)) 66+/-15% predicted) and 19 control subjects (age 67+/-9 yrs, FEV(1) 95+/-18% pred). State 3 and 4 mitochondrial oxygen consumption (V'(O(2),m)), ATP synthesis, citrate synthase, cytochrome oxidase (COX) and complex I-III activities, as well as reactive oxygen species (ROS) production, were determined. In COPD patients, in both muscles, COX activity (VL: COPD 3.0+/-0.8 versus control 2.0+/-0.8; EI: 3.7+/-1.6 versus 2.4+/-0.9 micromol min(-1) mg(-1)) and ROS production (VL: 1,643+/-290 versus 1,285+/-468; EI: 1,033+/-210 versus 848+/-288 arbitrary units) were increased, whereas state 3 V'(O(2),m) was reduced (VL: 2.9+/-0.3 versus 3.6+/-0.4; EI: 3.6+/-0.3 versus 4.1+/-0.4 mmol min(-1) kg(-1)). Skeletal muscle mitochondria of patients with chronic obstructive pulmonary disease show electron transport chain blockade and excessive production of reactive oxygen species. The concurrent involvement of both vastus lateralis and external intercostalis suggests a systemic (rather than a local) mechanism(s) already occurring in relatively early stages (Global Initiative for Chronic Obstructive Lung Disease stage II) of the disease.

Diagnóstico y manejo del derrame pleural maligno / Diagnosis and management of the malignant pleural. Efussion

El derrame pleural maligno es una entidad frecuente y debilitante, manifestación de la enfermedad neoplásica avanzada. Su presencia empeora la calidad de vida del paciente e implica una esperanza de vida reducida a unos pocos meses. Previo a iniciar un tratamiento, se debe diagnosticar el derrame pleural como maligno mediante una citología de líquido pleural y/o una histología de pleura positiva para malignidad, lo que a veces requiere emplear varios procedimientos diagnósticos.Una vez diagnosticado, se plantean una serie de consideraciones que el facultativo debe tener en cuenta a la hora de desarrollar una estrategia terapéutica. Factores, como el estado general del paciente y su índice de calidad de vida, parámetrosradiológicos y bioquímicos del derrame y las distintas opciones terapéuticas deben considerarse para conseguirel objetivo principal del tratamiento que es aliviar la sintomatología, así como evitar la reaparición del derrame. La pleurodesis con talco (mediante talco en slurry o talco poudrage) es la técnica más empleada y que ofrece mejores resultados aunque no está exenta de posibles complicaciones

TMalignant pleural effusion is a frequent and weakening entity, manifestation of advanced neoplastic disease. Its presence deteriorates the patient's quality of life and implies a life expectancy that is reduced to a few months. Prior to initiating treatment, the pleural effusion should be diagnosed as malignant by means of a pleural fluid cytology and/or histologyof pleura positive for malignancy. This often requires the use of several diagnostic procedures. Once diagnosed, a series of consideration that the professional should take into account when planning a therapeutic strategy are established.These are factors such as the patient's general condition and quality of life index, radiological and biochemical parameters of the effusion. Furthermore, the different therapeutic options should be considered to achieve the primary objective of the treatment, this being to relieve the symptoms and avoid the reappearance of the effusion. Talc pleurodesis (via slurry or poudrage) is the technique used most and the one that offers the best results, although it is not exemptof possible complications (AU)

New analytical potential energy surface for the F(2P)+CH4 hydrogen abstraction reaction: kinetics and dynamics.

A new potential energy surface for the gas-phase F(2P)+CH4 reaction and its deuterated analogues is reported, and its kinetics and dynamics are studied exhaustively. This semiempirical surface is completely symmetric with respect to the permutation of the four methane hydrogen atoms, and it is calibrated to reproduce the topology of the reaction and the experimental thermal rate constants. For the kinetics, the thermal rate constants were calculated using variational transition-state theory with semiclassical transmission coefficients over a wide temperature range, 180-500 K. The theoretical results reproduce the experimental variation with temperature. The influence of the tunneling factor is negligible, due to the flattening of the surface in the entrance valley, and we found a direct dependence on temperature, and therefore positive and small activation energies, in agreement with experiment. Two sets of kinetic isotope effects were calculated, and they show good agreement with the sparse experimental data. The coupling between the reaction coordinate and the vibrational modes shows qualitatively that the FH stretching and the CH3 umbrella bending modes in the products appear vibrationally excited. The dynamics study was performed using quasi-classical trajectory calculations, including corrections to avoid zero-point energy leakage along the trajectories. First, we found that the FH(nu',j') rovibrational distributions agree with experiment. Second, the excitation function presents an oscillatory pattern, reminiscent of a reactive resonance. Third, the state specific scattering distributions present reasonable agreement with experiment, and as the FH(nu') vibrational state increases the scattering angle becomes more forward. These kinetics and dynamics results seem to indicate that a single, adiabatic potential energy surface is adequate to describe this reaction, and the reasonable agreement with experiment (always qualitative and sometimes quantitative) lends confidence to the new surface.

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Seudoaneurisma arterial pulmonarsecundario a cateterismo coronario / Pulmonary artery pseudoaneurysm secondary to coronary catheterizarion

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Lipoma mediastínico y síndrome de vena cava superior / Mediastal lipoma and superior vena cava syndrome

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Can we predict the conformational preference of amides?

To what extent, if any, is the conformation of secondary amides revealed by theory? This question has now been addressed by computational methods using calculations at the B3LYP/6-31G level of theory and (1)H NMR spectroscopy. Both gas-phase and solvent studies predict a Z-anti conformation to be the lowest in energy for an evaluated series of acetamides. Moreover, Z-anti conformations may also be inferred from the chemical shifts of the N-CH alpha protons determined by NMR spectroscopy. Thus, a proton situated anti to the N-H proton consistently appears approximately 0.8 ppm further downfield than a proton situated gauche to the N-H proton. This finding, which could only be derived by using the DFT calculations of conformational preference as a guide to interpret the NMR data, might prove to be useful as a simple and convenient methodology for establishing amide conformation experimentally.

Understanding diastereofacial selection in carbohydrate-based domino cycloadditions: semiempirical and DFT calculations.

The sequential cycloaddition of nitroalkenes with methyl vinyl ether was investigated by semiempirical (PM3) and density functional methods (B3LYP/6-31G*). The asymmetric version was also examined with a threoconfigured carbohydrate auxiliary. This produces a larger, more flexible system that complicates the calculation. Most transition structures were then fully optimized at the PM3 level and further refinement was done at ab initio levels. This study represents a model case that enables the rationalization of the high facial selectivity observed in carbohydrate-based nitrone- and nitronate-alkene cycloadditions. The selective endo orientation of the [4+2] pathway results from Coulombic attraction and secondary orbital interactions in the transition state. The stereochemical outcome is largely influenced by a combination of steric shielding from the bulky chiral substituent at C4 and the anomeric effect that places the nitronate C6-alkoxy group in a pseudoaxial arrangement. The resulting conformation favors the subsequent exo approach of methyl vinyl ether to the less hindered re face of the nitronate. It is also remarkable to note that solvation energies stabilize significantly a particular transition structure, thereby explaining the marked stereoselection observed in a polar medium.

Conversion to controlled-release levodopa/carbidopa treatment and quality of life as measured by the Nottingham Health Profile. The STAR Study Group.

BACKGROUND: Controlled-release levodopa-carbidopa (CRLC) improves some aspects of Parkinson's disease (PD) in patients previously treated with standard levodopa formulations (SL). However, little is known about the effect of this strategy on the health-related quality of life (QoL). OBJECTIVE: To assess the QoL and clinical changes due to the conversion of treatment from SL to CRLC in patients with mild to moderate PD. PATIENTS AND METHODS: Through the Nottingham Health Profile (NHP), QoL was measured in 276 non-selected PD patients included in a multicenter, open study. Guidelines for switching to CRLC and optimization of treatment were given. Assessment of patients was carried out by means of the Hoehn & Yahr, UPDRS, and Schwab & England scales, and questionnaires for dyskinesias and sleep. Examination of the NHP-Spanish Version-scaling properties by fitting data to the Rasch model, disclosed that 3 NHP scales (Emotional reactions, Pain, and Physical mobility) and the NHP distress index (NHPD) were suitable for efficacy analysis. RESULTS: Comparison of scores at baseline and at the end of the study showed significant improvement (paired Student t-test, p < 0.0001) in all these four scales associated with the change to CRLC. Responsiveness to change of the NHP was high. In the present study, changes in QoL were not contingent to baseline factors such as age, gender, stage of disease or ADL capabilities. CONCLUSION: Conversion to CRLC significantly improves the QoL of patients with mild to moderate PD.

Controlled release levodopa in Parkinson's disease: influence of selection criteria and conversion recommendations in the clinical outcome of 450 patients. STAR Study Group.

We present the results of an open, prospective, multicentric study including 450 patients with mild to moderate Parkinson's disease (PD) converted from standard Sinemet to Sinemet CR (controlled release; Dupont Pharma, Pavia, Italy). Patients with complex fluctuations and diphasic dyskinesias were excluded and the conversion was made after some recommendations, depending on the clinical problems and the daily dosage and administration schedule of standard (STD) Sinemet. The condition of more than 60% of the patients improved after the change and 80% of them preferred the CR formulation by the end of the study. We found a moderate, but significant, improvement in most of the efficacy parameters used, such as the Unified Parkinson's Disease Rating Scale (UPDRS), the Schawb and England scale, and dyskinesias and sleep questionnaires. Forty-five patients (10%) discontinued the study due to adverse effects (mainly gastrointestinal disturbances, functional deterioration, and dyskinesias). We conclude that Sinemet CR is a useful and safe therapeutic option in patients with mild and moderate PD. Selection of the patients is the most important outcome factor.