Evaluación de la función muscular del cuádriceps en pacientes con EPOC modera-severa / Evaluation of quadricep muscle function in patients with moderate-severe COPD

Objetivo: el objetivo del estudio fue evaluar la función muscular periférica de pacientes con EPOC moderadasevera, mediante la medición de la fuerza muscular isométrica e isotónica del cuádriceps y la masa muscular mediante ecografía. Método: fueron incluidos pacientes con EPOC moderada-severa estables, remitidos a Rehabilitación Respiratoria. En la extremidad dominante, se midió la fuerza isométrica (dinamómetro hidráulico), test 1RM y se realizó una ecografía para obtener el área transversal y dimensiones de diversas secciones musculares. Resultados: participaron 34 pacientes con EPOC estable: GOLD 2 (n = 11), GOLD 3 (n = 12) y GOLD 4 (n = 11) Los GOLD 4 tenían un IMC P50 (P25 - P75) 25,3 (22,5 - 28,8), significativamente menor que los GOLD 3: 32,0 (27,5 - 34,0); p = 0,025. Se evidenció debilidad del cuádriceps (1RM/peso <0,60 1RM/IMC <120%), de forma global: 0,33 (0,22 - 0,41) y 93% (61 - 112) respectivamente, y en cada grupo, sin diferencias significativas entre ellos. Tampoco hubo diferencias significativas entre los grupos en las mediciones de ecografía muscular. La fuerza isotónica (1RM) se correlacionó con el grosor del cuádriceps QT (r = 0,529; p = 0,003) y el grosor del músculo vasto intermedio Q1(r = 0,514; p = 0,004) La fuerza isométrica se correlacionó con el QT (0,621; p <0,001), Q1 (0,441; p = 0,009) y el área transversal AQ (r = 0,587; p <0,001) Para cada grupo, el QT y la fuerza isométrica se correlacionaron significativamente. Conclusión: en nuestra serie de pacientes se demuestra la existencia de debilidad muscular del cuádriceps, independientemente del grado de severidad de la enfermedad y en estrecha relación con la masa muscular de dicho músculo. Palabras clave: disfunción muscular, fuerza isotónica, 1RM, fuerza isométrica, ecografía muscular

Objective: The objective of this study was to evaluate peripheral muscle function in patients with moderate-severe COPD by measuring isometric and isotonic muscular strength of the quadriceps and muscle mass through ultrasound. Method: This study included stable patients with moderate-severe COPD who were referred to pulmonary rehabilitation. In the dominant extremity, isometric strength (hydraulic dynamometer) and the 1RM test were measured and an ultrasound was done to determine the transversal area and dimensions of different sections of muscle. Results: 34 stable patients with COPD participated: GOLD 2 (n = 11), GOLD 3 (n = 12) and GOLD 4 (n = 11). GOLD 4 patients had a BMI P50 (P25 - P75) 25.3 (22.5 - 28.8), which was significantly lower than GOLD 3 patients: 32.0 (27.5 - 34.0); p = 0.025. Weakness in the quadriceps was observed (1 RM/weight <0.60; 1 RM/BMI <120%) overall: 0.33 (0.22 - 0.41) and 93% (61 - 112), respectively, and in each group, without significant differences between groups. There were also no significant differences between groups for ultrasound muscle measurements. Isotonic strength (1 RM) correlated to quadricep thickness QT (r = 0.529; p = 0.003) and vastus intermedius muscle thickness Q1(r = 0.514; p = 0.004). Isometric strength correlated to QT (0.621; p <0.001), Q1 (0.441; p = 0.009) and transversal area AQ (r = 0.587; p <0.001). QT and isometric strength were significantly correlated in each group. Conclusion: In our study, patients showed muscular weakness in the quadriceps, regardless of the degree of disease severity and this weakness was closely related to the mass of said muscle

Efectos del entrenamiento al ejercicio en pacientes con síndrome overlap SAHS-EPOC / Effects of exercise training in patients with SAHS-COPD overlap syndrome

Objetivo: comprobar el efecto beneficioso sobre la capacidad de esfuerzo de un programa de entrenamiento al ejercicio combinado (RR) con tratamiento de ventilación mecánica no invasiva (VMNI), frente a cada uno de ellos de forma aislada, en pacientes con síndrome overlap EPOC-SAHS. Método: estudio analítico experimental en el que los pacientes se incluyeron de forma prospectiva y con asignación aleatoria a seguir la terapia habitual con VMNI o formar parte del grupo en programa RR. Un tercer grupo tuvo las dos intervenciones; RR y VMNI. Se estudió la repercusión sobre el tiempo de resistencia (test de ejercicio submáximo) y la distancia recorrida (prueba de paseo de los 6 minutos). Se midió también repercusión sobre síntomas medidos con mMRC y CRDQ así como el intercambio gaseoso. Se analizaron parámetros inflamatorios como IL6, IL8, PCR y TNF. Resultados: se analizaron un total de 30 pacientes distribuidos de forma homogénea en los 3 brazos del estudio. Los pacientes sometidos a RR, tanto de forma aislada como combinada con VMNI obtuvieron una mejoría en el tiempo de endurance (grupo RR 8,89 min pre, 25,9 min post, p = 0,008; grupo RRVMNI 6,8 min pre, 12,2 min post, p= 0,03) mientras que sólo el grupo sometido a VMNI-RR obtuvo mejoría estadísticamente significativa en el T6MM (282 m pre, 323 m post, p = 0,017). Los tres grupos obtuvieron mejoría en los cuestionarios de calidad de vida medidos por el CRDQ mientras que sólo el grupo sometido a VNI y el grupo mixto obtuvieron mejoría en la mMRC. En cuanto a parámetros gasométricos, sólo el grupo mixto obtuvo mejoría en los niveles de pCO2 (56 mmHg pre, 48 mmHg post, p = 0,02). No hubo mejorías estadísticamente significativas en cuanto a la evolución de parámetros inflamatorios. Conclusiones: este trabajo demuestra el efecto beneficioso sobre la capacidad de esfuerzo de un programa de entrenamiento al ejercicio combinado con tratamiento de VMNI, frente a cada uno de ellos de forma aislada, en pacientes con síndrome overlap

Objective: To compare the beneficial effect of an exercise training program (RR) combined with non-invasive mechanical ventilation (NIMV) on effort capacity, compared to each treatment separately, in patients with COPD-SAHS overlap syndrome. Methods: An experimental analytical study in which patients were prospectively included and randomly assigned to receive habitual NIMV therapy or form a part of the RR program group. A third group underwent both RR and NIMV treatments. The effects on endurance time (submaximal exercise test) and distance covered (6-minute walk test) were studied. The effect on symptoms measured with mMRC and CRDQ as well as gas exchange were also studied. Inflammatory parameters like IL6, IL8, CRP and TNF were analyzed. Results: A total of 30 patients homogeneously distributed between the three arms of the study were analyzed. Patients who underwent RR, both alone and in combination with NIMV, showed an improvement in endurance time (RR group: 8.89 min pre, 25.9 min post, p = 0.008; RR-NIMV group: 6.8 min pre, 12.2 min post, p = 0.03) while only the group undergoing RR-NIMV showed statistically significant improvement in the 6MWT (282 m pre, 323 m post, p = 0.017). All three groups showed improvement with regard to quality of life measured by the CRDQ while only the group undergoing NIMV and the mixed group showed improvement in the mMRC. With regard to gasometric parameters, only the mixed group showed improvement in pCO2 levels (56 mmHg pre, 48 mmHg post, p = 0.02). There were no statistically significant improvements with regard to the evolution of inflammatory parameters. Conclusions: This study shows the beneficial effect of an exercise training program combined with NIMV treatment on effort capacity, compared to each treatment separately, in patients with COPD-SAHS overlap syndrome

Relación entre el grado de extensión del enfisema y alteraciones morfológicas musculares periféricas en pacientes con EPOC / Relationship between the degree to which emphysema has extended and morphological changes in peripheral musclesin patients with COPD

Nuestro objetivo fue evaluar si existían diferencias en distintos parámetros basales según la prevalencia de enfisema y analizar las alteraciones estructurales y morfológicas de la fibra muscular periférica del paciente EPOC frente al sujeto sano y las posibles diferencias según el predominio enfisematoso que presente. Para ello, estudiamos a 19 pacientes varones (edad 65 ± 3,2) diagnosticados de EPOC (FEV1 44,6 ± 13,2 en % del teórico) y 8 sujetos sanos no fumadores. En base a los resultados de la TC de alta resolución, 10 pacientes fueron considerados con 'predominio enfisema' (PE) y 9 sin 'predominio enfisema' (NPE). Se realizó una estimación de la fuerza muscular por el test de una repetición máxima (Test 1RM), test de esfuerzo máximo, submáximo y prueba de paseo de los 6 minutos, valoración del índice de la disnea basal (IDB) y calidad de vida (CRDQ) y biopsia del vasto lateral del músculo cuádriceps. Los pacientes con PE presentan a esfuerzo máximo una significativa menor carga de trabajo y consumo de oxígeno máximo (VO- 2peak de 55,1 ± 12,6 versus 60,5 ± 15,9) y una menor fuerza muscular periférica (1RM) en tres de los cinco ejercicios realizados. No existían diferencias en el test de endurance ni en la distancia paseada. Tampoco existían diferencias significativas entre los dos grupos en las distintas categorías ni en el total del CRDQ. Sin embargo, los pacientes con PE puntuaban significativamente peor en todos los dominios del IDB (IDB focal score de 4,5 ± 1,4 versus 5,8 ± 3,5). Los pacientes con EPOC presentan en el músculo cuádriceps un menor porcentaje de fibras tipo I (33,5 ± 10,3 versus 51,8 ± 3,6) y mayor porcentaje de fibras tipo II (3,2 ± 1,3 versus 1 ± 0,4) con respecto al sujeto sano y una menor relación capilar/fibra e inferior densidad capilar. El descenso en el porcentaje en la fibras tipo I es significativamente mayor en el paciente EPOC con PE (30,9 ± 8,9 versus 35,7 ± 6,2). En conclusión, los pacientes con EPOC con PE refieren significativamente menor capacidad de esfuerzo máximo, mayor disnea y menor fuerza muscular periférica que los pacientes EPOC con NPE. Los pacientes con EPOC presentan en el músculo cuádriceps un menor porcentaje de fibras tipo I y mayor porcentaje de fibras tipo II con respecto al sujeto sano y esta alteración en el porcentaje de las fibras del músculo periférico es significativamente mayor en el paciente EPOC con PE

Our aims were to assess whether there are differences in different baseline parameters depending on the prevalence of emphysema, and analyze the structural and morphological alterations of peripheral muscle fibers in COPD patients compared to healthy subjects and differences according to the present dominance emphysema. We studied 19 male patients (age 65 ± 3.2) diagnosed with COPD (FEV1 44.6 ± 13.2%) and 8 healthy nonsmokers. Based on the results of the high resolution CT, 10 patients were considered to have 'predominant emphysema' (PE) and 9 without 'predominant emphysema' (NPE).An estimate of muscle strength test is performed by the one repetition maximum (1RM Test), maximal exercise test, submaximal test and walk 6 minutes, assessment of baseline dyspnea index (BDI) and quality of life (CRDQ) and biopsy of the vastus lateralis of the quadriceps muscle. Patients with PE presented a significantly lower maximum stress load and maximum oxygen consumption (VO2peak 55.1 ± 12.6 versus 60.5 ± 15.9) and had a lower peripheral muscle strength (1RM) in three five exercises. There were no differences in the endurance test or walking distance. There are no significant differences between groups in different categories or the total CRDQ. However, patients with PE score significantly worse in all domains of the IDB (IDB focal score of 4.5 ± 1.4 versus 5.8 ± 3.5). Patients with COPD quadriceps muscle in a lower percentage of type I (33.5 ± 10.3 versus 51.8 ± 3.6) and higher percentage of type II fibers (3.2 ± 1.3 versus 1 ± 0.4) compared to the healthy subject and a lower capillary/fiber ratio and capillary density lower. The decline in the percentage of type I fibers was significantly higher in COPD patients with PE (30.9 ± 8.9 versus 35.7 ± 6.2). In conclusion, patients with COPD with PE refer significantly lower maximal exercise capacity, more dyspnea and lower peripheral muscle strength that COPD patients with NPE.COPD patients have a lower percentage of type I fibers and greater percentage of type II fiber for healthy subject and this alteration in the percentage of fibers peripheral muscle is significantly higher in the COPD patient with PE

Valoración de la masa muscular por bioimpedancia en pacientes con EPOC / Assessmen tof musclemassusing bioelectricalimpedance in patients with COPD

OBJETIVO: recientemente se ha descrito un método para estimar la masa muscular total (MMT) a partir de los datos obtenidos en una bioimpedancia corporal. Los objetivos del presente trabajo fueron calcular diversos parámetros de MMT, a partir de los datos de la bioimpedancia y estudiar la relación entre estos parámetros y el resto de parámetros de bioimpedancia, así como su posible relación con parámetros clínicos y funcionales. MÉTODO: el presente trabajo es un estudio observacional transversal sobre pacientes con EPOC estable. A los pacientes incluidos se les realizó una evaluación clínica, funcional y de ejercicio. Mediante bioimpedancia, se calculó la MMT y tres parámetros asociados: su porcentaje respecto al peso total (MMTp), su porcentaje respecto a la masa magra y el índice de MMT. RESULTADOS: el grupo estaba compuesto por 85 pacientes con EPOC (79 hombres; edad 64(7) años; FEV1 61(9)%). Los hombres tenían significativamente mayor MMT que las mujeres (14,7(2,7) Kg vs 24,5(3,7) Kg, p < 0,001). Los valores de MMTp fueron los que tuvieron una mejor relación significativa, con parámetros de capacidad pulmonar (TLC r = 0,461, p < 0,001) y capacidad de ejercicio (consumo de oxígeno r = 0,325 p = 0,024; test 6 minutos r = 0,255; p = 0,019). El estudio multivariante confirmó estas asociaciones (R2 = 0,606, p < 0,001). CONCLUSIÓN: el estudio de la composición corporal por bioimpedancia permite hacer una estimación de la MMT que está relacionada con variables funcionales y de ejercicio en los pacientes con EPOC. La expresión de la MMTp es el parámetro con mayores relaciones con estas variables

OBJECTIVE: Recently, a method has been described to estimate total muscle mass (TMM), based on data obtained from a bioelectrical impedance of the body. The objective of this work was to calculate the various TMM parameters, based on the data provided by bioelectrical impedance, to then study the relationship between these parameters and other bio-impedance parameters, as well as their possible relationship with clinical and functional parameters. METHOD: the work is an observational, transversal study of patients with stable COPD. Patients included in this study underwent a clinical, functional and exercise assessment. Using bioelectrical impedance, TMM was calculated as were three associated parameters: percentage regarding total body weight (TMMp), percentage regarding lean mass and TMM index. RESULTS: the test group included 85 patients with COPD (79 men; 64 years of age (7); FEV1 61(9)%). Males had a significant higher TMM than women (14.7(2.7) Kg. vs. 24.5(3.7) Kg., p < 0.001). The TMMp values had a greater significant relationship with parameters for pulmonary capacity (TLC r = 0.461, p < 0.001) and exercise capacity (oxygen consumption r = 0.325 p = 0.024; test 6 minutes r = 0.255; p = 0.019). The multivariate study confirmed these associations (R2 = 0.606, p < 0.001). CONCLUSION: the body composition study using bioelectrical impedance allows an estimation of TMM to be formulated, which is related to functional variables and exercise in patients with COPD. The expression of TMMp is the parameter with the greatest relationship with these variables

Normativa SEPAR sobre disfunción muscular de los pacientes con enfermedad pulmonar obstructiva crónica / Guidelines for the evaluation and treatment of muscle dysfunction in patients with chronic obstructive pulmonary disease

La disfunción muscular de pacientes con enfermedad pulmonar obstructiva crónica (EPOC) constituye una de las comorbilidades más importantes, con repercusiones negativas en su capacidad de ejercicio y calidad de vida. En la presente normativa se ha resumido la literatura publicada más recientemente sobre los diferentes aspectos del tema y se ha utilizado también la escala Grading of Recommendations Assessment, Development, and Evaluation (GRADE) de recomendaciones sobre el grado de evidencia de las diferentes propuestas de la normativa. Respecto a una población control, se estima que en un tercio de los pacientes EPOC la fuerza del cuádriceps es un 25% inferior incluso en estadios precoces de su enfermedad. Aunque tanto los músculos respiratorios como los de las extremidades están alterados, estos últimos suelen verse mayormente afectados. Diversos factores y mecanismos biológicos están involucrados en la disfunción muscular de los pacientes. Se proponen diversas pruebas para evaluar y diagnosticar el grado de afectación de los músculos respiratorios y de las extremidades (periféricos), así como identificar la capacidad de esfuerzo de los pacientes (prueba de marcha de 6min y cicloergometría). Se describen también las posibles estrategias terapéuticas vigentes que incluyen las diversas modalidades de entrenamiento y de soporte farmacológico y nutricional.(AU)

In patients with chronic obstructive pulmonary disease (COPD), skeletal muscle dysfunction is a major comorbidity that negatively impacts their exercise capacity and quality of life. In the current guidelines, the most recent literature on the various aspects of COPD muscle dysfunction has been included. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) scale has been used to make evidence-based recommendations on the different features. Compared to a control population, one third of COPD patients exhibited a 25% decline in quadriceps muscle strength, even at early stages of their disease. Although both respiratory and limb muscles are altered, the latter are usually more severely affected. Numerous factors and biological mechanisms are involved in the etiology of COPD muscle dysfunction. Several tests are proposed in order to diagnose and evaluate the degree of muscle dysfunction of both respiratory and limb muscles (peripheral), as well as to identify the patients' exercise capacity (six-minute walking test and cycloergometry). Currently available therapeutic strategies including the different training modalities and pharmacological and nutritional support are also described.(AU)

Expresión local de reactantes de fase aguda en la enfermedad pulmonar obstructiva crónica / Local expression of acute-phase reactants in chronic obstructive pulmonary disease

Objetivo: Determinar la expresión de ARN, de proteína-C-reactiva (PCR) y amiloide-A-sérico (AAS) en parénquima pulmonar y tejido bronquial de pacientes EPOC en fase estable. Comparar dicha expresión de ARNm con la de sujetos fumadores sin la enfermedad. (..) (AU)

Objective: To determine the mRNA expression of C-reactive protein (CPR) and serum amyloid-A (SAA) in pulmonary parenchyma and (..) (AU)

Evolución de los indicadores bibliométricos de producción y repercusión de la revista Neumosur (2002-2006) / Evolution of the bibliometric indicators of production and impact of the Neumosur journal (2002-2006)

Objetivos. Evaluar la producción científica que la revista Neumosurha tenido entre los años 2002-2006 mediante un estudiobibliométrico de producción y repercusión.Métodos. Se recogieron todas las publicaciones de la revistaNeumosur entre los años 2002-2006 y se introdujeron en una basede datos, con lo que se realizó un estudio descriptivo. En unsegundo tiempo, se calcularon diversos indicadores bibliométricosde producción y repercusión para cada año de la revista como son:índice de Lotka, índice de cooperación, tasa de referencias, visibilidad,influencia, semiperiodo de las citas y el factor de impacto.Resultados. Durante el periodo de estudio, la revista Neumosurha publicado 102 artículos: 14 (13,7%) editoriales, 44 (43,1%)originales, 22 (21,6%) artículos de revisión, 15 (14,7%) notas clínicasy 7 (6,9%) cartas al director. De ellos, 81 (79,4%) eran artículoscitables. La cooperación disminuyó progresivamente hasta 3,04para el año 2006 con una producción similar a periodos previos asícomo el número de originales. La revista Neumosur ha recibido untotal de 5 citas internacionales y 26 citas de la revista Neumosur. Elfactor de impacto máximo alcanzado por la revista fue de 0,069 enel año 2004 que ascendió a 0,207 para ese mismo año teniendo encuenta las citas de la propia revista Neumosur.Conclusiones. La evolución de los indicadores de producción yrepercusión de la revista Neumosur reflejan una meseta para lamayoría de los indicadores con respecto al periodo anterior estudiado (AU)

Objectives. To evaluate the scientific production that the Neumosurjournal has had between the years 2002-2006 by means of a bibliometricstudy of production and impact.Methods. All the editions of the Neumosur journal between theyears 2002-2006 were included and were introduced into a data base,with which a descriptive study was made. Later, several bibliometricindicators of production and impact for every year of the journalwere calculated: Lotka’s index, cooperation index, reference rate, visibility,influence, half period of the citations and the impact factor.Results. During the period of study, the Neumosur journal haspublished 102 articles: 14 (13.7%) editorials, 44 (43.1%) originals, 22(21.6%) review articles, 15 (14.7%) clinical notes and 7 (6.9%) lettersto the director. Of those, 81 (79.4%) were citable articles. The cooperationdiminished progressively down to 3.04 for the year 2006 with aproduction similar to previous periods as well as the number of originals.The Neumosur journal has received a total of 5 internationalcitations and 26 national citations. The maximum impact factorreached by the journal was 0.069 in 2004 that rose to 0.207 for thesame year when considering citations of the Neumosur journal itself.Conclusions. The evolution of the production and impact indicatorsof the Neumosur journal reflect a plateau for most of the indicatorswith respect to the previously studied period (AU)

Evolución de los indicadores bibliométricos de producción y repercusión de la revista Neumosur (2002-2006) / Evolution of the bibliometric indicators of production and impact of the neumosur journal (2002-2006)

Objetivos. Evaluar la producción científica que la revista Neumosur ha tenido entre los años 2002-2006 mediante un estudio bibliométrico de producción y repercusión. Métodos. Se recogieron todas las publicaciones de la revista Neumosur entre los años 2002-2006 y se introdujeron en una base de datos, con lo que se realizó un estudio descriptivo. En un segundo tiempo, se calcularon diversos indicadores bibliométricos de producción y repercusión para cada año de la revista como son: índice de Lotka, índice de cooperación, tasa de referencias, visibilidad, influencia, semiperiodo de las citas y el factor de impacto. Resultados. Durante el periodo de estudio, la revista Neumosur ha publicado 102 artículos: 14 (13,7%) editoriales, 44 (43,1%) originales, 22 (21,6%) artículos de revisión, 15 (14,7%) notas clínicas y 7 (6,9%) cartas al director. De ellos, 81 (79,4%) eran artículos citables. La cooperación disminuyó progresivamente hasta 3,04 para el año 2006 con una producción similar a periodos previos así como el número de originales. La revista Neumosur ha recibido un total de 5 citas internacionales y 26 citas de la revista Neumosur. El factor de impacto máximo alcanzado por la revista fue de 0,069 en el año 2004 que ascendió a 0,207 para ese mismo año teniendo en cuenta las citas de la propia revista Neumosur. Conclusiones. La evolución de los indicadores de producción y repercusión de la revista Neumosur reflejan una meseta para la mayoría de los indicadores con respecto al periodo anterior estudiado

Objectives. To evaluate the scientific production that the Neumosur journal has had between the years 2002-2006 by means of a bibliometric study of production and impact. Methods. All the editions of the Neumosur journal between the years 2002-2006 were included and were introduced into a data base, with which a descriptive study was made. Later, several bibliometric indicators of production and impact for every year of the journal were calculated: Lotka’s index, cooperation index, reference rate, visibility, influence, half period of the citations and the impact factor. Results. During the period of study, the Neumosur journal has published 102 articles: 14 (13.7%) editorials, 44 (43.1%) originals, 22 (21.6%) review articles, 15 (14.7%) clinical notes and 7 (6.9%) letters to the director. Of those, 81 (79.4%) were citable articles. The cooperation diminished progressively down to 3.04 for the year 2006 with a production similar to previous periods as well as the number of originals. The Neumosur journal has received a total of 5 international citations and 26 national citations. The maximum impact factor reached by the journal was 0.069 in 2004 that rose to 0.207 for the same year when considering citations of the Neumosur journal itself. Conclusions. The evolution of the production and impact indicators of the Neumosur journal reflect a plateau for most of the indicators with respect to the previously studied period

Valoración de la capacidad laboral e incapacidad/invalidez en las enfermedades respiratorias / No disponible

No disponible

Human hepatic stellate cells secrete adrenomedullin: potential autocrine factor in the regulation of cell contractility.

BACKGROUND/AIMS: Hepatic stellate cells (HSCs) are perisinusoidal pericytes which have receptors for vasoactive factors, such as endothelin-1, which can regulate cell contractility in an autocrine manner. It is unknown whether human HSCs have receptors for and are able to synthesize the vasodilator peptide adrenomedullin (ADM), a peptide produced by most contractile cells. METHODS AND RESULTS: Stimulation of HSCs with ADM resulted in a dose-dependent raise in cAMP concentration (radioimmunoassay) and markedly blunted the endothelin-induced increase in [Ca2+]i and cell contraction, as assessed in cells loaded with fura-2 using a morphometric method. The existence of the receptor CRLR for ADM and their associated proteins RAMP-1 and RAMP-2 was demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR). Moreover, activated human HSCs spontaneously secreted ADM in the culture medium in a time-dependent manner. ADM secretion was markedly enhanced by tumour necrosis factor-alpha and interleukin-1beta. Specific mRNA for ADM (RT-PCR and Northern blot) was detected in HSCs and increased after incubation of cells with cytokines. CONCLUSIONS: Human HSCs have functional receptors for ADM, the stimulation of which blunts the contractile effect of endothelin-1. Cultured human HSCs secrete ADM in baseline conditions. This secretion is markedly increased by cytokines. These results suggest that ADM can regulate HSCs' contractility in an autocrine manner.

Long-term aquaretic efficacy of a selective nonpeptide V(2)-vasopressin receptor antagonist, SR121463, in cirrhotic rats.

Water retention in experimental cirrhosis can be reversed by blocking V(2)-vasopressin (AVP) receptors with the nonpeptide antagonist OPC-31260 or by using the kappa-opioid receptor agonist niravoline, a compound inhibiting central AVP release. However, reluctance to use these drugs in human beings has emerged because the former loses aquaretic efficacy in rats after 2 days of treatment and the latter may have adverse effects in humans. Recently, a new potent and selective nonpeptide V(2)-AVP receptor antagonist, SR121463, has been developed that could be useful for the treatment of dilutional hyponatremia in human cirrhosis. The current study assessed the aquaretic efficacy of 10-day chronic oral administration of SR121463 (0.5 mg/kg/day) in cirrhotic rats with ascites and impaired water excretion after a water load (minimum urinary osmolality >160 mOsm/kg and percentage of water load excreted <60%). Urine volume (UV), osmolality (U(Osm)V), and sodium excretion (U(Na)V) were measured daily. At the end of the 10-day treatment, mean arterial pressure also was measured. In basal conditions cirrhotic rats showed ascites, sodium retention, and impaired water excretion. UV, U(Osm)V, and U(Na)V did not change throughout the study in cirrhotic rats receiving the vehicle. In contrast, SR121463 increased UV and reduced U(Osm)V during the 10-day treatment. This resulted in a greater renal ability to excrete a water load and normalization in serum sodium and osmolality. During the first 6 days of treatment, SR121463 also increased U(Na)V without affecting mean arterial pressure. These data suggest that SR121463 could be of therapeutical value for chronic management of human cirrhosis.

[Peripheral muscle strength in stable COPD patients: correlation with respiratory function variables and quality of life]. / Fuerza de los músculos periféricos en pacientes con EPOC estable: correlación con parámetros funcionales respiratorios y de calidad de vida.

The aim of this study was to assess peripheral muscle strength in patients with chronic obstructive pulmonary disease (COPD) using a simple test and to look for correlation with function variables, physiological strength variables and quality of life parameters. Twenty-three COPD patients with moderate to severe air-flow limitation (FEV1 = 39 +/- 12%) in stable phase but displaying inability to carry out daily tasks were enrolled. Peripheral muscle strength was assessed in all patients by measuring the maximum load in a single repetition of five simple upper and lower extremity exercises performed at a multi-gymnastics station. Results were compared to respiratory function variables (FVC, FEV1, FEV1/FVC and gasometry), to results of an exercise test on a cycle ergometer with monitoring of respiratory gases (VEmax, VO2max and Wmax), to endurance (minutes) to dyspnea (Mahler's scale) and to quality of life (Chronic Respiratory Disease Questionnaire-CRDQ). No relation between functional parameters and endurance in minutes was found. Minute ventilation (VE) proved to be significantly related to oxygen intake (VO) and maximum work in the stress test. Dyspnea on Mahler's scale was unrelated, but fatigue variables and emotional function variables on the CRDQ were related. We conclude that peripheral muscle strength is unrelated to level of flow limitation or exercise tolerance in COPD patients. Peripheral muscle strength is related, however, to maximum work load and some aspects of quality of life.

Vascular endothelial growth factor production in peritoneal macrophages of cirrhotic patients: regulation by cytokines and bacterial lipopolysaccharide.

Vascular endothelial growth factor (VEGF) is an angiogenic peptide with vascular permeability and relaxing properties. This study assessed whether peritoneal macrophages of cirrhotic patients can be up-regulated to produce VEGF under proper stimulatory conditions. Macrophages were isolated from ascites. VEGF protein secretion and mRNA expression were measured in basal conditions and after stimulation with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), and interleukin-1 (IL-1). These substances induced a time- and dose-dependent increase in both VEGF production and transcript expression. Assays with actinomycin D showed that VEGF mRNA induction is secondary to both higher VEGF gene transcription and mRNA stability. Ascites and plasma concentration of VEGF was also measured in cirrhotic patients with (n = 15) and without (n = 10) spontaneous bacterial peritonitis (SBP). Plasma values did not differ between both groups of patients. However, ascites VEGF levels were higher in SBP patients than in noninfected cirrhotic patients (710 +/- 183 vs. 94 +/- 15 pg/mL; P <.025). These results indicate that cytokines and LPS markedly increase VEGF protein secretion and mRNA expression in macrophages of cirrhotic patients, and suggest that this substance could be an important mediator of the pronounced arterial vasodilation frequently occurring in SBP patients.

[Efficacy of a program for tobacco use cessation with a combined substitution treatment of nicotine (patches plus chewing gum) at 6 months of follow-up]. / Eficacia de un programa de deshabituación al tabaco con tratamiento sustitutivo combinado de nicotina (parches más chicles) a los 6 meses de seguimiento.

Our aim was to assess the efficacy after 6 months of combined smoking cessation therapy using nicotine substitution with both chewing gum and patches. Sixty-six (25 women, 41 men) heavy smokers (38.04 packs/year and 8.42 mean score on Fagerström test) were followed between September 1995 and March 1997. Most patients were referred by respiratory, cardiology or ear-nose-and-throat outpatient clinics. The patients were prescribed 24-hour nicotine substitution therapy with 21 mg patches, plus chewing gum providing 2 mg of nicotine (3 to 10 per day) for a minimum of 8 weeks and a maximum of 12, with gradually decreasing doses. The patients were checked 1, 2, 4, 8, 12 and 24 weeks after enrollment. Expired air carbon monoxide was measured to confirm abstinence at each checkup and a simple questionnaire was filled in to assess abstinence syndrome and detect the presence of treatment side effects. Rate of abstinence achieved with this protocol after six months of follow-up was 37.9%. The failure rate was highest in the first week (33%) but gradually decreased until week 12. No patients had to abandon treatment due to side effects.