Prevención no farmacológica de las exacerbaciones en la EPOC: efecto antiinflamatorio de la actividad física / Non-pharmacological prevention of exacerbations in COPD: anti-inflammatory effect of physical activity

The chronic obstructive pulmonary disease (COPD) is the chronic respiratory condition most prevalent in adults, caused mainly by smoking. Its burden is progressively increasing and, according to the World Health Organization, is one of the main causes of mortality and disability around the world. Patients with COPD present acute worsening of the disease, defined as acute exacerbations, which are the main cause of hospitalizations and deaths. Therefore, it is crucial to identify effective interventions focused in their prevention. Patients with COPD present dyspnoea and intolerance to exercise responsible for a progressive reduction in the level of physical activity, which is an independent risk factor for future exacerbations and mortality. On the other hand, it has been demonstrated that COPD patients with low level of physical activity present higher marker levels of systemic inflammation. Interventions able to increase the level of physical activity in COPD patients have demonstrated positive effects in quality of life and a few clinical trials suggest that improving physical activity is able to prevent exacerbations. We hypothesize that these effects could be explained by changes in systemic inflammation secondary to an increase of physical activity. (AU)

Artritis reumatoide y riesgo cardiovascular / Rheumatoid arthritis and cardiovascular risk

Cardiovascular disease (CVD) is the most frequent cause of premature death according to data from the American Heart Association and World Health Organization. Incidence and prevalence are on the rise. Rheumatoid Arthritis (RA) is the most common autoimmune disease. It is a chronic and systemic disease characterized by articular involvement with deformity ranging from persistent pain to premature disability. CVD is the most frequent cause of death in RA patients, even more than in diabetes mellitus 2 or chronic kidney disease. Multiple CVD risk scales have been tested in order to obtain a more accurate prediction of premature death by stroke or myocardial infarction in RA patients. Most of the scales, even those adjusted including RA features like inflammation and antibodies titles, have failed to properly predict the real CVD risk. Individually, RA specific autoantibodies have been related with increased CVD risk and multiple mechanistic explanations have arisen, generating even a new concept called "Autoimmune Atheromatosis". Nevertheless, this association fails to give a full understanding of the accelerated and aggressive atheromatosis process that RA patients develop. New studies oriented to mechanistic explanations are necessary in order to develop new diagnostic targets and prevention strategies. (AU)

Colesterolosis vesicular: algunos aspectos de su fisiopatología / Vesicular cholesterolosis: some aspects of its pathophysiology

Gallbladder cholesterolosis is a nosological clinical entity where the central element is the deposit of lipids in immune cells that reside under the gallbladder epithelium. The mechanisms involved in its development are not entirely clear, but they seem to have some resemblances that are observed in the wall of the arteries with atherosclerosis. The lipid-laden cells observed in the gallbladder wall appear to share many of the characteristics of atherosclerosis foam cells, which by means of scavenger receptors have endocited oxidized low-density lipoproteins and accumulate them in their cytoplasm. Foam cells, in themselves, are not dangerous, but in atherosclerosis at least they can become a problem when they are located in vessels and specific anatomic sites. The role they may have in the gallbladder is not known to date. We will review some considerations that seem relevant to us to elucidate if these entities share the same protagonist: macrophages transformed by modified lipids. (AU)

Etiología de la neumonía asociada a ventilación mecánica en un hospital clínico: Asociación con co-morbilidad, uso previo de antimicrobianos y mortalidad / Etiology of ventilator-associated pneumonia in a university hospital: Association with comorbidity, previous use of antibiotics and mortality

Ventilator-associated pneumonia (VAP) is a complication with an increased risk of morbidity and mortality. Inadequate antibiotic treatment is a risk factor of mortality which can be improved. For this reason it is important to know the local etiology of VAP. During a one year-period we investigated the etiology of VAP in a teaching hospital. Forty eight VAP were included, of which 19 were women. The median age was 59.5 (range 17-91 years), twelve VAP were early onset. Methicillin resistant Staphylococcus aureus (MRSA) was the main microorganism isolated, regardless of timing of diagnosis of VAP, followed by polimicrobial etiology, Acinetobacter sp and P. aeruginosa. Etiology was not associated with comorbidity; however previous antibiotic use was related with MRSA and polymicrobial etiology. Mortality was 35 percent and was mainly associated with P. aeruginosa isolation. Conclusion: MRSA was the main cause of VAP regardless of the timing of its occurrence.

La neumonía asociada a la ventilación mecánica (NAVM) es una complicación relacionada con un aumento de morbilidad y mortalidad. Dentro de los factores de mal pronóstico, el tratamiento antimicrobiano inadecuado es una de las variables que puede corregirse. Para esto debe conocerse la etiología institucional de la NAVM. Durante un año se recopilaron las NAVM con documentación microbiológica en un hospital universitario. En total, 48 neumonías fueron incluidas, 19 en pacientes femeninas, la mediana de la edad fue de 59,5 años (rango 17-91), 12 de ellas precoces. Staphylococcus aureus meticilina resistente (MRSA) fue el principal agente involucrado, independiente del momento de su génesis, seguido por la etiología polimicrobiana, Acinetobacter sp y Pseudomonas aeruginosa, en ese orden. La etiología no se asoció con la existencia de co-morbilidad, el uso previo de antimicrobianos se asoció con la presencia de MRSA y etiología polimicrobiana. La letalidad fue de 35 por ciento y se relacionó, principalmente, con la presencia de P. aeruginosa. Conclusión: La principal causa de NAVM en esta experiencia fue SAMR, independiente del momento evolutivo de su ocurrencia.

Papel del sistema inmune en el desarrollo de las enfermedades inflamatorias intestinales / Role of the immune system in inflammatory bowel diseases development

Las enfermedades inflamatorias intestinales (EII), entre las que se incluyen a la enfermedad de Crohn (EC) y colitis ulcerosa (CU), son patologías de etiología multifactorial, en las cuales se ha demostrado en los últimos años que el componente genético tiene un papel relevante. La incidencia de estas patologías ha ido en aumento en los países desarrollados y también en Chile. A pesar de los avances en su estudio, la etiología de las EII no está totalmente esclarecida, aunque es posible reconocer factores genéticos, inmunológicos y ambientales en su patogénesis. Entre los posibles mecanismos propuestos la respuesta alterada a antígenos bacterianos cumpliría un papel relevante en un subgrupo de pacientes con EC quienes presentan alguna mutación en los receptores que reconocen patógenos. Esta revisión analiza avances recientes en el conocimiento de las EII y destaca los hallazgos relacionados con alteraciones en los componentes del sistema inmune gastrointestinal y su posible relación con la patogenia de las EII. Un análisis detallado de la interrelación entre los diferentes integrantes del sistema inmune de la mucosa intestinal, tales como las células dendríticas, epiteliales, de Paneth y los linfocitos T y su actividad defectuosa podría brindar nuevas herramientas para el diseño de estrategias experimentales y terapéuticas de las EII.

Volumen sanguíneo intratorácico versus presión arterial de oclusión pulmonar como estimadores de precarga cardíaca en pacientes críticos / Intrathoracic blood volume versus pulmonary artery occlusion pressure as estimators of cardiac preload in critically ill patients

Background:Monitoring of cardiac preload by determination of pulmonary artery occlusion pressure (PAOP) has been traditionally used to guide fluid therapy to optimize cardiac output (CO). Since factors such as intrathoracic pressure and ventricular compliance may modify PAOP, volumetric estimators of preload have been developed. The PiCCO system is able to measure CO and intrathoracic blood volume (ITBV) by transpulmonary thermodilution. Aim: To compare a volumetric (ITBV) versus a pressure (PAOP) determination to accurately estimate cardiac preload in severely ill patients. Patients and Methods: From June 2001 to October 2003, 22 mechanically ventilated patients with hemodynamic instability underwent hemodynamic monitoring with pulmonary artery catheter (PAC) and PiCCO system. ITBV index (ITBVI), PAOP and CI were measured simultaneously by both methods. One hundred thirty eight deltas (D) were obtained from the difference of ITBVI, PAOP, CI-PAC and CI-PiCCO between 6-12 am and 6-12 pm. Linear regression analysis of DITBVI versus Ð CI-PiCCO and Ð PAOP versus DCI-PAC were made. Results: Mean age of patients was 60.8 ± 19.4 years. APACHE II was 23.9 ± 7. Fifteen patients met criteria for acute respiratory distress syndrome (ARDS). Delta ITBVI significantly correlated with DCI-PiCCO (r=0.54; 95% confidence interval = 0.41-0.65; p <0.01). There was no correlation between DPAOP and Ð CI-PAC. Conclusion: ITBVI correlated better with CI than PAOP, and therefore it seems to be a more accurate estimator of preload in unstable, mechanically ventilated patients.

Estrés oxidativo y sepsis / Oxidative stress and sepsis

El Shock Séptico es una importante causa de morbi-mortalidad en pacientes críticos que podría ser explicado, al menos en parte, por una desregulación de la respuesta inmuno-inflamatoria. La liberación de componentes microbianos produciría un desbalance con predominio de agentes prooxidantes como las especies reactivas de oxigeno (EROS), sobre las defensas antioxidantes. Las EROS dañan directamente los tejidos al atacar las biomoléculas e indirectamente actuando como mediadores pro inflamatorios. Estudios efectuados en pacientes críticos que cursan con sepsis, han demostrado disminución de lasdefensas antioxidantes. Esto compete a mecanismos enzimáticos y no enzimáticos entre los que han sido estudiados: actividad de enzimas antioxidantes, niveles plasmáticos de vitaminas antioxidantes y capacidad antioxidante del plasma, parámetros que también han sido correlacionados con elpronóstico de sobrevida de estos pacientes. Además, se ha evidenciado un incremento de los niveles plasmáticos de productos de lipoperoxidación, lo que representa aumento del daño oxidativo en las membranas celulares. Los parámetros relacionados con el estrés oxidativo podrían ser, potencialmente, marcadores útiles, y los agentes antioxidantes podrían ser considerados como una nueva oportunidad terapéutica en el manejo médico de estos pacientes.

Septic Shock is an important cause of morbility and mortality in critically ill patients that might be explained, at least partly, by a dysregulation of immune/inflammatory response. The liberation of microbial components could lead to the development of animbalance between pro-oxidant agents as reactive oxygen species (ROS) and the antioxidants systems, with a prevalence of the first. ROS are known to exert tissue damage by direct attack to biomolecules as well as to act as proinflammatory mediators. Studies performed in critical patients that presented sepsis, have demonstrated a decrease in antioxidants defences in these patients. This effect is characterized by an alteration in the activity of the antioxidant enzymes, as well as a drop in plasma levels ofantioxidant vitamins associated with a decrease of antioxidant capacity of plasma, parameters that have also been related to the prognosis of these patients. In addition, increased plasma levels of lipid peroxidation products have been found, which represents anincrease of the tissue damage caused by oxidative stress, mainly in biological membranes. The oxidative stress related parameters could be potentially used as markers and antioxidant agents couldbe considered as new therapeutic opportunities in the medicalmanagement of these patients.

Nuevas armas inmunológicas para la medicina del siglo XXI: Terapia biológica basada en el uso de anticuerpos monoclonales de última generación / New immunological weapons for Medicine at XXI century: biological therapy based on the use of last generation monoclonal antibodies

The fusion of a murine B cell and a myeloma cell generates a hybridoma that produces monoclonal antibody (mAb). These murine mAb induce the HAMA (human anti-mouse antibodies) response. Murine mAb have been modified by genetic engineering, producing molecules with a higher proportion of human protein. At present, chimeric, humanized and fully human mAb are available. mAb block interactions between target molecules and their ligands or trigger the lyses of mAb-coated tumor cells. Numerous mAb have been developed using the recombinant DNA technology and several are available in the market. Trastuzumab, against HER2/neu, is useful in breast cancer; rituximab, against CD20 in B lymphocytes is useful in lymphoma; alemtuzumab, against CD52 is used in lymphoma and leukemia; daclizumab and basiliximab block the IL-2 receptor interaction and reduce acute rejection in kidney transplantion; abciximab, an antagonist of GPIIb/IIIa platelet receptor, is used in patients undergoing acute coronary syndromes. In autoimmunity diseases, blocking tumor necrosis factor by infliximab and adalimumab has demonstrated excellent results. Thus, infliximab is useful in the treatment of rheumatoid arthritis (RA), Crohn's disease and ulcerative colitis while adalimumab is the first fully human mAb available for RA. Infliximab and adalimumab reduce signs and symptoms in RA and they also interfere with progression of joint damage. Finally, the direct benefits of antagonist treatment can occur at the expense of a major adverse effect in some other biological function (Rev Méd Chile 2003; 131: 1445-53).

Hepatitis colestásica por piroxicam: caso clínico / Cholestatic hepatitis associated to piroxicam use: report of one case

Most nonsteroidal antiinflammatory drugs can produce hepatotoxicity. We report a 22 years old female who presented with an acute cholestatic hepatitis after a prolonged period of piroxicam use. Hepatitis was attributed to this drug since all markers for hepatitis virus (A, B, C, E, Epstein Barr, Cytomegalovirus and Herpex Simplex) were negative, autoimmune markers were negative, serum iron and ceruloplasmin were normal, there was a temporal relationship between the administration of piroxicam and the hepatitis, the histological picture was compatible with this etiology and the patient had a favorable evolution after the discontinuance of the drug. This type of hepatotoxicity is not common but it must be born in mind when patients must receive nonsteroidal antiinflammatory drugs for prolonged periods

Hipersensibilidad retardada a antígenos de evocación: valores normales en adultos jóvenes chilenos / Delayed hypersensitivity to evocation antigens: standard values in chilean young adults

Delayed hypersensitivity skin test are widely accepted as in vivo measure of cellular immunity. Since genetic and environmental factors may affect these tests, each population must establish its own normal values. The aim of this work was to study delayed hypersensitivity in chilean normal young adults. We studied the response to 8 antigens using the Multitest CMI (Rhodia Merieux) in 50 students (22 females, 28 males), aged 18 to 25 years old. Skin tests were read at 24, 48 and 72 hours. At 48 h, 60 percent of women responded to 3 and 68 percent of men to 4 antigens. A mean response to 3.6 antigens was observed. Total score in men and women were 19.5ñ7.3 and 12.2ñ6.5 mm respectively (p<0.05). These figures are different from these published abroad and confirm the need for national standards