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Ante la gravedad del impacto sobre la salud del cambio climático y la degradación ambiental 32 sociedades, colegios y asociaciones de Medicina Interna de 29 países de habla hispana y lusa divulgan un documento de consenso en que llaman a la implicación de los médicos y todos los profesionales de salud en la lucha global contra las causas de estos cambios. Este compromiso requiere la cooperación de las organizaciones relacionadas con la salud, elaboración e implementación de buenas prácticas de sostenibilidad ambiental, sensibilización de los profesionales de la salud y de la población, promoción de la educación e investigación en esta área, refuerzo de la resiliencia climática y la sostenibilidad ambiental de los sistemas de salud, combatir las desigualdades y proteger a las poblaciones más vulnerables, adopción de comportamientos que protegen el medio ambiente, y defensa de la Medicina Interna como una especialidad central para habilitar al sistema de salud para responder a estos desafíos. (AU)
Facing the severity of the impact of climate change and environmental degradation on human health, 32 Internal Medicine societies, colleges, and associations of 29 Spanish and Portuguese-speaking countries issue a consensus document calling for the implication of doctors and all health professionals in the global fight against the causes of these changes. This commitment requires the cooperation of health-related organizations, elaboration and implementation of good environmental sustainability practices, greater awareness of professionals and population, promotion of education and research in this area, increasing climate resilience and environmental sustainability of health systems, combating inequalities and protecting the most vulnerable populations, adopting behaviors that protect the environment, and claiming Internal Medicine as a core specialty for empowerment of the health system to respond to these challenges. (AU)
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Humanos , Cambio Climático , Ambiente , Medicina Interna , Salud Única , Salud PúblicaRESUMEN
Facing the severity of the impact of climate change and environmental degradation on human health, 32 Internal Medicine societies, colleges, and associations of 29 Spanish and Portuguese-speaking countries issue a consensus document in which they call for the implication of doctors and all health professionals in the global fight against the causes of these changes. This commitment requires the cooperation of health-related organizations, elaboration and implementation of good environmental sustainability practices, greater awareness of professionals and population, promotion of education and research in this area, increasing climate resilience and environmental sustainability of health systems, combating inequalities and protecting the most vulnerable populations, adopting behaviors that protect the environment, and claiming Internal Medicine as a core specialty for empowerment of the health system to respond to these challenges.
RESUMEN
Metachronal propulsion is widespread in aquatic swarming organisms to achieve performance and maneuverability at intermediate Reynolds numbers. Studying only live organisms limits our understanding of the mechanisms driving these abilities. Thus, we present the design, manufacture, and validation of the Pleobot-a unique krill-inspired robotic swimming appendage constituting the first platform to study metachronal propulsion comprehensively. We combine a multi-link 3D printed mechanism with active and passive actuation of the joints to generate natural kinematics. Using force and fluid flow measurements in parallel with biological data, we show the link between the flow around the appendage and thrust. Further, we provide the first account of a leading-edge suction effect contributing to lift during the power stroke. The repeatability and modularity of the Pleobot enable the independent manipulation of particular motions and traits to test hypotheses central to understanding the relationship between form and function. Lastly, we outline future directions for the Pleobot, including adapting morphological features. We foresee a broad appeal to a wide array of scientific disciplines, from fundamental studies in ecology, biology, and engineering, to developing new bio-inspired platforms for studying oceans across the solar system.
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Procedimientos Quirúrgicos Robotizados , Natación , Comercio , Ecología , IngenieríaRESUMEN
La implantación de la telemedicina como una herramienta más en la atención a pacientes en el ámbito hospitalario es un reto para cualquier sistema sanitario. Dadas las dificultades y limitaciones, el Foro Internacional de Medicina Interna (FIMI) ha promovido este Consenso que incluye a 20 sociedades científicas de 17 países de Europa y América. El objetivo fue realizar una propuesta, a modo de marco general, que permitiese el desarrollo e implantación de la telemedicina en la atención clínica hospitalaria y que fuese útil para los diferentes países integrantes del FIMI. El documento que presentamos recoge el resumen ejecutivo de las recomendaciones de la FIMI que pretenden garantizar intervenciones sanitarias efectivas, seguras, eficientes, sostenibles y proporcionadas y basadas en la mejor evidencia científica disponible. Los autores consideran que este documento debe actualizarse en el plazo máximo de dos años (AU)
The implementation of telemedicine as another tool for patient care in the hospital setting is a challenge for any healthcare system. Given the difficulties and limitations, the International Forum on Internal Medicine (FIMI, for its initials in Spanish) has sponsored this consensus document with 20 scientific societies from 17 countries in Europe and the Americas. The aim was to propose a general framework that allows for the development and implementation of telemedicine in hospital clinical care that would be useful to FIMI member countries. The document we present includes recommendations from the FIMI in its executive summary that intend to guarantee effective, safe, efficient, sustainable, and proportional healthcare interventions based on the best scientific evidence available. The authors believe that this document must be updated within a maximum period of two years (AU)
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Humanos , Telemedicina/normas , Atención Hospitalaria/métodos , Medicina Interna , Congresos como AsuntoRESUMEN
The implementation of telemedicine as another tool for patient care in the hospital setting is a challenge for any healthcare system. Given the difficulties and limitations, the International Forum on Internal Medicine (FIMI, for its initials in Spanish) has sponsored this consensus document with 20 scientific societies from 17 countries in Europe and the Americas. The aim was to propose a general framework that allows for the development and implementation of telemedicine in hospital clinical care that would be useful to FIMI member countries. The document we present includes recommendations from the FIMI in its executive summary that intend to guarantee effective, safe, efficient, sustainable, and proportional healthcare interventions based on the best scientific evidence available. The authors believe that this document must be updated within a maximum period of two years.
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Telemedicina , Humanos , Atención a la Salud , Europa (Continente) , Medicina Interna , HospitalesRESUMEN
Objetivos: Cuantificar donantes, personas que aceptan tratamientos invasivos, que firmarían órdenes de no reanimar, que avalarían transfusiones a personas contra su voluntad, que aceptan el aborto, la eutanasia y la investigación experimental, en todos los casos vinculando la respuesta con fundamentaciones. Materiales y Métodos: Diseño prospectivo, de observación, longitudinal, analítico. En 2007-2008, se estudiaron 848 adolescentes de 13 escuelas públicas de enseñanza media del área de responsabilidad de un hospital del Gobierno de la Ciudad Autónoma de Buenos Aires, en quienes se aplicó una encuesta autoadministrada abierta-cerrada. Se interrogó sobre situaciones vinculadas a aspectos bioéticos. Resultados: Los donantes representan el 75% de la muestra, el 46% desea que le implementen todo tratamiento posible, el 30% firmaría una orden de no reanimación, el 32% avala las transfusiones a Testigos de Jehová, el 57% acepta el aborto; el 81%, la eutanasia; el 62%, la investigación experimental. No hay diferencias de aceptación del aborto y la eutanasia entre católicos y no creyentes (p 0,10 y 0,30, respectivamente). En el análisis multivariado, la implementación de todo tipo de tratamiento se vinculó a no firmar una orden de no reanimar (p 0,0000) y a no respetar la voluntad de los Testigos de Jehová (p 0,0024). La aceptación de la eutanasia se vincula con la aceptación de aborto (p 0,0000) y firmar una orden de no reanimar (p 0,0266). Conclusiones: Los valores más votados fueron la veracidad y la justicia. La escuela media es un sitio de alto impacto para educar en bioética y derechos de ciudadanía(AU)
Objectives: To quantify donors, people who would accept invasive treatments, who would sign orders not to resuscitate, who would support transfusions to persons against their will, who would accept abortion, euthanasia, and experimental research, in all cases supporting their choices with foundations. Materials and Methods: Prospective, observational, longitudinal and analytical study. During 2007-2008, 848 teenagers belonging to 13 public high schools in the area of responsibility of a hospital from Gobierno de la Ciudad Autónoma de Buenos Aires were studied. They were given a self-administered opened-closed survey which included questions about situations linked to bioethical aspects. Results: Donors represent 75% of the sample, 46% wish to get any possible treatment, 30% would sign a do-not-resuscitate order, 32% support transfusions to Jehovah's Witnesses, 57% accept abortion, 81% euthanasia, 62% experimental research. There are no differences on acceptance of abortion and euthanasia between Catholics and non-believers (p 0.10 and 0.30, respectively). In the multivariate analysis, the implementation of all kinds of treatment was linked to a refusal to sign a do-not-resuscitate order (p 0.0000) and to not respecting the will of the Jehovah's Witnesses (p 0.0024). The acceptance of euthanasia links itself, in the analysis multivariate, to accepting abortion (p 0.0000) and to signing a do-not-resuscitate order (p 0.0266). Conclusions: The majority vote in favor of veracity and justice. High school is a high impact point to educate on bioethics and rights of citizenship(AU)
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Humanos , Adolescente , Bioética , Adolescente , Eutanasia , AbortoRESUMEN
Introducción: La educación médica debería garantizar la formación de profesionales competentes que posean los conocimientos, las destrezas y las actitudes planificados en la capacitación. En general, los programas no tienen en cuenta a la urgencia, que no figura como materia específica en los programas de grado. Objetivos: Cuantificar las competencias adquiridas por los internos en el Departamento de Urgencias y en Terapia Intensiva, estableciendo el grado de cumplimiento entre lo planificado y lo logrado; desglosar el grado de cumplimiento según las diferentes áreas de la competencia clínica. Materiales y Métodos: Diseño prospectivo, de observación, longitudinal, analítico. Se incluyeron 93 alumnos del ciclo clínico que realizaron el internado rotatorio (2000-2009). Se valoró el cumplimiento de 37 competencias que se clasificaron por área: actitudes, conocimientos y destrezas, en números de 9, 5 y 23, respectivamente. Resultados: El cumplimiento global de las competencias en el área de emergentología y terapia intensiva es del 61,18% (IC95% 59,20-63,13). Al desglosar por área de la competencia clínica, se halla que las actitudes fueron del 66,26%; los conocimientos, del 63,28% y las destrezas, del 58,15%. Clasificándolas según el grado de cumplimiento, se establece una escala con cumplimiento alto (76-100%), medio (51-75%) y bajo (<51%). Conclusiones: Los aspectos actitudinales y cognitivos de las competencias tuvieron un cumplimiento medio. La mitad de las competencias vinculadas a destrezas tuvo un cumplimiento medio-alto.(AU)
Introduction: Medical education should guarantee the formation of competent professionals with the knowledge, skills and attitudes planned in training. Generally programs do not bear in mind the urgency, which does not appear as a specific subject in the university. Objectives: To quantify the competitions acquired by the boarders in the Emergency Department and the Intensive Care Unit, establishing the degree of fulfillment between what was planned and what was achieved; to perceive the degree of fulfillment according to the different areas of clinical competition. Materials and Methods: Prospective, observational, longitudinal and analytical study. We included 93 students from the clinical cycle who performed rotating boarding school (2000-2009). Fulfillment of 37 competitions classified by area: attitudes, knowledge and skills, in numbers of 9, 5 and 23, respectively, was evaluated. Results: The global fulfillment of the competitions was 61.18% (CI95%: 59.20-63.13). Specifically, in each area of the clinical competition, we found that the attitudes were 66.26%, knowledge 63.28% and skills 58.15%. Classifying them according to the degree of fulfillment, a scale is established: high (76-100%), medium (51-75%) and low (<51%). Conclusions: Attitude and cognitive aspects of the competitions had average fulfillment. Half of the competitions linked to skills had average-high fulfillment.(AU)
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Humanos , Estudiantes , Competencia Clínica , Cuidados Críticos , Urgencias MédicasRESUMEN
Objetivos. Establecer la importancia de la profilaxis para prevenir la hemorragia digestiva en pacientes críticos, determinar los predictores del desarrollo de hemorragia digestiva en estos enfermos y cuantificar la neumonía intrahospitalaria. Materiales y métodos. Diseño prospectivo, observacional, longitudinal. Se estudiaron 3438 pacientes durante dos años. Luego de aplicar los criterios de exclusión y de eliminación, se evaluó a 3213 pacientes. La muestra fue consecutiva, se formaron dos grupos: con profilaxis (sucralfato o ranitidina) y sin profilaxis. Se registraron los siguientes datos: puntaje Apache II, disfunciones, diagnósticos de riesgo, hemorragia digestiva, neumonía intrahospitalaria, mortalidad. Resultados. Incidencia de hemorragia digestiva: 4,57%; con profilaxis frente a sin profilaxis: 4,64% y 4,50% (p = 0,91). Predictores de hemorragia digestiva en análisis multivariado: trauma grave (p = 0,0004), insuficiencia respiratoria (p = 0,0021), pancreatitis (p = 0,0202), insuficiencia renal aguda (p = 0,0220) y ayuno (p <0,0001). En pacientes con puntaje Apache II ≥15: trauma grave (p = 0,0228) y ayuno (p = 0,0000). Incidencia de neumonía intrahospitalaria 10,05%; con profilaxis y sin profilaxis: 11,47% y 8,68% (p = 0,001)(AU)
Objectives. Set the importance of prophylaxis for gastrointestinal bleeding in criticallly ill patients; determine predictors of gastrointestinal bleeding and quantify hospital-acquired pneumonia. Materials and methods. Prospective, observational and longitudinal design. A total of 3438 patients were studied during two years. After applying exclusion and elimination criteria, 3213 patients were left. It was a consecutive sample, and there were two groups; with prophylaxis (sucralfate or ranitidine) and without prophylaxis. Apache II, organ failures, risk diagnoses, digestive tract bleeding, hospital-acquired pneumonia and mortality were registered. Results. Gastrointestinal bleeding incidence: 4.57%, with vs. without prophylaxis: 4.64% vs. 4.50% (p = 0.91). Gastrointestinal bleeding predictors in the multivariate analysis: serious trauma: (p = 0.0004), respiratory failure (p = 0.0021), pancreatitis (p = 0.0202), acute renal failure (p = 0.0220) and fasting (p <0.0001). In Apache II ≥15 patients: serious trauma (p = 0.0228) and fasting (p = 0.0000). Incidence of hospital-acquired pneumonia: 10.05%, with vs. without prophylaxis: 11.47% vs. 8.68% (p = 0.001). Conclusions. Prophylaxis did not reduce gastrointestinal bleeding, it was associated with serious trauma, respiratory failure, pancreatitis, acute renal failure and fasting, and considering only patients with the worst Apache II score, it was associated with serious trauma and fasting. Acquired pneumonia was higher in the prophylaxis group.(AU)
Asunto(s)
Humanos , Sistema Digestivo , Prevención de Enfermedades , Hemorragia , NeumoníaRESUMEN
AIMS: The aims of this study were to quantify donors among the investigated area, quantify arguments and myths about the donation and transplantation process, and fix predetermined donation variables in a logistical model. MATERIALS AND METHODS: We used an analytical, prospective design, using 848 students from 13 high schools in the Velez Sarsfield Hospital area in an open-closed inquiry. RESULTS: Females were 57.74% and average age was 16.64 +/- 0.06 years, including 65.09% Catholics. The 642 potential donors represented 75% of the study population with the fundamental aim being to "give life" (44.85%). The 193 (22.75%) opposed subjects cited as a principal reason fear and distrust (40.41%). There were 40.21% who had discussed the donation subject with their families. In our study 76.41% believed that human organ traffic exists and 36.88% thought that it is due to corruption. Also, 56.01% fear premature extraction of their organs. In addition, 73.23% of teenagers considered that individuals who refused to donate have the right to receive organs (P = not significant between donors and not a donor). The family discussion and the lack of fear about premature extraction were donation signals. About the low level of donation 43.27% blamed the government (lack of campaigns, information, and knowledge) whereas other reasons were fear, lack of clarity and distrust. In our study 49.17% seemed to wish to increase donation if they received more information. CONCLUSIONS: Individuals predispose to donation represented the great majority of the queried teenagers; education and family discussion were remarkable factors favoring the decision.
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Donantes de Tejidos/estadística & datos numéricos , Obtención de Tejidos y Órganos/estadística & datos numéricos , Adolescente , Argentina , Actitud Frente a la Salud , Catolicismo , Femenino , Humanos , Masculino , Trasplante de Órganos/normas , ConfianzaRESUMEN
Recent studies in infectious disease and autoimmune disease models have revealed that interleukin (IL)-22 might have both proinflammatory and anti-inflammatory functions. There is, however, lack of evidence for IL-22 directly repressing immune responses of leukocytes. We propose that IL-22 promotes innate immunity of tissues, as well as repairing and healing mechanisms during inflammation. Consequently, the restoration of tissue homeostasis helps to attenuate the inflammatory responses involving various immune cells.
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Inmunidad Mucosa/inmunología , Interleucinas/inmunología , Animales , Humanos , Inmunidad Innata/inmunología , Inflamación/inmunología , Transducción de Señal/inmunología , Interleucina-22RESUMEN
INTRODUCTION: The colonics polyps according to their number, size, location, age of presentation and mainly, according to their histology, have the potentiality of malignant degeneration, which makes of a continuous study and pursuit susceptible. OBJECTIVES: To evaluate the relation between the histologic type of the colon polyps, its location, the degree of dysplasia, the size, its possible commitment by carcinoma, the age, sex and the handling that has occurred them, in a series of 684 patients of the National Institute of Enfermedades Neoplásicas (INEN) between the 1 of January from 1974 to the 31 of March of the 2004. MATERIAL AND METHODS: The revision of clinical histories of 840 patients with the diagnosis of colon polyp was made who attended the service of Gastroenterology of the INEN between the 1 of January from 1974 to the 31 of March of 2004 and a card predesigned for each clinical history filled. The study is of observational, analytical type and of cross section. 1162 resecteds polyps evaluated themselves in this period. 156 patients by diagnosis related to cancer and familiar adenomatouspoliposis did not include themselves. The final sample was of 684 patients, in whom it was 1057 polyps. Other endoscopic findings were: internal hemorrhoids (172), colonic diverticulosis (50), anal fissure (4), and nonspecific ulcerative colitis (2). The statistical processing was made with program SPSS 12. For the qualitative variables the method of the Chi-square was used, for the quantitative variables analyzed the average, the rank and the variance. RESULTS: 1057 polyps extirpated, by means of the endoscopy polipectomy were 1016, with colectomy were 32 and with transanal resection without colectomy they 9. Within the histology of the 1057 polyps, 331 was briefed (31.3%) that were hyperplasic, 448 (42.4%) adenomas, 278 (26.3%) others and 35 (8.2%) adenocarcinomas on adenomas. The average age was of 50 years, was no significant difference with sex. The location but frequence of the adenomas was in the left colon (76.6%). Adenocarcinoma (carcinomas on adenomas), was present mainly in polyps villous type, with dysplasia severe and greater to 10 mm. Nevertheless, in smaller polyps of 5mm with dysplasia severe, was a polyp invaded by cancer, that represents the 0,8% of millimetric polyps. The made handling was mainly endoscopic, with 96% of the resected polyps this way, also slogan transanal resection and segmental colonic resection. The colectomy was necessary in 3% of all the made interventions, dysplasia severe or carcinoma was made in adenomatous polyps with, and in greater percentage in greater polyps of 20 mm (53%). The single polipectomy was sufficient in the level of invasion Haggitt 0. In patients with level of invasion Haggitt 1 and 2, the single polipectomy was the election treatment. On the other hand, in polyps with level of invasion Haggitt 3 and 4, the colectomy was the election treatment. One briefed two complications, one of perforation and peritonitis and another one of digestive hemorrhage loss (both: 0.29%), without mortality events. CONCLUSIONS: The Evaluation of colonic polyps in INEN is predominantly by endoscopy. The polyps are more frequent over the 50 years and have preferred location in the left colon. The carcinoma is more probable with severe dysplasia and greater size of the adenoma. All polyps, from the millimetric ones, including the hyperplasic, must be considered marks of neoplasia and extirpated in its totality.
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Pólipos del Colon/patología , Pólipos del Colon/cirugía , Adolescente , Adulto , Anciano , Niño , Endoscopía , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Introducción: Los pólipos colónicos de acuerdo a su número, tamaño, localización, edad de presentación y sobre todo, de acuerdo a su estirpe histológica, tienen la potencialidad de degeneración maligna, lo que los hace susceptibles de un continuo estudio y seguimiento. Objetivos: Evaluar la relación entre el tipo histológico de los pólipos de colón, su localización, el grado de displasia, el tamaño, su eventual compromiso por carcinoma, la edad, el sexo y el manejo que se les ha dado, en una serie de 684 pacientes del Instituto Nacional de Enfermedades Neoplásicas (INEN) entre el 1 de enero de 1974 al 31 de marzo del 2004. Material y métodos: Se realizó la revisión de historias clínicas de 840 pacientes con el diagnóstico de pólipo de colon que asistieron al Servicio de Gastroenterología del INEN entre el 1 de enero de 1974 al 31 de marzo de 2004 y se llenó una ficha prediseñada para cada historia clínica. El estudio es de tipo observacional, analítico y de corte transversal. Se evaluaron en este periodo 1162 pólipos resecados. No se incluyeron 156 pacientes por diagnóstico relacionado con cáncer y poliposis adenomatosa familiar. La muestra final fue de 684 pacientes, en los que se encontró 1057 pólipos. Otros hallazgos endoscópicos fueron: hemorroides internas (172), diverticulosis colónica (50), fisura anal (4), y colitis ulcerativa no específica (2). El procesamiento estadístico se realizó con el programa SPSS 12. Para las variables cualitativas se empleó el método de Chi-cuadrado, para las variables cuantitativas se analizaron la media, el rango y la varianza. Resultados: Se extirparon 1057 pólipos, mediante la polipectomía endoscópica fueron 1016, con uso de colectomía fueron 32 y con resección transanal sin colectomía fueron 09. Dentro de la histología de los 1057 pólipos, se consignaron 331 (31.3 por ciento) que fueron hiperplásicos, 448 (42.4 por ciento) adenomas, 278 (26.3 por ciento) otros y 35 (8.2 por ciento) adenocarcinomas sobre adenomas...
Introduction: The colonics polyps according to their number, size, location, age of presentation and mainly, according to their histology, have the potentiality of malignant degeneration, which makes of a continuous study and pursuit susceptible. OBJECTIVES: To evaluate the relation between the histologic type of the colon polyps, itslocation, the degree of dysplasia, the size, its possible commitment by carcinoma, the age, sex and the handling that has occurred them, in a series of 684 patients of the National Institute of Enfermedades Neoplásicas (INEN) between the 1 of January from 1974 to the 31 of March of the 2004. MATERIAL AND METHODS: The revision of clinical histories of 840 patients with the diagnosis of colon polyp was made who attended the service of Gastroenterology of the INEN betweenthe 1 of January from 1974 to the 31 of March of 2004 and a card predesigned for each clinical history filled. The study is of observational, analytical type and of cross section. 1162 resecteds polyps evaluated themselves in this period. 156 patients by diagnosis related to cancer and familiar adenomatouspoliposis did not include themselves. The final samplewas of 684 patients, in whom it was 1057 polyps. Other endoscopic findings were: internal hemorrhoids (172), colonic diverticulosis (50), anal fissure (4), and nonspecific ulcerative colitis (2). The statistical processing was made with program SPSS 12. For the qualitative variables the method of the Chi-square was used, for the quantitative variables analyzed theaverage, the rank and the variance. RESULTS: 1057 polyps extirpated, by means of the endoscopy polipectomy were 1016, with colectomy were 32 and with transanal resection without colectomy they 9. Within the histologyof the 1057 polyps, 331 was briefed (31.3 per cent) that were hyperplasic, 448 (42.4 per cent) adenomas,278 (26.3 per cent) others and 35 (8.2 per cent) adenocarcinomas on adenomas. The average age was of50 years, ...
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Humanos , Masculino , Adolescente , Adulto , Lactante , Niño , Persona de Mediana Edad , Femenino , Pólipos Adenomatosos , Pólipos del Colon/clasificación , Pólipos del Colon/patología , Estudios Epidemiológicos , Estudios Transversales , Estudios Observacionales como AsuntoRESUMEN
We report two cases of successfully endoscopy therapy with argon plasma in upper gastrointestinal bleeding secondary a complication of endoscopic sphynterotomy, who fails to previous injectotherapy attempts. The bleeding control was complete and without complications.
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Argón/uso terapéutico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/cirugía , Hemostasis Endoscópica/métodos , Anciano , Anciano de 80 o más Años , Hemorragia Gastrointestinal/diagnóstico , Gastroscopía/métodos , Humanos , Terapia por Láser , Masculino , Prevención Secundaria , Esfínter de la Ampolla Hepatopancreática/cirugía , Resultado del TratamientoRESUMEN
Con los objetivos de detectar las disfunciones orgánicas (DO) predictoras de mortalidad, en un modelo multivariado, establecer diferencias entre pacientes clínicos, quirúrgicos y cardiológicos en relación al desarrollo de disfunciones y mortalidad, buscar el mejor modelo matemático para estimar los pesos de las distintas disfunciones y confeccionar un score y comparar los resultados de la aplicación del nuevo score en relación a la cuantificación simple de las disfunciones, en un diseño prospectivo, observacional y longitudinal se estudiaron 699 pacientes de una muestra consecutiva ingresada a terapia intensiva. Se obtuvieron pesos de las DO a partir del estadístico de Wald, del coeficiente beta y de los odds ratio, confeccionándose un score con la suma de los mismos. Las disfunciones que se mostraron como predictoras de mortalidad fueron en orden decreciente según el peso: la neurológica, respiratoria, cardiovascular, metabólica, hepática y renal. No fueron predictoras las disfunciones hematológica y digestiva. En la población cardiológica ninguna disfunción fue variable predictora. El score originado a partir del estadístico de Wald presentó un área ROC superior al área de la cuantificación de las disfunciones con menor error standard y valores significativos para pendiente y linealidad a diferencia del otro método, presentando mejor discriminación en el punto de mayor exactitud diagnóstica para identificar a quienes tenían más riesgo de fallecer(AU)
With the objectives of detecting organic dysfunctions (DO) predictors of mortality, in a model multivariate, establish differences between patients clinical, surgical and cardiological in relation to the development of dysfunctions and mortality, look for the best mathematical model to estimate the weights of the different dysfunctions and make a score and compare the results of the application of the new score in relation to quantification simple of dysfunctions, in a prospective design, observational and longitudinal were studied 699 patients from a consecutive sample admitted to intensive therapy. Weights were obtained from the DO to from the Wald statistic, from the beta coefficient and of the odds ratio, making a score with the sum of them. The dysfunctions that were shown as predictors of mortality were in decreasing order according to the weight: the neurological, respiratory, cardiovascular, metabolic, hepatic and renal. They were not predictors the hematological and digestive dysfunctions. In the cardiological population no dysfunction it was variable predictor. The score originated from of the Wald statistic presented a superior ROC area to the area of ââquantification of dysfunctions with lower standard error and significant values for slope and linearity unlike the another method, presenting better discrimination in the point of greatest diagnostic accuracy to identify those who had more risk of dying(AU)
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Puntuaciones en la Disfunción de Órganos , MortalidadRESUMEN
The molecular events triggered by MHC recognition and how they lead to the emergence of mature CD4 and CD8 lineage thymocytes are not yet understood. To address these questions, we have examined what signals are necessary to drive the development of CD8 lineage thymocytes in TCRalpha(-) mice in which TCR/MHC engagement cannot occur. We find that the combination of constitutive Notch activity and constitutive Bcl-2 expression are necessary and sufficient to allow the appearance of mature CD8 lineage thymocytes in TCRalpha(-) mice. In addition, Notch activity alone in TCRalpha(-) mice can induce the up-regulation of HES1, suggesting that thymocytes are competent to respond to Notch signaling in the absence of MHC recognition. These data indicate that survival and lineage commitment represent distinct, parallel pathways that occur as a consequence of MHC recognition, both of which are necessary for the development of mature CD8 lineage T cells.
Asunto(s)
Complejo Mayor de Histocompatibilidad/inmunología , Transducción de Señal/inmunología , Linfocitos T/citología , Timo/citología , Timo/inmunología , Animales , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Linaje de la Célula/genética , Linaje de la Célula/inmunología , Supervivencia Celular/genética , Supervivencia Celular/inmunología , Inmunofenotipificación , Complejo Mayor de Histocompatibilidad/genética , Proteínas de la Membrana/deficiencia , Proteínas de la Membrana/genética , Proteínas de la Membrana/fisiología , Ratones , Ratones Mutantes , Ratones Transgénicos , Proteínas Proto-Oncogénicas c-bcl-2/deficiencia , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/fisiología , Receptores de Antígenos de Linfocitos T/deficiencia , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/fisiología , Receptores Notch , Transducción de Señal/genética , Linfocitos T/inmunologíaRESUMEN
Genetic modification of hematopoietic stem cells with genes that inhibit replication of human immunodeficiency virus-1 (HIV-1) could lead to development of T lymphocytes and monocytic cells resistant to HIV-1 infection after transplantation. We performed a clinical trial to evaluate the safety and feasibility of this procedure, using bone marrow from four HIV-1-infected pediatric subjects (ages 8 to 17 years). We obtained bone marrow, isolated CD34(+) cells, performed in vitro transduction with a retroviral vector carrying a rev-responsive element (RRE) decoy gene, and reinfused the cells into these subjects with no evidence of adverse effects. The levels of gene-containing leukocytes in peripheral blood samples in the 1 year after gene transfer/cell infusion have been extremely low. These observations support the potential of performing gene therapy for HIV-1 using hematopoietic cells, but emphasize the need for improved gene transfer techniques.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/terapia , Genes rev , Terapia Genética , Duplicado del Terminal Largo de VIH/genética , VIH-1/genética , Trasplante de Células Madre Hematopoyéticas , Replicación Viral/genética , Síndrome de Inmunodeficiencia Adquirida/genética , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/patología , Adolescente , Diferenciación Celular , Niño , Técnicas de Transferencia de Gen , Vectores Genéticos , Células Madre Hematopoyéticas/patología , Células Madre Hematopoyéticas/fisiología , Humanos , Proyectos Piloto , Retroviridae , Linfocitos T/inmunologíaAsunto(s)
Linfocitos T CD4-Positivos/citología , Linfocitos T CD8-positivos/citología , Proteínas de la Membrana/fisiología , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Diferenciación Celular , Proteínas de la Membrana/genética , Ratones , Modelos Biológicos , Receptores Notch , Transducción de SeñalRESUMEN
Using retroviral supernatants derived from the amphotropic murine packaging cell line PA317 and the amphotropic canine packaging cell line (DA), cord blood and mobilized peripheral blood CD34+ cells were transduced with the vector LN (neomycin resistance) and the vector L-TR/TAT neo (neomycin resistance in conjunction with a double-hammerhead ribozyme conferring anti-HIV activity). Different multiplicities of infection (MOI) were applied in the setup according to vector titrations on NIH-3T3 cells. PA317-based supernatants were tested at MOI of 10 and 30. Purified concentrated DA-derived vector preparations were tested at MOI of 10, 30, 100, and 300. Immediately after transduction, CD34+ cells were plated into colony assays in the presence and absence of G418 to evaluate the amount of gene transfer and potential toxic effects of the vectors on colony growth. The remaining cells were subjected to G418 selection in liquid culture for 12 days and subsequently challenged with HIV-1JR-FL to test for efficacy of the anti-HIV gene in macrophages derived from transduced CD34+ cells. Transduction by the PA317-packaged vectors was maximal at the lowest MOI used and did not increase with increasing MOI. In contrast, transduction by the DA-packaged vectors could be progressively increased using increased MOI. The net transduction efficiency per unit of reverse transcriptase activity in the DA vector preparations was 8.7-fold higher than in the PA317 vector supernatants. HIV-1 challenge of the cells transduced by the ribozyme vector derived from the PA317 packaging cells resulted in a 1.5 log inhibition of p24 output compared with the control cells containing neomycin resistance only. A 2.5 log inhibition of p24 output could be observed in the cell population transduced with DA-packaged vector supernatants. Compared with retroviral supernatants from PA317 packaging cell lines, DA packaging line-derived vector preparations demonstrated higher transduction efficiency into CD34+ cells, particularly at higher MOI, and increased efficacy of the transferred anti-HIV gene when challenged with HIV-1JR-FL. The increase in transduction efficiency may be due to a higher ratio of intact vs. defective vector particles in the DA-derived vector preparations.
Asunto(s)
Técnicas de Transferencia de Gen , Vectores Genéticos , Células Madre Hematopoyéticas/fisiología , Retroviridae , Animales , Antígenos CD34 , Perros , Farmacorresistencia Microbiana , Humanos , ARN CatalíticoRESUMEN
Transfer of "anti-HIV-1 genes" into hematopoietic stem cells of human immunodeficiency virus-1 (HIV-1)-infected individuals may be a potent therapeutic approach to render mature cells arising from transduced stem cells resistant to the destructive events associated with HIV-1 infection. To determine the feasibility of gene therapy for acquired immunodeficiency syndrome in individuals already infected with HIV-1, granulocyte colony-stimulating factor mobilized peripheral blood CD34+ cells were isolated from HIV-1-infected individuals and transduced with retroviral vectors containing three different anti-HIV-1-genes: the Rev binding domain of the Rev Responsive Element (RRE decoy) (L-RRE-neo), a double hammerhead ribozyme vector targeted to cleave the tat and rev transcripts (L-TR/TAT-neo), and the trans-dominant mutant of rev (M10) (L-M10-SN). As a control, a vector mediating only neomycin resistance (LN) was used. After 3 days of transduction on allogeneic stroma in the presence of stem cell factor, interleukin-6 (IL-6), and IL-3, the cultures were G418-selected, and then challenged with HIV-1(JR-FL) and a primary HIV-1 isolate. Compared with the control cultures, the L-RRE-neo-, L-TR/TAT-neo-, and L-M10-SN-transduced cultures displayed up to 1,000-fold inhibition of HIV-1 replication after challenge with HIV-1(JR-FL) and the primary HIV-1 isolate. Growth of the hematopoietic cells in long-term bone marrow culture was not perturbed by the presence of any of the anti-HIV-1 genes. This study shows that anti-HIV-1 genes can be introduced into CD34+ cells from individuals already infected with HIV-1, and strongly inhibit HIV-1 replication in primary monocytes derived from the CD34+ progenitors.