RESUMEN
INTRODUCTION: Erythema nodosum leprosum (ENL) is an immunological complication of leprosy. ENL results in morbidity and disability and if it is not treated can lead to death. The current treatment consists of thalidomide or high doses of oral corticosteroids for prolonged periods. Thalidomide is not available in many leprosy endemic countries. The use of corticosteroids is associated with morbidity and mortality. Identifying treatment regimens that reduce the use of corticosteroids in ENL is essential. Methotrexate (MTX) is used to treat many inflammatory diseases and has been used successfully to treat patients with ENL not controlled by other drugs, including prednisolone and thalidomide. We present the protocol of the 'MTX and prednisolone study in ENL' (MaPs in ENL) a randomised controlled trial (RCT) designed to test the efficacy of MTX in the management of ENL. METHODS AND ANALYSIS: MaPs in ENL is an international multicentre RCT, which will be conducted in leprosy referral centres in Bangladesh, Brazil, Ethiopia, India, Indonesia and Nepal. Patients diagnosed with ENL who consent to participate will be randomly allocated to receive 48 weeks of weekly oral MTX plus 20 weeks of prednisolone or 48 weeks of placebo plus 20 weeks of prednisolone. Participants will be stratified by type of ENL into those with acute ENL and those with chronic and recurrent ENL. The primary objective is to determine whether MTX reduces the requirement for additional prednisolone. Patients' reported outcome measures will be used to assess the efficacy of MTX. Participants will be closely monitored for adverse events. ETHICS AND DISSEMINATION: Results will be submitted for publication in peer-reviewed journals. Ethical approval was obtained from the Observational/Interventions Research Ethics Committee of the London School of Hygiene & Tropical Medicine (15762); The Leprosy Mission International Bangladesh Institutional Research Board (in process); AHRI-ALERT Ethical Review Committee, Ethiopia; Ethics Committee of the Managing Committee of the Bombay Leprosy Project; and The Leprosy Mission Trust India Ethics Committee; the Nepal Health and Research Council and Health Research Ethics Committee Dr. Soetomo, Indonesia. This study is registered at www.clinicaltrials.gov. This is the first RCT of MTX for ENL and will contribute to the evidence for the management of ENL.Trial registration numberNCT 03775460.
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Eritema Nudoso , Lepra Lepromatosa , Metotrexato/uso terapéutico , Prednisolona/uso terapéutico , Bangladesh , Brasil , Eritema Nudoso/tratamiento farmacológico , Etiopía , Humanos , India , Indonesia , Leprostáticos/uso terapéutico , Lepra Lepromatosa/tratamiento farmacológico , Londres , NepalRESUMEN
Kinetic studies using UV/visible and EPR spectroscopy were carried out to follow the distribution of electrons within beef heart cytochrome c oxidase (CcO), both active and cyanide-inhibited, following addition of reduced cytochrome c as electron donor. In the initial one-electron reduced state the electron is shared between three redox centers, heme a, CuA and a third site, probably CuB. Using a rapid freeze system and the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) a protein radical was also detected. The EPR spectrum of the DMPO adduct of this radical was consistent with tyrosyl radical capture. This may be a feature of a charge relay mechanism involved in some part of the CcO electron transfer system from bound cytochrome c via CuA and heme a to the a3CuB binuclear center.
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Complejo IV de Transporte de Electrones/química , Complejo IV de Transporte de Electrones/metabolismo , Animales , Bovinos , Óxidos N-Cíclicos , Citocromos c/química , Citocromos c/metabolismo , Espectroscopía de Resonancia por Spin del Electrón , Transporte de Electrón , Radicales Libres/química , Radicales Libres/metabolismo , Caballos , Hidrógeno/metabolismo , Cinética , Modelos Biológicos , Miocardio/enzimología , Oxidación-Reducción , Espectrofotometría , Marcadores de SpinRESUMEN
OBJECTIVES: To develop a valid and reliable quantitative measure of leprosy Type 1 reactions. METHODS: A scale was developed from previous scales which had not been validated. The face and content validity were assessed following consultation with recognised experts in the field. The construct validity was determined by applying the scale to patients in Bangladesh and Brazil who had been diagnosed with leprosy Type 1 reaction. An expert categorized each patient's reaction as mild or moderate or severe. Another worker applied the scale. This was done independently. In a subsequent stage of the study the agreement between two observers was assessed. RESULTS: The scale had good internal consistency demonstrated by a Cronbach's alpha >0.8. Removal of three items from the original scale resulted in better discrimination between disease severity categories. Cut off points for Type 1 reaction severities were determined using Receiver Operating Characteristic curves. A mild Type 1 reaction is characterized using the final scale by a score of 4 or less. A moderate reaction is a score of between 4.5 and 8.5. A severe reaction is a score of 9 or more. CONCLUSIONS: We have developed a valid and reliable tool for quantifying leprosy Type 1 reaction severity and believe this will be a useful tool in research of this condition, in observational and intervention studies, and in the comparison of clinical and laboratory parameters.
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Lepra/clasificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bangladesh , Brasil , Niño , Femenino , Humanos , Lepra/fisiopatología , Masculino , Nervio Mediano/fisiopatología , Persona de Mediana Edad , Sistema Nervioso/fisiopatología , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Nervio Cubital/fisiopatologíaRESUMEN
PURPOSE: To develop a scale to measure (social) participation for use in rehabilitation, stigma reduction and social integration programmes. METHOD: A scale development study was carried out in Nepal, India and Brazil using standard methods. The instrument was to be based on the Participation domains of the International Classification of Functioning, Disability and Health (ICF), be cross-cultural in nature and assess client-perceived participation. Respondents rated their participation in comparison with a "peer", defined as "someone similar to the respondent in all respects except for the disease or disability". RESULTS: An 18-item instrument was developed in seven languages. Crohnbach's alpha was 0.92, intra-tester stability 0.83 and inter-tester reliability 0.80. Discrimination between controls and clients was good at a Participation Score threshold of 12. Responsiveness after a "life change" was according to expectation. CONCLUSIONS: The Participation Scale is reliable and valid to measure client-perceived participation in people affected by leprosy or disability. It is expected to be valid in other (stigmatised) conditions also, but this needs confirmation. The scale allows collection of participation data and impact assessment of interventions to improve social participation. Such data may be compared between clients, interventions and programmes. The scale is suitable for use in institutions, but also at the peripheral level.
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Personas con Discapacidad , Indicadores de Salud , Salud Pública , Rehabilitación , Encuestas y Cuestionarios/normas , Algoritmos , Brasil , Comparación Transcultural , Personas con Discapacidad/psicología , Personas con Discapacidad/rehabilitación , Personas con Discapacidad/estadística & datos numéricos , Femenino , Humanos , India , Relaciones Interpersonales , Entrevistas como Asunto , Masculino , Nepal , Satisfacción del Paciente , Salud Pública/estadística & datos numéricos , Calidad de Vida , Rehabilitación/estadística & datos numéricos , Reproducibilidad de los Resultados , Factores SocioeconómicosRESUMEN
La rehabilitación de las personas discapacitadas puede llevarse a cabo de muchas maneras, de acuerdo con el contexto cultural y político presente. Algunos planteamientos com en Nepal han enfatizado la rehabilitación de la función física del cliente, mientras que otros prefieren el bienestar social y psicológico. Algunos se han fortalecido sobre la experiencia de los profesionales, mientras que otros enfatizan la capacidad de cuidados familiares y comunitarios y buscan reforzarlos. A parte de proporcionar toda clase de servicios para personas discapacitadas. la rehabilitación intenta modificar las actitudes de la sociedad y proporcionar la integración de personas discapacitadas a la sociedad con igualdad de derechos y oportunidades. Este trabajo repasa una serie de planteamientos y modelos que se propusieron en un debate internacional sobre el tema. Además, se decriben cuatro dimensiones para poder caracterizar y definir clases de rehabilitación basada en objetivos ya definidos para ellos. Para tanto, se puede distinguir distintos tipos de proyectos de rehabilitación. La dirección, evaluación y soporte técnico para estos proyectos de rehabilitación deben tener en cuenta estas características.
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Lepra , Lepra/rehabilitaciónRESUMEN
El retraso en la presentación a la clínica para el diagnóstico es un factor de riesgo reconocido en lepra, pero es el resultado de interacciones complejas, entre factores físicos, sociales, económicos y psicológicos. El estudio actual es una respuesta a la situación en una clínica de tipo ambulatorio de Nepal, donde la amplia variación en presentarse con retrasos era causa de preocupación. Se empleó un cuestionario para recoger información sobre las admisiones consecutivas de pacientes ambulatorios. La información incluye datos demográficos, el primer síntoma de lepra, primeras acciones, comportamiento inicial en las búsqueda de ayuda, los motivos para, finalmente, buscar tratamiento y experiencia de profisionales sanitarios. Un primer análisis encontró una asociación entre retraso e edad, medio rural, clasificacoón de lepra, tiempo utilizado en andar hasta llegar a la clínica, casa no compartida con otro individuo afectado de lepra y una primera acción no adecuada. La relación entre nivel educativo mínimo y tiempo total de despalzamiento casi resulta significativo. Otro análisis identifica la falta de percepción de la enfermedad y una primera acción no apropiada son los principales factores contribuyentes al retraso. Se requiere una educación sanitaria efectiva y más amplia para enfrentarse a esta situación.
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Lepra , Lepra/etnología , Lepra/tratamiento farmacológico , Nepal/etnologíaRESUMEN
Se informa del resultado de 132 pacientes con deterioro agudo de la función nwerviosa (NFI) a los nervios sensitivos y un 67% de los motores evidenciaron mejoría , sin diferencia estadísticamente significativo en la respuesta de varios nervios a la prednisolona. La duración y gravedad del deterioro no son indicadores significativos del resultado terapéutico. Un total de 32% de los nervios determinados no respondieron el tratamiento con prednisolona y un 12% de los nervios afectados continuaron con deterioro funcional a pesar del tratamiento. En el grupo tratado, el valor medio ojo-mano-pie (EHF) se incrementó desde 2.02 al 1.33 (el valor mediano pasó de 2 a 1). Aproximadamente un tercio de los pacientes no recibieron tratamiento con prednisolona, motivo suficiente para que algunos presentaron NFI nuevo frente a un historial de deterioro crónico y resultaron NFI omitidos. El grupo de pacientes "injustamente tratados" presentó una mejoría espontánea de la función nerviosa sensorial del NFI del 62% de la función motora a los 12 meses desde el inicio de NFI. El valor EHF no registró ninguma mejoría estadísticamente significativa.
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Lepra Tuberculoide , Lepra/clasificación , Lepra/complicaciones , Lepra/terapiaRESUMEN
A 12 -month cohort of 2664 new leprosy cases in Bangladesh has been analyzed to provide information about the sensitivity and specificity of two different methods of classifying leprosy into paucibaccilary (PB) and multibaccilary (MB), if the results of skin-smear examination are note taken into account. The two methods are: 1) a procedure based on counting skin lesions recommended by the World Health Organization (WHO) ( 6 skin lesions = MB); and 2) the "Bangladesh method" ( 10 skin and nerve lesions = MB). In the latter system, any degree of nerve enlargement is taken to be a nerve lesion. The WHO method was found to be 89% sensitive and 88% specific at detecting smear-positive MB cases frm among the cohort; the Bangladesh system, 92% sensitive and 88,6% specific. The WHO method did not detect 18 smear-positive cases as MN; the Bangladesh method left 13 smear-positive cases unclassified as MB. Several of these "missed" (false-negative) cases had a high bacterial index. The WHO system of classifying leprosy cases a MB is simple to appply and has a reasonable balance between sensitivity and specificity. However, it must be recognized that the system will lead to a small but significant number of skin-smear-positive MB cases being treated with a PB treatment regimen.