Differential Interleukin-8 thresholds for chemotaxis and netosis in human neutrophils.

In humans, IL-8 (CXCL8) is a key chemokine for chemotaxis of polymorphonuclear leukocytes and monocytes/macrophages when acting on CXCR1 and CXCR2. CXCL8 activity on neutrophils includes chemotaxis and eliciting the extrusion of neutrophil extracellular traps (NETs). In this study, we show that concentrations of IL-8 that induce NETosis surpass in at least one order of magnitude those required to elicit chemoattraction in human neutrophils. IL-8-induced NETosis was less dependent on G-proteins than migration, while extracellular Ca+2 chelation similarly inhibited both processes. Reactive oxygen species (ROS) were more important for NETosis than for chemotaxis as evidenced by neutralization with N-acetyl -cysteine. Interestingly, selective blockade with anti-CXCR1 mAb inhibited NETosis much more readily than chemotaxis, while pharmacological inhibition of both CXCR1 and CXCR2, or selective inhibition for CXCR2 alone, similarly inhibited both functions. Together, these results propose a model according to which low concentrations of IL-8 in a gradient attract neutrophils to the inflammatory foci, while high receptor-saturating concentrations of IL-8 give rise to NETosis once leukocytes reach the core of the inflammatory insult.

Guías de práctica clínica para la atención del embarazo en mujeres con enfermedades reumáticas autoinmunes del Colegio Mexicano de Reumatología. Parte I / Clinical practice guidelines for the management of pregnancy in women with autoimmune rheumatic diseases of the Mexican College of Rheumatology. Part I

Antecedentes. El embarazo en mujeres con enfermedades reumáticas autoinmunes se asocia a diversas complicaciones maternofetales. El desarrollo de guías de práctica clínica con la mejor evidencia científica disponible puede ayudar a homogeneizar la atención en estas pacientes. Objetivos. Proporcionar recomendaciones respecto al control prenatal, el tratamiento y el seguimiento más efectivo de la mujer embarazada con lupus eritematoso (LES), artritis reumatoide (AR) y síndrome por anticuerpos antifosfolípidos (SAF). Metodología. Para la elaboración de las recomendaciones se conformaron grupos nominales de expertos y se realizaron consensos formales, búsqueda sistematizada de la información, elaboración de preguntas clínicas, elaboración y calificación de las recomendaciones, fase de validación interna por pares y validación externa del documento final teniendo en cuenta los criterios de calidad del instrumento AGREE II. Resultados. Los grupos de trabajo contestaron las 37 preguntas relacionadas con la atención maternofetal en LES, AR y SAF, así como de fármacos antirreumáticos durante el embarazo y la lactancia. Las recomendaciones fueron discutidas e integradas en un manuscrito final y se elaboraron los algoritmos correspondientes. En esta primera parte se presentan las recomendaciones para mujeres embarazadas con LES. Conclusiones. La guía mexicana de práctica clínica para la atención del embarazo en mujeres con LES proporciona recomendaciones e integra la mejor evidencia disponible para el tratamiento y el seguimiento de estas pacientes (AU)

Background. Pregnancy in women with autoimmune rheumatic diseases is associated with several maternal and fetal complications. The development of clinical practice guidelines with the best available scientific evidence may help standardize the care of these patients. Objectives. To provide recommendations regarding prenatal care, treatment, and a more effective monitoring of pregnancy in women with lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphospholipid antibody syndrome (APS). Methodology. Nominal panels were formed for consensus, systematic search of information, development of clinical questions, processing and grading of recommendations, internal validation by peers, and external validation of the final document. The quality criteria of the AGREE II instrument were followed. Results. The various panels answered the 37 questions related to maternal and fetal care in SLE, RA, and APS, as well as to the use of antirheumatic drugs during pregnancy and lactation. The recommendations were discussed and integrated into a final manuscript. Finally, the corresponding algorithms were developed. We present the recommendations for pregnant women with SLE in this first part. Conclusions. We believe that the Mexican clinical practice guidelines for the management of pregnancy in women with SLE integrate the best available evidence for the treatment and follow-up of patients with these conditions (AU)

Guías de práctica clínica para la atención del embarazo en mujeres con enfermedades reumáticas autoinmunes del Colegio Mexicano de Reumatología. Parte II / Clinical practice guidelines for the management of pregnancy in women with autoimmune rheumatic diseases of the Mexican College of Rheumatology. Part II

Antecedentes. El embarazo en mujeres con enfermedades reumáticas autoinmunes se asocia a diversas complicaciones materno-fetales. El desarrollo de guías de práctica clínica con la mejor evidencia científica disponible puede ayudar a homogeneizar la atención en estas pacientes. Objetivos. Proporcionar recomendaciones respecto al control prenatal, el tratamiento y el seguimiento más efectivo de la mujer embarazada con lupus eritematoso sistémico, artritis reumatoide (AR) y síndrome por anticuerpos antifosfolípidos (SAF). Metodología. Para la elaboración de las recomendaciones se conformaron grupos nominales de expertos y se realizaron consensos formales, búsqueda sistematizada de la información, elaboración de preguntas clínicas, elaboración y calificación de las recomendaciones, fase de validación interna por pares y validación externa del documento final teniendo en cuenta los criterios de calidad del instrumento AGREE II. Resultados. Los grupos de trabajo contestaron las 37 preguntas relacionadas con la atención materno-fetal en lupus eritematoso sistémico, AR y SAF, así como de fármacos antirreumáticos durante el embarazo y lactancia. Las recomendaciones fueron discutidas e integradas en un manuscrito final y se elaboraron los algoritmos correspondientes. En esta segunda parte se presentan las recomendaciones para mujeres embarazas con AR, SAF y el uso de fármacos antirreumáticos durante el embarazo y lactancia. Conclusiones. La guía mexicana de práctica clínica para la atención del embarazo en mujeres con AR y SAF integra la mejor evidencia disponible para el tratamiento y el seguimiento de estas pacientes (AU)

Background. Pregnancy in women with autoimmune rheumatic diseases is associated with several maternal and fetal complications. The development of clinical practice guidelines with the best available scientific evidence may help standardize the care of these patients. Objectives. To provide recommendations regarding prenatal care, treatment, and a more effective monitoring of pregnancy in women with lupus erythematosus, rheumatoid arthritis (RA) and antiphospholipid syndrome (APS). Methodology. Nominal panels were formed for consensus, systematic search of information, development of clinical questions, processing and staging of recommendations, internal validation by peers and external validation of the final document. The quality criteria of the AGREE II instrument were followed. Results. The panels answered 37 questions related to maternal and fetal care in lupus erythematosus, RA and APS, as well as for use of antirheumatic drugs during pregnancy and lactation. The recommendations were discussed and integrated into a final manuscript. Finally, the corresponding algorithms were developed. In this second part, the recommendations for pregnant women with RA, APS and the use of antirheumatic drugs during pregnancy and lactation are presented. Conclusions. We believe that the Mexican clinical practice guidelines for the management of pregnancy in women with RA and APS integrate the best available evidence for the treatment and follow-up of patients with these conditions (AU)

Hormona anti-mülleriana en mujeres en edad reproductiva con lupus eritematoso sistémico / Anti-müllerian hormone in reproductive age women with systemic lupus erythematosus

El lupus eritematoso sistémico (LES) es una enfermedad autoinmune inflamatoria sistémica crónica; se considera que la fertilidad es normal en pacientes con LES, los factores asociados con una baja reserva folicular que condicionan falla ovárica son: actividad de la enfermedad, anticuerpos antiovario y el uso de agentes citotóxicos. La hormona anti-mülleriana (HAM) es un marcador para determinar la reserva folicular. Objetivo Determinar los niveles de HAM en mujeres con LES en edad reproductiva. Material y métodos. Incluimos a 65 mujeres, de 18 a 40 años, clasificadas como LES según los criterios ACR 1997. Se obtuvieron las características demográficas, clínicas, ginecoobstétricas y niveles séricos de HAM. Se realizó un análisis bivariado entre las pacientes con baja reserva ovárica y aquellas con reserva ovárica normal. Se realizó un análisis de correlación entre los índices de actividad y daño, así como la dosis acumulada de ciclofosfamida y los niveles de HAM. Resultados. La mediana del título de HAM fue de 0,61 ng/ml. La prevalencia de baja reserva ovárica en nuestro estudio fue del 3,07%. La mediana del MEX-SLEDAI fue de 1 punto y la de SLICC 2 puntos. Veinticinco pacientes (38,4%) habían utilizado ciclofosfamida y la dosis promedio acumulada fue de 7,5 g. Conclusiones. En nuestra población, se encontró una mediana del título de HAM de 0,61 ng/ml, similar a lo reportado anteriormente. La prevalencia de baja reserva ovárica fue del 3,07%. No se encontró correlación entre el uso de ciclofosfamida, la actividad de la enfermedad o los niveles de HAM (AU)

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune systemic and chronic disease. Fertility in SLE patients is considered normal; factors that have been associated in these patients with ovarian failure are: disease activity, autoantibodies, and the use of cytotoxic agents. The anti-Müllerian hormone (AMH) is a marker that helps to determine the follicular reserve. Objective. Determinate the objective was to determine AMH levels in women of reproductive age with SLE. Material and methods. We included 65 women with SLE classified according to the 1997 ACR criteria, 18- to 40-years old. We obtained demographic, clinical, obstetric, and gynecological characteristics as well as serum levels of AMH. We performed a bivariate analysis among patients with low ovarian reserve and those with normal ovarian reserve. We also performed a correlation analysis between activity and damage index and between the cumulative cyclophosphamide dose and AMH levels. Results. We found a median of serum AMH in SLE patients of .61 ng/mL. The prevalence of low ovarian reserve in our study was 3.07%. We found a median MEX-SLEDAI score of 1 point and the median SLICC score was 2 points. Twenty-five patients (38.4%) had used cyclophosphamide and their cumulative average dose was 7.5 grams. Conclusions. We found a median of AMH of .61 ng/mL in our population. The prevalence of low ovarian reserve in SLE patients was 3.07%. We did not find a correlation between AMH levels, the use of cyclophosphamide, and disease activity (AU)

Clinical practice guidelines for the management of pregnancy in women with autoimmune rheumatic diseases of the Mexican College of Rheumatology. Part I.

BACKGROUND: Pregnancy in women with autoimmune rheumatic diseases is associated with several maternal and fetal complications. The development of clinical practice guidelines with the best available scientific evidence may help standardize the care of these patients. OBJECTIVES: To provide recommendations regarding prenatal care, treatment, and a more effective monitoring of pregnancy in women with lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphospholipid antibody syndrome (APS). METHODOLOGY: Nominal panels were formed for consensus, systematic search of information, development of clinical questions, processing and grading of recommendations, internal validation by peers, and external validation of the final document. The quality criteria of the AGREE II instrument were followed. RESULTS: The various panels answered the 37 questions related to maternal and fetal care in SLE, RA, and APS, as well as to the use of antirheumatic drugs during pregnancy and lactation. The recommendations were discussed and integrated into a final manuscript. Finally, the corresponding algorithms were developed. We present the recommendations for pregnant women with SLE in this first part. CONCLUSIONS: We believe that the Mexican clinical practice guidelines for the management of pregnancy in women with SLE integrate the best available evidence for the treatment and follow-up of patients with these conditions.

Clinical practice guidelines for the management of pregnancy in women with autoimmune rheumatic diseases of the Mexican College of Rheumatology. Part II.

BACKGROUND: Pregnancy in women with autoimmune rheumatic diseases is associated with several maternal and fetal complications. The development of clinical practice guidelines with the best available scientific evidence may help standardize the care of these patients. OBJECTIVES: To provide recommendations regarding prenatal care, treatment, and a more effective monitoring of pregnancy in women with lupus erythematosus, rheumatoid arthritis (RA) and antiphospholipid syndrome (APS). METHODOLOGY: Nominal panels were formed for consensus, systematic search of information, development of clinical questions, processing and staging of recommendations, internal validation by peers and external validation of the final document. The quality criteria of the AGREE II instrument were followed. RESULTS: The panels answered 37 questions related to maternal and fetal care in lupus erythematosus, RA and APS, as well as for use of antirheumatic drugs during pregnancy and lactation. The recommendations were discussed and integrated into a final manuscript. Finally, the corresponding algorithms were developed. In this second part, the recommendations for pregnant women with RA, APS and the use of antirheumatic drugs during pregnancy and lactation are presented. CONCLUSIONS: We believe that the Mexican clinical practice guidelines for the management of pregnancy in women with RA and APS integrate the best available evidence for the treatment and follow-up of patients with these conditions.

Anti-Müllerian hormone in reproductive age women with systemic lupus erythematosus.

UNLABELLED: Systemic lupus erythematosus (SLE) is an inflammatory autoimmune systemic and chronic disease. Fertility in SLE patients is considered normal; factors that have been associated in these patients with ovarian failure are: disease activity, autoantibodies, and the use of cytotoxic agents. The anti-Müllerian hormone (AMH) is a marker that helps to determine the follicular reserve. OBJECTIVE: Determinate the objective was to determine AMH levels in women of reproductive age with SLE. MATERIAL AND METHODS: We included 65 women with SLE classified according to the 1997 ACR criteria, 18- to 40-years old. We obtained demographic, clinical, obstetric, and gynecological characteristics as well as serum levels of AMH. We performed a bivariate analysis among patients with low ovarian reserve and those with normal ovarian reserve. We also performed a correlation analysis between activity and damage index and between the cumulative cyclophosphamide dose and AMH levels. RESULTS: We found a median of serum AMH in SLE patients of .61 ng/mL. The prevalence of low ovarian reserve in our study was 3.07%. We found a median MEX-SLEDAI score of 1 point and the median SLICC score was 2 points. Twenty-five patients (38.4%) had used cyclophosphamide and their cumulative average dose was 7.5 grams. CONCLUSIONS: We found a median of AMH of .61 ng/mL in our population. The prevalence of low ovarian reserve in SLE patients was 3.07%. We did not find a correlation between AMH levels, the use of cyclophosphamide, and disease activity.

[Obesity studies in candidate genes]. / Estudios sobre la obesidad en genes candidatos.

There are more than 430 chromosomic regions with gene variants involved in body weight regulation and obesity development. Polymorphisms in genes related to energy expenditure--uncoupling proteins (UCPs), related to adipogenesis and insulin resistance--hormone-sensitive lipase (HLS), peroxisome proliferator-activated receptor gamma (PPAR gamma), beta adrenergic receptors (ADRB2,3), and alfa tumor necrosis factor (TNF-alpha), and related to food intake--ghrelin (GHRL)--appear to be associated with obesity phenotypes. Obesity risk depends on two factors: a) genetic variants in candidate genes, and b) biographical exposure to environmental risk factors. It is necessary to perform new studies, with appropriate control groups and designs, in order to reach relevant conclusions with regard to gene/environmental (diet, lifestyle) interactions.

Determinantes clínicos y bioquímicos del pronóstico a corto plazo en pacientes con cirrosis por alcohol

Se determinó el pronóstico a corto plazo en pacientes con cirrosis hepática por alcohol mediante la aplicación de la Escala de Orrego que valora parámetros clínicos y bioquímicos. Se estudiaron prospectivamente 50 pacientes con diagnóstico de cirrosis hepática por alcohol que ingresaron al departamento de clínica del hospital Vicente Corral Moscoso, entre el 1ro de Diciembre de 1987 al 31 de Mayo de 1988. Se demuestra que la hepatomegalia, encefalopatía hepática, tendencia hemorrágica, ascitis, además periféricos, astenia y anorexia, son datos significativos para valorar el pronóstico en el grupo de fallecidos (P<0.01); en cuanto a los datos de laboratorio la TGO, albúmina sérica y fosfatasa alcalina son los datos de laboratorio de mayor valor en el pronóstico a corto plazo (p<0.01). La aplicación de la escala de orrego es una manera útil y sencilla para determinar el pronóstico, pues demuestra que los pacientes con menor puntaje (lesión hepática moderada) tienen mejor pronóstico que aquellos cuyo puntaje es mayor (lesión hepática severa)(p<0.01). Las complicaciones determinaron una mortalidad del 38//similiar a la observada en otros países.

Síndrome de Cushing por carcinoma suprarrenal: a proposito de un caso

Se revisa el caso de un paciente ingresado al Departamento de Clínica del Hospital "Vicente Corral Moscoso", con diagnóstico de Síndrome de Cushing, cuya investigación demostró la presencia de un Carcinoma Suprarrenal derecho. El interés del mismo reside en que se trata del primer caso de Carcinoma suprarrenal diagnosticado en nuestro hospital, con cuyo motivo se desea alertar al médico clínico para qua ante la presencia de un niño o joven con un síndrome de Cushing piense en la frecuente associación con un carcinoma o adenoma suprarrenal y recuerde las diferentes etapas que deben cumplirse para llegar al diagnóstico definitivo primario