International standards for neurological classification of spinal cord injury: cases with classification challenges.

The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) is routinely used to determine levels of injury and to classify the severity of the injury. Questions are often posed to the International Standards Committee of the American Spinal Injury Association (ASIA) regarding the classification. The committee felt that disseminating some of the challenging questions posed, as well as the responses, would be of benefit for professionals utilizing the ISNCSCI. Case scenarios that were submitted to the committee are presented with the responses as well as the thought processes considered by the committee members. The importance of this documentation is to clarify some points as well as update the SCI community regarding possible revisions that will be needed in the future based upon some rules that require clarification.

Documento de consenso: recomendaciones sobre la utilización de ecuaciones para la estimación del filtrado glomerular en niños / Consensus document: Recommendations for the use of equations to estimate glomerular filtration rate in children

La aparición de las guías K/DOQI en el año 2002 sobre definición, evaluación y clasificación en estadios de la enfermedad renal crónica (ERC) han supuesto un cambio importante en la forma de evaluar la función renal en adultos y en niños. Estas guías, recientemente actualizadas, recomiendan que el estudio de la función renal se realice a partir de la medida de la concentración sérica de creatinina y de la estimación del filtrado glomerular (FG) obtenido mediante una ecuación. Sin embargo, la implementación de esta recomendación en los informes del laboratorio clínico en población pediátrica ha sido casi nula. Los estudios aparecidos en los últimos años sobre la importancia de la detección y seguimiento de los pacientes con ERC, la aparición de nuevas ecuaciones de estimación del FG y los avances en los laboratorios clínicos respecto a los métodos de medida de creatinina y de cistatina C han determinado la colaboración entre los servicios de pediatría y de los laboratorios clínicos con objeto de establecer recomendaciones homogéneas y basadas en la mejor evidencia científica sobre la utilización de las ecuaciones de estimación del FG en este grupo de población. El objetivo de este documento es proporcionar recomendaciones sobre la evaluación de la función renal y la utilización de ecuaciones de estimación del FG en niños. Los destinatarios de estas recomendaciones son los pediatras, nefrólogos, bioquímicos clínicos, analistas clínicos y todos los profesionales de la salud relacionados con el estudio y la evaluación de la función renal de este grupo de pacientes (AU)

The appearance of the K/DOQI guidelines in 2002 on the definition, evaluation and staging of chronic kidney disease (CKD) have led to a major change in how to assess renal function in adults and children. These guidelines, recently updated, recommended that the study of renal function is based, not only on measuring the serum creatinine concentration, but this must be accompanied by the estimation of glomerular filtration rate (GFR) obtained by an equation. However, the implementation of this recommendation in the clinical laboratory reports in the paediatric population has been negligible. Numerous studies have appeared in recent years on the importance of screening and monitoring of patients with CKD, the emergence of new equations for estimating GFR, and advances in clinical laboratories regarding the methods for measuring plasma creatinine and cystatin C, determined by the collaboration between the departments of paediatrics and clinical laboratories to establish recommendations based on the best scientific evidence on the use of equations to estimate GFR in this population. The purpose of this document is to provide recommendations on the evaluation of renal function and the use of equations to estimate GFR in children from birth to 18 years of age. The recipients of these recommendations are paediatricians, nephrologists, clinical biochemistry, clinical analysts, and all health professionals involved in the study and evaluation of renal function in this group of patients (AU)

International Standards for Neurological Classification of Spinal Cord Injury: cases with classification challenges.

The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) is routinely used to determine the levels of injury and to classify the severity of the injury. Questions are often posed to the International Standards Committee of the American Spinal Injury Association regarding the classification. The committee felt that disseminating some of the challenging questions posed, as well as the responses, would be of benefit for professionals utilizing the ISNCSCI. Case scenarios that were submitted to the committee are presented with the responses as well as the thought processes considered by the committee members. The importance of this documentation is to clarify some points as well as update the SCI community regarding possible revisions that will be needed in the future based upon some rules that require clarification.

[Consensus document: recommendations for the use of equations to estimate glomerular filtration rate in children]. / Documento de consenso: recomendaciones sobre la utilización de ecuaciones para la estimación del filtrado glomerular en niños.

The appearance of the K/DOQI guidelines in 2002 on the definition, evaluation and staging of chronic kidney disease (CKD) have led to a major change in how to assess renal function in adults and children. These guidelines, recently updated, recommended that the study of renal function is based, not only on measuring the serum creatinine concentration, but this must be accompanied by the estimation of glomerular filtration rate (GFR) obtained by an equation. However, the implementation of this recommendation in the clinical laboratory reports in the paediatric population has been negligible. Numerous studies have appeared in recent years on the importance of screening and monitoring of patients with CKD, the emergence of new equations for estimating GFR, and advances in clinical laboratories regarding the methods for measuring plasma creatinine and cystatin C, determined by the collaboration between the departments of paediatrics and clinical laboratories to establish recommendations based on the best scientific evidence on the use of equations to estimate GFR in this population. The purpose of this document is to provide recommendations on the evaluation of renal function and the use of equations to estimate GFR in children from birth to 18 years of age. The recipients of these recommendations are paediatricians, nephrologists, clinical biochemistry, clinical analysts, and all health professionals involved in the study and evaluation of renal function in this group of patients.

Induction of autoimmune diabetes in non-obese diabetic mice requires interleukin-21-dependent activation of autoreactive CD8⁺ T cells.

Non-obese diabetic (NOD) mice lacking interleukin (IL)-21 or IL-21 receptor do not develop autoimmune type 1 diabetes (T1D). We have shown recently that IL-21 may promote activation of autoreactive CD8(+) T cells by increasing their antigen responsiveness. To investigate the role of IL-21 in activating diabetogenic CD8(+) T cells in the NOD mouse, we generated IL-21-deficient NOD mice expressing the highly pathogenic major histocompatibility complex (MHC) class-I-restricted 8.3 transgenic T cell receptor (TCR). IL-21 deficiency protected 8.3-NOD mice completely from T1D. CD8(+) T cells from the 8.3-NOD.Il21(-/-) mice showed decreased antigen-induced proliferation but displayed robust antigen-specific cytolytic activity and production of effector cytokines. IL-21-deficient 8.3 T cells underwent efficient homeostatic proliferation, and previous antigen stimulation enabled these cells to cause diabetes in NOD.Scid recipients. The 8.3 T cells that developed in an IL-21-deficient environment showed impaired antigen-specific proliferation in vivo even in IL-21-sufficient mice. These cells also showed impaired IL-2 production and Il2 gene transcription following antigen stimulation. However, IL-2 addition failed to reverse their impaired proliferation completely. These findings indicate that IL-21 is required for efficient initial activation of autoreactive CD8(+) T cells but is dispensable for the activated cells to develop effector functions and cause disease. Hence, therapeutic targeting of IL-21 in T1D may inhibit activation of naive autoreactive CD8(+) T cells, but may have to be combined with other strategies to inhibit already activated cells.

Trombosis venosa renal en recién nacida portadora de la mutación G20210A del gen de la protombina / Renal venous thrombosis in a neonate carrying the G20210a mutation of the prothrombin gene

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[Acute pancreatitis with fluid collections complicated with cutaneous fistula]. / Pancreatitis aguda necrotizante con colecciones líquidas complicadas con fístulas cutáneas.

The presence of acute fluid collections is an habitual event in an acute pancreatitis, generally followed by a favourable outcome. We present a case about an ancient woman suffering from an acute necrotizing pancreatitis with tense fluid collections that produced espontaneously several cutaneous fistula. We find no report on literature about this uncommon complication. We revised clinical management of acute fluid collections and pancreatic fistulas.

Anomalías renales congénitas en neonatos con reflujo vesicoureteral fetal. Detección con gammagrafía renal-99mTc-DMSA / Congenital renal abnormalities in neonates with fetal vesicoureteral reflux. Detection by 99M-technetiumM-Dimercaptosuccinic acid renal scintigraphy

Antecedentes: El reflujo vesicoureteral (RVU) "fetal" se caracteriza por una preponderancia masculina, reflujo de alto grado y anomalías parenquimatosas renales, estableciéndose una asociación entre RVU estéril y lesión renal. Objetivos Determinar, mediante gammagrafía renal con 99m tecnecio ácido dimercapto-succínico (99mTc-DMSA), la incidencia de anomalías renales congénitas en lactantes con RVU detectado posnatalmente por hidronefrosis prenatal o por cribado familiar, y especular sobre los mecanismos de acción de estas lesiones. Métodos: Se han revisado retrospectivamente las gammagrafías renales de lactantes con RVU y sin antecedentes de infección del tracto urinario (ITU), considerando anomalías renales: captación diferencial menor o igual al 40 por ciento o presencia de defectos corticales. Los hallazgos gammagráficos se han correlacionado con los de la ecografía posnatal. Resultados: Dieciocho pacientes cumplieron los criterios de inclusión; 15 niños y 3 niñas con RVU grado V, IV, III y II en 5, 10, 6 y 6 de las 36 unidades renales. La gammagrafía mostró alteraciones parenquimatosas en el 50 por ciento (9/18) de los pacientes y el 33 por ciento (9/27) de las unidades renales refluyentes; la mayoría fueron niños (7 niños, 2 niñas) con RVU de GV o GIV (6/9; 66 por ciento). La sensibilidad de la ecografía posnatal para detectar signos de lesión renal fue baja (22 por ciento). Conclusiones: Lactantes con RVU estéril, especialmente varones con RVU de alto grado, pueden presentar ya al nacimiento anomalías parenquimatosas renales, lo cual sugiere una etiopatogenia congénita de lesión renal independiente de la ITU. Estos defectos identificados por gammagrafía con frecuencia no son detectados en la ecografía posnatal. Por ambos motivos recomendamos la gammagrafía renal DMSA en la evaluación inicial de lactantes con RVU fetal (AU)

Pancreatitis aguda necrotizante con colecciones líquidas complicadas con fístulas cutáneas / Acute pancreatitis with fluid collections complicated with cutaneous fistula

La formación de colecciones líquidas peripancreáticas en el seno de una pancreatitis aguda es una complicación frecuente con buena evolución en la mayoría de los casos. Presentamos el caso de una mujer con pancreatitis aguda grave con colecciones líquidas a tensión que produjeron de manera espontánea fístulas cutáneas múltiples. No hemos encontrado datos en la literatura acerca de esta excepcional complicación. Revisamos el manejo terapéutico de las colecciones líquidas y fístulas pancreáticas (AU)

[Role of direct radionuclide cystography and renal study by dimercaptosuccinic acid (DMSA) in the diagnosis and follow-up of vesicoureteral reflux]. / La cistografía isotópica directa y la gammagrafía renal con ácido dimercaptosuccínico (DMSA) en el diagnóstico y seguimiento del reflujo vesicoureteral.

AIM: To evaluate the role of isotopic studies in the diagnosis and follow-up of vesicoureteral reflux (VUR) and to present the results of our current protocol. MATERIAL AND METHODS: Forty three patients with VUR were retrospectively studied with a mean follow-up of 43 years (1-11 years). VUR was diagnosed by voiding cystourethrography and followed-up by direct radionuclide cystography. During the follow-up all patients were studied by means of renal DMSA scintigraphy (21 were also studied during the acute phase of febrile urinary tract infection). RESULTS: Eighty three renal units were examined. Voiding cystourethrography was positive for VUR in 49 renal units (59%; 8 grade I, 18 grade II, 15 grade III, and 8 grade IV). During the follow-up, direct radionuclide cystography showed decrease or disappearance of VUR in 29 renal units (35%; 4 grade I, 16 grade II, 7 grade III, and 2 grade IV). DMSA studies performed during the follow-up showed cortical lesions in 17 renal units (5 with VUR grade II, 7 with grade III, and 5 grade IV). Nine of 21 patients examined by DMSA during the acute phase of febrile urinary tract infection showed cortical damage (43%), and 6 of them (67%) progressed to cortical lesion in the follow-up DMSA. CONCLUSIONS: The present protocol allows for the correct diagnosis and control of VUR, the early detection of acute renal damage, and the control of its evolution.

La cistografía isotópica directa y la gammagrafía renal con ácido dimercaptosuccínico (DMSA) en el diagnóstico y seguimiento del reflujo vesicoureteral / Role of direct radionuclide cystography and renal study by dimercaptosuccinic acid (DMSA) in the diagnosis and follow-up of vesicoureteral reflux

Objetivo: Valorar la utilidad de la cistografía isotópica directa (CID) y de la gammagrafía renal con ácido dimercaptosuccínico (DMSA) en el diagnóstico y seguimiento del RVU, según los resultados obtenidos a partir del protocolo actual de nuestro centro. Material y Métodos: Se han estudiado retrospectivamente 43 pacientes diagnosticados de RVU con un período de seguimiento medio de 4 ñ 3 años (1-11 años). El diagnóstico de RVU se realizó mediante cistografía radiológica (CUMS) y el seguimiento mediante CUMS y/o CID. Durante el seguimiento se realizó gammagrafía renal con DMSA a todos los pacientes. Veintiún pacientes también fueron estudiados con DMSA durante la fase aguda de la infección urinaria febril. Resultados: Se exploraron 83 unidades renales. En el momento del diagnóstico la CUMS fue positiva para RVU en 49 unidades renales (59 per cent; 8 grado I, 18 grado II, 15 grado III y 8 grado IV). Durante el seguimiento por CID se observó disminución o desaparición del RVU en 29 unidades renales (35 per cent; 4 grado I, 16 grado II, 7 grado III y 2 grado IV). Durante el seguimiento el DMSA mostró lesiones corticales en 17 unidades renales (5 con RVU grado II, 7 grado III y 5 grado IV). Nueve de los 21 pacientes estudiados con DMSA durante la fase aguda de la infección urinaria febril presentaron afectación cortical (43 per cent), de los cuales 6 evolucionaron a lesión cortical en el DMSA de control (67 per cent). Conclusiones: El protocolo descrito permite diagnosticar y controlar el RVU, identificar precozmente la afectación renal y controlar su evolución (AU)

The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages.

In this work, we characterize genes in Mycobacterium tuberculosis that are regulated by IdeR (iron-dependent regulator), an iron-responsive DNA-binding protein of the DtxR family that has been shown to regulate iron acquisition in Mycobacterium smegmatis. To identify some of the genes that constitute the IdeR regulon, we searched the M. tuberculosis genome for promoter regions containing the consensus IdeR/DxR binding sequence. Genes preceded by IdeR boxes included a set encoding proteins necessary for iron acquisition, such as the biosynthesis of siderophores (mbtA, mbtB, mbtI), aromatic amino acids (pheA, hisE, hisB-like) and others annotated to be involved in the synthesis of iron-storage proteins (bfrA, bfrB). Some putative IdeR-regulated genes identified in this search encoded proteins predicted to be engaged in the biosynthesis of lipopolysaccharide (LPS)-like molecules (rv3402c), lipids (acpP) and peptidoglycan (murB). We analysed four promoter regions containing putative IdeR boxes, mbtA-mbtB, mbI, rv3402c and bfrA-bfd, for interaction with IdeR and for iron-dependent expression. Gel retardation experiments and DNase footprinting analyses with purified IdeR showed that IdeR binds to these IdeR boxes in vitro. Analysis of the promoters by primer extension indicated that the IdeR boxes are located near the -10 position of each promoter, suggesting that IdeR acts as a transcriptional repressor by blocking RNA polymerase binding. Using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) coupled to molecular beacons, we showed that mRNA levels of mbtA, mbtB, mbtI, rv3402c and bfd are induced 14- to 49-fold in cultures of M. tuberculosis starved for iron, whereas mRNA levels of bfrA decreased about threefold. We present evidence that IdeR not only acts as a transcriptional repressor but also functions as an activator of bfrA. Three of the IdeR- and iron-repressed genes, mbtB, mbtI and rv3402c, were induced during M. tuberculosis infection of human THP-1 macrophages.

Identification and characterization of two divergently transcribed iron regulated genes in Mycobacterium tuberculosis.

SETTING: Low iron availability in the host induces the expression of iron acquisition systems and virulence genes in many pathogens. IdeR is a mycobacterial iron dependent regulator that controls the iron starvation and oxidative stress responses in Mycobacterium smegmatis. It is important to determine the role of IdeR and its regulon in M. tuberculosis, as identification of iron regulated genes can aid in the design of new drugs and generation of attenuated strains. OBJECTIVE: A potential IdeR binding site was found in the M. tuberculosis genome flanked by two divergently oriented open reading frames, irg1 and irg2. The aim of this study was to determine whether irg1 and irg2 were iron and IdeR regulated genes. DESIGN: Interaction of IdeR with the putative binding sequence was examined by gel shift and footprinting assays. Transcriptional fusions of irg1 and irg2 to IacZ were used to study the effect of iron levels on the expression of these genes. RESULTS: IdeR binds to the predicted binding site, which overlaps with the irg1 promoter. irg1 and irg2 expression was decreased by iron in M. tuberculosis and in wild type M. smegmatis, but not in a M. smegmatis ideR mutant. CONCLUSION: Two M. tuberculosis iron/IdeR regulated genes were identified. irg1 is predicted to be the M. tuberculosis hisE gene, which is involved in histidine biosynthesis. It is directly upstream of the M. tuberculosis hisG. irg2 encodes a putative membrane protein that is a member of the PPE family.

Extra and intracellular expression of Mycobacterium tuberculosis genes.

To understand how Mycobacterium tuberculosis survives and grows in an infected host, we are studying the mycobacterial transcriptional machinery and its response to stresses encountered in vitro and in vivo. Much has been learned about sigma factors and other transcriptional regulators concerning their roles in controlling mycobacterial gene expression. It has recently been shown that sigma A is the essential housekeeping sigma factor and the alternative sigma factor sigma B, not essential for growth in a laboratory setting, is required for a robust protective response to various environmental stresses. We are also studying the mechanism by which the R522H mutation in sigma A prevents the transcription of certain genes, including some that are believed necessary for virulence. Also under investigation is the mycobacterial iron acquisition apparatus and its regulation, as metabolism of this essential element plays a key role in microbial pathogenesis. We have identified and characterized the major mycobacterial iron regulator IdeR that blocks the synthesis of the iron uptake machinery and have identified target genes in M. smegmatis and M. tuberculosis that are directly repressed by IdeR. Recent studies have examined the control of M. tuberculosis gene expression in vivo. Among these new approaches are an in vivo expression technology system to identify M. tuberculosis genes that are induced in macrophages and mice and a novel RT-PCR method that allows an accurate comparison between the levels of specific mRNAs in M. tuberculosis grown in vitro with those found in bacteria growing in human macrophages.

Compliance with AZT treatment regimen of HIV-seropositive injection drug users: a neglected issue.

Although treatment with zidovudine (AZT) is now recommended for asymptomatic and symptomatic HIV-infected persons with CD4+ cell counts of 0.20 to 0.50 x 10(9)/L and under, data gathered from a small convenience sample of current and former injection drug users with AIDS in the New York City metropolitan region suggest that noncompliance with HIV/AIDS-related therapeutic regimen may be common in this population. This paper enumerates the reasons for noncompliance offered by these informants, reviews the general literature on treatment compliance to identify additional potential reasons for non-adherence to AZT treatment regimen, and outlines some suggestions for future research into this important issue that may prompt changes in the antiviral delivery system.