Espondiloencondrodisplasia con desregulación inmune relacionada a ACP5. Reporte de cuatro casos / Spondyloenchondrodysplasia with immune dysregulation related to ACP5. A report of 4 cases

La espondiloencondrodisplasia con desregulación inmune relacionada a ACP5 (SPENCDI #607944, por la sigla de spondyloenchondrodysplasia with immune dysregulation y el número que le corresponde en OMIM, Online Mendelian Inheritance in Man) es una displasia inmuno-ósea poco frecuente con manifestaciones heterogéneas y gravedad variable. Presenta lesiones espondilometafisarias, disfunción inmune y compromiso neurológico. Se reportan aspectos clínicos, radiológicos y genéticos de cuatro niñas con SPENCDI en un hospital pediátrico. Todas presentaron manifestaciones esqueléticas y tres de ellas enfermedad inmunológica grave. Se encontró en tres pacientes la variante probablemente patogénica c.791T>A; p.Met264Lys en homocigosis, y en una paciente las variantes c.791T>A; p.Met264Lys y c.632T>C; p.lle211Thr (variante de significado incierto con predicción patogénica según algoritmos bioinformáticos) en heterocigosis compuesta en ACP5. La presencia de la variante repetida c.791T>A sugiere la posibilidad de un ancestro en común en nuestra población. El reconocimiento y diagnóstico de esta entidad es importante para lograr un oportuno abordaje, que deberá ser multidisciplinario, orientado hacia la prevención de posibles complicaciones.

Spondyloenchondrodysplasia with immune dysregulation related to ACP5 (SPENCDI, OMIM number 607944) is an uncommon immune-skeletal dysplasia with heterogeneous manifestations and variable severity. It is characterized by spondylar and metaphyseal lesions, immune dysfunction, and neurological involvement. Here we report the clinical, radiological and genetic aspects of 4 girls with SPENCDI treated at a children's hospital. They all had skeletal manifestations and 3 developed severe immune disease. In 3 patients, the likely pathogenic variant c.791T>A; p.Met264Lys (homozygous mutation) was observed, while 1 patient had variants c.791T>A; p.Met264Lys and c.632T>C; p.lle211Thr (variant of uncertain significance with pathogenic prediction based on bioinformatics algorithms) caused by a compound heterozygous mutation in ACP5. The repeated presence of variant c.791T>A suggests the possibility of a common ancestor in our population. The recognition and diagnosis of this disorder is important to achieve a timely approach, which should be multidisciplinary and aimed at preventing possible complications.

Spondyloenchondrodysplasia with immune dysregulation related to ACP5. A report of 4 cases. / Espondiloencondrodisplasia con desregulación inmune relacionada a ACP5. Reporte de cuatro casos.

Spondyloenchondrodysplasia with immune dysregulation related to ACP5 (SPENCDI, OMIM number 607944) is an uncommon immune-skeletal dysplasia with heterogeneous manifestations and variable severity. It is characterized by spondylar and metaphyseal lesions, immune dysfunction, and neurological involvement. Here we report the clinical, radiological and genetic aspects of 4 girls with SPENCDI treated at a children's hospital. They all had skeletal manifestations and 3 developed severe immune disease. In 3 patients, the likely pathogenic variant c.791T>A; p.Met264Lys (homozygous mutation) was observed, while 1 patient had variants c.791T>A; p.Met264Lys and c.632T>C; p.lle211Thr (variant of uncertain significance with pathogenic prediction based on bioinformatics algorithms) caused by a compound heterozygous mutation in ACP5. The repeated presence of variant c.791T>A suggests the possibility of a common ancestor in our population. The recognition and diagnosis of this disorder is important to achieve a timely approach, which should be multidisciplinary and aimed at preventing possible complications.

La espondiloencondrodisplasia con desregulación inmune relacionada a ACP5 (SPENCDI #607944, por la sigla de spondyloenchondrodysplasia with immune dysregulation y el número que le corresponde en OMIM, Online Mendelian Inheritance in Man) es una displasia inmuno-ósea poco frecuente con manifestaciones heterogéneas y gravedad variable. Presenta lesiones espondilometafisarias, disfunción inmune y compromiso neurológico. Se reportan aspectos clínicos, radiológicos y genéticos de cuatro niñas con SPENCDI en un hospital pediátrico. Todas presentaron manifestaciones esqueléticas y tres de ellas enfermedad inmunológica grave. Se encontró en tres pacientes la variante probablemente patogénica c.791T>A; p.Met264Lys en homocigosis, y en una paciente las variantes c.791T>A; p.Met264Lys y c.632T>C; p.lle211Thr (variante de significado incierto con predicción patogénica según algoritmos bioinformáticos) en heterocigosis compuesta en ACP5. La presencia de la variante repetida c.791T>A sugiere la posibilidad de un ancestro en común en nuestra población. El reconocimiento y diagnóstico de esta entidad es importante para lograr un oportuno abordaje, que deberá ser multidisciplinario, orientado hacia la prevención de posibles complicaciones.

Perfil de atención de pacientes con errores congénitos del metabolismo en un hospital pediátrico entre 2008 y 2018 / Profile of care of patients with inborn errors of metabolism in a pediatric hospital between 2008 and 2018 / Perfil do atendimento de pacientes com erros inatos do metabolismo em um hospital pediátrico entre 2008 e 2018

Resumen Los errores congénitos del metabolismo (ECM) son un grupo de enfermedades poco frecuentes que generan gran morbimortalidad. El objetivo de este trabajo fue describir el perfil de atención clínico y bioquímico de los ECM no incluidos en la pesquisa neonatal en menores de 15 años atendidos en un hospital pediátrico, entre enero de 2008 y diciembre de 2018. Se realizó un estudio descriptivo y retrospectivo en el que se evaluaron los registros hospitalarios: motivo de consulta, diagnóstico, evolución clínica, tiempos y costos diagnósticos de pacientes con sospecha y diagnóstico confirmado de ECM entre 2008 y 2018 en un hospital público pediátrico de Mendoza, Argentina. Se incluyeron 59 pacientes con ECM: enfermedades de depósito lisosomal (32,2%) y alteración metabólica de aminoácidos y acidurias orgánicas (27,1%), entre otros. La edad media fue de 2,6 años y la relación varón/mujer 1,5. La media de tiempo entre la primera consulta por sospecha de ECM y el diagnóstico fue de 11 meses. Hubo correspondencia entre el diagnóstico y el motivo de consulta (p=0,003). El 22% evolucionó al deterioro progresivo, 25,4% permanecieron estables, 28,8% con secuelas y 23,8% fallecieron. El costo directo total de los exámenes bioquímicos fue 61 560 UB=1 809 248 pesos argentinos=46 785 dólares estadounidenses (valor a finales de 2018). En conclusión, este trabajo refleja la variabilidad de los ECM, su evolución clínica, similar a lo publicado y el perfil bioquímico local.

Abstract Inborn errors of metabolism (IEM) are a group of rare diseases that cause high morbidity and mortality. The objective of the present study was to describe the clinical-biochemical profile of patients, under 15 years old, with IEM not included in newborn screening, in a pediatric hospital, from January 2008 to December 2018. A descriptive and retrospective study was carried out in which hospital records were evaluated: reason for consultation, diagnosis, clinical evolution, diagnostic times and costs of patients with suspected and confirmed diagnosis of IEM between 2008 and 2018 in a public pediatric hospital from Mendoza, Argentina. A total of 59 patients with IEM were evaluated: lysosomal storage diseases (32.2%) and metabolic alteration of amino acids and organic acidurias (27.1%), among others. The mean age was 2.6 years and the male/female ratio was 1.5. The mean time between the first consultation for suspected IEM and diagnosis was 11 months. There was correspondence between the diagnosis and the reason for consultation (p=0.003). Twenty-two percent evolved to progressive deterioration, 25.4% remained stable, 28.8% with sequelae and 23.8% died. The total direct cost of the biochemical tests was 61 560 UB=1 809 248 Argentine pesos=46 785 US dollars (value at the end of 2018). Concluding, this work reflects the variability of IEM and its clinical evolution, similar to what has been published, and the local biochemical profile.

Resumo Os erros inatos do metabolismo (EIM) são um grupo de doenças pouco frequentes que geram alta morbimortalidade. O objetivo deste trabalho foi descrever o perfil clínico e bioquímico de atendimento dos EIM não incluídos na triagem neonatal em menores de 15 anos atendidos em um hospital pediátrico, entre janeiro de 2008 e dezembro de 2018. Foi realizado um estudo descritivo e retrospectivo em que foram avaliados os registros hospitalares: motivo da consulta, diagnóstico, evolução clínica, tempos e custos diagnósticos de pacientes com diagnóstico suspeito e confirmado de EIM entre 2008 e 2018 em um hospital pediátrico público em Mendoza, Argentina. Foram avaliados 59 pacientes com EIM: doenças de depósito lisossômico (32,2%) e alteração metabólica de aminoácidos e acidúrias orgânicas (27,1%), entre outras. A média de idade foi de 2,6 anos e a relação homem/mulher foi de 1,5. O tempo médio entre a primeira consulta por suspeita de EIM e o diagnóstico foi de 11 meses. Houve correspondência entre o diagnóstico e o motivo da consulta (p=0,003). Evoluíram 22% para piora progressiva, 25,4% permaneceram estáveis , 28,8% com sequelas e 23,8% faleceram. O custo direto total dos testes bioquímicos foi de 61 560 UB=1 809 248 pesos argentinos=46 785 U$S (valor no final de 2018). Concluindo, este trabalho reflete a variabilidade da EIM e sua evolução clínica, semelhante ao que vem sendo publicado, e o perfil bioquímico local.

Equivalence class formation via class-specific consequences in children diagnosed with autism spectrum disorder / Formação de classes de equivalência via consequências específicas das classes em crianças diagnosticadas com transtorno do espectro do autismo / Formación de clases equivalentes a través de consecuencias específicas de clase en niños diagnosticados con trastorno del espectro autista

Previous equivalence-class formation studies, with class-specific consequences, found inter-subject variability, probably due to loss of efficacy of the consequences as reinforcers. This study evaluated (a) the efficacy of introducing variations of events (within a category) as class-specific consequences and (b) the inclusion of these consequences into the equivalence classes. Two children diagnosed with Autism Spectrum Disorder (ASD), and with intellectual disabilities, were given identity matchingto-sample training (Set A - Sample A1, S+A1/S-A2 and Sample A2, S+A2/S-A1) and simple discrimination reversal training (Set B - S+B1/S-B2 and reversals). Two sets of assorted videos on the same theme plus two sets of assorted food items within the same category were used as class-specific consequences. The data show that the variety of elements was efficient to maintain reinforcement efficacy and encourage the use of similar procedures in the applied context. Both participants showed strong evidence of equivalence class formation, confirming the theoretical prediction regarding the inclusion of the class-specific consequences in the classes. The data confirm that equivalence relations can be found in three-term contingencies.

Estudos anteriores sobre a formação de classes de equivalência, com consequências específicas para as classes, apontaram variabilidade intersujeitos provavelmente devida a perda de eficácia das consequências como reforçadores. O presente estudo avaliou (a) a eficácia da introdução de variações de eventos (dentro de uma categoria) como consequências específicas das classes e (b) a inclusão de tais consequências nas classes. Duas crianças diagnosticadas com Transtorno do Espectro do Autismo (TEA), e com deficiência intelectual, foram submetidas a treino de emparelhamento ao modelo (Conjunto A - Modelo A1, S+A1/S-A2 e Modelo A2, S+A2/S-A1) e treino de reversões de discriminações simples (Conjunto B - S+B1/S-B2 e reversões). Dois conjuntos de vídeos variados de um mesmo tema e dois conjuntos de alimentos variados dentro de uma mesma categoria foram usados como consequências específicas. Os dados mostram que a variedade de elementos foi eficiente para manter a eficácia do reforçamento e encoraja o uso de procedimentos similares em contexto aplicado. Ambos os participantes mostraram forte evidência de formação de classes de equivalência, confirmando a predição teórica sobre a inclusão de consequências específicas nas classes. Os dados confirmam que relações de equivalência podem ser encontradas em contingências de três termos.

Estudios previos de formación de clases de equivalencia, con consecuencia específica de clase, encontraron variabilidad interindividual probablemente debido a la pérdida de eficacia de las consecuencias como reforzadores. Este estudio evaluó (a) la eficacia de la introducción de variaciones de eventos (dentro de una categoría) como consecuencias específicas de clase y (b) la inclusión de tales consecuencias en las clases de equivalencia. Dos niños diagnosticados con Trastorno del Espectro Autista y con discapacidad intelectual, recibieran entrenamiento de igualación de identidad a la muestra (Conjunto A - Muestra A1, S+A1/S-A1 y Muestra A2, S+A2/S-A1) y entrenamiento de inversión de la discriminación simple (Conjunto B - S+B1/S-B2 y inversiones). Se utilizaron dos conjuntos de vídeos diversos de un mismo tema, más dos conjuntos de alimentos diversos dentro de la misma categoría como consecuencias específicas de clase. Los datos muestran que la variedad de elementos fue eficiente para mantener la eficacia del refuerzo y fomentan el uso de procedimientos similares en contexto aplicado. Ambos los participantes mostraron una fuerte evidencia de la formación de clases de equivalencia, lo que confirma la predicción teórica sobre la inclusión de las consecuencias específicas de clase en las clases de equivalencia. Los datos confirman que las relaciones de equivalencia pueden ser encontradas en las contingencias de tres términos.

General overview of the Seventh International Symposium on Stem Cell Therapy and Cardiovascular Innovations.

The Seventh International Symposium on Stem Cell Therapy and Cardiovascular Innovations was held in Madrid on the 6th and 7th of May 2010. Gathering for the seventh consecutive year the most relevant researchers and opinion leaders on cardiovascular cell therapy, it has become the most important worldwide event on this field. A comprehensive review of the last developments on cell therapy, surgery for heart failure and tissue engineering was made, and the results of three clinical trials were reported. The Symposium was dedicated to the memory of Professor Helmut Drexler.

Early translation of adipose-derived cell therapy for cardiovascular disease.

Over the past decade, cell therapy has emerged as a new approach to reversing myocardial ischemia. Several types of adult stem cells have been studied in both preclinical and clinical conditions for this purpose: bone marrow cells, circulating cells, and myoblasts. Nevertheless, the quest for the ideal "anti-ischemic" cell is still ongoing. Recently, the existence of a population of stem cells located in adipose tissue (adipose-derived stem cells) has been observed. These are able to differentiate into multiple cell lineages including cardiomyocytic differentiation. In this review we discuss the basic principles of adipose-derived stem cells (types and characteristics, harvesting, and expansion), the initial experimental studies, and the currently ongoing clinical trials.

Lymphadenopathy after BCG vaccination in a child with chronic granulomatous disease.

We report a 15-month-old boy who developed an ulcer in the left axillary fold following bacillus Calmette-Guerin vaccination. Subsequent immunologic and genetic studies led to the diagnosis of chronic granulomatous disease. His mother had "lupus-like" lesions, described in some carriers of this disease, that were thus related to her son's diagnosis. Although in healthy subjects this vaccination is usually harmless, in instances of impaired immunity it may cause adverse reactions. When a vaccine-related complication occurs, an underlying immunodeficiency should be sought.

Evidence for CTLA4 as a susceptibility gene for systemic lupus erythematosus.

Several lines of evidence implicate the Cytotoxic T Lymphocyte Antigen 4 (CTLA4) gene in susceptibility to autoimmune disease. We have examined the association of systemic lupus erythematosus (SLE) with polymorhisms within the CTLA4 gene that were previously proposed to regulate CTLA-4 function: a single nucleotide polymorphism (SNP) in position +49 of exon 1 and a dinucleotide repeat in the 3' untranslated region (3'UTR). The 3'UTR repeat showed a significant association with SLE, with one allele conferring susceptibility and another conferring protection to the disease. The associated alleles do not support previous suggestions of an allele size-dependent effect of the 3' UTR polymorphism in autoimmunity development and instead suggest that it is in linkage disequilibrium with a true causative locus. No association of the exon 1 SNP with SLE was found in our population. Given the conflicting results obtained in different studies on the association of SLE with this polymorphism, we performed a meta-analysis including seven previously published studies and the present one. Significantly increased and decreased risks for SLE were found for carriers of the G allele and the A allele, respectively. The functional characterization of disease-associated CTLA4 gene variants is now required to elucidate their role in the pathogenesis of SLE and other autoimmune diseases.

Efectos radiográficos de la cocaína aspirada sobre los senos paranasales / Radiographic effects of the aspirated cocaine by paranasal sinuses

La cocaína es un compuesto aromático lipofílico, derivado de las hojas de ERITROXYLON COCA, su abuso produce una vasculitis necrosante con la consiguiente formación de granulomas en el tabique nasal que pueden conducir a la perforación del tabique e inflamación de la mucosa nasal. El objetivo de esta investigación es evaluar las alteraciones radiográficas consecuentes al abuso de la cocaína aspirada el los senos paranasales. Para efectuar esta investigación se tomaron 32 pacientes consumidores de cocaína aspirada que ingresaban a los centros de rehabilitación suspendiendo el hábito y se les realizó un estudio de senos paranasales (Waters, Cadwell y lateral); se repitió el estudio de senos paranasales a 15 pacientes en un intervalo de 10 a 12 semanas, y se compararon entre sí utilizando tablas de frecuencia. Los resultados indican que el proceso inflamatorio Etmoidal, el proceso inflamatorio Maxilar, y el septum nasal sinuoso, son las patologías que mas incidencia presentan en el primer estudio radiográfico; sin que se produzcan otros cambios en el segundo estudio radiográfico.