RESUMEN
IntroductionPallid breath-holding spells are common and dramatic forms of recurrent syncope in infancy. They are very stressful despite their harmless nature and sometimes require treatment. OBJECTIVE: The objective of this study was to evaluate the efficacy of belladonna in severe breath-holding spells. METHODS: This is a multicentric, retrospective series involving 84 children with severe pallid breath-holding spells. Inclusion criteria were >1 pallid breath-holding spell with loss of consciousness, paediatric cardiology evaluation, and follow-up >6 months. In total, 45 patients received belladonna and 39 patients did not receive treatment, according to physician preference. RESULTS: Mean age was 11 months, ranging from 4 to 18 months, with 54% of males. Mean spell duration was 30 seconds (interquartile range 15, 60), and the frequency was four episodes per month (interquartile range 0.5, 6.5). Comparison of baseline characteristics between groups showed similar demographics, with the single difference in the severity of the spells, being more severe in the treated group. When comparing the treated and non-treated groups at 3 months, only two (5%) patients had a complete remission in the first group, whereas 20 (44%) had remission in the belladonna group (p<0.01). When considering the characteristics of the spells before and after the initiation of treatment with belladonna, 75% of the patients presented a positive response, with 44% of the patients presenting with complete resolution of the spells (p<0.01). No major adverse reaction was reported, with only 5% minor adverse events. CONCLUSIONS: Belladonna is highly effective to alleviate severe breath-holding spells in young children, without any major adverse effects.
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Anemia Ferropénica/tratamiento farmacológico , Alcaloides de Belladona/uso terapéutico , Hierro/uso terapéutico , Trastornos Respiratorios/tratamiento farmacológico , Síncope/prevención & control , Anemia Ferropénica/complicaciones , Apnea/etiología , Alcaloides de Belladona/efectos adversos , Cianosis/etiología , Electrocardiografía Ambulatoria , Femenino , Humanos , Lactante , Masculino , Trastornos Respiratorios/etiología , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
For some authors, the human sensitivity to numerosities would be grounded in our ability to process non-numerical magnitudes. In the present study, the developmental relationships between non numerical and numerical magnitude processing are examined in people with Williams syndrome (WS), a genetic disorder known to associate visuo-spatial and math learning disabilities. Twenty patients with WS and 40 typically developing children matched on verbal or non-verbal abilities were administered three comparison tasks in which they had to compare numerosities, lengths or durations. Participants with WS showed lower acuity (manifested by a higher Weber fraction) than their verbal matched peers when processing numerical and spatial but not temporal magnitudes, indicating that they do not present a domain-general dysfunction of all magnitude processing. Conversely, they do not differ from non-verbal matched participants in any of the three tasks. Finally, correlational analyses revealed that non-numerical and numerical acuity indexes were both related to the first mathematical acquisitions but not with later arithmetical skills.
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Solución de Problemas , Síndrome de Williams/fisiopatología , Niño , Preescolar , Femenino , Humanos , MasculinoRESUMEN
Congenital heart defect (CHD) occurs in 40% of Down syndrome (DS) cases. While carrying three copies of chromosome 21 increases the risk for CHD, trisomy 21 itself is not sufficient to cause CHD. Thus, additional genetic variation and/or environmental factors could contribute to the CHD risk. Here we report genomic variations that in concert with trisomy 21, determine the risk for CHD in DS. This case-control GWAS includes 187 DS with CHD (AVSD = 69, ASD = 53, VSD = 65) as cases, and 151 DS without CHD as controls. Chromosome 21-specific association studies revealed rs2832616 and rs1943950 as CHD risk alleles (adjusted genotypic P-values <0.05). These signals were confirmed in a replication cohort of 92 DS-CHD cases and 80 DS-without CHD (nominal P-value 0.0022). Furthermore, CNV analyses using a customized chromosome 21 aCGH of 135K probes in 55 DS-AVSD and 53 DS-without CHD revealed three CNV regions associated with AVSD risk (FDR ≤ 0.05). Two of these regions that are located within the previously identified CHD region on chromosome 21 were further confirmed in a replication study of 49 DS-AVSD and 45 DS- without CHD (FDR ≤ 0.05). One of these CNVs maps near the RIPK4 gene, and the second includes the ZBTB21 (previously ZNF295) gene, highlighting the potential role of these genes in the pathogenesis of CHD in DS. We propose that the genetic architecture of the CHD risk of DS is complex and includes trisomy 21, and SNP and CNV variations in chromosome 21. In addition, a yet-unidentified genetic variation in the rest of the genome may contribute to this complex genetic architecture.
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Variaciones en el Número de Copia de ADN , Síndrome de Down/diagnóstico , Cardiopatías Congénitas/genética , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , Cromosomas Humanos Par 21/genética , Proteínas de Unión al ADN/genética , Síndrome de Down/complicaciones , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Cardiopatías Congénitas/etiología , Humanos , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Factores de Transcripción/genéticaRESUMEN
Forty percent of people with Down syndrome exhibit heart defects, most often an atrioventricular septal defect (AVSD) and less frequently a ventricular septal defect (VSD) or atrial septal defect (ASD). Lymphoblastoid cell lines (LCLs) were established from lymphocytes of individuals with trisomy 21, the chromosomal abnormality causing Down syndrome. Gene expression profiles generated from DNA microarrays of LCLs from individuals without heart defects (CHD(-); n = 22) were compared with those of LCLs from patients with cardiac malformations (CHD(+); n = 21). After quantile normalization, principal component analysis revealed that AVSD carriers could be distinguished from a combined group of ASD or VSD (ASD+VSD) carriers. From 9,758 expressed genes, we identified 889 and 1,016 genes differentially expressed between CHD(-) and AVSD and CHD(-) and ASD+VSD, respectively, with only 119 genes in common. A specific chromosomal enrichment was found in each group of affected genes. Among the differentially expressed genes, more than 65% are expressed in human or mouse fetal heart tissues (GEO dataset). Additional LCLs from new groups of AVSD and ASD+VSD patients were analyzed by quantitative PCR; observed expression ratios were similar to microarray results. Analysis of GO categories revealed enrichment of genes from pathways regulating clathrin-mediated endocytosis in patients with AVSD and of genes involved in semaphorin-plexin-driven cardiogenesis and the formation of cytoplasmic microtubules in patients with ASD-VSD. A pathway-oriented search revealed enrichment in the ciliome for both groups and a specific enrichment in Hedgehog and Jak-stat pathways among ASD+VSD patients. These genes or related pathways are therefore potentially involved in normal cardiogenesis as well as in cardiac malformations observed in individuals with trisomy 21.
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Síndrome de Down/complicaciones , Síndrome de Down/patología , Defectos del Tabique Interventricular/complicaciones , Defectos de los Tabiques Cardíacos/complicaciones , Proteínas Hedgehog/metabolismo , Linfocitos/patología , Transducción de Señal , Animales , Línea Celular , Cromosomas Humanos/genética , Defectos de los Tabiques Cardíacos/genética , Defectos de los Tabiques Cardíacos/metabolismo , Defectos de los Tabiques Cardíacos/patología , Defectos del Tabique Interventricular/genética , Defectos del Tabique Interventricular/metabolismo , Defectos del Tabique Interventricular/patología , Humanos , Ratones , Fenotipo , Transcriptoma , Adulto JovenRESUMEN
OBJECTIVE: To report a case of a massive ingestion of ethylene glycol in an infant successfully treated by fomepizole without hemodialysis. DESIGN: Descriptive case report. SETTING: Pediatric intensive care unit. PATIENT: A 5-mo-old boy who ingested 200 mL of an antifreeze solution. INTERVENTIONS: Antidotal therapy with a total of seven doses of fomepizole administered intravenously with an interval of 12 hrs (15 mg/kg as loading dose, then 10 mg/kg). Hemodialysis was not performed. MEASUREMENTS AND MAIN RESULTS: Iterative determination of ethylene glycol concentration was obtained in blood and urine. Kinetics were calculated for ethylene glycol and fomepizole elimination. The infant made a complete recovery with no change in renal function. CONCLUSIONS: Although not yet approved for this indication in the child, fomepizole seemed safe and effective in a case of severe ethylene glycol poisoning, without the need for hemodialysis.