[The Prefrontal Symptoms Inventory (PSI) in acquired brain injury: agreement between the scores of patients, relatives and professionals]. / Inventario de sintomas prefrontales (ISP) en el daño cerebral adquirido: concordancia entre puntuaciones de paciente, familiar y profesional.

INTRODUCTION: The use of self-reports about symptoms of malfunctioning in daily life derived from functional deficits of a prefrontal origin has become widespread in clinical practice, since they allow incremental ecological validity to be added to other specific tests. Yet it remains to be determined whether self-assessment is sufficient on its own or if the participation of an external evaluator would be preferable. SUBJECTS AND METHODS: The Prefrontal Symptoms Inventory (PSI) was administered to 115 subjects being treated for a range of brain pathologies. The same test, referring to the patient, was administered to one of the professionals closely following the development of the case and, whenever possible (n = 88), a relative or caregiver. The psychometric goodness of the PSI was explored in the three samples, and the degree of correlation and agreement among the three assessments was estimated. RESULTS: The three assessments showed significant correlation, although the patients reported fewer symptoms than their relatives and caregivers in terms of executive functioning. The assessments of relatives and patients were superposed and showed a high degree of agreement as regards both profile and magnitude. CONCLUSIONS: In addition to the mandatory neuropsychological assessment, we recommend the administration of questionnaires or inventories about symptoms such as the PSI, with proven psychometric robustness, that make it possible to explore the impact of brain dysfunctions in daily functioning. Since many of these dysfunctions are accompanied by different degrees of anosognosia, they should be administered to external observers, relatives or professionals, with the intention of obtaining a more adequate assessment of the magnitude of the functional difficulties.

TITLE: Inventario de sintomas prefrontales (ISP) en el daño cerebral adquirido: concordancia entre puntuaciones de paciente, familiar y profesional.Introduccion. El uso de autoinformes sobre sintomas de mal funcionamiento en la vida diaria derivados de deficits funcionales de origen prefrontal se ha generalizado en la practica clinica, dado que permiten aportar validez ecologica incremental a otras pruebas especificas. Sin embargo, queda por determinar si la autoevaluacion es suficiente por si misma o es preferible la participacion de un evaluador externo. Sujetos y metodos. Se administro el inventario de sintomas prefrontales (ISP) a 115 sujetos en tratamiento por diversas patologias cerebrales. La misma prueba, referida al paciente, se administro a algun profesional que siguiera estrechamente la evolucion del caso y, cuando fue posible (n = 88), a un familiar o cuidador. Se exploro la bondad psicometrica del ISP en las tres muestras y se estimo el grado de correlacion y concordancia entre las tres evaluaciones. Resultados. Las tres evaluaciones mostraron correlacion significativa, aunque los pacientes declararon menos sintomas que sus familiares y cuidadores en funcionamiento ejecutivo. Las evaluaciones de familiares y pacientes se superpusieron y mostraron un alto grado de concordancia en perfil y magnitud. Conclusiones. Se recomienda, junto con la obligada evaluacion neuropsicologica, la cumplimentacion de cuestionarios o inventarios de sintomas como el ISP, con probada robustez psicometrica, que permitan explorar el impacto de las disfunciones cerebrales en el funcionamiento cotidiano. Dado que muchas de estas disfunciones se acompañan de diversos grados de anosognosia, se recomienda su administracion a observadores externos, familiares o profesionales, de cara a obtener una evaluacion mas adecuada de la magnitud de las dificultades funcionales.

Parada cardíaca: presentación mortal de una miocarditis viral / Cardiac arrest: Fatal presentation of viral myocarditis

La miocarditis es un trastorno inflamatorio del miocardio que cursa con la necrosis de los miocitos. La principal causa son las infecciones virales. La presentación clínica es muy variada: desde formas leves hasta formas fulminantes que cursan con la muerte y que se inician frecuentemente con síntomas banales. Presentamos el caso de un niño de 18 meses que acude a urgencias por astenia y anorexia de 24h de evolución, con antecedente de fiebre en el contexto de infección respiratoria de vías altas la semana anterior. A su llegada a urgencias y durante las primeras horas de observación la exploración física fue rigurosamente normal. Posteriormente presentó empeoramiento progresivo del estado general (palidez y mala perfusión periférica) con alteraciones analíticas (acidosis metabólica, insuficiencia renal e hiperglucemia) y de forma brusca parada cardiorrespiratoria sin respuesta a maniobras de reanimación cardiopulmonar (AU)

Myocarditis is an inflammatory disease of the myocardium accompanied by necrosis of myocytes. The main causes are viral infections. The clinical presentation varies from mild forms to devastating ones which usually begin with trivial symptoms with progression, in some cases, to death. We report the case of an 18 month-old male toddler consulting for asthenia and anorexia for the last 24h and a previous history of respiratory tract infection with high fever in the last week. Upon arrival at the emergency room and during the first hours of admission, physical examination was perfectly normal. Later, his general state gradually deteriorated, with biochemical disturbances (metabolic acidosis, renal failure and hyperglycaemia) and, eventually, a sudden cardiac arrest, with no response to cardiopulmonary resuscitation manoeuvres (AU)

[Cardiac arrest: fatal presentation of viral myocarditis]. / Parada cardíaca: presentación mortal de una miocarditis viral.

Myocarditis is an inflammatory disease of the myocardium accompanied by necrosis of myocytes. The main causes are viral infections. The clinical presentation varies from mild forms to devastating ones which usually begin with trivial symptoms with progression, in some cases, to death. We report the case of an 18 month-old male toddler consulting for asthenia and anorexia for the last 24h and a previous history of respiratory tract infection with high fever in the last week. Upon arrival at the emergency room and during the first hours of admission, physical examination was perfectly normal. Later, his general state gradually deteriorated,with biochemical disturbances (metabolic acidosis, renal failure and hyperglycaemia) and, eventually, a sudden cardiac arrest, with no response to cardiopulmonary resuscitation manoeuvres.

Roles for 147 embryonic lethal genes on C.elegans chromosome I identified by RNA interference and video microscopy.

Early embryonic development involves complex events such as the regulation of cell division and the establishment of embryonic polarity. To identify genes involved in these events, we collected four-dimensional time-lapse video recordings of the first three cell divisions and analysed terminal phenotypes after RNA interference of 147 embryonic lethal genes previously identified in a systematic screen of Caenorhabditis elegans chromosome I. Over half gave defects in early processes such as meiosis, the assembly or position of the first mitotic spindle, cytokinesis, and proper nuclear positioning. For some phenotypic classes, the majority of genes are involved in a shared biochemical process. In addition, we identified loss-of-function phenotypes for genes of unknown function, but for which homologues exist in other organisms, shedding light on the function of these uncharacterized genes. When applied to the whole genome, this approach should identify the vast majority of genes required for early cell processes, paving the way for a greatly improved understanding of these processes and their regulation at the molecular level.

Mutation and haplotype analyses in 26 Spanish Sanfilippo syndrome type A patients: possible single origin for 1091delC mutation.

Mucopolysaccharidosis IIIA, also known as Sanfilippo syndrome type A, is an autosomal recessive storage disorder caused by deficiency of sulfamidase. The disease results in severe central nervous system degeneration often with mild somatic features that may delay the clinical diagnosis. Molecular analyses would allow early and unequivocal heterozygote detection, providing a useful tool for genetic counselling. About 40 mutations have been reported in the sulfamidase gene, with a very uneven distribution in different patient populations. We have previously described the high prevalence of mutation 1091delC in a small number of Spanish Sanfilippo A patients. The aim of the present work is to extend the mutational study to a total of 26 unrelated patients and perform haplotype analysis in order to study the origin of some mutations. The whole coding region of the gene was scanned by SSCP analysis and sequencing. This allowed the identification of 14 different mutations, corresponding to 90% of the mutant alleles. Seven of these mutations were only found in this Spanish group of patients, three of which, R150W, R433Q and R433W, are described here for the first time. We have also analyzed four internal polymorphisms and constructed the corresponding haplotypes. Chromosomes bearing mutation 1091delC show a conserved haplotype suggesting a common origin for this mutation. Moreover, all other mutations found twice or more also have conserved haplotypes for those polymorphic markers.

Effectiveness of specific RNA-mediated interference through ingested double-stranded RNA in Caenorhabditis elegans.

BACKGROUND: In Caenorhabditis elegans, injection of double-stranded RNA (dsRNA) results in the specific inactivation of genes containing homologous sequences, a technique termed RNA-mediated interference (RNAi). It has previously been shown that RNAi can also be achieved by feeding worms Escherichia coli expressing dsRNA corresponding to a specific gene; this mode of dsRNA introduction is conventionally considered to be less efficient than direct injection, however, and has therefore seen limited use, even though it is considerably less labor-intensive. RESULTS: Here we present an optimized feeding method that results in phenotypes at least as strong as those produced by direct injection of dsRNA for embryonic lethal genes, and stronger for genes with post-embryonic phenotypes. In addition, the interference effect generated by feeding can be titrated to uncover a series of hypomorphic phenotypes informative about the functions of a given gene. Using this method, we screened 86 random genes on consecutive cosmids and identified functions for 13 new genes. These included two genes producing an uncoordinated phenotype (a previously uncharacterized POU homeodomain gene, ceh-6, and a gene encoding a MADS-box protein) and one gene encoding a novel protein that results in a high-incidence-of-males phenotype. CONCLUSIONS: RNAi by feeding can provide significant information about the functions of an individual gene beyond that provided by injection. Moreover, it can be used for special applications for which injection or the use of mutants is sometimes impracticable (for example, titration, biochemistry and large-scale screening). Thus, RNAi by feeding should make possible new experimental approaches for the use of genomic sequence information.

Functional genomic analysis of C. elegans chromosome I by systematic RNA interference.

Complete genomic sequence is known for two multicellular eukaryotes, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, and it will soon be known for humans. However, biological function has been assigned to only a small proportion of the predicted genes in any animal. Here we have used RNA-mediated interference (RNAi) to target nearly 90% of predicted genes on C. elegans chromosome I by feeding worms with bacteria that express double-stranded RNA. We have assigned function to 13.9% of the genes analysed, increasing the number of sequenced genes with known phenotypes on chromosome I from 70 to 378. Although most genes with sterile or embryonic lethal RNAi phenotypes are involved in basal cell metabolism, many genes giving post-embryonic phenotypes have conserved sequences but unknown function. In addition, conserved genes are significantly more likely to have an RNAi phenotype than are genes with no conservation. We have constructed a reusable library of bacterial clones that will permit unlimited RNAi screens in the future; this should help develop a more complete view of the relationships between the genome, gene function and the environment.

[Metabolic changes in critically ill children]. / Alteraciones metabólicas en niños críticamente enfermos.

OBJECTIVE: Our aim was to analyze the incidence of metabolic disturbances in critically ill children and to evaluate their correlation with severity of illness, complications, mortality and length of hospital stay. PATIENTS AND METHODS: We retrospectively studied 360 children who were admitted into a Pediatric Intensive Care Unit (PICU) between January 1995 and May 1996. We analyzed age, sex, initial diagnosis, complications, length of hospital stay and initial and final concentrations of serum glucose, calcium, phosphorus, magnesium and alkaline phosphatase. RESULTS: The incidence of different metabolic disturbances at admission to the PICU was: hyperglycemia 51.9%, hypoglycemia 1.9%, hypocalcemia 24.5%, hypercalcemia 5.8%, hyperphosphatemia 7.3%, hypophosphatemia 7.9%, hypomagnesemia 47.4% and hypermagnesemia 3%. Patients with shock had lower concentrations of calcium and higher phosphorus levels, while children with sepsis had lower magnesium concentrations. Patients who died had a higher incidence of hyperphosphatemia and higher values of serum glucose and magnesium at admission, while patients who survived had lower concentrations of calcium and higher incidence of hypomagnesemia. We did not find any correlation between the initial values for metabolites and length of stay in the PICU. CONCLUSIONS: Metabolic disturbances in critically ill children are frequent findings, correlate with important complications and can be prognostic markers. Thus, regular controls of different metabolites must be performed so we can precociously detect these disturbances and correct them.

[The determination in the blood of the enzyme neuron-specific enolase in children with acute encephalopathies: the prognostic value in neurological sequelae]. / Determinación en sangre de la enzima enolasa específica neuronal en niños con encefalopatías agudas: valor pronóstico de secuelas neurológicas.

OBJECTIVE: The objective of this study was to evaluate if there is a correlation between blood levels of the enzyme neuron-specific enolase in children with non-traumatic acute encephalopathies with severe alterations in consciousness and the neurological sequellae. PATIENTS AND METHODS: Neuron-specific enolase (EC 4.2.1.11) activity in plasma was measured by radioimmunoassay in 9 children aged 7 months to 5 years, who suffered acute encephalopathy and coma of non-traumatic origin. The etiology was acute viral encephalitis (n = 4), near drowning (n = 2), shock (n = 2) and cardiac arrest (n = 1). Blood samples were obtained between 24 and 72 hours after the onset of encephalopathy. The neurological status was evaluated 18 months after the onset of encephalopathy in the 8 surviving patients (1 patient with brain death criteria died in the acute stage). RESULTS: Enzyme activities were significantly higher in the children who showed neurological sequelae (median 68.9 ng/ml, range 35.0-95.6, n = 4) than in those who did not present neurological abnormalities (median 15.8 ng/ml, range 9.7-18.7, n = 5), with p < 0.05. No differences were found between the latter and the control group (median 7.7 ng/ml, range 4.1-12.7, n = 10). CONCLUSIONS: It appears that the presence of elevated neuron-specific enolase in blood is predictive of neurological outcome in children with acute encephalopathies of non-traumatic origin.