[A newborn infant with hypotonia and tongue fasciculations: it is not always spinal muscular atrophy]. / Neonato con hipotonia y fasciculaciones linguales: no siempre es atrofia muscular espinal.

TITLE: Neonato con hipotonia y fasciculaciones linguales: no siempre es atrofia muscular espinal.

Neonato con hipotonía y fasciculaciones linguales: no siempre es atrofia muscular espinal / A newborn infant with hypotonia and tongue fasciculations: it is not always spinal muscular atrophy

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Presentación de dos casos de vasa previa, ¿se podría haber evitado el desenlace? / Presentation of two cases of vasa previa. Could the outcome have been avoided?

Introducción: La vasa previa (VP) es una rara condición obstétrica en la cual los vasos sanguíneos fetales, libres de tejido placentario y no protegidos por gelatina de Wharton, pasan a nivel del segmento uterino inferior entre la presentación fetal y el cérvix, recubiertos solo por membranas amnióticas. Esta condición conlleva un elevado riesgo de mortalidad perinatal (2,4-56,4%), debido al riesgo de la-ceración de los vasos fetales durante el parto o la ruptura de membranas amnióticas, y consecuentemente la exanguinación fetal. Casos clínicos: Presentamos dos casos clínicos de gestaciones con VP sin diagnóstico prenatal, que presentaron hemorragia fetal durante el parto, requiriendo maniobras de reanimación avanzada y transfusión urgente de concentrado de hematíes, con una adecuada evolución. Conclusión: Resaltar la importancia del diagnóstico prenatal de VP, mediante estudio ecográfico según protocolo, que puede mejorar significativamente los resultados perinatales

Introduction. The vasa previa (VP) is a rare obstetric condition in which the fetal blood vessels, free of placental tissue and not protected by Wharton's gelatin, pass at the level of the lower uterine segment between the fetal presentation and the cervix, coated only by amniotic membranes. This condition carries a high risk of perinatal mortality (2.4-56.4%), due to the risk of laceration of the fetal vessels during delivery or the rupture of amniotic membranes, and consequently fetal exanguination. Cases report: We present two clinical cases of pregnancies with VP without prenatal diagnosis, which presented fetal hemorrhage during labor, requiring advanced resuscitation maneuvers and urgent transfusion of packed red blood cells, with an adequate evolution. Conclusion: Highlight the importance of prenatal diag-nosis of VP, by means of an echographic study according to protocol, which can significantly improve perinatal results

Análisis del control metabólico de pacientes con diabetes mellitus tipo 1 que acuden a campamentos de verano en Castilla-La Mancha / Analysis of metabolic control of patients with type 1 diabetes attending summer camps in Castilla-La Mancha

Objetivo: Describir el grado de control metabólico en jóvenes con diabetes mellitus tipo 1 (DM1) y analizar los factores que pueden influir en él. Material y métodos: Se realizó un estudio descriptivo y observacional, con una recogida de datos retrospectiva, en el que se incluyó a pacientes con DM1 que acudieron a los campamentos de verano organizados por la Fundación Sociosanitaria de Castilla-La Mancha durante los años 2009 y 2010. Se determinó la hemoglobina glucosilada (HbA1c) en sangre capilar (método DCA 2000+). Se llevó a cabo un análisis estadístico mediante el programa SPSS. Resultados: Se incluyeron en el estudio 85 pacientes, con una media edad de 13,5 años. El 100% de los pacientes recibía una pauta de insulinoterapia intensiva: infusión subcutánea continua de insulina (8,2%), insulina detemir (10,6%), insulina glargina (70,6%) e insulina NPH (neutral protamine Hagedorn) (10,6%). Se realizó una media de 5,4 autoanálisis diarios (rango: 3-12). El valor medio de HbA1c era del 7,6% (rango: 5,7-13,7), presentando el 33% una HbA1c ≤7%, el 32% una HbA1c >7% y ≤8%, y un 35% una HbA1c >8%. No se encontraron diferencias significativas en función de la consulta de procedencia ni de la pauta de insulina empleada, y se observaron valores de HbA1c significativamente menores en los pacientes con menos de 2 años de evolución.Conclusiones: El factor que más influye en la HbA1c de los pacientes analizados es el tiempo de evolución de la enfermedad, sin diferencias significativas en función de la pauta de insulinoterapia (AU)

Objective: To describe the degree of metabolic control in youth with type 1 diabetes mellitus (DM1) and analyze the factors that influence in this control. Material and methods: We performed a descriptive, observational and retrospective study which includes patients with DM1 attending summer camps organized by the Fundación Sociosanitaria de Castilla-La Mancha during the years 2009 and 2010. Glycosylated hemoglobin (HbA1c) is measured in capillary blood (method DCA 2000+). Statistical analysis was performed using SPSS. Results: We collected 85 patients with mean age of 13.5 years. 100% of patients receiving intensive insulin regimen: continuous subcutaneous insulin infusion (8.2%), detemir (10.6%), glargine (70.6%) and NPH (10.6%). The mean HbA1c is 7.6% (5.7 to 13.7%), with 33% HbA1c ≤7%, 32% HbA1c >7% and ≤8%, and 35% HbA1c ≥8%. No significant differences were found depending on the consultation of origin or the pattern of insulin used, with values of HbA1c significantly lower in patients with less than 2 years of evolution. Conclusions: The factor that most influences the HbA1c of the patients analyzed is the time to disease progression, with no differences according to the pattern of insulin (AU)

Fracturas patológicas en un paciente con citrulinemia tipo 1 e inmovilización prolongada / Pathological fractures in patient with citrullinemia type 1 and prolonged immobilization

La citrulinemia clásica, o tipo 1, es un defecto congénito del ciclo de la urea debido al déficit de la enzima ácido argininosuccínico sintetasa. Las formas de comienzo neonatal conllevan una mayor gravedad clínica. Se presenta el caso de un niño de 7 años de edad con citrulinemia, diagnosticada en el periodo neonatal, y una encefalopatía severa secundaria a una hiperamoniemia grave. El paciente nunca ha tenido deambulación autónoma. Acude al servicio de urgencias por presentar un llanto persistente y un quejido intenso de 12 horas de evolución. Presenta la rodilla izquierda en flexión y con tumefacción. No refiere ningún antecedente traumático. En la radiografía ósea se detecta una fractura supracondílea del fémur. En los 12 meses siguientes presenta otras 3 fracturas patológicas. Se estudia su caso en el servicio de endocrinología infantil y se establece el diagnóstico de osteoporosis secundaria a una inmovilización prolongada. Se inicia una pauta con alendronato oral como tratamiento de uso compasivo, y el paciente presenta una evolución favorable, sin fracturas óseas a partir de entonces y con una mejoría densitométrica. En los últimos años se han publicado diversos estudios sobre el papel del alendronato oral en el tratamiento de la osteoporosis en pacientes pediátricos, sobre todo secundaria a enfermedades neuromusculares, osteogénesis imperfecta o enfermedades del tejido conectivo. Es un tratamiento que puede administrarse de forma ambulatoria, y contribuye a disminuir tanto el número de ingresos hospitalarios como el coste económico, proporcionando así a los pacientes una mayor calidad de vida. Por el momento sólo está aprobado su uso en el contexto de ensayos clínicos o como uso compasivo en niños con baja densidad mineral ósea y clínica asociada (AU)

Classic citrullinemia, or type 1, is a congenital defect of urea cycle due to a synthetase argininosuccinic acid enzyme deficit. Neonatal beginning types entail a higher clinical severity. A seven years old boy diagnosed of citrullinemia in neonatal period wih severe encefalopathy secondary to serious hyperammoniemia is discussed. The patient has never had independent ambulation.He went to the Emergency Room because of persistent crying and intense moan of 12 hours evolution. He has a bent and swollen left knee. There is no traumatic episode before. Bone X-ray shows a femoral supracondylar fracture. During the following 12 months the patient suffers three more pathological fractures. This case is studied in Pediatric Endocrinology and the patient is diagnosed of secondary osteoporosis due to prolonged immobilization. Oral alendronate treatment is given as a compassionate use with satisfactory evolution, without bone fractures since then and with a densitometric improvement. During the last years many different studies have been published about oral alendronate rol in treatment of pediatric osteoporosis, above all secondary osteoporosis to muscular dystrophy, osteogenesis imperfecta or connective tissue diseases. It is an ambulatory treatment so it decreases hospital admissions and economic costs what helps patients to improve their quality of life. Currently it is only approved in clinical trials or as compassionate use in children with low bone mineral density and associated clinic (AU)

Effect of processing on functional properties of animal blood plasma.

A number of functional and physical properties such as solubility, foam capacity, emulsifying stability and interfacial tension were compared for standard plasma, plasma decationed by ion exchange and plasma deionized by ultrafiltration (UF). The changes in functional properties can determine the use of a protein as an additive to a food product or invalidate its use. All samples had good functional properties and hence could be used in the formulation of food products. Results showed that ion exchange and UF improved emulsifying capacity while having little effect on the other functional properties.

A novel mutation in the mitochondrial DNA tRNA Leu (UUR) gene associated with late-onset ocular myopathy.

We identified a novel G3283A transition in the mitochondrial DNA tRNA(Leu (UUR)) gene in a patient with ptosis, ophthalmoparesis and hyporeflexia. Muscle biopsy showed cytochrome oxidase positive ragged-red fibers, and defects of complexes I, III and IV of the mitochondrial respiratory chain. The mutation was heteroplasmic in muscle of the proband, being absent in her blood. Ragged-red fibers harbored greater levels of mutant genomes than normal fibers. The G3283A mutation affects a strictly conserved base pair in the TPsiC stem of the gene and was not found in controls, thus satisfying the accepted criteria for pathogenicity.

Demineralization of animal blood plasma by ion exchange and ultrafiltration.

The blood waste from slaughterhouses is strictly controlled due to its high pollutant load, the treatment for its purification being of great economic interest. The separation of proteins, the most valuable components of blood, in a chromatographic column requires the use of well treated plasma, in particular the removal of inorganic salts. Accordingly, a demineralization process is usually required. In this paper, ion exchange and ultrafiltration demineralization techniques were tested and the results compared. In the ion exchange experiments, the blood plasma was treated with cationic and anionic resins in packed columns, studying the removal of the major cations and anions, protein loss and pH evolution in both the loading and elution steps. In the demineralization process by means of membranes, a 10KDa ultrafiltration membrane was used, the blood plasma being filtered to concentrate all the proteins in the retentate while removing the inorganic ions and other compounds in the permeate. The evolution of the major anions and cations in the plasma and the protein loss were studied at different volumetric concentration factors. The results obtained enable us to draw conclusions as regards the advantages and disadvantages of each technique at a laboratory scale and to offer some considerations regarding the operation at an industrial scale.

[Mitochondrial respiratory chain diseases. Evaluation and variability in 52 patients]. / Enfermedades de la cadena respiratoria mitocondrial. Evaluación y variabilidad en 52 pacientes.

INTRODUCTION: Clinical, electrophysiological, genetic and biochemical deficiencies variability were evaluated in 52 patients diagnosed of mitochondrial respiratory chain diseases (MRCD). PATIENTS AND METHODS: 26 men and 26 women, aged 19 to 79 years, were tested by clinical examination, electrophysiological techniques, muscle biopsy and genetic and biochemical studies. RESULTS: The patients were classified into seven phenotypes: myopathy, chronic progressive external ophthalmoplegia, progressive ophthalmoplegia plus ataxia, Kearns-Sayre syndrome, mitochondrial encephalomyopathy with lactic acidosis and stroke episodes (MELAS), myoclonic encephalopathy with ragged-red fibers (MERRF), and encephalopathies. Each phenotype may begin by different ways. The electromiography showed myopathy in 39 cases and various types of neuropathy in 10. Ragged-red COX negative fibers or widespread electron microscopic abnormalities were found in 47 cases. Simple deletions, multiple deletions and three different point mutations were observed. Deficiency of complexes I, II, III and IV were found alone or in different associations. CONCLUSIONS: MRCD shows wide variations in clinical, genetic and biochemical studies. Some patients with nonspecific manifestations, mainly of central nervous system, need careful attention and to be on account of diagnostic suspicion.

Effect of nitric oxide on mitochondrial respiratory activity of human articular chondrocytes.

OBJECTIVE: To investigate the effect of nitric oxide (NO) on mitochondrial activity and its relation with the apoptosis of human articular chondrocytes. MATERIALS AND METHODS: Mitochondrial function was evaluated by analysing respiratory chain enzyme complexes, citrate synthase (CS) activities, and mitochondrial membrane potential (Delta psi m). The activities of the mitochondrial respiratory chain (MRC) complexes (complex I: NADH CoQ(1) reductase, complex II: succinate dehydrogenase, complex III: ubiquinol cytochrome c reductase, complex IV: cytochrome c oxidase) and CS were measured in human articular chondrocytes isolated from normal cartilage. The Delta psi m was measured by 5,5',6,6'-tetracholoro-1,1',3,3'-tetraethylbenzimidazole carbocyanide iodide (JC-1) using flow cytometry. Apoptosis was analysed by flow cytometry. The mRNA expression of caspases was analysed by ribonuclease protection analysis and the detection of protein synthesis by western blotting. Sodium nitroprusside (SNP) was used as an NO compound donor. RESULTS: SNP at concentrations higher than 0.5 mmol/l for 24 hours induced cellular changes characteristic of apoptosis. SNP elicited mRNA expression of caspase-3 and caspase-7 and down regulated bcl-2 synthesis in a dose and time dependent manner. Furthermore, 0.5 mM SNP induced depolarisation of the mitochondrial membrane at 5, 12, and 24 hours. Analysis of the MRC showed that at 5 hours, 0.5 mM SNP reduced the activity of complex IV by 33%. The individual inhibition of mitochondrial complex IV with azide modified the Delta psi m and induced apoptosis. CONCLUSIONS: This study suggests that the effect of NO on chondrocyte survival is mediated by its effect on complex IV of the MRC.

Two pathogenic mutations in the mitochondrial DNA tRNA Leu(UUR) gene (T3258C and A3280G) resulting in variable clinical phenotypes.

We studied two patients with ragged-red fibers and combined defects of the mitochondrial respiratory chain in their muscle biopsy. One had mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, and harbored a T3258C transition in the tRNA(Leu(UUR)) gene. The other showed myopathy plus cardiomyopathy and had an A3280G mutation in the same gene. Both mutations were heteroplasmic, abundant in muscle of the patients, less abundant in blood, and still less abundant in blood from their maternal relatives. In both patients, single muscle fiber analysis revealed greater abundance of mutant genomes in ragged-red fibers than in normal fibers, supporting the pathogenicity of both mutations.

Myoglobinuria and COX deficiency in a patient taking cerivastatin and gemfibrozil.

The authors describe a patient who presented with myoglobinuria after starting cerivastatin-gemfibrozil therapy. Muscle histochemistry revealed ragged-red fibers and cytochrome c oxidase negative (COX) fibers, and biochemistry showed a defect of COX activity. Immunoblot analysis showed a 60% reduction of COX I and COX II polypeptides. Cerivastatin myotoxicity might be related to a depletion of essential metabolites needed to anchor COX subunit I to mitochondrial membrane.

Tratamiento grupal en trastornos de la conducta alimentaria / Group treatment of eating disorders

El presente trabajo describe el tratamiento grupal de los trastornos de la conducta alimentaria desarrollado en un Centro de Salud Mental. La orientación teórica que guía la intervención fue la de grupo operativo. El grupo está formado por diecisiete pacientes (media de la edad =18,88; desviación típica =2,12) que acuden con una periodicidad semanal a lo largo de veintiuna sesiones. Para la recogida de información se ha empleado un protocolo que recoge datos acerca de la clínica previa al tratamiento, la situación actual y la valoración subjetiva de su participación, así como el Inventario de Trastornos de la Conducta Alimentaria (EDl). El perfil de puntuaciones en el EDl después de la intervención se aproxima al de los sujetos sin trastornos de la conducta alimentaria. Podemos concluir que la intervención grupal facilita un clima de confianza que puede permitir una mayor individualización y un lugar para la expresión del deseo (AU)

This work describes the group treatment of eating disorders developed in a Mental Health Center. The theoretical orientation that guides was the one of the operative group in which a place of listening was provided and the recognition of their individuality, the appearance of desire, the place occupied within the family dynamic and their relationship with others. The group is formed by seventeen patients (mean age =18,88; standard desviation =2,12) who attend on a weekly basis throughout twenty one sesions. A protocol that gathers data about the symptoms previous to treatment their current situation and their subjective value about their level of participation was used. We also used the Ealing Disorders Inventary (EDl). The scores obtained of the EDl after the intervention is similar lo the subjects without eating disorders. We can conclude that group intervention provides of a trust atmosphere where a better autonomy and express ion of their desire is favoured (AU)

Molecular analysis of the superoxide dismutase 1 gene in Spanish patients with sporadic or familial amyotrophic lateral sclerosis.

We performed a genetic analysis of the Cu/Zn superoxide dismutase gene (SOD1) in Spanish patients with sporadic or familial amyotrophic lateral sclerosis (ALS). We found mutations in 2 of 11 families (18%) with ALS. In addition, 1 of the 87 sporadic ALS patients studied harbored a mutation in the same gene. We identified G37R in exon 2 of the SOD1 gene in 1 family. Another patient, with sporadic ALS, showed a novel N65S in exon 3. In addition, we found a novel I112M in exon 4 in another family. Our data highlight the genetic heterogeneity of patients with ALS harboring mutations in the SOD1 gene and confirm that families with autosomal dominant inheritance of the trait, regardless of their ethnic background, are more likely to carry mutations in such a gene.

Cosegregation of the mitochondrial DNA A1555G and G4309A mutations results in deafness and mitochondrial myopathy.

We report a patient with progressive external ophthalmoplegia (PEO), exercise intolerance, and deafness after aminoglycoside exposure, harboring two pathogenic mutations in her mtDNA: an A1555G in the 12S rRNA gene and a G4309A in the tRNA(Ile) gene. Muscle histochemistry showed abundant ragged-red fibers, and biochemistry revealed normal respiratory chain function. The A1555G mutation was homoplasmic in blood from the proband and from all maternal relatives. The G4309A mutation was abundant in the proband's muscle, less abundant in her blood, still less abundant in the mother's blood, and absent in blood from other maternal relatives. Family members were asymptomatic. Our data suggest that the former mutation resulted in aminoglycoside-induced deafness and the latter caused PEO plus exercise intolerance.

Molecular heterogeneity of myophosphorylase deficiency (McArdle's disease): a genotype-phenotype correlation study.

We report on 54 Spanish patients with McArdle's disease from 40 unrelated families. Molecular analysis revealed that the most common R49X mutation was present in 70% of patients and 55% of alleles. The G204S mutation was less frequent and found in 14.8% of patients and 9% of mutant alleles. The W797R mutation was observed in 16.5% of patients, accounting for 13.7% of mutant alleles. Moreover, 78% of mutant alleles among Spanish patients can be identified by using polymerase chain reaction-restriction fragment length polymorphism analysis for the R49X, G204S, and W797R mutations, which makes noninvasive diagnosis possible through molecular genetic analysis of blood DNA. Six novel mutations were found. Three were missense mutations, E348K, R601W, and A703V; two nonsense mutations, E124X and Q754X; and one single base pair deletion, 533 delA. No clear genotype-phenotype correlation emerges from our study. Most of the mutations of uncharged and solvent inaccessible residues and the truncations must disrupt the basic structure of the protein. The mutations of charged residues would be expected to interfere with internal hydrogen bonding networks, introducing severe incompatible partnering that is caused by poor packing or electrostatic repulsions.

Mitochondrial dysfunction associated with a mutation in the Notch3 gene in a CADASIL family.

BACKGROUND: Cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by recurrent subcortical ischemic strokes and dementia caused by mutations in the Notch3 gene. In Drosophila melanogaster, Notch signaling has a pleiotropic effect, affecting most tissues of the organism during development. OBJECTIVE: To characterize a potential mitochondrial dysfunction associated with mutations in the Notch3 gene. METHODS: Biochemical, histochemical, molecular, and genetic analyses were performed on muscle biopsy specimens and fibroblasts obtained from patients of a Spanish family with CADASIL. Additional biochemical and molecular analyses of the N(55e11) mutant of D. melanogaster were performed. RESULTS: In muscle biopsy specimens, a significant decrease was found in the activity of complex I (NADH [reduced form of nicotinamide adenine dinucleotide] dehydrogenase), and in one patient, histochemical analysis showed the presence of ragged-red fibers with abnormal cytochrome c oxidase staining. Reduced fibroblast activity of complex V (ATP synthase) was found. Supporting data on patients with CADASIL, it was found that the mutation N(55e11) in Drosophila decreases the activity of mitochondrial respiratory complexes I and V. CONCLUSIONS: Mitochondrial respiratory chain activity responds, directly or indirectly, to the Notch signaling pathway. Mitochondrial dysfunction in patients with CADASIL may be an epiphenomenon, but results of this study suggest that the pathophysiology of the disease could include a defect in oxidative phosphorylation.

Sustitución de figuras parentales en el duelo infanto-juvenil / Sustitution of family figures in the child and adolescent fight

El propósito de este trabajo fue analizar la elaboración del duelo infanto-juvenil a través del estudio de las historias de niños y adolescentes que acudieron al Servicio de Salud Mental de Parla tras haber sufrido la pérdida de una de sus figuras parentales (debido a la muerte de uno de ellos o por separación). Asimismo, se trató de determinar si la presencia de figuras sustitutas y la relación con la familia ejercen algún efecto modulador sobre el nivel de adaptación de los sujetos. Para ello, se contó con una muestra de 35 sujetos a quienes que se les aplicó un cuestionario para recoger información sobre variables hipotéticamente relevantes en la elaboración del duelo. La única variable que mostró dependencia estadísticamente significativa con el nivel de adaptación de sujeto fue la relación con la familia del progenitor perdido o discontinuo (AU)

Thyroid hormone regulates oxidative phosphorylation in the cerebral cortex and striatum of neonatal rats.

We have previously shown that thyroid hormone (T(3)) regulates mitochondrial gene expression, morphology and transmembrane potential in the developing brain. Here, we have analysed the effect of thyroid hormone on mitochondrial function in different brain regions. For this purpose we have determined, in control, hypothyroid and T(3)-treated hypothyroid neonatal rats, the rate of oxidative phosphorylation in isolated mitochondria and the activity of the respiratory complexes in tissue homogenates. Our results showed a decrease in oxidative phosphorylation rate (only in the presence of NADH-generating substrates) and mitochondrial complexes I and III activity in the cerebral cortex and striatum of hypothyroid neonates, but not in the other areas analysed (hippocampus, cerebellum, thalamus, mid brain and brain stem). In parallel with mitochondrial activity, the levels of mitochondrially encoded transcripts were decreased only in the cerebral cortex and striatum of hypothyroid rats. The administration of T(3) corrected all these parameters. In summary, this study showed a down-regulation of mitochondrial gene expression accompanied by a decrease in mitochondrial activity in the cerebral cortex and striatum of developing hypothyroid neonatal rats.

Early-onset multisystem mitochondrial disorder caused by a nonsense mutation in the mitochondrial DNA cytochrome C oxidase II gene.

We report the first nonsense mutation (G7896A) in the mtDNA gene for subunit II of cytochrome c oxidase (COX) in a patient with early-onset multisystem disease and COX deficiency in muscle. The mutation was heteroplasmic in muscle, blood, and fibroblasts from the patient and abundantly present in COX-deficient fibers, but less abundant in COX-positive fibers; it was not found in blood samples from the patient's asymptomatic maternal relatives. Immunoblot analysis showed a reduced concentration of both COX II and COX I polypeptides, suggesting impaired assembly of COX holoenzyme.