Síndrome de Mauriac: Uma Apresentação Rara de Uma Doença Mais Comum

Introdução: A diabetes mellitus tipo 1 (DM1) é uma doença metabólica crónica cuja incidência anual tem vindo a aumentar. Pode cursar com alterações sistémicas, como a hepatomegalia e o atraso de crescimento, decorrentes de controlo glicémico inadequado. Caso clínico: Adolescente de 14 anos com o diagnóstico de DM1 desdeos três anos de idade e com mau controlo glicémico, internada numa Unidade de Cuidados Intensivos por cetoacidose grave. Do exame objectivo destacavam-se baixa estatura, hepatomegalia não dolorosa e estadio pubertário P1, M2 de Tanner. Analiticamente apresentava aumento das transaminases, hipercolestorolemia e hipertrigliceridemia. Discussão: A síndrome de Mauriac, caracteriza -se por: DM tipo 1 mal controlada, baixa estatura, atraso pubertário, hipercolesterolémia, aumento das transaminases e hepatomegalia por depósito hepático de glicogénio. O mecanismo fi siopatológico não está totalmente esclarecido, sendo provavelmente a combinação de vários factores etiológicos. É uma situação rara, cujo diagnóstico, essencialmente clínico, assume extrema importância dada a reversibilidade do quadro com a optimização terapêutica.

Undetectable Levels of CSF Amyloid-β Peptide in a Patient with 17β-Hydroxysteroid Dehydrogenase Deficiency

17β-hydroxysteroid dehydrogenase 10 (HSD10) deficiency is a rare X-linked inborn error of isoleucine catabolism. Although this protein has been genetically implicated in Alzheimer's disease pathogenesis, studies of amyloid-β peptide (Aβ) in patients with HSD10 deficiency have not been previously reported. We found, in a severely affected child with HSD10 deficiency, undetectable levels of Aβ in the cerebrospinal fluid, together with low expression of brain-derived neurotrophic factor, α-synuclein, and serotonin metabolites. Confirmation of these findings in other patients would help elucidating mechanisms of synaptic dysfunction in this disease, and highlight the role of Aβ in both early and late periods of life.

Mutations in the MECP2 Gene Are Not a Major Cause of Rett Syndrome-Like or Related Neurodevelopmental Phenotype in Male Patients

Rett syndrome is a genetic neurodevelopmental disorder that affects mainly girls, but mutations in the causative MECP2 gene have also been identified in boys with classic Rett syndrome and Rett syndrome-like phenotypes. We have studied a group of 28 boys with a neurodevelopmental disorder, 13 of which with a Rett syndrome-like phenotype; the patients had diverse clinical presentations that included perturbations of the autistic spectrum, microcephaly, mental retardation, manual stereotypies, and epilepsy. We analyzed the complete coding region of the MECP2 gene, including the detection of large rearrangements, and we did not detect any pathogenic mutations in the MECP2 gene in these patients, in whom the genetic basis of disease remained unidentified. Thus, additional genes should be screened in this group of patients.

Travelers' Diarrhea in Children Visiting Tropical Countries

We studied a group of 174 Portuguese children (aged 2 mo-16 y) who mostly traveled to tropical Portuguese-speaking countries and found an attack rate of 21.8% for travelers' diarrhea, much lower than previously described. We also showed that African rate analysis by region may hide significant differences between countries.

Long-Term Lamivudine Treatment of Children with Chronic Hepatitis B: Durability of Therapeutic Responses and Safety

Lamivudine has been demonstrated safe and efficacious in the short term in a large cohort of children with chronic hepatitis B (CHB), but optimal duration of treatment has not been elucidated and limited data on the safety of long-term lamivudine administration have been reported. In addition, the durability of favourable therapeutic outcomes after lamivudine therapy in children has not been well characterized. The aim of this study was to examine the safety of lamivudine and the durability of clinical responses in a group of children who received up to 3 years of treatment for CHB. One hundred and fifty-one children from centres in nine countries who had previously received lamivudine in a large prospective trial were enrolled. During the first year, children had been randomized to either lamivudine or placebo treatment. Subsequently, in a separate extension study, those who remained hepatitis B e antigen (HBeAg) positive were given lamivudine for up to 2 years and those who were HBeAg negative were observed for additional 2 years. Results of these studies have been previously reported. In this study, these children were followed for 2 additional years. Data gathered from medical record review included weight, height, signs and symptoms of hepatitis, alanine aminotransferase (ALT) levels, serologic markers, hepatitis B virus (HBV) DNA levels and serious adverse events (SAEs). Other pharmacological treatments for CHB were allowed according to the practices of individual investigators and were documented. Subjects were divided into two groups for analysis, those who had achieved virological response (VR), defined as HBeAg negative and undetectable HBV DNA by the bDNA assay by the end of the extension study at 3 years, and those who had not. In those who had achieved VR by the end of the extension study, long-term durability of HBeAg seroconversion was 82% and >90% in those who had received lamivudine for 52 weeks and at least 2 years respectively. This compares to 75% for those who had achieved seroconversion after placebo. In those who had not achieved VR by the end of the extension study, an additional 11% did so by the end of the study; they had all received lamivudine in the previous trial, and none had received further treatment during the study. Eight children lost hepatitis B surface antigen during the study and all had received lamivudine at some point during the previous trials. Evaluation of safety data revealed no SAEs related to lamivudine. There was no effect of treatment on weight or height z scores. Clinically benign ALT flares (>10 times normal) were seen in 2% of children. Favourable outcomes from lamivudine treatment of CHB in children are maintained for at least several years after completion of treatment. Up to 3 years of lamivudine treatment is safe in children.

Dominant and Recessive RYR1 Mutations in Adults with Core Lesions and Mild Muscle Symptoms

INTRODUCTION: Ryanodine receptor gene (RYR1) mutations have been associated with central core disease (CCD), multiminicore/minicore/multicore disease (MmD), and susceptibility to malignant hyperthermia (MH). METHODS: Patients with muscle symptoms in adulthood, who had features compatible with CCD/MmD, underwent clinical, histological, and genetic (RYR1 and SEPN1 genes) evaluations. Published cases of CCD and MmD with adult onset were also reviewed. RESULTS: Eight patients fulfilled the criteria for further analysis. Five RYR1 mutations, 4 of them unreported, were detected in 3 patients. Compound heterozygosity was proven in 1 case. CONCLUSIONS: To our knowledge, this is the only report of adult onset associated with recessive RYR1 mutations and central core/multiminicores on muscle biopsy. Although adult patients with CCD, MmD, and minimally symptomatic MH with abnormal muscle biopsy findings usually have a mild clinical course, differential diagnosis and carrier screening is crucial for prevention of potentially life-threatening reactions to general anesthesia.

Banque mondiale et développement. Pertinences scientifiques des discours et pratiques de développement de la Banque mondiale dans les PED des années 80 à nos jours.

RÉSUMÉ « De nos jours, notent Samoff et Carrol, la Banque mondiale doit être considérée à la fois comme une banque, une agence de développement et un institut de recherche » (2004, p9). L’institution de Bretton Woods est en effet devenue notamment dans le cadre du développement des PED, à la fois une banque de prêt et une institution de savoir ; « le laboratoire d’idées sur le développement le plus important au monde », précisent Wilks et Lefrançois (2002). Cependant, si elle reste un partenaire idéologique et financier pour le développement de ces pays, la Banque mondiale est aussi en même temps dans le paysage des relations économiques internationales contemporaines une véritable superpuissance, une figure importante de la dominance mondiale d’aujourd’hui. Les programmes de développement qu’elle professe et met en œuvre dans les PED y sont de ce fait également les discours et pratiques de développement dominants. Mais le discours de développement de la Banque mondiale dans les PED, outre qu’il y soit le savoir dominant du développement, se veut aussi par ailleurs un discours d’érudition : un corps de connaissances savant de développement, qui dans sa formulation comme dans son contenu revendique l’appartenance à une certaine rationalité, vise à une certaine « scientificité ». Partant, la question autour de laquelle s’organise la présente thèse et qui est au cœur de sa problématique est la suivante : le programme de développement que la Banque mondiale destine aux PED dans sa dimension discursive en particulier, est-il pour autant rationnel et raisonnable ? En d’autres termes : de quel crédit scientifique et moral peut jouir ce programme; de quelle cohérence, de quel réalisme, et de quelle adéquation sociale, peut se prévaloir un tel système de pensées et d’actions de développement ? Mais interroger les bien-fondés épistémologiques de son programme de développement dans les PED revient aussi au plans politique et social à questionner cette position de dominance qu’occupe la Banque mondiale dans ces pays. Aussi notre questionnement général s’enchaîne-t-il comme suit: ce pouvoir d’autorité de la Banque mondiale dans les PED, tire t-il sa légitimité d’un fondement rationnel convaincant, capable de résister à la critique, ou plutôt, s’enracine t-il dans une confusion idéologique sciemment instaurée et entretenue ou comme dit Rist, dans le « pouvoir de celui qui parvient à l’imposer» ?

Hincha sin violencia : aplicación del proyecto PED en la escuela.

Presenta el programa 'Hincha sin violencia' -dentro del programa PED (Fundación Prevención Escolar contra la Droga)- generado en 1996 con el título 'Seguidor si Ira' y desarrollado en varios países europeos e iberoamericanos, con el fin de prevenir problemas de violencia y consumo de drogas. El artículo se centra en la experiencia desarrollada en el CEP El Olivar de Coslada, titulada 'Disfrutar con el movimiento y educar a través de él', presenta sus bases teóricas y las aplicaciones prácticas destinadas a la ayuda y orientación de padres para tratar con sus hijos el problema de la drogadicción.

The Ped-APS registry: The antiphospholipid syndrome in childhood

In recent years, antiphospholipid syndrome (APS) has been increasingly recognised in various paediatric autoimmune and nonautoimmune diseases, but the relatively low prevalence and heterogeneity of APS in childhood made it very difficult to study in a systematic way. The project of an international registry of paediatric patients with APS (the Ped-APS Registry) was initiated in 2004 to foster and conduct multicentre, controlled studies with large number of paediatric APS patients. The Ped-APS Registry is organised as a collaborative project of the European Forum on Antiphospholipid Antibodies and Juvenile Systemic Lupus Erythematosus Working Group of the Paediatric Rheumatology European Society. Currently, it documents a standardised clinical, laboratory and therapeutic data of 133 children with antiphospholipid antibodies (aPL)-related thrombosis from 14 countries. The priority projects for future research of the Ped-APS Registry include prospective enrolment of new patients with aPL-related thrombosis, assessment of differences between the paediatric and adult APS, evaluation of proinflammatory genotype as a risk factor for APS manifestations in childhood and evaluation of patients with isolated nonthrombotic aPL-related manifestations. © The Author(s), 2009.

Curso de procesamiento electronico de datos (PED) aplicado a temas de poblacion

El curso de Procesamiento Electronico de Datos aplicado a temas de poblacion dictado por CELADE en 1976 se estructuro con el objeto de entregar, por un lado, una base solida en computacion y, por otro, el uso intensivo de un paquete de programas utiles en el procesamiento de censos y encuestas. Contempla 5 modulos que se desarrollan a traves de actividades teorico-practicas y esta especialmente dirigido al personal de institutos nacionales de estadistica u otras oficinas gubernamentales de los paises de la region

Direttiva PED: iter tecnico-procedurale ed elementi di analisi di rischio per la valutazione di conformità delle attrezzature e degli insiemi a pressione

Il presente elaborato ha ad oggetto la direttiva PED (Pressure Equipment Directive) relativa agli apparecchi a pressione. Tale norma è stata recepita in Italia con il D.Lgs. n. 93/2000 ed è entrata in vigore definitivamente nel 2002. Essa è finalizzata alla libera circolazione delle attrezzature a pressione nella comunità europea e ne disciplina la progettazione, la costruzione, l'equipaggiamento e l'installazione in sicurezza, definendo per ciascuna delle fasi sopra elencate quali siano i documenti da presentare, gli accorgimenti da rispettare e i controlli a cui sottostare. Il presente lavoro di tesi, svolto presso lo stabilimento di Ravenna di ENI Versalis, ha avuto l’obiettivo di individuare i punti di contatto fra quanto richiesto dalla direttiva PED e quanto solitamente emerge dall’applicazione delle tecniche per l’analisi di rischio, degli standard internazionali e aziendali e delle norme di buona tecnica. Il risultato del lavoro consiste nella definizione di un iter tecnico-procedurale standardizzato ad uso dell’utilizzatore delle attrezzature a pressione tramite la quale l’azienda possa procedere alla compilazione delle Note Tecniche destinate al fabbricante delle attrezzature stesse, secondo quanto richiesto dalla direttiva. Tali Note Tecniche devono contenere le indicazioni relative ai valori progettuali di temperatura e pressione e ai Requisiti Essenziali di Sicurezza (RES) che devono essere soddisfatti, permettendo così al fabbricante di poter svolgere una corretta analisi di rischio e all’utilizzatore di ottenere la massima sicurezza negli impianti. L’elaborato è strutturato come segue. Dopo il Capitolo 1, avente carattere introduttivo, nel Capitolo 2 vengono illustrate le principali novità introdotte dalla direttiva PED e descritti i punti cardine della procedura di valutazione della conformità richiesta per le attrezzature a pressione. Nel Capitolo 3 viene esaminata l’integrazione della direttiva PED con la direttiva Macchine e la direttiva ATEX. Nel Capitolo 4 sono descritte le principali tecniche di analisi di rischio che possono essere utilizzate per rispondere ai Requisiti Essenziali di Sicurezza (RES) richiesti in fase di compilazione della Nota Tecnica. Nel Capitolo 5 si fornisce una descrizione dettagliata dell’iter tecnico-procedurale messo a punto per la valutazione di conformità delle attrezzature e degli insiemi a pressione. Nel Capitolo 6 vengono illustrati ad uno ad uno i punti che devono essere presenti in una Nota Tecnica, ciascuno dei quali costituisce un Requisito Essenziale di Sicurezza. Nel Capitolo 7 viene approfondito uno dei Requisiti più critici, l’incendio esterno. Infine nel Capitolo 8 sono riportate le considerazioni conclusive.

The influence of mouse Ped gene expression on postnatal development

The Ped (preimplantation embryo development) gene, whose product is Qa-2 protein, is correlated with a faster rate of preimplantation development (Ped fast phenotype) in mice that express Qa-2 protein compared with mice with an absence of Qa-2 protein (Ped slow phenotype). In the current study, we have used two congenic mouse strains differentially expressing the Ped gene, strain B6.K1 (Ped slow; Qa-2 negative) and strain B6.K2 (Ped fast; Qa-2 positive), to investigate the effects of Ped gene expression on postnatal growth profiles, systolic blood pressure and adult organ allometry. At birth, B6.K1 mice were moderately lighter than B6.K2 mice. B6.K1 mice became heavier during postnatal life (P

Mutations in CTC1, Encoding Conserved Telomere Maintenance Component 1, Cause Coats Plus

Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.