Efficacy and tolerability of vigabatrin in West syndrome

West syndrome (WS) is a severe epileptic encephalopathy of childhood, characterized by spasms, developmental deterioration and hipsarhythymia. Objective: To evaluate the safety and efficacy of vigabatrin (VGB) in the treatment of WS. Method: We evaluated every patient diagnosed with WS seen at the pediatric epilepsy clinic and exposed to VGB. Patients were interviewed according to a semistructured questionnaire and we analyzed gender, age, etiology (cryptogenic or symptomatic), associated diseases, age of seizure onset, neuroimaging findings, EEG prior and after VGB, use of other antiepileptic drugs, time for seizure control, electroretinogram, visual complaints, adverse events and family history of epilepsy. Results: Twenty-three patients were evaluated, 16 boys, ages ranging from 1.25 years to 11.5 years (mean=5y3m). Sixteen (69.5%) patients were seizure free, five (22%) had partial seizure control and in two (8.5%) there was no improvement. Only one patient presented gabaergic retinopathy. Six (26%) patients presented adverse events: somnolence, aggressivity or retinopathy. Patients with seizure onset after 6 months of age presented better results after VGB introduction (p 0.05). After VGB, no patient presented hipsarrhythymia and 50% had a normal EEG. Conclusion: Although VGB may be associated with serious adverse events such as gabaergic retinopathy, our results show that it should be considered in the treatment of WS.632B46947

Computerized ICU Data Management Pitfalls and Promises

journal articleBiomedical Informatic

P07-05. HIV and STI prevalence among men who have sex with men (MSM) recruited through respondent driven sampling (RDS) in Buenos Aires, Argentina

Fil: Pando, María A. Centro Nacional de Referencia para el SIDA; Argentina.Fil: Marone, Rubén. Nexo Asociación Civil; Argentina.Fil: Balán, Iván C. Columbia University. HIV Center for Clinical and Behavioral Studies; Estados Unidos.Fil: Dolezal, Curtis. Columbia University. HIV Center for Clinical and Behavioral Studies; Estados Unidos.Fil: Squiquera, Luis. Nexo Asociación Civil; Argentina. Fil: Balan, Iván C. Columbia University. HIV Center for Clinical and Behavioral Studies; Estados Unidos.Fil: Picconi, María Alejandra. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Servicio Virus Oncogénicos; Argentina.Fil: Gonzales, J. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Servicio Virus Oncogénicos; Argentina.Fil: Rey, Jorge. Hospital de Clínicas José de San Martín; Argentina.Fil: Fernandez Toscano, M. Hospital de Clínicas José de San Martín; Argentina.Fil: Rodriguez Fermepín, Marcelo. UBA. Laboratorio de Inmunología Clínica; Argentina.Fil: Gallo Vaulet, Lucia. UBA. Laboratorio de Inmunología Clínica; Argentina.Fil: Carballo Dieguez, Alex. Columbia University. HIV Center for Clinical and Behavioral Studies; Estados Unidos.Fil: Avila, María M. Centro Nacional de Referencia para el SIDA; Argentina.Background MSM constitute one of the populations most affected by HIV and other STIs in Argentina. Previous prevalence studies were based on convenience samples. RDS, a methodology designed to access hidden populations, is being used for the first time in Argentina to recruit MSM. Methods RDS recruitment started in November 2007 with 16 first generation participants (seeds) who were selected for their potential to tap in MSM networks. Recruitment is ongoing. Men must be 18 years of age or older, be residents of Buenos Aires, self-report having sex with men at least 10 times in their lives and at least once in the past six months. They must have a coupon indicating they have been referred by a study participant. Specimens are being collected for HIV and STI diagnosis. All data are weighted using the RDS Analysis Tool (RDSAT). Results To date, 333 MSM were recruited through RDS showing a prevalence of 11.3, 16.6, 7.9, 17.6, 4.0 and 88.3% for HIV, HBV, HCV, T. pallidum, Chlamydia and HPV, respectively. Chlamydia and HPV diagnoses were only performed in 73 and 79 participants, respectively. Among HPV positive individuals, 47.8% had almost one of these high risk types (16, 58, 33, 45, 18 and 31) and 32% had multiple infections with 2 or more types. Conclusion Compared with previous studies, these results show similar HIV, HBV and T. pallidum prevalences but higher HCV prevalence. For the first time, an elevated prevalence of HPV was detected on MSM, with high frequency of types associated with ano-genital cancer. Preliminary analyses of socio demographic data show that RDS helps recruit a diversity of MSM, particularly of lower socio-economic level usually missed with other recruitment methods. The high prevalence of coinfections in this population should be taken into account if MSM are part of vaccine trials given that STI may increase HIV sexual transmission

Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes

Dysfunctional skeletal muscle calcium homeostasis plays a central role in the pathophysiology of several human and animal skeletal muscle disorders, in particular, genetic disorders associated with ryanodine receptor 1 (RYR1) mutations, such as malignant hyperthermia, central core disease, multiminicore disease and certain centronuclear myopathies. In addition, aberrant skeletal muscle calcium handling is believed to play a pivotal role in the highly prevalent disorder of Thoroughbred racehorses, known as Recurrent Exertional Rhabdomyolysis. Traditionally, such defects were studied in human and equine subjects by examining the contractile responses of biopsied muscle strips exposed to caffeine, a potent RYR1 agonist. However, this test is not widely available and, due to its invasive nature, is potentially less suitable for valuable animals in training or in the human paediatric setting. Furthermore, increasingly, RYR1 gene polymorphisms (of unknown pathogenicity and significance) are being identified through next generation sequencing projects. Consequently, we have investigated a less invasive test that can be used to study calcium homeostasis in cultured, skin-derived fibroblasts that are converted to the muscle lineage by viral transduction with a MyoD (myogenic differentiation 1) transgene. Similar models have been utilised to examine calcium homeostasis in human patient cells, however, to date, there has been no detailed assessment of the cells’ calcium homeostasis, and in particular, the responses to agonists and antagonists of RYR1. Here we describe experiments conducted to assess calcium handling of the cells and examine responses to treatment with dantrolene, a drug commonly used for prophylaxis of recurrent exertional rhabdomyolysis in horses and malignant hyperthermia in humans

Mutation Screening of Multiple Genes in Spanish Patients with Autosomal Recessive Retinitis Pigmentosa by Targeted Resequencing

Retinitis Pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterised ultimately by the loss of photoreceptor cells. RP is the leading cause of visual loss in individuals younger than 60 years, with a prevalence of about 1 in 4000. The molecular genetic diagnosis of autosomal recessive RP (arRP) is challenging due to the large genetic and clinical heterogeneity. Traditional methods for sequencing arRP genes are often laborious and not easily available and a screening technique that enables the rapid detection of the genetic cause would be very helpful in the clinical practice. The goal of this study was to develop and apply microarray-based resequencing technology capable of detecting both known and novel mutations on a single high-throughput platform. Hence, the coding regions and exon/intron boundaries of 16 arRP genes were resequenced using microarrays in 102 Spanish patients with clinical diagnosis of arRP. All the detected variations were confirmed by direct sequencing and potential pathogenicity was assessed by functional predictions and frequency in controls. For validation purposes 4 positive controls for variants consisting of previously identified changes were hybridized on the array. As a result of the screening, we detected 44 variants, of which 15 are very likely pathogenic detected in 14 arRP families (14%). Finally, the design of this array can easily be transformed in an equivalent diagnostic system based on targeted enrichment followed by next generation sequencing

Drosophila Sperm Swim Backwards in the Female Reproductive Tract and Are Activated via TRPP2 Ion Channels

Sperm have but one purpose, to fertilize an egg. In various species including Drosophila melanogaster female sperm storage is a necessary step in the reproductive process. Amo is a homolog of the human transient receptor potential channel TRPP2 (also known as PKD2), which is mutated in autosomal dominant polycystic kidney disease. In flies Amo is required for sperm storage. Drosophila males with Amo mutations produce motile sperm that are transferred to the uterus but they do not reach the female storage organs. Therefore Amo appears to be a mediator of directed sperm motility in the female reproductive tract but the underlying mechanism is unknown.Amo exhibits a unique expression pattern during spermatogenesis. In spermatocytes, Amo is restricted to the endoplasmic reticulum (ER) whereas in mature sperm, Amo clusters at the distal tip of the sperm tail. Here we show that flagellar localization of Amo is required for sperm storage. This raised the question of how Amo at the rear end of sperm regulates forward movement into the storage organs. In order to address this question, we used in vivo imaging of dual labelled sperm to demonstrate that Drosophila sperm navigate backwards in the female reproductive tract. In addition, we show that sperm exhibit hyperactivation upon transfer to the uterus. Amo mutant sperm remain capable of reverse motility but fail to display hyperactivation and directed movement, suggesting that these functions are required for sperm storage in flies.Amo is part of a signalling complex at the leading edge of the sperm tail that modulates flagellar beating and that guides a backwards path into the storage organs. Our data support an evolutionarily conserved role for TRPP2 channels in cilia