RESUMEN
The hereditary spastic paraplegias (HSPs) are a genetically and clinically heterogeneous group of upper-motor-neuron degenerative diseases characterized by selective axonal loss in the corticospinal tracts and dorsal columns. Although numerous mechanisms involving defective subcellular transportation, mitochondrial malfunction, and increased oxidative stress have been proposed, the pathogenic basis underlying the neuronal loss is unknown. We have performed linkage analysis to refine the extent of the SPG5 disease locus and conducted sequence analysis of the genes located within this region. This identified sequence alterations in the cytochrome P450-7B1 (CYP7B1) associated with this pure form of HSP. In the liver, CYP7B1 offers an alternative pathway for cholesterol degradation and also provides the primary metabolic route for the modification of dehydroepiandrosterone neurosteroids in the brain. These findings provide the first direct evidence of a pivotal role of altered cholesterol metabolism in the pathogenesis of motor-neuron degenerative disease and identify a potential for therapeutic intervention in this form of HSP.
Asunto(s)
Colesterol/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Homeostasis/genética , Paraplejía Espástica Hereditaria/genética , Esteroide Hidroxilasas/genética , Secuencia de Aminoácidos , Secuencia de Bases , Mapeo Cromosómico , Familia 7 del Citocromo P450 , Humanos , Hígado/metabolismo , Datos de Secuencia Molecular , Linaje , Análisis de Secuencia de ADN , Paraplejía Espástica Hereditaria/metabolismoRESUMEN
BACKGROUND: Many physicians enter data into the electronic medical record (EMR) as unstructured free text and not as discrete data, making it challenging to use for quality improvement or research initiatives. OBJECTIVES: The objective of this research paper was to develop and implement a structured clinical documentation support (SCDS) toolkit within the EMR to facilitate quality initiatives and practice-based research in a multiple sclerosis (MS) practice. METHODS: We built customized EMR toolkits to capture standardized data at office visits. Content was determined through physician consensus on necessary elements to support best practices in treating patients with demyelinating disorders. We also developed CDS tools and best practice advisories within the toolkits to alert physicians when a quality improvement opportunity exists, including enrollment into our DNA biobanking study at the point of care. RESULTS: We have used the toolkit to evaluate 541 MS patients in our clinic and begun collecting longitudinal data on patients who return for annual visits. We provide a description and example screenshots of our toolkits, and a brief description of our cohort to date. CONCLUSIONS: The EMR can be effectively structured to standardize MS clinic office visits, capture data, and support quality improvement and practice-based research initiatives at the point of care.