Showing papers by "Charles H. Vite published in 2005"
TL;DR: The data demonstrate that widespread improvement of neuropathology in a large mammalian brain can be achieved using multiple injection sites during one operation and suggest that this could be an effective treatment for the central nervous system component of human lysosomal enzyme deficiencies.
Abstract: Genetic diseases affecting the brain typically have widespread lesions that require global correction. Lysosomal storage diseases are good candidates for central nervous system gene therapy, because active enzyme from genetically corrected cells can be secreted and taken up by surrounding diseased cells, and only small amounts of enzyme (<5% of normal) are required to reverse storage lesions. Injection of gene transfer vectors into multiple sites in the mouse brain has been shown to mediate widespread reversal of storage lesions in several disease models. To study a brain closer in size to the human brain, we evaluated the extent of storage correction mediated by a limited number of adeno-associated virus vector injections in the cat model of human alpha-mannosidosis. The treated cats showed remarkable improvements in clinical neurological signs and in brain myelination assessed by quantitative magnetic resonance imaging. Postmortem examination showed that storage lesions were greatly reduced throughout the brain, even though gene transfer was limited to the areas surrounding the injection tracks. The data demonstrate that widespread improvement of neuropathology in a large mammalian brain can be achieved using multiple injection sites during one operation and suggest that this could be an effective treatment for the central nervous system component of human lysosomal enzyme deficiencies.
137 citations
TL;DR: It is suggested that nonambulatory tetraparesis is significantly more common in dogs with CVD and veer or lean in 1 direction and to have resting nystagmus may be useful in distinguishing the 2 conditions.
Abstract: Objective—To determine the frequency of specific signs of neurologic dysfunction in dogs with central vestibular disease (CVD) or peripheral vestibular disease (PVD) and whether the degree of head tilt, rate of nystagmus, and number of beats of postrotatory nystagmus can be used to help distinguish CVD from PVD. Design—Prospective clinical study. Animals—40 client-owned dogs with vestibular system dysfunction. Procedure—A standard neurologic examination was performed, along with an expanded vestibular system examination that assessed the degree of head tilt, rate of nystagmus, and number of beats of postrotatory nystagmus. Results—Dogs with CVD were significantly more likely to be nonambulatory than were dogs with PVD. Dogs with PVD were significantly more likely to veer or lean in 1 direction and to have resting nystagmus than were dogs with CVD. Median rate of resting nystagmus was significantly higher for dogs with PVD, but no significant differences between groups were detected in regard to presence o...
31 citations
TL;DR: Although a higher mortality rate has been reported for dogs with neurological symptoms and RMSF infection, all of the dogs in this study improved with appropriate medical therapy and supportive care.
Abstract: Five dogs from the northeastern United States were presented with clinical signs of neurological disease associated with Rocky Mountain spotted fever (RMSF) infection. Four of the five dogs had vestibular system dysfunction. Other neurological signs included paresis, tremors, and changes in mentation. All of the dogs had an elevated indirect fluorescent antibody titer or a positive semiquantitative enzyme screening immunoassay titer for Rickettsia rickettsii at the time of presentation. Although a higher mortality rate has been reported for dogs with neurological symptoms and RMSF infection, all of the dogs in this study improved with appropriate medical therapy and supportive care.
12 citations