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Biomedical subjects

R J Lederman

Publications and source records attributed to R J Lederman.

5 recordsLinked to original sources
PubMed2012

MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) cardiomyopathy patients currently have no therapeutic options. We evaluated catheter-based transendocardial delivery of a recombinant adeno-associated virus (rAAV) expressing a small nuclear U7 RNA (U7smOPT) complementary to specific cis-acting splicing signals. Eliminating specific exons restores the open reading frame resulting in translation of truncated dystrophin protein. To test this approach in a clinically relevant DMD model, golden retriever muscular dystrophy (GRMD) dogs received serotype 6 rAAV-U7smOPT via the intracoronary or transendocardial route. Transendocardial injections were administered with an injection-tipped catheter and fluoroscopic guidance using X-ray fused with magnetic resonance imaging (XFM) roadmaps. Three months after treatment, tissues were analyzed for DNA, RNA, dystrophin protein, and histology. Whereas intracoronary delivery did not result in effective transduction, transendocardial injections, XFM guidance, enabled 30&#xb1;10 non-overlapping injections per animal. Vector DNA was detectable in all samples tested and ranged from <1 to >3000 vector genome copies per cell. RNA analysis, western blot analysis, and immunohistology demonstrated extensive expression of skipped RNA and dystrophin protein in the treated myocardium. Left ventricular function remained unchanged over a 3-month follow-up. These results demonstrated that effective transendocardial delivery of rAAV-U7smOPT was achieved using XFM. This approach restores an open reading frame for dystrophin in affected dogs and has potential clinical utility.

Animals↗
PubMed1978

Progressive dialysis encephalopathy.

The clinical features of 42 patients with the only recently recognized and generally fatal neurological syndrome of progressive dialysis encephalopathy are reviewed and the electroencephalographic and neuropathological findings are summarized. Despite apparently successful hemodialysis, these patients develop a wide spectrum of neurological abnormalities. Of these, sudden onset of hesitant, nonfluent speech is the most characteristic and usually the earliest sign. Both dysphasic and dysarthritic elements are found, though the former predominate. Myoclonus, dementia, seizures, and gait difficulty are also seen in the majority of these patients. EEGs are more abnormal than would be expected for the clinical severity, with some type of high-voltage spike-wave pattern intermixed with abundant slow activity. The combination of clinical and EEG features in the appropriate setting is virtually diagnostic. Transient episodes with variable periods of complete or partial remission have been recognized. Neuropathological changes are surprisingly mild and nonspecific. The cause is uncertain; current speculation focuses on aluminum as the offending neurotoxin. Treatment remains unsatisfactory.

Adult↗
PubMed1978

Interval computed tomography in multiple sclerosis.

Computed tomography demonstrated areas of abnormal attenuation in the white matter in 14 patients with multiple sclerosis (MS). Nine were studied two or more times. Acute MS lesions exhibit decreased or normal attenuation without contrast enhancement and increased attenuation with it. On later scans these lesions show decreased attenuation with or without contrast material. Some lesions remain decreased in attenuation and some become normal both with and without contrast material.

Adolescent↗