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 Research

Peripheral Nerve Toxicity of High-Dose Chemotherapy
At City of Hope, I have developed expertise in the neurological complications of hematopoietic stem cell transplantation. My particular focus has been on immune-mediated neurological complications and how these can be distinguished from the toxic, infectious, and metabolic problems that are so common in transplant patients. More recently, in the clinical and neurophysiology laboratory of the Division of Neurology, studies of chemotherapy-associated peripheral neuropathies have been carried out, monitoring nerve condition and sensory thresholds (quantitative sensory testing). In a detailed study with George Somlo, M.D., and colleagues in the Department of Medical Oncology, we have shown that high-dose paclitaxel (Taxol) given in association with autologous peripheral blood stem cell transplantation reproducibly damaged peripheral nerves. Treatment with the chemoprotectant drug amifostine did not decrease the severity of the peripheral neuropathy. Other related studies include an assessment of height on peripheral nerve damage from  high-dose chemotherapy and a proposed study of etoposide neuropathy in allogeneic transplant patients.

Viral Infection of the Nervous System
I have had a long-standing interest in the pathogenesis of herpes simplex virus (HSV) latency and reactivation in nervous system tissue. Since the mid 1980's, animal model studies of HSV pathogenesis at City of Hope and Beckman Research Institute have been carried out in the Neurology Laboratory (now the Laboratory of Neurovirology and Neuroimmunology) of Edouard Cantin, Ph.D. For current projects of HSV pathogenesis in this laboratory, please see Dr. Cantin's entry under the Department of Virology. In addition, I have collaborated for many years with Dr. Tsuyoshi Sekizawa of the Department of Neurology, Tohoku University, in Sendai, Japan. Recently, we published the results of an experimental study showing that intradermal doxorubicin can eliminate latently infected neurons in mice by "suicide" axoplasmic transport of the drug. In regard to clinical neurovirolgy, I have recently become involved as the City of Hope principal investigator of a national protocol evaluating an immunoglobin treatment of West Nile virus encephalitis. This National Institutes of Health-sponsored study is organized by the Collaborative Anti-viral Study Group (CASG) of the University of Alabama at Birmingham.
 

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