Biomedical subjects
Publications and source records attributed to David B Clifford.
Progressive multifocal leukoencephalopathy is a lethal complication of immunodeficiency for which no direct therapy has been achieved. The issues that have made this disease especially difficult to address are discussed, and an outline for development of future interventions is provided. A controlled trial of therapy utilizing an international group of trial groups is proposed.
Mitoxantrone is a recently approved drug for patients with secondary progressive multiple sclerosis (SPMS). However, cardiac side effects limit Mitoxantrone use in SPMS and its lifetime cumulative dose should not exceed 140 mg/m2. Additionally, Mitoxantrone is contraindicated for use in SPMS patients with a baseline left ventricular ejection fraction (LVEF) of < or = 50%. The goal of this study was to monitor LVEF more frequently than ordinarily recommended since experience with Mitoxantrone use in SPMS patients is limited. An unexpected decline in LVEF in one of the SPMS patients being treated with Mitoxantrone prompted further investigation into this finding. In our clinic, 47 patients on Mitoxantrone were followed prospectively; 28 of 47 patients had received a minimum of three doses and underwent a repeat LVEF evaluation prior to their fourth dose of Mitoxantrone. Of these 28 patients, five of 28 (17.8%) had a significant decline in LVEF from baseline. It is suggested that more stringent cardiac monitoring guidelines than current Food and Drug Administration (FDA) recommendations be used to avert potential cardiac complications in SPMS patients on Mitoxantrone.
AIDS dementia complex is a relatively recently discovered source of cognitive and motor decline, clearly linked to CNS infection by HIV. While this condition is generally subacutely progressive, and leads to death in a short time-span in untreated patients, improvement in function and prognosis may be achieved by application of highly active antiretroviral therapy. Although this therapy is essential, it may also be necessary in the long term to provide additional neuroprotection, blocking secondary mechanisms of neurotoxicity. With current therapy, infection is never completely eradicated, and significant portions of toxicity seem mediated by indirect mechanisms that may continue even during antiretroviral therapy.