Neurology
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Amezinium metilsulfate is a new, indirectly acting sympathomimetic drug which exclusively affects postganglionic sympathetic neurons and inhibits both intraneuronal monoamine oxidase and norepinephrine reuptake. We examined the short-term effects of amezinium in five patients with severe neurogenic orthostatic hypotension. Single-dose administration of amezinium (10 mg) raised both the supine and sitting mean blood pressures by 15 to 45 mm Hg for 8 hours, with a slight increase in the plasma norepinephrine level. ⋯ The heart rate was increased in two patients. The results indicate that amezinium is of therapeutic value for the treatment of neurogenic orthostatic hypotension. The adrenergic effect of amezinium on the blood pressure and heart rate apparently was related to a slight increase in endogenous norepinephrine in the presence of alpha- and beta-adrenoreceptor supersensitivity.
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We have studied the effects of various monoclonal antibody (MAb) infusions in patients with chronic progressive multiple sclerosis in the hope of developing an immunologically specific, nontoxic form of therapy for this disease. The immunologic responses to anti-T12, anti-T4, and anti-T11 MAb infusions were assessed in subjects with chronic progressive multiple sclerosis as part of phase I clinical studies. It was found that in vivo anti-T-cell MAb infusions specifically suppress in vitro measurements of the human immune response: anti-T11 MAb decreased T-cell activation by phytohemagglutinin, and anti-T4 MAb infusions abolished pokeweed mitogen-induced immunoglobulin synthesis without lysis of the CD4 + T-cell subpopulations. ⋯ Murine anti-T-cell MAb can provide a specific, benign form of acute immunosuppression in humans. Repeated administration of these reagents in more chronic diseases can result in anti-idiotypic antibodies that block binding of the anti-T-cell MAbs to the T-cell surface. While the clinical usefulness of currently used murine MAbs in chronic diseases is restricted by the development of human anti-mouse antibodies, newer, more immunosuppressive MAbs may eliminate this problem.
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The clinical use of monoclonal antibodies (MAbs) in multiple sclerosis (MS) is an exciting clinical prospect whose current use is subject to several limitations. Clinical studies to date have shown that infusion of murine MAbs, the preparations presently available, is associated with the production of antimurine antibody, which makes the long-term use of this therapy infeasible in most patients. ⋯ The target antigens often undergo modulation and the cells reappear in the circulation with full function in spite of ongoing therapy. The use of MAbs in MS needs further clarification through randomized, controlled clinical trials.