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Neuronal injury in ischemic stroke is partly mediated by cytotoxic reactive oxygen species. Although the antioxidant ascorbic acid (AA) or vitamin C does not penetrate the blood-brain barrier (BBB), its oxidized form, dehydroascorbic acid (DHA), enters the brain by means of facilitative transport. We hypothesized that i.v. DHA would improve outcome after(More)
Methylnaltrexone, a peripherally acting mu-opioid receptor antagonist with restricted ability to cross the blood-brain barrier, reverses opioid-induced constipation (OIC) without affecting analgesia. A double-blind study in patients with advanced illness and OIC demonstrated that methylnaltrexone significantly induced laxation within four hours after the(More)
Methylnaltrexone, a peripheral mu-opioid receptor antagonist with restricted ability to cross the blood-brain barrier, may relieve opioid-induced constipation (OIC) without reversing analgesia. A total of 154 patients with advanced illness and OIC enrolled in a double-blind, randomized, placebo-controlled trial, with optional open-label phases (up to 4(More)
Previous studies have shown that a single dose of methylnaltrexone, a unique peripheral opioid antagonist, reverses opioid-induced gut hypomotility in humans. Because repeated drug doses are likely to be needed to treat patients with opioid-induced or postsurgical bowel dysfunction, the authors have now examined the safety, pharmacological activity, and(More)
Prostate-specific membrane antigen (PSMA) is an integral, non-shed membrane glycoprotein that is a well-characterized and clinically validated marker of prostate cancer. The expression profile and other biological properties of PSMA make it an attractive target for antibody-drug conjugate (ADC) therapy of prostate cancer, as well as a broad range of other(More)
To evaluate the effect of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) on patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) who were intolerant to zidovudine because of neutropenia, we performed a randomized, open-label study in which patients were assigned to one of two groups. Zidovudine was(More)
Methylnaltrexone, a peripherally-acting quaternary opioid antagonist, is an investigational treatment for opioid-induced constipation in patients with advanced illness. This randomized, parallel-group, repeated dose, dose-ranging trial included a double-blind phase for one week followed by an open-label phase for a maximum of three weeks. Opioid-treated(More)
In a previous randomized Phase III trial (P. O. Livingston et al, J. Clin. Oncol., 12: 1036-1044, 1994), we demonstrated that immunization with GM2 and bacille Calmette-Guerin reduced the risk of relapse in stage III melanoma patients who were free of disease after surgical resection and who had no preexisting anti-GM2 antibodies. That vaccine formulation(More)
Methylnaltrexone is an investigational peripheral opioid receptor antagonist, a quaternary derivative of naltrexone. Methylnaltrexone has greater polarity and lower lipid solubility, thus it does not cross the blood-brain barrier in humans. Methylnaltrexone offers the therapeutic potential to block or reverse the undesired side effects of opioids that are(More)
Immunization with GMK vaccine (G(M2) ganglioside conjugated to keyhole limpet hemocyanin mixed with QS-21 adjuvant) induces anti-G(M2) antibodies in close to 100% of patients. We found previously that anti-G(D2) antibodies could be induced in some patients using G(D2)-keyhole limpet hemocyanin + QS-21 (GDK). In this trial, we wished: (a) to determine(More)