Annals of the New York Academy of Sciences
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The ethical issues and conflicts facing anthropology have precedents in the past because they are intrinsic to anthropological practice. What is different about them now is that they are played out in new sites, with added complexities, and without changed relations of anthropologists to those with stakes in their research, especially "the people" they study. A review of the unintended consequences of the American Anthropological Association's efforts to define a code of ethics in the 1960s offers lessons that are applicable today.
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Neuropathic pain is associated with abnormal tactile and thermal responses that may be extraterritorial to the injured nerve. Importantly, tactile allodynia and thermal hyperalgesia may involve separate pathways, since complete and partial spinal cord lesions have blocked allodynia, but not hyperalgesia, after spinal nerve ligation (SNL). Furthermore, lesions of the dorsal column, and lidocaine microinjected into dorsal column nuclei block only tactile allodynia. ⋯ Finally, afferent drive may induce descending facilitation from the rostroventromedial medulla (RVM). Blocking afferent drive with bupivicaine also restored lost potency of PAG morphine, as did CCK antagonists in the RVM. This observation is consistent with afferent drive activating descending facilitation from the RVM, and thus diminishing opioid activity, and may underlie the clinical observation of limited responsiveness of neuropathic pain to opioids.
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Ann. N. Y. Acad. Sci. · Jan 2000
Review Comparative StudyDX-8951f: summary of phase I clinical trials.
Exatecan mesylate (DX-8951f) is a new hexacyclic camptothecin analogue with favorable attributes compared to topotecan and CPT-11, including watersolubility, greater potency against topoisomerase I, lack of esterase-dependent activation, broad antitumor activity, and low cross-resistance against MDR-1 overexpressing tumors. In preclinical studies, the compound demonstrated a favorable toxicology profile with hematologic dose-limiting toxicity and moderate gastrointestinal toxicity, linear pharmacokinetics, P450 hepatic metabolism (CYP3A4 and CYP1A2), and predominately fecal excretion. The results of six U. ⋯ Pharmacokinetics were linear within the dose range tested. A pharmacokinetic/pharmacodynamic model predictive of DX-8951f-induced neutropenia in individual patients was developed. The daily x5, every 3-week schedule with the drug administered as a 30-minute intravenous infusion was selected for future phase II clinical trials based on its superior antitumor activity.
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Ann. N. Y. Acad. Sci. · Jan 2000
ReviewPreclinical and clinical trials of topoisomerase inhibitors.
CPT-11, developed by Yakult Honsha, has achieved the position of standard chemotherapy for colorectal cancer in the United States and in Western countries because CPT-11 + 5FU + LV showed survival benefit compared with 5FU-LV in two randomized controlled trials. CPT-11 has been distributed to almost all countries. In Japan, combination therapy of CDDP + CPT-11 was significantly superior to CDDP-VP-16 in the treatment of extensive disease small cell lung cancer. ⋯ The new topoisomerase I inhibitors of indolocarbazol derivatives, NB-506 and J107088, developed by Banyu Co., have strong antitumor activity and a wide therapeutic ratio. The phase I trial of J107088 is currently ongoing in the United States and Japan. These do not show any cross-resistance to MDR drugs.