Annals of the New York Academy of Sciences
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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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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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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
ReviewClara cell secretory protein (CC16): features as a peripheral lung biomarker.
Clara cell protein (CC16 or CC10) is a 15.8-kDa protein secreted all along the tracheobronchial tree and especially in the terminal bronchioles where Clara cells are localized. Even though the exact in vivo function of CC16 remains to be clarified, evidence is accumulating that CC16 plays an important protective role in the respiratory tract against oxidative stress and inflammatory response. CC16, however, presents also a major interest as a peripheral lung marker for assessing the cellular integrity or the permeability of the lung epithelium. ⋯ By contrast, serum CC16 increases in acute or chronic lung disorders characterized by an increased airways permeability. The sensitivity of serum CC16 to an increased leakiness of the lung allows for the detection of defects of the epithelial barrier at ozone levels below current air-quality guidelines. Although the clinical significance of these early epithelial changes detected by serum CC16 remains to be determined, these results clearly show that the assay in serum of lung secretory proteins such as CC16 represents a new noninvasive approach to evaluate the integrity of the respiratory tract.