Biological warfare and the 'Hiroshima' issue of JAMA.
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Biomedical subjects
Publications and source records attributed to M Sapir.
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OBJECTIVE: To assess the relationship between ethnicity and decision-makers expressing healthcare wishes in a group of frail older persons enrolled in the Program of All-inclusive Care for the Elderly (PACE). DESIGN: A retrospective chart review of 1193 participants in the PACE program. SETTING: Program of All-inclusive Care for the Elderly, a comprehensive managed care demonstration program serving frail older participants at 10 sites across the nation. PARTICIPANTS: A total of 1193 older adults, all of whom met state criteria for nursing home level of care. Three hundred were non-Hispanic whites, 364 were black, 156 were Hispanic, and 288 were Asian. MEASUREMENTS: Demographic characteristics of the patients and the presence or absence of an alternative decision-maker; the characteristics of alternative decision-makers included the relationship to the participant as recorded in the patient's medical record. RESULTS: Ninety-one percent of white patients expressed their own healthcare wishes in contrast to only 85% of Hispanic, 83% of Asian, and 67% of black patients. An alternative decision-maker was identified for about 15% of Asians and Hispanics and for one-third of blacks, but only about 8% of whites had an alternative decision-maker. Black and Hispanic patients were most likely to have a daughter as an alternative decision-maker, Asians were most likely to have a son, and whites patients were most likely to have a spouse as an alternative decision-maker. Blacks, particularly black men, were the most likely to have a relative other than a spouse or child as an alternative decision-maker. CONCLUSIONS: In this population, we found significant ethnic variation in the person identified to be the decision-maker in a group of frail older people. Ethnic variation reflected sociodemographic as well as cultural differences. However, there are important limitations to this study, and caution should be used in extrapolating the results to other populations or in attributing the results to ethnicity alone. An awareness of cross-cultural patterns in identified or de facto decision-makers can be significant for healthcare workers when they approach patients and their families about issues surrounding end of life decisions.
OBJECTIVE: To assess the relationship between ethnicity and Health Care wishes, including Advance Directives, in a group of frail older persons in PACE (Program For All Inclusive Care Of The Elderly). DESIGN: Retrospective chart review of 1193 participants in the PACE program. SETTING: Program of All Inclusive Care Of The Elderly (PACE), a comprehensive managed care demonstration program serving frail older participants at 10 sites across the nation. PARTICIPANTS: A total of 1193 older adults, all of whom met state criteria for nursing home level of care. There were 385 non-Hispanic whites, 364 blacks, 156 Hispanics, and 288 Asians. MEASUREMENTS: Presence or absence of advance directives, type of health care wishes selected including living will, durable power of attorney, and health care proxy. RESULTS: Frail older white, black, Hispanic and Asian Americans differ significantly in their health care wishes and how they choose to express them. Blacks were significantly more likely to select aggressive interventions and less likely than non-Hispanic whites and Hispanics to utilize a written instrument for expressing health care wishes. Whites were significantly more likely to utilize written documents for advance directives, whereas Asians were more likely to select less aggressive interventions but were unlikely to use written advance directives. CONCLUSIONS: In this population, we found significant ethnic variations in choice of health care wishes. Although health care wishes are an individual decision, an awareness of cross cultural patterns can assist practitioners in addressing the concerns of their patients, as well as assisting Health Care Policy Development.
This study was aimed at evaluating the ability of a new functionally selective partial M1 agonist, AF150(S), to reverse cognitive impairments in rats. A memory deficits-induced animal model was used that involved AF64A (3 nmol/2 microliters/side) bilaterally injected ICV. AF150(S) was administered PO. The pharmacodynamic profile of the compound was established and its general toxicity was evaluated. Animals were tested on three behavioral tasks: step-through passive avoidance, Morris water maze reference memory paradigm, and radial arm maze working memory paradigm. The sign-free dose of AF150(S) was > 40 mg/kg whereas the LD50 was > 500 mg/kg. In comparison, the effective dose in reversing performance impairments on the various tasks was much lower (0.5-5 mg/kg). The data suggest that AF150(S) possesses potential cognitive enhancement abilities, probably due to a specific increase of cholinergic function.
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This study evaluated the ability of the selective MAO-B inhibitor, L-deprenyl, to reverse cognitive impairments appearing in aged rats, using the reference memory, Morris Water Maze paradigm. L-Deprenyl significantly improved learning and memory deficits associated with old age in doses of 1.25 and 5 mg/kg PO (escape latency measure) and doses of 1.25, 2.5 and 5 mg/kg PO (path length measure). L-Deprenyl also improved reversal learning impairments in doses of 1.25, 2.5 and 5 mg/kg PO, as expressed by the escape latency measure. The data suggest that L-deprenyl possesses potential cognitive enhancement abilities probably due to an increase in dopaminergic activity.
AF102B [(+-)-cis-2-methyl-spiro(1,3-oxathiolane-5,3')quinuclidine], a structurally rigid analog of acetylcholine, was investigated in a number of neurochemical, pharmacological and behavioral tests related to cholinergic functions. AF102B induced atropine-sensitive contractions of isolated guinea pig ilea and trachea preparations with EC50 values of 3.5 and 3 microM being 87- and 1.3-fold less potent than acetylcholine, respectively. Binding studies using the radioligands pirenzepine, cis-dioxolane and quinuclidinyl benzilate in rat cerebral cortex and quinuclidinyl benzilate in cerebellar homogenates indicated that AF102B was a potent and highly selective M1-type muscarinic probe, being more selective for M1 receptors than oxotremorine, carbachol and AF102A (the trans-isomer of AF102B). AF102B had a 3-fold higher apparent affinity for M1 receptors than the prototype M1 agonist, McN-A-343, cis- and trans-AF30 (other rigid analogs of acetylcholine). Treatment of rat cortical homogenates with Cu++ ions did not modify the affinity observed for the muscarinic antagonists atropine, scopolamine and pirenzepine, whereas increasing the proportion of high affinity sites for the agonists oxotremorine-M, carbachol and McN-A-343. The apparent affinity of AF102B also increased by Cu++ treatment suggesting that this compound interacts with rat cerebral cortex muscarinic receptors as an agonist. AF102B did not affect high affinity choline transport, choline acetyltransferase and acetylcholinesterase activities in rat brain preparations. In rats treated with AF64A (the cholinotoxin ethylcholine aziridinium ion; 3 nmol/2 microliters/side i.c.v.), AF102B (1 mg/kg p.o. or i.p.), AF102A (1 mg/kg i.p.), cis-AF30 (1 mg/kg, i.p.) and physostigmine (0.06 mg/kg i.p.), each reversed cognitive impairments in a step-through passive avoidance task. Both AF102B and AF102A (1 mg/kg i.p.), but not physostigmine (0.1 mg/kg i.p.), were effective also in reversing reference memory impairments in a Morris water maze test. Repetitive administrations of AF102B (0.2 mg/kg/day i.p.) improved AF64A-induced working memory deficits in the Morris water maze test, but did not affect open field behavior. The data show that the selective M1 agonist AF102B can restore AF64A-induced cognitive impairments, without producing adverse central and peripheral side effects at the effective doses and this can indicate its potential use for the treatment of Alzheimer's disease.
This study examined the effect of a specific M1 cholinergic agonist, AF102B, on place learning of aged and young rats. Spatial reference memory was tested in the Morris Water Maze task, while spatial working memory was tested on an 8-arm radial maze. Both memory functions were impaired in aged rats compared to young animals. However, the administration of AF102B significantly reduced the age-related cognitive impairments observed in both tasks. This data supports the assertion of the "cholinergic hypothesis," namely that specific enhancement of cholinergic function may reverse geriatric cognitive deficits.
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(+-)-cis-2-Methyl-spiro(1,3-oxathiolane-5,3')quinuclidine (AF102B), a new muscarinic agonist of utmost rigidity, exhibits a high selectivity for M1 muscarinic receptors. In rats having a cholinergic hypofunction induced by the intracerebroventricular administration of ethylcholine aziridinium (AF64A), AF102B reversed cognitive impairments in a step-through passive avoidance task and in an 8-arm radial maze. AF102B reversed cognitive impairments at significantly lower doses than those needed to induce side-effects. In addition, AF102B exhibited low toxicity. The results suggest that AF102B may prove useful for treatments of cholinergic deficiencies and cognitive impairments, like those reported in Alzheimer's disease.
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This paper discusses the problems related to enhanced exposure of workers to natural radiation and other pollutants in the working and living environment, with particular attention to radon. A method is proposed for regulating this high priority problem, which also considers the variable borderline between the controllable and uncontrollable exposure contributions. It is based on the principles of an integrated health policy regarding air quality. The complex multiple source exposure in private dwellings, at the workplace and through consumer goods should be taken into account as discussed in recent WHO and ILO reports. The important role of ventilation practices for future health is put forward. As far as regulation of exposure to ionizing radiation is concerned the present Euratom Basic Safety Standards are considered inadequate. Particular attention is given to a specification of justification and optimization and to a practical use of a hierarchy of limits as defined in the IAEA/ILO/WHO/NEA Basic Safety Standards.
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