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111.
C V Owen J A Acquavella J Lynch M G Bird 《American Industrial Hygiene Association journal》1992,53(9):540-547
An industrial hygiene methodology that was developed in support of an epidemiologic case-control study is described. This study was conducted to investigate a potentially increased incidence of colorectal cancer among employees who worked at a unit that manufactured polypropylene by a heavy diluent process. Retrospective epidemiologic case-control studies typically have exposure assessment problems because industrial hygiene monitoring data are often not available. Misleading job titles are another problem that can provide a poor framework for estimating exposures. In addition, a job title-based exposure assessment assumes individual work patterns are not important in assessing worker exposures, although this is contradictory to industrial hygiene experience. The design of the case-control study provided an innovative industrial hygiene approach to circumvent these typical exposure estimating problems. The industrial hygiene methodology of the case-control study included assessing historical exposures, developing an exposure estimating matrix, selecting candidate etiologic agents based on a joint toxicologic and industrial hygiene review, administering a work activity questionnaire, calculating exposure scores, and conducting a statistical analysis. The study design also provided an additional exposure measurement independent of the toxicologic and industrial hygiene review. This provided an opportunity to compare the likelihood of exposure misclassification and, as expected, showed that a more detailed exposure estimate resulted in less misclassification. 相似文献
112.
Sleep hypoxia in myotonic dystrophy and its correlation with awake respiratory function. 总被引:2,自引:1,他引:1
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BACKGROUND--Tiredness and daytime respiratory failure occur frequently in myotonic dystrophy. Sleep hypoxaemia was studied in 12 patients with myotonic dystrophy and correlations were sought with their daytime lung and respiratory muscle function. METHODS--All patients underwent overnight sleep studies, clinical assessment, measurement of flow-volume loops and carbon monoxide transfer factor, arterial blood gas analysis, and physiological assessment of both thoracic muscle function and upper airways obstruction. RESULTS--The mean nadir of oxygen saturation during sleep was 75% (95% confidence interval 69% to 81%). A mean of 3.4% of total sleep duration was spent at an oxygen saturation level below 85%. Five of the 12 patients had an apnoea index of > 5, the group mean apnoea/hypopnoea index being 15.8 events/sleep hour. The mean awake arterial oxygen tension (PaO2) was 10.7 kPa. There was a trend to hypercapnoea with a mean awake arterial carbon dioxide tension of 6.1 kPa; carbon dioxide retention worsened during sleep. Respiratory muscle dysfunction was mainly evident as a low maximum expiratory mouth pressure. Upper airway obstruction assessed by physiological criteria was found in four of the 12 patients. The proportion of total sleep duration with oxygen saturation levels below 85% was directly related to body mass index (weight/height2) and inversely related to the awake PaO2. Body mass index was inversely related to the overnight nadir of oxygen saturation. CONCLUSIONS--Patients with myotonic dystrophy are often hypoxic during sleep and the subgroup that are obese, or have symptoms of sleep apnoea, or both, are particularly at risk. Sleep studies should be considered in this subgroup of patients with myotonic dystrophy. 相似文献
113.
Centrally active modulators of glutamate receptors facilitate the induction of long-term potentiation in vivo. 总被引:3,自引:0,他引:3
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U St?ubli Y Perez F B Xu G Rogers M Ingvar S Stone-Elander G Lynch 《Proceedings of the National Academy of Sciences of the United States of America》1994,91(23):11158-11162
An experimental drug, 1-(1,3-benzodioxol-5-ylcarbonyl)piperidine, that facilitates glutamatergic transmission in brain after systemic administration was tested for its effects on the induction of long-term potentiation in the hippocampus of rats. Intraperitoneal injections of the drug markedly increased the degree and duration of long-term potentiation; similar results were obtained with an analogue of 1-(1,3-benzodioxol-5-ylcarbonyl)piperidine that was also found to improve retention of memory in a radial maze task and in an odor-matching problem. These results define tools for enhancing long-term potentiation in vivo and confirm an important prediction from the hypothesis that long-term potentiation is a substrate of memory. 相似文献
114.
Autoradiographic techniques were used to test if positive modulators of AMPA-type glutamate receptors have regionally differentiated effects on ligand binding. Cyclothiazide, a drug with ten fold greater effects on `flip' than `flop' splice variants of the receptors, had unequal effects across the subdivisions of hippocampus; i.e., it reduced [3H]AMPA binding in field CA3 with an EC50 of 24 μM and in field CA1 and dentate gyrus with EC50s between 60 and 100 μM. The EC50 for the drug's influence on binding was also significantly lower in the superficial than in the deeper layers of the neocortex, though these differences were not as pronounced as those in the hippocampus. The ampakine CX614, a compound with a modest preference for flop variants, had a slightly lower EC50 for its effects on [3H]AMPA binding in CA1 than in CA3. This result was confirmed with [3H]fluorowillardiine binding. The effects of the ampakine in neocortex tended to be greater in the deeper than superficial layers but this did not reach statistical significance. These results indicate that differential effects of modulators on AMPA receptor subunits are reflected in their relative potency across brain subdivisions. This raises the possibility that subclasses of positive modulators will exhibit a measurable degree of selectivity in their physiological and behavioral influences. 相似文献
115.
Using radio-biotelemetry, the timecourse of recovery and sensitivity to ambient temperature (Ta) of the thermogenic response
of methylenedioxymethamphetamine (MDMA or “Ecstasy”) was examined. Ambient temperatures of 17 and 22°C produced very different
response profiles, with the lower temperature producing a hypothermic response to 10 and 15 mg/kg doses of MDMA, and the higher
temperature producing a profound hyperthermia to the same doses. Although the peak responses to the drug had subsided within
5 h of administration, residual effects, in the form of an elevation of body temperature during the “low” phase of the diurnal
cycle, were present for a further 48 h. Long-lasting disruption of the thermoregulatory system following a short series of
MDMA administrations (10 mg/kg once per day for 4 days) was shown by exposing the rats in the undrugged state to a thermoregulatory
challenge, consisting of 60-min exposure to a Ta of 30°C, at 1 week before, and at 4 weeks and 14 weeks after the drug administration.
MDMA-treated rats showed a prolonged hyperthermic response to the challenge at both post-drug intervals compared with fenfluramine-treated
rats and saline-treated controls. Thus, the results indicate both that MDMA’s thermogenic effects are more sensitive to Ta
than previously demonstrated, and that the serotonergic neurotoxicity of the drug may produce long-lasting changes in thermoregulatory
mechanisms.
Received: 7 December 1997/Final version: 23 January 1998 相似文献
116.
Rebecca J Sommer Adam J Hume Jessica M Ciak John J Vannostrand Megan Friggens Mary K Walker 《Toxicological sciences》2005,83(2):363-371
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes cardiovascular toxicity in laboratory animals, including alteration in several processes in which beta-adrenergic receptor (beta-AR) signaling plays important roles. Thus, our laboratory investigated the effects of TCDD on beta-AR expression and signal transduction. Fertile chicken eggs were injected with vehicle (corn oil), 0.24 or 0.3 pmol TCDD/g egg on incubation day 0 (D0) or D5. On D10, heart function was assessed by ECG in ovo. Exposure to TCDD increased the incidence of arrhythmias and decreased the positive chronotropic responsiveness of the heart to isoproterenol. The reduced beta-AR responsiveness was, in part, independent of any overt morphological changes in the heart as chick embryos exposed to TCDD on D5 displayed an intermediate responsiveness to beta-AR agonist in the absence of the dilated cardiomyopathy observed in chick embryos exposed to TCDD on D0. TCDD did not decrease the chronotropic response of the heart to agents that stimulate signals downstream of the beta-AR. In fact, TCDD-exposed embryos were more sensitive than controls to forskolin, increasing heart rates (HR) 21.8 +/- 3.5 beats per min (bpm) above baseline versus control values at 6.3 +/- 2.7 bpm above baseline. TCDD exposure also augmented the negative chronotropic response of the heart to verapamil, decreasing HR -23.2 +/- 7.4 bpm relative to baseline versus control embryos at -12.7 +/- 5.9 bpm below baseline. Finally, the mean cardiac beta1-AR mRNA expression in D10 embryos was not significantly altered by exposure to TCDD on D0. These findings establish that a functional end point of the developing chick heart is sensitive to TCDD exposure and that the TCDD-induced reduction in beta-AR responsiveness may result from alterations in signal transduction upstream of adenylyl cyclase. 相似文献
117.
Gloria J. Bazzoli Rebecca Stein Jeffrey A. Alexander Douglas A. Conrad Shoshanna Sofaer & Stephen M. Shortell 《The Milbank quarterly》1997,75(4):533-561
The collaboration among public–private partnerships that applied to the Community Care Network (CCN) demonstration program of the Hospital Research and Educational Trust is examined. These partnerships link broad-based community coalitions with health and human service providers in efforts to improve community health and local service delivery. Although they willingly collaborated in identifying community health needs, coordinating services, and reporting to the community, partnership participants showed less alacrity in joining forces to reduce redundancy and increase efficiency. Such patterns suggest that organizations might best profit from working together on activities that maintain existing power relations and that have the potential to add prestige and attract new clients. Collaboration in these areas may be essential to building a foundation of trust that leads to future cooperation in more sensitive areas. 相似文献
118.
119.
Mark A. Beilke Debra Riding In Rebecca Hamilton Gary A. Stone Elaine K. Jordan Gene Brashears Wayne Nusbaum David Huddleston Clarence J. Gibbs Jr. Maneth Gravell 《Journal of neuroimmunology》1991,33(2):129-143
HLA-DR expression in neuroendothelial cells (NEC) was studied during the course of SIV encephalitis in rhesus monkeys. HLA-DR determinants were detected on NEC in monkeys with SIV encephalitis, but not in control animals. In situ hybridization with an SIV probe indicated that HLA-DR expression was not a consequence of SIV replication within NEC. Cultured rhesus NEC stimulated with gamma interferon expressed HLA-DR to a higher degree than cultured brain fibroblasts or astrocytes. These data support the contention that NEC participate in retrovirus-induced inflammation and autoimmunity within the central nervous system. 相似文献
120.
Jisun Oh Matthew R Ban Brooke A Miskie Rebecca L Pollex Robert A Hegele 《Lipids in health and disease》2007,6(1):7