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M Rothman 《Canadian Metallurgical Quarterly》1997,18(6):437-447
To study factors influencing the distribution of local anaesthetics in the subarachnoid space, an in vitro model is constructed which takes into account the natural curvature of the spinal column and the volume occupation of spinal cord and nerve fibres to resemble the in vivo situation. Three Marcaine solutions of different baricity (1003, 1008, 1030 kg/m3) are injected with a 22 G, a 27 G Quincke point needle and a 18 G multiport catheter into three models of non-pathological spinal columns with injection flow speeds of 0.6, 0.2 or 0.1 ml/s. Methylene blue is added for visual and qualitative assessment of drug distribution. Baricity is the main actor in the spreading of the drug solution. For all other variables, no significant difference is found after ten minutes, though the initial distribution may differ according to the geometry used. A hypobaric solution yields a remarked difference between fast and slower injections. The position of the catheter should be controlled. 相似文献
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AK Henderson D Rosen GL Miller LW Figgs SH Zahm SM Sieber N Rothman HE Humphrey T Sinks 《Canadian Metallurgical Quarterly》1995,6(5):544-546
We conducted a nested case-control study with 1,925 women enrolled in a polybrominated biphenyl (PBB) registry to examine the association between breast cancer and serum PBBs. Twenty women who developed breast cancer were matched to 290 control subjects on sex, race, and age. Women with serum PBB levels of 2.0-3.0 parts per billion (ppb) [odds ratio (OR) = 3.5; 95% confidence interval (CI) = 0.9-13] or 4.0 ppb or greater (OR = 3.1; 95% CI = 0.8-12) had a higher estimated risk for breast cancer than women with less than 2.0 ppb. The odds ratios were unchanged when available breast cancer risk factors were included in the analysis. 相似文献
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Pharmacological study of Phe-Met-Leu-Phe-amide (FMRFa) receptors is hindered by the lack of selective ligands. The classification of these selective ligands is further hampered by the limited availability of functional assays. In this study, we evaluated several synthetic FMRFa analogs for agonist and antagonist activity by measuring their abilities to produce [35-S]-GTP-gamma-S stimulation or to inhibit FMRFa-induced [35S]-GTP-gamma-S binding in squid optic lobes. Analogs included acetyl-Phe-norLeu-Arg-Phe-amide (acFnLRFa), desamino-Tyr-Phe-Leu-Arg-amide (daYFLRa), desamino Tyr-Phe-norLeu-Arg-Phe-amide (daYFnLRFa), desamino Tyr-Phe-norLeu-Arg-[TIC]-amide (daYFnLR[TIC]a), desamino Tyr-Trp-norLeu-Arg-amide (daYWnLRa), (D)-Tyr-Phe-norLeu-Arg-Phe-amide (D)-YFnLRFa), Phe-Leu-Arg-Phe-amide (FLRFa), and the D-amino acid analogs of FMRFa (D-FMRFa, F-(D)-MRFa and FM-(D)-RFa). For agonist studies, full dose-response curves were generated and analyzed for potency and efficacy (maximal percent effect). FMRFamide as well as analogs ac-FnLRFa, daYFnLRFa, daYFnLR[TIC]a, D-YFnLRFa, FLRFa, and (D)-FMRFa stimulated [35S]-GTP-gamma-S binding. Analogs daYWnLRa, daYFLRa, F-(D)-MRFa, and FM-(D)-RFa failed to stimulate either [35S]-GTP-gamma-S binding or to inhibit FMRFa-induced [35S]-GTP-gamma-S binding. The rank order of potency was daYFnLRFa > or = daYFnLRF[TIC]a > acFnLRFa > (D)YFnLRFa > FLRFa > or = FMRFa > (D)-FMRFa. The order of efficacy was daYFnLRFa = acFnLRFa = (D)-YFnLRFa > FLRFa = FMRFa > or = (D)-FMRFa > or = daYFnLRF[TIC]a. Peptide analog daYFnLR[TIC]a was less efficacious (59% maximal stimulation) than analogs daYFnLRFa, acFnLRFa, and (D)-YFnLRFa (113-146% maximal stimulation). A maximal concentration of daYFnLR[TIC]a (10 microM) reduced daYFnLRFa, acFnLRFa, and (D)-YFnLRFa induced [35S]-GTP-gamma-S stimulation, indicating that daYFnLR[TIC]a is a partial agonist at the receptor stimulated by the FMRFamide analogs. Analysis of the structural requirements needed for promoting [35S]-GTP-gamma-S binding show that elongation (i.e., daYFnLRFa, D-YFnLRFa) or modification of Phe1 (ac-FnLRFa) leads to increased efficacy and potency. Moreover, elimination of the C-terminal Phe (daYWnLRa, daYFLRa,) leads to a loss of biological activity. However, substitution with L-1,2,3,4 tetrahydroisoquinoline-3-carboxylic acid, a rigid analog of the C-terminal Phe (daYFnLR[TIC]a), leads to decreased efficacy but not loss of potency. The data suggest that immobilization or modification of the C-terminal Phe may produce highly selective and potent FMRFamide antagonists. These results agree with published receptor radioligand studies and indicate that the [35S]GTP-gamma-S assay may be useful in classifying novel FMRFamide-selective ligands. 相似文献
26.
BK Rothman 《Canadian Metallurgical Quarterly》1998,65(3):201-9; discussion 215-23
Biomedical practices and research in procreation are shaped by three ideologies deeply rooted in American society: patriarchy with its control of women's bodies in the interest of men's procreative concerns and with its focus on 'seeds' and therefore genetics; technology as an ideology of efficiency, productivity, rationality, and control; and capitalism both as an ideology and as a practice, a mechanism that markets technologies of procreation. 相似文献
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Improvements on a localized, automatic shimming method described by Gruetter and Boesch (J. Magn. Reson. 96, 323-334 (1992)) and Gruetter (Magn. Reson. Med. 29, 804-811 (1993)) are presented. A spin-echo sequence employing a double sech refocusing scheme is used to acquire a field map along linear projections that improves the signal-to-noise ratio by at least a factor of two over the stimulated echo sequence previously used. To further improve the reliability of shim adjustments, a variance-weighted polynomial regression analysis is performed. This also extends the scope of application of this technique to global shimming. Localized 1H spectra of human brain shimmed by this method are presented. 相似文献
29.
3-Benzyl-3-ethyl-2-piperidinone (3-BEP) belongs to a family of compounds that includes alpha- substituted gamma-butyrolactones, gamma-thiobutyrolactones, 2-pyrrolidinones and hexahydro-2H-azepin-2-ones. Many of these drugs exhibit potent in vivo anticonvulsant activity in mice. Previous electrophysiological studies demonstrated that they potentiate gamma-aminobutyric acid- (GABA) mediated chloride currents. This GABAA receptor modulation was thought to be the main mechanism of anticonvulsant activity. We report that 3-BEP also modulates sodium channels. It decreased sodium currents in cultured rat hippocampal neurons in a voltage- and concentration-dependent manner. The drug's apparent affinity increased as neurons were depolarized. At a holding potential of -60 mV, the apparent IC50 was 487 microM. This concentration is comparable to its EC50 for GABAA modulation (575 microM). Current blockade occurred over all activation voltages tested. The steady state inactivation curve was shifted by 600 microM 3-BEP from V50 = -65.3 mV to -72.0 mV, and recovery from inactivation was slowed from tau = 4.9 to 12.8 msec. Sodium current inhibition was not observed for three related compounds, suggesting a degree of chemical specificity for this activity. We conclude that in addition to its known effects on GABAA receptors, 3-BEP modulates sodium channels. Therefore this compound may prevent seizures by both enhancing inhibition and diminishing neuronal excitability. 相似文献
30.
Davidson Richard J.; Schwartz Gary E.; Rothman Larry P. 《Canadian Metallurgical Quarterly》1976,85(6):611
Assessed the cortical concomitants of selective mode-specific attention in Ss differing in the capacity for sustained attentional involvement. 10 high- and 10 low-scoring Ss on the Tellegen Absorption Scale were required to (a) simply attend to either a randomly flashing light or a randomly produced tapping sensation on the forearm during one block of trials and to (b) count the flashes and the taps during another trial block. The EEG was recorded from the left occipital and left sensorimotor regions and was filtered for alpha activity and quantified on line. Selective mode-specific attention produced reliable shifts in cortical patterning between kinesthetic and visual attention trials. During the counting condition, high-scoring Ss showed significantly greater specificity in cortical patterning than did low-scoring Ss. This difference was primarily a function of high-scoring Ss' ability to inhibit activation in the occipital region while counting taps. Findings suggest that high scores on the Absorption scale are associated with a flexible attentional style and that, given the requisite task demands, attentionally absorbed Ss show greater mode-specific cortical patterning during selective attention than do low scorers. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献