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Unlike recordings derived from optic nerve or corpus callosum, compound action potentials (CAPs) recorded from rodent spinal cord white matter (WM) have a characteristic single-peak shape despite the heterogeneity of axonal populations. Using a double sucrose gap technique, we analyzed the CAPs recorded from dorsal, lateral, and ventral WM from mature rat spinal cord. The CAP decay was significantly prolonged with increasing stimulus intensities suggesting a recruitment of higher threshold, slower conducting axons. At 3.5 mm conduction distance, a hidden higher threshold, slower conducting component responsible for prolongation of CAP decay was uncovered in 22 of 25 of dorsal WM strips by analyzing the stimulus-response relationships and a normalization-subtraction procedure. This component had a peak conduction velocity (CV) of 5.0 ± 0.2 (SE) m/s as compared with 9.3 ± 0.5 m/s for the lower threshold peak (P < 0.0001). Oxygen-glucose deprivation (OGD), along with its known effects on CAP amplitude, significantly (P < 0.015) shortened the CAP decay. The hidden higher threshold, slower conducting component showed greater sensitivity to OGD compared with the lower threshold, faster conducting component, suggesting a differential sensitivity of axonal populations of spinal cord WM. At longer conduction distances and lower temperatures (9.8 mm, 22-24°C), the slower peak could be directly visualized in CAPs at higher stimulation intensities. A detailed analysis of single-peak CAPs to identify their fast and slow conducting components may be of particular importance for studies of axonal physiology and pathophysiology in small animals where the conduction distance is not sufficiently long to separate the CAP peaks. 相似文献
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Masucci GL Yu E Ma L Chang EL Letourneau D Lo S Leung E Chao S Hyde D Gorgulho A Muacevic A Larson DA Fehlings MG Sahgal A 《Expert review of anticancer therapy》2011,11(12):1923-1933
Spinal metastases are a relatively common manifestation in advanced cancer patients. Low-dose conventional radiotherapy has long been the mainstay of treatment under the assumption that patients have a limited life expectancy in the order of 3-6 months. However, with new developments in systemic therapies, patients are surviving longer than expected. As the spinal retreatment rates, secondary to conventional radiation, can approach 20-50%, retreatments are likely to be more frequent. Rather than a second course of even lower-dose conventional radiation, spine stereotactic body radiotherapy (SBRT) has been developed predominantly to overcome the limitations of conventional reirradiation. Spine SBRT permits a second course of high-dose radiation aimed at local tumor control while sparing the spinal cord, and other surrounding normal tissues, of a toxic dose. The focus of this review is to provide an overview of reirradiation spine SBRT, and address key issues surrounding safe and effective practice. 相似文献
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A Choppin I Irwin L Lach MG McDonald AE Rettie L Shao C Becker MP Palme X Paliard S Bowersox DM Dennis P Druzgala 《British journal of pharmacology》2009,158(6):1536-1547
Background and purpose:
Tecarfarin (ATI-5923) is a novel vitamin K epoxide reductase inhibitor that is metabolized by esterase (mainly human carboxylesterase 2) to a single major metabolite, ATI-5900, in rats, dogs and humans. Tecarfarin is not significantly metabolized by CYP450 enzymes. The objective of this study was to test and compare the efficacy of tecarfarin with that of warfarin, when administered either intravenously or once a day orally, to produce stable anticoagulation in beagle dogs.Experimental approach:
Effects on coagulation were assessed by measuring the activity levels of Factor VII and Factor X and thromboplastin-induced coagulation times, reported as prothrombin time (PT).Key results:
Continuous intravenous infusions and oral administration of tecarfarin and warfarin caused a dose-dependent decrease in activity of Factor VII and Factor X, and associated increase in PT. Intravenous fresh frozen canine plasma or subcutaneous vitamin K1 treatment reversed the anticoagulant effects of orally administered tecarfarin. Consistent with the inhibitory effects of amiodarone on CYP2C9, co-administration of amiodarone significantly increased the anticoagulation effect of warfarin and plasma warfarin concentrations. In contrast, amiodarone had no effect on the anticoagulation induced by tecarfarin or tecarfarin plasma concentrations in this model.Conclusions and implications:
Overall, the data presented herein indicate that tecarfarin, via a vitamin K-dependent mechanism, causes changes in key parameters of haemostasis in beagle dogs that are consistent with effective anticoagulation. Compared to warfarin it has a decreased potential to interact metabolically with drugs that inhibit CYP450 enzymes and, therefore, may offer an improved safety profile for patients. 相似文献77.
Murphy AM Milo-Manson G Best A Campbell KA Fehlings D 《Developmental medicine and child neurology》2008,50(7):510-514
This randomized double blind AB/BA cross-over trial evaluates the effect of oral modafinil versus placebo on spasticity, function, and quality of life in children with cerebral palsy (CP). Outcomes were measured at the start and end of both 8-week treatment periods (modafinil and placebo). The order of the treatment periods was randomly assigned. There was a 4-week wash-out period between treatments. Primary outcomes include the Modified Ashworth Score (MAS), and the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD), a disorder-specific quality of life measure. Ten children were randomized and eight children completed the study. The mean age of participants was 11 years 5 months (SD 1 y 5 mo, range 8 y 8 mo-12 y 11 mo). Five of the participants were male and three female. Seven children had a diagnosis of spastic quadriplegic CP and one child had spastic diplegia with overflow tone to the upper extremities. The Gross Motor Function Classification System ranged from Level III to V with one child at Level III, six children at Level IV, and one at Level V. The CPCHILD pre- to post-total scores showed a slight improvement in quality of life during the placebo period and a slight deterioration in the modafinil period (overall mean change of 7.1, SD 7.6). A t-test between post differences was statistically significant (t=2.65, p=0.03) in favor of the placebo period. The MAS for elbow flexors, ankle flexors, and hip adductors did not show any significant reduction post-modafinil or post-placebo (p values ranged from 0.41-0.79). This study did not find evidence that modafinil reduces spasticity or has a positive impact on quality of life in children with spastic CP. 相似文献
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Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: clinical trial design 总被引:1,自引:0,他引:1
Lammertse D Tuszynski MH Steeves JD Curt A Fawcett JW Rask C Ditunno JF Fehlings MG Guest JD Ellaway PH Kleitman N Blight AR Dobkin BH Grossman R Katoh H Privat A Kalichman M;International Campaign for Cures of Spinal Cord Injury Paralysis 《Spinal cord》2007,45(3):232-242
The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the fourth of four papers. Here, we examine the phases of a clinical trial program, the elements, types, and protocols for valid clinical trial design. The most rigorous and valid SCI clinical trial would be a prospective double-blind randomized control trial utilizing appropriate placebo control subjects. However, in specific situations, it is recognized that other trial procedures may have to be considered. We review the strengths and limitations of the various types of clinical trials with specific reference to SCI. It is imperative that the design and conduct of SCI clinical trials should meet appropriate standards of scientific inquiry to insure that meaningful conclusions about efficacy and safety can be achieved and that the interests of trial subjects are protected. We propose these clinical trials guidelines for use by the SCI clinical research community. 相似文献
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