Journal of neurotrauma
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Journal of neurotrauma · Jan 2002
Misclassification and treatment effect on primary outcome measures in clinical trials of severe neurotrauma.
The power of clinical trials depends mainly on the choice of the primary outcome measure, the statistical test, and the sample size. The most widely used outcome measure has been the five-category Glasgow Outcome Scale (GOS). Contrary to intuition, we show that more categories do not necessarily increase the power of a trial and actually can decrease power. ⋯ In the recently completed hypothermia trial, the use of a dichotomized GOS (good recovery/moderate disability versus severe disability/vegetative/dead) is shown to be more sensitive than use of three or more categories of the GOS. The results point to the importance of training study investigators who will collect the outcome data. The results also indicate that the number of categories should be carefully determined using the pilot data or the data from phase II trials.
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Journal of neurotrauma · Dec 2001
Comparative StudyContrasting effects of dopamine therapy in experimental brain injury.
Management of cerebral perfusion pressure (CPP) is thought to be important for the treatment of traumatic brain injury (TBI). Vasopressors have been advocated as a method of increasing mean arterial blood pressure (mABP) and cerebral perfusion pressure (CPP) in the face of rising intracranial pressure (ICP). There are unresolved issues and theoretical risks about this therapy. ⋯ This occurred in the absence of ADCw changes, except in the contralateral hippocampus, where both water content and ADCw values rose with treatment, suggesting extracellular accumulation of water. In conclusion, although dopamine is capable of partially restoring CBF after injury, situations exist in which dopamine therapy worsens the swelling process. It is possible therefore that subgroups of patients exist who experience adverse effects of vasopressor treatment, and consequently the effects of vasopressor therapy in the clinical setting need to be more carefully evaluated.
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Journal of neurotrauma · Nov 2001
Neurobehavioral assessment of outcome following traumatic brain injury in rats: an evaluation of selected measures.
Neurobehavioral assessment of outcome has played an integral part in traumatic brain injury (TBI) research. Given the fundamental role of neurobehavioral measurement, it is critical that the tasks used are of the highest psychometric quality. The purpose of this paper is to evaluate several, commonly used neurobehavioral measures along the dimensions of reliability, sensitivity, and validity. ⋯ In the assessment of validity, the results of a factor analysis supported the convergent and discriminative validity of the measures. And in cases in which the preclinical and clinical research have assessed the same construct, the animal model neurobehavioral measures had predictive (or external) validity. Thus, according to the psychometric standards by which measurement instruments are evaluated, the results indicated that these measures provide a valid assessment of neurobehavioral function after fluid percussion TBI.
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Journal of neurotrauma · Nov 2001
Comparative StudyComparison of dopamine and norepinephrine after traumatic brain injury and hypoxic-hypotensive insult.
After severe brain trauma, blood-brain barrier disruption and alteration of cerebral arteriolar vasoreactive properties may modify the cerebral response to catecholamines. Therefore, the goal of the present study was to compare the effects of dopamine and norepinephrine in a model of brain injury that consisted of a weight-drop model of injury complicated by a 15-min hypoxic-hypotensive insult (HH). Sprague-Dawley rats (n = 7 in each group) received, after brain injury, an infusion of either norepinephrine (TNE group) or dopamine (TDA group) in order to increase cerebral perfusion pressure (CPP) above 70 mm Hg. ⋯ LCBF decreased similarly in T, TNE and TDA groups. In conclusion, norepinephrine and dopamine are not able to restore values of CPP above 70 mm Hg in a model of severe brain trauma. Furthermore, their systemic vasopressor properties are altered.
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After contusion-derived spinal cord injury, (SCI) there is localized tissue disruption and energy failure that results in early necrosis and delayed apoptosis, events that contribute to chronic central pain in a majority of patients. We assessed the extent of contusion-induced apoptosis of neurons in a known central pain-signaling pathway, the spinothalamic tract (STT), which may be a contributor to SCI-induced pain. ⋯ Apoptosis in the injured spinal cord correlated well with prompt decreases in Bcl-xL protein levels and Bcl-xL/Bax protein ratios at the contusion site. We interpret these results as evidence that regulation of Bcl-xL may play a role in neural sparing after spinal injury and pain-signaling function.