Showing papers by "Michael E. Sughrue published in 2004"

Anti-adhesion molecule strategies as potential neuroprotective agents in cerebral ischemia: A critical review of the literature

Abstract: Despite recent advances in the understanding of the pathophysiology of cerebral ischemia, current approaches attempting to prevent ischemic brain damage after an acute stroke remain quite inadequate. Today, ischemic stroke remains the third leading cause of death in industrialized nations, and the leading cause of disability requiring long term institutional care in the U.S and other industrialized nations. While one treatment, tissue plasminogen activator, has shown efficacy in clinical trials, safety concerns limit its role in clinical practice to a narrow time window of use. Acute cerebral ischemia has been shown to evoke a profound and deleterious upregulation of the inflammatory response, initiated within the cerebral microvasculature. Recently, research efforts have focused on targeting individual components of the inflammatory cascade, such as leukocyte activation and adhesion, in an attempt to develop potential neuroprotective agents. While these strategies have shown promise preclinically, clinical trials have yet to show clear benefit. Here, we review the current understanding of the pathophysiologic consequences of acute cerebral ischemic injury. Additionally, we discuss the role of the inflammatory cascade, with specific attention given to the deleterious role played by leukocyte activation and adhesion in stroke. Finally, relevant efforts to translate these basic science observations into clinical efficacy in acute stroke trials are critically reviewed.

Pilomyxoid astrocytoma: a review.

Abstract: Pilomyxoid astrocytoma (PMA) is a recently described type of brain tumor. PMA shares similar features with pilocytic astrocytoma (PA), the most common central nervous system (CNS) tumor in the pediatric population, yet displays subtle histologic differences. Previous studies have shown PMA to behave more aggressively than PA, with shorter progression-free and overall survival as well as a higher rate of recurrence and CNS dissemination. These findings suggest that PMA may be a unique and distinct neoplasm. This review summarizes the histologic, clinical, and radiographic characteristics of PMA. In addition, the current treatment options and research endeavors involving this disease are described. Increased recognition of PMA within the medical community has the potential to affect the treatment and prognosis of pediatric low-grade astrocytomas.

Systems and methods for qualifying symmetry to evaluate medical images

Abstract: A method and related software are provided for analyzing images such as computerized tomography images obtained from a standard perfusion CT software package. This method converts image values to relative differences, which represents meaningful side-to-side asymmetry. This conversion may be performed by comparing a small region of the scan to the corresponding region in the contralateral hemisphere, quantifying the degree of relative difference using statistical techniques, and representing this quantity of relative difference in a two dimensional or three diemnsional relative difference map.

A modified transorbital baboon model of reperfused stroke.

Abstract: BACKGROUND AND PURPOSE Although pathophysiological studies of focal cerebral ischemia in nonhuman primates can provide important information not obtainable in rodent models, primate experimentation is limited by considerations of cost, availability, effort, and ethics. A reproducible and quantitative model that minimizes the number of animals necessary to detect differences between treatment groups is therefore crucial. METHODS Eight male baboons (weight, 22+/-2 kg) underwent left transorbital craniectomy followed by 1 hour of temporary ipsilateral internal carotid artery occlusion at the level of the anterior choroidal artery together with bilateral temporary occlusion of both anterior cerebral arteries (A1) proximal to the anterior communicating artery. A tightly controlled nitrous oxide-narcotic anesthetic allowed for intraoperative motor evoked potential confirmation of middle cerebral artery (MCA) territory ischemia. Animals survived to 72 hours or 10 days if successfully self-caring. Outcomes were assessed with a 100-point neurological grading system, and infarct volume was quantified by planimetric analysis of both MRI and triphenyltetrazolium chloride-stained sections. RESULTS Infarction volumes (on T2-weighted images) were 32+/-7% (mean+/-SEM) of the ipsilateral hemisphere, and neurological scores averaged 29+/-9. All animals demonstrated evidence of hemispheric infarction, with damage evident in both cortical and subcortical regions in the MCA vascular territory. Histologically determined infarction volumes differed by <3% and correlated with absolute neurological scores (r=0.9, P:=0.003). CONCLUSIONS Transorbital temporary occlusion of the entire anterior cerebral circulation with strict control of physiological parameters can reliably produce reperfused MCA territory infarction. The magnitude of the resultant infarct with little interanimal variability diminishes the potential number of animals required to distinguish between 2 treatment regimens. The anatomic distribution of the infarct and associated functional deficits offer comparability to human hemispheric strokes.

Effectively bridging the preclinical/clinical gap: the results of the ASTIN trial.

Abstract: To the Editor: Recently, the results of the Acute Stroke Therapy by Inhibition of Neutrophils (ASTIN) were published.1 In this trial, 966 patients presenting within 6 hours of acute stroke received varying doses of either placebo or UK-279,276, a CD11b/CD18 inhibitor. Additionally, a subgroup of 204 patients was co-administered tissue plasminogen activator (tPA) when clinically appropriate. The trial was stopped early when interim analysis demonstrated futility in achieving the primary end point of increased functional improvement from the patient’s baseline as measured by the Scandinavian Stroke Scale (SSS) at 90 days. Post hoc analysis found that patients co-administered tPA and UK-279,276 exhibited a mean improvement of 1.6 points on the SSS, but this study was neither designed nor powered to achieve statistical significance in this group. While the study utilized a novel approach to clinical trial design and management, there are limitations in the design of this study that, while stated by the authors, merit additional attention. The first of these is the study’s diminished emphasis on UK-279,276 as an adjuvant for …

Objective quantification of perfusion-weighted computed tomography in the setting of acute aneurysmal subarachnoid hemorrhage

Abstract: Perfusion-weighted computed tomography (CTP) is a relatively recent innovation that estimates a value for cerebral blood flow (CBF) using a series of axial head CT images which tracks the time course of signal from an administered bolus of intravenous contrast. We introduce a novel computer-based method for objective quantification of CBF values calculated from CTP images. Our method corrects for the inherent variability of the CTP methodology seen in the subarachnoid hemorrhage (SAH) patient population to potentially aid in the diagnosis of cerebral vasospasm (CVS). This method analyzes and quantifies side-to-side asymmetry of CBF and represents relative differences in a construct termed a relative difference map (RDM). Herein, we present our preliminary results that show that analysis of histograms of the RDM in left and right hemispheres, as well as different vascular territories of the brain, can be used for detection and diagnosis of cerebral vasospasm in patients with SAH. While this method has been designed specifically to analyze postprocessed CTP images, it could be potentially applied to quantification and analysis of MR perfusion data, as well.