Biomedical subjects

J F Dashe

Publications and source records attributed to J F Dashe.

5 recordsLinked to original sources

PubMed2000

Effect of citicoline on ischemic lesions as measured by diffusion-weighted magnetic resonance imaging. Citicoline 010 Investigators.

We examined the effect of the neuroprotective and neuroreparative agent citicoline on the growth of cerebral ischemic lesions in a double-blind placebo-controlled study involving patients with acute ischemic stroke using diffusion-weighted magnetic resonance imaging (DWI). Patients with acute ischemic stroke symptom onset 24 hours or less before the start of treatment, National Institutes of Health Stroke Scale (NIHSS) scores of 5 or higher, and lesions of 1 to 120 cc in cerebral gray matter by DWI were enrolled. DWI, T2-weighted magnetic resonance imaging (MRI), perfusion-weighted MRI, and magnetic resonance angiography were obtained at baseline, week 1, and week 12. Citicoline (500 mg/day) was administered orally for 6 weeks, and patients were followed for 12 weeks. The primary assessment was progression of ischemic lesion volume from baseline to 12 weeks as measured by MRI. A total of 100 patients entered the study. The primary MRI analysis included 40 placebo-treated patients and 41 citicoline-treated patients with both baseline and week 12 MRI data and failed to demonstrate a significant difference in lesion volume change from baseline to week 12. From baseline to week 12, ischemic lesion volume [all values mean (SE)] expanded by 180% (107) among placebo-treated patients compared with 34% (19) among citicoline-treated patients. In a secondary analysis, lesion volume decreased from week 1 to week 12 by 6.9 cc (2.8) on placebo versus 17.2 cc (2.6) on citicoline. Baseline variables that were predictors of change in lesion size over 12 weeks were the volume of hypoperfusion (strongest association), baseline NIHSS score, lesion volume on DWI, arterial lesion by magnetic resonance angiography, and categorized elapsed time (< or =12 or >12 hours) from stroke onset to first dose. A marked association between lesion volume reduction and improvement of NIHSS score by seven or more points was observed. Significant correlations between lesion volumes and clinical measures were found, replicating values reported in the literature for smaller case series. We observed a reduction in lesion volume growth from baseline to week 12 with citicoline treatment, with a significantly greater reduction in volume from week 1 to week 12 with citicoline. We found a significant inverse relationship between lesion volume change over 12 weeks as measured by MRI and clinical outcome for ischemic stroke. This relationship supports the role of DWI as a surrogate marker of clinically meaningful lesion progression in stroke clinical trials. The hypothesis that citicoline reduces lesion growth and improves clinical outcome will be tested further.

Aged↗

PubMed1997

Carotid occlusive disease and stroke risk in coronary artery bypass graft surgery.

To clarify the perioperative stroke risk in patients with carotid stenosis or occlusion having coronary artery bypass graft (CABG) surgery, we retrospectively reviewed the records of 1,022 patients who had CABG during a 2-year period (1992, 1993). Of these, 224 had preoperative carotid duplex studies, usually for bruit or remote symptoms. We analyzed clinical and neuroimaging findings for all patients who had strokes to determine infarct topography and presumed mechanism, either low perfusion or embolism. Perioperative stroke was always ipsilateral to severe (> or = 70%) carotid disease, and occurred in 2 (8.0%) of 25 patients with carotid occlusion, 3 (50.0%) of 6 patients with 70 to 99% stenosis, and 9 (4.7%) of 193 patients with less than 70% stenosis. Borderzone infarcts occurred with all degrees of carotid stenosis. Stroke frequency had a positive correlation with the degree of carotid stenosis. Eight (1.0%) of the 798 patients not studied by carotid duplex had stroke in various vascular distributions. Overall, stroke occurred in 22 (2.2%) of the 1,022 patients having CABG surgery. Our results suggest that while the overall risk of perioperative stroke in CABG surgery is low, the risk is increased in patients with severe extracranial carotid stenosis or occlusion. The role of carotid disease and the mechanism of borderzone infarction in CABG surgery remain unsettled.

Aged↗

PubMed1996

Clinical outcome in ischemic stroke predicted by early diffusion-weighted and perfusion magnetic resonance imaging: a preliminary analysis.

Perfusion and diffusion-weighted magnetic resonance imaging (MRI) can demonstrate, respectively, cerebral ischemia and ischemic brain injury in the first several hours after onset of symptoms, when proton density and T2-weighted MRI may appear normal. It is hypothesized that these techniques could distinguish regions destined for infarction from those that will not progress to infarction. We provide preliminary evidence from an analysis of 19 patients with severely disabling clinical deficits attributable to ischemia in at least an entire division of the middle cerebral artery, that initial perfusion and diffusion MRI were more accurate than conventional MRI in predicting no, partial or complete improvement--17 of 19 cases (p < 0.0001) versus 10 of 19 cases, respectively. In the subset of patients studied within 6 h of onset, diffusion/perfusion MRI was an even better predictor than conventional MRI--11 of 12 versus four of 12, respectively. In this small sample of patients with severe clinical deficits, perfusion and diffusion MRI were highly accurate in distinguishing those who would improve from those who would not. These results need to be confirmed in a larger prospective study, which may support a future role in the initial screening, selection, and evaluation of patients with stroke for acute pharmacologic interventions.

Brain Ischemia↗

PubMed1989

Electron-lucent degenerating geniculate terminals in cat striate cortex.

Degenerating geniculate axon terminals in cat striate cortex have been previously described as electron-dense. After electrolytic lesion of the lateral geniculate nucleus, we observed degenerating terminals in layer 4 of striate cortex which were electron-lucent. The lucent terminals --which co-exist with the dense terminals--are characterized by a pale matrix, large size, distorted mitochondria, and a paucity of synaptic vesicles. They preferentially (82.5%) contact dendritic spines. Lucent terminals were common in layer 4, rare in layer 6, and absent from layers 1 through 3 and layer 5. This distribution is consistent with the projection of the lateral geniculate nucleus to the striate cortex. Thus, geniculate terminals undergo both the electron-lucent and electron-dense degeneration reactions in cat striate cortex, and the lucent terminals make a significant contribution to the amount of degeneration present. The relationship of lucent degeneration to other forms of degeneration is discussed.

Animals↗

PubMedDate not supplied

Clinical correlations of diffusion and perfusion lesion volumes in acute ischemic stroke.

The aim of this study was to describe the clinico-radiological correlations of magnetic resonance (MR) perfusion and diffusion-weighted imaging (DWI) abnormalities in ischemic stroke. Eighteen patients had undergone MR imaging and clinical evaluation within 24 h of symptom onset and at or after 7 days. During the first 24 h the volume of perfusion abnormality (measured on the relative mean transit time map) was larger than the DWI lesion in 12/18 patients. In 6/18 patients the DWI lesion volume was larger. Acutely (<24 h) all lesion volumes showed a significant correlation with acute clinical severity measured by the National Institutes of Health Stroke Scale score. The correlations of the hypoperfusion volume (rho = 0.86, p = 0.0001) and the volume 'tissue at risk' (larger than the DWI and perfusion lesion volumes, rho = 0.86, p = 0. 0001) with acute clinical severity were slightly higher than for the DWI lesion volume (rho = 0.76, p = 0.0001). The difference between the volume of tissue at risk (acutely) and the infarct on follow-up T(2)-weighted imaging correlated significantly with change in clinical severity from acute to chronic time points (rho = 0.72, p = 0.001). Such clinico-radiological relationships may support the use of DWI and perfusion MR in decisions concerning the administration and evaluation of stroke therapies.

Acute Disease↗