bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased CD8
+
T Cells Associated With
Chlamydia pneumoniae
in Symptomatic Carotid Plaque
Authors: Nadareishvili Zurab G. , Koziol Deloris E. , Szekely Brian , Ruetzler Christl , LaBiche Ronald , McCarron Richard , DeGraba Thomas J.
Published: October 2007

Background and Purpose

—

The presence of
Chlamydia pneumoniae
has been reported in carotid atheroma, but its causative effect in the activation of an atherosclerotic plaque to a prothrombotic state remains unproved. Antigen- mediated activation of T lymphocytes within plaque may represent a mechanism by which infection can result in plaque conversion. The goal of the present study was to characterize the T-cell subtype profile related to the presence of
C pneumoniae
in patients with symptomatic versus asymptomatic carotid atherosclerosis.

Methods

—

We studied 14 plaques (5 symptomatic and 9 asymptomatic) positive for
C pneumoniae
confirmed by polymerase chain reaction and 14 plaques (6 symptomatic and 8 asymptomatic) from age- and stenosis-matched patients negative for
C pneumoniae
by polymerase chain reaction. T-cell subpopulations of T-helper, T-cytotoxic, and T-memory lymphocytes were identified through indirect enzyme immunohistochemistry with anti-CD3+, anti-CD4+, anti-CD8+, and anti-CD45RO+ monoclonal antibodies, respectively. Results are expressed as the number of positive cells per millimeter squared.

Results

—

In the absence of
C pneumoniae
, symptomatic plaques had a modest but significant increase of CD3+ (89.6 versus 55.3,
P
=0.013), CD4+ (57.3 versus 32.7,
P
=0.01), and CD45RO+ (82.8 versus 43.7,
P
=0.007), but not CD8+ T cells (28.5 versus 25.5,
P
=0.245) compared with asymptomatic. However, in the presence of
C pneumoniae
, there was significant increase of all T-lymphocyte subtypes in symptomatic plaques, including CD8+ (76.8 versus 30.3,
P
=0.03), CD3+ (192.1 versus 80.4,
P
=0.004), CD4+ (111.9 versus 37.9,
P
=0.003), and CD45RO+ (120.2 versus 72.9,
P
=0.003) cells compared with asymptomatic plaques. With use of 2-way ANOVA, both the presence of chlamydia and symptoms were associated with significantly higher T-cell counts (
P
<0.005 for all subtypes).

Conclusions

—

Although all patients with symptomatic disease show a modest elevation in the concentration of intraplaque lymphocytes, a preferential increase in CD8+ class I-restricted T cells is observed in symptomatic carotid plaque positive for
C pneumoniae
. These data provide incentive to further explore the role of
Chlamydia
in the modification of immune-mediated mechanisms in active atherosclerotic plaque.
Low Levels of High-Density Lipoprotein Cholesterol Are Associated With Echolucent Carotid Artery Plaques
Authors: Mathiesen Ellisiv B. , Bønaa Kaare H. , Joakimsen Oddmund
Published: October 2007

Background and Purpose

—

Ultrasound-assessed plaque morphology is an independent predictor of ischemic stroke. The purpose of this population-based cross-sectional nested case-control study was to examine the risk factors associated with carotid plaque morphology.

Methods

—

Ultrasonography of the right carotid artery was conducted on 6727 participants in a population health survey (response rate 79%). Plaque echogenicity, defined as reflectance of the emitted ultrasound signal, was scored as echolucent, predominantly echolucent, predominantly echogenic, or echogenic. Information on cardiovascular risk factors in all 216 participants who had carotid stenosis and in 223 control subjects matched by age and sex who did not have carotid stenosis was obtained from measurements of blood pressure, weight, height, and nonfasting blood samples and from a self-administered questionnaire.

Results

—

In both univariate and multivariate analyses, low levels of HDL cholesterol and increasing degree of stenosis were independently associated with an increased risk of having an echolucent plaque. For 1-SD increase in HDL cholesterol, the adjusted odds of being in a lower plaque echogenicity category decreased by ≈30% (OR 0.69, 95% CI 0.52 to 0.93).

Conclusions

—

These findings indicate that low levels of HDL cholesterol are associated with an increased risk of having echolucent, rupture-prone atherosclerotic plaques.
Combination of a Free Radical Scavenger and Heparin Reduces Cerebral Hemorrhage After Heparin Treatment in a Rabbit Middle Cerebral Artery Occlusion Model
Authors: Zhao Bing-Qiao , Suzuki Yasuhiro , Kondo Kazunao , Ikeda Yasuhiko , Umemura Kazuo
Published: October 2007

Background and Purpose

—

We sought to investigate the effects of EPC-K1, a free radical scavenger, on reducing heparin-produced cerebral hemorrhage in a rabbit model of middle cerebral artery (MCA) photothrombosis and to investigate whether the combination of EPC-K1 and heparin enhances neuroprotection from cerebral ischemic damage.

Methods

—

In the heparin-alone group (n=8), heparin was administered intravenously for 24 hours, starting from 3 hours after MCA occlusion. In the EPC-K1-alone group (n=8), EPC-K1 was administered as a bolus injection (10 mg/kg) twice at 3 and 6 hours after MCA occlusion. In the combination group (n=8), EPC-K1 and heparin both were administered as in the single-drug procedures. In the vehicle group (n=10), saline were infused for 24 hours.

Results

—

Heparin prolonged activated partial thromboplastin time by ≈3 times that of control animals. In the heparin-treated animals, the hemorrhage size was significantly increased (
P
<0.0001) and neurological symptoms were significantly worse (
P
<0.01) than in control animals at 48 hours. The combination of EPC-K1 and heparin dramatically reduced heparin-produced cerebral hemorrhage (
P
<0.0001), with a significant reduction in infarct volume (reduction by 63.2% and 57.2% of heparin-alone and control animals, respectively,
P
<0.0001) and a significant improvement in neurological symptoms (
P
<0.01 versus heparin-alone and control animals, respectively).

Conclusions

—

These data indicate that free radical formation may play a key role in intracerebral hemorrhage exacerbated by heparin treatment and that the combination of a free radical scavenger and heparin augmented neuroprotection from acute brain ischemia. The results of the present study may suggest a potential clinical approach for the treatment of acute stroke.
Utility of Perfusion-Weighted CT Imaging in Acute Middle Cerebral Artery Stroke Treated With Intra-Arterial Thrombolysis:
Authors: Lev Michael H. , Segal Alan Z. , Farkas Jeffery , Hossain Syeda T. , Putman Christopher , Hunter George J. , Budzik Ronald , Harris Gordon J. , Buonanno Ferdinando S. , Ezzeddine Mustapha A. , Chang Yuchiao , Koroshetz Walter J. , Gonzalez R. Gilberto , Schwamm Lee H.
Published: October 2007

Background and Purpose

—

The goal of this study was to evaluate the utility of perfusion-weighted CT (PWCT) in predicting final infarct volume and clinical outcome in patients with acute middle cerebral artery (MCA) stroke.

Methods

—

Twenty-two consecutive patients with MCA stem occlusion who underwent intra-arterial thrombolysis within 6 hours of stroke onset had noncontrast CT and CT angiography with whole-brain PWCT imaging before treatment. Infarct volumes were computed from the initial PWCT and follow-up scans; clinical outcome was measured with the modified Rankin scale.

Results

—

Initial PWCT lesion volumes correlated significantly with final infarct volume (
P
=0.0002) and clinical outcome (
P
=0.01). For the 10 patients with complete recanalization, the relationship between initial and final lesion volume was especially strong (
R
2
=0.94,
P
<0.0001, slope of regression line=0.92). For those without complete recanalization, there was progression of lesion volume on follow-up imaging (
R
2
=0.50,
P
=0.01, slope of regression line=1.61). All patients with either initial PWCT lesion volumes >100 mL or no recanalization had poor outcomes (Rankin scores, 4 to 6). Mean admission NIH Stroke Scale scores and mean lesion volumes in the poor outcome group were significantly different compared with the good or fair outcome (Rankin scores, 0 to 3) group (21±4 versus 17±5,
P
=0.05, and 106±79 versus 29±37 mL,
P
=0.01). Patients with initial volumes <100 mL and partial or complete recanalization all had good (Rankin scores, 0 to 2) or fair (Rankin score, 3) outcomes.

Conclusions

—

Lesion volumes on admission PWCT images approximate final infarct volume for patients with early complete recanalization of MCA stem occlusion. For those without complete recanalization, there is subsequent enlargement of lesion volume on follow-up. Initial PWCT lesion volumes also have predictive value; volumes >100 mL are associated with a poor clinical outcome. In these highly selected patients, initial PWCT lesion volume was a stronger predictor of clinical outcome than was initial NIH Stroke Scale score.
Predictors of Fatal Brain Edema in Massive Hemispheric Ischemic Stroke
Authors: Kasner Scott E. , Demchuk Andrew M. , Berrouschot Jörg , Schmutzhard Erich , Harms Lutz , Verro Piero , Chalela Julio A. , Abbur Rekha , McGrade Harold , Christou Ioannis , Krieger Derk W.
Published: October 2007

Background and Purpose
—

Early identification of stroke patients at risk for fatal brain edema may be useful in selecting patients for aggressive interventions. Prior studies suggested that early nausea/vomiting and major hypodensity on baseline computed tomography (CT) were predictive of herniation.

Methods
—

This study was a retrospective multicenter case-control study of patients with large middle cerebral artery (MCA) strokes admitted within 48 hours of symptom onset. Medical records, laboratory data, and CT scans were analyzed. Cases, defined as patients who died of massive brain swelling, were compared with all remaining patients as controls.

Results
—

Two hundred one patients with large MCA strokes were identified: 94 (47%) died of brain swelling, 12 (6%) died of non-neurological causes, and 95 (47%) survived at day 30. Multivariable analysis, adjusted for age and clustered by center, identified the following predictors of fatal brain edema: history of hypertension (OR 3.0, 95% CI 1.2 to 7.6,
P
=0.02), history of heart failure (OR 2.1, 95% CI 1.5 to 3.0,
P
<0.001), elevated white blood cell count (OR 1.08 per 1000 white blood cells/μL, 95% CI 1.01 to 1.14,
P
=0.02), >50% MCA hypodensity (OR 6.3, 95% CI 3.5 to 11.6,
P
<0.001), and involvement of additional vascular territories (anterior cerebral artery, posterior cerebral artery, or anterior choroidal artery; OR 3.3, 95% CI 1.2 to 9.4,
P
=0.02). Initial level of consciousness, National Institutes of Health Stroke Scale score, early nausea/vomiting, and serum glucose were associated with neurological death in bivariable but not multivariable analyses.

Conclusions
—

Among patients with large MCA infarctions, an increased risk of fatal brain edema is associated with history of hypertension or heart failure, increased baseline white blood cell count, major early CT hypodensity involving >50% of the MCA territory, and involvement of additional vascular territories. These data confirm and expand on prior research with a broad-based patient population. The presence of these risk factors identifies those stroke patients who may require aggressive therapeutic approaches.
Protective Effect of Endothelin Type A Receptor Antagonist on Brain Edema and Injury After Transient Middle Cerebral Artery Occlusion in Rats
Authors: Matsuo Yoshiyuki , Mihara Shin-ichi , Ninomiya Mitsuyoshi , Fujimoto Masafumi
Published: October 2007

Background and Purpose

—

Recent evidence strongly suggests that endothelins (ETs) play an important role in the regulation of blood-brain barrier (BBB) functions. The aim of the present study was to evaluate the role of ETs on edema formation and BBB permeability change after cerebral ischemia/reperfusion.

Methods

—

We examined the brain tissue ET-1 content and evaluated the time and dose response of the therapeutic effects of the specific ET type A receptor (ET
A
) antagonist, S-0139, on brain edema formation, development of infarction, and disruption of BBB after 1 hour of middle cerebral artery occlusion (MCAO) in rats.

Results

—

After 1-hour MCAO and reperfusion, the brain ET-1 content did not change during the first 3 hours, increased at 6 hours, and rose almost continuously over 48 hours in the ischemic region as well as in the ischemic rim. Rats infused with S-0139 (0.03 to 1.0 mg/kg per hour) during reperfusion showed dose-dependent and significant attenuation of the increase in brain water content 24 hours after reperfusion. When the infusion of S-0139 was begun after 10 minutes and 1 hour of reperfusion, the brain edema formation and infarct size were significantly attenuated. Furthermore, posttreatment with S-0139 significantly attenuated the increased Evans blue dye-quantified albumin extravasation and improved the mortality of animals after cerebral ischemia/reperfusion.

Conclusions>

—

Our data demonstrate that infusion with S-0139, an ET
A
antagonist, results in significant reduction of brain injury and plasma extravasation after transient MCAO. Thus, ETs may contribute to cerebral ischemia/reperfusion injury at least partly by increasing the BBB permeability via ET
A
s.
Development of Performance Measures for Acute Ischemic Stroke
Authors: Holloway Robert G. , Vickrey Barbara G. , Benesch Curtis , Hinchey Judith A. , Bieber Jacque
Published: October 2007

Background and Purpose
—

The purpose of the present study was to develop and rate performance measures for hospital-based acute ischemic stroke.

Methods
—

A national multidisciplinary panel of 16 individuals (2 stroke specialists, 2 general neurologists, 2 internists, 2 neuroscience nurses, 2 stroke advocacy organization representatives, 1 stroke rehabilitationist, 1 family practitioner, 1 emergency room physician, 1 neuroradiologist, 1 managed care organization director, and 1 hospital association representative) from 10 medical societies or lay organizations assisted in the development of 44 potential stroke performance measures. We developed evidence summaries for each of the performance measures and graded the level of evidence associated with each measure. The panel received a summary of the literature pertaining to each measure and rated the measures by use of a modified Delphi approach for 6 dimensions of quality, including validity of evidence, feasibility, impact on outcomes, room for improvement, plausibility, and an overall rating (little reason to do, could do, should do, and must do).

Results
—

Highly rated and agreed on performance measures for the overall rating include warfarin in atrial fibrillation, antithrombotics on hospital discharge, carotid imaging in appropriate patients, and use of stroke units. Additional measures notable for high agreement were heparins for deep-vein thrombosis prophylaxis and use of a stroke protocol. Panelists rated time-related thrombolytic measures such as head CT within 25 minutes highly on the room for improvement dimension but low on the overall dimension. Neurologists tended to rate measures lower than did nonneurologists (
P
<0.01) for all 9 measures pertaining to thrombolytic management.

Conclusions
—

Highly rated and agreed on performance measures exist in all domains of hospital-based stroke care.
Cyclooxygenase-2 Inhibitor NS-398 Protects Neuronal Cultures From Lipopolysaccharide-Induced Neurotoxicity
Authors: Araki Eiichi , Forster Colleen , Dubinsky Janet M. , Ross M. Elizabeth , Iadecola Costantino
Published: October 2007

Background and Purpose—The prostanoid-synthesizing enzyme cyclooxygenase (COX)-2 is markedly upregulated after cerebral ischemia and may participate in the mechanisms by which postischemic inflammation contributes to the late stages of ischemic brain injury. In the present study, we sought to provide additional evidence for a role of COX-2 in the mechanisms of neurotoxicity associated with inflammation.

Methods—Nine-day-old neuronal-glial cultures, prepared from the cerebral cortex of newborn C57BL/6J mice, were exposed to lipopolysaccharide (LPS), a potent proinflammatory agent. The contribution of COX-2 was investigated by using the COX-2 inhibitor NS-398.

Results—LPS produced a dose-dependent (0.001 to 10 μg/mL) and selective neuronal death that was well developed 72 hours after treatment. The effect was associated with a marked increase in the concentration of the COX reaction product prostaglandin E2(PGE2) and of the cytokine tumor necrosis factor-α (TNF-α). NS-398 (10 μmol/L) blocked the PGE2increase, attenuated the TNF-α increase, and prevented the neuronal death produced by LPS. TNF-α-blocking antibodies attenuated LPS-induced neuronal death, but the protection was less pronounced than that afforded by NS-398. LPS failed to elevate PGE2or to produce cell death in neuron-enriched cultures, suggesting that glial cells are required for these effects.

Conclusions—COX-2, in part through TNF-α-related mechanisms, contributes to LPS-induced neuronal death. The data support the hypothesis that COX-2, in addition to its role in glutamate excitotoxicity, participates in the cytotoxicity associated with inflammation.
Stress Hyperglycemia and Prognosis of Stroke in Nondiabetic and Diabetic Patients
Authors: Capes Sarah E. , Hunt Dereck , Malmberg Klas , Pathak Parbeen , Gerstein Hertzel C.
Published: October 2007

Background and Purpose

“Stress” hyperglycemia may be associated with increased mortality and poor recovery in diabetic and nondiabetic patients after stroke. A systematic review and meta-analysis of the literature relating acute poststroke glucose levels to the subsequent course were done to summarize and quantify this relationship.

Methods

A comprehensive literature search was done for cohort studies reporting mortality and/or functional recovery after stroke in relation to admission glucose level. Relative risks in hyperglycemic compared with normoglycemic patients with and without diabetes were calculated and meta-analyzed when possible.

Results

Thirty-two studies were identified; relative risks for prespecified outcomes were reported or could be calculated in 26 studies. After stroke of either subtype (ischemic or hemorrhagic), the unadjusted relative risk of in-hospital or 30-day mortality associated with admission glucose level >6 to 8 mmol/L (108 to 144 mg/dL) was 3.07 (95% CI, 2.50 to 3.79) in nondiabetic patients and 1.30 (95% CI, 0.49 to 3.43) in diabetic patients. After ischemic stroke, admission glucose level >6.1 to 7.0 mmol/L (110 to 126 mg/dL) was associated with increased risk of in-hospital or 30-day mortality in nondiabetic patients only (relative risk=3.28; 95% CI, 2.32 to 4.64). After hemorrhagic stroke, admission hyperglycemia was not associated with higher mortality in either diabetic or nondiabetic patients. Nondiabetic stroke survivors whose admission glucose level was >6.7 to 8 mmol/L (121 to 144 mg/dL) also had a greater risk of poor functional recovery (relative risk=1.41; 95% CI, 1.16 to 1.73).

Conclusions

Acute hyperglycemia predicts increased risk of in-hospital mortality after ischemic stroke in nondiabetic patients and increased risk of poor functional recovery in nondiabetic stroke survivors.
Geographic Variation in the Rate of Carotid Endarterectomy in Canada
Authors: Feasby Thomas E. , Quan Hude , Ghali William A.
Published: October 2007

Background and Purpose

—

Carotid endarterectomy (CEA) is an important method of stroke prevention, but its usage in Canada is not well known. The indications for CEA have been well informed by the recent clinical trials, but the impact of this information on the rate and regional variation in the rate of CEA is unknown. This study sought to determine the rate and the regional variation in the rate of CEA in Canada, its provinces, and census divisions for 1994–1997.

Methods

—

Discharge data from all hospitals in Canada except Quebec were obtained from the Canadian Institute for Health Information for 1994–1997 and were searched for CEA by residential site. Rates and variations in rates were calculated.

Results

—

The national age- and sex-adjusted rate per 100 000 people of CEA for those aged ≥40 years rose from 31.7 in 1994 to 40.5 in 1997. Provincial rates in 1997 varied from a low of 25.7 in Saskatchewan to high of 82.8 in Prince Edward Island. The census division rates varied even more, from a low of 0 in several divisions to a high of 179.

Conclusions

—

The recent slight increase in CEA rates may reflect the release of new efficacy results for CEA, especially for asymptomatic carotid stenosis, but the rates are still far below US levels. The marked regional variation in rates may reflect differing views on the appropriateness of indications such as asymptomatic carotid stenosis for CEA and the inconsistency of published clinical practice guidelines.
Cocaine Use Is an Independent Risk Factor for Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage
Authors: Conway James E. , Tamargo Rafael J.
Published: October 2007

Background and Purpose

—

Although acute cocaine use has been temporally associated with aneurysmal subarachnoid hemorrhage (aSAH), the prevalence of vasospasm and the clinical outcome of patients experiencing aSAH associated with cocaine exposure are unclear. We have analyzed this patient population in our institution to address these issues.

Methods

—

Between 1992 and 1999, 440 patients presented to our institution with aSAH. This sample was retrospectively analyzed to determine which patients had used cocaine within 72 hours of aSAH as documented by urine toxicology studies or patient history. These patients were then compared with control aSAH patients without recent cocaine exposure through univariable and multivariable analyses.

Results

—

Twenty-seven aSAH patients (6.1% of total) had either urine toxicology positive for cocaine metabolites (20 patients, 74%) or a history of cocaine use within 72 hours of aSAH (7 patients, 26%). Cocaine users were more likely to experience cerebral vasospasm defined as a delayed clinical deficit (from 3 to 16 days after aSAH) unexplained by concurrent CT scan and either responsive to hypervolemic and/or hypertensive therapy or accompanied by angiographic confirmation of vessel narrowing than control subjects (63% versus 30%; odds ratio [OR], 3.90; 95% confidence interval [CI], 1.77 to 8.62;
P
=0.001). Patients using cocaine were younger than control subjects (mean age, 36 versus 52 years;
P
<0.0001). Aneurysms of the anterior circulation were observed more frequently in cocaine users than in control subjects (97% versus 84%; OR, 6.89; 95% CI, 1.18 to 47.47;
P
=0.029). A significant difference was not observed, however, in the discharge Glasgow Outcome Scale (GOS) scores between the 2 groups (
P
=0.73). Differences were not observed between the 2 groups when the distributions of sex, hypertension, admission Glasgow Coma Scale subarachnoid hemorrhage grade, and multiple aneurysms were analyzed. Logistic regression models identified variables independently associated with vasospasm and discharge GOS score. Only a thick blood clot on the admission CT (OR, 7.46; 95% CI, 3.95 to 14.08;
P
<0.0001) and recent cocaine use (OR, 6.41; 95% CI, 2.14 to 19.23;
P
=0.0009) were independently associated with vasospasm. Cocaine use was not independently associated with the discharge GOS score.

Conclusions

—

We conclude that there is an increased prevalence of vasospasm in aSAH patients with recent cocaine exposure but no difference in clinical outcome. In addition, these patients are younger and more likely to have anterior circulation aneurysms.
Association Between Infection With
Helicobacter pylori
and
Chlamydia pneumoniae
and Risk of Ischemic Stroke Subtypes
Authors: Heuschmann Peter U. , Neureiter Daniel , Gesslein Markus , Craiovan Benjamin , Maass Matthias , Faller Gerhard , Beck Georg , Neundoerfer Bernhard , Kolominsky-Rabas Peter L.
Published: October 2007

Background and Purpose

—

Helicobacter pylori
and
Chlamydia pneumoniae
have been associated epidemiologically and pathogenetically with coronary atherosclerosis. However, population-based data on chronic infection and stroke are lacking. Therefore, we investigated the association of both bacterial pathogens and ischemic stroke subtypes in a population-based case-control study.

Methods

—

Patients with first ischemic stroke in the population-based Erlangen Stroke Project were collected as cases. Neighborhood controls were drawn from the study population, matched for age, sex, and place of residence. IgG antibodies to
H pylori
were measured by enzyme immunoassay, and IgG antibodies to
C pneumoniae
were measured by microimmunofluorescence technique. Conditional logistic regression was used. Analyses were stratified for etiologic stroke subtypes according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria.

Results

—

A total of 145 case and 260 control subjects were included. Chronic
H pylori
infection was associated with a higher risk of stroke caused by small-artery occlusion (adjusted odds ratio, 3.31; 95% CI, 1.15 to 9.56) and a lower risk of cardioembolic stroke (adjusted odds ratio, 0.21; 95% CI, 0.06 to 0.71). Overall, elevated
H pylori
as well as elevated
C pneumoniae
antibodies were not associated with ischemic stroke.

Conclusions

—

Our population-based study does not provide evidence of any strong association between the immune response to
C pneumoniae
as a marker of prior infection and ischemic stroke. Further studies are required to reveal the role of chronic
H pylori
infection as an independent risk factor for the subgroup small-artery occlusion.
Glutamate Injury–Induced Epileptogenesis in Hippocampal Neurons
Authors: Sun David A. , Sombati Sompong , DeLorenzo Robert J.
Published: October 2007

Background and Purpose

—

Stroke is the major cause of acquired epilepsy. The mechanisms of ischemia-induced epileptogenesis are not understood, but glutamate is associated with both ischemia-induced injury and epileptogenesis in several models. The objective of this study was to develop an in vitro model of epileptogenesis induced by glutamate injury in hippocampal neurons as observed during stroke.

Methods

—

Primary hippocampal cultures were exposed to 5 μmol/L glutamate for various durations. Whole-cell current clamp electrophysiology was used to monitor the acute effects of glutamate on neurons and chronic alterations in neuronal excitability up to 8 days after glutamate exposure.

Results

—

A single, 30-minute, 5-μmol/L glutamate exposure produced a subset of neurons that died and a larger population of injured neurons that survived. Neuronal injury was characterized by prolonged reversible membrane depolarization, loss of synaptic activity, and neuronal swelling. Surviving neurons manifested spontaneous, recurrent, epileptiform discharges in neural networks characterized by paroxysmal depolarizing shifts and high-frequency spike firing that persisted for the life of the culture.

Conclusions

—

This study demonstrates that glutamate injury produced a permanent epileptiform phenotype expressed as spontaneous, recurrent epileptiform discharges for the life of the hippocampal neuronal culture. These results suggest a novel in vitro model of glutamate injury–induced epileptogenesis that may help elucidate some of the mechanisms that underlie stroke-induced epilepsy.
A New Method for Predicting Recovery After Stroke
Authors: Tilling Kate , Sterne Jonathan A.C. , Rudd Anthony G. , Glass Thomas A. , Wityk Robert J. , Wolfe Charles D.A.
Published: October 2007

Background and Purpose

—

Several prognostic factors have been identified for outcome after stroke. However, there is a need for empirically derived models that can predict outcome and assist in medical management during rehabilitation. To be useful, these models should take into account early changes in recovery and individual patient characteristics. We present such a model and demonstrate its clinical utility.

Methods

—

Data on functional recovery (Barthel Index) at 0, 2, 4, 6, and 12 months after stroke were collected prospectively for 299 stroke patients at 2 London hospitals. Multilevel models were used to model recovery trajectories, allowing for day-to-day and between-patient variation. The predictive performance of the model was validated with an independent cohort of 710 stroke patients.

Results

—

Urinary incontinence, sex, prestroke disability, and dysarthria affected the level of outcome after stroke; age, dysphasia, and limb deficit also affected the rate of recovery. Applying this to the validation cohort, the average difference between predicted and observed Barthel Index was −0.4, with 90% limits of agreement from −7 to 6. Predicted Barthel Index lay within 3 points of the observed Barthel Index on 49% of occasions and improved to 69% when patients’ recovery histories were taken into account.

Conclusions

—

The model predicts recovery at various stages of rehabilitation in ways that could improve clinical decision making. Predictions can be altered in light of observed recovery. This model is a potentially useful tool for comparing individual patients with average recovery trajectories. Patients at elevated risk could be identified and interventions initiated.
Association of Surgical Specialty and Processes of Care With Patient Outcomes for Carotid Endarterectomy
Authors: Hannan Edward L. , Popp A. John , Feustel Paul , Halm Ethan , Bernardini Gary , Waldman John , Shah Dhiraj , Chassin Mark R.
Published: October 2007

Background and Purpose

—

Because there is considerable variation in practice patterns and outcomes for carotid endarterectomy (CE), there is a need to study the processes of care that are associated with adverse outcomes. The purpose of this study was to examine the impact of processes of care and surgical specialty on adverse outcomes for CE.

Methods

—

A retrospective cohort study based on a voluntary CE registry containing 3644 patients undergoing CE between April 1, 1997, and March 31, 1999, in New York hospitals was used in the study. A multivariable statistical model was used to identify significant independent patient risk factors and to examine the association of processes of care and surgical specialty with outcomes after adjustment for differences in patient risk factors.

Results

—

The overall adverse outcome (in-hospital death or stroke) rate was 1.84%. After adjustment for differences in 7 patient risk factors that were significantly related to adverse outcomes, the use of ≥1 specific processes of care (eversion endarterectomy, protamine, or shunts) was found to be associated with lower odds of an adverse outcome relative to patients undergoing CE without the processes (OR=0.42,
P
=0.006). Similarly, patients undergoing surgery performed by vascular surgeons had lower odds of experiencing an adverse outcome (OR=0.36,
P
=0.009). Processes of care and surgical specialty were highly correlated with one another.

Conclusions

—

Processes of care and surgical specialty are significant interrelated determinants of adverse outcome for CE.
Redo Carotid Endarterectomy Versus Primary Carotid Endarterectomy
Authors: AbuRahma Ali F. , Jennings Tucker G. , Wulu John T. , Tarakji Lisa , Robinson Patrick A.
Published: October 2007

Background and Purpose—Several authorities have recently advocated carotid stenting for recurrent carotid stenosis because of the perception that redo surgery has a higher complication rate than primary carotid endarterectomy (CEA). This study compares the early and late results of reoperations versus primary CEA.

Methods—All reoperations for recurrent carotid stenosis performed during a recent 7-year period by a single vascular surgeon were compared with primary CEA. Because all redo CEAs were done with polytetrafluoroethylene (PTFE) or vein patch closure, we only analyzed those primary CEAs that used the same patch closures. A Kaplan-Meier life-table analysis was used to estimate stroke-free survival rates and freedom from ≥50% recurrent stenosis.

Results—Of 547 primary CEAs, 265 had PTFE or saphenous vein patch closure, and 124 reoperations had PTFE or vein patch closure during the same period. Both groups had similar demographic characteristics. The indications for reoperation and primary CEA were symptomatic stenosis in 78% and 58% of cases and asymptomatic ≥80% stenosis in 22% and 42% of cases, respectively (P<0.001). The 30-day perioperative stroke and transient ischemic attack rates for reoperation and primary CEA were 4.8% versus 0.8% (P=0.015) and 4% versus 1.1%, respectively, with no perioperative deaths in either group. Cranial nerve injury was noted in 17% of reoperation patients versus 5.3% of primary CEA patients; however, most of these injuries were transient (P<0.001). Mean hospital stay was 1.8 days for reoperation versus 1.6 days for primary CEA. Cumulative rates of stroke-free survival and freedom from ≥50% recurrent stenosis for reoperation and primary CEA at 1, 3, and 5 years were 96%, 91%, and 82% and 98%, 96%, and 95% versus 94%, 92%, and 91% and 98%, 96%, and 96%, respectively (no significant differences).

Conclusions—Reoperation carries higher perioperative stroke and cranial nerve injury rates than primary CEA. However, reoperations are durable and have stroke-free survival rates that are similar to primary CEA. These considerations should be kept in mind when carotid stenting is recommended instead of reoperation.
Feasibility of an Affected Sibling Pair Study in Ischemic Stroke
Authors: Meschia James F. , Brown Robert D. , Brott Thomas G. , Hardy John , Atkinson Elizabeth J. , O’Brien Peter C.
Published: October 2007

Background and Purpose

—

We sought to determine pedigree availability for a concordant sibling pair study of genetic risk factors in ischemic stroke.

Methods

—

Probands with confirmed ischemic stroke were prospectively enrolled. Family histories were obtained by systematic interview. A study neurologist prospectively assigned stroke subtype.

Results

—

Of 310 probands (median age, 75 years; range, 26 to 97 years; 48% women), 75% had at least 1 living sibling; 10%, at least 1 concordant living sibling; 2%, at least 1 concordant sibling living in the same city; and 7%, at least 1 concordant living and 1 discordant living sibling. Likelihood of having a concordant sibling increased significantly with proband age, even after adjustment for sibship size (
P
=0.002). Positive family history of stroke was not related to either proband stroke subtype or risk factor profile.

Conclusions

—

Approximately 10 probands were screened to find 1 potentially concordant living sibling. A concordant sibling pair study should be multicentered and enable enrollment of siblings from diverse geographic areas.
MR Perfusion Imaging in Moyamoya Syndrome
Authors: Calamante F. , Ganesan V. , Kirkham F.J. , Jan W. , Chong W.K. , Gadian D.G. , Connelly A.
Published: October 2007

Background and Purpose

—

Ischemic symptoms in patients with moyamoya syndrome (MMS) are usually due to hemodynamically mediated perfusion failure, and identification of abnormal tissue perfusion in these patients is therefore clinically important. Although dynamic susceptibility contrast (DSC) MRI can be used to study tissue perfusion, there are potential technical problems in MMS. This study investigates the scope and limitations of perfusion MRI in the clinical evaluation of such patients.

Methods

—

Thirteen patients with bilateral MMS were studied with the use of structural, diffusion, and perfusion MRI. The DSC MRI data were analyzed both visually and by a quantitative regional analysis, and the relationship between perfusion status and clinical symptoms was investigated.

Results

—

Extensive bilateral DSC MRI abnormalities were observed in all the patients. There was a very heterogeneous distribution of bolus arrival time. The areas of abnormality included the major arterial border zones in all cases, although these usually appeared normal on structural and diffusion MRI. Only the most clinically unstable patients had peak width (defined as time to peak minus bolus arrival time) >5 seconds on the quantitative regional analysis. Several technical limitations of perfusion quantification in MMS are described, as well as the implications of these limitations in patients with other forms of occlusive large-vessel disease.

Conclusions

—

The technical limitations of DSC MRI described in this study are important for the accurate interpretation of perfusion MRI in MMS. Despite these limitations, these preliminary findings suggest that the use of quantitative regional analysis of summary parameters may provide clinically useful information in patients with MMS.
Postischemic (6-Hour) Treatment With Recombinant Human Tissue Plasminogen Activator and Proteasome Inhibitor PS-519 Reduces Infarction in a Rat Model of Embolic Focal Cerebral Ischemia
Authors: Zhang Li , Zhang Zheng Gang , Zhang Rui Lan , Lu Mei , Adams Julian , Elliott Peter J. , Chopp Michael
Published: October 2007

Background and Purpose
—

The proteasome inhibitor PS-519 blocks activation of nuclear factor-κB, a major mediator of inflammation. We tested the hypothesis that combination treatment of recombinant human tissue plasminogen activator (rhtPA) and PS-519 extends the therapeutic window for treatment of stroke with rhtPA without increasing incidence of hemorrhagic transformation.

Methods
—

The middle cerebral artery (MCA) of male Wistar rats (n=56) was occluded by an embolus. After embolization, animals were randomly divided into the following groups: PS-519 treatment groups: PS-519 was given at 2, 4, or 6 hours after MCA occlusion; rhtPA treatment groups: rhtPA was given at 2 or 4 hours after MCA occlusion; combination treatment groups: PS-519 and rhtPA were given at 2, 4, or 6 hours after MCA occlusion; control group: the same volume of saline was given at 2 hours after MCA occlusion.

Results
—

Administration of PS-519 alone at 2 or 4 hours, but not 6 hours, significantly (
P
<0.05) reduced infarct volume and improved neurological recovery compared with the control group. Administration of rhtPA alone at 2 hours, but not 4 hours, significantly (
P
<0.05) reduced infarct volume and improved neurological recovery compared with the control group. Furthermore, combination treatment with rhtPA and PS-519 even at 6 hours significantly (
P
<0.05) reduced infarct volume, improved neurological recovery, and did not increase the incidence of hemorrhagic transformation compared with the control group or the group treated with PS-519 alone.

Conclusions
—

Our data suggest that combination treatment with PS-519 and rhtPA extends the neuroprotective effect to at least 6 hours after embolization.
Joint Effect of the
APOE
Gene and Midlife Systolic Blood Pressure on Late-Life Cognitive Impairment
Authors: Peila R. , White L.R. , Petrovich H. , Masaki K. , Ross G.W. , Havlik R.J. , Launer L.J.
Published: October 2007

Background and Purpose

—

The aim of this study was to explore the joint effect of the
APOE
ε4 allele and midlife systolic blood pressure (SBP) on the risk for poor cognitive function in late life.

Methods

—

The study includes 3605 surviving members of the cohort of the Japanese-American men followed prospectively over 26 years (1965–1991) as a part of the Honolulu Heart Program. In 1965 men were aged 45 to 68 years and were living in the island of Oahu, Hawaii. For this study the sample was divided into 4 categories: normal SBP (<160 mm Hg)/No ε4, as the reference category; normal SBP/ε4; high SBP/no ε4; high SBP/ε4. The relative risk (RR) of late-life intermediate and poor cognitive function relative to good function was measured by the Cognitive Abilities Screening Instrument (CASI) test.

Results

—

After adjusting for age, education, smoking, alcohol use, and body mass index, the RR for poor cognitive function (CASI <74) compared with good cognitive function (CASI ≥82) in never-treated subjects was 1.3 (95% CI 0.9 to 1.9) for the normal SBP/ε4 category, 2.6 (0.7 to 10.0) for the high SBP/no ε4, and 13.0 (1.9 to 83.8) for the high SBP/ε4. Adjustment for diabetes, prevalent stroke, coronary disease, and ankle-brachial index reduced the RR of poor cognition by 25.5% (RR 13.0 to 10.8) in those with both risk factors. In the treated group, the RR was 1.9 (0.7 to 4.5) for those with both risk factors.

Conclusions

—

The results suggest that midlife high SBP has a stronger adverse effect on cognitive function in persons with higher genetic susceptibility, but this effect may be modified by antihypertensive treatment.
Matrix Metalloproteinase Expression Is Related to Hemorrhagic Transformation After Cardioembolic Stroke
Authors: Montaner J. , Alvarez-Sabín J. , Molina C.A. , Anglés A. , Abilleira S. , Arenillas J. , Monasterio J.
Published: October 2007

Background and Purpose

—

In animal models of cerebral ischemia, matrix metalloproteinase (MMP) expression was significantly increased and related to blood-brain barrier disruption, edema formation, and hemorrhagic transformation (HT). MMP inhibitors reduce HT after embolic ischemia in tissue-type plasminogen activator-treated animals. We aimed to determine the relationship between MMPs and HT after human ischemic stroke.

Methods

—

Serial MMP-2 and MMP-9 determinations were performed by means of ELISA in 39 cardioembolic strokes in the middle cerebral artery territory. Hemorrhagic events were classified according to clinical and CT criteria (hemorrhagic infarction [HI] and parenchymal hematoma [PH]). HT was evaluated on CT at 48 hours (early HT) and again between day 5 and 7 (late HT).

Results

—

HT was present in 41% of the patients (43.75% early HI, 25% early PH and 31.25% late HI). MMP-2 values were within normal range and were unrelated to HT. Increased expression of MMP-9 (normal range <97 ng/mL) was found among patients with and without HT (159.3±82 versus 143.9±112.6 ng/mL;
P
=0.64). According to HT subtypes, the highest baseline MMP-9 levels corresponded to patients with late HI (240.4±111.2 versus 102.5±76.7 ng/mL for all other patients,
P
=0.002). Baseline MMP-9 was the only variable associated with late HI in the multiple logistic regression model (OR 9; CI 1.46, 55.24;
P
=0.010). Peak of MMP-9 at the 24-hour time point (250.6 ng/mL) was found before appearance of PH.

Conclusions

—

MMPs are involved in some subtypes of HT after human cardioembolic stroke. Baseline MMP-9 level predicts late HI and a 24-hour peak precedes early PH.
Policing Hate Crime in London
Authors: Kielinger Vicky , Paterson Susan
Published: October 2007

Since the bomb attacks that occurred in London on July 7, 2005, hate and faith-hate crimes and other incidents have become a major focus of the police and government in the United Kingdom. This article presents some of the research that has taken place on the nature and policing of hate crime over the past 5 years in the London Metropolitan Police Service. Focusing in particular on recent research into anti-Semitism where a new typology of incidents has been developed, the article reveals that the majority of hate incidents reported to the police in London are perpetrated by people with whom victims come into contact in their daily lives, rather than predominantly by strangers or extremists. This provides the police with a number of challenges for both strategic thinking and operational practice. It also highlights the continual need for close liaison and consultation with minority communities and vulnerable groups within London.
Too Few Jews to Count? Police Monitoring of Hate Crime Against Jews in the United Kingdom
Authors: Iganski Paul
Published: October 2007

Despite its significance as a specific category of hate crime, anti-Jewish crime has received little attention in the scholarly literature on policing hate crime. Whereas hate crimes against Jews figure prominently in the annual hate crime statistics published by the Federal Bureau of Investigation in the United States, there are no routinely published police data on anti-Jewish incidents in the United Kingdom. Given the concerns about a rise in anti-Semitism in Britain in recent years, this article expands on written and oral testimony provided by the author to the All-Party Parliamentary Inquiry Into Anti-Semitism. It illuminates the inadequacies in the police monitoring of, and use of data on, anti-Jewish incidents and discusses the shortcomings in the context of the value of hate crime data for police services.
When a Crime Committed by a Teenager Becomes a Hate Crime
Authors: Levin Jack , Rabrenovic Gordana , Ferraro Vincent , Doran Tara , Methe Daniela
Published: October 2007

This article examines the conditions under which a crime committed by a teenager comes to be viewed as a hate-motivated offense. In Study 1, the age of the perpetrator and the level of evidence were experimentally manipulated for male and female subjects. The dependent variable consisted of the likelihood that an interracial encounter was a hate crime. Our results suggest that female subjects were significantly more likely than their male counterparts to view the offense as a hate crime. In addition, we found significant differences in the influence of various forms of evidence. The difference was nonsignificant between the teenage and adult offenders. In Study 2, we content analyzed hate crime prosecutions as reported in major newspapers. Surprisingly, our results indicate that many teens were prosecuted and convicted on a hate crime charge. Studies 1 and 2 collectively suggest that teenage hate crime defendants are no longer the recipients of lenient treatment by the courts or in the court of public opinion.
When Hate Comes to Town
Authors: Rabrenovic Gordana
Published: October 2007

During the 1990s, many recently arrived immigrants and refugees in search of secure and stable places to raise their families moved to smaller, mostly homogenous American cities and towns. In these smaller communities, a lack of experience with ethnic and racial minorities along with the fear-provoking impact of 9/11 gave racial supremacists an opportunity to expand their membership base by promoting racial hatred and fears across these communities. This research examines response to hate provocation in one small New England city and shows how a community can successfully organize against racial hostilities and prevent violence. The results of the research suggest that racial violence is more likely to erupt if there is no community-wide response to racial provocations and also that the media can play an important role in countering hate messages by presenting truthful information and covering issues fairly.
Methodological Issues in Cross-Cultural Counseling Research
Authors: Ægisdóttir Stefanía , Gerstein Lawrence H. , Çinarbaş Deniz Canel
Published: October 2007

Concerns about the cross-cultural validity of constructs are discussed, including equivalence, bias, and translation procedures. Methods to enhance equivalence are described, as are strategies to evaluate and minimize types of bias. Recommendations for translating instruments are also presented. To illustrate some challenges of cross-cultural counseling research, translation procedures employed in studies published in five counseling journals are evaluated. In 15 of 615 empirical articles, a translation of instruments was performed. In 9 studies, there was some effort to enhance and evaluate equivalence between language versions of the measures employed. In contrast, 2 studies did not report using thorough translation and verification procedures, and 4 studies employed a moderate degree of rigorousness. Suggestions for strengthening translation methodologies and enhancing the rigor of cross-cultural counseling research are provided. To conduct cross-culturally valid research and deliver culturally appropriate services, counseling psychologists must generate and rely on methodologically sound cross-cultural studies. This article provides a schema for performing such studies.