bluuebunny/crossref_metadata_2025 huggingface dataset:
Docosahexaenoic Acid Complexed to Albumin Elicits High-Grade Ischemic Neuroprotection
Authors: Belayev Ludmila , Marcheselli Victor L. , Khoutorova Larissa , Rodriguez de Turco Elena B. , Busto Raul , Ginsberg Myron D. , Bazan Nicolas G.
Published: November 2004

Background and Purpose—

High-dose human albumin therapy is strongly neuroprotective in models of brain ischemia and trauma and is currently being studied in a pilot-phase clinical stroke trial. Among its actions in ischemia, albumin induces the systemic mobilization of n-3 polyunsaturated fatty acids and may help to replenish polyunsaturated fatty acids lost from neural membranes.

Methods—

We complexed 25% human albumin to docosahexaenoic acid (DHA; 22:6n-3) and compared its neuroprotective efficacy with that of native albumin in rats with 2-hour focal ischemia produced by intraluminal suture-occlusion of the middle cerebral artery.

Results—

In animals treated with DHA–albumin, 0.63 g/kg, the improvement in neurobehavioral scores at 72 hours significantly exceeded that of other treatment groups, and the extent of histological protection (86% reduction in cortical infarction) was highly significant and tended to surpass the degree of cortical protection produced by native albumin at 1.25 g/kg (65%). DHA–albumin 0.63 g/kg, but not native albumin, also significantly reduced subcortical infarction and markedly diminished brain swelling. Lipidomic analysis of DHA–albumin-treated postischemic brains revealed a large accumulation of the neuroprotective DHA metabolite, 10,17
S
-docosatriene, in the ipsilateral hemisphere.

Conclusions—

The high-grade neuroprotection afforded by the DHA–albumin complex at relatively low albumin doses is clinically advantageous in that it might reduce the likelihood of acute intravascular volume overload and congestive heart failure sometimes induced when patients with compromised cardiovascular function are treated with high-dose albumin.
The Risk and Benefit of Endarterectomy in Women With Symptomatic Internal Carotid Artery Disease
Authors: Alamowitch Sonia , Eliasziw Michael , Barnett Henry J.M.
Published: November 2004

Background and Purpose—

Perioperative risk and long-term benefit of carotid endarterectomy (CE) are not detailed in women with symptomatic internal carotid artery (ICA) stenosis. Our aim was to compare the efficacy of CE versus medical therapy in women and men with symptomatic ICA stenosis.

Methods—

Data were taken from the North American Symptomatic Carotid Endarterectomy Trial (873 women, 2012 men) and the ASA and Carotid Endarterectomy trial (335 women, 813 men).

Results—

The 30-day perioperative risk of death was higher in women than in men (2.3% versus 0.8%,
P
=0.002). Higher perioperative risk of stroke and death was also observed (7.6% versus 5.9%) but not statistically significant. With ≥70% stenosis, the 5-year absolute risk reduction (ARR) in stroke from CE was similar between women (15.1%) and men (17.3%). With 50% to 69% stenosis, CE was not beneficial in women (ARR=3.0%,
P
=0.94), contrary to men (ARR=10.0%,
P
=0.02). Medically treated women had low risk for stroke. A stroke prognosis instrument (SPI-II) assigned points to 7 factors that identified higher risk for medically treated women: 3 points for hemispheric (not retinal) event, history of diabetes, previous stroke; 2 for age older than 70 years, stroke (not transient ischemic attack); 1 for severe hypertension, history of myocardial infarction. CE was beneficial only for 29.0% of women with 50% to 69% stenosis who had the highest total score of 8 to 15 (ARR=8.9%).

Conclusions—

Women and men with ≥70% symptomatic stenosis had similar long-term benefit from CE, although the perioperative risks were higher for women. CE was not beneficial for women with 50% to 69% stenosis without other risk factors for stroke.
Combining Insulin-Like Growth Factor Derivatives Plus Caffeinol Produces Robust Neuroprotection After Stroke in Rats
Authors: Zhao Xiurong , Liu Shi-Jie , Zhang Jie , Strong Roger , Aronowski Jarek , Grotta James C.
Published: November 2004

Background and Purpose—

Insulin-like growth factor-1 (IGF-1) and caffeinol are both neuroprotective and probably have different mechanisms of action; therefore, they may be more effective in combination.

Methods—

We tested the N-terminal tripeptide of IGF-1, Gly-Pro-Glu (GPE), and its analogue, G2MePE, alone and with caffeinol in a rat middle cerebral artery (MCA) suture occlusion model. We randomly assigned rats to 6 groups of 8 to 12 animals: (1) control; (2) GPE, 3 mg/kg per hour; (3) G2MePE, 0.3 mg/kg per hour; (4) caffeinol, a mixture of caffeine (10 mg/kg) with ethanol (0.32 g/kg); (5) GPE with caffeinol (combination of group 2 with 4); and (6) G2MePE with caffeinol (combination of group 3 with 4). Drugs were started 75 minutes after suture occlusion, at the start of reperfusion. Three days after MCA occlusion, neurological deficit (Neurological Deficit Score [NDS]) and lesion volume were measured.

Results—

GPE and caffeinol improved NDS by 34% and 36%, respectively (
P
<0.01), and also decreased cortical but not striatal lesion volume compared with control (GPE cortex, 121 mm
3
; caffeinol cortex, 134 mm
3
; and control, 221 mm
3
;
P
<0.01). GPE plus caffeinol did not have more efficacy than either GPE or caffeinol alone. G2MePE slightly improved NDS (19.7%,
P
=0.05) but not lesion volume. However, G2MePE plus caffeinol very significantly improved NDS (64%) and lesion volume in both cortex (combination 95 mm
3
versus control 221 mm
3
) and striatum (combination 74 mm
3
versus control 110 mm
3
) (
P
<0.001), and was significantly more effective than either caffeinol or G2MePE alone.

Conclusion—

Both GPE and caffeinol significantly protect cortex after MCA occlusion. At the doses used in this study, the GPE analogue G2MePE by itself had minimal protective effects, but when combined with caffeinol, it demonstrated robust beneficial effects on cortical and subcortical lesion size and behavioral deficit. Further study of this combination appears justified.
Incidence, Manifestations, and Predictors of Worsening White Matter on Serial Cranial Magnetic Resonance Imaging in the Elderly
Authors: Longstreth W.T. , Arnold Alice M. , Beauchamp Norman J. , Manolio Teri A. , Lefkowitz David , Jungreis Charles , Hirsch Calvin H. , O’Leary Daniel H. , Furberg Curt D.
Published: November 2004

Background and Purpose—

Magnetic resonance imaging (MRI) scans in the elderly commonly show white matter findings that may raise concerns. We sought to document incidence, manifestations, and predictors of worsening white matter grade on serial imaging.

Methods—

The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people aged 65 years and older, of whom 1919 have had extensive initial and follow-up evaluations, including 2 MRI scans separated by 5 years. Scans were read without clinical information in standard side-by-side fashion to determine worsening white matter grade.

Results—

Worsening was evident in 538 participants (28%), mostly (85%) by 1 grade. Although similar at initial scan, participants with worsening white matter grade, compared with those without, experienced greater decline on modified Mini-Mental State examination and Digit-Symbol Substitution test (both
P
≤0.001) after controlling for potential confounding factors, including occurrence of transient ischemic attack or stroke between scans. Independent predictors of worsening white matter grade included cigarette smoking before initial scan and infarct on initial scan. Otherwise, predictors differed according to white matter grade on initial scan. For low initial grade, increased age, increased diastolic blood pressure, increased high-density lipoprotein cholesterol, and decreased low-density lipoprotein cholesterol were associated with increased risk of worsening. For high initial grade, any cardiovascular disease and low ankle–arm index were associated with decreased risk of worsening, whereas use of diuretics and statins were associated with increased risk.

Conclusion—

Worsening white matter grade on serial MRI scans in elderly is common, is associated with cognitive decline, and has complex relations with cardiovascular risk factors.
Depressive Symptoms and Mortality in Men
Authors: Gump Brooks B. , Matthews Karen A. , Eberly Lynn E. , Chang Yue-fang
Published: November 2004

Background and Purpose—

Depression may be a risk factor for cardiovascular disease (CVD) mortality. We evaluated long-term mortality risk associated with depressive symptoms measured at middle age among men at high risk for coronary heart disease (CHD).

Methods—

12 866 men without definite evidence of CHD at study entry but who had above average risk of CHD based on blood pressure, blood cholesterol levels, and/or cigarette smoking were recruited into the Multiple Risk Factor Intervention Trial (MRFIT). Survivors at the end of the trial were followed-up for mortality for an additional 18 years. Men who had completed the Center for Epidemiologic Studies Depression (CES-D) scale near the end of the trial (n=11 216) were used in a prospective analysis of post-trial all-cause and cause-specific mortality during 18-year follow-up after CES-D assessment.

Results—

Greater depressive symptoms measured at the end of the trial were associated with significantly higher risk of all-cause mortality and for cause-specific death, a higher risk of CVD, and, more specifically, stroke mortality (all
P
values <0.02) but not CHD mortality (
P
=0.48) in linear trend analyses. The significant associations were strongest for those reporting the greatest depression: hazard ratio (HR)=1.15 (95% CI, 1.03 to 1.28;
P
<0.01) for all-cause mortality for those in the highest depressive symptom quintile, HR=1.21 for CVD mortality (95% CI, 1.03 to 1.41;
P
<0.05), and HR=2.03 for stroke mortality (95% CI, 1.20 to 3.44;
P
<0.01) compared with those in the lowest quintile. These associations were adjusted for age, intervention group, race, educational attainment, smoking at baseline and visit 6, trial averaged systolic blood pressure, alcohol consumption, and fasting cholesterol, as well as the occurrence of nonfatal cardiovascular events during the trial.

Conclusions—

Greater depressive symptoms are associated with an increase in the risk of all-cause and, more specifically, CVD mortality in men. Stroke but not CHD was the form of CVD with which depressive symptoms were associated.
Safety and Feasibility of Recombinant Factor VIIa for Acute Intracerebral Hemorrhage
Authors: Mayer Stephan A. , Brun Nikolai C. , Broderick Joseph , Davis Stephen , Diringer Michael N. , Skolnick Brett E. , Steiner Thorsten
Published: November 2004

Background and Purpose—

Hematoma growth occurs in 38% of intracerebral hemorrhage (ICH) patients scanned by computed tomography (CT) within 3 hours of onset. Activated recombinant factor VII (rFVIIa) promotes hemostasis at sites of vascular injury and may minimize hematoma growth after ICH.

Methods—

In this randomized, double-blind, placebo-controlled, dose-escalation trial, 48 subjects with ICH diagnosed within 3 hours of onset were treated with placebo (n=12) or rFVIIa (10, 20, 40, 80, 120, or 160 μg/kg; n=6 per group). The primary endpoint was the frequency of adverse events (AEs). Safety assessments included serial electrocardiography (ECG), troponin I and coagulation testing, lower extremity Doppler ultrasonography, and calculation of edema:ICH volume ratios.

Results—

Mean age was 61 years (range, 30 to 93) and 57% were male. At admission, mean National Institutes of Health Stroke Scale (NIHSS) score was 14 (range, 1 to 26), median Glasgow Coma Scale score was 14 (range, 6 to 15), and mean ICH volume was 21 mL (range, 1 to 151). Mean time from onset to treatment was 181 minutes (range, 120 to 265). Twelve serious AEs occurred, including 5 deaths (mortality 11%). Six AEs were considered possibly treatment-related, including rash, vomiting, fever, ECG T-wave inversion, and 2 cases of deep vein thrombosis (placebo and 20-μg/kg groups). No myocardial ischemia, consumption coagulopathy, or dose-related increase in edema:ICH volume occurred.

Conclusion—

This small phase II trial evaluated a wide range of rFVIIa doses in acute ICH and raised no major safety concerns. Larger studies are justified to determine whether rFVIIa can safely and effectively limit ICH growth.
Impaired Functional Recovery After Stroke in the Stroke-Prone Spontaneously Hypertensive Rat
Authors: McGill J.K. , Gallagher L. , Carswell H.V.O. , Irving E.A. , Dominiczak A.F. , Macrae I.M.
Published: November 2004

Background and Purpose—

To identify if the stroke-prone spontaneously hypertensive rat (SHRSP) exhibits impaired functional recovery after stroke compared with its normotensive reference strain, the Wistar Kyoto rat (WKY).

Methods—

In study 1, a 2-mm distal middle cerebral artery occlusion (middle cerebral artery occlusion) was performed in both strains and recovery assessed using a 33-point neurological score. Because SHRSPs displayed much larger infarcts than WKYs, study 2 and study 3 involved extending the length of middle cerebral artery (MCA) occlusion in the WKY to increase the volume and distribution of infarction to comparable levels with SHRSP. Animals were assessed with the neurological score, tapered beam walk, and cylinder tests.

Results—

In study 1, infarct volume (expressed as a percent of contralateral hemisphere) was WKY 13.1±3% and SHRSP 19.8±1%. Initial neurological deficit was greater (WKY 25±1, SHRSP 22±1, out of a possible 33) and subsequent recovery was poorer in SHRSP. In studies 2 and 3, infarct volume and distribution (study 2, WKY 21.8±1.3%, SHRSP 22.9±3%; study 3, WKY 17.2±2%, SHRSP 16.5±3%) and initial neurological deficit at 2 hours after middle cerebral artery occlusion (study 2 WKY 23±1, SHRSP 22±2; study 3 WKY 25±1 and SHRSP 23±1; mean±SEM) were comparable between strains. However, whereas WKY recovered toward normal scores, SHRSP scored significantly lower 2 weeks (study 2) and 4 weeks (study 3) after middle cerebral artery occlusion. Beam walk data revealed long-term impairment in SHRSP contralateral limb use, compared with WKY, at days 3, 7, and 28 (
P
<0.05).

Conclusions—

SHRSP exhibit impaired functional recovery after stroke compared with WKY.
Heritability of Carotid Artery Atherosclerotic Lesions
Authors: Moskau Susanna , Golla Astrid , Grothe Christoph , Boes Monika , Pohl Christoph , Klockgether Thomas
Published: November 2004

Background and Purpose—

Ultrasound examination of the carotid arteries yields several quantitative measures that may serve as intermediate phenotypes in genetic studies. This study was undertaken to compare the heritabilities of 3 ultrasound measures: intima-media thickness (IMT), plaque score, and maximal stenosis.

Methods—

We studied 565 individuals from 154 families ascertained by an affected parent with carotid artery atherosclerosis. IMT, plaque score, and maximal stenosis of the carotid arteries were examined by B-mode ultrasound and analyzed quantitatively. Heritability estimates were obtained by variance component analysis as implemented in the program SOLAR (sequential oligogenic linkage analysis routines). Covariates were age, sex, weight, height, body mass index (BMI), arterial hypertension, diabetes mellitus, amount of nicotine consumed, and plasma levels of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, LDL/HDL ratio, lipoprotein(a) [Lp(a)], triglycerides, factor VIII, factor XIII, fibrinogen, and von Willebrand factor (vWF).

Results—

After accounting for the covariables age, sex, hypertension, diabetes mellitus, and Lp(a), heritability of IMT was estimated as
h
2
=0.61±0.17 (
P
=0.001). Variation of plaque score was influenced by age, sex, hypertension, diabetes mellitus, hypercholesterolemia, amount of nicotine consumed, factor VIII, and vWF. When these were considered, no significant heritability could be detected. Heritability of stenosis was estimated as
h
2
=0.47±0.07 (
P
=0.006), with age, sex, BMI, hypertension, diabetes mellitus, amount of nicotine consumed, and LDL/HDL ratio as covariates.

Conclusions—

Among the 3 ultrasound measures studied, IMT had the highest heritability. IMT was strongly influenced by genetic determinants other than those influencing known risk factors. This makes IMT a promising candidate for use as an intermediate phenotype in genetic studies aiming to identify novel genes for atherosclerosis.
Impaired Vascular Mechanotransduction in a Transgenic Mouse Model of CADASIL Arteriopathy
Authors: Dubroca Caroline , Lacombe Pierre , Domenga Valérie , Maciazek Jacqueline , Levy Bernard , Tournier-Lasserve Elisabeth , Joutel Anne , Henrion Daniel
Published: November 2004

Background and Purpose—

CADASIL is an inherited small-vessel disease responsible for lacunar strokes and cognitive impairment. The disease is caused by highly stereotyped mutations in
Notch3
, the expression of which is highly restricted to vascular smooth muscle cells (VSMCs). The underlying vasculopathy is characterized by degeneration of VSMCs and the accumulation of granular osmiophilic material (GOM) and Notch3 protein within the cell surface of these cells. In this study, we assessed early functional changes related to the expression of mutant
Notch3
in resistance arteries.

Methods—

Vasomotor function was examined in vitro in arteries from transgenic mice that express a mutant
Notch3
in VSMC. Tail artery segments from transgenic and normal wild-type male mice were mounted on small-vessel arteriographs, and reactivity to mechanical (flow and pressure) forces and pharmacological stimuli were determined. Mice were studied at 10 to 11 months of age when VSMC degeneration, GOM deposits, and Notch3 accumulation were not yet present.

Results—

Passive arterial diameter, contraction to phenylephrine, and endothelium-dependent relaxation to acetylcholine were unaffected in transgenic mice. By contrast, flow-induced dilation was significantly decreased and pressure-induced myogenic tone significantly increased in arteries from transgenic mice compared with wild-type mice.

Conclusions—

This is the first study to our knowledge providing evidence that mutant
Notch3
impairs selectively the response of resistance arteries to flow and pressure. The data suggest an early role of vascular dysfunction in the pathogenic process of the disease.
Expression and Function of Recombinant S1179D Endothelial NO Synthase in Human Pial Arteries
Authors: Sorenson Joseph , Santhanam Anantha Vijay R. , Smith Leslie A. , Akiyama Masahiko , Sessa William C. , Katusic Zvonimir S.
Published: November 2004

Background and Purpose—

Mutation of serine 1179 to aspartate on the endothelial NO synthase (eNOS) increases NO production in the absence of stimulation by agonists. The present study was designed to determine the effect of recombinant S1179DeNOS gene expression on the vasomotor function of human pial arteries.

Methods—

Pial arteries were isolated from 28 patients undergoing temporal lobectomy for intractable seizures. Adenoviral vectors (10
10
pfu/mL) encoding β-galactosidase (AdCMVLacZ) or S1179DeNOS (AdCMVS1179DeNOS) were used for ex vivo gene transfer, and vasomotor function was evaluated in control and transduced arteries.

Results—

Contractions to cumulative additions of U46619 were not affected by expression of LacZ or S1179DeNOS. Endothelium-dependent relaxations to bradykinin or endothelium-independent relaxations to Diethylaminodiazen-1-ium-1,2-dioate were significantly reduced in arteries expressing S1179DeNOS. A superoxide dismutase mimetic, manganese (III) tetrakis (4-benzoic acid) porphyrin chloride, failed to improve the reduced relaxations to bradykinin. The levels of cGMP were significantly elevated in arteries expressing S1179DeNOS.

Conclusions—

Our results support the concept that high local production of NO in pial arterial wall causes adaptive reduction of vasodilator reactivity to NO.
Optimizing Discharge Planning
Authors: Saposnik Gustavo , Webster Fiona , O’Callaghan Chris , Hachinski Vladimir
Published: November 2004

Background and Purpose—

The length of stay (LOS) is the main cost-determining factor for inpatients with acute stroke. Although studies have identified variables associated with LOS, few have analyzed predictors of longer stay after receiving thrombolytic therapy for acute stroke.

Methods—

We studied all consecutive acute stroke patients receiving intravenous recombinant tissue plasminogen activator (rtPA) admitted to the London Health Sciences Center, in London, Ontario, Canada, from 1999 to 2003. Longer stay was defined as LOS ≥7 days after admission. Demographic as well as baseline clinical, laboratory, and imaging variables were analyzed to identify predictors of LOS. Significant variables were entered into a multivariate logistic regression analysis.

Results—

Among 216 acute stroke patients receiving rtPA, the median LOS was 6 days. LOS was >7 days in 102 (49%) patients. Age ≥70 (odds ratio [OR], 2.2; 95% CI, 1.2 to 4.0), lack of improvement at 24 hours (OR, 2.5; 95% CI, 1.4 to 4.4), prestroke modified Rankin Scale ≥2 (OR, 2.4; 95% CI, 1.2 to 4.9), baseline National Institutes of Health Stroke Scale score ≥15 (OR, 9.4; 95% CI, 3.2 to 27.6), cortical involvement (OR, 2.2; 95% CI, 1.2 to 3.9), and new infarction on the control computed tomography (CT; OR, 2.8; 95% CI, 1.4 to 5.9) were independent predictors of longer stay.

Conclusions—

Lack of improvement at 24 hours after rtPA, cortical involvement, and new infarction on the 24-hour CT scan are relevant variables that can independently affect the LOS. These new variables may be useful for establishing policy in relation to the organization and planning of the health care system.
Homocysteine-Lowering Treatment With Folic Acid, Cobalamin, and Pyridoxine Does Not Reduce Blood Markers of Inflammation, Endothelial Dysfunction, or Hypercoagulability in Patients With Previous Transient Ischemic Attack or Stroke
Authors: Dusitanond P. , Eikelboom J.W. , Hankey G.J. , Thom J. , Gilmore G. , Loh K. , Yi Q. , Klijn C.J.M. , Langton P. , van Bockxmeer F.M. , Baker R. , Jamrozik K.
Published: November 2004

Background and Purpose—

Epidemiological and laboratory studies suggest that increasing concentrations of plasma homocysteine (total homocysteine [tHcy]) accelerate cardiovascular disease by promoting vascular inflammation, endothelial dysfunction, and hypercoagulability.

Methods—

We conducted a randomized controlled trial in 285 patients with recent transient ischemic attack or stroke to examine the effect of lowering tHcy with folic acid 2 mg, vitamin B
12
0.5 mg, and vitamin B
6
25 mg compared with placebo on laboratory markers of vascular inflammation, endothelial dysfunction, and hypercoagulability.

Results—

At 6 months after randomization, there was no significant difference in blood concentrations of markers of vascular inflammation (high-sensitivity C-reactive protein [
P
=0.32]; soluble CD40L [
P
=0.33]; IL-6 [
P
=0.77]), endothelial dysfunction (vascular cell adhesion molecule-1 [
P
=0.27]; intercellular adhesion molecule-1 [
P
=0.08]; von Willebrand factor [
P
=0.92]), and hypercoagulability (P-selectin [
P
=0.33]; prothrombin fragment 1 and 2 [
P
=0.81]; D-dimer [
P
=0.88]) among patients assigned vitamin therapy compared with placebo despite a 3.7-μmol/L (95% CI, 2.7 to 4.7) reduction in total homocysteine (tHcy).

Conclusions—

Lowering tHcy by 3.7 μmol/L with folic acid-based multivitamin therapy does not significantly reduce blood concentrations of the biomarkers of inflammation, endothelial dysfunction, or hypercoagulability measured in our study. The possible explanations for our findings are: (1) these biomarkers are not sensitive to the effects of lowering tHcy (eg, multiple risk factor interventions may be required); (2) elevated tHcy causes cardiovascular disease by mechanisms other than the biomarkers measured; or (3) elevated tHcy is a noncausal marker of increased vascular risk.
Yield and Accuracy of Urgent Combined Carotid/Transcranial Ultrasound Testing in Acute Cerebral Ischemia
Authors: Chernyshev Oleg Y. , Garami Zsolt , Calleja Sergio , Song Joon , Campbell Morgan S. , Noser Elizabeth A. , Shaltoni Hashem , Chen Chin-I , Iguchi Yasuyuki , Grotta James C. , Alexandrov Andrei V.
Published: November 2004

Background and Purpose—

We routinely perform an urgent bedside neurovascular ultrasound examination (NVUE) with carotid/vertebral duplex and transcranial Doppler (TCD) in patients with acute cerebral ischemia. We aimed to determine the yield and accuracy of NVUE to identify lesions amenable for interventional treatment (LAITs).

Methods—

NVUE was performed with portable carotid duplex and TCD using standardized fast-track (<15 minutes) insonation protocols. Digital subtraction angiography (DSA) was the gold standard for identifying LAIT. These lesions were defined as proximal intra- or extracranial occlusions, near-occlusions, ≥50% stenoses or thrombus in the symptomatic artery.

Results—

One hundred and fifty patients (70 women, mean age 66±15 years) underwent NVUE at median 128 minutes after symptom onset. Fifty-four patients (36%) received intravenous or intra-arterial thrombolysis (median National Institutes of Health Stroke Scale (NIHSS) score 14, range 4 to 29; 81% had NIHSS ≥10 points). NVUE demonstrated LAITs in 98% of patients eligible for thrombolysis, 76% of acute stroke patients ineligible for thrombolysis (n=63), and 42% in patients with transient ischemic attack (n=33),
P
<0.001. Urgent DSA was performed in 30 patients on average 230 minutes after NVUE. Compared with DSA, NVUE predicted LAIT presence with 100% sensitivity and 100% specificity, although individual accuracy parameters for TCD and carotid duplex specific to occlusion location ranged 75% to 96% because of the presence of tandem lesions and 10% rate of no temporal windows.

Conclusions—

Bedside neurovascular ultrasound examination, combining carotid/vertebral duplex with TCD yields a substantial proportion of LAITs in excellent agreement with urgent DSA.
Sex-Based Differences in Response to Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke
Authors: Kent David M. , Price Lori Lyn , Ringleb Peter , Hill Michael D. , Selker Harry P.
Published: November 2004

Background and Purpose—

Women experience worse outcomes after stroke compared with men. Prior work has suggested sex-based differences in coagulation and fibrinolysis markers in subjects with acute stroke. We explored whether sex might modify the effect of recombinant tissue plasminogen activator (rtPA) on outcomes in patients with acute ischemic stroke.

Methods—

Using a combined database including subjects from the National Institute of Neurological Disorders and Stroke (NINDS), Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) A and B, and the Second European Cooperative Acute Stroke Study (ECASS II) trials, we examined 90-day outcomes in patients randomized to rtPA versus placebo by sex. We used logistic regression to control for potential confounders.

Results—

Among 988 women treated between 0 and 6 hours from symptom onset, patients receiving rtPA were significantly more likely than those receiving placebo to have a modified Rankin Score ≤1 (40.5% versus 30.3%,
P
<0.0008). Among 1190 men, the trend toward benefit in the overall group did not reach statistical significance (38.5% versus 36.7%,
P
=0.52). An unadjusted analysis showed that women were significantly more likely to benefit from rtPA compared with men (
P
=0.04). Controlling for age, baseline National Institutes of Health Stroke Scale, diabetes, symptom onset to treatment time, prior stroke, systolic blood pressure, extent of hypoattenuation on baseline computed tomography scan and several significant interaction terms (including onset to treatment time–by-treatment and systolic blood pressure–by treatment) did not substantially change the strength of the interaction between gender and rtPA treatment (
P
=0.04).

Conclusions—

In this pooled analysis of rtPA in acute ischemic stroke, women benefited more than men, and the usual gender difference in outcome favoring men was not observed in the thrombolytic therapy group. For patients presenting at later time intervals, when the risks and benefits of rtPA are more finely balanced, sex may be an important variable to consider for patient selection.
An fMRI Investigation of Speech and Tone Segmentation
Authors: LoCasto Paul C. , Krebs-Noble Donna , Gullapalli Rao P. , Burton Martha W.
Published: November 2004

Recent research strongly indicates that phonological tasks activate a subregion of the inferior frontal gyrus. The purpose of the present fMRI study was to investigate the extent to which activation of this region during phonological processing is due to speech processes per se such as articulatory recoding or to other cognitive task demands such as working memory. Thus, we compared activation patterns during segmentation of speech and tone sequences to a tone discrimination task. In particular, participants performed same/different judgments on pairs of words, pseudowords, and tone sequences that required segmentation of a continuous acoustic signal as well as tone pairs that did not require segmentation. Accuracy and reaction time data showed that speech and tone sequence segmentation conditions patterned more similarly to each other than to tone discrimination pairs. Analyses of group data revealed strong activation of the region at the border of the left inferior and middle frontal gyrus for all three segmentation conditions compared to tone discrimination, but no consistent differences were observed when word and pseudoword segmentation were directly contrasted. Analyses of individual subjects indicated that a large number of participants activated a small area of the middle frontal gyrus during the speech conditions compared to the sequences. These results suggest that a significant portion of active frontal areas is recruited for extracting acoustic information and maintaining it in memory for decision. However, some regions at the border of the inferior/middle frontal gyrus may be unique to speech segmentation.
Evidence for Neural Effects of Repetition that Directly Correlate with Behavioral Priming
Authors: Maccotta Luigi , Buckner Randy L.
Published: November 2004

Stimulus repetition associates with neural activity reductions during tasks that elicit behavioral priming. Here we present direct evidence for a quantitative relation between neural activity reductions and behavioral priming. Fifty-four subjects performed a word classification task while being scanned with functional MRI. Activity reductions were found in multiple high-level cortical regions including those within the prefrontal cortex. Importantly, activity within several of these regions, including the prefrontal cortex, correlated with behavior such that greater activity reductions associated with faster performance. Whole-brain correlational analyses confirmed the observation of anatomic overlap between regions showing activity reductions and those showing direct brain–behavioral correlations. The finding of a quantitative relation between neural and behavioral effects in frontal regions suggests that repetition reduces frontally mediated processing in a manner that ultimately facilitates behavior.
Neural Correlates of Syntactic Ambiguity in Sentence Comprehension for Low and High Span Readers
Authors: Fiebach Christian J. , Vos Sandra H. , Friederici Angela D.
Published: November 2004

Syntactically ambiguous sentences have been found to be difficult to process, in particular, for individuals with low working memory capacity. The current study used fMRI to investigate the neural basis of this effect in the processing of written sentences. Participants with high and low working memory capacity read sentences with either a short or long region of temporary syntactic ambiguity while being scanned. A distributed left-dominant network in the peri-sylvian region was identified to support sentence processing in the critical region of the sentence. Within this network, only the superior portion of Broca's area (BA 44) and a parietal region showed an activation increase as a function of the length of the syntactically ambiguous region in the sentence. Furthermore, it was only the BA 44 region that exhibited an interaction of working memory span, length of the syntactic ambiguity, and sentence complexity. In this area, the activation increase for syntactically more complex sentences became only significant under longer regions of ambiguity, and for low span readers only. This finding suggests that neural activity in BA 44 increases during sentence comprehension when processing demands increase, be it due to syntactic processing demands or by an interaction with the individually available working memory capacity.
Interference of Left and Right Cerebellar rTMS with Procedural Learning
Authors: Torriero Sara , Oliveri Massimiliano , Koch Giacomo , Caltagirone Carlo , Petrosini Laura
Published: November 2004

Increasing evidence suggests cerebellar involvement in procedural learning. To further analyze its role and to assess whether it has a lateralized influence, in the present study we used a repetitive transcranial magnetic stimulation interference approach in a group of normal subjects performing a serial reaction time task.

We studied 36 normal volunteers: 13 subjects underwent repetitive transcranial magnetic stimulation on the left cerebellum and performed the task with the right (6 subjects) or left (7 subjects) hand; 10 subjects underwent repetitive transcranial magnetic stimulation on the right cerebellum and performed the task with the hand ipsilateral (5 subjects) or contralateral (5 subjects) to the stimulation; another 13 subjects served as controls and were not submitted to repetitive transcranial magnetic stimulation; 7 of them performed the task with the right hand and 6 with the left hand. The main results show that interference with the activity of the lateral cerebellum induces a significant decrease of procedural learning: Interference with the right cerebellar hemisphere activity induces a significant decrease in procedural learning regardless of the hand used to perform the serial reaction time task, whereas left cerebellar hemisphere activity seems more linked with procedural learning through the ipsilateral hand.

In conclusion, the present study shows for the first time that a transient interference with the functions of the cerebellar cortex results in an impairment of procedural learning in normal subjects and it provides new evidences for interhemispheric differences in the lateral cerebellum.
Visual Activation in Prefrontal Cortex is Stronger in Monkeys than in Humans
Authors: Denys Katrien , Vanduffel Wim , Fize Denis , Nelissen Koen , Sawamura Hiromasa , Georgieva Svetlana , Vogels Rufin , Van Essen David , Orban Guy A.
Published: November 2004

The prefrontal cortex supports many cognitive abilities, which humans share to some degree with monkeys. The specialized functions of the prefrontal cortex depend both on the nature of its inputs from other brain regions and on distinctive aspects of local processing. We used functional MRI to compare prefrontal activity between monkey and human subjects when they viewed identical images of objects, either intact or scrambled. Visual object-related activation of the lateral prefrontal cortex was observed in both species, but was stronger in monkeys than in humans, both in magnitude (factors 2–3) and in spatial extent (fivefold or more as a percentage of prefrontal volume). This difference was observed for two different stimulus sets, at two field strengths, and over a range of tasks. These results suggest that there may be more volitional control over visual processing in humans than in monkeys.
Left Inferior Prefrontal Cortex Activity Reflects Inhibitory Rather Than Facilitatory Priming
Authors: Cardillo Eileen R. , Aydelott Jennifer , Matthews Paul M. , Devlin Joseph T.
Published: November 2004

Functional neuroimaging has demonstrated reduced activation correlated with behavioral priming effects, a finding generally interpreted in terms of facilitated retrieval of target items in the context of related primes. Without a neutral prime, however, one cannot separate facilitatory effects of related primes from inhibitory effects of unrelated primes. Here we report an auditory semantic priming paradigm with congruent (“The boy bounced the ball”), neutral (“The next item is ball”), and incongruent (“Pasta is my favorite kind of ball”) sentence trials. As previously reported, reduced left inferior prefrontal cortex activation was observed for congruent relative to incongruent trials; however, the neutral condition allowed us to show that the effect arose from increased activation in the incongruent condition rather than reduced activation for congruent trials. Our results suggest that the left inferior prefrontal cortex inhibits interference from prepotent representations in order to select a task-appropriate target, and is consistent with its broader role in behavioral inhibition.
Morphosyntax, Prosody, and Linking Elements: The Auditory Processing of German Nominal Compounds
Authors: Koester Dirk , Gunter Th. C. , Wagner S. , Friederici A. D.
Published: November 2004

The morphosyntactic decomposition of German compound words and a proposed function of linking elements were examined during auditory processing using event-related brain potentials. In Experiment 1, the syntactic gender agreement was manipulated between a determiner and the initial compound constituent (the “nonhead” constituent), and between a determiner and the last constituent (“head”). Although only the head is (morpho)syntactically relevant in German, both constituents elicited a left-anterior negativity if its gender was incongruent. This strongly suggests that compounds are morphosyntactically decomposed. Experiment 2 tested the function of those linking elements which are homophonous to plural morphemes. It has been previously suggested that these indicate the number of nonhead constituents. The number agreement was manipulated for both constituents analogous to Experiment 1. Number-incongruent heads, but not nonhead constituents, elicited an N400 and a subsequent broad negativity, suggesting that linking elements are not processed as plural morphemes. Experiment 3 showed that prosodic cues (duration and fundamental frequency) are employed to differentiate between compounds and single nouns and, thereby, betwen linking elements and plural morphemes. Number-incongruent words elicited a broad negativity if they were produced with a single noun prosody; the same words elicited no event-related potential effect if produced with a compound prosody. A dual-route model can account for the influence of prosody on morphosyntactic processing.
Mickey and Mr. Gumpy
Authors: Davies Máire Messenger
Published: November 2004

This article reviews aspects of children's global culture from a number of perspectives: political/economic, including children's cultural 'rights' as asserted in the International Convention on the Rights of the Child (1989); psychological, including evolutionary psychology and theories of mind studies; and empirical media studies, incorporating data based on 6-to 13-year-old children's own discussions. It suggests that psychologically functional and pleasurable aspects of children's media need to be incorporated into more familiar arguments in media and cultural studies about commodification and 'Disneyfication'. Some children's stories may necessarily be universal as well as global.
Embarrassment, Education and Erotics
Authors: Bragg Sara , Buckingham David
Published: November 2004

This article discusses parents' and young people's accounts of family television viewing, produced as part of a research project into responses to sexual content in the media. The analysis identifies how practices of media consumption, such as parents 'discussing' social issues in drama with their children, are gendered and gendering. These in turn contribute to young people's understandings of gender and sexual identities. The article argues that familiar anecdotes, for example, about the 'embarrassment' of communally watching sexual images on television, can be an occasion for challenging or reinforcing family power relations and making identity claims, both at the time of viewing and of retelling.
The Pleasures and Pains of Pikachu
Authors: Jordan Tim
Published: November 2004

Pokémon is a phenomenon that has enticed children throughout the world. The essential components of the Pokémon universe are introduced first by outlining the logics of life in Pokémon and then by presenting the main components through which these logics are realized: videogames, cartoons, cards, movies and merchandising. These five components and associated logics are then outlined as a form of branded hyperdifferentiating capitalism. In Pokémon, everything that seems single in fact multiplies, producing innumerable opportunities to define commodities that are yet held together by the Pokémon 'brand'. This aspect of Pokémon is carried mainly by the videogames and cards. A second axis of Pokémon is then explored in the potential it offers for children to explore their emotional development both in and out of family life. Here, numerous resources are found through which the inner subconscious development of children can be explored using Pokémon characters and stories as metaphors. This aspect of Pokédmon is carried mainly by cartoons and movies. In conclusion, it is noted that although Pokémon offers resources-that may participate in the emotional development of children, these resources are also intimately tied into commodification.
The Wall Street Culture
Authors: Sjoberg Katarina
Published: November 2004

This article concerns Wall Street financial actors and how these actors construct a culture. The focus is twofold: on the one hand, prevailing discourses that provide a popular ideational setting and frame for Wall Street financial actors and their activities; and, on the other hand, how these actors perceive themselves and their work. The perspective used parallel understandings of financial markets as cultural and social phenomena, stressing that professional finance cannot solely be understood in terms of structured economic mechanisms with relatively clear causes and effects. The findings point out that in a sociocultural system cherishing moneymaking as a strong value orientation, financial actors are given the means to both influence and direct money transactions and investments, as well as to preserve the prestige attached to such activities. At the same time, this orientation also provides them with the means to build images of themselves and their work, incorporating these as part of their self-identification.
Comparison between exhaled and sputum oxidative stress biomarkers in chronic airway inflammation
Authors: Corradi M. , Pignatti P. , Manini P. , Andreoli R. , Goldoni M. , Poppa M. , Moscato G. , Balbi B. , Mutti A.
Published: November 2004

The aim of the present study was to compare aldehyde levels resulting from lipid peroxidation in exhaled breath condensate (EBC) and induced sputum (IS) supernatant of subjects with asthma and chronic obstructive pulmonary disease (COPD).

Aldehydes (malondialdehyde (MDA), acrolein,n-hexanal (C6),n-heptanal (C7),n-nonanal (C9), 4-hydroxynonenal (HNE) and 4-hydroxyhexenal (HHE)) in both biological fluids were measured by liquid chromatography-tandem mass spectrometry.

MDA concentrations in sputum were 132.5 nM (82.5–268.8) and 23.7 nM (9–53.7) in EBC. Similarly, C6, C7 and C9 concentrations in IS were 1.5–4.7-fold higher than in EBC. Acrolein levels were 131.1 nM (55.6–264.6) in IS and 45.3 nM (14.4–127.1) in EBC. The concentrations of HNE and HHE in IS were not significantly different from the levels in EBC. Aldehyde levels in EBC did not show any correlation with aldehyde levels in IS or with differential sputum cellular count. In COPD, MDA in EBC, but not its IS counterpart, was negatively correlated with the severity of disease.

In conclusion, the data presented here show that aldehydes can be detected in both exhaled breath condensate and supernatant of induced sputum, but that their relative concentrations are different and not correlated with each other. Therefore, with regard to lipid peroxidation products, exhaled breath condensate and induced sputum must be considered as independent techniques.
Thrombin induces collagen gel contraction partially through PAR1 activation and PKC-ϵ
Authors: Fang Q. , Liu X. , Abe S. , Kobayashi T. , Wang X.Q. , Kohyama T. , Hashimoto M. , Wyatt T. , Rennard S.I.
Published: November 2004

The ability of fibroblasts to contract three-dimensional collagen gels has been used as anin vitromodel of the tissue contraction which characterises both normal repair and fibrosis. Among its actions, thrombin can activate the protease-activated receptor (PAR)1 and, thereby, stimulate inflammation and repair. The current study evaluated whether thrombin could stimulate fibroblast-mediated collagen gel contraction by activating PAR1 and whether its downstream signalling depends on protein kinase C (PKC)-ϵ.

Human foetal lung fibroblasts (HFL-1) were cultured in three-dimensional collagen gels and the area of the gels was measured by image analyser.

Both thrombin and TFLLR, a selective PAR1 agonist, stimulated collagen gel contraction mediated by HFL-1. After RNA interference-mediated PAR1 knockdown in HFL-1, both thrombin and the PAR1 agonist-induced gel contraction were partially inhibited (by 22.4±2.2% and 17.6±5.6%, respectively). The gel contraction stimulated by thrombin was also reduced by a nonspecific PKC inhibitor and a calcium-independent PKC-ϵ inhibitor. Both thrombin and TFLLR significantly increased PKC-ϵ activity, and this effect was blocked by PAR1 knockdown.

Thrombin stimulates collagen gel contraction at least partially through activation of protease-activated receptor 1 and protein kinase C-ϵ, and may contribute to tissue remodelling in inflammatory airway and lung diseases.
Levofloxacinversusclarithromycin in COPD exacerbation: focus on exacerbation-free interval
Authors: Lode H. , Eller J. , Linnhoff A. , Ioanas M. ,   the Evaluation of Therapy-Free Interval in COPD Patients Study Group
Published: November 2004

Antibiotic treatment of bacterial exacerbation of chronic obstructive pulmonary disease (COPD) shows some immediate clinical benefits and may also minimise the frequency of further recurrences.

Patients (n=511) were enrolled into a randomised double-blind multicentric study comparing the exacerbation-free interval (EFI), efficacy and safety of 7-day levofloxacinversus10-day clarithromycin in patients with COPD exacerbation. Patients were monitored over a 1-yr period. A total of 434 patients (per protocol population) received the medication for ≥5 days.

The median EFI in the per protocol population was 300 days for levofloxacin and 350 days for clarithromycin. For patients with a new documented exacerbation during follow-up (n=223), the median EFI was 100.5 days in the levofloxacin group and 95 days for clarithromycin. No significant differences in EFI between groups could be observed when stratifying the study population according to microbial aetiology and severity of bronchial obstruction. Levofloxacin and clarithromycin showed similar clinical success rates. The bacteriological success rate was significantly higher in the levofloxacin group. Both antibiotics were well tolerated.

In summary, levofloxacin was associated with a significantly higher bacteriological eradication rate but similar exacerbation-free interval in patients with chronic obstructive pulmonary disease exacerbation compared to clarithromycin.