bluuebunny/crossref_metadata_2025 huggingface dataset:
CD34
+
Cells Home, Proliferate, and Participate in Capillary Formation, and in Combination With CD34
−
Cells Enhance Tube Formation in a 3-Dimensional Matrix
Authors: Rookmaaker Maarten B. , Verhaar Marianne C. , Loomans Cindy J.M. , Verloop Robert , Peters Erna , Westerweel Peter E. , Murohara Toyoaki , Staal Frank J.T. , van Zonneveld Anton Jan , Koolwijk Pieter , Rabelink Ton J. , van Hinsbergh Victor W.M.
Published: July 2005

Objective—

Emerging evidence suggests that human blood contains bone marrow (BM)-derived endothelial progenitor cells that contribute to postnatal neovascularization. Clinical trials demonstrated that administration of BM-cells can enhance neovascularization. Most studies, however, used crude cell populations. Identifying the role of different cell populations is important for developing improved cellular therapies.

Methods and Results—

Effects of the hematopoietic stem cell–containing CD34
+
cell population on migration, proliferation, differentiation, stimulation of, and participation in capillary-like tubule formation were assessed in an in vitro 3-dimensional matrix model using human microvascular endothelial cells. During movement over the endothelial monolayer, CD34
+
cells remained stuck at sites of capillary tube formation and time- and dose-dependently formed cell clusters. Immunohistochemistry confirmed homing and proliferation of CD34
+
cells in and around capillary sprouts. CD34
+
cells were transduced with the LNGFR marker gene to allow tracing. LNGFR gene–transduced CD34
+
cells integrated in the tubular structures and stained positive for CD31 and UEA-1. CD34
+
cells alone stimulated neovascularization by 17%. Coculture with CD34
−
cells led to 68% enhancement of neovascularization, whereas CD34
−
cells displayed a variable response by themselves. Cell–cell contact between CD34
+
and CD34
−
cells facilitated endothelial differentiation of CD34
+
cells.

Conclusions—

Our data suggest that administration of CD34
+
-enriched cell populations may significantly improve neovascularization and point at an important supportive role for (endogenous or exogenous) CD34
−
cells.
Tendon Xanthomas in Familial Hypercholesterolemia Are Associated With Cardiovascular Risk Independently of the Low-Density Lipoprotein Receptor Gene Mutation
Authors: Civeira Fernando , Castillo Sergio , Alonso Rodrigo , Meriño-Ibarra Erardo , Cenarro Ana , Artied Marta , Martín-Fuentes Paula , Ros Emilio , Pocoví Miguel , Mata Pedro
Published: July 2005

Objective—

To investigate the significance of tendon xanthomas (TX) in heterozygous subjects with familial hypercholesterolemia (hFH).

Methods and Results—

951 men and women with genetic diagnosis of hFH were studied, of whom 278 (29.2%) presented TX. TX frequency increased with age from 6.9% in subjects 20 to 30 years to 38.3% at 51 to 60 years, with a decrease in those older than 60 years. Total and low-density lipoprotein (LDL) cholesterol were higher in TX
+
than in TX
−
subjects (439.0±78.5 mg/dL and 363.1±76.5 mg/dL versus 400.6±73.4 and 323.3±71.0, respectively;
P
=0.001). High-density lipoprotein (HDL) cholesterol was lower in TX
+
than in TX
−
subjects (50.4±15.0 mg/dL versus 53.1±14.8 mg/dL;
P
=0.005). Lp(a), apolipoprotein E genotype, and type of LDL receptor gene mutation showed no differences between groups. 102 TX
+
reported premature cardiovascular disease (CVD) (36.7%) versus 93 TX
−
(13.8%) (
P
=0.001). The relative odds for premature CVD were higher in women (4.49 versus 2.26), and increased in hFH younger than 51 years to 3.60 (95% CI, 1.703 to 7.608) in men and to 17.1 (95% CI, 2.697 to 108.920) in women. In the multivariate analysis, age, male sex, LDL cholesterol, and hypertension showed significant positive association with TX, whereas body mass index showed negative association with TX.

Conclusions—

TX are associated with cardiovascular risk factors and higher CVD, indicating that their detection indicates the need for more aggressive lipid-lowering intervention.
Rosiglitazone Attenuates Atherosclerosis in a Model of Insulin Insufficiency Independent of Its Metabolic Effects
Authors: Calkin Anna C. , Forbes Josephine M. , Smith Craig M. , Lassila Markus , Cooper Mark E. , Jandeleit-Dahm Karin A. , Allen Terri J.
Published: July 2005

Objectives—

Recent studies have demonstrated a role for thiazolidinediones in attenuating atherosclerosis. However, these studies were performed in insulin-resistant animal models in association with reductions in insulin and glucose levels. To assess the vascular effects of thiazolidinediones, independent of their metabolic effects, we observed the effect of rosiglitazone on diabetes-associated atherosclerosis in a model of insulin insufficiency.

Methods and Results—

Control and diabetic apolipoprotein E–deficient mice received rosiglitazone or placebo. Diabetic mice demonstrated a 3-fold increase in plaque area, which was attenuated by rosiglitazone. There was no significant difference in glucose, insulin, or cholesterol levels between treated and untreated diabetic animals. Rosiglitazone attenuated the increase in superoxide production observed in diabetic mice. A 4-fold increase in the reverse cholesterol transport marker ABCA1 was observed in treated diabetic mice. Rosiglitazone reduced angiotensin II receptor gene expression in control and diabetic mice, and macrophage accumulation was increased in diabetic mice compared with controls and was attenuated by rosiglitazone.

Conclusions—

These findings suggest peroxisome proliferator-activated receptor-γ ligands such as rosiglitazone confer vascular protection independent of their effects on metabolic control. These antiatherosclerotic effects may have important clinical ramifications not only in insulin resistance/type 2 diabetes and also in type 1 diabetes.
Association Between Prostaglandin E Receptor Subtype EP4 Overexpression and Unstable Phenotype in Atherosclerotic Plaques in Human
Authors: Cipollone Francesco , Fazia Maria Luigia , Iezzi Annalisa , Cuccurullo Chiara , De Cesare Domenico , Ucchino Sante , Spigonardo Francesco , Marchetti Antonio , Buttitta Fiamma , Paloscia Leonardo , Mascellanti Marco , Cuccurullo Franco , Mezzetti Andrea
Published: July 2005

Objective—

We recently demonstrated that inducible cyclooxygenase/PGE synthase-1 (COX-2/mPGES-1) are overexpressed in symptomatic plaques in association with PGE
2
-dependent metalloproteinase (matrix metalloproteinase [MMP]) biosynthesis and plaque rupture. However, it is not known which of the 4 PGE
2
receptors (EP1–4) mediates macrophage metalloproteinase generation. The aim of this study was to characterize EP1–4 expression in plaques from symptomatic and asymptomatic patients undergoing carotid endarterectomy and correlate it with the extent of inflammatory infiltration, COX-2/mPGES-1 and MMP expression and clinical features of patients’ presentation.

Methods and Results—

Plaques were analyzed for COX-2, mPGES-1, EP1–4, MMP-2, and MMP-9 by immunohistochemistry, reverse-transcription polymerase chain reaction and Western blot; zymography was used to detect MMP activity. We observed strong EP4 immunoreactivity, only very weak staining for EP2, and no expression of EP1 and EP3 in atherosclerotic plaques. EP4 was more abundant in MMP-rich symptomatic lesions, whereas EP2 was no different between symptomatic and asymptomatic plaques. Finally, MMP induction by PGE
2
in vitro was inhibited by the EP4 antagonist L-161 982, but not by its inactive analog L-161 983 or by the EP2 antagonist AH6809.

Conclusions—

This study shows that EP4 overexpression is associated with enhanced inflammatory reaction in atherosclerotic plaques. This effect might contribute to plaque destabilization by inducing culprit metalloproteinase expression.
Endogenous NO Blockade Enhances Tissue Factor Expression via Increased Ca
2+
Influx Through MCP-1 in Endothelial Cells by Monocyte Adhesion
Authors: Sakamoto Takayuki , Ishibashi Toshiyuki , Sakamoto Nobuo , Sugimoto Koichi , Egashira Kensuke , Ohkawara Hiroshi , Nagata Kenji , Yokoyama Keiko , Kamioka Masashi , Ichiki Toshihiro , Sugimoto Naotoshi , Kurabayashi Masahiko , Suzuki Koji , Takuwa Yoh , Maruyama Yukio
Published: July 2005

Objective—

Ca
2+
plays an important role in tissue factor (TF) gene expression. We investigated the role of endogenous nitric oxide (NO) in the induction of TF expression in endothelial cells (ECs) by monocyte adhesion and the mechanisms of NO action.

Methods and Results—

Inhibition of endogenous NO by

N
ω

-nitro-
l
-arginine methyl ester (
l
-NAME) enhanced TF promoter activity and protein expression induced in human coronary ECs by monocyte adhesion, as well as EC surface TF activity.
l
-NAME also induced monocyte chemoattractant protein-1 (MCP-1) expression, which was blocked by an NO donor, NOC18. Exogenous MCP-1 enhanced TF expression induced by monocyte adhesion, whereas adenovirus-mediated expression of the mutant MCP-1, 7ND, abolished the
l
-NAME enhancement of TF expression induced by monocyte adhesion. Monocyte attachment to
l
-NAME–treated ECs increased Ca
2+
influx, which was prevented by NOC18, anti–MCP-1 antibody or 7ND. These results indicate that the binding of increased MCP-1 induced by endogenous NO blockade to CCR2 mediated the enhancement of Ca
2+
influx only when monocytes adhered to ECs, which upregulated TF expression in ECs triggered by monocyte adhesion.

Conclusion—

MCP-1/CCR2 may play a role in Ca
2+
influx-dependent TF regulation in the monocyte–EC interaction in the impairment of NO synthesis.
Prevention of Cardiac Hypertrophy by Atorvastatin in a Transgenic Rabbit Model of Human Hypertrophic Cardiomyopathy
Authors: Senthil Vinitha , Chen Suet N. , Tsybouleva Natalie , Halder Tripti , Nagueh Sherif F. , Willerson James T. , Roberts Robert , Marian A.J.
Published: July 2005

Cardiac hypertrophy, a major determinant of morbidity and mortality in hypertrophic cardiomyopathy (HCM), is considered a secondary phenotype and potentially preventable. To test this hypothesis, we screened 30 5- to 6-month-old β-myosin heavy chain Q403 transgenic rabbits by echocardiography and selected 26 without cardiac hypertrophy. We randomized the transgenic rabbits to treatment with atorvastatin (2.5 mg/Kg/d), known to block hypertrophic signaling or a placebo. We included 15 nontransgenic rabbits as controls. Cardiac phenotype was analyzed serially before, 6 and 12 months after randomization. Serum total cholesterol levels were reduced by 49% with atorvastatin administration. Left-ventricular mass, wall thickness; myocyte size, myocardial levels of molecular markers of hypertrophy, lipid peroxides, and oxidized mitochondrial DNA; and the number of terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive myocytes were increased significantly in the placebo but not in the atorvastatin group. Myocardium catalase mRNA levels were decreased by 5-fold in the placebo but were normal in the atorvastatin group. Catalase protein level and activity were not significantly changed. Levels of membrane-bound Ras and phospho-p44/42 mitogen-activated-protein kinase (MAPK) were increased in the placebo group (≈2.5 fold) but were reduced in the atorvastatin group. Levels of GTP- and membrane-bound RhoA and Rac1, phospho-p38, and phospho-c-Jun NH2-terminal kinases were unchanged. Thus, atorvastatin prevented development of cardiac hypertrophy; determined at organ, cellular, and molecular levels, partly through reducing active Ras and p44/42 MAPK. The results indicate potential beneficial effects of atorvastatin in prevention of cardiac hypertrophy, a major determinant of morbidity in all forms of cardiovascular diseases, and beckon clinical studies in humans with HCM.
Mitochondria-Derived Reactive Oxygen Species Dilate Cerebral Arteries by Activating Ca
2+
Sparks
Authors: Xi Qi , Cheranov Sergei Y. , Jaggar Jonathan H.
Published: July 2005

Mitochondria regulate intracellular calcium (Ca
2+
) signals in smooth muscle cells, but mechanisms mediating these effects, and the functional relevance, are poorly understood. Similarly, antihypertensive ATP-sensitive potassium (K
ATP
) channel openers (KCOs) activate plasma membrane K
ATP
channels and depolarize mitochondria in several cell types, but the contribution of each of these mechanisms to vasodilation is unclear. Here, we show that cerebral artery smooth muscle cell mitochondria are most effectively depolarized by diazoxide (−15%, tetramethylrhodamine [TMRM]), less so by levcromakalim, and not depolarized by pinacidil. KCO-induced mitochondrial depolarization increased the generation of mitochondria-derived reactive oxygen species (ROS) that stimulated Ca
2+
sparks and large-conductance Ca
2+
-activated potassium (K
Ca
) channels, leading to transient K
Ca
current activation. KCO-induced mitochondrial depolarization and transient K
Ca
current activation were attenuated by 5-HD and glibenclamide, K
ATP
channel blockers. MnTMPyP, an antioxidant, and Ca
2+
spark and K
Ca
channel blockers reduced diazoxide-induced vasodilations by >60%, but did not alter dilations induced by pinacidil, which did not elevate ROS. Data suggest diazoxide drives ROS generation by inducing a small mitochondrial depolarization, because nanomolar CCCP, a protonophore, similarly depolarized mitochondria, elevated ROS, and activated transient K
Ca
currents. In contrast, micromolar CCCP, or rotenone, an electron transport chain blocker, induced a large mitochondrial depolarization (−84%, TMRM), reduced ROS, and inhibited transient K
Ca
currents. In summary, data demonstrate that mitochondria-derived ROS dilate cerebral arteries by activating Ca
2+
sparks, that some antihypertensive KCOs dilate by stimulating this pathway, and that small and large mitochondrial depolarizations lead to differential regulation of ROS and Ca
2+
sparks.
CD14+CD34
low
Cells With Stem Cell Phenotypic and Functional Features Are the Major Source of Circulating Endothelial Progenitors
Authors: Romagnani Paola , Annunziato Francesco , Liotta Francesco , Lazzeri Elena , Mazzinghi Benedetta , Frosali Francesca , Cosmi Lorenzo , Maggi Laura , Lasagni Laura , Scheffold Alexander , Kruger Manuela , Dimmeler Stefanie , Marra Fabio , Gensini Gianfranco , Maggi Enrico , Romagnani Sergio
Published: July 2005

Endothelial progenitor cells (EPCs) seem to be a promising tool for cell therapy of acute myocardial infarction, but their nature is still unclear. We show here that EPCs obtainable from peripheral blood (PB) derive from the adhesion-related selection in culture of a subset of CD14+ cells, which, when assessed by the highly-sensitive antibody-conjugated magnetofluorescent liposomes (ACMFL) technique, were found to express CD34. These CD14+CD34
low
cells represented a variable proportion at individual level of CD14+ cells, ranging from 0.6% to 8.5% of all peripheral-blood leukocytes, and constituted the dominant population among circulating KDR+ cells. By using the ACMFL technique, virtually all CD14+ cells present in the bone marrow were found to be CD14+CD34
low
double-positive cells. EPCs, as well as purified circulating CD14+CD34
low
cells, exhibited high expression of embryonic stem cell (SC) markers Nanog and Oct-4, which were downregulated in a STAT3-independent manner when they differentiated into endothelial cells (ECs). Moreover, circulating CD14+CD34
low
cells, but not CD14+CD34− cells, proliferated in response to SC growth factors, and exhibited clonogenicity and multipotency, as shown by their ability to differentiate not only into ECs, but also into osteoblasts, adipocytes, or neural cells. The results of this study may reconcile apparently contradictory data of the literature, showing the generation of PB-derived EPCs from either CD34+ or CD14+ cells. We suggest that the use of this previously unrecognized population of circulating CD14+CD34
low
cells, which exhibit both phenotypic and functional features of SCs, may be useful in improving cell-based therapies of vascular and tissue damage.
Can Transcranial Doppler Discriminate Between Solid and Gaseous Microemboli?
Authors: Markus Hugh S. , Punter Martin
Published: July 2005

Background and Purpose—

Transcranial Doppler ultrasound can reliably detect both gaseous and solid cerebral emboli. However, conventional equipment is unable to discriminate between gaseous and solid emboli. This is a major limitation in situations in which the 2 coexist, because they may have very different clinical relevance. Recently, a novel Embo-Dop system, using insonation at 2 ultrasound transducer frequencies, has been developed. An initial study with a small sample size suggested it provided excellent discrimination. We performed a validation study in subjects with embolic signals of known nature.

Methods—

Gaseous embolic signals were obtained in 7 patients with known patient foramen ovale by intravenous injection of agitated saline injections. Solid embolic signals were obtained in patients with symptomatic carotid stenosis (N=23). Discrimination of the 2 using the Embo-Dop system dual-frequency system was assessed. It was compared with discrimination using embolic signal maximum intensity with an intensity threshold.

Results—

One hundred forty-five solid embolic signals were recorded from carotid stenosis patients. Seventy-three were classified as solid and 72 as gaseous by the Embo-Dop system. Six hundred forty-eight gaseous embolic signals were recorded from 7 patients with patent foramen ovale. Six hundred twenty-five were classified as gaseous and 23 as solid. This gave a sensitivity of 50.3% and specificity of 96.5% for detecting solid embolic signals. Discrimination was better than using a simple intensity threshold.

Conclusions—

The Embo-Dop dual-frequency system allows better discrimination than a simple intensity threshold but it is not accurate enough for use in clinical or research studies. Further work is needed to develop reliable clinical systems for discrimination of emboli.
Prognostic Implications of Right-Sided Insular Damage, Cardiac Autonomic Derangement, and Arrhythmias After Acute Ischemic Stroke
Authors: Colivicchi Furio , Bassi Andrea , Santini Massimo , Caltagirone Carlo
Published: July 2005

Background and Purpose—Acute stroke is associated with impairment of cardiac autonomic balance and increased incidence of arrhythmias. These abnormalities appear more relevant in the case of involvement of the right insula in the infarct area. The aim of this study was to assess the impact of right-sided insular damage, cardiac autonomic derangement, and arrhythmias on clinical outcome after acute ischemic stroke.

Methods—Holter monitoring for 24 hours was performed in 208 consecutive patients with first-ever acute ischemic stroke. Time- and frequency-domain measures of heart rate variability and arrhythmias were considered in all cases. All patients were followed for a 12-month period after the initial event.

Results—During the 12-month follow-up period, 48 patients died (1-year probability of death, 0.23; 95% CI, 0.17 to 0.30). Multivariate analysis demonstrated that age (hazard ratio [HR], 1.06; 95% CI, 1.01 to 1.10;P=0.0087), stroke severity on admission (HR, 1.25; 95% CI, 1.13 to 1.39;P=0.0001), presence of right-sided insular damage (HR, 2.01; 95% CI, 1.13 to 1.39;P=0.0187), as well as lower values of the SD of all normal-to-normal RR intervals (HR, 3.32; 95% CI, 1.67 to 6.24;P=0.002), and presence of nonsustained ventricular tachycardia during Holter monitoring (HR, 2.99; 95% CI, 1.58 to 5.67;P=0.0007) were independent predictors of 1-year mortality.

Conclusions—The integration of traditional risk stratifiers with autonomic and arrhythmic markers, and the careful search for right-sided insular involvement, may represent an effective approach for identification of stroke patients at risk for early mortality.
A Negative D-Dimer Assay Does Not Rule Out Cerebral Venous Thrombosis
Authors: Crassard Isabelle , Soria Claudine , Tzourio Christophe , Woimant France , Drouet Ludovic , Ducros Anne , Bousser Marie-Germaine
Published: July 2005

Background and Purpose—

Cerebral venous thrombosis (CVT) is an infrequent variety of cerebrovascular disease with a wide spectrum of clinical presentations and a notoriously difficult diagnosis. Previous reports have emphasized the potential clinical utility of D-dimer assay in CVT diagnosis.

Methods—

A rapid sensitive D-dimer assay was performed at entry in 73 patients with CVT <30 days duration, examined in our institution between 1999 and 2003.

Results—

The mean value of D-dimer levels was 1521 ng/mL; 7 patients (10% of all patients and 26% of those presenting with isolated headache) had values <500 ng/mL. In a multivariate analysis, isolated headache was the only variable associated with a negative D-dimer assay.

Conclusion—

A negative D-Dimer assay does not confidently rule out CVT, particularly in the setting of recent isolated headache.
Enhancing the Development and Approval of Acute Stroke Therapies
Authors: Fisher Marc
Published: July 2005

Background—

Previous Stroke Therapy Academic Industry Roundtable (STAIR) meetings focused on preclinical evidence of drug efficacy and enhancing acute stroke trial design and performance. A fourth (STAIR-IV) was held to discuss relevant issues related to acute stroke drug development and regulatory approval.

Summary of Review—

The STAIR-IV meeting had 3 main focus areas. The first topic was novel approaches to statistical design of acute stroke trials and appropriate outcome measures. The second focus was the need for better cooperation among participants in stroke therapy development that may be addressed through a national consortium of stroke trial centers in the United States and elsewhere. Lastly, regulatory issues related to the approval of novel mono and multiple acute stroke therapies were discussed.

Conclusions—

The development of additional acute stroke therapies represents a large unmet need with many remaining challenges and also opportunities to incorporate novel approaches to clinical trial design that will lead to regulatory approval. The STAIR-IV meeting explored new concepts of trial methodology and data analysis, initiatives for implementing a US clinical trialist consortium, and pertinent regulatory issues to expedite approval of novel therapies.
Elevated Serum Aminotransferase Level as a Predictor of Intracerebral Hemorrhage
Authors: Kim Hyeon Chang , Kang Dae Ryong , Nam Chung Mo , Hur Nam Wook , Shim Jee Seon , Jee Sun Ha , Suh Il
Published: July 2005

Background and Purpose—

Serum aminotransferase levels are known to be associated with cardiovascular risk factors, but the relation with stroke incidence is not well known. We investigated the relation between serum aminotransferase levels and the incidence of stroke.

Methods—

We measured serum aspartate and alanine aminotransferase levels and traditional cardiovascular risk factors in 108 464 Korean men, aged 35 to 59 years, in 1990 and 1992. Serum aminotransferase levels were classified into 3 categories (<35, 35 to 69, and ≥70 IU/L). The outcomes were hospital admissions and deaths from stroke subtypes (ischemic stroke, intracerebral hemorrhage [ICH], and subarachnoid hemorrhage [SAH]) from 1993 to 2002.

Results—

During the 10 years, 1728 ischemic, 1051 hemorrhagic (718 ICH and 222 SAH), and 243 unspecified stroke events occurred. After adjustment for age and other traditional risk factors and according to Cox proportional-hazards models, serum aminotransferase level had an independent positive associations with ICH. However, ischemic stroke and SAH were not associated with aminotransferase levels. Compared with the level <35 IU/L, the adjusted relative risks (95% confidence interval) of ICH for an aspartate aminotransferase level of 35 to 69 and ≥70 IU/L were 1.49 (1.21 to 1.83) and 4.21 (3.06 to 5.77), respectively. The corresponding risks for alanine aminotransferase were 1.34 (1.09 to 1.65) and 2.89 (2.09 to 4.01), respectively. These associations were consistent regardless of the level of obesity, blood pressure, fasting glucose, alcohol intake, and follow-up length.

Conclusions—

These findings suggest that an elevated aminotransferase level is a predictor of ICH. The biologic significance of aminotransferase level for the development of ICH merits further study.
Clinical-Diffusion Mismatch Predicts the Putative Penumbra With High Specificity
Authors: Prosser Jane , Butcher Ken , Allport Louise , Parsons Mark , MacGregor Lachlan , Desmond Patricia , Tress Brian , Davis Stephen
Published: July 2005

Background and Purpose—

Perfusion-diffusion (PWI-DWI) mismatch may represent the ischemic penumbra. The complexities associated with perfusion-weighted imaging (PWI) have restricted its use. Mismatch between stroke severity, assessed with the National Institutes of Health Stroke Scale (NIHSS), and the volume of the diffusion-weighted imaging (DWI) lesion (clinical-diffusion mismatch; CDM) has been suggested as a surrogate for PWI-DWI mismatch. We compared CDM with PWI and DWI in acute stroke.

Methods—

Seventy-nine hemispheric stroke patients were imaged within 24 hours of symptom onset and subacutely (3 to 5 days). CDM was defined as NIHSS ≥8 and DWI ≤25 mL. DWI lesion and PWI (Tmax+4s) volumes were measured by planimetric techniques. Acute PWI-DWI mismatch was examined as a continuous variable (mismatch volume=PWI
vol
−DWI
vol
) and a categorical variable (mismatch=PWI
vol
−DWI
vol
/DWI
vol
×100>20%). Early infarct expansion was calculated as DWI
subacute vol
/DWI
acute vol
.

Results—

In the 54 sub–6-hour patients, CDM detected PWI-DWI mismatch with a specificity of 93% (95% confidence interval [CI], 62% to 99%), a positive predictive value of 95% (95% CI, 77% to 100%), but a sensitivity of only 53% (95% CI, 34% to 68%). Alternate DWI and NIHSS cutpoints did not improve test performance characteristics. In addition, subacute DWI expansion was significantly greater in patients with CDM (
P
=0.01) compared with those without.

Conclusions—

CDM (NIH ≥8, DWI ≤25 mL) predicts the presence of PWI-DWI mismatch with high specificity and low sensitivity. CDM also predicts DWI expansion. CDM may be a useful selection tool in acute stroke therapies, including thrombolysis.
Linkage of Ischemic Stroke to the
PDE4D
Region on 5q in a Swedish Population
Authors: Nilsson-Ardnor Sofie , Wiklund Per-Gunnar , Lindgren Petter , Nilsson Anna Karin , Janunger Tomas , Escher Stefan A. , Hallbeck Björn , Stegmayr Birgitta , Asplund Kjell , Holmberg Dan
Published: July 2005

Background and Purpose—

Recent Icelandic studies have demonstrated linkage for common forms of stroke to chromosome 5q12 and association between phosphodiesterase4D (
PDE4D
) and ischemic stroke. Using a candidate region approach, we wanted to test the validity of these findings in a different population from northern Sweden.

Methods—

A total of 56 families with 117 affected individuals were included in the linkage study. Genotyping was performed with polymorphic microsatellite markers with an average distance of 4.5 cM on chromosome 5. In the association study, 275 cases of first-ever stroke were included together with 550 matched community controls. Polymorphisms were tested individually for association of
PDE4D
to stroke.

Results—

Maximum allele-sharing lod score in favor of linkage was observed at marker locus D5S424 (lod score=2.06;
P
=0.0010). Conditional logistic regression calculations revealed no significant association of ischemic stroke to the defined at-risk allele in
PDE4D
(odds ratio, 1.1; 95% confidence interval, 0.84 to 1.45). A protective effect may though be implied for 2 of the polymorphisms analyzed in
PDE4D
.

Conclusions—

Using a candidate region approach in a set of stroke families from northern Sweden, we have replicated linkage of stroke susceptibility to the
PDE4D
gene region on chromosome 5q. Association studies in an independent nested case-control sample from the same geographically located population suggested that different alleles confer susceptibility/protection to stroke in the Icelandic and the northern Swedish populations.
Risk of Hemorrhagic Stroke With Aspirin Use
Authors: Gorelick Philip B. , Weisman Steven M.
Published: July 2005

Background—

Low-dose aspirin is an important therapeutic option in the secondary prevention of myocardial infarction (MI) and ischemic stroke, especially in light of its unique cost-effectiveness and widespread availability. In addition, based on the results of a number of large studies, aspirin is also widely used in the primary prevention of MI. This review provides an update of the available data to offer greater clarity regarding the risks of aspirin with respect to hemorrhagic stroke, as well as insights regarding patient selection to minimize the risk of this complication.

Summary of Review—

In the secondary prevention of cardiovascular, cerebrovascular, and ischemic events, the evidence supports that the benefits of aspirin treatment significantly outweigh the risk of a major hemorrhage. The evidence from primary prevention of MI studies, including that from the recent Women’s Health Study evaluation of aspirin use in healthy women, demonstrate that the increased risk for hemorrhagic stroke is small, is comparable to the secondary prevention studies, and fails to achieve statistical significance. A reasonable estimate of the risk of hemorrhagic stroke associated with the use of aspirin in primary prevention patients is 0.2 events per 1000 patient-years, which is comparable to estimates of the risk associated with the use of aspirin in secondary prevention patients.

Conclusions—

When considering whether aspirin is appropriate, the absolute therapeutic cardiovascular benefits of aspirin must be balanced with the possible risks associated with its use, with the most serious being hemorrhagic stroke.
Staged Cerebral Revascularization in a Patient With an Occluded Common Carotid Artery
Authors: Rabb Craig H. , Moneta Gregory L.
Published: July 2005

Background and Purpose—

We report a management strategy for cerebral revascularization in a patient with an occluded common carotid artery by first performing a subclavian to external carotid artery bypass, followed by superficial temporal artery middle cerebral artery (STA-MCA) bypass.

Methods—

The patient presented with symptomatic left hemispheric hemodynamic insufficiency, associated with occlusion of the ipsilateral internal and common carotid arteries. The STA was not detectable. The patient was treated initially with a subclavian to external carotid artery bypass, with partial improvement in symptoms.

Results—

Angiography demonstrated improvement in perfusion and STA filling, which was used for STA-MCA bypass, with resolution of symptoms.

Conclusion—

Our experience with this case has led us to consider a staged approach for management of patients with an occluded common carotid artery.
Moyamoya Syndrome in an Adolescent With Essential Thrombocythemia
Authors: Kornblihtt Laura I. , Cocorullo Silvia , Miranda Carlos , Lylyk Pedro , Heller Paula G. , Molinas Felisa C.
Published: July 2005

Background—

Essential thrombocythemia (ET) is a chronic myeloproliferative disorder with increased frequency of thrombotic events, including transient ischemic attacks (TIAs) and stroke. Moyamoya syndrome is a rare cerebrovascular disease characterized by progressive occlusion of intracerebral arteries with a typical “puff of smoke” angiographic pattern. We report the development of moyamoya syndrome in a patient with ET.

Case Description—

The patient is an 18-year-old female who presented at age 13 with recurrent TIAs. Persistent thrombocytosis was found, a diagnosis of ET was made, and treatment with anagrelide was started. Despite normal platelet counts, she experienced recurrent TIAs and stroke. Severe stenosis of the supraclinoid segment of the left internal carotid artery (LICA) and abnormal collateral vessels were found, and moyamoya syndrome was diagnosed on the basis of the characteristic angiographic appearance. An intracranial stent was placed in the LICA, and since then, she has had an uneventful outcome after a 46-month follow-up.

Conclusion—

To our knowledge, the development of moyamoya phenomenon has not been reported in ET, and the relationship between these 2 disorders remains unclear. Besides, this is the first intracranial carotid stent implanted successfully in a patient with moyamoya.
Intensive Treatment With Atorvastatin Reduces Inflammation in Mononuclear Cells and Human Atherosclerotic Lesions in One Month
Authors: Martín-Ventura Jose Luis , Blanco-Colio Luis Miguel , Gómez-Hernández Almudena , Muñoz-García Begoña , Vega Melina , Serrano Javier , Ortega Luis , Hernández Gonzalo , Tuñón José , Egido Jesús
Published: July 2005

Background and Purpose—

To investigate the effect of short-term high-dose atorvastatin on blood and plaque inflammation in patients with carotid stenosis.

Methods—

Twenty patients undergoing carotid endarterectomy without previous statin treatment were randomized to receive either atorvastatin 80 mg/d (n=11) or no statins (n=9) for 1 month. We studied inflammatory mediators in plasma (enzyme-linked immunosorbent assay), peripheral blood mononuclear cells (PBMCs; quantitative RT-PCR and EMSA) and plaques (immunohistochemistry and Southwestern histochemistry).

Results—

Atorvastatin significantly decreased total and low-density lipoprotein cholesterol and prostaglandin E
2
plasma levels. PBMCs from treated patients showed impaired NF-κB activation and MCP-1 and COX-2 mRNA expression. Carotid atherosclerotic plaques demonstrated a significant reduction in macrophage infiltration, activated NF-κB, and COX-2 and MCP-1 expression.

Conclusions—

Intensive treatment with atorvastatin decreases inflammatory activity of PBMCs and carotid atherosclerotic plaques in 1 month. These data strongly suggest that the antiinflammatory effect of high doses of statins in humans can be seen very early.
Plasminogen Activator Inhibitor-1 4G/5G Polymorphism and Risk of Stroke
Authors: Wiklund Per-Gunnar , Nilsson Lennart , Ardnor Sofie Nilsson , Eriksson Per , Johansson Lars , Stegmayr Birgitta , Hamsten Anders , Holmberg Dan , Asplund Kjell
Published: July 2005

Background and Purpose—

Impaired fibrinolytic function secondary to elevated plasminogen activator inhibitor-1 (PAI-1) levels has been implicated in ischemic stroke. PAI-1 levels are determined by genetic factors and environmental factors, triglyceride levels in particular. The aim of this study was to investigate the common functional 4/5 guanosine (4G/5G) polymorphism in the promoter region of the PAI-1 gene and the risk of stroke.

Methods—

A nested case–control study design was applied, using baseline data for 2 independent cohorts obtained at population-based surveys in northern Sweden. In study A, there were 113, and in study B, there were 275 individuals without major concomitant disease at baseline who later experienced a first-ever stroke. Blood samples obtained at baseline were analyzed for potential risk factors, including the 4G/5G polymorphism of the PAI-1 gene.

Results—

The 4G allele of the PAI-1 polymorphism was associated with an increased risk of future ischemic stroke in both studies (odds ratio [OR] of 4G homozygosity, 1.87; 95% CI, 1.12 to 3.15 in study A; OR of 4G homozygosity, 1.56; 95% CI, 1.12 to 2.16 in study B). Individuals with the combination of hypertriglyceridemia and 4G homozygosity were at the greatest risk of developing stroke. Multiple logistic regression analysis identified 4G homozygosity, systolic blood pressure, and diabetes as independent predictors of ischemic stroke.

Conclusions—

Identical findings in 2 independent studies strongly suggest a true and clinically important association between PAI-1 4G/5G genotype and risk of future ischemic stroke. The observed modification of the genotype effect by triglycerides may be interpreted as a gene–environment interaction.
Role of the Contralateral Inferior Frontal Gyrus in Recovery of Language Function in Poststroke Aphasia
Authors: Winhuisen Lutz , Thiel Alexander , Schumacher Birgit , Kessler Josef , Rudolf Jobst , Haupt Walter F. , Heiss Wolf D.
Published: July 2005

Background and Purpose—

Functional neuroimaging studies have demonstrated right inferior frontal gyrus (IFG) activation in poststroke aphasia. It remains unclear whether this activation is essential for language performance. We tested this hypothesis in a positron emission tomography (PET) activation study during a semantic task with repetitive transcranial magnetic stimulation (rTMS) on right-handed patients experiencing poststroke aphasia and examined whether rTMS stimulation over the right and left IFG would interfere with language performance.

Methods—

Eleven patients with left-sided middle cerebral arterial infarction, 50 to 75 years of age, were tested with the Aachen Aphasia Test Battery and underwent
15
O-H
2
O PET activation during a semantic task within 2 weeks after stroke. PET activation images were coregistered to T1-weighted MRIs. Stimulation sites were determined on renderings of head and brain over the maximum activation within left and right IFG. rTMS was performed with 20% maximum output (2.1 T), 10-s train duration, at 4Hz frequency. A positive rTMS effect was defined as an increased reaction time latency or error rate in the semantic task.

Results—

PET activations of the IFG were observed on the left (3 patients) and bilaterally (8 patients). Right IFG stimulation was positive in 5 patients with right IFG activation, indicating essential language function. In a verbal fluency task, these patients had a lower performance than patients without right-sided TMS effect.

Conclusions—

In some poststroke aphasics, right IFG activation is essential for residual language function. However, its compensatory potential seems to be less effective than in patients who recover left IFG function. These results suggest a hierarchy in recovery from poststroke aphasia and a (limited) compensatory potential of the nondominant hemisphere.
Carotid Intima-Media Thickness, Plaques, and Framingham Risk Score as Independent Determinants of Stroke Risk
Authors: Touboul Pierre-Jean , Labreuche Julien , Vicaut Eric , Amarenco Pierre
Published: July 2005

Background and Purpose—

The Framingham stroke risk score (FSRS) and Framingham cardiovascular risk score (FCRS) estimate the individual absolute cardiovascular and stroke risks. Common carotid artery intima-media thickness (CCA-IMT) and carotid plaques (CPs) are markers of subclinical atherosclerosis and help in the early identification of presymptomatic individuals. The purpose of this study was to correlate Framingham risk score (FRS) with CCA-IMT and CPs and evaluate their respective contribution to stroke risk.

Methods—

In 510 consecutive patients with brain infarction and 510 matched controls, we calculated the FSRS and FCRS for each individual and performed carotid ultrasonography. Mean CCA-IMT was measured off-line at a central core laboratory, and presence of CPs was assessed.

Results—

FRS progressively increased according to tertiles of CCA-IMT (
P
for trend <0.0001). The part of the variances of FSRS and FCRS explained by CCA-IMT was respectively 11% and 20%. The relationships between CCA-IMT and FRS were significantly different between patients with or without CPs (
P
for interaction <0.005). With increasing CCA-IMT, the 10-year FRS gradually increased between 10% and 20% in the presence of CPs and between 5% and 20% in the absence of CPs. Multiple conditional logistic regression for matched sets showed that CCA-IMT, FCRS, and CPs were independently associated with stroke risk, with an odds ratio of 1.68 (1.25 to 2.26;
P
=0.0006), 2.16 (1.57 to 2.98;
P
<0.0001), and 2.73 (1.68 to 4.44;
P
<0.0001), respectively, meaning that each of them may be important for evaluation of the individual cardiovascular risk.

Conclusions—

CCA-IMT, CPs, and FRSs correlated well. The CCA-IMT value may help discriminate between subjects at low or high 10-year risk.
Project Discovery
Authors: Shulman Vivian , Armitage Deirdre
Published: July 2005

This study reports on a 5-year project to improve urban, middle-level student achievement through the implementation of two initiatives. First, teachers at a participating New York City middle school engaged in weekly curriculum-planning workshops to reformulate classroom curricula into interdisciplinary, discovery-oriented activities. Second, undergraduate college students from an urban public college, representing a variety of academic disciplines, were recruited to work as classroom tutors, or “teaching scholars,” in the middle school. Gains in student achievement were demonstrated by a significant increase in the number of students meeting state standards on standardized test scores in mathematics and English. Survey responses and interviews of teachers revealed that teachers felt energized and empowered and that the school climate had improved. An unanticipated benefit was the desire of a significant number of college student “teaching scholars” to change career plans and pursue teaching as a profession, specifically in urban, high-need schools.
All Things to All People
Authors: Hunter Richard C. , Donahoo Sarah
Published: July 2005

When confronted with the problems of urban school districts, such as an ever-increasing achievement gap, the underfunding of school districts, increased shortages of qualified teachers, greater emphasis on accountability, and the loss of public confidence, African American superintendents have considerable difficulty leading their school districts. This article begins with a discussion of urban school district funding disparities and their impact on district operations. The article then discusses stakeholder expectations and how they affect the job performance of these superintendents. The text also describes what politicians, school boards, the media, parents, community members, and school district staff want superintendents to do and how they make it difficult for them to meet these goals. In addition, the article discusses recent changes that could serve as a harbinger of the future regarding the racial composition of superintendents in both traditional settings and reformed school districts.
Increasing Meta-Cognitive Competence through Conflict Resolution
Authors: Heydenberk Roberta Anna , Heydenberk Warren R.
Published: July 2005

The purpose of this study was to determine the effects of conflict resolution and related social skill development on students’ meta-cognitive competencies. The investigation was conducted throughout a 5-year period in elementary schools in the Philadelphia School District and in a neighboring urban school district. Sample subjects were fourth-and fifth-grade students. Each of the student samples (10 treatment groups and 8 comparison groups) were assessed for significant pretest to posttest differences using a one-tailed t test with an alpha level of .05. One-tailed t tests with an alpha level of .05 established that treatment group students demonstrated significant improvement in meta-cognitive skills. The research hypothesis was accepted. Consequently, the veracity of integrating conflict resolution and social skills training into curricula was affirmed.
I Just Want to Play
Authors: McGinnis Lee , McQuillan Julia , Chapple Constance L.
Published: July 2005

Golf does not inherently privilege men or women physically, yet men are much more likely to participate in golf. The authors explore the institutional(e.g., societal level) and interactional barriers to women’s golf participation and uncover strategies women use to negotiate playing and persisting in golf. Guided by research on tokenism in occupations, statistical discrimination, and feminist research in the sociology of sport, the authors use 10 interviews with recreational women golfers to explore these issues. Similar to women in predominantly male occupations, the women in this study report heightened visibility and experiences with typecasting on the golf course. In addition, social closure operates in the form of unwelcoming courses; women reported feeling ignored, overlooked, or unimportant on the course. The authors discuss several strategies the women in the sample use to overcome sexism and persist in golf.
Masculinities, Sport, and Power
Authors: Pringle Richard
Published: July 2005

Although feminists have increasingly found Foucauldian theorising effective for examining issues associated with female sport and exercise contexts, the Gramscian-inspired concept of masculine hegemony remains dominant in masculinities research. This article compares and contrasts the theoretical tools stemming from the writings of Gramsci and Foucault with respect to their use for examining sport and masculinities. It is argued that it is troublesome to combine Foucauldian and Gramscian concepts without acknowledging fundamental theoretical differences. Questions of concern are also discussed with respect to how the concept of hegemonic masculinity has been used in studies of sport and masculinities. It is suggested that the concept of masculine hegemony does not simply refer to a dominant form of masculinity but is underpinned by particular understandings of power that some may find problematic. The conclusion discusses how Foucauldian theorising could be advantageous for future examinations of sport and masculinities.
Hidden Dragons
Authors: Hanson Sandra L.
Published: July 2005

In this research, the authors take a multicultural feminist approach to examining Asian American women’s participation in sport during the high school years. Data come from the nationally representative, longitudinal National Educational Longitudinal Survey. Asian American women are virtually invisible in the sport literature in part because of simplistic stereotypes of submissive, subservient Asian American women. Findings suggest considerable diversity across groups of Asian American women in sport participation. They also show that Asian American women, as a whole, have a different pattern of sport participation than other women. However, they are not less involved in sport. They are slightly less involved in sport than are young Asian American men, but this gender effect exists across race and ethnic groups. Implications of these findings for understanding the complexity of Asian American culture and the importance of examining Asian American gender systems as unique products of Asian American history and culture are discussed.
Reading the Catsuit
Authors: Schultz Jaime
Published: July 2005

During the 2002 U.S. Open, Serena Williams received a great deal of attention for wearing an outfit described as ”a body-clinging, faux leather, black cat-suit.” It was not necessarily the catsuit itself that the popular media found especially controversial but rather the visibility of her physique the outfit provided. The ways in which Serena Williams, the outfit, and her body were discussed offers a particular site at which to interrogate the production of blackness in 21st-century, U.S. society. This article argues that the processes of differentiation the popular media used to characterize her are located within racialized discourse. By representing Williams through oppositional rhetorics, that is, setting her multiple identities in contradistinction to other women on the tour, accounts concerning her appearance in the catsuit reproduce the hegemonic racialized order in women’s tennis.
“Babes” & Boards
Authors: Rinehart Robert
Published: July 2005

The proliferation of action or extreme sports in recent years leads to a reassessment of fundamental, foundational questions regarding the nature of sport. One such question is Does the much-vaunted alternative ethos of action sports lead to a concomitant paradigm shift in fundamental attitudes toward race, class, or gender differences within these new sport forms? In this article, the focus is on advertising in slick, national skating magazines and more particularly on the gendered nature of advertising and how it reflects and promotes gender segmentation in markets. In examining such print advertising, several metathemes emerge: There are images that (a) reify the naturalized maleness of North American sport;(b) objectify girls and woman as a naturalized position; (c) objectify girls and woman in sexualized manners, so that they create misogynist views in their audiences; and (d) attempt to set up the brand advertisers as outlaws, as oppositional to mainstream sport culture.