bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucose-6-Phosphate Dehydrogenase Modulates Cytosolic Redox Status and Contractile Phenotype in Adult Cardiomyocytes
Authors: Jain Mohit , Brenner Daniel A. , Cui Lei , Lim Chee Chew , Wang Bo , Pimentel David R. , Koh Stanley , Sawyer Douglas B. , Leopold Jane A. , Handy Diane E. , Loscalzo Joseph , Apstein Carl S. , Liao Ronglih
Published: July 2003

Reactive oxygen species (ROS)–mediated cell injury contributes to the pathophysiology of cardiovascular disease and myocardial dysfunction. Protection against ROS requires maintenance of endogenous thiol pools, most importantly, reduced glutathione (GSH), by NADPH. In cardiomyocytes, GSH resides in two separate cellular compartments: the mitochondria and cytosol. Although mitochondrial GSH is maintained largely by transhydrogenase and isocitrate dehydrogenase, the mechanisms responsible for sustaining cytosolic GSH remain unclear. Glucose-6-phosphate dehydrogenase (G6PD) functions as the first and rate-limiting enzyme in the pentose phosphate pathway, responsible for the generation of NADPH in a reaction coupled to the de novo production of cellular ribose. We hypothesized that G6PD is required to maintain cytosolic GSH levels and protect against ROS injury in cardiomyocytes. We found that in adult cardiomyocytes, G6PD activity is rapidly increased in response to cellular oxidative stress, with translocation of G6PD to the cell membrane. Furthermore, inhibition of G6PD depletes cytosolic GSH levels and subsequently results in cardiomyocyte contractile dysfunction through dysregulation of calcium homeostasis. Cardiomyocyte dysfunction was reversed through treatment with either a thiol-repleting agent (L-2-oxothiazolidine-4-carboxylic acid) or antioxidant treatment (Eukarion-134), but not with exogenous ribose. Finally, in a murine model of G6PD deficiency, we demonstrate the development of in vivo adverse structural remodeling and impaired contractile function over time. We, therefore, conclude that G6PD is a critical cytosolic antioxidant enzyme, essential for maintenance of cytosolic redox status in adult cardiomyocytes. Deficiency of G6PD may contribute to cardiac dysfunction through increased susceptibility to free radical injury and impairment of intracellular calcium transport. The full text of this article is available online at http://www.circresaha.org.
Diverse Mechanisms of Myocardial p38 Mitogen-Activated Protein Kinase Activation
Authors: Tanno Masaya , Bassi Rekha , Gorog Diana A. , Saurin Adrian T. , Jiang Jie , Heads Richard J. , Martin Jody L. , Davis Roger J. , Flavell Richard A. , Marber Michael S.
Published: July 2003

The ischemic activation of p38α mitogen-activated protein kinase (p38α-MAPK) is thought to contribute to myocardial injury. Under other circumstances, activation is through dual phosphorylation by MAPK kinase 3 (MKK3). Therefore, the mkk3
−/−
murine heart should be protected during ischemia. In retrogradely perfused mkk3
−/−
and mkk3
+/+
mouse hearts subjected to 30 minutes of global ischemia and 120 minutes of reperfusion, infarction/risk volume was similar (50±5 versus 51±4,
P
=0.93, respectively), as was intraischemic p38-MAPK phosphorylation (10 minutes ischemia as percent basal, 608±224 versus 384±104,
P
=0.43, respectively). This occurred despite undetectable activation of MKK3/6 in mkk3
−/−
hearts. However, tumor necrosis factor (TNF)-induced p38-MAPK phosphorylation was markedly diminished in mkk3
−/−
vs mkk3
+/+
hearts (percent basal, 127±23 versus 540±267, respectively,
P
=0.04), suggesting an MKK-independent activation mechanism by ischemia. Hence, we examined p38-MAPK activation by TAB1-associated autophosphorylation. In wild-type mice and mkk3
−/−
mice, the p38-MAPK catalytic site inhibitor SB203580 (1 μmol/L) diminished phosphorylation during ischemia versus control (10 minutes ischemia as percent basal, 143±2 versus 436±96,
P
=0.003, and 122±25 versus 623±176,
P
=0.05, respectively) and reduced infarction volume (infarction/risk volume, 57±5 versus 36±3,
P
<0.001, and 50±5 versus 29±3,
P
=0.003, respectively) but did not alter TNF-induced activation, although in homogenates of ischemic hearts but not TNF-exposed hearts, p38-MAPK was associated with TAB1. Furthermore, adenovirally expressed wild-type and drug-resistant p38α-MAPK, lacking the SB203580 binding site, was phosphorylated when H9c2 myoblasts were subjected to simulated ischemia. However, SB203580 (1 μmol/L) did not prevent the phosphorylation of resistant p38α-MAPK. These findings suggest the ischemic activation of p38-MAPK contributing to myocardial injury is by TAB1-associated autophosphorylation.
Intravenous Transfusion of Endothelial Progenitor Cells Reduces Neointima Formation After Vascular Injury
Authors: Werner Nikos , Junk Stefan , Laufs Ulrich , Link Andreas , Walenta Katrin , Böhm Michael , Nickenig Georg
Published: July 2003

Endothelial cell damage is one important pathophysiological step of atherosclerosis and restenosis after angioplasty. Accelerated reendothelialization impairs neointima formation. We evaluated the role of intravenously transfused endothelial progenitor cells (EPCs) on reendothelialization and neointima formation in a mouse model of arterial injury. Spleen-derived mouse mononuclear cells (MNCs) were cultured in endothelial basal medium. A total of 91.8±3.2% of adherent cells showed uptake of acetylated low-density lipoprotein (Dil-Ac-LDL) and lectin binding after 4 days. Immunostaining and long-term cultures confirmed the endothelial progenitor phenotype. To determine the effect of stem cell transfusion on reendothelialization, mice received either fluorescent-labeled spleen-derived MNCs or in vitro differentiated EPCs intravenously after endothelial injury of the carotid artery. Transfused cells were strictly restricted to the injury site, and lectin binding confirmed the endothelial phenotype. Homing of transfused cells to the site of injury was only detectable in splenectomized mice. Cell transfusion caused enhanced reendothelialization associated with a reduction of neointima formation. Systemically applied spleen-derived MNCs and EPCs home to the site of vascular injury, resulting in an enhanced reendothelialization associated with decreased neointima formation. These results allow novel insights in stem cell biology and provide additional information for the treatment of vascular dysfunction and prevention of restenosis after angioplasty. The full text of this article is available online at http://www.circresaha.org.
Acute Stroke in the Very Elderly
Authors: Olindo S. , Cabre P. , Deschamps R. , Chatot-Henry C. , René-Corail P. , Fournerie P. , Saint-Vil M. , May F. , Smadja D.
Published: July 2003

Background and Purpose—

Stroke incidence increases with increasing age and has an impact on daily living in many areas. With increasing life expectancy, old people will constitute the majority of stroke victims. We present the first stroke study focusing on very old patients in a black Caribbean population (Martinique, French West Indies).

Methods—

All Martinican patients suffering from their first-ever stroke during 1 calendar year between June 1, 1998, and May 31, 1999, were included. Epidemiological, clinical, neuroimaging, management, and outcome data during the first month were collected and compared between very old patients (≥85 years) and patients aged <85 years.

Results—

One hundred patients aged ≥85 years and 480 patients aged <85 years were included (sex ratio, women/men, 2.84 and 0.85, respectively; mean±SD age, 88.8±3.6 and 65.8±13.3 years, respectively). The incidence of first-ever stroke was 1.64/1000 per year in the Martinique population and 18.2/1000 per year in patients aged ≥85 years. Elderly patients showed a significantly lower proportion of diabetes (19.1% versus 32.2%;
P
=0.012) and smoking (0% versus 8.4%;
P
=0.004) and a higher proportion of peripheral artery disease (23.4% versus 11.4%;
P
=0.002). Prevalence of hypertension was identical in the 2 groups (70%). There were no significant differences in stroke types or ischemic stroke subtypes between the 2 groups. Active medical care was poorer in older than in younger patients (hospitalization rate, 89% versus 94.4%; admission to neurological ward, 8% versus 23.8%; rate of performance of a CT scan, 82% versus 94%). The 30-day case fatality rate was approximately twice as high in elderly patients (31% versus 16.7%;
P
=0.0009), and disability (Rankin Scale score ≥3) in survivors was markedly higher (78% versus 48%;
P
<0.0001).

Conclusions—

In Martinique, the incidence of first-ever stroke in very old black Caribbean patients seems similar to that in white patients. They have the same pathological type and subtype of stroke as do young patients. The poorer stroke outcome found in the elderly during the first month may be related in large part to less active management than in younger patients.
Association of Exercise-Induced, Silent ST-Segment Depression With the Risk of Stroke and Cardiovascular Diseases in Men
Authors: Kurl S. , Laukkanen J.A. , Tuomainen T.-P. , Rauramaa R. , Lakka T.A. , Salonen R. , Eränen J. , Sivenius J. , Salonen J.T.
Published: July 2003

Background and Purpose—

There are few if any data on the prognostic importance of silent myocardial ischemia during exercise with regard to the risk of stroke and cardiovascular diseases (CVDs) among asymptomatic men. In this prospective study, we investigated the relation of silent myocardial ischemia and the risk of stroke and CVD death in men with and without conventional risk factors.

Methods—

The study sample included 1726 middle-aged men with no history of stroke, coronary heart disease, or atrial fibrillation at baseline. Silent myocardial ischemia was defined as a horizontal or downsloping ST-segment depression (⪖1 mm) during exercise electrocardiography. A total of 86 CVD-related deaths and 78 strokes occurred during an average follow-up of 10 years.

Results—

Men with silent ischemia during exercise had a 3.5-fold increased risk of CVD death and a 2.2-fold increased risk of stroke compared with men without silent ischemia, after adjusting for conventional risk factors. Silent ischemia during exercise was associated with a 3.8-fold (95% confidence interval [CI], 1.5 to 9.5) increased risk for CVD in smokers, a 3.9-fold (95% CI, 2.1 to 7.3) increased risk in hypercholesterolemic subjects, a 3.6-fold (95% CI, 1.9 to 6.8) increased risk in the hypertensives, and 3.8-fold (95% CI, 2.0 to 7.1) increased risk in overweight men. The respective relative risks for stroke were 3.8 (95% CI, 1.1 to 12.5), 3.5 (95% CI, 1.7 to 7.4), 3.4 (95% CI, 1.6 to 7.1), and 2.9 (95% CI, 1.4 to 6.1).

Conclusions—

Exercise-induced silent myocardial ischemia is an important indicator of increased risk of stroke and CVD in men with other risk factors, such as smoking, hypercholesterolemia, hypertension, and being overweight.
Ultrarapid, Convection-Enhanced Intravascular Hypothermia
Authors: Mack William J. , Huang Judy , Winfree Christopher , Kim Grace , Oppermann Marcelo , Dobak John , Inderbitzen Becky , Yon Steve , Popilskis Sulli , Lasheras Juan , Sciacca Robert R. , Pinsky David J. , Connolly E. Sander
Published: July 2003

Background and Purpose—

Hypothermia has been shown to be neuroprotective in a variety of clinical settings. Unfortunately, poor delivery techniques and insufficient data in appropriate preclinical models have hampered its development in human stroke. To address these limitations, we have devised a 10F intravascular catheter capable of rapid systemic cooling of nonhuman primates.

Methods—

Placed in the inferior vena cava via a transfemoral approach, the catheter was used to induce mild systemic hypothermia 3 hours after the onset of hemispheric stroke in baboons.

Results—

Cooling was achieved at a rate of 6.3±0.8°C/h. Target brain temperatures (32.2±0.2°C) were reached at the same time (47.7±6.32 minutes) as target esophageal temperatures (32.0±0.0°C). Hypothermia was maintained for 6 hours in all animals. Animals did not experience the infections, coagulopathy, or cerebral edema commonly seen with surface cooling methods in human stroke.

Conclusions—

These data suggest that a brief episode of mild core hypothermia instituted at a clinically relevant time point can be achieved in primate stroke and that our intravascular cooling technique provides safe, rapid, and reproducible hypothermia.
Drug-Induced Hypothermia Reduces Ischemic Damage
Authors: Leker Ronen R. , Gai Naomi , Mechoulam Raphael , Ovadia Haim
Published: July 2003

Background and Purpose—

Cannabinoids confer neuroprotection in several experimental paradigms, but the responsible mechanisms remain unknown. Therefore, we sought to examine whether the synthetic CB1 agonist HU-210 is capable of reducing ischemic damage and to determine the mechanisms responsible for such protection.

Methods—

Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (PMCAO). After dose-response and therapeutic time window-finding experiments, the rats were injected with HU-210 (45 μg/kg IV) or vehicle 1 hour after PMCAO. Physiological parameters and cerebral blood flow in the peri-infarct zone were monitored. The animals were examined with a motor disability scale, and the infarct volumes were measured 72 hours later. We also examined the effects of the selective CB1 antagonist SR-141716 and of controlled warming on the neuroprotection conferred by HU-210.

Results—

HU-210 reduced blood pressure and heart rate but did not alter the cerebral blood flow in the infarct border zone. Motor disability and infarct volumes were significantly reduced (by up to 77%;
P
<0.05) in animals treated with HU-210. A single injection of HU-210 significantly lowered the body temperature compared with vehicle as measured both at 1 hour (32.3±1.3°C versus 35±1.6°C;
P
=0.0024) and at 24 hours (31.5±2.5°C versus 37.25±0.3°C;
P
=0.0031) after PMCAO. The protective effects of HU-210 were partially reversed by pretreatment with SR-141716 but were completely abolished by warming of the animals to the levels observed in controls.

Conclusions—

HU-210 confers robust protection against ischemic damage. This protection is mediated at least in part by binding to CB1 receptors and is also associated with the indirect protective effects of hypothermia.
Differences in Vascular Risk Factors Between Etiological Subtypes of Ischemic Stroke
Authors: Schulz U.G.R. , Rothwell P.M.
Published: July 2003

Background—

To understand the mechanisms of stroke and to target prevention, we need to know how risk factors differ between etiological subtypes. Hospital-based studies may be biased because not all stroke patients are admitted. If risk factors differ between patients who are admitted and those who are not, then case-control studies will be biased. If the likelihood of admission also depends on stroke subtype, then case-case comparisons may also be biased.

Methods—

We compared risk factors and ischemic stroke subtypes (TOAST classification) in hospitalized and nonhospitalized patients in 2 population-based stroke incidence studies: the Oxford Vascular Study (OXVASC) and Oxfordshire Community Stroke Project (OCSP). We also performed a meta-analysis of risk factor–stroke subtype associations with other published population-based studies.

Results—

In OXVASC and OCSP, stroke subtypes differed between hospitalized (293 of 647) and nonhospitalized patients (
P
<0.0001), with more cardioembolic strokes (odds ratio [OR], 1.8; 95% CI, 1.3 to 2.6) and fewer lacunar strokes (OR, 0.4; 95% CI, 0.3 to 0.7). Premorbid blood pressure and cholesterol were higher in hospitalized patients (both
P
<0.0001). Risk factor–stroke subtype associations in hospitalized patients were consequently biased (
P
=0.001). Meta-analysis of data from all patients in OXVASC, OCSP, and 2 other studies demonstrated consistent risk factor–stroke subtype associations. However, contrary to previous hospital-based studies, there was only a weak (OR, 1.4; 95% CI, 1.1 to 1.8) and inconsistent (
P
heterogeneity
=0.01) association between small-vessel stroke and hypertension and no association with diabetes (OR, 1.0; 95% CI, 0.7 to 1.3).

Conclusions—

Prevalences of risk factors and stroke subtypes differ between hospitalized and nonhospitalized patients with ischemic stroke, which may bias hospital-based risk factor studies. Meta-analysis of population-based studies suggests that vascular risk factors differ between stroke subtypes.
Prehemorrhage Risk Factors for Fatal Intracranial Aneurysm Rupture
Authors: Juvela Seppo
Published: July 2003

Background and Purpose—

The goal of this study was to investigate predictive preictal risk factors for fatal subarachnoid hemorrhage (SAH) in a patient population with verified intracranial aneurysms without surgical selection of patients and with complete follow-up.

Methods—

A total of 142 patients with 181 unruptured aneurysms diagnosed between 1956 and 1978 were followed up for a total of 2577 person-years until death, SAH, or the years 1997 to 2000. The predictive value of several factors known before SAH was tested for case fatality.

Results—

During follow-up, 34 first episodes of hemorrhage from a previously verified unruptured aneurysm occurred. Of these bleeding episodes, 17 were fatal. Patients who died after the bleeding had higher blood pressure values (mean±SD, 148±11/92±8 mm Hg; mean pressure, 111±9 mm Hg) before hemorrhage than did those with nonfatal bleeding (mean±SD, 135±15/83±11 mm Hg; mean, 101±12 mm Hg) (
P
<0.05). Patients with fatal SAH were also older (54±7 versus 47±13 years,
P
=0.068) and had aneurysms larger in diameter (13±8 versus 10±5 mm) than those who survived. They had a higher prevalence of definite hypertension (56% versus 12%,
P
<0.05), more frequently used antihypertensive medication (29% versus 6%) by the end of follow-up, and tended to have higher blood pressure at the beginning of follow-up (140±21/85±11 versus 134±17/80±9 mm Hg). After adjustment for age, aneurysm size, and sex, the only indisputable significant independent risk factor for fatal SAH compared with nonfatal SAH was systolic blood pressure before aneurysm rupture (odds ratio, 1.11 per 1 mm Hg; 95% CI, 1.01 to 1.23;
P
=0.032). The adjusted odds ratio of definite hypertension for fatal SAH was 12.67 (95% CI, 1.53 to 104.70;
P
=0.018).

Conclusions—

Increased systolic blood pressure values and long-term hypertension before aneurysm rupture seem to predict fatal SAH independently of aneurysm size or patient age or sex at the time of rupture.
Hypoxia-Induced Stroke Tolerance in the Mouse Is Mediated by Erythropoietin
Authors: Prass Konstantin , Scharff Anna , Ruscher Karsten , Löwl Diana , Muselmann Claudia , Victorov Ilya , Kapinya Krisztian , Dirnagl Ulrich , Meisel Andreas
Published: July 2003

Background and Purpose—

Cellular response to hypoxia is mainly controlled by hypoxia-inducible factor 1 (HIF-1). The HIF-1 target gene erythropoietin (EPO) has been described as neuroprotective. Thus, we hypothesize EPO to be an essential mediator of protection in hypoxic preconditioning.

Methods—

We randomized Sv129 mice into groups for different pretreatments, different hypoxia-ischemia intervals, or different durations of ischemia. For hypoxic preconditioning, the animals were exposed to a hypoxic gas mixture (8% O
2
and 92% N
2
) for 30, 60, 180, 300, or 360 minutes. At 0, 24, 48, 72, or 144 hours later, we performed middle cerebral artery occlusion and allowed reperfusion after 30, 45, 60, or 120 minutes, or occlusion was left to be permanent. We studied EPO gene expression in brain tissue with a real-time reverse transcriptase-polymerase chain reaction and measured HIF-1 DNA-binding activity with an electrophoretic mobility shift assay. To block endogenously produced EPO, we instilled soluble EPO receptor into the cerebral ventricle.

Results—

Hypoxic preconditioning for 180 or 300 minutes induced relative tolerance to transient focal cerebral ischemia, as evidenced by a reduction of infarct volumes to 75% or 54% of the control, respectively. Hypoxic pretreatment was effective only when applied 48 or 72 hours before middle cerebral artery occlusion. Sixty minutes after hypoxia, we found a marked activation of HIF-1 DNA-binding activity and a 7-fold induction of EPO transcription. Infusion of soluble EPO receptor significantly reduced the protective effect of hypoxic pretreatment by 40%.

Conclusions—

Endogenously produced EPO is an essential mediator of ischemic preconditioning.
Evaluation of Hyperintense Vessels on FLAIR MRI for the Diagnosis of Multiple Intracerebral Arterial Stenoses
Authors: Iancu-Gontard Daniela , Oppenheim Catherine , Touzé Emmanuel , Méary Eric , Zuber Mathieu , Mas Jean-Louis , Frédy Daniel , Meder Jean-François
Published: July 2003

Background and Purpose—

Hyperintense vessel sign (HVS) on fluid-attenuated inversion recovery (FLAIR) has been described in hyperacute stroke patients with arterial occlusion. We sought to determine whether HVS was more frequent in patients with intracerebral arterial stenoses than in those without stenosis regardless of the presence of a brain infarct.

Methods—

In this case-control study (19 symptomatic patients with multiple intracerebral arterial stenoses compared with 19 age-matched asymptomatic patients without stenosis), we looked for HVS (ie, focal or tubular hyperintensities in the subarachnoid space) on FLAIR images. We compared the proportion of HVS-positive patients in the 2 groups and evaluated the concordance between the arterial distribution of stenoses on angiogram and that of HVS on FLAIR.

Results—

HVS was found in 13 of 19 patients (68%) in the study group and 1 of 19 control patients (5.2%) (
P
<0.0001). The concordance between the territorial distribution of stenoses on angiogram and HVS on FLAIR was higher for the right and left middle cerebral artery (κ=0.6 and 0.63, respectively) compared with the right and left anterior cerebral artery (κ=0.35 and 0.2, respectively). HVSs were observed in 1 of 7 patients with posterior cerebral artery stenoses on angiogram. HVSs were seen equally in patients with acute focal (7 of 10) or diffuse (6 of 9) cerebral involvement. In the 6 HVS-positive patients with acute stroke confirmed by MRI, additional HVSs were observed in a different arterial territory than that of the stroke lesion.

Conclusions—

Although their significance remains unclear, multiple HVSs are more frequently observed in symptomatic patients with multiple intracerebral stenoses than in asymptomatic patients without stenosis.
Risk, Types, and Severity of Intracranial Hemorrhage in Patients With Symptomatic Carotid Artery Stenosis
Authors: Cheung Raymond T.F. , Eliasziw Michael , Meldrum Heather E. , Fox Allan J. , Barnett Henry J.M.
Published: July 2003

Background and Purpose—

We sought to report the occurrence and risk factors of intracranial hemorrhage during long-term follow-up of patients with internal carotid artery stenosis, with and without carotid endarterectomy.

Methods—

From the prospective data of the North American Symptomatic Carotid Endarterectomy Trial, 3 types of intracranial hemorrhage were recognized: petechiae within infarction (PTI), intracerebral hematoma (ICH), and subarachnoid hemorrhage (SAH). The 30-day and 5-year risks of intracranial hemorrhage (PTI or ICH) were estimated from Kaplan-Meier event-free survival curves. Cox proportional-hazards regression modeling was used to identify risk factors.

Results—

Of 1039 strokes that occurred in 749 of 2885 patients during an average follow-up of 5 years, there were 24 PTIs, 14 ICHs, and 1 SAH. The 5-year risk of intracranial hemorrhage was 1.7% in both medically and surgically treated patients, but the 30-day risk of 0.64% in surgically treated patients was 10 times higher than the risk of 0.07% in medically treated patients (
P
=0.01). Approximately 50% of all intracranial hemorrhages were either disabling or fatal, and ICHs were more likely to be fatal than PTIs. Old age, a history of hypertension, intermittent claudication and smoking, and infarct on brain images were risk factors for intracranial hemorrhage in medically treated patients, whereas diabetes mellitus was the sole risk factor in surgically treated patients.

Conclusions—

Intracranial hemorrhages are uncommon in patients with internal carotid artery stenosis but are associated with high mortality and morbidity. The risk factors for intracranial hemorrhage are different between medically and surgically treated patients.
Thrombolysis With Recombinant Tissue Plasminogen Activator and Tirofiban in Stroke
Authors: Seitz Rüdiger J. , Hamzavi Magnolia , Junghans Ulrich , Ringleb Peter A. , Schranz Corinna , Siebler Mario
Published: July 2003

Background and Purpose—

We sought to investigate the feasibility of the combined use of low-dose recombinant tissue plasminogen activator (rtPA) and tirofiban, a glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonist, for systemic thrombolysis in acute stroke.

Methods—

Consecutive patients who were treated with systemic application of low-dose rtPA and body weight–adjusted tirofiban (rtPA+T group; n=37) were evaluated retrospectively during 1999–2001. Patients in the rtPA+T group were compared with a group of patients treated with a dose of 0.9 mg/kg body weight in a different center (rtPA group; n=119). The 41 patients with infarctions of the middle cerebral artery territory who were not eligible for thrombolytic treatment because of medical contraindications or arrival in the hospital >3 hours after stroke onset served as controls. For matched comparisons, the National Institutes of Health Stroke Scale on admission and the Rankin Scale on discharge 5 days after stroke were used.

Results—

The patients treated with rtPA+T or rtPA improved (
P
<0.05) compared with the controls at discharge; patients in the rtPA+T and rtPA groups reached a Rankin Scale score of 0 to 2 in 63% and 55%, respectively, while only 16% of the controls achieved this score. Death rates (8% in rtPA+T group and 5% in rtPA group) were similar among the 2 treatment groups. They included 1 fatal hemorrhage in the rtPA+T group and 4 fatal hemorrhages in the rtPA group. Five percent of the untreated patients developed symptomatic, nonfatal cerebral hemorrhage.

Conclusions—

Systemic combined thrombolysis with rtPA+T seems to be a feasible treatment in acute stroke.
Prophylactic but Not Delayed Administration of Simvastatin Protects Against Long-Lasting Cognitive and Morphological Consequences of Neonatal Hypoxic-Ischemic Brain Injury, Reduces Interleukin-1β and Tumor Necrosis Factor-α mRNA Induction, and Does Not Affect Endothelial Nitric Oxide Synthase Expression
Authors: Balduini Walter , Mazzoni Erika , Carloni Silvia , De Simoni Maria Grazia , Perego Carlo , Sironi Luigi , Cimino Mauro
Published: July 2003

Background and Purpose—

Prophylactic administration of simvastatin has been shown to protect against brain damage and its long-lasting behavioral consequences in neonatal rats. To establish the drug treatment window, we evaluated the effectiveness of simvastatin administered at different intervals before and after stroke. Furthermore, we determined whether simvastatin affected endothelial nitric oxide synthase (eNOS) or inflammatory cytokines in brain tissue or cholesterol levels in serum.

Methods—

On postnatal day 7, male rats were subjected to hypoxia-ischemia (HI). The experiment included sham-operated controls and HI animals receiving daily saline or activated simvastatin (20 mg/kg) injections from postnatal day 1 to day 7 (HI-simvastatin 1–7 group), from postnatal day 4 to day 11 (HI-simvastatin 4–11 group), or from postnatal day 7 to day 14 (HI-simvastatin 7–14 group). The neuroprotective effect of simvastatin was evaluated at adulthood by means of behavioral and histological analyses. Cytokines and eNOS expression were assessed by reverse transcriptase-polymerase chain reaction and Western blotting.

Results—

Animals in both the HI-simvastatin 1–7 and HI-simvastatin 4–11 groups performed better than HI rats in either the T-maze or the circular water maze and showed significantly attenuated brain damage. Expression of interleukin-1β and tumor necrosis factor-α mRNA in cortex was significantly increased in HI but not in HI-simvastatin 1–7 animals. In the same brain area, simvastatin treatment did not affect the increase of eNOS expression observed after HI
.

Conclusions—

These findings indicate that prophylactic but not delayed administration of simvastatin improves functional outcome in neonatal rat stroke. The reduced induction of cytokines suggests that the neuroprotective effect of simvastatin may be related to a dampening of the inflammatory response.
Leukoaraiosis
Authors: Inzitari Domenico
Published: July 2003

Background—

Leukoaraiosis, a term that defines an abnormal appearance of the subcortical white matter of the brain on neuroimaging (bilateral patchy or diffuse areas of low attenuation on CT or hyperintense T2 MR areas), has gained evidence in retrospective studies to demonstrate its association with stroke and in prospective studies to demonstrate its prognostic value related to the occurrence of stroke, both ischemic and hemorrhagic, or the occurrence of vascular death.

Summary of Review—

The subtype of ischemic stroke most strongly predicted by leukoaraiosis is lacunar infarct, which is likely caused by the same underlying small-vessel pathology. Leukoaraiosis has been shown to predispose to intracerebral hemorrhage at both the basal-ganglionic and lobar sites, primarily when leukoaraiosis is extensive and patients are treated with anticoagulants because of prior ischemic events.

Conclusions—

Leukoaraiosis shares with stroke common pathophysiological mechanisms and, because it is likely an expression of the same disease, must be regarded as an intermediate surrogate of stroke rather than a true stroke risk factor.
Angiotensin II Produces Superoxide-Mediated Impairment of Endothelial Function in Cerebral Arterioles
Authors: Didion Sean P. , Faraci Frank M.
Published: July 2003

Background and Purpose—

Angiotensin II (Ang II) produces oxidative stress in vascular cells in culture and in extracranial conduit arteries. The goal of this study was to examine the hypothesis that Ang II produces superoxide-mediated impairment of endothelial function in cerebral microvessels.

Methods—

Diameter of cerebral arterioles (baseline diameter=104±3 μm) was measured with the use of a closed cranial window in anesthetized rabbits. Topical application of Ang II was used to avoid effects on arterial pressure.

Results—

Ang II (0.1 to 1 μmol/L for 2 hours) had no effect on baseline diameter (change in diameter of −3±2% in response to 1 μmol/L Ang II) but produced concentration-dependent inhibition of vasodilatation to the endothelium-dependent agonist bradykinin. For example, 1 μmol/L Ang II inhibited responses to 1 nmol/L bradykinin by almost 80%. These inhibitory effects of Ang II were prevented by the superoxide scavenger 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron; 10 mmol/L) or diphenylene iodonium (DPI; 3 μmol/L), an inhibitor of NAD(P)H oxidase. Ang II did not inhibit vasodilatation in response to nitroprusside, an endothelium-independent vasodilator.

Conclusions—

These findings are the first evidence that local Ang II produces superoxide-mediated vascular dysfunction in cerebral microvessels. The results with DPI suggest that the source of superoxide may be an NAD(P)H oxidase.
Studies of the Polarimetric Covariance Matrix. Part II: Modeling and Polarization Errors
Authors: Hubbert J. C. , Bringi V. N.
Published: June 2003

A polarimetric radar covariance matrix model is described to study the behavior of the co-to-cross covariances in precipitation. The 2 × 2 propagation matrix with attenuation, differential attenuation, and differential phase is coupled to the backscatter matrix leading to a propagation-modified covariance matrix model. System polarization errors are included in this model as well. This model is used to study the behavior of the magnitude and phase of the co-to-cross covariances and the linear depolarization ratio (LDR) in rainfall. It is shown that the model predictions are consistent with data collected with the Colorado State University (CSU)–University of Chicago–Illinois State Water Survey (CHILL) radar in intense rainfall. A method is also given for estimating the system polarization errors from covariance matrix data collected in intense rainfall.
Intercomparison of Spectroradiometers for Global and Direct Solar Irradiance in the Visible Range
Authors: Martínez-Lozano José A. , Utrillas Maria P. , Pedrós Roberto , Tena Fernando , Díaz Juan P. , Expósito Francisco J. , Lorente Jerónimo , de Cabo Xavier , Cachorro Victoria , Vergaz Ricardo , Carreño Virgilio
Published: June 2003

This paper presents the results of the analysis of the spectral, global, and direct solar irradiance measurements in the visible range (400–700 nm) that were made in the framework of the first Iberian UV–visible (VIS) instruments intercomparison. The instruments used in this spectral range were four spectroradiometers: three Licor 1800s equipped with different receiver optics and one Optronic 754. For the direct solar irradiance measurements the spectroradiometers were equipped with collimators with different fields of view. Parallel studies have been carried out with the data given by the spectroradiometers with their original calibration file and with the same data that is corrected, following in situ calibration of the instruments using a laboratory reference lamp. To compare the series of spectral data the relative values of mean absolute deviation (MAD) and root-mean-square deviation (rmsd) have been used. The results obtained from the measurements of global irradiance show that the Licor 1800s presented very significant differences at the beginning and at the end of the day due to the deviation from ideal cosine response of the collection optics (i.e., cosine errors). This forced the analysis to be limited to the measurements corresponding to solar elevations higher than 30°. For this solar elevation range, the results of the intercomparison between the Licor instruments, before their in situ calibration, showed differences of about 5% in the visible range. The results from the measurements of direct irradiance show that, if correction factors are considered, these deviations are reduced to 3%, and when the Licors are compared with the Optronic, the deviations are less than 2%.
Mapping and Wavenumber Resolution of Line-Integral Data for Observations of Low-Mode Internal Tides
Authors: Dushaw Brian D.
Published: June 2003

Techniques are developed for using line-integral tomography data to estimate the spectra, maps, and energy of low-mode internal-tide radiation; the extension of these techniques to other phenomena is obvious. Sparse arrays of line integrals over paths 300–1000 km long can generally determine the direction of propagation of semidiurnal radiation well, but the magnitude of the wavenumbers is ambiguous because of sidelobes in the spectrum. Both wavenumber magnitude and direction can generally be determined for diurnal internal-tide radiation. Spectra for the semidiurnal and diurnal internal tides are estimated for the region of the Atlantic Ocean between Puerto Rico and Bermuda using data obtained during the Acoustic Mid-Ocean Dynamics Experiment (AMODE) in 1991–92. Simulations of semidiurnal internal-tide radiation, consisting of wave packets or highly irregular wave crests, are used to show that the line-integral data provide better mapping resolution than point data, but the best results are, of course, obtained when both types of data are used. As a practical example of the formalism of these simulations, maps of M2 internal-tide variability are derived from the AMODE tomography data. Because the inverse problem is underdetermined with the sparse arrays that are deployed in the ocean, the inverse solution generally underestimates the energy of the radiative field. In the simulations employed here, the energy is underestimated by 33% ± 10%, but the exact amount by which the energy is underestimated is dependent on the assumptions made for the simulations, such as the array geometry and the nature of the tidal variability.
A GPS-Tracked Surf Zone Drifter*
Authors: Schmidt W. E. , Woodward B. T. , Millikan K. S. , Guza R. T. , Raubenheimer B. , Elgar Steve
Published: June 2003

A drifter designed to measure surf zone circulation has been developed and field tested. Drifter positions accurate to within a few meters are estimated in real time at 0.1 Hz using the global positioning system (GPS) and a shore-to-drifter radio link. More accurate positions are estimated at 1 Hz from postprocessed, internally logged data. Mean alongshore currents estimated from trajectories of the 0.5-m-draft drifters in 1–2-m water depth agree well with measurements obtained with nearby, bottom-mounted, acoustic current meters. Drifters deployed near the base of a well-developed rip current often followed eddylike paths within the surf zone before being transported seaward.
Numerical Modeling of Bioluminescence Distributions in the Coastal Ocean*
Authors: Shulman Igor , Haddock Steven H. D. , McGillicuddy Dennis J. , Paduan Jeffrey D. , Bissett W. Paul
Published: June 2003

Bioluminescence (BL) predictability experiments (predictions of the intensity, depth, and distance offshore of the BL maximum) were conducted using an advective–diffusive tracer model with velocities and diffusivities from a fine-resolution model of the Monterey Bay, California, area. For tracer initialization, observations were assimilated into the tracer model while velocities and diffusivities were taken from the hydrodynamic model and kept unchanged during the initialization process. This dynamic initialization procedure provides an equilibrium tracer distribution that is balanced with the velocity and diffusivity fields from the hydrodynamic model. This equilibrium BL distribution was used as the initial BL field for 3 days of prognostic calculations. Two cross-shore surveys of bioluminescence data conducted at two locations (north of the bay and inside the bay) were used in four numerical experiments designed to estimate the limits of bioluminescence predictions by tracers. The cross-shore sections extended to around 25 km offshore, they were around 30 m deep, and on average they were approximately 35 km apart from each other. Bioluminescence predictability experiments demonstrated a strong utility of the tracer model (combined with limited bioluminescence observations and with the output from a circulation model) in predicting (over a 72-h period and over 25–35-km distances) the location and intensity of the BL maximum. Analysis of the model velocity fields and observed and model-predicted bioluminesence fields shows that the BL maximum is located in the frontal area representing a strong reversal of flow direction.
Scandinavian Rational Choice Sociology
Authors: Edling Christofer , Stern Charlotta
Published: July 2003

The present status of rational choice sociology in Scandinavia is discussed in the form of a review, examining representative work and highlighting important scholars. Despite a reputation of having a strong Scandinavian rational choice tradition, rational choice sociology is practically non-existent in Denmark, Finland and Iceland. Rational choice sociology in Scandinavia is by-and-large concentrated in Oslo and Stockholm universities, where insightful discussions and relevant applications are found, but not in impressive numbers.
Vocational Training and Career Employment Precariousness in Great Britain, the Netherlands and Sweden
Authors: Korpi Tomas , de Graaf Paul , Hendrickx John , Layte Richard
Published: July 2003

The skills, qualifications and credentials generated by educational systems are strongly related to labour market attainment. The centrality of the educational system for the structuring of individuals' life chances has generated a long-lived and intense debate around the proper design of educational systems. The purpose of this article is to examine whether vocational training provided within the educational system protects graduates against employment precariousness over the life course. The extent and character of vocational training are related here to the transition from school to work, the risk of unemployment once established on the labour market, and the likelihood of finding new employment if unemployed. The data used consist of life history data from Great Britain, the Netherlands and Sweden. The results suggest that the impact of vocational training on labour market precariousness changes over people's work career. Vocational training reduces precariousness during the transition from school to work, whereas there is no difference in the impact of general and vocational education on unemployment risk once established on the labour market. Instead, among those who do become unemployed there are indications that general education may be more beneficial.
On the Embodied Nature of Action
Authors: Bruun Henrik , Langlais Richard
Published: July 2003

A theory of the embodiment of action is proposed. Reflections on relations between human intentions, the human body and the notion of agency lead us to argue that phenomenological analysis is not sufficient for such a theory. Our consideration, that the most fundamental level of embodied agency is that of life itself, brings us to the philosophy of biology and the theory of the organism: briefly, certain parts of the natural environment are intrinsic to the constitution of organisms and, in their more sophisticated configuration, as agents. Action is embodied in the sense that certain physiological processes are internal in relation to it and play a constitutive role in its performance. The way in which environment, context and consciousness affect and constitute the nature of agency at personal and sub-personal levels is elaborated. We see that human agents perceive and act upon their world through a complex shifting between those levels. A summary of the ways in which the social sciences can be enriched by this more comprehensive view of human agency provides the basis of justification for claiming Actor-Network Theory (ANT), originally developed by sociologists studying science and technology, as a promising framework for the continuation of this reasoning.
Critical Reflexivity, Contradictions and Modern Cuban Consciousness
Authors: Haddad Angela T.
Published: July 2003

To survive the economic trauma caused by the demise of the Soviet Block, the Cuban government enacted economic and social reforms that are causing hardships in the lives of Cubans. This article shows that a synthesis of the theories of Marx and Mead provides a useful perspective for understanding Cubans' critical reflections on daily encounters that contradict abstract revolutionary values. Existing sources and qualitative data show a complex interplay between the abstract values of equality, communalism and nationalism, which have been incorporated into definitions of self, and Cubans' efforts to meet their needs. The results presented suggest that Cubans' incorporation into the self of revolutionary attitudes contributes to their reluctance to reject and criticize the revolutionary regime. For Cubans, the formation and expression of critical responses to the existing social system are all the more difficult because of the striking absence of alternative ideologies.
Employees' and Employers' Preferences for Working Time Reduction and Working Time Differentiation
Authors: Tijdens Kea G.
Published: July 2003

Working time reduction is high on the political agenda of the European Union and its member states. In Dutch banks, reduced working time (RWT) was agreed in collective bargaining; however, employers are able to exclude employees from RWT. A total of 82 per cent of employees were assigned RWT. Using large-scale survey data based on 17,308 employees, regression analyses were performed to investigate which employees had favourable RWT attitudes and which employees were assigned RWT. With regard to employee attitudes, the maximizing income hypothesis was mostly supported. Low-income, breadwinning and part-time employees were less in favour of RWT. The maximizing non-working hours hypothesis is only partly supported. Female employees had more favourable attitudes to RWT, but this showed little correlation with the presence of young children. Supervisors had less favourable attitudes to RWT. There was little support for the minimizing working hours hypothesis. Attitudes of employees in redundant jobs hardly differed from other employees, which is surprising given that RWT is aimed at work sharing. In explaining employers' strategies, this article shows that RWT was not assigned at random; its primary aim was to strengthen the banks' long-term transformation from administrative bureaucracies to commercial organizations. The banks did not seem to be aiming for a short-term increase in productivity as RWT was not assigned less frequently to insufficiently staffed departments or more frequently to employees in redundant jobs. Finally, the labour market hypothesis is barely supported. Only one bank assigned RWT less frequently to jobs that were in short supply.
Introduction to the Special Issue: Science, Knowledge and Society
Authors: Thorlindsson Thorolfur , Vilhjalmsson Runar
Published: July 2003

Our changing times provide numerous opportunities for interesting research into different aspect of the knowledge-based society. Science is becoming a powerful institution influencing people's daily lives in various ways. But it is also increasingly influenced by social, economic and political forces shaping its direction and controlling its applications. The boundaries between private and public, nature and society, are increasingly challenged by scientific and technical advances. Technological products or tools embody knowledge and mediate it at the same time. Creating and disseminating knowledge by means of such tools is problematic in many ways, although the tools tend to be taken for granted as objective and neutral. The status and authority of experts in the knowledge-based society is neither automatic nor self-evident. The maintenance of expert status and control requires legitimation and validation displays to fight off public disinterest and scepticism, or legal challenge. Despite the importance of science and technology, mundane and tacit forms of knowledge are still crucial. The implications of recent scientific and technological developments for public welfare seem to indicate that the knowledge society and the welfare state can coexist in a mutually supportive relationship.
The Problem of Tools
Authors: Thurk Jessica , Fine Gary Alan
Published: July 2003

Based on ethnographic research at the National Weather Service and at a large firm of architects in Chicago, we explore the role of technology in mediating knowledge. We consider meteorological databases and computer-aided design systems as tools that standardize and provide access to knowledge, making information transferable across organizational contexts. However, knowledge is always situated and grounded in practice. These tools, even as they standardize, create possibilities for generating and codifying knowledge that is locally meaningful, potentially giving rise to communication problems. Technology is appropriated as part of the local culture, even as it transforms that culture, altering the meaning of knowledge and the nature of creativity at work.
The Social as Trans-Genic
Authors: Bertilsson Thora Margareta
Published: July 2003

This article has a triple aim: (1) it explores how the stunning advance of modern bioscience is affecting the social world, and how once-set boundaries are now being quickly transgressed; (2) it is suggested that the theoretical divides between modernists and post-modernists can be fruitfully viewed, from a sociology of knowledge perspective, as traces of a much more profound and ongoing evolutionary discourse now also affecting the social and the human sciences; (3) concerns are expressed regarding the destabilization of both the natural and the social world alike as a consequence of bioscience: the long-term social effects of the emphasis on individual choice, as presently argued, will eventually erode the system of collective responsibility altogether.