bluuebunny/crossref_metadata_2025 huggingface dataset:
Percutaneous Coronary Intervention Results in Acute Increases in Oxidized Phospholipids and Lipoprotein(a)
Authors: Tsimikas Sotirios , Lau Herbert K. , Han Kyoo-Rok , Shortal Brian , Miller Elizabeth R. , Segev Amit , Curtiss Linda K. , Witztum Joseph L. , Strauss Bradley H.
Published: June 2004

Background—

This study was performed to assess whether oxidized low-density lipoprotein (OxLDL) levels are elevated after percutaneous coronary intervention (PCI).

Methods and Results—

Patients (n=141) with stable angina pectoris undergoing PCI had serial venous blood samples drawn before PCI, after PCI, and at 6 and 24 hours, 3 days, 1 week, and 1, 3, and 6 months. Plasma levels of OxLDL-E06, a measure of oxidized phospholipid (OxPL) content on apolipoprotein B-100 detected by antibody E06, lipoprotein(a) [Lp(a)], autoantibodies to malondialdehyde (MDA)-LDL and copper-oxidized LDL (Cu-OxLDL), and apolipoprotein B-100-immune complexes (apoB-IC) were measured. OxLDL-E06 and Lp(a) levels significantly increased immediately after PCI by 36% (
P
<0.0001) and 64% (
P
<0.0001), respectively, and returned to baseline by 6 hours. In vitro immunoprecipitation of Lp(a) from selected plasma samples showed that almost all of the OxPL detected by E06 was bound to Lp(a) at all time points, except in the post-PCI sample, suggesting independent release and subsequent reassociation of OxPL with Lp(a) by 6 hours. Strong correlations were noted between OxLDL-E06 and Lp(a) (
r
=0.68,
P
<0.0001). MDA-LDL and Cu-OxLDL autoantibodies decreased, whereas apoB-IC levels increased after PCI, but both returned to baseline by 6 hours. Subsequently, IgM autoantibodies increased and peaked at 1 month and then returned to baseline, whereas IgG autoantibodies increased steadily over 6 months.

Conclusions—

PCI results in acute plasma increases of Lp(a) and OxPL and results in short-term and long-term immunologic responses to OxLDL. OxPL that are released or generated during PCI are transferred to Lp(a), suggesting that Lp(a) may contribute acutely to a protective innate immune response. In settings of enhanced oxidative stress and chronically elevated Lp(a) levels, the atherogenicity of Lp(a) may stem from its capacity as a carrier of proinflammatory oxidation byproducts.
Clopidogrel Resistance Is Associated With Increased Risk of Recurrent Atherothrombotic Events in Patients With Acute Myocardial Infarction
Authors: Matetzky Shlomi , Shenkman Boris , Guetta Victor , Shechter Michael , Beinart Roy , Goldenberg Ilan , Novikov Ilya , Pres Hanna , Savion Naphtali , Varon David , Hod Hanoch
Published: June 2004

Background—

Although clopidogrel reduces the risk of cardiovascular episodes after coronary events and stenting, a substantial number of incidents continue to occur.

Methods and Results—

The antiplatelet effect of clopidogrel was studied prospectively in 60 consecutive patients who underwent primary angioplasty (percutaneous coronary intervention [PCI]) with stenting for acute ST-segment–elevation myocardial infarction (STEMI) to determine whether variability in response to clopidogrel affects clinical outcomes. Patients were stratified into 4 quartiles according to the percentage reduction of ADP-induced platelet aggregation. Although patients in the first quartile were resistant to the effects of clopidogrel (ADP-induced platelet aggregation at day 6, 103±8% of baseline), ADP-induced aggregation was reduced to 69±3%, 58±7%, and 33±12% of baseline, respectively, in patients in quartiles 2 through 4 (
P
<0.01 for all). In addition, epinephrine-induced platelet aggregation and platelet aggregation under flow conditions, assessed by the cone-and-plate(let) analyzer method, were reduced significantly less in the first quartile than in quartiles 2 through 4. Whereas 40% of patients in the first quartile sustained a recurrent cardiovascular event during a 6-month follow-up, only 1 patient (6.7%) in the second quartile and none in the third and fourth quartiles suffered a cardiovascular event (
P
=0.007).

Conclusions—

Up to 25% of STEMI patients undergoing primary PCI with stenting are resistant to clopidogrel and therefore may be at increased risk for recurrent cardiovascular events.
Lead, Cadmium, Smoking, and Increased Risk of Peripheral Arterial Disease
Authors: Navas-Acien Ana , Selvin Elizabeth , Sharrett A. Richey , Calderon-Aranda Emma , Silbergeld Ellen , Guallar Eliseo
Published: June 2004

Background—

Lead and cadmium exposure may promote atherosclerosis, although the cardiovascular effects of chronic low-dose exposure are largely unknown. The objective of the present study was to evaluate the association between blood levels of lead and cadmium and peripheral arterial disease.

Methods and Results—

We analyzed data from 2125 participants who were ≥40 years of age in the 1999 to 2000 National Health and Nutrition Examination Survey (NHANES). Peripheral arterial disease was defined as an ankle brachial index <0.9 in at least 1 leg. Lead and cadmium levels were measured by atomic absorption spectrometry. After adjustment for demographic and cardiovascular risk factors, the ORs of peripheral arterial disease comparing quartiles 2 to 4 of lead with the lowest quartile were 1.63 (95% CI, 0.51 to 5.15), 1.92 (95% CI, 0.62 to 9.47), and 2.88 (95% CI, 0.87 to 9.47), respectively (
P
for trend=0.02). The corresponding ORs for cadmium were 1.07 (95% CI, 0.44 to 2.60), 1.30 (95% CI, 0.69 to 2.44), and 2.82 (95% CI, 1.36 to 5.85), respectively (
P
for trend=0.01). The OR of peripheral arterial disease for current smokers compared with never smokers was 4.13. Adjustment for lead reduced this OR to 3.38, and adjustment for cadmium reduced it to 1.84.

Conclusions—

Blood lead and cadmium, at levels well below current safety standards, were associated with an increased prevalence of peripheral arterial disease in the general US population. Cadmium may partially mediate the effect of smoking on peripheral arterial disease.
Carvedilol but Not Metoprolol Reduces β-Adrenergic Responsiveness After Complete Elimination From Plasma In Vivo
Authors: Kindermann Michael , Maack Christoph , Schaller Susanne , Finkler Nadine , Schmidt Kathrin I. , Läer Stephanie , Wuttke Henrike , Schäfers Hans-Joachim , Böhm Michael
Published: June 2004

Background—

Carvedilol but not metoprolol exhibits persistent binding to β-adrenergic receptors (β-ARs) even after washout in cell culture experiments. Here, we determined the significance of this phenomenon on human β-ARs in vitro and in vivo.

Methods and Results—

Experiments were conducted on human atrial trabeculae (n=8 to 10 per group). In the presence of metoprolol, isoproterenol potency was reduced compared with controls (
P
<0.001). In the presence of carvedilol, isoproterenol identified 2 distinct binding sites of high (36±6%; −8.8±0.4 log mol/L) and low affinity (−6.5±0.2 log mol/L). After β-blocker washout, isoproterenol potency returned to control values in metoprolol-treated muscles, whereas in carvedilol-treated preparations, isoproterenol potency remained decreased (
P
<0.001 versus control). In vivo studies were performed in 9 individuals receiving metoprolol succinate (190 mg/d) or carvedilol (50 mg/d) for 11 days in a randomized crossover design. Dobutamine stress echocardiography (5 to 40 μg · kg
−1
· min
−1
) was performed before, during, and 44 hours after application of study medication. β-Blocker medication reduced heart rate, heart rate–corrected velocity of circumferential fiber shortening, and cardiac output compared with baseline (
P
<0.02 to 0.0001). After withdrawal of metoprolol, all parameters returned to baseline values, whereas after carvedilol, all parameters remained reduced (
P
<0.05 to 0.001) despite complete plasma elimination of carvedilol.

Conclusions—

Carvedilol but not metoprolol inhibits the catecholamine response of the human heart beyond its plasma elimination. The persistent β-blockade by carvedilol may be explained by binding of carvedilol to an allosteric site of β-ARs.
Circulating CD34-Positive Cells Provide an Index of Cerebrovascular Function
Authors: Taguchi Akihiko , Matsuyama Tomohiro , Moriwaki Hiroshi , Hayashi Takuya , Hayashida Kohei , Nagatsuka Kazuyuki , Todo Kenichi , Mori Katsushi , Stern David M. , Soma Toshihiro , Naritomi Hiroaki
Published: June 2004

Background—

Increasing evidence points to a role for circulating endothelial progenitor cells, including populations of CD34- and CD133-positive cells present in peripheral blood, in maintenance of the vasculature and neovascularization. Immature populations, including CD34-positive cells, have been shown to contribute to vascular homeostasis, not only as a pool of endothelial progenitor cells but also as a source of growth/angiogenesis factors at ischemic loci. We hypothesized that diminished numbers of circulating immature cells might impair such physiological and reparative processes, potentially contributing to cerebrovascular dysfunction.

Methods and Results—

The level of circulating immature cells, CD34-, CD133-, CD117-, and CD135-positive cells, in patients with a history of atherothrombotic cerebral ischemic events was analyzed to assess possible correlations with the degree of carotid atherosclerosis and number of cerebral infarctions. There was a strong inverse correlation between numbers of circulating CD34- and CD133-positive cells and cerebral infarction. In contrast, there was no correlation between the degree of atherosclerosis and populations of circulating immature cells. Analysis of patients with cerebral artery occlusion revealed a significant positive correlation between circulating CD34- and CD133-positive cells and regional blood flow in areas of chronic hypoperfusion.

Conclusions—

These results suggest a possible contribution of circulating CD34- and CD133-positive cells in maintenance of the cerebral circulation in settings of ischemic stress. Our data demonstrate the utility of a simple and precise method to quantify circulating CD34-positive cells, the latter providing a marker of cerebrovascular function.
Body Mass Index and Blood Pressure Influences on Left Ventricular Mass and Geometry in African Americans
Authors: Fox Ervin , Taylor Herman , Andrew Michael , Han Hui , Mohamed Emad , Garrison Robert , Skelton Thomas
Published: June 2004

A unique interaction between the influences of body mass index and blood pressure on left ventricular mass index and geometry may contribute to the higher prevalence of left ventricular hypertrophy in African Americans. This cross-sectional study assessed separate and joint influences of body mass index and blood pressure on left ventricular mass index and geometry in 1729 African American participants of the Atherosclerotic Risk in Communities Study. The association between both left ventricular mass index and relative wall thickness and body mass index in each blood pressure category and between these variables and blood pressure in each body mass index category was assessed adjusting for age, diabetes status, hypertension medication, and smoking status. We found that left ventricular hypertrophy and concentric geometry were highly prevalent and that body mass index and blood pressure were independently associated with left ventricular mass index. The adjusted association between blood pressure and left ventricular mass index was stronger with higher body mass index categories; however, there was no significant interaction suggesting merely an additive relationship (not synergistic/multiplicative as tested for in the interaction analysis). Although relative wall thickness was greater with higher categories of body mass index and blood pressure, the mean difference in relative wall thickness between body mass index and blood pressure categories was not statistically significant. The effect on left ventricular geometry as measured by relative wall thickness supports the theory that there is a pathophysiological component in the mechanism of hypertrophy.
Electrocardiographic Strain Pattern and Prediction of Cardiovascular Morbidity and Mortality in Hypertensive Patients
Authors: Okin Peter M. , Devereux Richard B. , Nieminen Markku S. , Jern Sverker , Oikarinen Lasse , Viitasalo Matti , Toivonen Lauri , Kjeldsen Sverre E. , Julius Stevo , Snapinn Steven , Dahlöf Björn
Published: June 2004

The ECG strain pattern of lateral ST depression and T-wave inversion is a marker for left ventricular hypertrophy (LVH) and adverse prognosis in population studies. However, whether ECG strain is an independent predictor of cardiovascular (CV) morbidity and mortality in the setting of aggressive antihypertensive therapy is unclear. ECGs were examined at study baseline in 8854 hypertensive patients with ECG LVH who were treated in a blinded manner with atenolol- or losartan-based regimens. Strain was defined by the presence of a downsloping convex ST segment with an inverted asymmetrical T wave opposite to the QRS axis in leads V
5
and/or V
6
and was present in 971 patients (11.0%). The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study composite end point of CV death or nonfatal myocardial infarction or stroke occurred in 1035 patients (11.7%). In Cox analyses adjusting only for treatment effect, ECG strain was a significant predictor of CV death (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.78 to 2.86), fatal/nonfatal myocardial infarction (HR 2.16, 95% CI 1.67 to 2.80), fatal/nonfatal stroke (HR 1.76, 95% CI 1.39 to 2.21), and the composite CV end point (HR 1.99, 95% CI 1.70 to 2.33). After further adjusting for standard CV risk factors, baseline blood pressure, and severity of ECG LVH, ECG strain remained a significant predictor of CV mortality (HR 1.53, 95% CI 1.18 to 2.00), myocardial infarction (HR 1.55, 95% CI 1.16 to 2.06), and the composite CV end point (HR 1.33, 95% CI 1.11 to 1.59). Thus, ECG strain is a marker of increased CV risk in hypertensive patients in the setting of aggressive blood pressure lowering, independent of baseline severity of ECG LVH.
Altered Subcellular Distribution of Na
+
,K
+
-ATPase in Proximal Tubules in Young Spontaneously Hypertensive Rats
Authors: Hinojos Cruz A. , Doris Peter A.
Published: June 2004

During early development of hypertension, the spontaneously hypertensive rat (SHR) demonstrates increased proximal tubule sodium reabsorption. Our previous observations of reduced Na
+
,K
+
-ATPase catalytic α1 and γ subunit transcript abundance in SHR proximal tubule led us to test the hypothesis that increased proximal tubule sodium reabsorption may be attributable to altered subunit protein abundance, post-translational modification, or a shift in subcellular α1 and γ distribution toward the basolateral membrane. We now extend previous gene expression studies by analyzing total cellular α1 and γ protein abundance in proximal tubule from SHR compared with matched Wistar–Kyoto (WKY) controls. We also used sucrose density-gradient centrifugation to isolate basolateral, early, and late endosomal membrane–enriched fractions as well as cell surface biotinylation to test the hypothesis of altered subunit subcellular distribution in the SHR proximal tubule. At 4 weeks of age, significantly greater amounts of α1 were present in basolateral membrane–enriched fractions of SHR than WKY (21.1±1.8% versus 12.3±1.8%;
P
<0.005), and there was a concomitant reduction of α1 in late endosomal membrane–enriched fractions of SHR (63.3±2.7% versus 74.8±4.3%;
P
<0.05). This finding was confirmed in cell surface biotinylation studies that showed higher α1 (1.45±0.1-fold greater;
P
<0.05) and γ-subunit (3.48±0.7-fold greater;
P
<0.01) abundance in 4-week-old SHR proximal tubule plasma membrane compared with matched WKY samples. These studies support the hypothesis that development of hypertension in SHR may involve an altered subcellular distribution of proximal tubule Na
+
,K
+
-ATPase subunits.
Is There a Rationale for Angiotensin Blockade in the Management of Obesity Hypertension?
Authors: Sharma Arya M.
Published: June 2004

Obesity, currently affecting >20% of the adult population in most Western countries, is a major risk factor for the development of hypertension. Hypertension in obese patients is, in the majority of instances, further complicated by the concomitant presence of dyslipidemia and insulin resistance. The latter is reflected by derangement of glucose homeostasis, ranging from hyperinsulinemia to frank type 2 diabetes. Hypertension in obese patients is also associated with an increased risk for left ventricular hypertrophy, endothelial dysfunction, renal hyperfiltration, microalbuminuria, and elevated markers of inflammation. Sodium retention, volume expansion, and increased cardiac output are common findings in obese individuals. These changes are largely attributable to increased activity of the sympathetic nervous system and insufficient suppression of the renin-angiotensin system. Recent data show increased expression of angiotensin II–forming enzymes in adipose tissue, and increased activity of the renin-angiotensin system has recently been implicated in the development of insulin resistance and type 2 diabetes. Accordingly, antihypertensive agents that block the renin-angiotensin system might be a beneficial strategy for treatment of obesity-related hypertension. Both angiotensin-converting enzyme inhibitors and angiotensin type-1 receptor blockers have been associated with favorable metabolic properties and end-organ protection in addition to their antihypertensive effects. Data from ongoing large trials will provide an indication of the protective and preventive effects of these treatment strategies while offering insights into the mechanisms linking obesity, hypertension, and other facets of the metabolic syndrome.
Perinatal
l
-Arginine and Antioxidant Supplements Reduce Adult Blood Pressure in Spontaneously Hypertensive Rats
Authors: Racasan Simona , Braam Branko , van der Giezen Dionne M. , Goldschmeding Roel , Boer Peter , Koomans Hein A. , Joles Jaap A.
Published: June 2004

Embryo cross-transplantation and cross-fostering between spontaneously hypertensive rats (SHR) and normotensive rats (WKY) suggest that perinatal environment modulates the genetically determined phenotype. In SHR the balance between NO and reactive oxygen species (ROS) is disturbed. We hypothesized that increasing NO and diminishing ROS in perinatal life would ameliorate hypertension in adult SHR. Pregnant SHR and WKY and their offspring received
l
-arginine plus antioxidants (vitamin C, vitamin E, and taurine) during the last 2 weeks of pregnancy and then until either 4 or 8 weeks after birth. Systolic blood pressure (SBP) and urinary excretion of protein, nitrates (NO
x
), and thiobarbituric acid reactive substances (TBARS) were measured. At 48 weeks of age rats were euthanized for glomerular counts. Perinatal supplements reduced SBP persistently in SHR and prevented the SBP increase observed in aging WKY. Initially NO
x
excretion was lower and TBARS excretion higher in SHR than WKY. There was a direct effect on NO
x
excretion in supplemented pregnant SHR and their offspring, but no increase was observed after stopping the supplements. TBARS excretion was only depressed up to 14 weeks by the supplements despite persistent differences in SBP. Consistent effects on nephron number were absent. Mild proteinuria, present in control SHR at 48 weeks, was prevented in all supplemented rats. Perinatal supplementation of NO substrate and antioxidants results in persistent reduction of SBP and renal protection in SHR, although effects on NO
x
and TBARS were only transient. This suggests a critical role for perinatal pro- and antioxidant balance in programming BP later in life.
Simvastatin Combined With Ramipril Treatment in Hypercholesterolemic Patients
Authors: Koh Kwang Kon , Son Ji Won , Ahn Jeong Yeal , Kim Dae Sung , Jin Dong Kyu , Kim Hyung Sik , Han Seung Hwan , Seo Yiel-Hea , Chung Wook-Jin , Kang Woong Chol , Shin Eak Kyun
Published: June 2004

Mechanisms underlying biological effects of statin and angiotensin-converting enzyme inhibitor therapies differ. Thus, we studied vascular responses to combination therapy in hypercholesterolemic patients. A randomized, double-blind, placebo-controlled, crossover trial was conducted with 50 hypercholesterolemic patients with simvastatin and either placebo or ramipril (study I) and in 45 hypercholesterolemic diabetic patients with simvastatin or ramipril with placebo or simvastatin combined with ramipril (study II) for 2 months with 2 months washout. In study I simvastatin combined with ramipril significantly reduced blood pressure after 2 months. Simvastatin alone or combined with ramipril significantly changed lipoproteins, improved percent flow-mediated dilator response to hyperemia by 30±5% and 53±6%, respectively (
P
<0.001), and reduced plasma levels of malondialdehyde by 4±7% (
P
=0.026) and 25±4% (
P
<0.001), respectively. Monocyte chemoattractant protein-1 levels decreased by 3±3% and 12±2%, respectively (
P
=0.049 and
P
=0.001, respectively), C-reactive protein levels changed by 0% and 18%, respectively (
P
=0.036 and
P
<0.001, respectively), and plasminogen activator inhibitor-1 antigen levels changed by −7±7% and 17±5%, respectively (
P
=0.828 and
P
<0.001, respectively). In study II ramipril alone did not significantly change lipoproteins and C-reactive protein levels, however, simvastatin combined with ramipril significantly changed lipoproteins and C-reactive protein levels more than ramipril alone (
P
<0.001 and
P
=0.048 by ANOVA, respectively). Ramipril alone or simvastatin combined with ramipril significantly improved the percent flow-mediated dilator response to hyperemia (both
P
<0.001), however, simvastatin combined with ramipril showed significantly more improvement than ramipril alone (
P
<0.001 by ANOVA). Simvastatin combined with ramipril significantly improved endothelium-dependent vasodilation and fibrinolysis potential and reduced plasma levels of oxidant stress and inflammation markers in hypercholesterolemic patients.
Myocyte Enhancer Factor 2 Mediates Vascular Inflammation via the p38-Dependent Pathway
Authors: Suzuki Etsu , Satonaka Hiroshi , Nishimatsu Hiroaki , Oba Shigeyoshi , Takeda Ryo , Omata Masao , Fujita Toshiro , Nagai Ryozo , Hirata Yasunobu
Published: June 2004

Although it has been established that myocyte enhancer factor 2 (MEF2) plays pivotal roles in the development of the cardiovascular system as well as skeletal muscle cells, little is known of its role in vascular inflammatory diseases such as atherosclerosis and restenosis after angioplasty. To investigate the role of MEF2 in vascular inflammation and that of p38 in the activation of MEF2, we infected cultured rat vascular smooth muscle cells (VSMCs) with an adenovirus construct expressing a dominant-negative mutant of MEF2A (MEF2ASA) or mitogen-activated protein kinase kinase 6 (MEK6AA), and examined their effects on the expression of monocyte chemoattractant protein-1 (MCP-1), which is known to play important roles in vascular inflammation. We also examined the role of MEF2 in vivo using a rat model of transluminal wire-induced injury of the femoral artery. Angiotensin II (Ang II)–induced expression of MCP-1 mRNA was significantly inhibited by infection with adenoviruses encoding MEF2ASA (AdMEF2ASA) or MEK6AA. Ang II–induced increase of MCP-1 promoter activity was also significantly suppressed by overexpression of MEF2ASA or MEK6AA. Ang II stimulated the transactivating function of MEF2A and this activation was inhibited by overexpression of MEK6AA. Infection with AdMEF2ASA suppressed MCP-1 expression in the femoral artery after the transluminal mechanical injury. AdMEF2ASA infection also inhibited macrophages infiltration and neointimal formation in the wire-injured femoral arteries. These results suggested that MEF2 activation via the p38-dependent pathway mediates vascular inflammation via stimulation of MCP-1 expression in VSMCs and macrophages infiltration.
Uncontrolled Expression of Vascular Endothelial Growth Factor and Its Receptors Leads to Insufficient Skin Angiogenesis in Patients With Systemic Sclerosis
Authors: Distler Oliver , Distler Jörg H. W. , Scheid Annette , Acker Till , Hirth Astrid , Rethage Janine , Michel Beat A. , Gay Renate E. , Müller-Ladner Ulf , Matucci-Cerinic Marco , Plate Karl H. , Gassmann Max , Gay Steffen
Published: June 2004

Systemic sclerosis (SSc) skin lesions are characterized by disturbed vessel morphology with enlarged capillaries and an overall reduction in capillary density, suggesting a deregulated, insufficient angiogenic response. It has been postulated that this phenomenon is due to reduced expression of the potent angiogenic factor vascular endothelial growth factor (VEGF). In contrast to this hypothesis, we demonstrate that the expression of both VEGF and its receptors VEGFR-1 and VEGFR-2 is dramatically upregulated in skin specimens of SSc patients throughout different disease stages. Interestingly, upregulation of VEGF was not mediated by hypoxia-inducible transcription factor-1 (HIF-1) as indicated by only a weak expression of the oxygen-sensitive α-subunit of HIF-1 in the skin of SSc patients. This was unexpected on measuring low P
o
2
values in the SSc skin by using a polarographic oxygen microelectrode system. Considering our observation that PDGF and IL-1β costimulated VEGF expression, we propose that chronic and uncontrolled VEGF upregulation that is mediated by an orchestrated expression of cytokines rather than VEGF downregulation is the cause of the disturbed vessel morphology in the skin of SSc patients. Consequently, for therapeutic approaches aiming to improve tissue perfusion in these patients, a controlled expression and timely termination of VEGF signaling appears to be crucial for success of proangiogenic therapies.
Pediatric Stroke Belt
Authors: Fullerton Heather J. , Elkins Jacob S. , Johnston S. Claiborne
Published: June 2004

Background and Purpose—

Numerous studies have demonstrated higher stroke mortality rates in adults residing in the Southeastern United States (the “Stroke Belt”). If the Stroke Belt is solely caused by regional differences in atherosclerotic stroke risk factors, it should not apply to children.

Methods—

For the years 1979 to 1998, we determined rates of death from stroke in children <20 years of age based on death certificates, and compared age-adjusted stroke mortality rates in 11 Stroke Belt states versus other US states. For comparison, the same methods were applied to adults.

Results—

Children in Stroke Belt states have an increased risk of death from stroke compared with children in other states (relative risk [RR], 1.21; 95% CI, 1.12 to 1.29). The greater risk in Stroke Belt states was apparent for ischemic and hemorrhagic stroke, for all age groups and both sexes, and persisted after adjustment for ethnicity. The geographic disparity in children was similar in magnitude to that in adults.

Conclusions—

Similar to adults, children in Stroke Belt states have a higher risk of death from stroke than children in other US states. Stroke risk factors that are applicable to both children and adults should be considered in attempts to explain this geographic variation.
D-JNKI1, a Cell-Penetrating c-Jun-N-Terminal Kinase Inhibitor, Protects Against Cell Death in Severe Cerebral Ischemia
Authors: Hirt Lorenz , Badaut Jérôme , Thevenet Jonathan , Granziera Cristina , Regli Luca , Maurer Fabienne , Bonny Christophe , Bogousslavsky Julien
Published: June 2004

Background and Purpose—

In 2 models of severe ischemic injury, we have evaluated the neuroprotective action of D-JNKI1, a cell-penetrating and protease-resistant peptide selectively inhibiting the c-Jun-N-terminal kinase (JNK).

Methods—

Hippocampal slices from newborn rats were subjected to oxygen (5%) and glucose (1 mmol/L) deprivation for 30 minutes. Cell death was evaluated with propidium iodide, and the evoked potential responses were recorded in the CA1 region after stimulation in CA3. Male ICR-CD1 mice were subjected to permanent endoluminal “suture” middle cerebral artery occlusion (MCAo). The lesion size was determined after 24 hours by triphenyl-tetrazolium chloride staining, and neurological scores and rotarod treadmill performance were used to evaluate the neurological outcome.

Results—

In vitro, D-JNKI administration 6 hours after oxygen glucose deprivation reduced cell death at 24 hours from 21%±8% (n=10) to 5%±3% (n=7,
P
<0.01). This protective effect was still seen at 48 hours, paralleled by an improved amplitude of the evoked potential response. In vivo in the mouse, D-JNKI1 administration 3 hours after ischemia significantly reduced the infarct volume from 162±27 mm
3
(n=14) to 85±27 mm
3
(n=9,
P
<0.001). The functional outcome was also improved.

Conclusions—

JNK inhibition prevents cell death induced by oxygen and glucose deprivation in hippocampal slice cultures in vitro and by permanent suture MCAo in vivo. D-JNKI1 is a powerful neuroprotectant in models of both mild and severe cerebral ischemia, with an extended therapeutic window. Further investigations are needed to identify the relevant JNK target(s) mediating ischemic neuronal death.
White Matter Hyperintensity on Cranial Magnetic Resonance Imaging
Authors: Kuller Lewis H. , Longstreth W.T. , Arnold Alice M. , Bernick Charles , Bryan R. Nick , Beauchamp Norman J.
Published: June 2004

Background and Purpose—

We have previously reported that several “silent” infarcts found on magnetic resonance imaging (MRI) were a risk factor for stroke. Several recent reports have shown that high white matter grade (WMG) and increasing WMG over time were risk factors for stroke. We tested the hypothesis that high WMG ≥2 was a predictor of risk for stroke, independent of other risk factors.

Methods—

We examined the extent of white matter hyperintensity on cranial MRI of 3293 participants from the Cardiovascular Health Study (CHS). The degree of white matter hyperintensity was graded from least severe (grade=0) to most severe (grade=9). Participants were followed-up for an average of 7 years for the occurrence of a stroke. Clinical stroke diagnoses were based on hospital records reviewed by an adjudication committee expert in stroke diagnosis. During this period, 278 strokes occurred.

Results

The relative risk of stroke increased significantly as the WMG increased. The risk of stroke was 2.8% per year for participants with high WMG (grades ≥5), compared with only 0.6% for participants with grades 0 to 1.

Conclusions

The risk of stroke with high WMG is independent of traditional stroke risk factors and persists when controlling for MRI infarcts, another subclinical imaging marker of cerebrovascular disease. Assessment of white matter disease may be valuable in assessing future risk of stroke.
Cerebral Venous Flow Velocity Predicts Poor Outcome in Subarachnoid Hemorrhage
Authors: Niesen Wolf-Dirk , Rosenkranz Michael , Schummer Wolfram , Weiller Cornelius , Sliwka Ulrich
Published: June 2004

Background and Purpose—

Predictors of clinical outcome in aneurysmal subarachnoid hemorrhage (SAH) vary in reliability. Measurement of cerebral venous hemodynamics by transcranial color-coded duplexsonography (TCCS) has become of increasing interest lately, and correlation with intracranial pressure (ICP) seems to be high. The aim of the presented study was to assess changes of cerebral venous hemodynamics in SAH and evaluate its relationship with clinical outcome.

Methods—

We performed sequential TCCS of venous peak flow velocities (vp-FVs) in the transversal sinus in 28 consecutive patients with aneurysmal SAH (Hunt and Hess scale 1 to 5). Measurement was initiated at onset of arterial vasospasm up to 5 days after SAH. All patients had a continuous ICP monitoring. Clinical outcome was evaluated with the modified ranking scale (MRS) 30 days after SAH. Patients were divided according to outcome: group I good recovery (MRS 0-III) and group II poor outcome (death or MRS IV-V). Maximum vp-FV, time-averaged vp-FV (mv-FV), and ICP were compared between groups.

Results—

Vp-FV and mv-FV as well as ICP of group II exceeded values of group I (
P
<0.001 for all 3 parameters). Vp-FV showed a positive correlation with ICP (
r
=0.63;
P
<0.001). A vp-FV exceeding 35.4 cm/s (sensitivity 100%; specificity 90.9%), an mv-FV exceeding 27.3 cm/s (sensitivity 94.1%; specificity 81.8%), and an ICP exceeding 24 mm Hg (sensitivity 87.5%; specificity 81.8%) predicted poor outcome (receiver operating characteristic analysis).

Conclusions—

Increased ICP values correlate with increased venous flow velocities. In SAH, increased ICP and increased venous flow velocities are associated with poor outcome. Flow velocity of the transversal sinus is a highly sensitive, reliable, and early predictor of outcome in SAH.
Treatment of Stroke With Erythropoietin Enhances Neurogenesis and Angiogenesis and Improves Neurological Function in Rats
Authors: Wang Lei , Zhang Zhenggang , Wang Ying , Zhang Ruilan , Chopp Michael
Published: June 2004

Background and Purpose—

Erythropoietin (EPO) promotes proliferation and differentiation of erythroid progenitors and the survival of maturing erythroid cells. Here, we investigated the role of EPO in brain repair after stroke.

Methods—

Rats were treated with recombinant human EPO (rhEPO) at 24 hours after the onset of embolic stroke. An array of behavior tests was performed. Rats were euthanized 28 days after stroke for measurements of infarct volume, angiogenesis, and neurogenesis. In vitro, neurospheres derived from the subventricular zone (SVZ) of the rat and cerebral endothelial cells derived from the mouse were treated with rhEPO. Capillary-like tube formation and neuronal differentiation were measured.

Results—

Treatment with rhEPO significantly improved functional recovery, along with increases in density of cerebral microvessels at the stroke boundary and numbers of BrdU, doublecortin, and nestin immunoreactive cells in the SVZ. rhEPO treatment significantly increased brain levels of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF). In vitro, rhEPO enhanced capillary tube formation of cerebral endothelial cells, which was inhibited by a specific VEGF receptor 2 antagonist (SU1498). Incubation of neurospheres derived from stroke SVZ with anti-EPO neutralizing antibody inhibited neurogenesis, whereas incubation of stroke-derived neurospheres with rhEPO enhanced neurogenesis.

Conclusion—

Our data suggest that EPO-increased VEGF and BDNF may be involved in angiogenesis and neurogenesis, which could contribute to functional recovery.
Prospective Study of Plasma Carotenoids and Tocopherols in Relation to Risk of Ischemic Stroke
Authors: Hak A. Elisabeth , Ma Jing , Powell Calpurnyia B. , Campos Hannia , Gaziano J. Michael , Willett Walter C. , Stampfer Meir J.
Published: June 2004

Background and Purpose—

Intake of fruits and vegetables has been related to lower risk of ischemic stroke, but nutrients responsible for this apparent benefit remain ill-defined. Tocopherols (vitamin E) have also been proposed to be protective.

Methods—

We conducted a prospective, nested case-control analysis among male physicians without diagnosed cardiovascular disease followed-up for up to 13 years in the Physicians’ Health Study. Samples from 297 physicians with ischemic stroke were analyzed with paired controls, matched for age and smoking, for 5 major carotenoids (α- and β-carotene, β-cryptoxanthin, lutein, and lycopene), retinol, and α- and γ-tocopherol.

Results—

Baseline plasma levels of α-carotene and β-carotene and lycopene tended to be inversely related to risk of ischemic stroke with an apparent threshold effect. As compared with men whose plasma levels were in the lowest quintile, the multivariate adjusted odds ratios (ORs) of ischemic stroke among men with levels in the second through fifth quintiles were 0.59 (95% CI, 0.36 to 0.98) for α-carotene, 0.62 (95% CI, 0.38 to 1.01) for β-carotene, and 0.61 (95% CI, 0.37 to 1.00) for lycopene. A tendency toward an inverse association was found for β-cryptoxanthin, but the result was not statistically significant. No association was found for lutein, retinol, and tocopherols.

Conclusion—

Our data suggest that higher plasma levels of carotenoids, as markers of fruit and vegetable intake, are inversely related to risk of ischemic stroke and provide support for recommendations to consume fruits and vegetables regularly.
Predictors of Hyperacute Clinical Worsening in Ischemic Stroke Patients Receiving Thrombolytic Therapy
Authors: Leigh Richard , Zaidat Osama O. , Suri Muhammad F. , Lynch Gwendolyn , Sundararajan Sophia , Sunshine Jeffrey L. , Tarr Robert , Selman Warren , Landis Dennis M.D. , Suarez Jose I.
Published: June 2004

Background and Purpose—Although long-term outcome determinants in acute ischemic stroke (AIS) patients have been defined, less is known about those predicting hyperacute worsening after thrombolytic therapy (TT). We investigated predictors of short-term clinical worsening (National Institutes of Health Stroke Scale [NIHSS] change ≥4 within 24 hours of admission).

Methods—We studied 201 AIS patients who received TT within 6 hours of symptom onset. We determined baseline demographics, comorbidities, NIHSS at baseline and at 24 hours after TT, head computed tomography scan before and within 24 hours after TT, and angiographic recanalization in patients treated with intra-arterial (IA) thrombolysis. Significance of relationships was evaluated byttest or Wilcoxon signed rank sum test. Logistic regression model (LRM) was fitted to determine independence of significant variables.

Results—Of 201 patients, 13% worsened, 39% improved, and 48% remained unchanged 24 hours after TT. Most patients (72%) received IA thrombolysis. Patients who deteriorated, compared with those who improved, were more likely to have complicating intracranial hemorrhage (ICH;P<0.001), absent recanalization (P=0.026), and higher blood glucose (BG;P=0.049). Hyperglycemia (>150 mg/dL) was greater in patients who worsened even in presence of recanalization (P=0.004, odds ratio [OR] 6.47). LRM showed that adjusted OR for increased risk of bad outcome and mortality for an increase of BG by 50 mg/dL is 1.56 and 1.38, respectively.

Conclusions—Hyperglycemia and ICH are independent predictors of hyperacute worsening in AIS patients receiving TT. Although recanalization is the purpose of IA thrombolysis, its impact on clinical improvement may not be apparent without strict BG control.
Very Long-Term Outcome After Stroke in Auckland, New Zealand
Authors: Anderson Craig S. , Carter Kristie N. , Brownlee Wallace J. , Hackett Maree L. , Broad Joanna B. , Bonita Ruth
Published: June 2004

Background and Purpose—

Limited information exists on the long-term outcome from stroke. We aimed to determine survival and health status at 21-year follow-up of patients who participated in a population-based stroke incidence study undertaken in Auckland, New Zealand.

Methods—

During 12 months beginning March 1, 1981, half of all residents of Auckland with acute first-ever or recurrent stroke (n=680) were assessed and followed up prospectively during the next 2 decades. In 2002, their vital status and health-related quality of life (HRQoL) using the 36-item short-form questionnaire (SF-36) were determined by telephone interviews. Kaplan–Meier survival probabilities for the stroke cohort were compared with life table estimates for the New Zealand population. The SF-36 profile of 21-year stroke survivors was compared with a standardized New Zealand population.

Results—

Overall, 626 of the original cohort had died and 4 were lost to follow-up, leaving 50 (7%) individuals (57% male; mean age 70 years) available in 2002, of whom 12% were residents of an institutional care facility and 19% required help with everyday activities. The stroke cohort had nearly twice the mortality rate of the New Zealand population, but the SF-36 profile of very long-term stroke survivors was broadly similar to the general population.

Conclusions—

Because stroke is generally a disease of older people and has a high case fatality, it is not surprising that <1 in 10 people survive 2 decades after onset. However, of those who do, their HRQoL profile suggests that they meld relatively successfully within the general population, despite ongoing disability and a higher mortality risk.
Adaptive Blind Separation with an Unknown Number of Sources
Authors: Ye Ji-Min , Zhu Xiao-Long , Zhang Xian-Da
Published: June 2004

The blind source separation (BSS) problem with an unknown number of sources is an important practical issue that is usually skipped by assuming that the source number n is known and equal to the number m of sensors. This letter studies the general BSS problem satisfying m ≥ n. First, it is shown that the mutual information of outputs of the separation network is a cost function for BSS, provided that the mixing matrix is of full column rank and the m×m separating matrix is nonsingular. The mutual information reaches its local minima at the separation points, where the m outputs consist of n desired source signals and m−n redundant signals. Second, it is proved that the natural gradient algorithm proposed primarily for complete BSS (m n) can be generalized to deal with the overdetermined BSS problem (m>n), but it would diverge inevitably due to lack of a stationary point. To overcome this shortcoming, we present a modified algorithm, which can perform BSS steadily and provide the desired source signals at specified channels if some matrix is designed properly. Finally, the validity of the proposed algorithm is confirmed by computer simulations on artificially synthesized data.
Unsupervised Spike Detection and Sorting with Wavelets and Superparamagnetic Clustering
Authors: Quiroga R. Quian , Nadasdy Z. , Ben-Shaul Y.
Published: June 2004

This study introduces a new method for detecting and sorting spikes from multiunit recordings. The method combines the wave let transform, which localizes distinctive spike features, with super paramagnetic clustering, which allows automatic classification of the data without assumptions such as low variance or gaussian distributions. Moreover, an improved method for setting amplitude thresholds for spike detection is proposed. We describe several criteria for implementation that render the algorithm unsupervised and fast. The algorithm is compared to other conventional methods using several simulated data sets whose characteristics closely resemble those of in vivo recordings. For these data sets, we found that the proposed algorithm outperformed conventional methods.
An Asymptotic Statistical Theory of Polynomial Kernel Methods
Authors: Ikeda Kazushi
Published: June 2004

The generalization properties of learning classifiers with a polynomial kernel function are examined. In kernel methods, input vectors are mapped into a high-dimensional feature space where the mapped vectors are linearly separated. It is well-known that a linear dichotomy has an average generalization error or a learning curve proportional to the dimension of the input space and inversely proportional to the number of given examples in the asymptotic limit. However, it does not hold in the case of kernel methods since the feature vectors lie on a submanifold in the feature space, called the input surface. In this letter, we discuss how the asymptotic average generalization error depends on the relationship between the input surface and the true separating hyperplane in the feature space where the essential dimension of the true separating polynomial, named the class, is important. We show its upper bounds in several cases and confirm these using computer simulations.
A Neural Root Finder of Polynomials Based on Root Moments
Authors: Huang De-Shuang , Ip Horace H.S. , Chi Zheru
Published: June 2004

This letter proposes a novel neural root finder based on the root moment method (RMM) to find the arbitrary roots (including complex ones) of arbitrary polynomials. This neural root finder (NRF) was designed based on feedforward neural networks (FNN) and trained with a constrained learning algorithm (CLA). Specifically, we have incorporated the a priori information about the root moments of polynomials into the conventional backpropagation algorithm (BPA), to construct a new CLA. The resulting NRF is shown to be able to rapidly estimate the distributions of roots of polynomials. We study and compare the advantage of the RMM-based NRF over the previous root coefficient method—based NRF and the traditional Muller and Laguerre methods as well as the mathematica roots function, and the behaviors, the accuracies of the resulting root finders, and their training speeds of two specific structures corresponding to this FNN root finder: the log σand the σ FNN. We also analyze the effects of the three controlling parameters {δP0 θp η} with the CLA on the two NRFs theoretically and experimentally. Finally, we present computer simulation results to support our claims.
Effect of coating on oxidation of impure (C,Mn) iron at 700°c: Yttrium–impurity interactions
Authors: Buscail H. , Josse-Courty C. , Jacob Y.P. , Le Coze J.
Published: June 2004

A study of the interactions between carbon and manganese impurities and yttrium has been performed during the oxidation of iron base specimens under an oxygen partial pressure of 0·04 Pa and at a temperature of 700°C. It was found that yttrium coated specimens always exhibit better oxidation behaviour than uncoated specimens. For a manganese containing alloy (Fe–0·2Mn), the protective effect of yttrium is attributed to the formation of a YMnO3 subscale at the oxide-metal interface. On Fe and Fe–0·054C substrates the beneficial effect is attributed to the formation of Fe2 YO4 (which is more protective than YMnO3). The best improvement is obtained with coated Fe–0·18Mn–0·041C alloys as a result of the formation of a YMnO3 subscale at the scale-alloy interface, and because the yttrium coating hinders carbon segregation at the oxide-alloy interface, thus producing better scale adhesion.
Development of Mox Ruy Sez (CO)n electrocatalysts by screen printing and sintering for fuel cell applications
Authors: Sebastian P.J. , Rodríguez F.J.
Published: June 2004

Electrocatalysts based on molybdenum, ruthenium, and selenium were prepared by screen printing Ru3 (CO)12 + Se and Ru3 (CO)12 + Mo(CO)6 + Se mixtures and subsequent sintering at 250°C in air or Se atmosphere in a tubular furnace. The catalysts were characterised using techniques such as XRD, SEM, TEM, voltammetry, and polarisation (current–potential) measurements. The results indicate that screen printed Rux Sey (CO)n and Mox Ruy Sez (CO)n are near amorphous in nature and possess appreciable catalytic activity for the oxygen reduction reaction in a polymer electrolyte (Nafion membrane) fuel cell. The electrocatalytic activity seems to diminish with selenium incorporation in the lattice of the carbonyl clusters formed during synthesis.
Electrodeposited Cu2O thin films for solar conversion
Authors: Sebastian P.J. , Quintana J. , Avila F. , Mathew X.
Published: June 2004

Thin films of Cu2O were electrodeposited and characterised by techniques including XRD, SEM–EPMA, and spectrophotometry. The structure, morphology, composition, and optical properties of the films depend on the electrochemical bath and deposition parameters. The kind of substrate pretreatment process also seems to have an effect on film properties. The electrodeposited Cu2O films may be used for photovoltaic, photothermal, and oxygen sensor applications.