bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemostatic Factors as Predictors of Coronary Events and Total Mortality
Authors: Salomaa Veikko , Rasi Vesa , Kulathinal Sangita , Vahtera Elina , Jauhiainen Matti , Ehnholm Christian , Pekkanen Juha
Published: July 2002

The role of hemostatic factors as predictors of coronary heart disease (CHD) and total mortality is poorly understood. Therefore, we carried out a prospective cohort study in Finland. In 1992, a random population sample of 2378 men and women aged 45 to 64 years was investigated and then followed up until December 31, 1998. During the follow-up, 133 CHD events were observed; 73 were among participants free of CHD at baseline. The total number of deaths was 124. After adjustment for traditional risk factors and prevalent CHD at baseline and correction for regression dilution bias, a 1-SD increase in plasminogen was associated with a 1.41-fold (95% CI 1.09 to 1.81) increase in CHD risk. The predictive power of plasminogen depended significantly on the level of total cholesterol being stronger for persons with high cholesterol. A 1-SD increase in fibrinogen was associated with a 1.23-fold (95% CI 1.05 to 1.44) increase in all-cause mortality, but its association with CHD events did not reach statistical significance. Factor VII antigen or coagulant activity or lipoprotein(a) were not independent predictors of CHD risk. These findings support the role of plasminogen as a risk factor for CHD events.
Cellular Antioxidant Effects of Atorvastatin In Vitro and In Vivo
Authors: Wassmann Sven , Laufs Ulrich , Müller Kirsten , Konkol Christian , Ahlbory Katja , Bäumer Anselm T. , Linz Wolfgang , Böhm Michael , Nickenig Georg
Published: July 2002

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may exert direct effects on vascular cells and beneficially influence endothelial dysfunction. Because reactive oxygen species (ROS) may lead to vascular damage and dysfunction, we investigated the effect of atorvastatin on ROS production and the underlying mechanisms in vitro and in vivo. Cultured rat aortic vascular smooth muscle cells were incubated with 10 μmol/L atorvastatin. Angiotensin II–induced and epidermal growth factor–induced ROS production were significantly reduced by atorvastatin (dichlorofluorescein fluorescence laser microscopy). Atorvastatin downregulated mRNA expression of the NAD(P)H oxidase subunit nox1, whereas p22phox mRNA expression was not significantly altered (reverse transcription–polymerase chain reaction, Northern analysis). Membrane translocation of rac1 GTPase, which is required for the activation of NAD(P)H oxidase, was inhibited by atorvastatin (Western blot). mRNA expression of superoxide dismutase isoforms and glutathione peroxidase was not modified by atorvastatin, whereas catalase expression was upregulated at mRNA and protein levels, resulting in an increased enzymatic activity. Effects of atorvastatin on ROS production and nox1, rac1, and catalase expression were inhibited by
l
-mevalonate but not by 25-hydroxycholesterol. In addition, spontaneously hypertensive rats were treated with atorvastatin for 30 days. ROS production in aortic segments was significantly reduced in statin-treated rats (lucigenin chemiluminescence). Treatment with atorvastatin reduced vascular mRNA expression of p22phox and nox1 and increased aortic catalase expression. mRNA expression of superoxide dismutases, glutathione peroxidase, and NAD(P)H oxidase subunits gp91phox, p40phox, p47phox, and p67phox remained unchanged. Translocation of rac1 from the cytosol to the cell membrane was also reduced in vivo. Thus, atorvastatin exerts cellular antioxidant effects in cultured rat vascular smooth muscle cells and in the vasculature of spontaneously hypertensive rats mediated by decreased expression of essential NAD(P)H oxidase subunits and by upregulation of catalase expression. These effects of atorvastatin may contribute to the vasoprotective effects of statins.
Increased Carotid Artery Intima-Media Thickness in Subjects With Primary Hypoalphalipoproteinemia
Authors: Baldassarre Damiano , Amato Mauro , Pustina Linda , Tremoli Elena , Sirtori Cesare R. , Calabresi Laura , Franceschini Guido
Published: July 2002

The plasma concentration of high-density lipoprotein cholesterol (HDL-C) is inversely correlated with the incidence of atherosclerotic vascular events. In the present study, we evaluated pre-intrusive atherosclerosis in subjects with plasma HDL-C at the extremities of normal distribution. Fifty-five subjects with primary hypoalphalipoproteinemia (HypoALP) or hyperalphalipoproteinemia (HyperALP) were compared with fifty-five control subjects with average HDL-C levels, matched for sex, age, and plasma cholesterol. The average and maximal intima-media thicknesses (Avg-IMT and Max-IMT) of 48 carotid segments for each subject were approximately 40% greater in HypoALP than in control subjects (0.94±0.06 versus 0.69±0.04 mm,
P
=0.004, and 1.86±0.16 versus 1.35±0.10 mm,
P
=0.025, respectively). The IMT values in HyperALP subjects (Avg-IMT, 0.71±0.04 and Max-IMT, 1.38±0.14 mm) were the same as in controls. In a large cohort of hyperlipidemic subjects (n=559), significantly greater Avg-IMT and Max-IMT were found in subjects belonging to the first HDL-C quintile (<42 mg/dL) than in all the others. The measurement of carotid IMT in cases with HypoALP and HyperALP, and in a large series of hyperlipidemic patients, thus indicates that a low HDL-C is associated with significant pre-intrusive atherosclerosis, whereas a HDL-C level above average values does not lead to a further reduction of arterial wall thickening.
Autoimmunity to Human Heat Shock Protein 60,
Chlamydia pneumoniae
Infection, and Inflammation in Predicting Coronary Risk
Authors: Huittinen Tiina , Leinonen Maija , Tenkanen Leena , Mänttäri Matti , Virkkunen Hanna , Pitkänen Taina , Wahlström Eva , Palosuo Timo , Manninen Vesa , Saikku Pekka
Published: July 2002

Abstract—

Heat shock protein 60 (Hsp60) and
Chlamydia pneumoniae
infection have both been associated with cardiovascular diseases. Our aim was to study the role of Hsp60 antibodies as coronary risk predictors and their association with
C pneumoniae
infection and inflammation. This was a prospective, nested, case-control study. The cases consisted of 239 middle-aged Finnish men who developed myocardial infarction or coronary death during the follow-up. Baseline levels of IgA and IgG antibodies to human-specific and
C pneumoniae
-specific Hsp60 were measured by enzyme immunoassay. Human Hsp60 IgA, but not IgG or
C pneumoniae
Hsp60, antibodies were a significant risk factor for coronary events (odds ratio 2.0, 95% CI 1.1 to 3.6, when the fourth and first quartiles are compared). When an elevated human Hsp60 IgA antibody level (above the second quartile) was present simultaneously with a high
C pneumoniae
IgA antibody level (the third quartile) and an elevated C-reactive protein level (the second quartile), compared with all factors at low levels, the risk was 7.0 (95% CI 2.6 to 19.1) without adjustment and 5.0 (95% CI 1.8 to 14.2) when adjustment was made for age and smoking. In conclusion, an elevated human Hsp60 IgA antibody level was a risk factor for coronary events, especially when it was present together with
C pneumoniae
infection and inflammation.
Insulin Inhibits Apoptosis of Macrophage Cell Line, THP-1 Cells, via Phosphatidylinositol-3-Kinase–Dependent Pathway
Authors: Iida Kaoruko Tada , Suzuki Hiroaki , Sone Hirohito , Shimano Hitoshi , Toyoshima Hideo , Yatoh Shigeru , Asano Tomoichiro , Okuda Yukichi , Yamada Nobuhiro
Published: July 2002

Abstract—

Hyperinsulinemia has recently been reported as a risk factor for atherosclerotic diseases such as coronary heart disease; however, its precise mechanism is not well understood. To elucidate the role of insulin in the development of atherogenesis, we have investigated the effect of insulin on cell survival in macrophages, which are known to be important in the atherosclerotic process. Apoptosis was induced in macrophage cell lines derived from human monocytes or murine macrophages by serum starvation. Insulin administration retarded macrophage apoptosis by means of DNA laddering, dimethylthiazol diphenyltetrazolium bromide assay, and annexin V binding assay. Insulin also enhanced mRNA expression and protein production of the antiapoptotic Bcl-XL gene in a dose-dependent manner within the range of physiological concentrations. In the exploration of the signaling pathway involved in these antiapoptotic effects of insulin, pretreatment of cells with a specific inhibitor of phosphatidylinositol-3-kinase significantly suppressed insulin-mediated cell survival and insulin-induced Bcl-XL expression in macrophages. These data indicate that the survival effect of insulin on the apoptosis of macrophages is associated with the upregulation of Bcl-XL expression, and it may be mediated through the phosphatidylinositol-3-kinase signaling pathway. These mechanisms could be involved in the possible role of insulin in the development of atherosclerosis.
Both Apolipoprotein E and Immune Deficiency Exacerbate Neointimal Hyperplasia After Vascular Injury in Mice
Authors: Zhu Binghua , Reardon Catherine A. , Getz Godfrey S. , Hui David Y.
Published: July 2002

In this study, we investigated the role of T and B lymphocytes in neointimal hyperplasia after endothelial denudation. Catheter-induced endothelial denudation of wild-type mice resulted in rapid infiltration of lymphocytes to the site of injury. Mice defective in recombination-activating gene 2 (
RAG2
−/−
) showed increased neointimal formation 14 days after vascular injury in comparison to their wild-type immune-competent littermates. Immunohistochemical studies revealed the preponderance of smooth muscle cells and a significantly higher number of proliferating cells in the neointima of the
RAG2
−/−
mice. The neointima size and the number of proliferating smooth muscle cells in the injured vessel of
RAG2
−/−
mice were similar to those observed in the injured arteries of apolipoprotein E (apoE)-deficient (
apoE
−/−
) mice. Interestingly, mice with double
apoE
and
RAG2
gene mutations (
apoE
−/−
RAG2
−/−
) displayed similar neointimal characteristics as mice with a single gene defect, suggesting a similar mechanism for apoE and lymphocyte protection against injury-induced neointimal formation. The protective role of lymphocytes against neointimal formation after vascular injury directly contrasts to their reported role in the promotion of atherosclerosis, which was observed in both
apoE
+/+
and
apoE
−/−
mice. Thus, these results support the hypothesis of different etiology between hyperlipidemia-induced atherosclerosis and injury-induced vascular occlusion.
Hemodynamic and Metabolic Changes in Transient Ischemic Attack Patients
Authors: Bisschops Robertus H.C. , Kappelle L.J. , Mali Willem P.T.M. , van der Grond Jeroen
Published: July 2002

Background and Purpose

—

We investigated whether patients with transient ischemic attack (TIA) have systemic low flow to the brain or an abnormal intracranial flow distribution caused by an abnormal anatomy of the circle of Willis. Furthermore, we investigated whether metabolic changes were present in the brain.

Methods

—

Forty-four patients with clinically diagnosed TIA were prospectively included in our study. Clinical and neurological data were compiled. MR imaging; quantitative flow measurements of the internal carotid, middle cerebral, and basilar arteries; MR angiography of the circle of Willis; and
1
H-MR spectroscopy were performed in all patients within 3 days of onset of symptoms.

Results

—

Compared with control subjects, TIA patients did not have altered flow volume in any of the arteries and had normal flow distribution through the circle of Willis. In TIA patients, the
N
-acetylaspartate (NAA)/choline ratio in noninfarcted regions was significantly decreased in the symptomatic hemisphere (1.73±0.16) compared with the asymptomatic hemisphere (1.84±0.19,
P
<0.05) and control subjects (1.90±0.17,
P
<0.001). In the symptomatic hemisphere, the lactate/NAA ratio was significantly increased (0.04±0.08) compared with control subjects (0.00±0.01,
P
<0.05). Patients with a history of prior TIA had a significantly decreased NAA/choline ratio in both the symptomatic (
P
<0.05) and asymptomatic (
P
<0.05) hemispheres compared with TIA patients without a prior TIA.

Conclusions

—

TIA patients have neurological deficits that are transient; however, metabolic damage to the brain is present up to 3 days after the onset of the symptoms. These metabolic changes are not restricted to the symptomatic hemisphere or to areas close to ischemic lesions.
Transesophageal Echocardiography for Quantifying Size of Patent Foramen Ovale in Patients With Cryptogenic Cerebrovascular Events
Authors: Schuchlenz Herwig W. , Weihs Wolfgang , Beitzke Albrecht , Stein Jörg-Ingolf , Gamillscheg Andreas , Rehak Peter
Published: July 2002

Background and Purpose

—

Patent foramen ovale (PFO) is a risk factor for paradoxical embolism, and severe shunting and wide opening of PFO are risk factors for severe and recurrent cerebrovascular events. Neither contrast echocardiography nor 2-dimensional (2D) measurement of PFO size have been validated or compared with invasive balloon sizing.

Methods

—

We performed transesophageal echocardiography (TEE) in 100 patients with cryptogenic stroke and catheter closure of PFO. The amount of contrast shunting through the PFO during cubital and femoral contrast delivery and the PFO size measured by 2D TEE were compared with balloon sizing.

Results

—

There was a significant correlation (
r
2
=0.8;
P
<0.0001) between 2D TEE measurement and invasive balloon sizing. Mean balloon-sized PFO diameter was significantly larger than mean PFO diameter measured by 2D TEE (8.3±2.6 versus 5.2±1.7 mm). Semiquantitative contrast TEE correlated with PFO size (
r
2
=0.7;
P
<0.0001) only if the contrast agent was administered through a femoral vein. Correlation was poor when the contrast agent was administered via a cubital vein.

Conclusions

—

We conclude that 2D TEE measurement of a PFO size is more accurate than the traditionally used contrast technique.
Activation-Induced Resetting of Cerebral Metabolism and Flow Is Abolished by β-Adrenergic Blockade With Propranolol
Authors: Schmalbruch Ina K. , Linde Rasmus , Paulson Olaf B. , Madsen Peter L.
Published: July 2002

Background and Purpose

—

It has previously been shown that activation will increase cerebral blood flow (CBF) and cerebral glucose uptake (CMR
glc
) in excess of cerebral oxygen uptake (CMRO
2
). Our purpose was to investigate the influence of β-adrenergic blockade with propranolol on the activation-induced uncoupling of cerebral glucose and oxygen metabolism.

Methods

—

Using awake rats, we determined the cerebral arteriovenous differences of oxygen [(a−v)
O2
], glucose [(a−v)
glc
], and lactate [(a−v)
lac
] both under baseline conditions and during activation. The molar ratio between CMRO
2
and CMR
glc
, the oxygen-glucose index (OGI), was calculated.

Results

—

Without β-adrenergic blockade, activation decreased the (a−v)
O2
but not the (a−v)
glc
, reducing the OGI from 6.1 during baseline conditions to 4.0 under activation (
P
<0.01). The (a−v)
O2
decreased, indicating that the ratio CBF/CMRO
2
had increased. Under baseline conditions, a slight flux of lactate from the brain was observed. Activation increased the arterial lactate concentration, and during this condition, the lactate flux from the brain was reversed into a slight lactate uptake. Propranolol administration did not change the behavior of the animals during activation. After administration of propranolol, baseline values were unaffected, but β-adrenergic blockade totally abolished the activation-induced uncoupling of (a−v)
O2
from (a−v)
glc
, because both remained constant with an unchanged OGI. The unchanged (a−v)
O2
indicates that CBF remained unchanged compared with CMRO
2
.

Conclusions

—

β-Adrenergic blockade by propranolol abolishes the activation-induced uncoupling of cerebral oxygen to glucose metabolism and the changes in (a−v)
O2
. This may be of most significance to studies of cerebral activation by the blood oxygen level–dependent fMRI method.
Clomethiazole Acute Stroke Study in Ischemic Stroke (CLASS-I)
Authors: Lyden P. , Shuaib A. , Ng K. , Levin K. , Atkinson R.P. , Rajput A. , Wechsler L. , Ashwood T. , Claesson L. , Odergren T. , Salazar-Grueso E.
Published: July 2002

Background and Purpose

—

A previous trial (the Clomethiazole Acute Stroke Study) generated the hypothesis that clomethiazole is effective in patients with a major ischemic stroke (total anterior circulation syndrome), and this was tested in the present study.

Methods

—

A total of 1198 patients with major ischemic stroke and a combination of limb weakness, higher cortical dysfunction, and visual field deficits were randomly assigned to clomethiazole (68 mg/kg IV over 24 hours) or placebo. The study drug was initiated within 12 hours of symptom onset. Functional outcome and neurological recovery were assessed at days 7, 30, and 90, with the proportion of patients with a Barthel Index ≥60 at last follow-up as the primary outcome measure.

Results

—

The patients were randomly assigned equally, and the two treatment groups were well matched for baseline characteristics, including stroke severity (mean National Institutes of Health Stroke Scale score 16.9±5.2). Ninety-six percent were classified as total anterior circulation syndrome. The proportion of patients reaching a Barthel Index score of ≥60 was 42% in the clomethiazole-treated group and 46% in the placebo-treated group (odds ratio, 0.81; 95% CI, 0.62 to 1.05;
P
=0.11). There was no evidence of efficacy on any secondary outcome variables (modified Rankin Score, National Institutes of Health Stroke Scale, Scandinavian Stroke Scale, and 30-day CT infarct volumes) compared with placebo. Subgroup analysis showed a similar lack of treatment effect in patients treated early (<6 hours) and in those treated later (6 to 12 hours). Somnolence was an expected pharmacological effect of clomethiazole, and this occurred during treatment as an adverse event in half of the patients randomly assigned to study drug.

Conclusions

—

The target population was selected, and sufficient drug was given to produce the expected pharmacological effect in the brain. Clomethiazole does not improve outcome in patients with major ischemic stroke.
Severity of Angina Pectoris and Risk of Ischemic Stroke
Authors: Tanne David , Shotan Avraham , Goldbourt Uri , Haim Moti , Boyko Valentina , Adler Yehuda , Mandelzweig Lori , Behar Solomon
Published: July 2002

Background and Purpose

—

Ischemic stroke and coronary heart disease (CHD) share risk factors and pathogenic process, ie, atherosclerosis and thrombosis. We examined the relationship between severity of angina pectoris and its accompanying characteristics and the risk of incident ischemic stroke.

Methods

—

We traced 3122 patients with stable CHD, included in a secondary prevention trial of lipid modification, the Bezafibrate Infarction Prevention trial. CHD was documented by a history of myocardial infarction ≥6 months and <5 years before enrollment and/or stable angina pectoris with evidence of ischemia confirmed by ancillary diagnostic testing. Severity of angina pectoris was assessed according to the Canadian Cardiovascular Society angina classification, and heart failure functional class according to the New York Heart Association (NYHA) classification. Patients with severe heart failure or unstable angina on enrollment were excluded.

Results

—

During a mean follow-up period of 8.2 years, 186 patients developed an ischemic stroke. The cumulative rate of ischemic stroke increased in a dose-response manner from 4.7% in patients with no angina to 5.7%, 8.4%, and 12.9% in patients with angina classes 1, 2, and 3, respectively (
P
<0.001). Patients with NYHA functional class 1 had a 5.5% rate of ischemic stroke versus 7.3% and 9.6% in patients with classes 2 and 3, respectively (
P
=0.05). In a Cox proportional-hazard model adjusting for conventional risk factors and potential confounders, the hazard ratio associated with angina class 1 was 1.20 (95% CI, 0.83 to 1.74); class 2, 1.66 (95% CI, 1.12 to 2.45); and class 3, 2.35 (95% CI, 1.08 to 5.13), as compared with patients with no angina. Hazard ratios of ischemic stroke associated with conventional risk factors were 1.55 for a 10-year age increment, 2.16 for diabetes mellitus, 1.81 for current smoking, and 1.29 for a 20 mm Hg increase in systolic blood pressure.

Conclusions

—

Severity of angina pectoris in patients with stable CHD predicts an increased risk of subsequent ischemic stroke. The association between angina class and incident ischemic stroke is independent of traditional vascular risk factors.
Ethnic Differences in Patient Perceptions of Atrial Fibrillation and Anticoagulation Therapy
Authors: Lip Gregory Y.H. , Kamath Sridhar , Jafri Marian , Mohammed Afzal , Bareford David
Published: July 2002

Background and Purpose

—

We hypothesized that different ethnic groups would have different levels of knowledge and perceptions of atrial fibrillation (AF) and of their antithrombotic therapy. To investigate this further, we conducted a cross-sectional survey of patients with documented chronic AF who were attending the anticoagulation clinic in our city center teaching hospital, serving a multiethnic population.

Methods

—

We surveyed 119 patients (77 male; mean age 69±9 years [mean±SD]); of these, 39 were Indo-Asian (33%), 27 Afro-Caribbean (23%), and 53 white (44%).

Results

—

Only 63% of patients in the overall study cohort were aware of their cardiac condition, with Indo-Asians and Afro-Caribbeans significantly less aware of AF compared with the white patients (
P
<0.001). When questioned about the perception of the severity of the underlying condition, the majority (61%) felt that AF was “not serious.” A large proportion were unaware that AF predisposed to thrombosis and stroke; among the ethnic groups, Indo-Asians appeared to be the least aware of the stroke and thromboembolic associations of AF. Only 52% in the whole cohort were aware of the reason(s) for commencing their warfarin, whereas the remainder began warfarin therapy simply because their “doctor told them to.” Most patients in the whole cohort were aware of warfarin being used to prevent blood clots (65%) or stroke (66%), but Indo-Asians and Afro-Caribbeans were less so. Only 45% of the study cohort believed that there was some risk associated with warfarin therapy in the form of either “bleeding” or “poisoning.” Only a minority of Indo-Asians and Afro-Caribbeans with AF felt that their doctor had given them enough information about their warfarin therapy, and many from these ethnic groups felt that they were careless about taking their warfarin.

Conclusions

—

In conclusion, many patients with AF possess very limited knowledge of AF as well as its consequences and therapy. In particular, our study has highlighted significant differences between different ethnic groups in terms of their knowledge of the risks, actions, and benefits of warfarin as well as of AF itself.
Magnetic Resonance Perfusion-Weighted Imaging of Acute Cerebral Infarction
Authors: Yamada Kei , Wu Ona , Gonzalez R. Gilberto , Bakker Dirk , Østergaard Leif , Copen William A. , Weisskoff Robert M. , Rosen Bruce R. , Yagi Katsumi , Nishimura Tsunehiko , Sorensen A. Gregory
Published: July 2002

Background and Purpose

—

Various calculation methods are available to estimate the transit-time on MR perfusion-weighted imaging (PWI). Each method may affect the results of PWI. Steno-occlusive disease in the parent vessels is another factor that may affect the results of the PWI. The purpose of this study was to elucidate the effect of the calculation methods and underlying vasculopathy on PWI.

Methods

—

From a pool of 113 patients who had undergone PWI during the study period, a total of 12 patients with nonlacunar ischemic strokes who were scanned within 24 hours after onset of symptom were selected for the study. The patient population consisted of 6 patients who had extracranial internal carotid artery stenosis (>70%) and 6 individuals without stenosis. Seven different postprocessing methods were evaluated: first moment, ratio of area to peak, time to peak (TTP), relative TTP, arrival time, full-width at half-maximum, and deconvolution methods. Follow-up MR or CT images were used to determine the areas that evolved into infarcts, which served as the gold standard. Sensitivity and specificity of each transit time technique were calculated.

Results

—

Calculation methods with high sensitivity were the first moment (sensitivity, 74%), TTP (sensitivity, 77%), and deconvolution methods (sensitivity, 81% to 94%). Between the 2 groups with and without internal carotid artery stenosis, the specificity of most of the techniques was lower in the internal carotid artery stenosis group. The first moment and deconvolution methods maintained relatively high specificity even in the stenosis group.

Conclusions

—

The calculation technique and presence of underlying vasculopathy have a direct impact on the results of PWI. The methods with high sensitivity even in the presence of steno-occlusive disease were the first moment and deconvolution methods with arterial input function derived from the peri-infarct arteries; the deconvolution method was the superior choice because of higher lesion conspicuity.
Acute Intravenous–Intra-Arterial Revascularization Therapy for Severe Ischemic Stroke
Authors: Hill Michael D. , Barber Philip A. , Demchuk Andrew M. , Newcommon Nancy J. , Cole-Haskayne Andrea , Ryckborst Karla , Sopher Laurel , Button Allison , Hu William , Hudon Mark E. , Morrish William , Frayne Richard , Sevick Robert J. , Buchan Alastair M.
Published: July 2002

Background

—

Intravenous alteplase for acute ischemic stroke is least efficacious for patients with proximal large-artery occlusions and clinically severe strokes. Intra-arterial therapy has the theoretical advantage of establishing a neurovascular diagnosis and high symptomatic artery patency rate but the disadvantage of requiring extra time and technical expertise. A combination of these two approaches may provide the best chance of improving outcome in severe acute ischemic stroke. We sought to assess the safety and feasibility of this approach.

Methods

—

This was a prospective, open-label study. Sequential patients arriving to our center within 3 hours of stroke onset who were treated with intravenous alteplase were screened for possible additional intra-arterial therapy using noninvasive neuroimaging. Clinical measures and outcomes were recorded prospectively.

Results

—

A total of 861 patients with ischemic stroke were admitted to Calgary hospitals during the study period. Eight patients over 21 months underwent a combined intravenous–intra-arterial approach. Six received intra-arterial alteplase and 1 underwent intracranial angioplasty; in a final patient, technical aspects prevented intra-arterial therapy. Early neurovascular and/or neurometabolic imaging identified the location of occlusion and tissue-at-risk (DWI-PWI mismatch) in all 8 patients. Two patients had a poor outcome, 1 patient suffered a significant groin hematoma, and there were no instances of symptomatic intracerebral hemorrhage.

Conclusions

—

Intravenous followed by intra-arterial therapy is a promising approach to the treatment of severe acute ischemic stroke. Early noninvasive neurovascular and neurometabolic imaging is very helpful in choosing candidates for this type of therapy. On-going monitoring of alteplase-treated patients may allow the opportunity to perform rescue intra-arterial therapy.
Improving Delivery of Acute Stroke Therapy
Authors: Morgenstern Lewis B. , Staub Lara , Chan Wenyaw , Wein Theodore H. , Bartholomew L. Kay , King Mary , Felberg Robert A. , Burgin W. Scott , Groff Janet , Hickenbottom Susan L. , Saldin Kamaldeen , Demchuk Andrew M. , Kalra Anjali , Dhingra Anupma , Grotta James C.
Published: July 2002

Background and Purpose

—

Only a small minority of acute stroke patients receive approved acute stroke therapy. We performed a community and professional behavioral intervention project to increase the proportion of stroke patients treated with approved acute stroke therapy.

Methods

—

This study used a quasi-experimental design. Intervention and comparison communities were compared at baseline and during educational intervention. The communities were based in 5 nonurban East Texas counties. The multilevel intervention worked with hospitals and community physicians while changing the stroke identification skills, outcome expectations, and social norms of community residents. The primary goal was to increase the proportion of patients treated with intravenous recombinant tissue plasminogen activator (rTPA) from 1% to 6% of all cerebrovascular events in the intervention community.

Results

—

We prospectively evaluated 1733 patients and validated 1189 cerebrovascular events. Intravenous rTPA treatment increased from 1.38% to 5.75% among all cerebrovascular event patients in the intervention community (
P
=0.01) compared with a change from 0.49% to 0.55% in the comparison community (
P
=1.00). Among the ischemic stroke patients, an increase from 2.21% to 8.65% was noted in the intervention community (
P
=0.02). The comparison group did not appreciably change (0.71% to 0.86%,
P
=1.00). Of eligible intravenous rTPA candidates, treatment increased in the intervention community from 14% to 52% (
P
=0.003) and was unchanged in the comparison community (7% to 6%,
P
=1.00).

Conclusions

—

An aggressive, multilevel stroke educational intervention program can increase delivery of acute stroke therapy. This may have important public health implications for reducing disability on a national level.
The Concept of Patient Motivation
Authors: Maclean Niall , Pound Pandora , Wolfe Charles , Rudd Anthony
Published: July 2002

Background and Purpose

—

The purpose of this work was to investigate how stroke rehabilitation professionals understand the concept of motivation and the ways that they use this concept in their clinical practice.

Methods

—

This qualitative study used semistructured, in-depth interviews with the professionals working in the stroke unit of an inner-city teaching hospital in the UK.

Results

—

Motivation was a frequently used concept and was described as an important determinant of rehabilitation outcome. Motivation was attributed to patients on the basis of their demeanor (proactivity was equated with motivation, passivity with lack of motivation) and their compliance with rehabilitation (compliance was seen as indicative of motivation, noncompliance as a lack of motivation). These criteria were found to have blurred boundaries. The determinants of motivation were located partly in personality factors but also in social factors. Central among the social factors were aspects of the professionals’ own behavior taken to positively and negatively affect motivation. Some professionals reported treating unmotivated patients differently from motivated ones, especially if these unmotivated patients were elderly. Motivation was described as a potentially dangerous label.

Conclusions

—

Professionals are wary of the concept of motivation yet commonly use it in their clinical practice. The blurred boundaries of the criteria used to identify motivation mean that patients must strike a delicate balance between proactivity and compliance to avoid being categorized as unmotivated. The way the concept of motivation is used in clinical practice might have negative implications for patient care, eg, when reticent yet motivated patients are labeled unmotivated.
Higher Incidence of Falls in Long-Term Stroke Survivors Than in Population Controls
Authors: Jørgensen Lone , Engstad Torgeir , Jacobsen Bjarne K.
Published: July 2002

Background and Purpose

—

The incidence of falls among noninstitutionalized individuals with long-standing stroke has not been examined previously, although fractures are more common and the consequences more severe for stroke patients than for elderly people in general.

Methods

—

For 4 months (September to December 1998), we followed 111 home-living patients who had suffered a stroke a mean of 10 years previously and 143 control subjects randomly selected from the same municipality, matched with respect to age and sex. Falls were registered daily by use of “fall calendars.” Before the fall registration period, information about morbidity, use of medication, and activities of daily living had been registered. Height, weight, vision, blood pressure, motor function, and body sway had been measured, and depressive symptoms as well as cognitive function had been assessed.

Results

—

During follow-up, 23% of the patients and 11% of the control subjects fell once or more, and the risk of falling at least once was more than twice as high for the patients with stroke, when controlled for potential confounders (relative risk=2.2; 95% CI, 1.1 to 4.3). Among the stroke patients, depressive symptomatology predicted falls, and the relative risk for falling increased by 1.5 per standard deviation increase in the depression score.

Conclusions

—

We conclude that falls are more frequent among noninstitutionalized long-term stroke survivors than among community control subjects and that the risk of falling and depressive symptoms are related in stroke patients.
ATLANTIS Trial
Authors: Albers Gregory W. , Clark Wayne M. , Madden Kenneth P. , Hamilton Scott A.
Published: July 2002

Background and Purpose

—

Only a single study has demonstrated beneficial effects of intravenous tissue plasminogen activator (tPA) in stroke patients.

Methods

—

We evaluated the clinical outcomes of the 61 patients enrolled in the Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study who were randomized to receive intravenous tPA or placebo within 3 hours of symptom onset.

Results

—

Despite a significant increase in the rate of symptomatic intracranial hemorrhage, tPA-treated patients were more likely to have a very favorable outcome (score of ≤1) on the National Institutes of Health Stroke Scale at 90 days (
P
=0.01).

Conclusions

—

These data support current recommendations to administer intravenous tPA to eligible ischemic stroke patients who can be treated within 3 hours of symptom onset.
Postoperative Hyperthermia Is Associated With Cognitive Dysfunction After Coronary Artery Bypass Graft Surgery
Authors: Grocott Hilary P. , Mackensen G. Burkhard , Grigore Alina M. , Mathew Joseph , Reves J.G. , Phillips-Bute Barbara , Smith Peter K. , Newman Mark F. ,   the Neurologic Outcome Research Group (NORG),   Cardiothoracic Anesthesiology Research Endeavors (CARE) Investigators of the Duke Heart Center
Published: July 2002

Background and Purpose
—

Temperature is a well-known modulator of experimental cerebral injury. We hypothesized that hyperthermia would be associated with a worsened cognitive outcome after coronary artery bypass graft surgery (CABG).

Methods

—

Three hundred consenting patients undergoing cardiopulmonary bypass for CABG had hourly postoperative temperatures recorded. The degree of postoperative hyperthermia was determined by using the maximum temperature within the first 24 hours as well as by calculating the area under the curve for temperatures >37°C. Patients underwent a battery of cognitive testing both before surgery and 6 weeks after surgery. By use of factor analysis, 4 cognitive domains (scores) were identified, and the mean of the 4 scores was used to calculate the cognitive index (CI). Cognitive change was calculated as the 6-week CI minus the baseline CI. Multivariable linear regression (controlling for age, baseline cognitive function, and temperature during cardiopulmonary bypass) was used to compare postoperative hyperthermia with the postoperative cognitive change.

Results

—

The maximum temperature within the first 24 hours after CABG ranged from 37.2°C to 39.3°C. There was no relationship between area under the curve for temperatures >37°C and cognitive dysfunction (
P
=0.45). However, the maximum postoperative temperature was associated with a greater amount of cognitive dysfunction at 6 weeks (
P
=0.05).

Conclusions

—

This is the first report relating postoperative hyperthermia to cognitive dysfunction after cardiac surgery. Whether the hyperthermia caused the worsened outcome or whether processes that resulted in the worsened cognitive outcome also produced hyperthermia requires further investigation. In addition, interventions to avoid postoperative hyperthermia may be warranted to improve cerebral outcome after cardiac surgery.
Combined Clinical and Imaging Information as an Early Stroke Outcome Measure
Authors: Johnston Karen C. , Wagner Douglas P. , Haley E. Clarke , Connors Alfred F.
Published: July 2002

Background and Purpose

—

Imaging information has been proposed as a potential surrogate outcome in stroke clinical trials. The purpose of this study was to determine whether an early outcome measure combining clinical and imaging information is better than either alone in predicting 3-month outcome in acute ischemic stroke patients.

Methods

—

Clinical information (National Institutes of Health Stroke Scale) and imaging information (CT infarct volume), measured at 1 week from 201 patients from the Randomized Trial of Tirilazad Mesylate in Acute Stroke (RANTTAS) study, were used in a multivariable logistic regression analysis to predict excellent and devastating 3-month outcome. The combined models were compared with the infarct volume models and the clinical models. Discrimination, calibration, and change in global model chi-square were assessed.

Results

—

The combined models and models using clinical information alone had areas under the receiver operating characteristic curves that did not differ significantly (probability value = 0.092 to 0.4), ranging from 0.83 to 0.95. The imaging alone models performed less well (
P
<0.005) and had areas under the receiver operating characteristic curves that ranged from 0.70 to 0.80.

Conclusions

—

The National Institutes of Health Stroke Scale at 1 week is highly predictive of 3-month outcome in ischemic stroke patients. The addition of 1-week infarct volume does not improve the accuracy of the predictive model.
Phosphatidylinositol 3–Kinase Inhibitor Failed to Reduce Cerebral Vasospasm in Dog Model of Experimental Subarachnoid Hemorrhage
Authors: Kimura Hitoshi , Sasaki Kenroh , Meguro Toshinari , Zhang John H.
Published: July 2002

Background and Purpose

—

Phosphatidylinositol 3–kinase (PI3-kinase) is involved in smooth muscle contraction induced by growth factors and/or G protein–coupled receptor agonists. To evaluate the role of PI3-kinase in the pathogenesis of delayed vasospasm, we applied 2 PI3-kinase inhibitors to an established canine double-hemorrhage model of experimental subarachnoid hemorrhage.

Methods

—

Twenty-four dogs underwent double blood injections via the cisterna magna on days 0 and 2. The dogs were killed on day 7. Dogs were treated with either vehicle (dimethyl sulfoxide), wortmannin, or LY294002 once per day on day 2 through day 6. Angiography was performed before blood injection and before the dogs were killed. The basilar arteries were collected for morphology, Western blot analysis, and PI3-kinase activity.

Results

—

The residual diameter of the basilar arteries in the dimethyl sulfoxide treatment group, which was compared with day 0 angiogram, decreased markedly on day 7 (the percentage of the residual diameter was 47.8±0.8%). Wortmannin and LY294002 did not significantly change residual diameter on day 7. Both PI3-kinase inhibitors abolished PI3-kinase activity compared with the vehicle treatment group. However, both PI3-kinase inhibitors failed to significantly attenuate PI3-kinase protein expression (Western blot) (
P
>0.05, ANOVA).

Conclusions

—

Delayed treatment, which was to mimic the clinical situation, with PI3-kinase inhibitors failed to reverse vasospasm. PI3-kinase may not play an important role in the delayed vasospasm. The possible effect of PI3-kinase inhibitors in the early stage of vasospasm was not investigated in the present study.
Routine Duplex Surveillance Does Not Improve the Outcome After Carotid Endarterectomy
Authors: Post Piet N. , Kievit Job , van Baalen Jary M. , van den Hout Wilbert B. , van Bockel J. Hajo
Published: July 2002

Background
—

Doppler ultrasound (duplex) tests are commonly applied after carotid endarterectomy to detect possible recurrent stenosis. The appropriate frequency and the benefits are unknown. We investigated the costs and effects of various follow-up strategies to determine the optimal strategy after carotid endarterectomy.

Methods
—

Using decision-analytic methods, a Monte Carlo Markov model was constructed. Probabilities and costs were obtained by systematic literature review. From empirical data regarding restenosis, a disease model was constructed to test the effect of various follow-up strategies using duplex testing and angiography. Main outcome measures were quality-adjusted life-years (QALYs), probability of stroke, and costs (for both the Dutch and the American situation).

Results
—

The average quality-adjusted life expectancy for a 66-year-old patient was 6.31 years for the symptom-guided strategy (with duplex scanning only being performed in case of symptoms of cerebral ischemia). The mean lifetime costs for this strategy were $5 600 for the US and 4 600 Euro for the Netherlands. The cumulative probability of stroke was 13%. Yearly routine duplex tests up to 5 years after operation resulted in similar QALYs and a similar probability of stroke, but higher costs ($7 300 for the US and 5 600 Euro for The Netherlands situation). No other strategy, including routine duplex surveillance, increased QALYs. When MR instead of conventional angiography was used as confirmatory test, no improvement was observed either.

Conclusions
—

Routine duplex surveillance does not result in an increase in quality-adjusted life expectancy, but it does increase costs. After successful carotid endarterectomy, a symptom-guided follow-up is an appropriate approach.
Vascular Aphasias
Authors: Godefroy O. , Dubois C. , Debachy B. , Leclerc M. , Kreisler A.
Published: July 2002

Background and Purpose
—

Aphasia is frequent in stroke patients and is associated with poor prognosis. However, characteristics and determinants of vascular aphasias remain controversial. The aim of this study was to evaluate aphasia characteristics at the acute stage in patients admitted to a stroke unit.

Methods
—

The study was performed in 308 patients consecutively assessed with a standardized aphasia battery.

Results
—

Aphasia was observed in 207 patients; global and nonclassified aphasias accounted for 50% of aphasic syndromes at the acute stage, whereas classic aphasias (Wernicke’s, Broca’s, transcortical, and subcortical aphasias) were less frequent. Age differed across aphasic syndromes in ischemic stroke patients only; patients with conduction aphasia were younger, and patients with subcortical aphasia were older. Sex did not significantly differ across aphasic syndromes. The presence of a previous stroke was more frequent in nonclassified aphasia.

Conclusions
—

This study shows (1) that vascular aphasias are frequently severe or nonclassic at the acute stage, a finding explained in part by the presence of a previous stroke; (2) that the age effect is due mainly to its influence on infarct location; and (3) that the main determinant of aphasia characteristics is lesion location.
Manganese Superoxide Dismutase Deficiency Exacerbates Cerebral Infarction After Focal Cerebral Ischemia/Reperfusion in Mice
Authors: Kim Gyung W. , Kondo Takeo , Noshita Nobuo , Chan Pak H.
Published: July 2002

Background and Purpose

—

Superoxide anion radicals (O
2
·−
) are implicated in ischemia/reperfusion injury, although a direct relationship has not been elucidated. Recently, a specific method of hydroethidine (HEt) oxidation by O
2
·−
was developed to detect O
2
·−
production in a variety of experimental brain injury models. To clarify the role of O
2
·−
in the mechanism of ischemia/reperfusion, we investigated O
2
·−
production after ischemia/reperfusion and ischemia/reperfusion injury in mutant mice deficient in mitochondrial manganese superoxide dismutase (MnSOD) and in wild-type littermates.

Methods

—

Ischemia/reperfusion was performed for 60 minutes using intraluminal suture blockade of the middle cerebral artery in the mutant or wild-type mice. We evaluated fluorescent kinetics of HEt or ethidium, the oxidized form of HEt, in brains after an intravenous injection of HEt, followed by measurement of cellular O
2
·−
production using specific HEt oxidation by O
2
·−
before and after ischemia/reperfusion. Furthermore, we compared O
2
·−
production and subsequent infarct volume in the mice using triphenyltetrazolium chloride after ischemia/reperfusion.

Results

—

HEt oxidation to ethidium is primarily a result of mitochondrially produced O
2
·−
under physiological conditions. Cerebral ischemia/reperfusion produced O
2
·−
prominently in neurons shortly after reperfusion, followed by a delayed increase in endothelial cells. A deficiency in MnSOD in mutant mice increased mitochondrial O
2
·−
production and exacerbated cerebral infarction, worsening neurological deficits after ischemia/reperfusion.

Conclusion

—

These results suggest that mitochondrial O
2
·−
production may be a critical step underlying the mechanism of ischemia/reperfusion injury and that MnSOD may protect against ongoing oxidative cell death after ischemia/reperfusion.
Predictors of Hemorrhagic Transformation in Patients Receiving Intra-Arterial Thrombolysis
Authors: Kidwell Chelsea S. , Saver Jeffrey L. , Carneado Joaquin , Sayre James , Starkman Sidney , Duckwiler Gary , Gobin Y.Pierre , Jahan Reza , Vespa Paul , Villablanca J.Pablo , Liebeskind David S. , Vinuela Fernando
Published: July 2002

Background and Purpose
—

Hemorrhagic transformation (HT) is a major complication of intra-arterial (IA) thrombolytic therapy. Identifying significant predictors of hemorrhage after thrombolysis would be useful in guiding patient selection for IA treatment.

Methods
—

Data were collected retrospectively on consecutive patients with acute focal cerebral ischemia within the anterior or posterior circulation who were treated with combined intravenous (IV)-IA or pure IA thrombolysis over an 8-year period at the UCLA Medical Center.

Results
—

Eighty-nine patients were treated. Median baseline National Institutes of Health Stroke Scale (NIHSS) score was 16, and mean age was 69 years. Twenty-six patients received IA tissue plasminogen activator (tPA) only, 22 received IV-IA tPA, and 41 received IA urokinase only. Asymptomatic HT occurred in 29 patients (33%), minor symptomatic HT (1- to 3-point worsening in NIHSS score) occurred in 10 patients (11%), and major symptomatic HT (≥4-point worsening in NIHSS score) occurred in 6 patients (7%). The rate of any HT was similar in patients treated with pure IA thrombolysis (39%) versus combined IV-IA thrombolysis (41%). In pure IA cases, the rate of any HT was 50% with tPA versus 32% with urokinase (
P
=0.2). Eighty-six percent of the patients with HT versus 39% of the patients without HT were dead or disabled (modified Rankin score >2) at day 7 (
P
<0.0001). On multivariate analysis, independent predictors of any HT were higher NIHSS score, longer time to recanalization, lower platelet count, and higher glucose level. A model using these variables correctly predicted HT with positive predictive value 70% and overall accuracy 78%.

Conclusions
—

In this large series of IA thrombolysis, rates of HT were similar to those demonstrated in prior series and clinical trials. Higher NIHSS score, longer time to recanalization, lower platelet count, and higher glucose level were independent predictors of any HT.