bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol Consumption and Subclinical Findings on Magnetic Resonance Imaging of the Brain in Older Adults
Authors: Mukamal Kenneth J. , Longstreth Jr W.T. , Mittleman Murray A. , Crum Rosa M. , Siscovick David S.
Published: October 2007

Background and Purpose

—

Subclinical findings on MRI of the brain are associated with poorer cognitive and neurological function among older adults. We sought to determine how alcohol consumption is related to these findings.

Methods

—

As part of the Cardiovascular Health Study, 3660 adults aged 65 years and older underwent MRI of the brain from 1992 to 1994. We excluded 284 participants with a confirmed history of cerebrovascular disease. We assessed self-reported intake of beer, wine, and liquor at the annual clinic visit closest to the date of the MRI and grouped participants into 6 categories: abstainers, former drinkers, <1 drink weekly, 1 to <7 drinks weekly, 7 to <15 drinks weekly, and ≥15 drinks weekly. Neuroradiologists assessed white matter grade, infarcts, ventricular size, and sulcal size in a standardized and blinded manner. We used multivariate regression to control for sociodemographic and clinical characteristics.

Results

—

We found a U-shaped relationship between alcohol consumption and white matter abnormalities. Compared with abstainers, individuals consuming 1 to <7 drinks had an OR of 0.68, and those consuming ≥15 drinks weekly had an OR of 0.95 (p for quadratic term=0.01). Heavier alcohol consumption was associated with a lower prevalence of infarcts (OR for ≥15 drinks weekly relative to abstainers 0.59;
P
for trend=0.004), but larger ventricular size (OR for ≥15 drinks weekly relative to abstainers 1.32;
P
for trend=0.006) and sulcal size (OR for ≥15 drinks weekly relative to abstainers 1.53;
P
for trend=0.007).

Conclusions

—

Moderate alcohol consumption is associated with a lower prevalence of white matter abnormalities and infarcts, thought to be of vascular origin, but with a dose-dependent higher prevalence of brain atrophy on MRI among older adults. The extent to which these competing associations influence overall brain function will require further study.
Differences in Long-Term Outcome Between Patients Treated in Stroke Units and in General Wards
Authors: Glader Eva-Lotta , Stegmayr Birgitta , Johansson Lennarth , Hulter-Åsberg Kersin , Wester P.O.
Published: October 2007

Background and Purpose
—

The long-term beneficial effects of stroke unit care have been proved in several randomized trials. However, there is a question of large-scale applicability in routine clinical practice of interventions used by dedicated investigators in small randomized trials. The objective of this study was to compare, 21/2 years after stroke, patients who had been treated in stroke units and those treated in general wards in routine clinical practice.

Methods
—

This is a prospective cohort study based on 8194 patients who were included, during the first 6 months in 1997, in Riks-Stroke, the Swedish National Register for quality assessment of acute stroke. Two years after the event, 5189 patients were still alive and 5104 were followed up with a postal questionnaire to which 4038 responded.

Results
—

Among the group of patients who were independent in activities of daily living (ADL) functions before the stroke, patients who were treated in stroke units were less often dependent in ADL functions, after adjustment for case mix (OR, 0.79; CI, 0.66 to 0.94). If they also lived at home before the stroke, then they had a lower case-fatality rate 2 years after the stroke (OR, 0.81; CI, 0.72 to 0.92).

Conclusions
—

Long-term beneficial effects of treatment in stroke units were shown for patients who were independent in ADL functions before the stroke. No benefits were shown for patients who were dependent on help for primary ADL before the stroke. Further studies on this group of patients with more detailed outcome measures are needed.
Ebselen Protects Both Gray and White Matter in a Rodent Model of Focal Cerebral Ischemia
Authors: Imai H. , Masayasu H. , Dewar D. , Graham D.I. , Macrae I.M.
Published: October 2007

Background and Purpose

—

The neuroprotective efficacy of an intravenous formulation of the antioxidant ebselen has been comprehensively assessed with specific regard to conventional quantitative histopathology, subcortical axonal damage, neurological deficit, and principal mechanism of action.

Methods

—

Transient focal ischemia (2 hours of intraluminal thread-induced ischemia with 22 hours of reperfusion) was induced in the rat. Ebselen (1 mg/kg bolus plus 1 mg/kg per hour IV) or vehicle was administered at the start of reperfusion and continued to 24 hours. Neurological deficit was assessed 24 hours after ischemia. Gray matter damage was evaluated by quantitative histopathology. Axonal damage was determined with amyloid precursor protein immunohistochemistry used as a marker of disrupted axonal flow and Tau-1 immunohistochemistry to identify oligodendrocyte pathology. Oxidative damage was determined by 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 4-hydroxynonenal (4-HNE) immunohistochemistry.

Results

—

Ebselen significantly reduced the volume of gray matter damage in the cerebral hemisphere (by 53.6% compared with vehicle,
P
<0.02). Axonal damage was reduced by 46.8% (
P
<0.002) and the volume of oligodendrocyte pathology was reduced by 60.9% (
P
<0.005). The neurological deficit score was reduced by 40.7% (
P
<0.05) and the volume of tissue immunopositive for 8-OHdG and 4-HNE was reduced by 65% (
P
<0.002) and 66% (
P
<0.001), respectively, in ebselen-treated animals.

Conclusions

—

Delayed (2-hour) treatment with intravenous ebselen significantly reduced gray and white matter damage and neurological deficit associated with transient ischemia. The reduction in tissue displaying evidence of oxidative stress suggests that the major mechanism of action is attenuation of free radical damage.
Initial Experience of Platelet Glycoprotein IIb/IIIa Inhibition With Abciximab During Carotid Stenting
Authors: Kapadia Samir R. , Bajzer Christopher T. , Ziada Khaled M. , Bhatt Deepak L. , Wazni Oussama M. , Silver Mitchell J. , Beven Edwin G. , Ouriel Kenneth , Yadav Jay S.
Published: October 2007

Background and Purpose—

Abciximab has been shown to decrease periprocedural ischemic complications after coronary intervention. However, the adjunctive use of abciximab in carotid stenting has not been adequately studied. We sought to determine the efficacy and safety of abciximab in carotid stenting.

Methods—

Carotid stenting was performed in 151 consecutive patients determined to be at high surgical risk by a vascular surgeon. Of these, 128 consecutive patients received adjuvant therapy with abciximab (0.25 mg/kg bolus before the lesion was crossed with guidewire and 0.125 μg · kg
−1
· min
−1
infusion for 12 hours.). A heparin bolus of 50 U/kg was given, and activated clotting time was maintained between 250 to 300 seconds. All patients received aspirin and thienopyridine. Procedural and 30-day outcomes were compared between the control (n=23) and abciximab (n=128) groups.

Results—

The 2 groups had similar baseline characteristics. Procedural events were more frequent in the control group (8%; 1 major stroke and 1 neurological death) compared with the abciximab group (1.6%; 1 minor stroke and 1 retinal infarction;
P
=0.05). On 30-day follow-up, 1 patient presented with delayed intracranial hemorrhage in the abciximab group. There were no other major bleeding complications.

Conclusions—

Adjunctive use of abciximab for carotid stenting is safe with no increase in the risk of intracranial hemorrhage. This adjunctive therapy with potent glycoprotein IIb/IIIa inhibition may help to reduce periprocedural adverse events in patients undergoing carotid stenting.
Procedural Safety and Short-Term Outcome of Ambulatory Carotid Stenting
Authors: Al-Mubarak Nadim , Roubin Gary S. , Vitek Jiri J. , New Gishel , Iyer Sriram S.
Published: October 2007

Background and Purpose

—

Ambulatory procedures increase patient comfort and enhance cost-effectiveness. We sought to determine the feasibility and safety of ambulatory carotid stenting.

Methods

—

A selected group of patients was admitted and discharged the same day after the carotid stenting procedure. Immediate and short-term outcomes are reported.

Results

—

A total of 98 ambulatory carotid stenting procedures (98 hemispheres in 92 patients) were performed. There were 66 men (72%), and the mean age was 70±9 years. Of the patients, 28% had neurological symptoms related to the treated artery within 3 months before the procedure. Sixteen percent of the patients had prior carotid endarterectomy, 4% had prior ipsilateral neck radiation, and 8% had complete occlusion of the contralateral internal carotid artery. Successful access site hemostasis was ensured in all patients with suture-mediated vascular closure devices in 96 (98%) and manual compression in 2. Clinical follow-up was available for 96% of the patients at a mean time of 6±4 months. There were no neurological events, deaths, repeated procedures, or major access site complications.

Conclusions

—

Ambulatory carotid stenting is both safe and feasible. This approach will enhance the applicability of the procedure by increasing patient comfort and potentially reducing procedural costs.
Effects of Citicoline on Phospholipid and Glutathione Levels in Transient Cerebral Ischemia
Authors: Adibhatla Rao Muralikrishna , Hatcher J.F. , Dempsey R.J.
Published: October 2007

Background and Purpose

—

Cytidine-5′-diphosphocholine (citicoline or CDP-choline) is an essential intermediate in the biosynthesis of phosphatidylcholine, an important component of the neural cell membrane. Citicoline provided significant neuroprotection after transient forebrain ischemia in gerbils. This study was undertaken to examine changes and effects of citicoline on phospholipids and glutathione synthesis after transient cerebral ischemia and reperfusion.

Methods

—

Ten-minute transient forebrain ischemia was induced by bilateral carotid artery occlusion in male Mongolian gerbils with reperfusion up to 6 days. Citicoline (500 mg/kg IP in saline) was given to gerbils just after the end of ischemia, at 3-hour reperfusion, and daily thereafter until 1 day before euthanasia. Hippocampal lipids were extracted and analyzed by thin-layer and gas chromatography. Glutathione was measured by using an enzymatic recycling assay. Glutathione reductase activity was determined by measuring NADPH oxidation.

Results

—

Significant decreases in phospholipids occurred at 1-day reperfusion. Citicoline significantly restored the phosphatidylcholine, sphingomyelin, and cardiolipin levels but did not affect phosphatidylinositol and phosphatidylserine at 1 day. The phospholipids returned to sham levels over days 2 to 6 and were unaffected by citicoline. Ceramide levels significantly increased by 3 and 6 days of reperfusion and were unaltered by citicoline. Ischemia resulted in significant decreases in glutathione and glutathione reductase activity over 3 days of reperfusion. Citicoline significantly increased total glutathione and glutathione reductase activity and decreased the glutathione oxidation ratio, an indicator of glutathione redox status.

Conclusions

—

Our data indicated that the effects of citicoline on phospholipids occurred primarily during the first day of reperfusion, with effects on glutathione being important over the 3-day reperfusion period.
Contrast-Enhanced Magnetic Resonance Angiography of the Cervical Vessels
Authors: Phan Thanh , Huston John , Bernstein Matthew A. , Riederer Stephen J. , Brown Robert D.
Published: October 2007

Background and Purpose

—

Contrast-enhanced magnetic resonance angiography (CEMRA) permits acquisition of high-spatial-resolution, venous-suppressed, 3D MR angiograms of the cervical carotid and vertebral arteries. In this study, an elliptic centric-view ordering with either MR fluoroscopic triggering or test bolus timing was used. The use of CEMRA of the cervical vessels has changed our clinical practice and is replacing conventional angiography for the evaluation of most carotid and vertebral artery diseases.

Methods

—

We retrospectively reviewed our experience with the use of CEMRA performed in 422 patients from January through December 1999.

Results

—

CEMRA was performed to evaluate transient ischemic attack and ischemic stroke in 239 patients, asymptomatic carotid bruit in 88 patients, and other neurological symptoms in 95 patients. Carotid endarterectomies were performed in 97 patients (103 procedures), and conventional angiography was performed in 12 of these patients. CEMRA was used to evaluate for the presence of an arterial dissection in 85 of the 239 patients with transient ischemic attack and ischemic stroke. Of this group, 32 patients had cervical arterial dissection, and pseudoaneurysm was detected in 11 of these patients. Compared with ultrasonography of the cervical vessels, CEMRA provided additional information in 43 of 422 patients and led to changes in the decision as to whether to perform carotid endarterectomy in 5 patients.

Conclusions

—

Use of CEMRA permits noninvasive evaluation of patients suspected of having carotid or vertebral disease and avoids the potential complications of conventional angiography.
Decline in US Stroke Mortality
Authors: Howard George , Howard Virginia J. , Katholi Charles , Oli Madan K. , Huston Sara
Published: October 2007

Background and Purpose

—

Although stroke mortality rates have declined rapidly over the past 30 years, the decline has slowed to a plateau. Here, we assess whether the race-sex-region groups have participated equally in this decline and whether there are groups in which stroke mortality rates are still declining, and we predict how these rates will eventually differ.

Methods

—

Data on stroke mortality in the United States between 1968 and 1996 were analyzed in a 3-step procedure: (1) we calculated “crude” age-adjusted stroke mortality rates by race, sex, and county; (2) we “smoothed” the rates across counties and years; and (3) we fit a model to describe the temporal pattern. From this model we calculated the percent decline in stroke mortality, the anticipated additional decline (thereby identifying regions that will continue to decline), and the anticipated eventual stroke mortality rates.

Results

—

Maps by race-sex-region group describe the above parameters. White men have experienced the largest decline in stroke mortality, and black men have seen the smallest. Generally, stroke mortality appears to still be slowly declining for blacks but not for whites. Geographic differences in stroke mortality are predicted to persist.

Conclusions

—

The analysis suggests that the Deep South (Alabama and Mississippi) will fall from the stroke belt and be replaced by other regions (notably Oregon, Washington, and Arkansas). New York City and southern Florida had low stroke mortality rates in 1968, have experienced large declines, and continue to experience declines, resulting in even larger relative heterogeneity of stroke mortality rates. The reasons for these differences in the pattern of the decline in stroke mortality are not understood.
Trend of Stroke Hospitalization, United States, 1988–1997
Authors: Fang Jing , Alderman Michael H.
Published: October 2007

Background and Purpose

—

Age-adjusted stroke mortality in the United States has declined in recent decades. However, the course of stroke incidence is less certain. To address this issue, we determined trends of stroke hospitalization and in-hospital case fatality during 1988–1997.

Methods

—

Stroke hospitalization was estimated from National Hospital Discharge Survey as numerator and Current Population Survey as denominator. Hospitalization rates were determined and stratified by patient characteristics. Average length of hospital stay was also determined. In-hospital mortality was specified by sex, age, and other patient characteristics. The change in these rates over 10 years and average annual percent changes were calculated.

Results

—

During 1988–1997, age-adjusted stroke hospitalization rate increased 18.6% (from 560 to 664/100 000;
P
=0.043), while total hospitalization increased from 592 811 to 821 760. This increase was limited to persons aged ≥65 years. Patients in the South had the highest stroke hospitalization rates, and those in the West had the lowest. Overall, 58% of strokes were classified as ischemic, 13% as hemorrhagic, and 29% as other. Over these 10 years, stroke patients having coincident diabetes, hypertension, and congestive heart failure increased 17.4% (
P
=0.17), 34% (
P
=0.05), and 31% (
P
=0.091), respectively. The average length of hospital stay fell from 11.1 to 6.2 days (44.1%;
P
=0.012). As a result, despite an increase in hospitalizations for stroke, the total person-days in hospital actually decreased by 22% (
P
=0.06).

Conclusions

—

The declining age-adjusted stroke mortality in the United States has not been accompanied by a fall in hospitalization over recent years. Thus far, however, decrease in length of stay has more than offset increased admission. At the same time, the sharp drop in hospital case fatality rates suggests that continuing decline in stroke mortality may be due, in large part, to improved survival after acute stroke.
Heterogeneity Affecting Outcome From Acute Stroke Therapy
Authors: Kent Thomas A. , Soukup Vicki M. , Fabian Roderic H.
Published: October 2007

Background

—

Stroke patients are heterogeneous not only with respect to etiology but also in terms of preexisting clinical conditions. Approximately one fifth of patients with acute stroke are hyperglycemic and/or have had a recent infectious or inflammatory condition.

Summary of Review

—

Experimental research indicates that these factors can alter and accelerate the evolution of stroke and reperfusion injury, although these effects are complex and some may have a favorable impact. Both conditions involve activation of inflammatory and reactive oxygen mechanisms. In addition, hyperglycemia has concomitant deleterious vascular and metabolic effects that worsen infarct size and encourage hemorrhagic transformation in reperfusion models. Clinical data are less extensive but in general support an adverse impact on outcome.

Conclusions

—

After examining these data in detail, we concluded that the presence of these clinical conditions could assist in identification of those at increased risk for complications of reperfusion therapy. Furthermore, consideration of these factors may provide a rational basis for combination therapy and improve the clinical relevance of experimental stroke models.
Right Sylvian Fissure Subarachnoid Hemorrhage Has Electrocardiographic Consequences
Authors: Hirashima Yutaka , Takashima Shutaro , Matsumura Nobuhisa , Kurimoto Masanori , Origasa Hideki , Endo Shunro
Published: October 2007

Background and Purpose
—

Abnormal ECG changes are frequently observed in patients with subarachnoid hemorrhage (SAH). Recently, evidence has been obtained that right insular cortex mediates sympathetic cardiovascular effects. We therefore assessed the laterality and location of SAH dominance in inducing cardiovascular changes as measured by ECG, blood pressure, and heart rate.

Methods
—

After exclusion of 11 SAH patients who died within 1 month after onset, we studied 118 consecutive patients. Data were obtained from records of blood pressure and pulse on admission. Abnormal ECG changes were determined from ECGs on admission and almost 1 month later. From brain CT scans performed immediately after admission, the amount of SAH in each of the 8 cisterns and fissures was measured semiquantitatively.

Results
—

Twenty-six patients had abnormal changes on admission ECG, while 92 patients did not. Systolic blood pressure, diastolic blood pressure, and the amounts of blood in the left ambient cistern, left suprasellar cistern, quadrigeminal cistern, right ambient cistern, right suprasellar cistern, right sylvian fissure, and the set of all cisterns were significantly greater in the group with ECG change than in the group without ECG change. Multivariate logistic regression analysis with stepwise method indicated that systolic blood pressure >160 mm Hg (
P
=0.0006) and the amounts of SAH in the quadrigeminal cistern (
P
=0.022) and right sylvian fissure (
P
=0.0019) were independently associated with abnormal ECG change.

Conclusions
—

Cardiac consequences are possible in patients with massive right sylvian fissure SAH or when systolic blood pressure is >160 mm Hg.
Evaluation of Risk Factors for Stroke/Embolism and of Complications Due to Anticoagulant Therapy in Atrial Fibrillation
Authors: Wehinger Cornelius , Stöllberger Claudia , Länger Thomas , Schneider Barbara , Finsterer Josef
Published: October 2007

Background and Purpose
—

We sought to assess in outpatients with atrial fibrillation and oral anticoagulation (1) whether the complication rate is influenced by the presence of the risk factors age >65 years, arterial hypertension, diabetes, or previous stroke; (2) whether the complication rate is influenced by the number of additional drugs taken by patients; and (3) whether problems and interventions differ between patients with or without complications.

Methods
—

Clinical characteristics, drugs, problems, interventions, and complications were registered during 2 years.

Results
—

Three hundred sixty patients (mean age, 68 years; 43% female) were observed for 383 patient-years. Patients aged >65 years had more serious, life-threatening, or fatal complications (11% versus 5.3%/100 patient-years;
P
=0.0428) than younger patients. Patients with diabetes had more life-threatening and fatal complications (2.8% versus 0.6%/100 patient-years;
P
=0.0354) than patients without. The complication rate did not differ regarding the presence of previous stroke or hypertension. Patients who took ≤3 drugs had fewer complications than patients who took more (4.3% versus 24.4%/100 patient-years;
P
=0.0041). Patients with complications complained more of chest (48% versus 28%/100 patient-years;
P
=0.0113) and abdominal pain (30% versus 13%/100 patient-years;
P
=0.0057), more frequently failed to keep appointments (134% versus 107%/100 patient-years;
P
=0.0321), had a higher tracking rate (134% versus 105%/100 patient-years;
P
=0.0272), and took more additional drugs (4.6 versus 3.5 drugs per day;
P
=0.0063) than patients with no complications.

Conclusions
—

Patients with increased age or diabetes mellitus or those who take >3 drugs per day have an increased complication rate and thus need especially careful monitoring of oral anticoagulation, including adequate pain control.
Risk of Early Death and Recurrent Stroke and Effect of Heparin in 3169 Patients With Acute Ischemic Stroke and Atrial Fibrillation in the International Stroke Trial
Authors: Saxena Ritu , Lewis Stephanie , Berge Eivind , Sandercock Peter A.G. , Koudstaal Peter J. ,   for the International Stroke Trial Collaborative Group
Published: October 2007

Background and Purpose

—

We sought to investigate the apparently high risk of early death after an ischemic stroke among patients with atrial fibrillation (AF), identify the main factors associated with early death, and assess the effect of treatment with different doses of subcutaneous unfractionated heparin (UFH) given within 48 hours.

Methods

—

We studied the occurrence of major clinical events within 14 days among 18 451 patients from the International Stroke Trial, first for all treatment groups combined. Then, among patients with AF, we examined the effects of treatment with subcutaneous UFH started within 48 hours and continued until 14 days after stroke onset.

Results

—

A total of 3169 patients (17%) had AF. Seven hundred eighty-four patients were allocated to UFH 12 500 IU SC BID, 773 to UFH 5000 IU SC BID, and 1612 to no heparin. Within each of these groups, half of the patients were randomly assigned to aspirin 300 mg once daily. Compared with patients without AF, patients with AF were more likely to be female (56% versus 45%), to be old (mean age, 78 versus 71 years), to have an infarct on prerandomization CT (57% versus 47%), and to have impaired consciousness (37% versus 20%). The initial ischemic stroke type was more often a large-artery infarct (36% versus 21%). A lacunar stroke syndrome was less common (13% versus 26%). Death within 14 days was more common in patients with AF (17% versus 8%) and more often attributed to neurological damage from the initial stroke (10% versus 4%). The frequency of recurrent ischemic or undefined stroke was not significantly different (3.9% versus 3.3%). The proportion of AF patients with further events within 14 days allocated to UFH 12 500 IU (n=784), UFH 5000 IU (n=773), and to no-heparin (n=1612) groups were as follows: ischemic stroke, 2.3%, 3.4%, 4.9% (
P
=0.001); hemorrhagic stroke, 2.8%, 1.3%, 0.4% (
P
<0.0001); and any stroke or death, 18.8%, 19.4% and 20.7% (
P
=0.3), respectively. No effect of heparin on the proportion of patients dead or dependent at 6 months was apparent.

Conclusions

—

Acute ischemic stroke patients with AF have a higher risk of early death, which can be explained by older age and larger infarcts but not by a higher risk of early recurrent ischemic stroke, although slightly more patients with AF died from a fatal recurrent stroke of ischemic or unknown type (1.3% versus 0.9%). In patients with AF the absolute risk of early recurrent stroke is low, and there is no net advantage to treatment with heparin. These data do not support the widespread use of intensive heparin regimens in the acute phase of ischemic stroke associated with AF.
A Population Study of Stroke in West Ukraine
Authors: Mihálka László , Smolanka Volodymyr , Bulecza Bogdan , Mulesa Svetlana , Bereczki Dániel
Published: October 2007

Background and Purpose

—

According to World Health Organization statistics, Ukraine has extremely high stroke mortality. No population-based prospective studies of stroke incidence have been performed yet in this European country with ≈50 million inhabitants. High reported rates of stroke mortality in official statistics conflict with some locally published incidence data in Ukraine. To obtain accurate data, we evaluated stroke incidence and 30-day case fatality in a prospective population study in the West Ukrainian city of Uzhgorod with a population of 126 000 inhabitants.

Methods

—

Case certification by neurologists and follow-up at 30 days after stroke for all patients identified by any level of the health service system were performed for a 12-month period.

Results

—

We identified 352 stroke cases. The age-standardized incidence was 341 and 238 of 100 000 and mortality was 83 and 69 of 100 000 with the use of the European or world standard population for standardization. Mean age of stroke patients was 63.4±12.5 years. Rate of hospitalization was 66%. Hospitalized patients were >10 years younger than those treated in their homes. The 30-day case fatality rates were 15.4% among hospitalized patients and 36.8% among those treated at home. Overall 30-day case fatality was 23.3%.

Conclusions

—

Stroke incidence and 30-day case fatality in this West Ukrainian city were similar to those of some West European countries and were much lower than what could be expected from World Health Organization statistics. The relatively low incidence rate seems accurate; because of the organization of local stroke services, it is not probable that a considerable proportion of patients with acute stroke could bypass all levels of the acute care health system. Local health statistics reported a much lower number of stroke cases and stroke deaths than found in our survey; thus, further study is needed to clarify the reason for the discrepancy between local data and the high reported stroke mortality in Ukraine.
Neuronal Expression of the DNA Repair Protein Ku 70 After Ischemic Preconditioning Corresponds to Tolerance to Global Cerebral Ischemia
Authors: Sugawara Taku , Noshita Nobuo , Lewén Anders , Kim Gyung W. , Chan Pak H.
Published: October 2007

Background and Purpose

Oxidative stress after ischemia/reperfusion has been shown to induce DNA damage and subsequent DNA repair activity. Ku 70/86, multifunctional DNA repair proteins, bind to broken DNA ends and trigger a DNA repair pathway. We investigated the involvement of these proteins in the development of neuronal tolerance to global cerebral ischemia after ischemic preconditioning.

Methods

Adult male Sprague-Dawley rats were subjected to either 5 minutes of lethal global ischemia with or without 3 minutes of sublethal ischemic preconditioning or 3 minutes of ischemia only. Neuronal injury was histologically assessed, and DNA damage was visualized by in situ labeling of DNA fragmentation and DNA gel electrophoresis. Ku expression was also examined by immunohistochemistry and Western blot analysis.

Results

Hippocampal CA1 neurons underwent DNA-fragmented cell death 3 days after 5 minutes of ischemia. However, these neurons showed a strong tolerance to 5 minutes of ischemia 1 to 3 days after ischemic preconditioning. Immunohistochemistry showed virtually no constitutive expression of Ku proteins in CA1 neurons; however, ischemic preconditioning induced neuronal Ku 70 expression 1 to 3 days later. Western blot confirmed an increase in Ku 70 in this region at the same time.

Conclusions

The temporal and spatial expression of Ku 70 corresponded to tolerance of the hippocampal CA1 neurons to subsequent ischemia, suggesting the involvement of Ku proteins in the development of neuronal tolerance after ischemic preconditioning.
Cost of Stroke in Australia From a Societal Perspective
Authors: Dewey Helen M. , Thrift Amanda G. , Mihalopoulos Cathy , Carter Robert , Macdonell Richard A.L. , McNeil John J. , Donnan Geoffrey A.
Published: October 2007

Background and Purpose

—

Accurate information about resource use and costs of stroke is necessary for informed health service planning. The purpose of this study was to determine the patterns of resource use among stroke patients and to estimate the total costs (direct service use and indirect production losses) of stroke (excluding SAH) in Australia for 1997.

Methods

—

An incidence-based cost-of-illness model was developed, incorporating data obtained from the North East Melbourne Stroke Incidence Study (NEMESIS). The costs of stroke during the first year after stroke and the present value of total lifetime costs of stroke were estimated.

Results

—

The total first-year costs of all first-ever-in-a lifetime strokes (SAH excluded) that occurred in Australia during 1997 were estimated to be A$555 million (US$420 million), and the present value of lifetime costs was estimated to be A$1.3 billion (US$985 million). The average cost per case during the first 12 months and over a lifetime was A$18 956 (US$14 361) and A$44 428 (US$33 658), respectively. The most important categories of cost during the first year were acute hospitalization (A$154 million), inpatient rehabilitation (A$150 million), and nursing home care (A$63 million). The present value of lifetime indirect costs was estimated to be A$34 million.

Conclusions

—

Similar to other studies, hospital and nursing home costs contributed most to the total cost of stroke (excluding SAH) in Australia. Inpatient rehabilitation accounts for ≈27% of total first-year costs. Given the magnitude of these costs, investigation of the cost-effectiveness of rehabilitation services should become a priority in this community.
Parity and Carotid Artery Atherosclerosis in Elderly Women
Authors: Humphries Karin H. , Westendorp Iris C.D. , Bots Michiel L. , Spinelli John J. , Carere Ronald G. , Hofman Albert , Witteman Jacqueline C.M.
Published: October 2007

Background and Purpose

—

It has been postulated that physiological changes in the cardiovascular system, lipids, and glucose metabolism during pregnancy may increase subsequent risk of cardiovascular disease. Examination of the association between parity and risk factors for atherosclerosis may contribute information regarding possible mechanisms.

Methods

—

The relationship of parity with cardiovascular risk factors and the presence of carotid atherosclerosis was examined in the Rotterdam Study, a population-based study comprising 4878 women aged 55 years and older. Carotid atherosclerosis was assessed by ultrasonographic detection of plaques in the common carotid artery and bifurcation. Logistic regression models were used to compute odds ratios and 95% confidence intervals, adjusted for confounding factors.

Results

—

Parity was inversely associated with high-density lipoprotein cholesterol, and alcohol intake. Parity was positively associated with body mass index, total/HDL cholesterol ratio, insulin resistance, age at menopause, and socioeconomic status. Relative to nulliparous women, parous women had 36% (9% to 71%) greater risk of carotid atherosclerosis, rising to 64% in women with ≥4 children (19% to 127%). Adjustment for known cardiovascular risk factors, including insulin resistance and current lipid levels, did not diminish the magnitude of this association.

Conclusions

—

Data demonstrated that there is a positive association between parity and risk of carotid artery plaques in elderly women and, further, that high parity is associated with lower HDL cholesterol levels and higher glucose/insulin ratios long after childbearing has ceased.
Triflusal Posttreatment Inhibits Glial Nuclear Factor-κB, Downregulates the Glial Response, and Is Neuroprotective in an Excitotoxic Injury Model in Postnatal Brain
Authors: Acarin Laia , González Berta , Castellano Bernardo
Published: October 2007

Background and Purpose—Nuclear factor-κB (NF-κB) and the signal transducer and activator of transcription 3 (STAT3) are important transcription factors regulating inflammatory mechanisms and the glial response to neural injury, determining lesion outcome. In this study we evaluate the ability of triflusal (2-acetoxy-4-trifluoromethylbenzoic acid), an antiplatelet agent inhibitor of NF-κB activation, to improve lesion outcome after excitotoxic damage to the immature brain.

Methods—Postnatal day 9 rats received an intracortical injection of the excitotoxinN-methyl-d-aspartate (NMDA) and oral administration of triflusal (30 mg/kg) either as 3 doses before NMDA injection (pretreatment) or as a single dose 8 hours after NMDA injection (posttreatment). After survival times of 10 and 24 hours, brains were processed for toluidine blue staining, tomato lectin histochemistry, and glial fibrillary acidic protein, NF-κB, and STAT3 immunocytochemistry.

Results—NMDA-lesioned animals that were not treated with triflusal showed activation of NF-κB in neuronal cells at first and in glial cells subsequently. Animals that received pretreatment with triflusal showed a strong downregulation of neuronal and glial NF-κB but a similar development of the glial response and an equivalent lesion volume compared with nontreated animals. In contrast, animals receiving triflusal posttreatment showed increased early neuronal NF-κB but a reduction in the subsequent glial NF-κB, accompanied by important downregulation of the microglial and astroglial response and a drastic reduction in the lesion size. STAT3 activation was not affected by triflusal treatment.

Conclusions—Triflusal posttreatment diminishes glial NF-κB, downregulates the glial response, and improves the lesion outcome, suggesting a neuroprotective role of this compound against excitotoxic injury in the immature brain.
Menstrual and Reproductive Factors for Subarachnoid Hemorrhage Risk in Women
Authors: Okamoto Kazushi , Horisawa Rokuro , Kawamura Takashi , Asai Akihiko , Ogino Masataka , Takagi Takuya , Ohno Yoshiyuki
Published: October 2007

Background and Purpose

—

We sought to examine the relationship between menstrual and reproductive factors and the risk of subarachnoid hemorrhage (SAH), using a case-control study.

Methods

—

Cases consisted of a consecutive series of 124 women patients with first spontaneous SAH aged 30 to 79 years and confirmed aneurysm(s) by angiography and/or CT scan. Hospital and community controls subjects were identified, matched to each case by age (±2 years).

Results

—

Increased SAH risk was associated with (1) earlier age at menarche (adjusted odds ratio [OR]=3.24 for age <13 years compared with age ≥13 years; 95% CI, 1.25 to 4.03) and (2) nulligravidity (adjusted OR=4.23; 95% CI, 1.05 to 7.56). No significant association of SAH risk was found with regularity of menstrual cycle, age at pregnancy, age at first birth, and number of births. The greatest risk was for the combined effect of nulligravidity and earlier menarche (<13 years) (adjusted OR=6.37; 95% CI, 1.12 to 36.2).

Conclusions

—

The combined effect of several variables related to menstrual and reproductive history may exert a greater influence on risk of SAH compared with a single menstrual or reproductive variable.
ERMANCIA: Epidemiology of Stroke in Martinique, French West Indies
Authors: Smadja Didier , Cabre Philippe , May Florence , Fanon Jean-Luc , René-Corail Patrick , Riocreux Christophe , Charpentier Jean-Christophe , Fournerie Pierre , Saint-Vil Martine , Ketterlé Jeannine ,   the ERMANCIA Study Group
Published: October 2007

Background and Purpose
—

The ERMANCIA (Etude Réalisée en Martinique et Centrée sur l’Incidence de Accidents vasculaires cérébraux) study was designed to provide the first comparable epidemiological data on stroke in a black Caribbean population.

Methods
—

ERMANCIA was a prospective community-based study performed in Martinique (French West Indies) from June 1, 1998, to May 31, 1999. The black at-risk population was approximately 360 000. Multiple sources were used to identify hospitalized and nonhospitalized patients with first-ever stroke.

Results
—

Five hundred eighty patients (285 men and 295 women; mean±SD age, 71.2±14 years) suffered from a first-ever in a lifetime stroke, yielding a crude annual incidence of 164/100 000 per year (95% CI, 151 to 177). The rates adjusted by age and sex to the French population (1999 census) and to the European population were 202 (95% CI, 185 to 218) and 151 (95% CI, 139 to 164), respectively. Thirty-eight patients (6.5%) were not hospitalized during the acute phase of the stroke; 92.8% had CT scan. Pathological types of strokes were infarction (79.8%, including 23% of lacunar strokes), intracerebral hemorrhage (14.3%), subarachnoid hemorrhage (3.4%), and undetermined (2.4%). The main risk factors for stroke were hypertension (69.1%) and diabetes (29.5%). The 30-day case fatality rate was 19.3% (15.8% for cerebral infarction and 37.3% for intracerebral hemorrhage).

Conclusions
—

In Martinique, the ERMANCIA population-based study showed a high stroke incidence and a high prevalence of hypertension and diabetes in the stroke population compared with those observed in continental France. Epidemiological data on stroke in African Caribbeans from Martinique are comparable to those reported in blacks from the United States and United Kingdom.
Spectroscopic Assessment of Alterations in Macromolecule and Small-Molecule Metabolites in Human Brain After Stroke
Authors: Graham Glenn D. , Hwang Jong-Hee , Rothman Douglas L. , Prichard James W.
Published: October 2007

Background and Purpose

—

We sought to measure the temporal evolution and spatial distribution of lesion macromolecules and small molecules (lactate,
N
-acetyl compounds, creatine, and choline) in stroke patients by using short echo time in vivo proton MR spectroscopy.

Methods

—

Single-voxel spectra with TE=22 ms were obtained with and without inversion recovery suppression of small-molecule resonances from 30 examinations of 24 patients 3 to 214 days after stroke. Subtraction of the suppressed from the unsuppressed spectra yielded metabolite spectra without overlap from macromolecules. Two-dimensional spectroscopic images were acquired with macromolecule and small-molecule suppression from 5 additional patients.

Results

—

Macromolecule signals were elevated in lesions relative to normal brain and tended to increase in the subacute period, even as lactate peaks declined. Regions of increased lactate, increased macromolecule signal at 1.3 ppm, and decreased
N
-acetyl compounds were closely correlated in the 2D spectroscopic images.

Conclusions

—

Short echo time spectra can be acquired in vivo in a manner that improves signal-to-noise ratio over long echo experiments and resolves overlapping macromolecule and small-molecule signals. The prominent macromolecule signals seen in the subacute period in association with persistently elevated lactate may represent mobile lipids in macrophages or other cells.
Changes in Intervention and Outcome in Elderly Patients With Subarachnoid Hemorrhage
Authors: Johansson Mats , Cesarini Kristina Giuliana , Contant Charles F. , Persson Lennart , Enblad Per
Published: October 2007

Background and Purpose

—

The elderly constitute a significant and increasing proportion of the population. The aim of this investigation was to study time trends in clinical management and outcome in elderly patients with subarachnoid hemorrhage.

Methods

—

Two hundred eighty-one patients ≥65 years of age with aneurysmal subarachnoid hemorrhage who were accepted for treatment at the Uppsala University Hospital neurosurgery clinic during 1981 to 1998 were included. Hunt and Hess grades on admission, specific management components, and clinical outcomes were recorded. Three periods were compared: A, 1981 to 1986 (before neurointensive care); B, 1987 to 1992; and C, 1993 to 1998.

Results

—

The volume of elderly patients (≥65 years of age) increased with time, especially patients ≥70 years of age. Furthermore the proportion of patients with more severe clinical conditions increased. A greater proportion of patients had a favorable outcome (A, 45%; B, 61%; C, 58%) despite older ages and more severe neurological and clinical conditions. In period C, Hunt and Hess I to II patients had a favorable outcome in 85% of cases compared with 64% in period A. This was achieved without any increase in the number of severely disabled patients.

Conclusions

—

Elderly patients with subarachnoid hemorrhage can be treated successfully, and results are still improving. The introduction of neurointensive care may have contributed to the improved outcome without increasing the proportion of severely disabled patients. A defeatist attitude toward elderly patients with this otherwise devastating disease is not justified.
Should Stroke Subtype Influence Anticoagulation Decisions to Prevent Recurrence in Stroke Patients With Atrial Fibrillation?
Authors: Evans Andrew , Perez Iñigo , Yu Gloria , Kalra Lalit
Published: October 2007

Background and Purpose

—

Long-term anticoagulation is routinely used for secondary stroke prevention in atrial fibrillation, often regardless of stroke subtype. Although the role of warfarin in cardioembolic stroke is established, it may not prevent recurrence in other stroke subtypes, even in the presence of atrial fibrillation.

Methods

—

This was a 2-year, prospective, intervention study conducted in a district general hospital. Participants included 386 acute stroke patients with atrial fibrillation. Subjects were characterized for stroke subtype on clinical, neuroimaging, carotid ultrasonographic, and echocardiographic criteria. Eligible patients were treated with adjusted-dose warfarin (international normalized ratio, 2.0 to 3.0). Aspirin (75 to 300 mg/d) was used in patients with contraindications or those who refused anticoagulation. The main outcome measures were rate of recurrent stroke by subtype and major and minor bleeding complications.

Results

—

The aspirin group (n=172) was comparable to the warfarin group (n=214) in terms of age, sex, risk factors, and initial stroke subtype. The rate of recurrent stroke was higher (9.5% versus 4.9%,
P
<0.02) but that of major bleeding was lower (0.6% versus 2.5%,
P
<0.05) with aspirin. The increased stroke rate with aspirin was due predominantly to cardioembolic recurrence in patients presenting initially with cardioembolic stroke (8.4% versus 1.9%,
P
<0.01). The recurrence rate in aspirin-treated patients who presented with lacunar stroke and atrial fibrillation was similar to that seen in patients receiving warfarin (8.8% versus 8.9%).

Conclusions

—

In this cohort of stroke patients with atrial fibrillation, anticoagulation was superior to aspirin in preventing cardioembolic but not lacunar recurrence. Determination of stroke subtype may be important in anticoagulation decisions for secondary prevention, and further studies are required.
Targeted
hsp70.1
Disruption Increases Infarction Volume After Focal Cerebral Ischemia in Mice
Authors: Lee Seung-Hoon , Kim Manho , Yoon Byung-Woo , Kim Young-Ju , Ma Sung-Jin , Roh Jae-Kyu , Lee Jae-Seon , Seo Jeong-Sun
Published: October 2007

Background and Purpose

—

Heat-shock proteins (HSPs) are highly conserved proteins that are induced by a variety of stresses. HSP70 is a 70-kDa HSP family known to have cytoprotective effects against various insults. The role of HSP70 in cerebral ischemia remains to be elucidated in vivo.

Methods

—

To investigate the effect of reduced HSP70 levels on cerebral ischemia, focal cerebral ischemia by intraluminal occlusion of the middle cerebral artery was induced in
hsp70.1
knockout mice. The expressions of
hsp70.1
and
hsp70.3
mRNAs and HSP70 protein were determined, and infarction volumes were measured and compared.

Results

—

Northern blots confirmed the absence of
hsp70.1
mRNA expression in the knockout mice. The mean infarction volume was significantly larger in
hsp70.1
knockout mice (92.5±8.3 mm
3
) than in the wild-type mice (59.3±8.9 mm,
3
P
<0.001). Western blots showed increased HSP70 expression in the ischemic hemisphere in both knockout and wild-type mice, but HSP70 expression levels in knockout mice were significantly lower than those in their wild-type littermates. Immunohistochemistry did not show any significant differences between the knockout and wild-type animals and showed increased HSP70 immunoreactivity in the ischemic hemisphere, with predominance in the cerebral cortex, especially in the penumbra.

Conclusions

—

Our results suggest that
hsp70.1
plays an important role in the early protection of the brain, at least after acute focal cerebral ischemia in mice.
C-Reactive Protein Levels and Viable

Chlamydia pneumoniae

in Carotid Artery Atherosclerosis
Authors: Johnston S. Claiborne , Messina Louis M. , Browner Warren S. , Lawton Michael T. , Morris Caroline , Dean Deborah
Published: October 2007

Background and Purpose

—

An elevated serum level of C-reactive protein, an inflammatory marker, is an independent predictor of stroke and coronary artery disease. To determine whether chronic infection with
Chlamydia pneumoniae
, which has been identified in atherosclerotic plaques, is responsible for systemic inflammation, we studied the association between serum C-reactive protein levels and infection of carotid artery atherosclerotic plaque with viable
C pneumoniae
.

Methods

—

Serum C-reactive protein levels were obtained before endarterectomy for carotid artery stenosis. Plaques were tested for
C pneumoniae
mRNA, an indicator of viability, and DNA by polymerase chain reaction of DNA and cDNA, respectively.

Results

—

Forty-eight samples were studied, of which 18 (38%; 95% CI, 23 to 50) were infected with viable
C pneumoniae
as evidenced by isolated chlamydial mRNA. All 18 of these samples, plus 1 additional sample, were positive for chlamydial DNA. Serum C-reactive protein levels were higher in those with viable
C pneumoniae
compared with those without infection (median, 8 mg/L versus undetectable;
P
=0.045 by Wilcoxon rank-sum test). In multivariable models, the only independent predictor of the presence of viable
C pneumoniae
was a detectable C-reactive protein level (odds ratio, 4.2; 95% CI, 1.1 to 17;
P
=0.04).

Conclusions

—

Viable
C pneumoniae
are present in a substantial portion of carotid artery atherosclerotic plaques and are associated with increased serum C-reactive protein levels. These findings may explain the link between elevated C-reactive protein levels and the risk of cardiovascular disease and stroke but should be reproduced in a larger cohort.